Changes in sexual behavior as a function of plasma sex steroid levels in post-menopausal women

Eight women who had been maintained on a combined estrogen-androgen drug since hysterectomy and bilateral oophorectomy 2 yr previously were investigated for changes in sexual behavior during the course of 1 treatment cycle. Following intramuscular injection of both sex steroids, plasma estradiol levels were within the normal range of young, cycling women but plasma testosterone exceeded the upper limit of normal female values. Sexual motivational behaviors (desire, fantasies and arousal) covaried with plasma steroid levels. Rates of coitus and orgasm, however, were unrelated to the changing levels of circulating hormones. A differential effect of the sex steroids on various aspects of sexual functioning was thus confirmed.     

Elastosis in benign and malignant breast disease

Elastosis, the presence of clumps of elastic fibers, is known to occur frequently in association with breast carcinoma. To test the hypothesis that the degree of elastosis increases progressively in fibrocystic disease with the severity of epitheliosis (epithelial hyperplasia, papillomatosis; widely believed to be the only premalignant component of fibrocystic disease) and increases further with intraductal and infiltrating duct carcinoma, breast tissue stained for elastic fibers from 84 women in the fifth decade of life was studied. Fourteen cases were evaluated in each of six disease categories: fibrocystic disease without epitheliosis; fibrocystic disease with epitheliosis, graded subjectively as mild, moderate, or severe (based on the degree of epithelial hyperplasia); intraductal carcinoma; and infiltrating duct carcinoma of the breast. Periductal elastosis and stromal elastosis were graded on a scale of 0 to 4 (absent to massive). The grades of both periductal elastosis and stromal elastosis were compared with those for the six disease categories ranked by increasingly advanced disease. The results indicate that the grades of periductal elastosis (Spearman rank correlation coefficient [R] = 0.54; P less than 0.001) and stromal elastosis (R = 0.75; P less than 0.001) increase progressively with the severity of breast disease.     

Airway mucosal permeability in the Ascaris suum-sensitive rhesus monkey.

The permeability of the airways to technetium 99m-labeled albumin was measured in Ascaris suum-sensitive rhesus monkeys. All 8 animals were skin-sensitive to Ascaris suum (AA) antigen, 4 being respiratory responders (R) and 4 nonresponders (NR) to aerosolized antigen. In the absence of antigen challenge there were no differences in the accumulation in the blood of radioactive material from the tracheobranchial tree between the R and NR animals. After a five-minute challenge with aerosolized AA, there was a threefold increase in the rate of accumulation of radioactive material in the blood over control for the R group with no effect noted in the NR group. Gel filtration data indicated that the radioactivity in the blood most likely represented low molecular weight albumin fragments, resulting from spontaneous degradation of Tc-albumin, that crossed the mucosa and partially bound to circulating albumin. It is concluded that hyperpermeability of the airway mucosa probably is not a factor that contributes to the selective responsiveness of the R group to aerosolized antigen, and that airway permeability is increased consequent to the allergic reaction mediating acute bronchoconstriction.     

Innervation of forebrain regions by medullary noradrenaline neurons, a biochemical study in cats with central tegmental tract lesions

In order to determine quantitatively the relative contribution of medullary noradrenaline neurons to the noradrenaline terminal innervation of forebrain regions in the cat, bilateral lesions of the central tegmental tract were performed at the level of the caudal pons in adult cats. The results indicate that the medullary neurons provide approximately 75% of the total noradrenaline innervation to the hypothalamus, only 20–25% of that of the thalamus and midbrain and no measurable contribution to the noradrenaline innervation of the cerebral cortex or hippocampus. These results are comparable to previous ones of bilateral locus coeruleus lesions in the cat which showed that the locus coeruleus neurons provide approx. 15% of the total noradrenaline innervation to the hypothalamus, 60% of that to the thalamus and midbrain and the entire innervation to the cerebral cortex and hippocampus.     

