Drug interactions and digitalis toxicity.
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Biomedical subjects
Publications and source records attributed to R E Mancini.
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Biochemical analysis and morphological studies were carried out in six patients with lymphomas during and after withdrawal treatment with chlorambucil, testosterone propionate (TP) and human chorionic gonadotropins (HCG). In the course of the treatment with chlorambucil patients developed severe oligozoospermia or azoospermia. The spermatogenesis recovered after a variable period of time following suspension of treatment. During the drug administration seminal fructose and citric acid concentrations increase but the recovery after withdrawal takes a longer period of time. Simultaneous treatment with HCG or TP normalized the biochemical parameters without restoring spermatogenesis.
Ribonucleic acid extracts (RNA) obtained from the lymph nodes and spleens of guinea pigs, which were immunized with testicular antigen emulsified in Freund's complete adjuvant (FCA), were injected intraperitoneally into normal guinea pigs. The transferred guinea pigs developed a delayed hypersensitivity to sperm antigens and testicular lesions which resembled the lesions obtained in the donor RNA guinea pigs. When the transfer was performed with RNA extracted from guinea pigs immunized with FCA alone or with 'immune' RNA treated with Ribonuclease, neither cellular immunity nor testicular lesions were observed.
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An antiserum was obtained in rabbits using as antigen a preparation rich in basement membranes isolated from normal rat testis. By passive hemagglutination test a titer of 1/20,000 was obtained when the antiserum was reacted with the specific antigen; no cross reactions were detected with other fractions extracted from the germinal cells of rat testis. A weak cross reaction was obtained when the antiserum was reacted with collagen extracted from rat testis. Moreover, the antiserum cross reacted with other isolated basement membranes such as glomerular basement membrane of rat kidney and sheep lens capsule. By the indirect immunofluorescent technique the localization of the antigen antibody reaction was detected at the seminiferous tubular wall and vessels. No reaction was observed in other structures of the testis except for a faint reaction at the interstitial collagen fibers. Both, serological and immunohistochemical techniques demonstrated: (1) the existence of common antigenic determinants among basement membranes of different organs of the rat, (2) a partial immunological identity among basement membranes of different species.
An acute and intense trauma was inflicted in one of the testes of adult guinea pigs. The immunological response and histological changes developed both in the injured and contralateral glands were studied at different intervals of time. It was observed: 1) Necrotic seminiferous tubules and a granulomatous cell reaction were seen in the injured gonad at 15 days. This was followed by a reduction of the mononuclear cell infiltration at 48 days. Finally a fibrotic tissue replaced the damaged areas at around 100 days. 2) Foci showing the classical picture of immunologic orchitis appeared in the contralateral gland at 15 and 48 days. Less frequent lesions were detected in the final period of the experiment. 3) These lesions were accompanied by cellular immunity detectable by the macrophage migration inhibition test at 15 and 48 days. With the exception of cytophilic activity also detected in same periods, no antibodies of hemagglutinating and sperm-agglutinating types could be found.
Classic experimental immunologic orchitis was induced in guinea pigs by injection of homologous testis homogenate in complete Freund's adjuvant. Blood samples were obtained periodically for 45 days and the animals were hemicastrated on the 8th day after sensitization. By the 8th day, cytophilic activity was found in the serum simultaneously with several foci or orchitis. Significant levels of this activity were found until day 29, but it was absent in animals sensitized with an unrelated antigen or with complete adjuvant alone. Low and transitory levels were detected in some guinea pigs when antigen was administered with incomplete Freund's adjuvant. It is concluded that cytophilic activity is organ-specific and requires complete Freund's adjuvant. Possible implications in experimental immunologic orchitis are discussed.
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Adult outbread male guinea pigs were autoimmunized without adjuvant. Homogenates were prepared with one of their own testes previously submitted "in vivo" and "in vitro" to thermal injury. Animals received a single or daily repeated intradermal injection without added adjuvant, in one or different skin sites. Guinea pigs daily sensitized in the same site during 30 days showed the presence of: a) dermal granuloma at the site of injection; b) several foci of typical allergic orchitis; c) delayed hypersensitivity detected by inhibition of macrophage migration; d) moderate titres of spermagglutinins and negligible levels of hemagglutinating antibodies. Guinea pigs receiving a single dose in one site only developed delayed hypersensitivity. Animals daily sensitized with the same dose of altered antigen in different sites, or with normal testis antigen either in one or different sites, showed negative results. The correlation among testicular lesion, dermal granuloma and cellular immunity is discussed. It is concluded that testis autosensitization is obtained in the absence of added adjuvant provided that a thermally injured gonad used as antigen is repeatedly injected in the same site.
Human spermatozoa separated from normal semen were washed with NaC1 (0.9%)and then were washed nine and 20 times with water. Soluble and insoluble fractions were thus obtained. Proteins, nucleoproteins, lipids, and carbohydrates were determined in both fractions. Different subproducts were obtained from the insoluble fraction, and analysis of diffusible proteins was made by disc electrophoresis. They were also used as antigens in immunoserologic reactions against anti-human seminal plasma, antihuman serum proteins, and anti-insoluble fraction of sperm cells. Aglycopeptide, isolated from human seminal plasma, was also employed as antigen against the antisera. The following results were observed: (1) the soluble fraction showed a high concentration of proteins and carbohydrates and a negligible amount of nucleic acid; (2) the insoluble fraction (nine times washed spermatozoa) had a high content of proteins, low concentration of carbohydrates, and no lipids; (3) cross reactions were observed by immunodiffusion test among spermatozoa washed nine times, spermatozoa washed 20 times, seminal plasma and soluble fraction against antiseminal plasma and anti-insoluble fraction SRM9, suggesting the presence of similar antigenic groups; and (4) immunoelectrophoresis showed three arcs for nine times washed speratozoa against anti-insoluble fraction and anti-seminal plasma.
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Two objective methods and one subjective method for measuring +Gz tolerance (inertial vector in a head-to-foot direction) were compared on the human centrifuge. Direct eye-level blood pressure (Pa), blood flow velocity in the superficial temporal artery (Qta), and subjective visual symptoms were used to determine tolerance to rapid onset acceleration (1 G/s) on the USAFSAM human centrifuge. Seven "relaxed" subjects with extensive centrifuge experience were exposed to gradually increasing +Gz plateaus until the subject reported 100% loss of peripheral centrifuge gondola lights (PLL) and 50% loss of central light (CLD); viz., blackout. Zero forward Qta occurred 6 s (range 4-9 s) before subjective blackout and when mean eye-level blood pressure had reached 20 +/- 1 mmHg (SE). The results of this study indicate that flow changes in the superficial temporal artery reflect flow changes in the retinal circulation during +Gz stress.
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