[Menkes' kinky hair disease--2 cases].
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Biomedical subjects
Publications and source records attributed to T Aoki.
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Antisera against five newly established AKR spontaneous leukemias (KSL) prepared by immunization of KSL cells in (C57B1/6 X C3Hf/He)F1 mice were preabsorbed with non-leukemic AKR lymphoid cells to remove antibodies against virus-associated surface antigens and alloantigens. In absorption tests the antisera showed no cross-reaction by immunofluorescence microscopy with thymocyte, fetal, male-specific H-Y, E and X.1 antigens; with known Gross murine leukemia virus-associated antigens; or with cell surface antigens on Friend, Moloney and Rauscher virus-induced tumors. It was thus shown that the antigens detected were leukemia-specific, were acquired by malignant transformation, and consisted of two types: (1) a common antigen in all the KSL, and (2) individual antigens found in four of the KSL which showed distinct patterns of partial cross-reactivity with the other KSL.
Soluble extracts from Moloney virus-induced leukemia cells were shown to contain immunogenic and immunosuppressive components. Immunogenic components were divided into two classes based on their ability to :(1) combine with humoral antibody to inhibit cytotoxic activity; or (2) stimulate blastogenesis in normal syngeneic lymphocytes. Immunosuppressive components were demonstrated by the inhibition of DNA synthesis in normal syngeneic lymphocytes and suppression of a mixed lymphocyte reaction. Stimulating components in many soluble preparations were completely masked by immunosuppressive components. However, all three components could be resolved by Sephadex G200 chromatography.
The author previously reported that the serum calcium (Ca) and inorganic phosphorus (P) levels were gradually decreased with advance in age in regularly menstruating women, but that they were rapidly increased soon after the menopause. In this experiment the changes of the serum Ca and P levels in postmenopausal women were studied more precisely in 410 peri- or post-menopausal subjects and 534 controls with regular menses. They were classified into 12 groups according to age or period since last menses. The clavicular cortical thickness was also measured as an index of bone resorption. Blood samples were taken between 9-11 A.M. after an overnight fast and the separated sera were applied to a Technicon Autoanalyzer SMA 12/60 and analyzed. The mean levels of Ca and P in serum were both increased following the menopause and reached a plateau in Groups F-3 (12-24 months since last menses) and G (2-5 years since last menses). In Group G (5-10 years since last menses) both the levels were slightly declined. Then a dissociation was observed in Groups I-1 and I-2. This was a successive decrease of Ca and a re-increase of P. This dissociation might be explained partly by the physiologic fall of parathyroid function. Furthermore the clavicular cortical thickness was measured with a micrometer in the middle of the clavicle on the chest X-ray film of the same subjects and the clavicular score was computed as Cortical width X 100/Whole width. The score was gradually but steadily reduced with the lapse of time after the menopause and in Group I-2 it was lowered to approximately 45% of that in the premenopausal groups. From these results it is certain that the decline of estrogen secretion led to the elevation of the serum Ca and P levels and subsequently to the reduction in the clavicular score.
Gibbon natural antibody examined by immunoelectron microscopy reacted with the entire envelope of type C virus and with areas on the cell surface equivalent to or smaller than the diameter of a virion in gibbon and human culture cells infected with or releasing type C viruses. The antibody activity was absorbed completely by two cell cultures infected with gibbon ape leukemia virus and by the virus itself, and partially by normal gibbon spleen cells and dog thymus-derived cells infected with baboon endogenous type C virus, and fresh white blood cells obtained from a patient with chronic myelogenous leukemia in acute blastic crisis.