Effect of remote aortic injury and thrombosis on cholesterol atherosclerosis

Recent tissue culture studies indicate that platelet factors enhance lipoproteins to stimulate proliferation of smooth muscle cells, a key event in atherogenesis. It was of interest to determine if continued remote aortic injury and thrombosis can increase the severity of hypercholesterolemia induced atherosclerosis. Four groups of rabbits were studied, two groups fed 0.5 g cholesterol per day, one group with and one group without massive abdominal aortic white mural non-occlusive thrombosis and injury induced with a permanent indwelling catheter, and two groups fed 1 g cholesterol per day, one group with and one group without similar thrombosis and injury. Serum lipids in the four groups were qualitatively and quantitatively not significantly different from each other at 4, 8, and 12 weeks. When they were sacrificed at 12 weeks the percent intimal surface area in the thoracic aorta (48 ± 22) and arch (75 ± 28) of the rabbits with thrombosis and fed 0.5 g cholesterol per day was significantly (p < 0.01) greater than the percent intimal area (20 ± 14) and (24 ± 18) of the rabbits without thrombosis. The percent intimal area with lesions in the rabbits fed 1 g cholesterol per day with thrombosis (59 ± 25) and (84 ± 30) was significantly greater (p < 0.01) than the percent area (24 ± 29) and (32 ± 32) of the rabbits without thrombosis. Since the effects could not be attributed to differing serum lipid levels it is possible that the increased severity of atherosclerosis in the remote arch and thoracic aorta was related to increased permeability, cell proliferation or collagen synthesis possibly stimulated by circulating factors released from the remote massive non-occlusive thrombus or from circulating platelets activated by contact with the injured abdominal aortic wall.     

Shock-related injury of pancreatic islets of langerhans in newborn and young infants

Variable degrees of injury of the pancreatic islets of Langerhans, with sparing of the acinar pancreas, were observed in three infants (age range, 1 day to 3 months) who died of profound shock. The duration of shock varied from 19 to 48 hours. In two of the infants, the shock stemmed from hypovolemia; in the remaining infant, the shock followed blood loss, sepsis, and heart failure. The islet lesions were devoid of cellular infiltrates, hemorrhage, and fibrin thrombi. Tissue manifestations of shock included acute renal tubular necrosis, massive hepatic centrilobular necrosis, ischemic enteropathy, and "shock" lung. Study of pancreatic sections from 30 children (age range, 13 hours to 15 years) with clinical and/or morphologic evidence of shock showed no additional instances of islet injury. These findings suggest that pancreatic islets in the young may be vulnerable to shock-induced ischemia. Studies are in progress in an animal model to test this hypothesis.     

Precocious thymic involution manifest by epithelial injury in the acquired immune deficiency syndrome

Thymuses from six heterosexual Haitian patients with the acquired immune deficiency syndrome (AIDS) were studied by light microscopy and the findings were compared with those from three control groups. The control groups included 1) five age-matched Haitian hospital patients; 2) ten age- and sex-matched Montreal patients who had died suddenly or had had brief illnesses; and 3) 20 middle-elderly Montreal patients who had experienced chronic, wasting illnesses or prolonged hospitalization. Thymuses from patients with AIDS demonstrated pronounced involution, effacement of the cortex and medulla, marked thymocyte depletion, variable degrees of plasma cell infiltration and fibrosis, and, above all, absence of Hassall's corpuscles. Thymuses from Haitian and Montreal control subjects who had died suddenly or had brief illnesses demonstrated minimal involution and abundant Hassall's corpuscles. Although thymuses from 12 of the chronically ill control subjects demonstrated marked involution, architectural effacement, and absence of Hassall's corpuscles, partial architectural preservation and variable numbers of Hassall's corpuscles were observed in eight of these subjects. Thus, the extent of thymic involution observed in patients with AIDS antedates that incurred with aging and supersedes that induced by sustained stress and inanition. The loss of Hassall's corpuscles in patients with AIDS suggests that the thymic epithelium either incurs a form of injury or undergoes precocious involution during the illness. Whether this lesion is central to the pathogenesis of AIDS or merely a reflection of intense, sustained stress coupled with accelerated physiologic involution is unknown. It is possible that the disappearance of Hassall's corpuscles may indicate important, although as yet cryptic events within the thymic microenvironment in this syndrome.     

Localization of antigen in experimental bronchoconstriction in guinea pigs

These experiments were done to examine the position of the antigen in the tracheobronchial mucosa in a situation in which the antigen caused allergic bronchoconstriction. Guinea pigs were sensitized to the tracer protein, horseradish peroxidase (M.W. 40,000), and these animals were challenged with an aerosol of this antigen while lung mechanics were measured. We found that airways resistance rose significantly in sensitized animals (p < 0.02) while nonsensitized animals exposed to the same aerosol showed no change. The animals were sacrificed and the antigen was localized with an electron microscopic histochemical technique. Studies were also done with isolated, perfused lungs from sensitised animals challenged intravenously with the antigen. In both the in vivo studies, in which bronchoconstriction was demonstrated, and the in vitro studies, in which mediator release was demonstrated, the antigen had a superficial distribution and was not seen to penetrate the epithelial or endothelial layers. These findings suggest that the antigen-antibody reaction may occur at these sites.     

