Showing papers in "Annals of the New York Academy of Sciences in 1979"

Asbestos exposure, cigarette smoking and death rates*

Abstract: The authors examine the relationship between exposure to asbestos dust cigarette smoking and mortality. The data covering 17800 asbestos workers in the United States and Canada were compiled from the records of the International Association of Heat and Frost Insulators and Asbestos Workers (ANNOTATION)

Continuous chaos—four prototype equations

Abstract: If oscillation is the typical behavior of 2-dimensional dynamical systems (Euclidean and on manifolds), then chaos, in the same way, characterizes 3-dimensional continuous systems. First a method t o obtain chaos in degenerate (relaxation type) dynamical systems in two variables is outlined whereby five basic flow patterns emerge. Second, following a piecewise linear degenerate equation, four prototypically simple quadratic differential equations in three variables that realize nondegenerate analogs of those five flows are presented. Finally a possible equation for an even higher type of qualitative behavior beyond chaos is proposed.

Pathological conditions resulting from instabilities in physiological control systems

Abstract: A large number of human diseases are characterized by changes in the qualitative dynamics of physiological control systems: Systems that normally oscillate. stop oscillating, or begin to oscillate in a new and unexpected fashion, and systems that normally d o not oscillate, begin oscillating. These changes in qualitative dynamics often have a sudden onset, and in many instances it has not been possible to identify the factors that lead to the disease. By dynarnical disease we mean a disease that occurs in an intact physiological control system operating in a range of control parameters that leads to abnormal dynamics and human p a t h ~ l o g y . ~ ’ In this paper, the changes in qualitative dynamics associated with the onset of the disease are identified with bifurcations in the dynamics of mathematical models of the physiological control systems. We shall consider in some detail dynamical diseases in the respiratory and haematopoietic systems. Our starting point is the ordinary differential equation

World PCBs map: storage and effects in man and his biologic environment in the 1970s.

Abstract: PCB residues are found in biota all over the world. A biologic magnification of PCBs has been demonstrated in the food chain: plankton-fish-fish eating birds. A world map of the PCBs residues in biota and some of their biologic effects are given in this study. The biologic effects of PCBs are varied and may generally be explained by the induction or inhibition of the activity of a large number of enzymes, which upsets quantitatively, normal biochemical processes. Harm to reproduction, growth, development, defense systems, tissues, and organs appeared in susceptible organisms as a result of such changes or as a chain reaction to heterostases. The adverse health effects, observed in persons occupationally exposed and in those accidentally poisoned, point to the risk for the general population of an ever-increasing environmental pollution by PCBs. There is need for an integrated approach, consisting of epidemiologic studies on high risk groups in the general population and in persons occupationally exposed, as well as periodic assessment of PCB residues in man, his food, and feed supplies.

Possible correlation between induction modes of hepatic enzymes by PCBs and their toxicity in rats.

Abstract: Acute toxicity of individual PCBs, which were categorized as either phenobarbital (PB)- or 3-methylcholanthrene (MC)-type inducers, was examined in young male Wistar rats, comparing their effects on growth rate, organ weight and liver lipid content, 5 days after a single i.p. injection. PB-type PCBs (2,4,3',4'- and 2,5,2'5'-tetrachlorobiphenyl), which slightly increased a content of cytochrome P450, did not show any significant toxicity at a dose of 100 mg/kg. On the contrary, MC-type PCBs (3,4,5,3',4'-pentachloro- and 3,4,5,3',4',5'-hexachlorobiphenyl), which markedly increased a content of cytochrome P448, strongly reduced growth rate and weights of thymus and spleen at a dose of 10 mg/kg. Liver enlargement accompanied by fatty liver was also observed only with MC-type PCBs. 3,4,3',4'-Tetrachlorobiphenyl was also toxic at a dose of 50 mg/kg, in keeping with its weak MC-type-inducing ability. Pretreatment with MC affected neither growth rate, spleen weight, nor liver lipid content. These results suggest that the toxic potency of PCBs is related to their MC-type inducing ability, but the toxic characteristics are different from those of MC itself.

