Showing papers by "Tufts University published in 1973"

Endocrine and metabolic effects of experimental obesity in man.

Abstract: Publisher Summary This chapter discusses the endocrine and metabolic effects of the experimental obesity in humans. All the changes witnessed in spontaneous obesity except for the increase in adipocyte number have been reproduced in experimental obesity. It has been found that endocrine and metabolic changes are associated with gain in weight. Normal subjects fattened by eating a mixed diet require more calories in relation to their body surface area for maintenance of the obese state than they require when at their natural weight and also more than the spontaneously obese generally require. There are marked differences in the ability of normal individuals to gain weight by taking calories in excess of those required for maintenance. When weight is gained by normal increase in the intake of fat alone, there is a higher proportion of weight gained to calories ingested, and the weight gained may be maintained by an intake that is no greater than that required to maintain the initial weight. The chapter also describes the hormonal and circulating factors that affect the resistance to insulin in experimental obesity. It also presents evidence for cellular factors in resistance to insulin in experimental obesity and their response to gain in weight and to dietary carbohydrate.

An acute effect of cigarette smoking on platelet function. A possible link between smoking and arterial thrombosis.

Abstract: In a controlled, double blind study, the smoking of a single cigarette has been shown to increase the platelet's response to a standard aggregating stimulus. This phenomenon appears to be specifically related to the inhaling of tobacco smoke; it does not follow the smoking of lettuce leaf filled cigarettes. The platelet effect seems independent of the rise in plasma free fatty acids which follows cigarette smoking. Smoking-induced potentiation of platelet aggregation may help to explain the increased incidence of arterial thrombi and/or atheromatous plaques in cigarette smokers.

The functions of sleep

Abstract: Theories of the function of sleep and review of sleep research, and study of mind-body relationship. Effects on sleep of stress, activity, drugs. Role of dreaming.

Effect of Reversible Inhibition of Deoxyribonucleic Acid Synthesis on the Yeast Cell Cycle

Abstract: Hydroxyurea (HU) preferentially inhibited deoxyribonucleic acid (DNA) replication and division in Saccharomyces cerevisiae. Growth, ribonucleic acid synthesis, and protein synthesis were less sensitive to this drug. Upon addition of HU, cells underwent one cycle of budding and the nuclei migrated into the necks between the mother cells and buds. Neither the nucleus nor the cells divided. Removal of HU allowed immediate resumption of DNA synthesis. Nuclear division, budding, and cell division occurred 1.5, 2, and 4 hr, respectively, after HU was removed. If protein synthesis was blocked at the time HU was removed, budding and cell division did not occur. These results were interpreted to indicate that HU prevents accumulation of the potential to initiate a new cell cycle. Images

Heart muscle viability following hypoxia: protective effect of acidosis.

Abstract: The mechanical performance of hypoxic heart muscle is further depressed by an acid pH. In contrast to preparations at normal or alkaline pH. however, hypoxic preparations at acid pH do not develop contracture and exhibit full recovery of mechanical activity upon reoxygenation.

Protective action of carotenoid pigments against photodynamic damage to liposomes.

Abstract: — When liposomes (a model membrane system) are subjected to a dye-sensitized photo-oxidation, lysis, as measured by glucose leakage or a change in light scattering, results. Before lysis occurs, the membrane lipids undergo peroxidative damage, as determined by the appearance of malondialdehyde. Carotenoids incorporated into the liposomal membrane protect against both lipid peroxidation and liposomal lysis. Other 1O2 quenchers and free radical absorbers also protect liposomes from photodynamic damage.

Inorganic Phosphate Transport in Escherichia coli: Involvement of Two Genes Which Play a Role in Alkaline Phosphatase Regulation

Abstract: Two classes of alkaline phosphatase constitutive mutations which comprise the original phoS locus (genes phoS and phoT) on the Escherichia coli genome have been implicated in the regulation of alkaline phosphatase synthesis. When these mutations were introduced into a strain dependent on a single system, the pst system, for inorganic phosphate (Pi) transport, profound changes in Pi transport were observed. The phoT mutations led to a complete Pi− phenotype in this background, and no activity of the pst system could be detected. The introduction of the phoS mutations changed the specificity of the pst system so that arsenate became growth inhibitory. Changes in the phosphate source led to changes in the levels of constitutive alkaline phosphatase synthesis found in phoS and phoT mutants. When glucose-6-phosphate or l-α-glycerophosphate was supplied as the sole source of phosphate, phoT mutants showed a 3- to 15- fold reduction in constitutive alkaline phosphatase synthesis when compared to the maximal levels found in limiting Pi media. However, these levels were still 100 times greater than the basal level of alkaline phosphatase synthesized in wild-type strains under these conditions. The phoS mutants showed only a two- to threefold reduction when grown with organic phosphate sources. The properties of the phoT mutants selected on the basis of constitutive alkaline phosphatase synthesis were similar in many respects to those of pst mutants selected for resistance to growth inhibition caused by arsenate. It is suggested that the phoS and phoT genes are primarily involved in Pi transport and, as a result of this function, play a role in the regulation of alkaline phosphatase synthesis.

