Showing papers by "Icahn School of Medicine at Mount Sinai published in 1975"

Induction of human endometrial estradiol dehydrogenase by progestins.

Abstract: Estradiol-17beta dehydrogenase activity in proliferative human endometrium (average of 1.5 nmole of estrone formed from estradiol/mg protein/h) was stimulated as much as as 6-fold during incubations of tissue slices in culture medium containing progesterone. Stimulation was already detectable at 7 h and the highest activity values were reached at 48-72 h of incubation in the presence of excess progesterone. Maximal stimulation was achieved with concentrations of the hormone of 0.25 mug/ml or higher. At concentrations approximately equal to midluteal plasma levels (20 ng/ml) more than 50% of the maximal response was observed. Norgestrel (17alpha-ethynyl-18-methyl-19-nortestosterone) was also effective in inducing enzymatic activity. The similarity of the effects obtained with progesterone (a possible substrate for estradiol dehydrogenase) and the synthetic progestin indicates that the stimulation of enzymatic activity was not due to substrate induction. Addition of estradiol to the culture medium had no influence on the activity of the enzyme. The induction of estradiol dehydrogenase by progesterone was inhibited by puromycin or actinomycin D. These observations indicate that progestational agents increase the rate of de novo synthesis of the enzyme. Stimulation of endometrial estradiol dehydrogenase was also observed after 2-3 day oral administration of medroxyprogesterone acetate to women in the follicular phase. In contrast, the enzymatic activity in endometrium obtained from women taking estrogens was found to be as low as in normal proliferative tissue. These in vitro and in vivo results point to progesterone as the agent responsible for the 10-fold increase in endometrial estradiol dehydrogenase activity observed during the luteal phase in menstruating women. Data obtained from superfusion studies of estrogen dynamics in endometrium indicate that changes in enzyme concentrations may play a physiologic role in the regulation of tissue levels of estradiol.

Parkinsonism: effects of levodopa treatment on concept formation.

Abstract: Concept formation was compared in 71 parkinsonian patients and 35 controls matched for age and WAIS verbal IQ. It was found that the patients formed significantly fewer concepts, as measured by the Wisconsin Card Sorting Test (WCST). The patients had difficulties in shifting sets and were unable to attend to the completion of a concept. Levodopa-treated patients were able to produce more correct responses, but were still unable to maintain the correct responses to produce more correct concepts than non-levodopa-treated patients. The behavior of the parkinsonian patients on the WCST is similar to that of patients who have undergone frontal lobectomy. In addition, the results indicate that levodopa therapy may improve “vigilance,” without increasing the patient9s overall cognitive ability.

Alcoholic hepatomegaly: accumulation of protein in the liver.

Abstract: The hepatomegaly that appears after long-term feeding of ethanol results in accumulation of protein that is quantitatively as important as the increase in lipid. The bulk of protein accumulated in the soluble fraction of the cell. Hepatic albumin and transferrin concentrations increase and colchicine-binding protein decreases, thus suggesting an intrahepatic retention of export proteins.

Hypervariable regions, idiotypy, and the antibody-combining site.

Abstract: Publisher Summary This chapter discusses the structure and role of the variable regions of the immunoglobulins (Ig) molecules Based on amino acid sequence data, hypervariable regions make up a significant part of the variable regions, occupy relatively constant locations in a variety of Ig molecules even from different species, and appear to be intimately associated with the antibody-combining site In addition, the idiotypic determinants that mark the antigenic individuality of particular Ig molecules are based on the properties of some or all of the hypervariable regions In contrast, outside the hypervariable regions there is a considerable invariance of sequence, and these invariant sections occur in approximately the same position in Igs of different V region subgroups The polymeric Ig molecules are intriguing, because one of them, IgM, is structurally the most complex, phylogenetically the most primitive, and ontogenetically the earliest of the Ig molecules The other polymeric Ig molecule, IgA, evolved relatively recently but retained that portion of the IgM Fc sequences responsible for polymerization and, in addition, developed a mechanism for transport across epithelial cells The most detailed view of the molecular orientation of the immunoglobulin V region, which is consistent with the known serological and immunochemical data is obtained by X-ray diffraction analyses