T‐cell growth factor‐mediated t‐cell proliferation*

Abstract: Recently, it was discovered that human T-lymphocytes (T-cells) could be maintained in indefinite proliferative culture with the aid of a soluble factor derived from media conditioned by the T-cell mitogen stimulation of peripheral blood mononuclear cells.', The cells were lymphoblastoid in appearance and expressed surface markers characteristic of human T-cells.2 Several observations suggested that the successful initiation of T-cell growth required exposure to a T-cell mitogen but that the subsequent continuous growth of the cells was mitogen-independent. These findings prompted investigation as to whether it was possible to expose cells first to a specific antigenic stimulus followed by continuous culture in the presence of the T-cell growth factor (TCGF). If successful, then we hoped it might be possible to obtain functional, differentiated, antigen-specific T-cells in continuous proliferative culture. Such experimentation did prove successful, and both human and murine antigen-specific cytolytic T-cells have been maintained in continuous proliferative culture for greater than two years. Studies designed to explore the nature of the T-cell growth factor (TCGF) which mediated the proliferation, suggested that TCGF was obligatory for the proliferative expansion of mitogenor antigen-activated T-cell clones. The experimentation reported herein confirms this hypothesis and indicates that TCGF is the second T-cell signal.

Major physiologic and histochemical characteristics of inherited dystrophy of the chicken

Abstract: Inherited muscular dystrophy of the chicken was first described more than 20 years ago.’ Since then. several genetic lines have been developed, some have even become extinct, and many studies have been undertaken of the morphologic, physiologic, and biochemical properties of muscles of birds with the disorder. Early research on the abnormality has been reviewed by Julian and Asmundson2 and Asmundson et ~ 1 . ~ This paper discusses some of the major characteristics of the dystrophic chicken that occur in the several lines developed and maintained at the University of California, at Davis, and describes how these properties have been investigated in our laboratory.

Dioxins, dibenzofurans and other polyhalogenated aromatics: production, use, formation, and destruction

Abstract: PCBs PCTs, and PCNs (FIGURE 2) can all be prepared by chlorination of the parent hydrocarbon. The PCBs especially have been widely used in a long series of various applications.*.’ The total world production of PCBs exceeds 500,000 tons. The three groups of compounds are all very stable to biodegradation and they have shown a pronounced tendency for bioaccumulation. For these reasons the use of PCBs is now, in several countries, restricted to “closed systems” such as transformers and capacitors. A mixture of PBBs, mainly the 2,2’,4,4‘,5,5’-hexabromo isomer,’ has been used as a flame retardant under the trade name Fire Master BP 6 or FF-1.

Sensitive dependence on initial condition and turbulent behavior of dynamical systems

Abstract: The qualitative features that we want t o discuss are those associated with sensitive dependence on initial condition. We shall try t o analyze sensitive dependence on initial condition, see how it manifests itself as turbulent behavior, and find the simplest examples in which it occurs. In applications, x, represents the state (at time t ) of the natural system under consideration, and may vary in some infinite dimensional space (as for instance in hydrodynamics). For the convenience of the mathematical discussion we shall, however, suppose that the state space Mof our system is finite dimensional. The time evolution is defined by maps f ': M M (t discrete or continuous). We shall assume that either M is R\" and there is some bounded open U C IR\" such that closure / ' U C I/ for I > 0, or that M is a compact differentiable manifold.* We assume that the mapfin ( I ) or the vector field X in (2) are C', i.e., r times continuously differentiable with r 2 1. In what follows I shall try to be mathematically correct, or a t least not misleading. It has t o be realized, however, that many of the questions to be discussed are poorly understood mathematically. I shall definitely not limit myself to those topics that are completely elucidated. I shall try to give an idea of what lies beyond, a t the cost of some conjectures and heuristic considerations.

Comparative toxicity of three halogenated dibenzofurans in guinea pigs, mice, and rhesus monkeys

Abstract: The chlorinated dibenzofurans have been reported to be present in a variety of polychlorinated biphenyls (PCBs)’” and in pentachlorophenol: They were also detected in the PCB-contaminated rice oil that was responsible for the human intoxication referred to as ‘Y~sho’.’.~ Polychlorinated dibenzofurans were also detected in tissues of patients with ‘Yusho’.’ A polychlorinated dibenzofuran fraction extracted from PCB’s was found to be highly toxic in chickens.* A mixture of polychlorinated dibenzofurans also caused toxic effects when fed to rats? 2,3,7,8Tetrachlorodibenzofuran (TCDF) has been evaluated for toxicity in chicks,” guinea pigs,” and mice.” The results reported in this manuscript extend earlier studies with TCDF in guinea pigs and mice, report the toxic effects in rhesus monkeys, and describe the toxic effects of 2,3,4,7,8-pentachlorodibenzofuran (PCDF) and 2,3,7&tetrabromodibenzofuran (TBDF) in guinea pigs.