Cost allocation for a spanning tree

Abstract: The problem of allocating cost in a spanning tree network is considered. A number of possible schemes are surveyed, and critically analyzed. Methods are suggested that are preferred given different emphases among the criteria for such a function.

Diagnostic Electrocardiographic Sequences in Acute Pericarditis Significance of PR Segment and PR Vector Changes

Abstract: Diagnostic electrocardiographic patterns were analyzed in 50 consecutive patients who had unequivocal clinical evidence of acute pericarditis. Distributions of P and QRS, and of P-R segment, ST-segment and T wave changes were plotted by lead and by mean frontal vector (A). Transient gross deviations of P-R segments, mainly in Stages 1 and/or 2, occurred in 41 patients (82%) and could produce an optical illusion of ST elevations when the J-points were actually on the baseline. A P-R was close to 180° opposite to A P and was not related to P wave or heart rate changes. In Stage 1, A ST tended to be concordant with A QRS and A T. T wave inversions in Stage 3 produced an A T which was distributed over an arc of 210° with no range of predilection. Transient increase in magnitude of a normally oriented PR vector was consistent with the subepicardial atrial injury of acute pericarditis. It is the analogue of the classic Stage 1 ST-segment abnormalities of subepicardial ventricular injury and was equally a...

Scanning electron microscopy of human T-cell and B-cell rosettes.

Abstract: The surface of human lymphocytes was studied by scanning electron microscopy. Lymphocytes from peripheral blood or tonsils were identified as thymus-derived (T) cells or thymus-independent (B) cells by virtue of the ability of T cells to form rosettes with sheep red cells and for some B cells to form rosettes with complement-coated human red blood cells. The rosettes were gluteraldehyde fixed and subsequently examined by scanning electron microscopy. Lymphocytes, both rosetting and non-rosetting, had multiple surface microvilli. As compared to rosetting B cells, rosetting T cells were generally smaller and smoother, with fewer and shorter microvilli. Microvilli appeared to be the sole cell-cell contact point between T cells and sheep red blood cells; B cells made contact through both villous and non-villous areas. Microvilli are an important mode of primary contact between lymphocytes and the outside world. (N Engl J Med 289:548–551, 1973)

Effect of Rifampin on the Structure and Membrane Attachment of the Nucleoid of Escherichia coli

Abstract: Deoxyribonucleic acid (DNA) of Escherichia coli was found to be attached to the cell membrane at about 20 points. This was determined by fractionation of X-irradiated cells with the M band (magnesium-Sarkosyl crystals) technique. The number of attachment points was computed from the relationship between the amount of DNA in M bands and the number of double-strand breaks introduced by the X-ray treatment. The number of attachment points was decreased fourfold by treatment of cells with rifampin. This effect was apparently due to the action of the drug on ribonucleic acid (RNA) polymerase since the drug did not affect a mutant whose RNA polymerase is resistant to rifampin. This suggests that there may be two classes of attachment points of DNA on the membrane, some of which are removed by rifampin treatment and some which are not. Rifampin treatment also resulted in the uncondensing of isolated nucleoids and in an axial appearance of the nucleoids in ultrathin sections. The results suggest that RNA polymerase plays a role, direct or indirect, in maintaining the structure of the bacterial nucleoid and in some of its attachment to the membrane.

