Spermatogenic Disturbance Induced in Mice by Combined Local Injection of Monoclonal Antibodies to Sertoli Cell and to Basal Lamina of Seminiferous Tubule

ABSTRACT: Two kinds of hybridoma clones, one producing monoclonal antibodies against Sertoli cell (TM-1) and the other the basal lamina of the seminiferous tubule (TM-2), were raised by fusion between P3X63Ag8-653 mouse myeloma cells and spleen cells of BALB/c mice (H-2^d) immunized with testicular homogenate of the same inbred mice. Immunohistochemically, TM-1 reacted specifically with cytoplasmic component of Sertoli cell and TM-2 with basal lamina of the seminiferous tubule. Using these monoclonal antibodies, spermatogenic disturbance was induced experimentally in BDF₁(H-2^b/d) by intratesticular injection of a set of these two antibodies. Single injection of either TM-1 or TM-2 failed to induce the lesion. This fact indicated that TM-1 antibody could reach the Sertoli cell to impair its function, which was otherwise inaccessible without coincidental action of TM-2 antibody. TM-2 antibody appeared to alter the permeability of the basal lamina of the tubule and lower its barrier effect.     

Lewy bodies in the sinoatrial nodal ganglion: clinicopathological studies

Lewy bodies (LB) are characteristic pathological findings for idiopathic Parkinson disease, and extracranial organs have also been known to exhibit these structures. Clinically, the possible involvement of LB in cardiac dysfunction has attracted attention based on the findings of studies using [123I] metaiodobenzyl guanidine (MIBG) scintigraphy. The purpose of the present study was to investigate the possible involvement of LB in heart disease. A total of 40 autopsy cases consisting of Lewy body disease and Parkinson syndrome were examined. The former were cases with intracranial LB regardless of clinical symptoms, and the latter were cases with parkinsonism but without intracranial LB. The presence of heart disease or an atrial arrhythmia and the results of an MIBG scintigraphy study were clinically examined. The sinoatrial node was examined microscopically and immunohistochemically. The results showed that heart disease and atrial arrhythmia complications were more frequent in cases with Lewy body disease than in cases with Parkinson syndrome and that LB were frequently found in extracranial organs, especially in the sinoatrial nodal ganglion, in cases with Lewy body disease. In the current report, we hypothesized that neuronal changes involving LB in the sinoatrial nodal ganglion may cause arrhythmia and ischemic heart disease as a result of vasoconstriction.     

Age/sex dependent and non-monotonous dose-response effect of diethylstilbestrol on the immune functions in mice

High amounts of estrogens are known to suppress immune functions in both human and animal models. Our supportive data is that the immune functions were activated by gonadectomy in young adults mice. However, recent reports indicate that estrogen is required for the normal development of thymus. These findings lead us to an assumption that sex hormone status induces much more complex effects on immune functions depending on the host age/sex and dose ranges. Here, low doses of DES (diet containing 0.4 or 4.0 microg/kg diet) were given for 2 months to young adult and aged C57BL/6 mice, and thymic and splenic parameters including flow-cytometric subpopulation analyses, mitogenic responses and NK activity were monitored. This study revealed that the low dose effects of exogenous estrogen are strongly dependent on the age and sex of the recipients and many parameters show non-monotonous dose response effect. In conclusion, effect of exogenous estrogens on immune functions should be assessed for all age and sex, and in expectation of non-monotonous dose-response relationship.     

Antipsoriatic and antimetabolic agents as stimulators of the beta-adrenergic adenylate cyclase response of epidermis

Using pig skin organ culture in vitro, we compared the effects of antipsoriatic and anti-metabolic agents on the beta-adrenergic response of epidermis. After a 24-h incubation with these chemicals, the beta-adrenergic response of epidermis was shown to be increased to various degrees. Among the chemicals, colchicine, actinomycin D, and puromycin had the most marked effect, and were followed by Ro 10–1670 and hydrocortisone, and then by anthralin, cycloheximide and N-5’(N-(3,4-dimethyloxycinnamoyl) anthranilic acid). Methotrexate and hydroxyurea apparently had no (or rather decreasing) effects on the beta-adrenergic response of epidermis. After the same treatment in vitro, thymidine incorporation of epidermal keratinocytes was compared. In the latter system, the inhibitory effects of puromycin, cycloheximide and actinomycin D were most marked, and were followed by those of colchicine and Ro ro-1670, and then hydrocortisone and anthralin. n-s' had no effect and hydroxyurea increased thymidine incorporation of keratinocytes. Our data indicate that most (but not all) anti-psoriatic agents do augment the beta-adrenergic response of epidermis, which might be associated with the clinical efficacy of these agents in psoriasis where a defective beta-adrenergic response is well documented. The augmentation effects of these chemicals, however, did not correlate with their inhibitory effects on keratinocyte proliferation, at least in the thymidine incorporation system in epidermal keratinocytes in vitro.     