Hereditary and acquired cardiomyopathies in experimental animals: mechanical, biochemical, and structural features.

Abstract: Evidence has been presented regarding alterations of contractile behavior muscle biochemistry, and ulstrastructure during the course of the hereditary hamster cardiomyopathy. Also, preliminary structural and mechanical data were presented on the acquired cardiomyopathy of diabetes mellitus in experimental animals. In the hamster model, contractile performance, measured as isometric tension and rate of tension development, was shown to be depressed throughout the course of the disease, whereas normalized force-velocity relationships returned to normal only during the compensated stages of hypertrophy. Force-frequency relationships were depressed in myopathic muscles, indicating the presence of alterations in the muscle activation system, namely, the biochemical and functional integrity of the sarcoplasmic reticulum. Analysis of the contractile proteins in myopathic muscle has revealed depressions of Ca2+ activity in purified myosin in addition to an independently increased neutral protease activity that results in the specific degradation of LC2 of myosin. Sympathetic time and norepinephrine turnover increase progressively during the course of the disease. These changes are accompanied by decreasing tissue levels of neorepinephrine and increasing levels of dopamine, indicating a shift in the rate-limiting step for norepinephrine synthesis. Alterations were also noted in nuclear protein composition and serotonin levels. Microscopically, the myolytic and calcification changes that characterize the hamster cardiomyopathy have been confirmed. In addition, contraction bands and lysosomal changes have been observed that may relate to cateholamine hypersensitivity. In the experimental model of diabetic cardiomyopathy, a significant alteration in relaxation process was demonstrated despite the fact that peak tension development and its rate of development were unaltered. Also, the length dependence of contractile behavior was altered when compared to that of age-matched controls, indicating a potential loss of contractility reserve. When animals with combined hypertension and diabetes were studied, bothe contraction and relaxation processes were affected to a greater degree.

Reproductive effects of halogenated aromatic hydrocarbons on nonhuman primates.

Abstract: During the past several years experiments have been conducted in this laboratory to determine the toxicologic effects in animals exposed to three halogenated hydrocarbons-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyls (PCBs) and polybrominated biphenyls (PBBs). TCDD and PCBs are considered to be worldwide environmental contaminants. PBBs have caused major environmental problems in the state of Michigan. The health implications of these compounds are further complicated by their extremely slow biodegradation and their ability to accumulate in body tissues and remain there for an indefinite period. As a result of their environmental and public health significance, a large amount of literature has been published on TCDD and PCB intoxication in humans and lower animals. There is also considerable research in progress to further clarify the toxicologic effects of the PBBs. However, there is a dearth of information on the effects of these halogenated hydrocarbons on reproduction in humans and closely related species, particularly when the exposure to these compounds is at low levels and occurs over an extended period. The rhesus monkey is a suitable animal model with which to study the effects of exposure to halogenated hydrocarbons. Many of the toxicologic signs produced by these halogenated hydrocarbons are similar to those observed in humans. Thus, the data obtained from research conducted on the nonhuman primate are helpful in postulating the injurious effects that may arise in the human population following exposure to these compounds. I n the presently reported research, the three compounds were evaluated for their toxicologic effects on nonhuman primates. Attempts have been made to simulate the levels to which humans may be exposed. Data are presented which indicate that low-level, long-term exposure to these compounds gives rise to reproductive abnormalities in the adult primate as well as fetal and neonatal toxicity.

Environmental mesothelioma in Turkey.

Abstract: The geologic structure of Turkey reveals that certain parts of Anatolia are rich in asbestos minerals. However, the literature concerning asbestos-related diseases was initially confined to case records of mesothelioma. The fact that asbestos could be considerably hazardous to health and create a major public health problem for this country was first suggested by the epidemiologic studies of the Chest Diseases Division of Hacettepe University carried out in asbestos mines and mills around MihalliqqikEskisehir and Sivas in 1972. In these studies, emphasis was placed on calcified pleural plaques and pulmonary fibrosis. The scope of these studies was widened to include the villages of Mihalliqqik and Maden-Elazig for investigation of the effects of environmental exposure to asbestos in peasants in rural regions. Similar surveys were conducted by Yazicioglu et al. in 1973-5 in southeastern Turkey. Our recent epidemiologic studies have revealed that asbestos-related diseases, primarily calcified pleural plaque (CPP), chronic fibrosing pleuritis (CFP), and malignant pleural mesothelioma (MPM), are endemic in some villages with or without asbestos deposits. This paper describes briefly the studies of the Chest Diseases Division of Hacettepe University of environmental asbestos-related diseases in Turkey.