Effects of progestins on estradiol receptor levels in human endometrium

Abstract: Medroxyprogesterone acetate (Provera) was administered orally during 2–4 days to women undergoing endometrial curettage during the follicular phase of the menstrual cycle. Estradiol (E2) receptor levels were estimated from the amounts of 3H–E2 tightly bound in nuclei after incubation of endometrial tissue with an excess of the labeled hormone. An average value (9 subjects) of 1.5 pmole E2/mg DNA ± 0.7 (mean ± SD) was found. This value is significantly lower than the average E2 receptor levels in proliferative endometrium of untreated subjects (3.2 ± 1.3, n = 33) and equals the level observed in the early secretory phase (1.5 ± 0.5, n = 5). These results indicate that one of the progestin effects on human endometrium is the reduction of E2 receptor levels.

Acetaldehyde oxidation by hepatic mitochondria: decrease after chronic ethanol consumption.

Abstract: Prolonged consumption of ethanol significantly reduces the capacity of rat liver mitochondria to oxidize acetaldehyde. This is associated with decreased mitochondrial respiration with acetaldehyde as substrate. The reduced ability of mitochondria to metabolize acetaldehyde may explain the high levels of acetaldehyde in the blood of alcoholics, which in turn could promote the perpetuation of liver injury.

Feminizing interstitial cell tumor of the testis: personal observations and a review of the literature.

Abstract: A 28-year-old man with evidence of feminization was demonstrated after 4 years of investigation to have a estrogen-secreting interstitial cell tumor. Such feminizing neoplasms are uncommon, only 37 having been described. They are usually benign and are characterized by gynecomastia, a testicular mass and, with lesser frequency, by decreased libido and potency and poor semen quality. The urinary excretion and plasma levels of estrogen are increased and, by selective testicular catheterization, the site of increased estrogen production can be localized. Secondary histologic changes occur in the nontumorous portions of the testis as well as in the contralateral testis; they are most marked in the area immediately adjacent to the tumor. Postoperatively, the gynecomastia regresses, the excessive levels of estrogen return to normal, libido improves, and the sperm count increases to normal.

Soft tissue sarcomas.

Abstract: The soft-tissue sarcomas are a group of rare but anatomically and histologically diverse neoplasms. This is due to the ubiquitous location of the soft tissues and the nearly three dozen recognized histologic subtypes of soft-tissue sarcomas.

The postnatal development of the sexually dimorphic duct system and of amylase activity in the submandibular glands of mice.

Abstract: The submandibular glands of developing and mature Strong A mice were studied by light and electron microscopy. The glands of both sexes show the same cell types during development, but during maturation the glands display a degree of sex-dimorphism. Striated ducts, which differentiate from the larger intralobular ducts present in the neonatal gland, first appear by 5 days of age and reach their mature condition by 20 days of age. Granular convoluted tubule cells, which differentiate from striated duct cells, are first seen at 15 days of age in both sexes. Subsequently, they show a more rapid development in males than in females, and are dimorphically represented by 20 days of age. Intercalated ducts in the neonatal gland contain nongranular and granular cells. With maturation the number of granular cells decreases, apparently due to their conversion into the nongranular type, with their eventual disappearance from the glands of adult males. Their retention in adult females further defines the sexual dimorphism shown by these glands. Amylase activity in gland homogenates is first detectable at 20 days of age in both sexes. During development the male glands show a rapid rise in levels of amylase activity, whereas female glands show a more gradual rise. In mature animals, male glands have higher levels of amylase activity than female glands. The developmental and adult status of amylase activity parallels that of the granular convoluted tubules.

The assessment of nocturnal REM erection in the differential diagnosis of sexual impotence.

Abstract: A new method for differentiating psychogenic from organic cases of sexual impotence is described based on the assesst of nocturnal REM erection in nine patients. It is our tentative impression that in psychogenic impotence nocturnal REM erection may be normal in amount and degree and an excellent indicator of erectile potential. In these cases a marked discrepancy exists between the amount and degree of nocturnal erection and the patient's daytime performance level attained during attempted coitus or masturbation. In the organic patients, on the contrary, such a discrepancy does not exist; instead, the maximal nocturnal erection attained corresponds closely to and mirrors the patient's impaired waking performance. This new method may be very useful in the diagnosis, prognosis, and decision as to type of treatment, especially in difficult cases.

