Granulocyte Colony-stimulating Factor-induced Aortitis with Lung Injury,Splenomegaly, and a Rash During Treatment for Recurrent Extraosseous Mucinous Chondrosarcoma

We herein report a case of aortitis induced by granulocyte colony-stimulating factor (G-CSF) that coincided with lung injury, splenomegaly, and cutaneous manifestations during treatment for recurrent extraosseous mucinous chondrosarcoma. Computed tomography revealed large-vessel vasculitis, splenomegaly, and pulmonary interstitial changes. Treatment with prednisolone was successful. Because sarcoma is a rare disease, this case is valuable for showing clinicians that G-CSF preparations could cause aortitis regardless of the patient''s underlying diseases or therapeutic pharmacological backgrounds.     

A new method of detection of islet cell antibodies (ICA) using peroxidase-labeled protein A,and incidence of ICA in Type I (insulin-dependent) diabetes

Summary We have developed a new method of detecting islet cell antibodies using peroxidase-labeled protein A, and have determined the incidence of ICA in Type 1 (insulin-dependent) diabetes in Japan. In our method, fresh frozen sections of human pancreas and serum samples were incubated and then treated with peroxidase-labeled protein A at room temperature. Conjugates of peroxidase and protein A were subjected to Sephadex G-200 column chromatography, and only the 80,000 dalton peak was employed. The treated sections were allowed to react with haematoxylin and eosin (HE) to confirm the localization of islet cells. With this method, human pancreatic tissues can be used regardless of age and blood type, and the stained sections can be stored for more than 5 years. Serum samples obtained from 52 patients with Type 1 diabetes, 54 with Type 2 (non-insulin-dependent) diabetes and 100 control subjects were examined. In patients with Type 1 diabetes, islet cell antibodies were detected in 14 of 14 (0.5 years after onset), 3 of 6 (0.5–1 years after onset), 7 of 16 (1–5 years after onset) and 2 of 16 (more than 5 years after onset). In contrast, only 4 of 54 patients with Type 2 diabetes and none of the controls were ICA positive. It is concluded that, with our newly developed method using peroxidase-labeled protein A, ICA is present in all Japanese Type 1 diabetic patients whose diabetic manifestations are less than 0.5 years duration from onset.     

NAD(P)H oxidase plays a crucial role in PDGF-induced proliferation of hepatic stellate cells

The proliferation of hepatic stellate cells (HSCs) is a critical step in hepatic fibrogenesis. Platelet-derived growth factor (PDGF) is the most potent mitogen for HSCs. We investigated the role of nonphagocytic NAD(P)H oxidase-derived reactive oxygen species (ROS) in PDGF-induced HSC proliferation. The human HSC line, LI-90 cells, murine primary-cultured HSCs, and PDGF-BB were used in this study. We examined the mechanism of PDGF-BB-induced HSC proliferation in relation to the role of a ROS scavenger and diphenylene iodonium, an inhibitor of NAD(P)H oxidase. We also measured ROS production with the aid of chemiluminescence. We showed that PDGF-BB induced proliferation of HSCs through the intracellular production of ROS. We also demonstrated that HSCs expressed key components of nonphagocytic NAD(P)H oxidase (p22phox, gp91phox, p47phox, and p67phox) at both the messenger RNA and protein levels. Diphenylene iodonium suppressed PDGF-BB-induced ROS production and HSC proliferation. Coincubation of H2O2 and PDGF-BB restored the proliferation of HSCs that was inhibited by diphenylene iodonium pretreatment. Phosphorylation of the mitogen-activated protein kinase (MAPK) family constitutes a signal transduction pathway of cell proliferation. Our data demonstrate that NAD(P)H oxidase-derived ROS induce HSC proliferation mainly through the phosphorylation of p38 MAPK. Moreover, an in vivo hepatic fibrosis model also supported the critical role of NAD(P)H oxidase in the activation and proliferation of HSCs. In conclusion, NAD(P)H oxidase is expressed in HSCs and produces ROS via activation of NAD(P)H oxidase in response to PDGF-BB. ROS further induce HSC proliferation through the phosphorylation of p38 MAPK.     