Stylistic strategies within a grammar of style

Abstract: Interpersonal behavior is frequently regarded as unpredictable and spontaneous. We do not feel that we are following rules or even a preordained pattern in the way we talk to others, move, respond emotionally, work, think-all the varied aspects of what, following Shapiro (1965) we can call personal style. Indeed, some of us might be horrified at the idea that, in all our actions, we are governed by implicit rules, just as Chomsky (e.g., 1968) has shown we are in our linguistic behavior (and has thereby himself aroused horrified responses), and are as little aware of it. In this paper, assuming the validity of the assumption of generative grammar that linguistic behavior is rule-governed, I want to extend that claim to a variety of other kinds of behavior that can be subsumed under terms like “character,” “personality,” or “personal style.” I will argue that the same kind of evidence that indicates a need for grammatical rules relating two levels of linguistic structure exists for this wider range of human functioning. Needless to say, the argument that implicit rules guide our behavior denies us neither autonomy nor creativity: these rules are predictive schemata, descriptive rather than prescriptive. In this paper, drawing on previous work, I use as a principal example the distinction between men’s and women’s typical personal style, in American middle-class culture; but the argument holds for the behavior of any individual or group that is felt by its members and by outsiders to function as a cohesive unit. The reader may wonder whether there is any justification-beyond my personal whim and the convenience of having previous work to draw upon-for using women’s language as a paradigm or model for the purpose of illustrating the more general thesis of the existence of a grammar of style. To this I would make the rejoinder that it is as good as ’my, and I must choose one. Thus, Chomsky (1965) chose the modal auxiliary system of English as his example attesting to the need for a grammar of the transformational type, although other examples might as well have been used. But even more to the point, women’s language is accessible to every member of this culture as a stereotype. Whether the stereotype is equally valid for all women is certainly debatable; but the fact of its existence, overt or subliminal, affects every one of us and its assumptions are generally agreed on. Hence it provides an especially clear case. And while women’s language, and women’s style, have long been recognized and commented upon as an aggregate of traits, not much has been done toward accounting for why these particular traits cluster togetherthat is, toward constructing an explanatory, as opposed to a merely descriptive, mode. I shall attempt a beginning of such a systematization: that is, I shall try to make pre-

Asbestosis among household contacts of asbestos factory workers

Abstract: Equally ubiquitous in the environment as industrial chemical wastes’ are inorganic microparticles such as asbestos. The environmental burden of asbestos pollution is a recent phenomenon which has grown with the rapid expansion of asbestos-utilizing industries.* The health consequences of poorly controlled occupational exposures to chemicals and dusts now found in the general environment have been known in many instances for well over 100 years.’ Reports of overt disease (usually seen only with occupational exposure) among nonoccupationally exposed individuals have frequently been considered medical curiosities when they appeared in the medical literature. However, the full extent of the health risks due to nonoccupational exposure to toxic agents is not known, for it is uncommon to inquire into the neighborhood residence history or occupation and exposures of a patient’s household contacts when investigating symptoms of a disease. The effects of such exposures may be mild or subclinical manifestations which are only contributory to a current health problem and their role goes unrecognized. In 1976, we reported on a systematic investigation of one such non-occupational exposure to asbestos dusts4 The group studied consisted of household contacts of workers in an asbestos factory manufacturing amosite asbestos insulation materials between 1941 and 1954. None of those reported had personal occupational exposure to asbestos. Yet 35% had asbestos-associated radiographic abnormalities. A source of home contamination in individual exposure was postulated as resulting from dust adhering to shoes, hair, and workclothes brought home for laundering. Changerooms and company laundered coveralls were not available a t this plant. We reported the identification of four pleural mesotheliomas among the family contacts of the 1,664 workers who were employed at some time by the factory. Since that time one additional pleural mesotherlioma death has occurred, raising the total mesothelioma deaths to date among the group under observation to five. This report extends the continuing clinical investigation of this cohort.

Toxicopathology characteristics of the halogenated aromatics.