Pathological Characteristics of Gastric Carcinomas in the Very Old

A total of 69 gastric carcinomas of very old people (aged ≥85) were collected and pathologically analyzed in comparison with those of young to middle-aged (30–39) and elderly (65–69) people, with special attention to their phase. In the very old, almost all (34/35) carcinomas in the early phase belonged to well-differentiated categories. In the advanced phase, half of them (17/34) were classified into poorly differentiated categories when determined from the predominant pattern, but a well-differentiated pattern almost always coexisted in the superficial site. Thus, the gastric carcinomas in the very old may principally develop as well-differentiated carcinomas which then progress to poorly differentiated carcinomas with time, in contrast to those of the young to middle-aged, most of which emerged from the very early phase as poorly differentiated lesions. The gross features of the carcinomas were also in line with these histological observations. The carcinomas of the elderly showed distinct similarity to those of the very old. The results suggest that poorly differentiated carcinomas of the young to middle-aged and the old may be better classified and analyzed separately in view of the generally recognized etiological (e.g., specifically close causal relationship with environmental factors of the intestinal-type carcinoma of the old) and biological (e.g., practically no tendency for hematogenous metastasis of the diffuse-type carcinoma of the young to middle-aged) differences, although in the General Rules for Gastric Cancer Study of Japan, both are placed in the same category, por (por2).     

Critical proline residues of the cytoplasmic domain of the IL-5 receptor {alpha} chain and its function in IL-5-mediated activation of JAK kinase and STAT5

The high-affinity receptor (R) for IL-5 consists of a uniquea chain (IL-5Rc) and a ß chain (ßc) thatisshared with the receptors for IL-3 and granulocyte macrophagecolony stimulating factor (GM-CSF). We defined two regions ofIL-5R for the IL-5-induced proliferative response, the expressionof nuclear proto-oncogenes, and the tyrosine phosphorylationof cellular proteins including ßc, SH2/SH3-containingproteins and JAK2 kinase. In the studies described here, wedemonstrate that IL-5, IL-3 or GM-CSF stimulation induces thetyrosine phosphorylation of JAK2, and to a lesser extent JAK1,and of STAT5. Mutational analysis revealed that one of the prolineresidues, particularly Pro352and Pro355, in the membrane-proximalproline-rich sequence (Pro352-Pro353-X-Pro355) of the cytoplasmicdomain of IL-5R is required for cell proliferation, and forboth JAK1 and JAK2 activation. In addition, transfectants expressingchimeric receptors which consist of the extracellular domainof IL-5R and the cytoplasmic domain of ßc respondedtoIL-5 for proliferation and tyrosine phosphorylation of JAK1.Intriguingly, electrophoretic mobility shift assay analysisrevealed that STAT5 was activated in cells showing either JAK1or JAK2 tyrosine phosphorylation. These results indicate thatactivation of JAK1, JAK2 and STAT5 is critical to coupling IL-5-inducedtyrosine phosphorylation and ultimately mitogenesis, and thatPro352 and Pro355 in the proline-rich sequence appear to playmore essential roles in cell growth andin both JAK1/STAT5 andJAK2/STAT5 activation than Pro353 does.     

ACUTE METHYL MERCURY INTOXICATION IN MICE — Effect on the Immune System —

Effect of organic mercury on the immune system was studied in experimental acute methyl mercury intoxication in mice. After 7 daily injections of methyl mercury hydroxide, marked atrophy of the thymic cortex and splenic lymphoid follicles were observed, associated with decrease of PHA- and LPS-responsiveness of splenic lymphocytes as well as conversely increased both PHA- and LPS-responsiveness of thymocytes. In addition, apparent decrease of antibody formation against sheep red blood cells was observed at 7 day after the last injection. However, all these changes restored to normal level within 4 weeks after the last injection. Histochemically, mercury deposits were massively found in the renal tubules and slightly in macrophages throughout the body at 7 day after the last injection. The mercury deposits in macrophages of the thymus, lymph nodes and liver increased in concentration thereafter, with concomitant decrease of those in renal tubules. Presence of mercury element in these deposits was confirmed by electron probe analysis. It was suggested that the organic mercury gave direct cytotoxic effect on lymphoctes, but the effect appeared to be soon detoxicated by macrophages.     

ELECTRON MICROSCOPIC OBSERVATION OF THE HUMAN THYMUS OF THE FETUS AND THE NEWBORN

The human fetal thymus has been systematically studied by electron microscopy. The basic structure of the thymic parenchyma is a spongy meshwork, loose in cortex and dense in medulla, composed of two types of epithelial reticulum cell. The meshworks are packed predominantly with thymocytes of variable stages of maturation and partly with macrophages. type, found only in the medulla, is hypertrophic and has characteristic The first type of epithelial reticulum cells is slender and electron opaque, forming supporting element of meshwork(the slender type). The second type, found only in the medulla, is hypertrophic and has characteristic vesicles of two sorts (the hypertrophic type), the large one of which is provided with microvillous projections and contains fine granular substance of moderate electron density which corresponds to the PAS positive granule of METCALF¹. SO it might be suggested that the hypertrophic ones have an endocrine activity. The HassaU's corpuscle is composed of cellular aggregation of the hypertrophic type. The function of the thymus in the human fetus is discussed laying stress on the epithelial reticulum cell.     

DISTRIBUTION OF IMMUNOGLOBULIN CONTAINING CELLS IN HUMAN BONE MARROW OF PATIENTS WITH LEUKEMIA

In the bone marrow of leukemic patients (31 cases), the number of Immunoglobulin containing cells per unit square significantly decreased to the level of approximately 20–50% of the age-matched control, although the serum level of immunoglobulin in these patients was almost comparable to the control level. The number of immunoglobulin containing cells in the bone marrow was inversely related with the degree of infiltration of leukemic cells and the correlation of Ig-G containing cell count (Y) and percentage of blast cells (X) was Y = 91.8–1.9X (r =−0.436, P<0.05). Follow-up examination of the bone marrow after chemotherapy revealed that the recovery of the number of immunoglobulin containing cells in the remission state appeared to occur in younger patients, but not in older ones.