Ken-ichi Honda

Transmission of symptomatic parvovirus B19 infection by fibrin sealant used during surgery

Human parvovirus B19 infection has been shown to be transmissible by blood and blood products and to result in transient aplastic crisis in patients with rapid red cell turnover. We report three cases of iatrogenic parvovirus B19 infection resulting from the use of the same batch of fibrin sealant under operation. Fibrin sealant, which is a typical haemostatic agent produced from blood, has been used during surgery. Human parvovirus is resistant to existing virus‐inactivating techniques, suggesting that infection may occur from blood products contaminated with it. Use of recombinant products for these proteins may thus be necessary.

Common antigenicity of mouse 42°C-specific heat-shock protein with mouse hsp 105

Abstract Mammalian cells incubated at 42°C synthesize a specific heat-shock protein at 42°C (42°C-hsp) that is not induced by heat-shock at 45°C or by other stresses that induce major heat shock proteins (Hatayama et al. (1986) Biochem. Biophys. Res. Commun. 137, 957–963). Antibody raised against a heat-shock protein with molecular weight of 105,000 (hsp 105) purified from mouse FM 3A cells cross-reacted to the 42°C-hsp of the same cells. The antibody reacted only weakly to hsp 105 and 42°C-hsp of human HeLa cells. These results suggested that hsp 105 and 42°C-hsp have the same antigenic determinant, and that 42°C-hsp may have a structure similar to that of hsp 105.

Lipolytic activity of anemia-inducing substance from tumor-bearing rabbits.

Anemia-inducing substance (AIS) is a protein of approximately 50,000 molecular weight secreted by malignant tumor tissue that depresses erythrocyte and immuno-competent cell functions; in this study, its biological effects on adipocytes were examined. Changes in body weight, total body fat, and food intake were investigated in rabbits after VX2 carcinoma transplantation, and the results showed reductions of 11%, 24%, and 30%, respectively, at 40 days after transplantation compared with baseline values (before transplantation). The values were even more markedly reduced 70 days after transplantation. When cyclic plasma perfusion (2 times/wk) was started at 40 days after transplantation, the values at 70 days after transplantation (30 days after beginning plasma perfusion) recovered to 91%, 84%, and 87%, respectively, of the baseline values. AIS fractions were isolated from rabbit plasma by using a phenyl-Sepharose column before transplantation, 40 and 70 days after transplantation, and 30 days after start of plasma perfusion, and AIS activity and lipolytic activity were measured. The results showed enhancement of AIS activity and lipolytic activity as the tumors grew. Lipolytic activity also returned to baseline value as AIS was removed by adsorption by plasma perfusion, and there was a high correlation between lipolytic activity and AIS kinetics. These results strongly suggest that AIS might be one of the substances involved in the enhanced lipolytic activity in advanced tumor-bearing subjects.

HeLa cells synthesize a specific heat shock protein upon exposure to heat shock at 42°C but not at 45°C

Abstract Upon exposure to heat shock, HeLa cells synthesize a small set of proteins having the molecular weights of 70,000, 73,000, 78,000, 85,000, 92,000, and 105,000. In addition to these proteins, we found an unusual heat shock protein induced by heat shock at 42°C, but not at 45°C. The 42°C-specific protein, the molecular weight of which was 90,000, was not produced in control cells and the induction of the protein was completely inhibited by actinomycin D. The protein was not induced by other treatments that induced most heat shock proteins. Thus, this 42°C-specific protein seems to have a peculiar induction mechanism and a specific function in the cells.

Insulin-Lowering Agents Inhibit Synthesis of Testosterone in Ovaries of DHEA-Induced PCOS Rats

Background: Insulin-lowering agents are reported to be useful in treating polycystic ovary syndrome (PCOS) anovulation. It has been suggested that lower insulin levels secondarily affect ovarian tissue, although the direct mechanism of action has not yet been verified. Here we investigated if these agents directly affect the ovary. Methods: Thirty female Wister rats were studied. Six control rats were injected subcutaneously with 0.2 ml sesame oil, while 24 rats used as PCOS models were injected subcutaneously with dehydroepiandrosterone (DHEA) and divided into four groups. Six rats were injected with only DHEA, while the remaining 18 rats received metformin, pioglitazone or troglitazone. The ovaries were immunohistochemically stained with anti- testosterone and anti-17β-HSD antibodies, and then evaluated for morphological changes. Results: In the DHEA administration group, the number of atretic follicles significantly increased compared to that of control rats. The insulin-lowering agents did not improve the multicystic appearance. Serum testosterone concentrations significantly increased with DHEA administration, but the increase was inhibited by oral administration of insulin-lowering agents. Testosterone deposits in ovarian tissue were also reduced by feeding rats insulin-lowering agents. Conclusion: Insulin-lowering agents affected ovarian tissue by inhibiting testosterone biosynthesis in vivo.

