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Biomedical subjects

H Kashiwagi

Publications and source records attributed to H Kashiwagi.

At least 19 recordsLinked to original sources

Effects of splenectomy on immune thrombocytopenic purpura in (NZW x BXSB) F1 mice: analyses of platelet kinetics and anti-platelet antibody production.

Effects of splenectomy on platelet kinetics and production of anti-platelet antibodies were studied in male (NZW x BXSB) F1 (W/B F1) mice, which are known as the animal model of immune thrombocytopenic purpura (ITP). Studies on organ localization of radiolabeled platelets revealed that splenic uptake significantly increases in W/B F1 mice in comparison with that of normal controls. W/B F1 mice showed a significant increase in platelet counts and, in contrast with sham-operated controls, high levels of platelet counts were maintained up to 6 weeks after splenectomy. Platelet lifespans (PLSs) did not reach normal levels, although prolonged PLSs were observed. In addition, platelet-associated antibody (PAA) values showed a tendency towards transient decrease, but there was no change in platelet-bindable serum antibodies (PBAs). These findings indicate that the suppression of anti-platelet antibody production is essential to the treatment of ITP; splenectomy may not be effective in treating severely affected ITP patients because, although the spleen is one of the major sites of platelet sequestration and antibody production, reticulo-endothelial systems (RESs) (liver, bone marrow, lymphnodes, etc.) other than the spleen are also responsible for the destruction of platelets. We therefore consider the W/B F1 mouse to be a useful model of human ITP, and believe that it provides valuable information for the development of new therapeutic agents in patients with ITP, especially those who do not respond to splenectomy.

Animals

Mechanisms of corticosteroid action in immune thrombocytopenic purpura (ITP): experimental studies using ITP-prone mice, (NZW x BXSB) F1.

To determine the mechanism by which platelet counts increase after corticosteroid therapy for human immune thrombocytopenic purpura (ITP), we studied the platelet kinetics using prednisolone (PDN)-treated ITP-prone mice, (NZW x BXSB) F1 (W/B F1). An increase in platelet counts was observed in W/B F1 mice (n = 10, mean +/- SD, 1,202 +/- 202 x 10(3)/microL) 4 weeks after treatment with PDN (2 mg/kg/d); no increase occurred in nontreated W/B F1 mice (n = 5,651 +/- 126, P less than .005). Prolonged platelet life-spans (PLSs) were observed in treated W/B F1 mice (1.29 +/- 0.40 days), but not in nontreated controls (0.60 +/- 0.24 days, P less than .01). No increase in platelet production (platelet turnover) was found in PDN-treated W/B F1 mice, but significant decreases in platelet-associated antibodies (PAAs) and platelet-bindable serum antibodies (PBAs) were noted. Studies on organ localization of radiolabeled platelets showed that hepatic uptake significantly decreased in the treated W/B F1 mice, but not in nontreated W/B F1 mice. To elucidate the effect of PDN on the reticulo-endothelial phagocytic activity in W/B F1 mice, we studied in vivo clearance of IgG-sensitized, 51Cr-labeled autologous erythrocytes. W/B F1 mice treated with PDN showed a marked impairment of their ability to clear these cells, although PDN had little effect on the number of splenic or hepatic macrophage Fc gamma receptors. These results and our previous findings of splenectomy suggest that PDN improves platelet counts not only by suppressing systemic reticulo-endothelial phagocytic function but also by reducing antibody production.

Animals

Anti-interleukin-6 autoantibodies in rheumatic diseases. Increased frequency in the sera of patients with systemic sclerosis.

OBJECTIVE: To investigate the presence and the roles of anti-interleukin-6 (anti-IL-6) autoantibodies in rheumatic diseases, and to further elucidate clinical and pathophysiologic significance of anticytokine autoantibodies. METHODS: Anti-IL-6 IgG autoantibodies were measured by the 125I-IL-6 binding activity of IgG, which was isolated from serum by protein A-Sepharose. RESULTS: Nine of 52 sera (17.3%) from patients with systemic sclerosis (SSc) contained anti-IL-6 antibodies, whereas only 1.9% of sera from normal subjects and 0-5% of sera from patients with other rheumatic diseases were positive for the antibodies. Moreover, anti-IL-6 autoantibodies were found predominantly among patients with the limited form of SSc (42.9%), compared with those with the diffuse form (7.9%). CONCLUSION: Anti-IL-6 IgG autoantibodies were detected in patients with SSc, particularly those with the limited form of the disease, at a significantly increased frequency compared with normal subjects and patients with other rheumatic diseases. These results suggest that the development of anti-IL-6 autoantibodies and IL-6 may have a role in the pathophysiology of SSc.

