AN EXPERIMENTAL STUDY ON THE SIGNIFICANCE OF THE BONE MARROW LYMPHOCYTE IN HAEMATOPOIETIC REGENERATION FOLLOWING ACUTE INJURY DUE TO 60CO IRRADIATION and CYTOTOXIC DRUGS*

Haematopoietic cells of the rat bone marrow were killed almost completely by using hydroxyurea (OHU), cytoslne arabinoslde (ara-C), ⁶⁰Co irradiation and busulfan. The relation between the regeneration of haematopoietic cells of the bone marrow and the behavior of the bone marrow lymphocytes and related cells was investigated quantitatively. Bone marrow lymphocytes and related cells were cytologlcally classified Into lymphocytes, transitional cells and blastic cells on the smeared preparation. Comparing the results of the experiment using OHU 2.5 g/kg with those using whole body irradiation of ⁶⁰Co 700R, the absolute number of nucleated cells In the bone marrow was reduced more prominently in the former case than in the latter. Nevertheless, regeneration of haematopoietic cells began earlier In the former case than in the latter. In the experiment using OHU 2.5 g/kg, haematopoietic cells in the bone marrow almost completely disappeared promptly after the treatment. On the contrary, the bone marrow lymphocytes were rather well preserved, making up 59% of control on the 1st day and 54% on the 2nd day. Moreover, it was evident that the decrease in number of bone marrow lymphocytes and the increase in number of transitional and blastic cells occurred simultaneously around the 4th day after the last dosage, just prior to the haematopoietic regeneration. On the 8th day after whole body irradiation with ⁶⁰Co 700R, in parallel with the appearance of haematopoietic regeneration, the bone marrow lymphocytes, transitional cells and blastic cells were the predominant populations In the regenerating bone marrow. In the experiment using ara-G 600 mg/kg, the number of transitional cells increased evidently prior to haematopoietic regeneration. The author concluded that regeneration of bone marrow haemato-poiesis can take place earlier and more rapidly, when the bone marrow lymphocytes are provided In sufficient numbers.     

CARCINOSARCOMA OF THE URINARY BLADDER

A case of carcinosarcoma of the urinary bladder in a 33-year-old man is presented. The tumor developed from the left anterolateral wall and protruded into the vesical lumen. The excised tumor revealed that more than 99% was sarcomatous component with the appearance of an osteochondrosarcoma. Small foci of papillo-tubular carcinoma were scattered in the sarcomatous area. The histological features, histogenesis and treatment of carcinosarcoma of the bladder are discussed in relation to the literature. ACTA PATHOL. JPN. 35: 981–988, 1985.     

Effect of vitamin K2 on cortical and cancellous bones in orchidectomized young rats

OBJECTIVES: The purpose of the present study was to compare the effect of vitamin K(2) on cortical and cancellous bones in orchidectomized young rats. METHODS: Forty male Sprague-Dawley rats, 6 weeks of age, were randomized by stratified weight method into four groups with 10 rats in each group: baseline controls (BLC), age-matched controls (AMC), orchidectomy (ORX), and ORX+vitamin K(2) administration (K). Vitamin K(2) (menatetrenone) was administered subcutaneously twice a week at dose of 30 mg/kg each. The experimental period was 8 weeks, and cortical and cancellous bone histomorphometry was performed on the tibial shaft and the proximal tibia, respectively. RESULTS: Cortical area (Ct Ar) and cancellous bone volume (BV/TV) were significantly greater in the AMC group than in the BLC group. Ct Ar was significantly lower in the ORX group than in the AMC group, and cancellous BV/TV was also significantly lower in the ORX group than in the AMC group as a result of significantly increased eroded surface (ES/BS). Although Ct Ar in the ORX+K group did not differ significantly from that in the ORX group, cancellous BV/TV was significantly greater in the ORX+K group than in the ORX group, but still significantly lower than in the AMC group. This protective effect of vitamin K(2) on cancellous bone was attributable to normalizing increased ES/BS. CONCLUSIONS: Vitamin K(2) appears to act more strongly on cancellous bone than on cortical bone in ORX young rats. High dose vitamin K(2) could partially prevent the reduction of cancellous bone gain by normalizing raised bone resorption in ORX young rats.     

New criteria for immunofluorescence assay for Q fever diagnosis in Japan

A study was made to evaluate the cutoff value of indirect immunofluorescent-antibody (IFA) test for Q fever diagnosis in Japan. We used 346 sera, including 16 from confirmed Q fever cases, 304 from Japanese pneumonia patients, and 26 from negative cases. Thirteen sera from the confirmed Q fever cases with an immunoglobulin M (IgM) titer of > or =1:128 and/or IgG titer of > or =1:256 by the IFA test were positive by both enzyme-linked immunosorbent assay (ELISA) and Western blotting assay (WBA), whereas 298 sera from pneumonia patients and 26 negative sera with an IgM titer of < or =1:16 and an IgG titer of < or =1:32 by the IFA test were negative by both ELISA and WBA. In the proposed "equivocal area," with an IgM titer of > or =1:32 and < or =1:64 and/or an IgG titer of > or =1:64 and < or =1:128, we found 9 sera, 3 from confirmed Q fever cases and 6 from Japanese pneumonia patients, by the IFA test. Three sera from the confirmed Q fever cases and one of the sera from pneumonia patients were IgM and/or IgG positive by both ELISA and WBA. These results suggest that a single cutoff value for the IFA test may cause false-positive and false-negative results. In conclusion, this study showed that an "equivocal area" should be used for the IFA test rather than a single cutoff value and that sera in the equivocal area should be tested by additional serological assays for confirmation.     