Abstract: Halogenated dibenzo-p-dioxins, dibenzofurans, biphenyls and napthalenes are structurally related compounds (FIGURE 1) of considerable environmental interest because of their ubiquitous occurrence, persistance in the environment, possible magnification in the food chain and relatively high toxicity of the more potent isomers. Numerous reports can be found that describe the lesions in various species of animals caused by these chemicals using various dosing regimens given over various periods of time. The purpose of this paper is to review these lesions in the common laboratory animal species including nonhuman primates, and discuss their apparent commonality.

A mathematical model for the growth of a single bacterial cell

Abstract: Changes in bacterial cell size and shape due to changes in the abiotic environment have been observed for decades.’ The changing surface-to-volume ratio has the potential of profoundly affecting cell Yet very few of the multitude of mathematical models suggested for the description of bacterial growth6’ allow for the possible inclusion of the effects of changes in cell geometry; most are models of how a whole culture will grow. The purpose of this paper is to describe a mathematical model for the growth of an individual cell. Other advantages of an individual cell model are the ease with which temporal and spatial events in the cell division cycle can be included. It is impossible to include such information in nonsegregated mathematical models and often computationally difficult to include such events in segregated models. Cell structure and the interactions of major metabolic pathways can readily and accurately be included in a single-cell model. Although similar information can be incorporated in whole culture models, such efforts have often been marred by subtle errors in model formulation’ which would have been readily avoided in formulating an individual cell model. Single-cell models do have limitations. They are accurate representations of the growth of a bacterial culture only if the moments of distribution of cellular properties higher than the first-order are not important. The single-cell model should accurately represent the growth of a synchronous culture and perhaps growth in a steady-state continuous culture. However, such an assumption would obviously fail in a culture where only 50% of the cells were viable. Such a limitation could conceivably be removed by dividing the culture into different subpopulations based on, for example, cell size and composition, and assigning one or more individual cells to that fraction. Several models for the growth of an individual cell have been po~tulated.~*~-” These models all contain one or more arbitrary constraints on the computer “growth” of the cell. Examples of such constraints are mode of growth (exponential), timing of cell division, culture conditions (balanced growth only), no explicit accounting of the abiotic environment (e.g. nutrient uptake), and cell shape. In this paper we present for the first time a single-cell model unconstrained in any way by the investigator. All that needs to be specified is the initial nutrient composition in the medium and temperature and pH. Cell growth, DNA initiation, crosswall formation, changes in cell size and

Axon-Schwann cell relationships in neuropathies of mutant mice.

Abstract: Interactions between axons and Schwann cells are important in normal peripheral nerve and in acute and chronic neuropathies.' In normal nerves, axons influence the proliferation of Schwann cells,'-* their differentiation into myelin-producing or unmyelinated cells,:'-$ and the thickness 9. lo and length l1 of their myelin sheaths. Conversely, Schwann cells have important effects on axons. Schwann cells may supply nutrients and trophic factors,', l 2 I * modulate the distribution of ions and neurotransmitters,15v 16 and influence the location of sodium channels along the axonal plasma membrane." Acute alterations in axons or Schwann cells further illustrate the interdependence of these components of peripheral nerve. Axonal transection leads to breakdown of the myelin sheath and Schwann cell multiplication,1s while exposure of nerves to compression, toxic substances, or immunologic agents may damage Schwann cells and cause demyelination, Schwann cell m~l t ip l ica t ion ,~~ and changes in the size of axons within the demyelinated segments.2a-25 Axon-Schwann cell interactions are also important in more protracted demyelinating neuropathies. Based on indirect evidence derived from detailed quantitative histologic analysis of the distribution of segmental demyelination and axonal degeneration in human nerve biopsies, it has been suggested that axonal abnormalities cause the failure of Schwann cells to maintain myelin in certain neuropathies,26 while the Schwann cells themselves are responsible for other demyelinating disorders.27 Both axons and Schwann cells are likely affected in other neuropathies. Techniques are now available that permit a more direct analysis of axon and Schwann cell interdependencies in normal and pathologic nerves. In tissue culture, neurons and Schwann cells have been separated and recombined to study normal Schwann cell proliferation and myelination.?, ?* * f i I n vivo combinations of axons and transplanted Schwann cells, each originating from a different animal or from animal and human nerves, have also been used to study Schwann cell differentiation 5 . and the pathogenesis of hereditary neuropathies.?Y39