Relationship of Bioassayable and Immunoassayable Plasma ACTH and Cortisol Concentrations in Normal Subjects and in Patients with Cushing's Disease

Abstract: Plasma ACTH and cortisol concentrations were determined at 5-min intervals over a 3- or 4-h sampling period in 2 normal subjects. Time spans studied were 10:00 AM-1:00 PM, 4:00 PM-8:00 PM, 8:00 PM-11:00 PM, and 4:00 AM-8:00 AM. Similar sampling for 3 h, (onset 9:00-9:30 AM) was performed on 4 patients with Cushing's disease, 3 untreated and 1 in remission following pituitary irradiation. Two of these patients were studied on 2 separate occasions. Plasma ACTH was determined by both immunoassay (I) and bioassay (B). Although in general, these studies demonstrated significant correlation between I-ACTH or B-ACTH concentrations and those of plasma cortisol, a striking finding in both subject categories was the presence of 30- to 50-min episodes during which marked rises in both I- and B-ACTH concentrations occurred without concomittant, or markedly diminished, increments in plasma cortisol concentrations. This could not be explained by biological inactivity of the ACTH, since a highly significant correlation was present between I- and B-ACTH concentrations at all times; r values ranged between 0.86 and 0.98 for normal subjects, and 0.76 and 0.96 for patients with Cushing's disease. The lack of correlation in these episodes also does not appear to be secondary to an 11-beta-hydroxylase block, differences in the rate of change of plasma ACTH concentrations, lack of adrenal "priming" by prior ACTH or incapacity of the adrenal gland to further increase secretion. I/B ACTH ratios were similar in the normal subjects (1.42-1.64) and in the patients with Cushing's disease (1.27-1.47). "Apparent" ACTH half lives calculated from "peaks" of ACTH secretion were 7-12 min for I-ACTH and 3-9 min for B-ACTH in the normal subjects; and 9-13 min and 7-9 min respectively, in the patients with Cushing's disease. Mean plasma ACTH I-and B-concentrations at comparable time periods were higher in patients with active Cushing's disease than in normal subjects. These studies also indicate that in Cushing's disease, the abnormality present resides in ACTH regulatory mechanisms, not in the nature of the ACTH secreted. Approximation of the total amount of immunoassayable ACTH secreted in one normal subject over a 24-h period yielded a value of 73 mug. Total mug/h secreted in the 2 normal subjects were highest in the hour preceding awakening (6:30-7:30 AM; 12.9 and 12.2 mug/h); were 5.3 and 4.0 mug/h between 10:00-11:00 AM, and 1.4 and 1.7 mug/h between 9:00-10:00 PM. In the 3 patients with clinically active Cushing's disease, apparent ACTH secretion between 10:00-11:00 AM varied from 19.2-34.3 mug/h, the magnitude of such secretion being positively correlated with the extent of increased adrenal cortical activity present.