Alterations in circulating thyroid hormones and thyrotropin in euthyroid patients with Graves' disease after total thyroidectomy: comparison between responders and nonresponders to TSH-releasing hormone

Eleven euthyroid patients with severe exophthalmos of Graves' disease who had been treated with antithyroidal drugs for one to three years prior to total thyroidectomy were studied. All patients were clinically and biochemically euthyroid at the time of operation. According to their responses of TSH to TRH prior to operation, the patients were divided into two groups: (1) five responders and (2) six nonresponders. In group 1, serum TSH levels increased significantly on the third day after thyroidectomy (from 1.5 +/- 0.3 to 8.6 +/- 1.4 microU/mL: P less than 0.05); serum T4 concentrations decreased significantly and were in the hypothyroid range by the third day. In group 2, serum TSH levels rose from 0.5 +/- 0.01 to 3.2 +/- 0.5 microU/ml (P less than 0.05) on the ninth postoperative day; serum T4 concentrations decreased on the third day after operation but did not attain hypothyroid levels until the 12th day. Thus after total thyroidectomy the following are concluded: (1) serum TSH levels even in treated euthyroid patients with Graves' disease, rose more gradually in TRH-nonresponders in comparison with TRH responders; (2) the time when serum TSH elevation occurs is dependent upon serum concentrations of thyroid hormones (serum T3 and T4).     

Characteristic features of folate-deficient neurological diseases in the elderly

Background:  Folic acid (folate) deficiency causes neurological disorders in aged people, the characteristic features of which were examined.
Methods:  Serum folate levels were determined in 343 neurological patients by chemiluminescence. We found 36 folate-deficient patients (10.5%) who were divided into elderly ≥ 65 years old (12 cases) and younger group, < 65 years old (24 cases), and were administered folate (15 mg/day) for 60 days.
Results:   Serum folate levels were not different between the elderly and younger group, while folate levels were lower in elderly females than elderly males. Neuropathy was more frequent in elderly male than elderly female patients. Elderly neurological patients with neuropathy more readily responded to folate supplementation than those without neuropathy. Folate-deficient patients with dementia were older than those without dementia, although nine younger patients had dementia and four of nine cases showed frontal dementia. Anemia or female sex was more frequent and neuropathy was less frequent among elderly patients with central nervous system involvement. Serum folate levels were lower in elderly anemic than nonanemic patients. Tube feeding was more frequent in elderly folate-deficient neurological patients than in younger ones. Folate therapy was less effective in elderly patients with dementia, although three cases improved. Elderly folate-deficient patients treated with tube feeding did not respond to the folate supplement.
Conclusion:   Folate deficiency was not rare among aged neurological patients, and its features were different from younger patients. Since folate-deficient neuroencephalopathies are responsive to folate supplementation in the elderly, the examination of elderly patients' serum folate level is valuable.     

Effects of hypoglycaemia on early embryogenesis in rat embryo organ culture

Summary As congenital malformations may be caused by perturbations of glycolytic flux on early embryogenesis [16], effects of hypoglycaemia were investigated by using rat embryo organ culture. Nine and one-half day old rat embryos were grown in vitro for 48 h (day 9 1/2 to 11 1/2) in the presence of hypoglycaemic serum for different hours during the culture period. Hypoglycaemic serum was obtained from rats given insulin intraperitoneally. On exposure to hypoglycaemic serum during the first 24 h of culture (day 9 1/2 to 10 1/2), embryos showed marked growth retardation and had increased frequencies of neural lesions (42.7% versus 0%, p<0.01), in contrast to hypoglycaemic exposure during the second 24 h of culture (day 10 1/2 to 11 1/2), where only minor growth retardation and low frequencies of neural lesions (2.4% versus 0%, NS) were seen. Even exposure to hypoglycaemic serum for a relatively short period (8 h) during the first 24 h of culture resulted in neural lesions at the frequency of 9.3–13.3%. The embryos exposed to hypoglycaemia demonstrated decreased glucose uptake and lactic acid formation, indicating decreased energy production via glycolysis that constitutes the principal energy pathway at this stage of embryonic development. These results suggest that hypoglycaemia during critical periods of embryogenesis has adverse effects on the development of the embryo and these effects might be mediated through metabolic interruption of embryogenesis.