Immunotopographic assessment of lymphoid and plasma cell malignancies in the bone marrow

To determine the utility of tissue section immunochemistry in the evaluation of bone marrow involved by lymphoid and plasma cell malignancies, snap-frozen, undecalcified bone marrow core and aspirate samples from 23 patients with these disorders were studied with a battery of monoclonal antibodies. With techniques that preserve architecture, difficult diagnostic cases characterized by core but not aspirate involvement, or the reverse, were resolved. By means of an extensive battery of monoclonal antibodies applied to serial sections, complex tumor cell phenotypes were established in all 23 cases. In addition to the identification of straightforward monoclonal surface immunoglobulin expression in small cleaved cell lymphomas (four cases), the battery approach added immunologic certainty in malignancies with unusual or difficult phenotypes: peripheral T-cell lymphomas with idiosyncratic antigen expression, and chronic lymphocytic leukemias and small cell lymphomas with faint surface immunoglobulin expression (four cases). For the chronic lymphocytic leukemias and the small cell lymphomas, the combined IgD+, B2+, B1+, Ia+, Leu-1+ phenotype taken as a whole had greater utility than any isolated marker. The acute lymphocytic leukemias and the myelomas studied demonstrate the wide range of B-cell antigens that must be detected to account for the variety of B-cell neoplasms encountered. Additionally, the previously undescribed phenotypic subset of CALLA+ myelomas, which is of prognostic relevance, was identified. Marrow frozen section immunotyping is a major asset in the evaluation of patients with lymphoma, leukemia, and myeloma when special care is accorded to tissue handling and to treatment of endogenous peroxidase/pseudoperoxidase and interstitial immunoglobulin.     

Influence of static tilt on soleus motoneuron excitability in man

The influence of whole head-body rotations with respect to gravity on the excitability of the human soleus motoneuron pool, was studied by mapping the H reflex amplitude as a function of static head displacements. In most subjects, the H reflex reached a minimum when the head was near the vertical position (90°), and of increased as a sinusoidal function of tilt in the sagital plane. These changes were attributed to the tonic labyrinthine reflexes which, unlike some findings in decerebrate cats, generally increase the extensor tone of the human lower limb when the head is displaced from the upright position.     

Immunologic mechanisms in hypersensitivity pneumonitis: I. Evidence for cell-mediated immunity and complement fixation in pigeon breeders' disease

Immunologic studies were performed on 5 patients with pigeon breeders' disease. Intradermal injection of pigeon serum produced an immediate wheal-and-flare reaction within 15 minutes and a secondary Arthus-type reaction within 4 to 8 hours. Immunofluorescent studies of the secondary reaction site showed IgG, C3, and C4 in 2 patients. Patients' sera produced multiple precipitin bands with pigeon serum when reacted by double diffusion in gel. IgG antibody isolated from each of the patients' serum formed precipitating immune complexes that fixed large amounts of complement (C4) when added to fresh human serum. Peripheral blood lymphocytes from 4 of the 5 patients produced macrophage migration inhibitory factor (MIF) when challenged with dilute pigeon serum. These studies are the first to show complement fixing antibodies and macrophage MIF production by lymphocytes from patients with hypersensitivity lung disease and suggest that both humoral and cellular immunity may be important in the pathogenesis of these disorders.     

Cytogenetics of murine thymic lymphomas induced by N-methyl-N-nitrosourea: Difference in incidence of trisomy 15 in thymic lymphomas induced in neonatal and adult mice

Chromosome complements of murine thymic lymphomas induced by an alkylating agent N-methyl-N-nitrosourea (MNUA) were analyzed microscopically and karyotypically using the Q-banding technique. The chemical carcinogen was injected intraperitoneally into either neonatal or 7-week-old CFW/D mice. In addition, thymic lymphomas induced in 7-week-old AKR mice and thymic lymphomas developed spontaneously in this strain were also examined. All six lymphomas induced in neonatal CFW/D had hyperdiploid cell lines that accounted for 90% of the cells analyzed. Chromosome analysis of lymphomas induced in adult CFW/D mice showed that only four out of nine lymphomas had predominantly hyperdiploid cell lines. The remaining five lymphomas had diploid modal chromosome number although they also carried a variant line characterized by 41 chromosomes. All eight lymphomas induced in adult AKR mice and six out of seven spontaneous AKR lymphomas showed predominantly diploid modal line. The remaining spontaneous lymphoma had a hyperdiploid stem line of 41 chromosomes. Microscopic and karyotypic analysis further identified trisomy 15 as the regular chromosome abnormality in the hyperdiploid cells in lymphomas of each group, whereas cells with diploid chromosome number had no detectable chromosome abnormality. Additional trisomies were also found, but their appearance was restricted to individual tumors. Thus, the incidence of trisomy 15 in lymphomas induced by MNUA in adult CFW/D and AKR mice, as well as in the spontaneous AKR lymphomas, is significantly lower than that in lymphomas induced in neonatal mice by the same carcinogen.     

