Biomedical subjects
Publications and source records attributed to F Furukawa.
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The spontaneous occurrence of retroviral gp70 immune complexes (ICs) in the blood of autoimmune New Zealand black and (New Zealand black X New Zealand white)F1 ([NZB X NZW]F1) mice is determined by a single dominant locus of the NZB strain (provisionally designated Agp-1). A combined effect of 2 unlinked dominant NZB loci (Ads-1 and Ads-2) is required for the production of anti-double-stranded DNA (anti-dsDNA) antibodies in these mice. The present genetic studies using (NZB X NZW)F1 X NZW backcross mice and their second through fourth generation progeny revealed that Agp-1 and Ads-1 exist in common or are closely linked on chromosome 17 of NZB mice and are related to the occurrence of renal disease. The renal disease and the serum level of both anti-dsDNA antibodies and gp70 ICs were more intense in (NZB X NZW)F1 hybrids than in NZB mice, indicating the contribution of NZW genes. In (NZB X NZW)F1 mice, a single dominant locus from the NZW strain, Agp-3, intensified the magnitude of gp70 IC formation, and a combined effect of 2 unlinked dominant loci from the NZW strain, Ads-3 and Ads-4, acted to increase the serum titers of anti-dsDNA antibodies. This study clearly indicates that the NZW loci Agp-3 and Ads-3 exist in common or are tightly linked on chromosome 17, are closely linked to the H-2 complex, and are associated with the severity of renal disease in (NZB X NZW)F1 hybrids.(ABSTRACT TRUNCATED AT 250 WORDS)
Using a sensitive and modified solid-phase radioimmunoassay for detecting anti-cardiolipin antibodies, sera of 45 patients with lepromatous leprosy were examined. Nine of the 45 (20%) showed positive levels of anti-cardiolipin antibodies. Inhibition tests revealed that these antibodies significantly cross-reacted with double-stranded (ds) DNA, but not with single-stranded (ss) DNA or extractable nuclear antigens (ENA). We describe the unique pattern of antibody cross-reactivity with cardiolipin and dsDNA in sera of patients with lepromatous leprosy.
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Immunoserological studies on polyclonal B cell activation were carried out on 39 patients with mucocutaneous lymph node syndrome (MCLS) and in age-matched healthy individuals. The incidence of anti-mite, P. acnes (Kato) and EB virus antibodies, recently proposed as aetiological agents by some investigators, was increased in the patient group. Serum immunoglobulin (Ig) M level and IgM-anti-dinitrophenyl (DNP) antibodies, which are considered to be parameters of polyclonal B cell activation, were determined in MCLS cases. The level of serum IgM in MCLS was significantly elevated (0.02 less than P less than 0.05). Levels of anti-DNP antibodies in seven cases of MCLS (18%) were significantly higher than those of the controls (P less than 0.01). Nine of the ten pair sera in MCLS showed a stage-dependent decrease in anti-DNP antibodies. These results suggest that polyclonal B cell activation occurs in MCLS.
The ultrastructural localization of immunoglobulin deposits in the dermoepidermal junction of MRL/l mice was examined using immunoperoxidase staining. All specimens that showed positive findings at the basement membrane zone of the skin on light microscopy had reaction products at the sub-basal laminar area when observed by electron microscopy. In the skin that had no distinct eruptions or which was distant from the lesions, the reaction products were distributed mostly just beneath the basal lamina in fine to course granular deposits. In the lesional skin, they formed a rather uniformly granular pattern among the irregularly arranged collagen fibrils and increased fine fibrillar amorphous material under the highly infolded basal lamina. Some of the reaction products were located just on the collagen fibrils and some appeared to be related to the free basal lamina. From the perspective of immunoelectron microscopy, the skin eruptions of MRL/l mice may serve as a good dermatological model of human systemic lupus erythematosus.
Histamine metabolism, i.e., concentration of histamine and activities of histamine-degrading enzymes, histamine-N-methyltransferase (HMT), and diamine oxidase (DAO), were examined in the Arthus reaction induced in guinea pig skin. The specific activity of HMT was 44.12 +/- 3.80 pmole/min/mg protein and was about 15 times greater than that of DAO in control specimens. However, HMT activity decreased time dependently to 35% of the control at 3 hr and to 10% 48 hr after the initiation of the reaction. DAO activity increased to 150% till 1 hr followed by a linear decrease to 35% at 6 hr and to 10% at 48 hr. Histamine concentration showed a prominent linear decrease to 15% of the control at 2 hr followed by an increase to about 85% at 6 hr. This biphasic change seemed to be well explained by the dynamic changes in the activities of histamine-degrading enzymes. Such decrease in enzyme activities were not observed in other experimentally induced inflammations including dinitrochlorobenzene allergic and croton oil dermatitis. The addition of tissue extract from the Arthus reaction sites resulted in about 30% inhibition in both of two enzyme activities, suggesting the presence of some inhibitory factor(s) in the reaction sites.
