Development of diabetes in Japanese subjects with impaired glucose tolerance: A seven year follow-up study

Summary Five hundred and seven subjects with postprandial glycosuria underwent a 50 g oral glucose tolerance test in an epidemiological survey of diabetes mellitus carried out in 1964–1965 in the town of Osaka, Japan. The oral glucose tolerance test was repeated 7 years later in 207 (40.8%) of the subjects. The results of the initial and the follow-up test were classified into three categories according to the new WHO criteria: normal, impaired glucose tolerance and diabetes. Most of the diabetic subjects (84.8%) remained unchanged between the initial and follow-up test. Of the subjects with impaired glucose tolerance at the time of the initial test, 38.5% showed diabetes in the follow-up test, while another 38.5% returned to normal. On the other hand, 13.5% of the normal subjects in the initial test developed impaired glucose tolerance or diabetes in the follow-up test. The rate of worsening to diabetes was related closely to the 2-h blood glucose value at the initial test. In addition, the rate of worsening was higher in males and obese subjects than in females and non-obese subjects. A multiple logistic analysis indicated that the fasting and 2-h glucose values were significantly predictive of worsening to diabetes.     

Endoscopic pancreatic sphincter balloon dilation for effective retrieval of pancreatic duct stone

To facilitate pancreatic stone retrieval, four patients with chronic pancreatitis and pancreatic stones underwent endoscopic pancreatic sphincter balloon dilation (EPSBD) rather than pancreatic sphincterotomy. Extracorporeal shock wave lithotripsy combined with endoscopic removal was carried out in three patients. Stone removal following EPSBD was completely successful in all four patients. Patients showed no severe complications during the dilation procedure. In one patient, to prevent pancreatitis, an endoscopic nasopancreatic drain was placed for 1 week after EPSBD. Compared with pancreatic sphincterotomy, EPSBD can be performed safely in patients with chronic pancreatitis to assist in the extraction of pancreatic duct stones. Use of the EPSBD procedure in cases of chronic pancreatitis provides a useful approach to improve endoscopic clearance of pancreatic duct stones.     

Relationship between efficacy of antiarrhythmic drug therapy and structural remodeling in patients with paroxysmal atrial fibrillation

OBJECTIVES: To evaluate whether the response to antiarrhythmic drug therapy in patients with paroxysmal atrial fibrillation affects the development of structural remodeling in the left atrium and ventricle. METHODS: This study included 230 patients (158 men and 72 women, mean age 67 +/- 11 years) in whom antiarrhythmic drug therapy was attempted for > or = 12 months to maintain sinus rhythm (mean follow-up period 45 +/- 27 months). The patients were divided into three groups according to the response to antiarrhythmic drug therapy: group A consisted of 78 patients without recurrence of atrial fibrillation, group B consisted of 87 patients with recurrence of atrial fibrillation and electrical and/or pharmacological cardioversion to restore sinus rhythm, and group C consisted of 65 patients with permanent conversion despite antiarrhythmic drug therapy. RESULTS: In group A, left atrial dimension (LAD), left ventricular end-diastolic dimension (LVDd), and left ventricular ejection fraction (LVEF) did not change after antiarrhythmic drug therapy. In group B, LAD increased significantly after antiarrhythmic drug therapy (from 32.6 +/- 6.4 to 36.0 +/- 6.5 mm, p < 0.01), Whereas either LVDd or LVEF did not change after antiarrhythmic drug therapy. In group C, LAD increased significantly after antiarrhythmic drug therapy (from 37.3 +/- 7.0 to 40.5 +/- 7.9 mm, p < 0.01) and LVEF was significantly reduced after antiarrhythmic drug therapy (from 69.4 +/- 6.2% to 66.5 +/- 8.9%, p < 0.05). LVDd did not change after antiarrhythmic drug therapy. The plasma concentration of human atrial natriuretic peptide during sinus rhythm at the initiation of antiarrhythmic drug therapy in group A (30.5 +/- 26.7 pg/ml) was significantly lower than those in group B (48.0 +/- 49.7 pg/ml) and group C (49.7 +/- 39.5 pg/ml). CONCLUSIONS: The development of structural remodeling in human myocardium can be prevented with antiarrhythmic drug therapy if sinus rhythm is maintained without recurrence of atrial fibrillation in patients with paroxysmal atrial fibrillation.     

Inhibition of growth and induction of apoptosis by all-trans retinoic acid in lymphoid cell lines transfected with the PML/RARα fusion gene

The interaction of an exogenous PML/RARα fusion gene associated with acute promyelocytic leukaemia, with all- trans retinoic acid (ATRA) was examined in two lymphoid cell lines. L1210 and MOLT-4 cells were transfected with PML/RARα cDNA in the expression vector pGD and stable transformants (L1210 PML/RAR α and MOLT-4 PML/RAR α) were selected with G418. ATRA inhibited the growth of these stable transformants, as assessed by [³H]thymidine incorporation, in a dose-dependent manner, but had no effect on the growth of control cells stably transformed with neomycin resistant gene alone. ATRA also induced apoptosis, as assessed by fragmentation of genomic DNA, in L1210 PML/RAR α and MOLT-4 PML/RAR α cells but not in control cells. The exogenous PML/RARα fusion gene therefore probably mediates the effects of ATRA on cell growth and apoptosis in these cell lines.     