Clinical findings among pcb‐exposed capacitor manufacturing workers*

Abstract: The polychlorinated biphenyls (PCBs) constitute a group of chemically stable compounds with wide use in industry since the 1930s, especially as dielectric fluids in capacitors and transformers.’ Paints and other surface coatings such as plastics and varnishes may also contain PCBs. These are also a component of carbonless carbon paper. Although PCBs have been used for almost half a century, and despite several experimental studies on biologic activity of P C B S , ~ ~ few reports concerning the effects of occupational exposure to PCB compounds have a ~ p e a r e d . ~ ~ Increased concern with these compounds, however, followed when it was found that they were ubiquitously distributed in the environment.”.” Simultaneous with these findings came the reports of adverse human health effects resulting from the accidental ingestion of PCBcontaminated rice oil in Japan. The disease called Yusho (Japanese for “oil disease”) became the clinical and pathologic paradigm for PCB-induced effects in humans.’’

Human health effects from accidental release of tetrachlorodibenzo-p-dioxin (TCDD) at Seveso, Italy

Abstract: This paper is a progress report of the epidemiologic work carried out under the supervision of the Lombardy Regional Authority during the two years elapsed from the accident in a TCP-producing factory (ICMESA) in Meda (Italy), which resulted in the contamination of several towns of a large, densely populated area called the Brianza di Seveso with a total population of 220,000 inhabitants. A wide follow-up program is in progress in the Seveso area; it includes a clinical screening of the population living in the contaminated area and longitudinal and systematic health control of different groups at risk; a long-term morbidity cohort study has been also undertaken. TCDD exposure following the ICMESA accident resulted in an increased chloracne frequency. Neurologic examinations showed both signs of idiopathic subclinical neurologic damage and cases of clinically detectable idiopathic polyneuropathy in adults. A limited percentage of idiopathic hepatomegaly was reported to be present on clinical investigation; no information, however, is given on the criteria by which the hepatomegaly was investigated. Some alterations were observed in some exposed people in one or more liver tests (mainly transaminases and gamma-GT). So far, immunologic investigations, cytogenetic examination and embryomorphology analysis on cases of therapeutical or spontaneous abortions have not given abnormal results.

The structure-activity relationships of halogenated biphenyls as enzyme inducers.

Abstract: Polyhalogenated biphenyls induce microsomal mixed-function oxygenases in many species including man. They can be divided into two classes of inducers. 3,4,5,3',4', 5'-Hexa- and 3,4,3',4'-tetrachlorobiphenyls appear to interact with the TCDD receptor, albeit at 100 to 1,000 times the dose. The structure required for 3-MC (TCDD)-type induction seems to be the presence of at least two adjacent halogens in the lateral positions (meta and para) of the benzene rings, and an absence of halogens in the ortho positions adjacent to the biphenyl bridge. It is likely that halogenation of the ortho positions prevents binding by blocking planar configuration. These isomers, although less toxic than TCDD, are much more toxic than other PCB isomers. Most halogenated biphenyl isomers are phenobarbital type inducers or are inactive. The structure-activity relationship for this type of induction is less clear, but active isomers include 2,4,2',4'-tetra-; 2,4,5,2',4',5'-; 2,3,4,2',3',4'-; 2,3,5,2',3'.5'-and 2,4,6,2',4',6'-hexachlorobiphenyls and 2,4,5,2',4',5'-hexabromobiphenyl. The inactivity of many of the lower chlorinated isomers as inducers (mono-through tetrachloro-) may be related to their rapid metabolism. The cytochrome which is induced by commercial PCB and PBB mixtures appears to be identical to a mixture of cytochromes from phenobarbital- and 3-MC-treated rats. These structure-activity relationships suggest that the "mixed inductive" effects and much of the toxicity of PCB and PBB mixtures are due to the presence of compounds related structurally to the active chlorinated dibenzofurans or 3,4,3',4'-tetrachlorobiphenyl.