Ultraviolet-Sensitive Mutator Strain of Escherichia coli K-12

Abstract: An ultraviolet (UV)-sensitive mutator gene, mutU, was identified in Escherichia coli K-12. The mutation mutU4 is very close to uvrD, between metE and ilv, on the E. coli chromosome. It was recessive as a mutator and as a UV-sensitive mutation. The frequency of reversion of trpA46 on an F episome was increased by mutU4 on the chromosome. The mutator gene did not increase mutation frequencies in virulent phages or in lytically grown phage λ. The mutU4 mutation predominantly induced transitional base changes. Mutator strains were normal for recombination and host-cell reactivation of UV-irradiated phage T1. They were normally resistant to methyl methanesulfonate and were slightly more sensitive to gamma irradiation than Mut+ strains. UV irradiation induced mutations in a mutU4 strain, and phage λ was UV-inducible. Double mutants containing mutU4 and recA, B, or C were extremely sensitive to UV irradiation; a mutU4 uvrA6 double mutant was only slightly more sensitive than a uvrA6 strain. The mutU4 uvrA6 and mutU4 recA, B, or C double mutants had mutation rates similar to that of a mutU4 strain. Two UV-sensitive mutators, mut-9 and mut-10, isolated by Liberfarb and Bryson in E. coli B/UV, were found to be co-transducible with ilv in the same general region as mutU4.

Disulfiram maintenance in outpatient treatment of alcoholism.

Abstract: Alcoholic outpatients during their first visit were questioned about the use of disulfiram (Antabuse) to control their drinking. Those who accepted disulfiram (49 of 121 patients) were randomly assigned to one of four treatment methods: (1) given disulfiram once a week; (2) given disulfiram twice weekly under supervision (disulfiram maintenance); (3) not given disulfiram, attending once a week; and (4) not given disulfiram, attending twice weekly. Patients who refused disulfiram were also told to come either (5) once or (6) twice weekly. In addition, all patients were offered standard clinic management which consisted of counseling, psychotherapy, and medication. During the eight-week follow-up period, disulfiram maintenance was shown to be significantly superior in keeping patients in treatment and encouraging their sobriety. The remaining five groups behaved essentially the same in terms of clinic attendance.

The effects of long term administration of psychotropic drugs on human sleep. II. The effects of reserpine.

Abstract: Reserpine 0.50 mg/day was administered over a period of four weeks to a group of normal young males. Laboratory sleep, home sleep, and mood were studied throughout the period of administration and for a month afterwards. Results were compared to identically administered long-term placebo. Total sleep was slightly increased at first; D-time and the number of D-periods were clearly increased by reserpine. These effects were prominent from day three, through the second week. D-latency and length of the sleep-dream cycle was decreased. Subjective aspects of sleep were not greatly changed. Mood scales indicated an increase in “fatigue” and a decrease in “vigor” during reserpine administration.

Cell‐mediated and serum blocking reactivity to tumor antigens in patients with malignant melanoma

Abstract: The reactivity of human lymphocytes, separated from peripheral blood by procedures involving sedimentation through plasmagel and settling on a glass surface, on survival or growth of melanoma tumor cells is reported Assay of reactivity was by either a colony inhibition in dilute agar (GEL) technique or a microcytotoxicity assay (MC) In 54 experiments with lymphocytes from normal donors, inhibition of melanoma cell viability, as compared to growth in medium alone, was seen 25 (463%) times, stimulation was observed seven (129%) times and no effect 22 (407%) times These results were not influenced by matching of the lymphocyte and tumor-cell donor for ABO blood group Inhibition was seen less often, however, in tests with the GEL method than in those with the MC assay Eighty-two experiments assessed the effect of lymphocytes from melanoma patients on melanoma cell viability Inhibition to an extent greater than that of normal lymphocytes tested at the same time was seen 65 (793%) times There was no difference in the frequency of detection of inhibition with lymphocytes from patients with local, regional, or widespread disease, although the percentage inhibition was less in the latter group No differences were seen between patients with clinically active versus inactive disease Only one of five patients who were within a week of death was reactive Reactivity was detected as frequently with allogeneic as with autochthonous melanoma target cells Serum blocking factor (SBF), capable of inhibiting in vitro cell-mediated reactivity to melanoma tumor cells, was assayed in serum from melanoma patients at various stages of disease SBF was detected at some time in 30% of patients with local, 889% with regional, and 800% with widespread disease It was found in 429% of those with clinically inactive and 706% with active melanoma However, detection of SBF was found to fluctuate from sample to sample taken at different times during the course of disease in individual patients regardless of clinical status The importance of sequential determinations of SBF activity for patient assessment is stressed

The effects of benzodiazepines on aggression: reduced or increased?

Abstract: The effects of various benzodiazepines on animal models of aggression are presented. The differences in response noted after single dose or after chronic drug administrations are stressed. The implications for predicting responses to these drugs in humans are discussed.