Prevalence of disease among vinyl chloride and polyvinyl chloride workers

Abstract: The emergence in January 1974, of vinyl chloride as a new occupational carcinogen producing hemangiosarcoma of the liver focused attention on the toxicologic effects of this chlorinated hydrocarbon.’ A considerable number of studies had been published on the rather puzding and unique syndrome of “acroosteolysis” (TABLE 1) describing mainly the bone lesions in the distal phalanges of the fingers, but also the associated sclerodermalike skin lesions and the striking vascular (arterial and arteriolar) changes, pathologically the main lesion, leading to secondary bone and skin changes (TABLES 2 and 3). Much less attention had been given to the hepatotoxic effects of vinyl chloride, although convincing experimental evidence had been produced”. 23 and scattered reports of ill-defined liver changes were included in some of the studies of vinyl chloride-exposed workers (TABLE 4). There was evidence that liver damage occurred in workers exposed to higher levels of vinyl chloride. In some studies the liver changes (hepatomegaly, tenderness on palpation, abnormal liver tests) were found to be reversible after cessation of exposure. On the other hand, some observations mentioned the progressive nature of the liver changes, when toxic exposure continued, to what was stated to be “chronic hepatitis.” Recent work from Germany16 reporting a detailed study of 20 polyvinyl chloride (PVC) workers brought a very important contribution to our present knowledge on the liver changes induced by this toxic exposure. The authors were alerted to the problem by the occurrence of upper gastrointestinal bleeding in several workers of a PVC-producing plant. Esophageal varices, splenomegaly, hepatomegaly, fibrosis of the liver capsule (by laparoscopy), delay in the secretion of bromsulphalein, and thrombocytopenia were the most prominent findings. The pathologic changes encompassed collagenous transformation of the liver sinusoids, focal activation of Kupffer cells, increased collagen deposition in the portal spaces, portal fibrosis, and septa1 and intralobular fibrosis. There are a few cases in the literature of lung changes in PVC workers. One case of pneumoconiosis in a 30-year-old worker who had inhaled PVC dust was reported.“ The lung biopsy showed granulomatous lesions (foreign body type) to be present. Fibrotic changes and altered pulmonary function tests were reported in 96 workers exposed to polyvinyl chloride dust; the changes were more pronounced in persons with long exposure.p6 I n the available literature on vinyl chloride and polyvinyl chloride adverse health effects there were no accurate data on the prevalence of disease in exposed workers, the relative prevalence of the various pathologic changes, their possible association and time sequence. We have undertaken clinical studies of a number of groups of vinyl chloride-

A sensitive bioassay for the determination of human plasma ACTH levels.

Abstract: A sensitive bioassay for the measurement of plasma ACTH is presented. The use of silicic acid adsorption of plasma, with a subsequent acid wash and aqueous acetone desorption, was successful in removing those substances which had interfered with the steroidogenic response of dispersed adrenal cells when unextracted plasma was employed. This extraction procedure extracted 72-76% of ACTH present in plasma. Two pg ACTH1-39 could be consistently detected. Alpha-hACTH1-39 and alpha-pACTH1-39 exhibited equal potencies. Beta-MSH was ineffective at dosage levels up to 2 x 10(8) pg. One x 10(8) pg of ACTH1-10, ACTH4-10, or alpha-MSH had a steroidogenic effect equivalent to that of 40 pg ACTH1-39. ACTH 17-39 and ACTH 11-24 were incapable of stimulating steroid production at doses of 1 x 10(8) pg. Excesses of the latter, but not of the former appeared to be able to antagonize the steroidogenic effect of ACTH1-39. Plasma from normal subjects, bioassayed by this extraction procedure, contained 12-186 pg/ml ACTH at 0400-0800: 14-93 pg/ml ACTH at 1000-1300, and less than 10-34 pg/ml ACTH at 1600-2200. Hypoglycemia and vasopressin administration were followed by increases in plasma ACTH concentratrations. Plasma ACTH concentrations in untreated patients with Cushing's disease (sampled over the period 0900-1300) ranged from 65-220 pg/ml. Three patients with Addison's disease (untreated or 12 h following replacement steroid withdrawal) had ACTH concentrations of 223, 370 and 1226 pg/ml. Markedly elevated ACTH concentrations were observed in a patient with Nelson's syndrome (391 and 835 pg/ml). Bioassayable ACTH was not detected in 2 patients with panhypopituitarism.

Effects of chronic ethanol administration on intestinal absorption in man in the absence of nutritional deficiency

Abstract: Chronic alcoholism is frequently associated with impaired intestinal absorption.Id6 A high incidence of malabsorption of xylose, fat, vitamin Blz , folic acid, and thiamine has been documented in malnourished chronic alcoholics, with recovery of absorptive function after withdrawal of alcohol and ingestion of a nutritious Acute ethanol administration has been reported to cause impairment in intestinal absorption in hamsters? and man,I0 and chronic ethanol feeding in rats results in malabsorption of vitamin Blzl1 and carbohydrates,l2 and decreased jejunal enzyme activitiesI3 despite adequate vitamin and protein intake. Chronic ethanol administration in man with a nutritious diet causes ultrastructural abnormalities in intestinal villous cells.I4 Since malnutrition alone may result in malab~orpt ion ,~~* l6 the relative importance of ethanol ingestion and depletion of nutrients in causing malabsorption in chronic alcoholic patients has been uncertain. To determine whether ethanol alone, in the absence of associated nutritional deficiency, causes impairment of small bowel function in man, we studied the effects of chronic alcohol administration under controlled metabolic ward conditions on intestinal absorption in human volunteers.