Against our will: male interruptions of females in cross‐sex conversation*

Abstract: A disturbing suggestion is sometimes made to the effect that women “ask for” discriminatory and even brutal treatment by men. In lay communities, the most blatant form of this suggestion (i.e., women invite rape) is increasingly deplored.’ However, when they are made in the context of empirical inquiry, suggestions with similar implications may go overlooked. In discussions of the initiation of simultaneous talk (cf. Zimmerman and West, 1975; West and Zimmerman, 1977) reports of males’ systematic interruptions of females often draw questions regarding women’s part in creating, sustaining or inviting men’s interruptions of their utterances. For example, I have observed females falling silent for longer and longer durations after repeated interruptions by males (Zimmerman and West, 1975: 117-124). One interpretation of this observation is that females engage in a form of silent protest against male intrusion into their turns. Another explanation I have heard offered for this finding is that females’ silence “encourages” males’ interruption. In fact, the topics women talk about, the “style” of “women’s talk,” and the extent to which they protest when men violate their conversational turnspace have all been offered as reasons for males’ interruptions of females. Male dominance in conversation might be likened to our cultural (and sometimes legal) conceptions of rape. Women are seen by some to invite rape by the clothes they wear, the “style” of “women’s walk” and, especially, for their failure to “put up a fight.”* However, the extent to which we find empirical bases for the existence of a struggle is the extent to which dominance in conversation and physical rape may both be defined as conflict situations and not willing submission.

STUDIES OF THE MECHANISMS OF TOXICITY OF 2,3,7,8‐TETRACHLORODIBENZO‐p‐DIOXIN (TCDD)

Abstract: The major interest of our laboratory relative to TCDD has been the biochemical mechanism or mechanisms of acute lethality of this compound. As has been noted by other speakers a t this conference, the major feature of a single lethal dose of TCDD across all animal species is a progressive weight loss and general debilitation of the animal with death occurring in a few weeks or a few months. Gross and histopathology have not, to date, provided information that has been particularly useful in focusing biochemical investigations. For example thymic involution is a consistent finding in all animal species. However, numerous investigations have yet to provide information as to the mechanism of thymic involution. Also the major pathologic effect of TCDD in mice and rats is degeneration of the liver. However, the degree of injury to the liver does not appear to be sufficient to be the cause of death. In addition, in the guinea pig, the species most sensitive to TCDD, little damage to the liver is seen. The extreme lethality of TCDD, particularly i n the guinea pig, suggests that TCDD is probably affecting some fundamental process in animal cells leading to a general disfunction of those cells. Studies of the biochemical effects of TCDD intoxication have focused on some of these fundamental processes. Thus, Greig and coworkers’ have shown that liver DNA synthesis stimulated by partial hepatectomy of rats does not appear to be inhibited by TCDD. Also Lucier et d2 have shown that state 3 and state 4 respiration of liver mitochondria, the process by which ATP is synthesized, and ADP:O are not affected in TCDD-treated rats. In our laboratory we have also examined state 3 and state 4 respiration of liver mitochondria from terminally i l l rats treated with TCDD and find state 3 and state 4 respiration is progressing normally. Work by Cunningham and Williams’ indicates that protein and lipid synthesis also appear to be continuing normally in TCDD-treated rats. Work by Vos el ~ 1 . ~ has indicated that TCDD has a marked effect on the immunocompetence of young rodents. However, work by Grieg el al.’ has shown that specific pathogenfree and germ-free rats are as susceptible to the lethal effects of TCDD as normal rats. Thus the reduced immunocompetence is not likely the cause of the acute lethality of TCDD. We have carried out a number of studies examining for effects of TCDD on other fundamental biochemical processes within mammalian cells. It must be stated at the outset that these and other studies have not yet provided us with information on which to base a logical hypothesis for the mechanism or mechanisms of the acute lethal effects of TCDD. However, the data that have been forthcoming from the various studies, in conjunction with data from future experiments, may eventually allow investigators in this field to postulate a mechanism for the acute lethal effects of TCDD. One of the initial studies in our laboratory was based on an article by Jackson’ who reported that TCDD at a concentration of 0.1 pg/liter in the culture medium caused a significant inhibition of all phases of mitosis of dividing endosperm cells of the African

Asbestos disease in United States shipyards.

Abstract: In 1968, the possibility that asbestos-associated disease might be a n important problem of shipyard workers was suggested. Harries' reported five cases of pleural mesothelioma among civilian employees of the Royal Navy Dockyard at Devonport. It was disturbing that none of the patients was an \"asbestos worker\"; rather, they were in other trades (boilermaker, shipwright, laborer, fitter, welder) which work in shipyards together with asbestos workers, but do not themselves often use asbestos. In addition, cases of asbestosis were noted. In the same year, Stumphius2 described similar findings at the Royal Van der Schelde yard in the Netherlands. Again, the mesotheliomas were among workers other than those in the usual asbestos trades. Since these initial communications, experiences have been detailed in many parts of the world identifying characteristic asbestos-associated disease among former shipyard Diseases have included pleural mesothelioma, peritoneal mesothelioma, pleural and parenchymal asbestosis and lung cancer. Curiously, there have been relatively few reports from the United States, although it is known that widespread asbestos exposure occurred in our shipyards during World War 11'6*'7 and serious asbestos disease had been found among insulation workers employed in shipyards.\" Further, evidence has been available that workers employed in manufacturing the asbestos insulation used in naval vessels during and after World War 11, have increased incidence of asbestos-associated cancer. as well as asbest~sis . '~-~ '

Cohort study of Michigan residents exposed to polybrominated biphenyls: epidemiologic and immunologic findings.