Adult

Clinical and immunological evaluation of intraoperative radiation therapy for patients with unresectable pancreatic cancer.

The clinical efficacy of intraoperative radiation therapy (IORT) and the changes of immunological parameters were investigated. Nine patients with unresectable pancreatic cancer were treated with IORT (2,500-3,500 cGy) and the changes of various immunological parameters were compared with those in 11 patients with advanced cancer who received external beam irradiation therapy (XRT), 2,500-3,500 cGy. After IORT, 71% of patients obtained pain relief, two of the nine patients showed a partial response, and the serum CA 19-9 level decreased in six patients. However, the median survival was only 210 days. Natural killer activity, lymphokine-activated killer activity, and interferon gamma-activated killer activity were not inhibited by IORT, and phytohemagglutinin-induced blastogenesis was actually augmented after IORT, whereas all these parameters were inhibited by XRT. Thus, it is suggested that IORT may augment or at least stabilize systemic antitumor immunity.

Aged

Progressive systemic sclerosis complicated with immune thrombocytopenia during D-penicillamine therapy.

Immune thrombocytopenia is a rare complication of progressive systemic sclerosis (PSS). A 47-year-old female with PSS treated with D-penicillamine developed immune thrombocytopenia, which promptly responded to prednisolone and withdrawal of D-penicillamine. Platelet-associated IgG was elevated and the bone marrow megakaryocyte count was normal. There was an inverse relationship between the level of platelet-associated IgG and the platelet count. A lymphocyte stimulation test sensitized by D-penicillamine was positive. The present case suggests that immune thrombocytopenia may be regarded as one of the D-penicillamine-related immune abnormalities. To our knowledge, its association with PSS has never been reported.

Blood Platelets

Sjögren's syndrome with hydronephrosis caused by pseudolymphoma.

A 67-year-old woman with Sjögren's syndrome was found to have left hydronephrosis and stenosis of the left ureter. Exploratory laparotomy disclosed a nodule at the ureteropelvic junction of the left ureter. Histopathological examinations of the biopsied specimen of this nodule showed lymphoid hyperplasia within the ureteral wall. Low dose prednisolone improved hydronephrosis and pseudolymphoma within several months. Hydronephrosis secondary to pseudo-lymphomatous infiltration of the ureter is a rare but, if properly treated, reversible complication of Sjögren's syndrome.

Aged

[Problems in ulcer surgery after the introduction of H2-receptor antagonists].

Recently, antisecretory drugs such as H2-receptor antagonists (H2-RA) or proton pump inhibitor have been used for peptic ulcer patients widely in Japan. However, there are possibilities that long term administration of H2-RA might cause changes in intragastric environment. The present study was designed to clarify the changes of surgical treatment in Japan Surgical Society training hospitals, before and after introduction of H2-RA. Serum gastrin and antral G-cell number was measured after administration of H2-RA (1 mg/kg 14 days continuous infusion) in rat. Also, acid secretion and gastrin response stimulated by adrenalin (40 ng/kg.min) were measured in duodenal ulcer patients. 1) In the view of surgical treatment, elective operation highly decreased after the introduction of H2-receptor antagonists, and showed the increase of the rate of emergency operation up to 70%. 2) Hypergastrinemia and antral G cell hyperplasia were observed after administration of H2-RA in rats. 3) Acid secretion stimulated by adrenalin which is considered as antral G cell dependent, showed a higher response in H2-RA treated cases than in those untreated. 4) Antrectomy was carried out in 43.4% of the patients treated with H2-RA versus 18.9% to the patients untreated.

Animals

[Effect of famotidine on gastrin cell, somatostatin cell, and prostaglandin E2 concentration of stomach in experimental pyloric stenosis model].

We investigated the effect of 4-weeks famotidine administration (15 mg/kg/day) on gastrin cell (G-cell), somatostatin cell (D-cell) and prostaglandin E2 (PGE2) of gastric mucosa in pyloric stenosis rats. As a result, the increase of G-cell number and serum gastrin level in pyloric stenosis rats were potentiated by famotidine administration. However, the increase of D-cell number in pyloric stenosis was remarkably abolished by famotidine administration, and G/D cell ratio was increased accordingly. Moreover, famotidine administration decreased PGE2 concentration in fundic mucosa of the stomach without altering PGE2 concentration in pyloric mucosa. Our results suggested that famotidine administration in pyloric stenosis had a possibility to worsen the balance of endocrine cell kinetics in stomach, and PGE2 in fundic mucosa would play a roll on the proliferation of D-cell in pyloric stenosis.