The carcinogenic potential of sodium hypochlorite was examined in F344 rats. Groups of 50 males or 50 females were given sodium hypochlorite in their drinking-water, at concentrations of 0.1 and 0.05% for males and 0.2 and 0.1% for females, for 104 wk. Similar numbers of male and female rats received distilled water without supplement throughout the experiment. All surviving rats were killed at wk 112 (after 8 wk on untreated tap-water). Rats of both sexes given the chemical showed a reduction in body-weight gain, but haematological and biochemical examination of the blood showed no changes due to treatment, and no significant lesions attributable to the treatment were detected in any tissue in the histopathological investigation. Although a variety of tumours developed in all groups, no dose-related change in either the incidence or latent period of tumours was observed for any organ or tissue in either sex. Under the experimental conditions described, therefore, sodium hypochlorite was not carcinogenic in F344 rats.
The effects of antioxidant administration during the post initiation phase of gastric tumor development were investigated in male Wistar rats treated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Animals (20/group) were given MNNG in the drinking water (100 mg/l) for 8 weeks, and for the duration of this treatment were also fed on diet supplemented with 10% sodium chloride. Thereafter, they were divided into 6 groups and were maintained on diet containing either 2% butylated hydroxyanisole (BHA), 1% BHA, 1% butylated hydroxytoluene (BHT), 1% ethoxyquin (EQ) or 1% DL-alpha-tocopherol (alpha-TP) for 32 weeks. A carcinogen control group was fed the basal diet without antioxidant supplementation. The experiment was terminated 40 weeks after the beginning of administration of MNNG and development of gastroduodenal tumors was determined histopathologically. EQ significantly increased the incidence of tumors in the glandular stomach. No modification of tumor development in this region of the organ were observed with 2% BHA, 1% BHA, 1% BHT or 1% alpha-TP, although both 2% BHA and 1% BHA induced and/or promoted tumor development in the forestomach. In addition, nephrocalcinosis was identified only in the kidneys of rats given EQ after MNNG treatment.
Pneumotoxicity of butylated hydroxytoluene (BHT) applied to the skin of CD-1 mice was investigated and compared with that of butylated hydroxyanisole (BHA). To 6 groups of 10 male mice and 10 female mice 0.1 ml of dimethylsulfoxide (DMSO) solutions containing 0, 5, 10, 20, or 30 mg of BHT or 30 mg of BHA were topically applied 3 times weekly for 4 weeks. Between the 4th and 8th day BHT-treated mice exhibited respiratory distress with subsequent dose-dependent mortality. At autopsy dead animals were found to have congestion and enlargement of the lung with oozing of froth from the trachea. Histologically, collapse of the alveoli and dilatation of the alveolar ducts associated with degeneration or necrosis of type I alveolar epithelial cells were evident. The lethal effect of BHT was more manifest in female than in male mice. In contrast, none of the BHA-treated or control mice showed lung abnormalities. In another series of experiments to study the species difference of BHT pneumotoxicity, F-344 rats of both sexes and male Syrian golden hamsters were exposed to BHT by dermal application 3 times weekly for 4 weeks at a dose of 240 mg in rats or 480 mg in hamsters. However, no pulmonary alterations were observed in either species.
We report autopsy findings of an immature neonate whose bladder included a focus of colonic type epithelium in the posterior wall. The small island of mucosa consisted of columnar epithelium with numerous goblet cells and crypt formation. There appeared to be several signet-ring cells in the transitional epithelium adjacent to this area. No gross congenital abnormalities of the bladder or inflammation of the lamina propria was observed. The island of colonic epithelium was considered to be aberrant enteric mucosal tissue rather than glandular metaplasia of the transitional cell epithelium.
We prepared a mouse monoclonal antibody that reacts specifically to human Langerhans cells (LC). The protein recognized by this antibody was mainly in the membranes of Birbeck granules and related structures. Using this antibody, we could identify LC in various tissues; these cells were in the skin, stratified squamous mucosal epithelia, lymph nodes, and the thymus. The antibody did not react with monocytes, tissue macrophages, lymphoid dendritic cells, follicular dendritic cells, or interdigitating cells. The antigen purified with this antibody was a heterogeneously glycosylated protein of Mr approximately 40,000 without interchain disulfide bonds. This antibody may be useful for identifying LC in various human tissues with or without abnormalities, and for studying the origin and fate of Birbeck granules of LC.
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A 12-year-old Japanese girl with a primary intracranial choriocarcinoma arising from the pituitary fossa is reported. There was a markedly high level of serum human chorionic gonadotropin (HCG) throughout the clinical course. Postmortem examination revealed metastatic lesions found in the cerebellum, dura mater, skull (clivus, sphenoidal bone), and lungs. Immunohistochemical characteristics of the primary intracranial tumor and lung lesions disclosed positive stainings for HCG and HCG-beta in the neoplastic syncytiotrophoblastic cells.
Sequential alteration of Syrian golden hamster pancreatic ducts and ductules was investigated by scanning electron microscope during and subsequent to 10 weekly subcutaneous injections of N-nitrosobis (2-oxopropyl) amine (BOP). By examining surface morphology of ductal cells and resin casts of the secretory branches arising from the common duct, a series of lesions ranging from slight derangement of the luminal dimensions and loss of cilia to marked projections of "finger-like" processes accompanied by pleomorphism at the cellular and microvilli levels and increase in numbers of goblet cells could be established. A ductal histogenesis is proposed on the basis of the present scanning electron microscopic and earlier light microscopic findings.