Adenosine diphosphate effect on contractility of human muscle actomyosin: inhibition by ethanol and acetaldehyde.

Abstract: Magnesium adenosine triphosphate (Mg-2+-ATP) is known to produce dissociation of muscle actin and myosin in vitro, while its hydrolysis leads to reassociation. The interaction of purified actin and myosin from human muscle, in the presence of Mg-2+-ATP, was stimulated by minute amounts of adenosine diphosphate (ADP), a product of ATP hydrolysis. By contrast, the dissociation of the actomyosin complex was inhibited by ADP. These data suggest that ADP serves to modulate muscle contraction. Ethanol and its primary metabolite, acetaldehyde, inhibited these effects of ADP. The inhibition was reversible when the preparations were freed of these compounds. The effects of ethanol and acetaldehyde on the response of actomyosin to ADP may play a role in the pathogenesis of alcoholic myopathy and cardiomyopathy.

Characterizing the hemophilic pseudotumor

Abstract: The term “orthopedie,” first used by Nicholas Andry in 1741, was derived from the Greek-ortho (straight) and puidiu (child)-literally, “to straighten the child.” Hemophilia is one of the most challenging tests the present-day orthopedist is faced with. Musculoskeletal hemorrhage is the most common manifestation of these coagulation disorders. Hemorrhage may occur into three distinct anatomic sites: (1 ) into the joint, with the formation of arthropathy; (2) into the soft tissues, with consequent contracture and/or neuropathy; and (3) into or in proximity to bone, with the formation of a pseudotumor. The latter is the least common lesion, but its formation is most serious as it represents a potential threat to both life and limb. Because of their relative rarity, few physicians have great experience in treating these lesions. Little is known about the basic pathology. This presentation, which is based upon a review of the literature and personal experience with those few cases followed at the Hemophilia Clinic of Mount Sinai Hospital, New York, will attempt to correlate the known pathology, characterize the lesion, and propose a rational plan of therapy. Starker 1 has been generally credited with describing the first pseudotumor, in 1918. Since then over 60 cases have been described. Fernandez de Valderrama and Matthews characterized the pseudotumor as “a progressive cystic swelling involving muscle, produced by recurrent hemorrhage and accompanied by radiographic evidence of bone involvement.” Gunning estimated an incidence of 1 % of severe hemophiliacs. Pseudotumors have been described in the long bones (especially those of the lower extremity), the pelvis, and the small bones of the hands and feet. The femur is the most common site, accounting for slightly over one-third of all reported cases. The pelvis, the next most common site, accounts for slightly under one-third of the cases. The tibia and the bones of the feet account for most of the rest, a few being reported in the hand or at the wrist. The average age at which the patient with a pseudotumor presented for medical care is quite interesting. Most every pseudotumor in the femur and pelvis presented in a mature patient. In contrast, those noted in the small bones of the hand and foot all occurred in the young patient with open epiphyseal growth plates. Even more interesting was the fact that many of the latter patients had or developed multiple pseudotumors, which has not been reported in the older patient with the more proximal lesion. The proximal lesion, as exemplified in the femur, was preceded by a history of trauma and developed over many years. At the hand and foot, trauma was less frequent and the patient sought medical advice within one year. These findings suggested to me that there may be two distinct clinical patterns, and further analysis seemed to confirm this. The large femoral pseudotumor usually presented as a painless expanding mass. A history of trauma may be elicited with slow resolution of a hematoma

Folate binding proteins.

Abstract: The physical and physiologic properties of serum, milk and cellular FABP have been presented. Several investigators have shown that FABP with similar characteristics is present throughout the body fluids and tissue. Thus, FABP appears to be established as a protein which can significantly influence folate metabolism.