A gouty family with increased phosphoribosylpyrophosphate synthetase activity: case reports, familial studies, and kinetic studies of the abnormal enzyme

Two male patients with urate overexcretion and clinical gout in a family showed activity of phosphoribosylpyrophosphate (PRPP) synthetase in erythrocyte lysates (3.1-fold) greater than that found in normal subjects. Hemolysates from 5 female persons in this family contained (2.7-fold) increased enzyme activity suggesting X-linked dominant transmission of the abnormality. Increased maximal velocity of the enzyme, aberrant protein pattern in polyacrylamide electrophoresis, and increased thermolability in purified enzyme suggested that this enzyme is a mutant one. From these findings, it was assumed that the characteristics of this enzyme were different from 4 previously reported enzymes.     

Regulation of vitamin D-1alpha-hydroxylase and -24-hydroxylase expression by dexamethasone in mouse kidney

We investigated the effects of dexamethasone on vitamin D-1alpha-hydroxylase and -24-hydroxylase expression and on vitamin D receptor (VDR) content in the kidneys of mice fed either a normal (NCD) diet or a calcium- and vitamin D-deficient (LCD) diet for 2 weeks. For the last 5 days mice received either vehicle or dexamethasone (2 mg/kg per day s.c.). Dexamethasone significantly increased plasma calcium concentrations without changing plasma concentrations of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) in both NCD and LCD groups. Northern blot and enzyme activity analyses in NCD mice revealed that dexamethasone increased renal VDR mRNA expression modestly and greatly increased 24-hydroxylase mRNA abundance and enzyme activity, but did not affect 1alpha-hydroxylase mRNA abundance and enzyme activity. In mice fed an LCD diet, dexamethasone increased renal VDR mRNA expression 1.5-fold, decreased 1alpha-hydroxylase mRNA abundance (52%) and activity (34%), and markedly increased 24-hydroxylase mRNA abundance (16-fold) and enzyme activity (9-fold). Dexamethasone treatment did not alter functional VDR number (B(max) 125-141 fmol/mg protein) or ligand affinity (K(d) 0.13-0.10 nM) in LCD mice. Subcutaneous injections of 1,25(OH)(2)D(3) (0.24 nmol/kg per day for 5 days) into NCD mice strongly increased renal 24-hydroxylase mRNA abundance and enzyme activity, while there was no effect of dexamethasone on renal 24-hydroxylase expression in these mice. This may be due to overwhelming induction of 24-hydroxylase by 1,25(OH)(2)D(3). These findings suggest that glucocorticoid-induced osteoporosis is caused by direct action of the steroids on bone, and the regulatory effect of glucocorticoids on renal 25-hydroxyvitamin D(3) metabolism may be less implicated in the initiation and progression of the disease.     

CD3 down-regulating factor in sera and culture supernatants of leukaemic cells from patients with adult T cell leukaemia

Immunological abnormality of T lymphocytes in patients with adult T cell leukaemia (ATL) is characterized by abnormal expression of the 55 kD chain of the receptor for interleukin 2 (IL-2R/p55) (Tac), and the down-regulation of CD 3 expression. Using serum and culture supernatants of leukaemic cells from ATL patients (Group A) whose CD 3 expression was down-regulated and those (Group B) whose CD 3 was not low, the possible mechanism of CD 3 down-regulation on ATL cells was discussed. When PBMC from normal individuals were cultured with sera from ATL patients for 24 h, CD 3 expression revealed by mean fluorescent intensity (MFI) was down-regulated by sera from ATL patients in Group A (MFI: Pt 1 = 51.6 ± 4.5, Pt 2 = 48.0 ± 6.9, control = 96.5 ± 6.6), not by sera from patients in Group B (MFI: Pt 3 = 105.5 ± 7.9, Pt 4 = 102.5 ± 8.3, control = 96.5 ± 6.6). When normal PBMC were cultured with supernatants of leukaemic cells from ATL patients in Group A, this CD 3 down-regulating activity was also detected (MFI: Pt 1 = 78.0 ± 10.2, Pt 2 = 70.6 ± 8.7, control = 94.0 ± 6.6). By using gel-chromatography, the fractionated supernatants from ATL patients in Group A decreased CD 3 expression of normal PBMC significantly (MFI: Pt 1 = 22.9 ± 5.8, Pt 2 = 28.8 ± 7.4, control = 92.1 ± 9.6). This CD 3 down-regulating activity in fractionated supernatant was not inhibited by any lymphokine antibodies, anti-IL-1α antibody (Ab), anti-IL-1B Ab, anti-IL-2 Ab, anti-IL-3 Ab, anti-IL-4 Ab, anti-IL-6 Ab, anti-TNF-α Ab and anti-IFN-γ Ab. Any known cytokines (IL-1, IL-2, IL-3, IL-4, IL-6, TNF-α and IFN-γ) could not modulate CD 3 expression of normal PBMC. These findings suggested that there are novel factor(s) with CD 3 down-regulating activity in the serum and culture supernatant of ATL patient and those factor(s) are involved in progression of ATL.