Effect of stimulated neutrophils from the synovial fluid of patients with rheumatoid arthritis on lymphocytes—A possible role of increased oxygen radicals generated by the neutrophils

Neutrophils from the synovial fluid (SFN) of 10 patients with active rheumatoid arthritis (RA) were investigated to determine the generation of oxygen intermediates (OI) (O2-, H2O2, OH .), chemiluminescence, and lysosomal enzymes (lysozyme and beta-glucuronidase). Lymphocytes from healthy individuals were cocultured at 37 degrees C for 17 hr with SFN from the patients and the number of OKT4+, OKT8+, and OKT3+ cells and the response to mitogens were determined. A markedly increased OI and slightly elevated lysosomal enzyme levels were observed in SFN from patients. Coculture of lymphocytes with SFN resulted in a decreased number of OKT4+ and OKT8+ cells and a greatly reduced response to Con A and mildly diminished response to PHA, while OKT3+ cells were not affected. The simultaneous addition of superoxide dismutase and catalase restored the impairment of monoclonal antibody reaction and lymphocyte responsiveness almost to control levels. It is suggested that the disturbed immunoreactivity of synovial fluid lymphocytes from RA patients may be due to increased OI generated by stimulated neutrophils.     

A LIGHT- AND ELECTRON-MICROSCOPIC STUDY OF THE SO-CALLED UNI-VISCERAL SHWARTZMAN REACTION

A morphological study was made on a particular model of Shwartzman reaction which was so designed as to occur mainly in the liver with minimal influence to the other parts of the body. The study was mainly focused on its mechanism; the role of the granulocytes, Kupffer cells, platelets and precipitated fibrin. It was revealed that Kupffer cells were severely damaged by the first, preparative injection and the most conspicuous finding after the second, provocative injection was marked granulocytic infiltration followed by massive hepatic cell necrosis. The infiltrating granulocytes sticked to the endothelium, degenerated Kupffer cells, or other granulocytes and, often aggregated around precipitated fibrin. The erythrocytes in the sinusoid also showed aggregation after the provocative injection of the endotoxin, which was, however, rather loose and easily washed out from the sinusoid by perfusion. It is suggested from the above observations that aggregation of granulocytes as well as precipitated fibrin plays an important role to disturb blood stream mechanically and leads to massive necrosis in the liver.     

Reduced NR2A expression and prolonged decay of NMDA receptor-mediated synaptic current in rat vagal motoneurons following axotomy

To elucidate characteristic changes in the N -methyl- d -aspartate (NMDA) receptor on neurons following axotomy, subunit expressions and functional features of the NMDA receptor were examined in the dorsal motor nucleus of vagus (DMV) of rats receiving vagal axotomy at the neck. Western blotting analysis demonstrated that the expression of NR2A decreased 2–3 days after in vivo axotomy, while expression of NR1 and NR2B, NR2C and NR2D subunits did not change significantly. To examine the functional changes, patch clamp recordings in whole-cell mode were employed on the axotomized DMV neurons identified by retrograde labelling with fluorescent dye. The amplitude ratios of ifenprodil-sensitive components of NMDA response and d , l -2-amino-5-phosphovaleric acid (APV)-sensitive evoked postsynaptic current increased after axotomy. In addition, APV-sensitive postsynaptic currents exhibited a longer decay time in identified axotomized vagal motoneurons than in control neurons. No significant differences in the current density of the NMDA response and the peak amplitude of APV-sensitive synaptic currents were observed between axotomized and intact DMV neurons. In conclusion, a decrease in NR2A expression results in the appearance of functional characteristics of the NMDA receptor predominantly containing the NR2B subunit. This might lead to a long-term increase of the susceptibility of neurons to excitotoxicity.     

Personality of seasonal affective disorder analyzed by Tri-dimensional Personality Questionnaire

BACKGROUND: Although there have been numerous reports in personality of mood disorders, there have been few reports in regard with personality of winter seasonal affective disorder (SAD). Furthermore, no reports have been published concerning summer SAD personality characteristics. Thus, this study was conducted to assess the personality of winter and summer SAD using Tri-dimensional Personality Questionnaire (TPQ) that have been used in a variety of mental disorders. METHODS: A total of 6135 Japanese were evaluated with TPQ, the Seasonal Pattern Assessment Questionnaire (SPAQ) and the Self-rating Depression Scale (SDS). Winter, summer and non-SAD groups were classified by SPAQ. We compared the difference of personality trait among these three groups in consideration of gender, age and SDS score influence. RESULTS: Winter SAD demonstrated higher "Novelty Seeking" and "Harm Avoidance"; summer SAD showed higher "Harm Avoidance" than the non-SAD group. "Harm Avoidance" in both SAD groups was re-analyzed using SDS score as a covariate, and "Novelty Seeking" in winter SAD using age as a covariate. As a result, the significance of high "Novelty Seeking" and high "Harm Avoidance" in winter SAD was excluded. However, "Harm Avoidance" remained the significant difference between summer and non-SAD. LIMITATION: SAD was diagnosed only by SPAQ and not by interview. The state-dependency of "Harm Avoidance" was not confirmed in identical patients over lapse of time. CONCLUSION: Patients with winter SAD have high "Harm Avoidance" dependent on the depressive state that is in accordance with non-seasonal depression. Patients with summer SAD have high "Harm Avoidance" possibly independent from the depressive state.