Animals

[Clinical significance of antinuclear antibody in patients with idiopathic thrombocytopenic purpura].

The clinical significance of antinuclear antibodies (ANA) in patients with chronic idiopathic thrombocytopenic purpura (ITP) was evaluated. Serum samples of 55 patients with ITP without clinical features of systemic lupus erythematosus (SLE) were examined. The average follow-up period was 5.5 years. Positive ANA was found in 23 of the 55 patients. Twelve of these 23 showed a high-titer of ANA. There was no difference in platelet counts between ANA positive patients and negative patients, and there was no correlation between platelet counts and antibody titers. Ten of the 23 positive sera had precipitating antibodies to nuclear antigens; 7 SS-A and 3 RNP antibodies. The platelet counts of the 7 cases with anti-SS-A antibody positive were slightly low compared with those of the anti-SS-A antibody negative patients. None of the 10 patients developed SLE during the average follow-up period of 8.1 years. These results suggest that ITP patients who have a high-titer of ANA or antibody against SS-A do not always develop SLE. It was concluded that ANA with a high titer or precipitin to nuclear antigens, particularly SS-A, dose not predict a high risk of developing SLE in the future.

Adult

[A recovered case of serious lung tuberculosis on wanderer].

This report is a case study of a vagrant whose state of tuberculosis showed noteworthy improvement due to clinical treatment. A 54-year-old male, vagrant, was admitted to the hospital in a state of preshock because of a serious stage of lung tuberculosis. The clinical course was severe, but after three months of intensive care the patient recovered. It was noted that the echocardiogram taken after recovery revealed improvement when compared with the one taken upon admission, which showed remarkable right ventricular overload. Furthermore, anti-tuberculosis agents proved to be very effective in this case. The patients respiratory functions improved more markedly than had been expected. The reason for reporting this case study is to bring attention to the improvements in the patient's clinical course and echocardiographic findings. These suggest that tuberculosis in vagrants may differ from the usual stage of tuberculosis diagnosed in elderly persons in terms of response to anti-tuberculosis agents and potential recovery.

Antitubercular Agents

Significance of plasma endothelin-1 levels in patients with systemic sclerosis.

Endothelin-1 (ET-1) is a novel potent vasoconstrictor peptide discovered in the supernatant fraction of cultured endothelial cells. We measured plasma levels of ET-1 using a sensitive sandwich enzyme immunoassay. Plasma concentrations of ET-1 in 31 patients with systemic sclerosis (SSc) (1.90 +/- 0.47 pg/ml) were higher than those (1.31 +/- 0.10 pg/ml) in 25 age and sex matched healthy subjects. Patients with SSc with diffuse scleroderma had higher levels of ET-1 compared with those with limited scleroderma. Plasma ET-1 levels correlated inversely with carbon monoxide diffusing capacity (DLco). Measurement of plasma ET-1 levels may be useful as a predictor of prognosis of SSc.

Adult

Preliminary criteria for classification of adult Still's disease.

We have attempted to design classification criteria for adult Still's disease by analyzing the data obtained through a multicenter survey of 90 Japanese patients with this disease and of 267 control patients. The proposed criteria consisted of fever, arthralgia, typical rash, and leukocytosis as major, and sore throat, lymphadenopathy and/or splenomegaly, liver dysfunction, and the absence of rheumatoid factor and antinuclear antibody as minor criteria. Requiring 5 or more criteria including 2 or more major criteria yielded 96.2% sensitivity and 92.1% specificity. However, an exclusion process will be needed for an accurate classification, since this disease is relatively rare.

Adolescent

[An experimental study of adrenalin-stimulated gastric acid secretion and gastrin secretion in rats of cysteamine-induced duodenal ulcer].

It is known that cysteamine-induced duodenal ulcers in rats are similar to the human duodenal ulcers in some aspects. We investigated their similarities in view of adrenalin-stimulated gastric acid secretion and gastrin secretion in these rats. Acid outputs decreased in the control group by the administration of adrenaline, but in the cysteamine-administered group acid outputs increased dose dependently. Serum gastrin levels and plasma noradrenaline levels increased by cysteamine administration. The abnormal gastric acid secretion by the adrenalin infusion in the process of cysteamine-induced duodenal ulcers in rats, which was resembled to that of duodenal ulcer patients, was recognized.

Animals