Carcino-Foetal Human Liver Ferritins

Abstract: FERRITIN is an iron-storage protein found in the cytoplasm of a wide variety of plant and animal cells1,2. Structurally, the molecule comprises a hollow protein shell, apoferritin, composed of 20 or 24 subunits, within which variable amounts of inorganic iron may be sequestered. These subunits may not be chemically identical since multiple molecular forms of differing charge, isoferritins, have been found in several organs by electrophoresis3,4 or electrofocusing5,6. Although the structural relationship of the isoferritins is unclear, these findings raise the possibility that the charge differences may represent primary structures coded by different genes. In addition to the isoferritins found in normal cells, an “abnormal” ferritin has also been found in malignant cell lines7 and in livers of tumour bearing animals8,9. As part of our investigations into tumour specific and embryonic antigens, we have examined the isoferritin profile in human hepatoma and compared it to that found in normal adult and foetal liver. Here we supply evidence for a unique isoferritin species in human hepatoma that is not present in normal adult liver. This tumour-specific isoferritin may correspond to a similar isoferritin found in foetal liver in early gestation.

MHPG excretion in depressive disorders: relation to clinical subtypes and desynchronized sleep.

Abstract: The urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) was significantly lower in patients with manic-depressive depressions than in patients with chronic characterological depressions. There was an inverse relationship between MHPG excretion and the amount of time spent in desynchronized sleep, particularly in the manic-depressive disorders. Excretion of MHPG was not related to the degree of retardation, agitation, or anxiety in these patients.

Prevention of Murine Lupus Nephritis by Carrier-Dependent Induction of Immunologic Tolerance to Denatured DNA

Abstract: Four nucleosides were covalently bound to isogeneic mouse immunoglobulin G (IgG) and injected into New Zealand mice. Mice that received the tetranucleoside isogeneic IgG from birth to 5 months of age failed to make antibody to denatured DNA. In contrast, mice that were similarly treated with tetranucleoside bovine serum albumin or tetranucleoside free of carrier produced the same amount of antibody to denatured DNA as did untreated mice of this strain. Mice that were rendered tolerant to denatured DNA by tetranucleoside isogeneic IgG failed to develop the chronic membranous glomerulonephritis that characterizes the renal lesions in animals of this strain.

Glutamic acid production with gel‐entrapped Corynebacterium glutamicum

Abstract: A glutamic acid producing microorganism (Corynebacterium glutamicum) is entrapped in a polyacrylamide gel. These immobilized microorganisms were used to produce glutamic acid in successive batches of fresh medium. Free microorganisms similarly used produced much less glutamic acid under similar conditions.

Immunologic rejection of diethylnitrosamine-induced hepatomas in strain 2 guinea pigs: participation of basophilic leukocytes and macrophage aggregates.

Abstract: The morphologic events associated with the immunologic rejection by strain 2 guinea pigs of ascites variants of two lines of diethylnitrosamine-induced tumors have been studied by light and electron microscopy. Tumor injection sites in the skin of control animals exhibited clusters of viable, actively mitotic tumor cells along with a modest inflammatory infiltrate composed of lymphocytes, macrophages, neutrophils, and rare basophils. In contrast, similar injections of either tumor line in specifically sensitized guinea pigs elicited typical delayed-type skin reactions associated with tumor cell necrosis and a more extensive inflammatory infiltrate including a selective increase in the number of basophilic leukocytes (12%, line 1, or 23%, line 10, of total inflammatory cells). That basophils may have a role in tumor resistance in vivo is suggested by the close anatomic associations observed between basophils and tumor cells, and by the fact that basophils were the only inflammatory cell to demonstrate a relative increase in frequency in the lesions of sensitized as compared with control animals. Moreover, intraperitoneal injection of line 1 tumor in specifically sensitized animals elicited a striking basophilia within 24 h. Unlike macrophages, basophils did not phagocytose tumor cells but did evidence occasional extrusion of granules and frequently exhibited loss of granule staining density, a change that may be related to release of mediator substances. Electron microscope studies of line 1 tumor rejection in the peritoneal cavities of specifically sensitized guinea pigs demonstrated aggregations of "activated" macrophages, lymphocytes, basophils, and damaged or dead tumor cells. These aggregates, held together by complex interdigitations of macrophage villi, closely resembled those occurring in vitro among peritoneal exudate cells whose migration from capillary tubes was inhibited by migration inhibition factor (MIF). Moreover, cells in these aggregates, as well as macrophages inhibited by MIF in vitro, lacked a normal coating of cell surface material.