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Sera from healthy humans contained naturally occurring antibody against group- or subgroup-specific antigen on the envelope of the following type C viruses isolated from primates: gibbon ape leukemia virus, simian (woolly monkey) sarcoma virus, baboon endogenous type C virus, and putative human type C viruses [HL23V isolated from blood cells of a patient with acute myelogenous leukemia (HL23) and HEL-12V from human embryonic diploid cells (CIH-32)]. Two sera also reacted with C57BL/6 mouse leukemia induced by Friend virus. These results were obtained by indirect immunoelectron microscopy with various virus-producing cells and by absorption tests using as targets gibbon lymphosarcoma cells that release gibbon ape leukemia virus. In a previous report, the presence of natural antibody in sera from healthy gibbon apes was demonstrated. When the specificities of the human and gibbon natural antibodies were compared, the human natural antibody reacted with two nonproducing culture cell lines of human lymphocytic leukemia (CEM-A and MOLT) and with human embryonic diploid (CIH-1(V-) cells [which became type C virus-producing CIH-32(V+) cells after many passages], but did not react with normal gibbon spleen monolayer cells. In contrast, gibbon natural antibody showed no reaction with CEM-A, MOLT, and CIH-1(V-) cells but reacted with gibbon spleen monolayer cells. Neither human nor gibbon natural antibody that was reactive with gibbon ape leukemia virus crossreacted with feline leukemia virus and mouse wild-type AKR leukemia virus. The gibbon lymphosarcoma cells releasing gibbon ape leukemia virus were used in a screening study of sera from healthy humans. Out of 72 sera screened by indirect immunoelectron microscopy using this system, 55 were positive (76%), i.e., 26 out of 35 males (74%) and 29 out of 37 females (78%). The highest incidence of antibody production was in 1- to 10-year-olds and 31- to 40-year-olds, with the adults exhibiting higher levels. Differences in incidence of natural antibody were not found to be sex-linked. These findings suggest that type C RNA viruses related to the gibbon ape leukemia virus and simian (woolly monkey) sarcoma virus family as well as the baboon endogenous type C virus family may be widespread in humans.
An inactivated and lyophilized preparation of a low virulence strain (Su) of Streptococcus pyogenes (group A) was designated OK-432. When 2- and 5-month-old AKR mice were inoculated im with OK-432 twice weekly throughout their life-spans, spontaneous leukemias occurred later and at a lower incidence than in control groups. By virus neutralization and cytotoxicity tests and by immunoelectron microscopy, antibodies against virus and cell-surface antigens of transplanted AKR leukemia were not detectable in sera of nonleukemic mice of any group. Whereas sera from mice treated with OK-432 were the only positive for interferon, viremia was clearly demonstrated in control groups by reverse transcriptase assays of the plasma.
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This review describes oncogenic C-type virus and virus-associated antigens as phenotypic expressions of virus activities in malignant cells and cell surface antigens acquired by malignant transformation. The range of host-immune responses to these antigens in experimental systems is discussed in relation to the immunotherapy and immunoprophylaxis of human cancer patients.
Serum calcium, inorganic phosphorus and alkaline-phosphatase were determined in 3,191 women as a part of a multiphasic health testing program. A fasting sample of blood was drawn between 9 and 11 a.m. and the separated serum was applied to a Technicon Autoanalyzer SMA 12/60 and measured. In 527 women, who were found to have no abnormalities on the other laboratory tests or by the physical examination, were the results of determination studied in relation to age and menstrual status. The values obtained from 13,258 men were employed as a control. In regularly menstruating women the serum calcium level was decreased with the advance of age. Once the menstrual cycle had got irregular toward the menopause, the serum calcium level was rapidly increased, reached maximum in 2-5 years after the menopause, and was slightly decreased thereafter. The serum inorganic phosphorus level also varied in a similar attitude. On the other hand both the serum calcium and phosphorus levels in men were gradually reduced with the advance of age and no fluctuation was observed. Alkaline-phosphatase in serum was distinctly enhanced in the postmenopause. These data indicate that the decline in estrogen secretion results in hypercalcemia and hyperphosphatemia and that a prophylactic estrogen therapy may be considered at the early stage of the postmenopause for preventing the increased bone resorption.
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Spleen cells from untreated young male and female C57BL/6 and C58 mice and of male C3H/He mice showed cytotoxic activity in vitro against BALB/c X-radiation-induced leukemia RL male 1 cells by 51Cr-releasing lymphocyte-mediated cytoxicity (LMC) tests, but old mice of these strains lacked LMC activity. In contrast, spleen cells from male and female AKR, BALB/c, and DBA/2 mice, and from female C3H/He mice had no appreciable LMC activity. The proportion of active cells in spleens from young (C57BL/6 times BALB/c)F1 or reciprocal hybrid mice was higher in females than in males. The specificity of the LMC reaction of RL male 1 cells, determined by LMC inhibition assays, was somewhat different from that of previously reported serologic X.1 tests. Thus the antigen detected by LMC has been tentatively designated X.1'. The main effector cells in this system were uncharacterized cells not adherent to glass surfaces or nylon-wool columns. These findings in RL male 1 leukemia extend the evidence for the presence of naturally occurring LMC. With the single unexplained exception of strain C3H/He, the LMC activity against RL male 1 cells, exhibited by untreated mice of various strains, corresponded with a previous classification of mouse strains immunologically as X.1 responders or as X.1 nonresponders according to their ability to reject X.1-positive leukemia cells.