A modified epon embedding and counterstaining procedure for light microscopic examination of Golgi impregnated neurons in vertebrates

Tissue blocks impregnated with the Golgi-Kopsch method were embedded in a modified Epon formulation (1.5 parts DDSA, 1 part Epon 812, 1.9% DMP-30). Sections 150 μm thick were cut with a steel knife on a sliding microtome. The surface of the sections were counterstained with basic dyes to localize Golgi-impregnated neurons within cyto-architectonically defined areas. Neither the embedding nor counterstaining procedure appeared to adversely affect the quality of the Golgi preparation.     

Proliferative responses of peripheral blood lymphocytes to polyclonal activation: A comparison of young and elderly individuals

Associated with human aging is a decline in immune activity, of both the cell-mediated and humoral types. In vivo, autoantibodies increase with aging and antibody responses to flagellin are decreased in the elderly as compared to the young. These abnormalities may be due to defects in helper or suppressor T cells, or innate defects in B cells. In vitro, the proliferative response of B cells to pokeweed mitogen (PWM) is dependent upon T cells. We studied the proliferative response of peripheral blood mononuclear cells (MNC) to polyclonal activation with PWM in young and elderly normal individuals and found that the number of IgA- and IgM-bearing B cells produced was increased in elderly subjects. This difference was statistically significant for IgA-bearing cells when MNC were placed with 5 and 15 μl of PWM for 5 days and with 15 μl of PWM for 6 days. Statistically significant increases in IgM-bearing cells were seen when MNC were placed with 5 μl of PWM for 5 days and 5 and 10 μl of PWM for 7 days. The differences in numbers of IgG-bearing cells were less consistent. Significant increases were seen when MNC were cultured with 10 μl of PWM for 5 days and 5 μl of PWM for 6 days. Our results suggest that in elderly normal individuals numbers of immunoglobulin-bearing cells are increased after polyclonal activation of MNC. This increase in immunoglobulin-bearing B cells associated with reports of in vivo humoral abnormalities suggests that there is loss of regulation of T cells on B cells in normal elderly individuals.     

Loss of organized fibronectin matrix from the surface of aging diploid fibroblasts (IMR-90)

Indirect immunoflourescence was used to investigate the production of a fibrillar fibronectin matrix by human diploid fibroblasts (IMR-90) as cells progress through their in vitro lifespan. Early and mid-passage cultures displayed a prominent fibrillar reticulum over the cell layer which formed within 24 hours of seeding. Even sparsely seeded early-passage cells exhibited fibrils of fibronectin on external surfaces. In contrast, fibrillar fibronectin was reduced or absent on surfaces of late-passage cells. However, the larger, non-proliferating, late-passage cells were producing fibronectin, as determined by radioimmunoassay of the medium.     

Mineral oil (follicular) lipidosis: II. Histologic studies of spleen, liver, lymph nodes, and bone marrow

Tissues obtained from 600 routine autopsies were studied. Mineral oil lipidosis was present in the spleen (76 per cent), liver (45 per cent), bone marrow (26 per cent), and lymph nodes; more than 50 per cent of the lymph nodes from the mesentery, porta hepatis, and mediastinum were affected. Mineral oil and its metabolic products produce a nonfibrogenic reaction in these tissues. The differential diagnosis of mineral oil lipidosis in lymph nodes with reaction to radiopaque oils and Whipple's disease is discussed. The presence of mineral oil in para-aortic (42 per cent) and internal iliac (15 per cent) lymph nodes could result in false-positive readings after lymphangiography.     

Isolation of bile ducts from rat liver: technique and preliminary ultrastructural characterization.

A technique is described for isolation from the liver of a fraction rich in bile ducts. Ultrastructurally the isolated bile ducts showed good overall cellular preservation. The staining of the isolated bile ducts with the ruthenium red procedure clearly demonstrates the surface coat on the luminal surface of biliary epithelial cells and the intracellular microfilaments. The technology presented in this paper should make possible a new approach to the investigation of the hepotobiliary system.