Metabolic and Morphologic Characteristics of Adipose Tissue Associated with the Growth of Malignant Tumors

Changes in total body fat and the metabolic and morphologic characteristics of adipose tissue were sequentially investigated in individual rabbits implanted with VX2 tumors to elucidate the pathology of the fat reduction in animals with malignant tumors as compared with that of diet‐restricted rabbits. Lipogenesis in normal, VX2–implanted, and diet‐restricted rabbit groups on day 40 after the start of the experiments was 19.1±2.9, 13.3±3.5, and 41.7±6.0×l05 cpm/g/h, respectively, and glycerol liberation by their adipose tissue was 199±21, 528±94, and 301±45 nmol/g/h, respectively. In addition, apoptotic cells were noted in the adipose tissue of VX2–implanted rabbits on days 20–30 after implantation, but not in diet‐restricted rabbits. The results showed clear differences between the total body fat reduction profiles of VX2–implanted rabbits and diet‐restricted rabbits, suggesting a characteristic lipid metabolism with enhanced lipolysis and diminished lipogenesis in VX2–implanted rabbits. The results strongly suggest that adipocyte apoptosis might be involved in these phenomena.

Excellent Results of Postoperative Radiotherapy for Endometrial Stromal Sarcoma of Low-Grade Malignancy

Endometrial stromal sarcoma of low-grade malignancy (ESSL) is a rare neoplasm, and neither preoperative diagnostic procedures nor standard therapy have yet been established. We treated 3 cases of ESSL in the past 27 years, and we report here one of these cases that was classified as stage III (according to the FIGO classification of endometrial carcinoma). Postoperative radiotherapy was used to treat a residual tumor, and the patient showed a complete response.

Neutropenia Accompanying Parvovirus B19 Infection after Gynecologic Surgery

The hematologic data and symptoms of 7 patients seropositive for parvovirus B19 IgM antibody after gynecologic surgery were analysed. Parvovirus may have been transmitted by fibrin glue prepared from heat-treated human plasma and used for hemostasis during surgery. The peripheral blood neutrophil count decreased to below 1 × 109/l between postoperative day (POD) 10 and 18, but recovered spontaneously to within the normal range. G-CSF injection was effective in preventing neutropenia or obtaining a prompt recovery. The reticulocyte count fell below 10 × 109/l between POD 13 and 19, and also recovered spontaneously. A slapped-cheek rash was not observed in any of the 7 patients.

Apoptosis of muscle cells causes weight loss prior to impairment of DNA synthesis in tumor-bearing rabbits

The mechanism of weight loss induced by the growth of malignant tumors is still unknown. We investigated it by focusing on apoptosis of skeletal muscle. VX2‐tumor was implanted into rabbits and the apoptotic index (AI) of skeletal muscle was measured by in situ end‐labeling assay. Plasma of the tumor‐bearing rabbits was perfused repeatedly through non‐coated charcoal resin. The AI reached 54.6% early after tumor implantation, when weight loss amounted to an 18% decrease in lean body mass (LBM) without change in muscle DNA synthesis or urinary 3‐methylhistidine/ creatinine ratio (3‐MH/Cr). When the decrease of LBM reached 30%, DNA synthesis was decreased by 48% and 3‐MH/Cr was increased by 104%, whereas AI was only 4.7%. The plasma perfusion did not prevent apoptosis in muscle, but unproved LBM, DNA synthesis, and 3‐MH/Cr. There may be two mechanisms of muscle depletion during the tumor growth: apoptosis in the early stage and metabolic abnormalities in muscle in the late stage.

Expression of apoptosis regulatory proteins in the skeletal muscle of tumor-bearing rabbits.

We reported finding that apoptosis occurred in skeletal muscle in the early stage after implantation. In the present study, we investigated expression of the apoptosis‐related proteins Bax and Bcl‐2 to determine the mechanism of the apoptosis. In the early stage of tumor bearing, 20 days after implantation, lean body mass (LBM) was reduced by 5.06±1.10% in the tumor‐bearing group, compared with an increase of 4.96±1.26% in the control group. The apoptotic index (AI) of the skeletal muscle in the tumor‐bearing group increased to 40.5±3.20% but was 0% in the control group, and Bax expression was strongly positive in 5 of the 10 rabbits in the tumor‐bearing group, and significantly stronger than in the control group (P=0.0002). In the late stage of tumor bearing, 40 days after implantation, the AI had declined to 0.93±0.96% in the tumor‐bearing group, but was still 0% in the control group. Bax expression was rarely detected in either the tumor‐bearing group or the control group, and there was no significant difference between the two groups (P=0.706). No significant changes in Bcl‐2 were observed in either group. The above results showed that apoptosis via Bax played a role in muscle wasting associated with progression of the malignant tumor. However, the apoptosis and expression of Bax were seen only in the early stage, within 20 days after implantation, not in the late stage. This suggested that the muscle wasting in the early stage might be caused by a different mechanism from that in the late stage.