Alterations of liver and spleen among workers exposed to vinyl chloride.

Abstract: Preliminary review of hepatic biopsy and autopsy specimens obtained from workers engaged for prolonged periods in the polymerization of vinyl chloride indicates a fibrotic precursor lesion in the liver. It is the only lesion in some instances but also was found in the uninvolved liver of patients with angiosarcoma and in two instances in liver biopsy specimens obtained before angiosarcoma developed. This precursor stage is characterized by a conspicuous subcapsular fibrosis, a nonpathognomonic progressive portal fibrosis, and a borderline increase of intralobular connective tissue, all associated with focal stimulation of sinusoidal lining cells and hepatocytes. This precursor stage is often accompanied by splenomegaly with enlarged Malpighian follicles and in some instances by portal hypertension requiring portacaval shunt because of variceal hemorrhage. The portal hypertension is explained by increased splenic blood flow in the face of nondistensible fibrotic portal tracts as well as Glisson's capsule. Transition to angiosarcoma is preceded by focal dilatation of sinusoids with even greater activation but dedifferentiation of their lining cells. This lesion is presumably the result of stimulation of various hepatic as well as splenic cells by vinyl chloride or its metabolites. The demonstrated evolution is identical with that following prolonged exposure to inorganic arsenicals. It is postulated also that other instances of inconspicuous hepatic fibrosis associated with splenomegaly and often with portal hypertension, a combination designated as Banti's syndrome or "idiopathic portal hypertension," are the result of a toxic, possibly environmental agent, particularly since the disease is found with greater frequency in some parts of the world. The delineation of the fibrotic precursor stage in the liver may assist in the epidemiologic studies of the vinyl chloride-induced injury.

Concentration of Clindamycin in Human Bone

Abstract: Thirty patients undergoing total hip replacement received clindamycin beginning the day before surgery. Mean clindamycin concentrations during surgery were 7.33 ± 3.37 μg/ml in serum and 2.63 ± 1.76 μg/g in bone; mean ratio of bone-serum concentration was 0.40 ± 0.30.

Changes in pulmonary function in workers exposed to vinyl chloride and polyvinyl chloride

Abstract: To determine whether occupational exposure to vinyl chloride gas and polyvinyl chloride dust is associated with changes in pulmonary function, spirometry and maximum expiratory flow-volume curves were obtained in 348 workers in a VC polymerization plant. The major finding was diminution in air flow in 200 workers (57.5 percent). This abnormality correlated with age and duration of exposure. A relationship with smoking was noted only in younger workers with exposures of less than 10 years. When age exceeded 40 years or exposure 20 years, prevalence of this impairment was similar in smokers and nonsmokers, suggesting that occupational or other environmental factors were operative.

Changes in morphine self-administration and morphine dependence after lesions of the caudate nucleus in rats

Abstract: Rats were trained to bar press for intravenous infusions of morphine sulfate during 1-hr daily test sessions. Small, centrally placed bilateral lesions of the caudate nucleus reduced rates of morphine self-administration to approximately one seventh of preoperative levels; postoperative rates were similar to preoperative rates when the postoperative unit infusion dose of morphine was one tenth of the preoperative dose. Caudate lesions also lowered the threshold dose at which morphine's rewarding property could be detected. Physical dependence was studied in other rats receiving a 3-day continuous infusion of morphine sulfate via implanted subcutaneous silicone reservoirs. Caudate lesions ameliorated withdrawal-induced weight loss and naloxone-induced “wet dog shakes”. Both the self-administration and dependence data are consistent with the idea that morphine blocks dopaminergic transmission in the striatum.

Pathology of angiosarcoma of the liver among vinyl chloride-polyvinyl chloride workers.

Abstract: We described the histologic features of 13 hepatic angiosarcomas which developed in workers engaged in the polymerization of vinyl chloride to polyvinyl chloride. Although the histologic features varied considerably in different portions of the angiosarcoma in the same liver and in the angiosarcomas of the liver from different patients, many features were similar such as sinusoidal, papillary, and cavernous growth patterns coincident with the precursor lesions of proliferation and atypia of sinusoidal lining cells.