Abstract: Polybrominated biphenyls (PBB) were dispersed widely in Michigan by a 1973 shipping accident in which PBB was introduced into cattle feed. Human exposure resulted principally from ingestion of contaminated dairy food products. To determine whether PBB exposure has or will cause acute or chronic illness, a prospective cohort study of 4545 persons has been undertaken. Three exposure groups were sought; all persons living on PBB-quarantined farms; persons who had received food directly from such farms; workers (and their families) engaged in PBB manufacture. Enrollment rates were 95.6, 95.1 and 78.0%. Also enrolled were 725 persons with low-level PBB exposure. All were queried concerning 17 symptoms and conditions related possibly to PBB. Venous blood was drawn on 3639 and analyzed for PBB by gas chromatography. Mean serum PBB levels were 26.9 ppb in quarantined farm families, 17.1 in recipients, 43.0 ppb in workers, and 3.4 ppb in the low exposure groups. No associations were found between serum PBB levels and symptom prevalence rates. To evaluate peripheral lymphocyte function, T and B cell quantitation and in vitro responses to 3 nonspecific mitogens were studied in 34 persons with highest PBB levels (mean, 787 ppb), and in 56 with low values (mean, 2.8 ppb). No statistically significant differences in lymphocyte number or function were noted.

Neuropathology of “spinning syndrome” induced by prenatal intoxication with a pcb in mice*

Abstract: A striking motor dysfunction, "spinning syndrome," developed with a high frequency in weaning mice whose dams received oral 3,4,3',4'-tetrachlorobiphenyl (4-CB) during gestation (day 10 through day 16). The syndrome is permanent and is characterized by swift circling movements sustained in one direction at a minimal rate of 40 turns/min (usually 50 to 150 turns/min), restlessness, and hyperkinesia. Twenty-four spinners and 4-CB nonspinners and age-matched controls were subjected to histopathologic, histofluorescent, histochemical, and electron microscopic studies. The most reliable histopathologic marker for prenatal 4-CB injury to the CNS is the presence of cylindrical CNS peninsulas (CCPs) in the spinal and cranial nerve roots. The CCPs consist of either CNS-type myelinated fibers, unmyelinated fibers, or astroglial bundles in varying proportions, and are enclosed by a basement membrane. The CCPs are also observed in 4-CB nonspinners but in none of 12 controls studied. A selective defect in synaptogenesis induced prenatally by 4-CB is proposed as the primary event pursuant to the development of the CCPs, while interference with synaptogenesis may have occurred selectively in the striatonigral dopaminergic system. This is suggested by electron microscopy on the nucleus accumbens and also by the responses to administration of dopaminergic agonists and antagonist. The 4-CB induced clinico-pathologic anomaly may serve as a singular model for understanding human neurologic disorders, in particular, Werdnig-Hoffmann disease and minimal brain dysfunction syndrome.

Mortality among shipyard workers in genoa, italy

Abstract: The dockyards of Genoa are exposed to many known or suspect carcinogenic agents, namely, asbestos, silica, polycyclic aromatic hydrocarbons, and halogenated hydrocarbons; other possibly harmful substances are trace amounts of aromatic amines, welding smokes, paints, and lipid-removing solvents. A cohort study of causes of death of 2190 dockyard workers in Genoa was conducted between January 1, 1960 and December 31, 1975. Mortality rates were calculated for 20 different occupational categories, for which there exist different levels of exposure to noxious substances. Two control groups were selected: the general male population of Genoa and all male employees (462) of San Martino Hospital, Genoa for the same period of time. Causes of death that demonstrated significant excesses for both control groups were: cancer of the colon, excluding the rectum; cancer of the larynx; cancer of the lung, bronchus, and trachea; cancer of the kidney, urinary bladder, and other urinary organs; respiratory diseases; and cirrhosis of the liver. The data obtained from these 20 job categories revealed different types and levels of risk for various carcinogenic agents.