[Symposium on serum hepatitis. 6. A follow-up study of posttransfusion hepatitis].
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Biomedical subjects
Publications and source records attributed to K Kosaka.
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Highly purified pork monocomponent insulin produced less anti-insulin antibody than conventional insulins in diabetic patients. The smaller amount of anti-insulin antibody produced by MC insulin bound pork insulin more strongly than beef insulin in both displacement and direct binding studies of 125I-insulin. On the contrary, anti-insulin antibody which was produced by conventional insulins (beef insulin or mixture of pork and beef insulin) bound beef insulin more strongly. No significant anti-a-component and anti-proinsulin antibodies were detected in diabetics treated with highly purified monocomponent pork insulin about two years, compared to significant production of these antibodies in diabetics treated with conventional insulins. These results suggest that the species difference of the insulin molecule itself plays a significant role for the production of anti-insulin antibody, as the impurities do, in insulin-treated diabetic patients. The production of anti-insulin and anti-a-component antibodies decreased clearly after switching to highly purified monocomponent from conventional insulin. No effect of the switching on insulin requirement was found; however, better control of diabetes was accomplished in relation to the level of fasting blood sugar.
Experiments on the quick-relief medical communications via the CS-2 satellite were carried out by using two types of 30/20 GHz small transportable earth stations whose antenna diameters are 1 and 2 m. As the terminal equipments, FM-SCPC systems with a one-telephone-equivalent channel were prepared for the transmission of voice, color freezed picture (9.6 kbps), supersonic echo signal and heart sound from a electrocardiograph. Signals from various medical equipments were transmitted by an FM-SCPC system from Simizu harbour (1 m station) to Tokyo transportable station (2 m), assuming that a person was injured in the ship and the ship came alongside the pier. Transmitted materials are mainly various kinds of pictures of affected parts, X-ray films and electrocardiograph with breathing sounds. It was found possible to send various medical information mentioned above via CS-2 by the 30/20 GHz simple communication systems with one-telephone-equivalent channel. Doctors suggested it would be possible to judge very well about the patients' emergency conditions and to give quick consult with inevitable treatment procedures for them. However, a few problems were found in the Hi-Fi reproduction of original colors and in the transmission of heart sounds in the very low frequency band less than 300 Hz.
Age-associated deterioration of mitochondrial energy transduction seems to be a major contributory factor to age-related decline in organ function. Free radicals are likely to be involved in the age-related decline in mitochondrial function. This study was designed to elucidate whether or not doxorubicin, a radical generating drug that was administered to 7-week-old rats, affects age-associated mitochondrial functional changes in diaphragm, heart, and liver. Mitochondria from each tissue were prepared from rats aged 7, 13, 20, 28, 35, and 55 weeks, and the activities of four complexes in the mitochondrial energy transduction system were measured enzymatically. In diaphragm mitochondria of the control group, the complex I activity in 28-week-old rats declined to 82% of the activity in rats aged 7 weeks, and the complex IV activity in 55-week-old rats declined to 70% of the activity in rats aged 7 weeks. On the contrary, a significant decrease in the activity of complex I in rats aged 20 weeks (84%) and that of complex IV in rats aged 35 weeks (86%) were observed in the doxorubicin-treated group. In heart mitochondria, age-related changes in activities of complexes I and IV did not appear in rats aged up to 55 weeks, whereas significant decreases in the activities of complexes I (78%) and IV (90%) were observed in rats aged 35 weeks in the doxorubicin group. Age-related changes in liver mitochondria were not found in rats aged up to 55 weeks, and no deleterious effects of doxorubicin were observed in liver mitochondrial function. From these results, the early appearance of aging effects on mitochondrial function was observed in rats treated with doxorubicin particularly in postmitotic cells.
Serum levels of gliclazide were determined by radioimmunoassay in seven healthy controls and in 18 diabetic in-patients receiving single oral dosing and consecutive dosing over 5 days. Following a single oral dose of 40 mg in the seven controls and eight diabetic patients, and 120 mg in ten diabetic patients, the serum levels of gliclazide peaked on average at 2 h, followed by a slow decline, the t1/2 being 16.5 h in the volunteers, 12.3 h in the diabetic patients receiving 40 mg, and 10.5 h in those receiving 120 mg. During consecutive administration, the serum levels both at fasting and at the peak reached a plateau in 2 days and no further accumulations were observed. The steady-state peak levels of gliclazide in the diabetic patients revealed a strongly positive correlation with the dose per m2 body surface area (r = 0.78, P less than 0.001), and their steady-state fasting levels correlated positively but weakly with the dose per m2 body surface area (r = 0.48, P less than 0.05). Thus, measuring either the fasting or the peak concentration of gliclazide will be useful for monitoring drug concentration in the serum. Pharmacokinetics of gliclazide will contribute to the elucidation of the relationship of serum level and clinical effectiveness in diabetic subjects.
There is a subset of dementia patients in the senium, in whom abundant neurofibrillary tangles (NFTs) are present mainly in the hippocampal region without significant numbers of senile plaques. This patient group was thought to be separable from those with Alzheimer's disease based on the results of ApoE allele analysis in addition to the substantial absence of amyloid beta deposits and has been designated as senile dementia of the tangle type (SDT). The clinical pictures of 4 autopsied patients with different amounts of NFTs were examined to characterize the clinical aspects of this type of senile dementia. SDT generally occurs in very old patients and was estimated to account for about 4-6% of patients with dementia in the senium excluding vascular dementia. Clinically, long-lasting memory disturbance is more prominent and personality as well as cognitive functions tend to be preserved. Delirium and other psychotic symptoms are often observed. NFTs and accompanying neuronal loss in the limbic, mainly in the hippocampal, region could be responsible for dementia.
The effects of 3 wk of near normoglycemia by continuous subcutaneous insulin infusion (CSII) on plasma immunoreactive somatostatin (IRS) responses to arginine (0.5 g X kg-1 X 30 min-1) in seven patients with insulin-dependent diabetes mellitus (IDDM) were compared with the same patients in poor glycemic control during conventional insulin therapy (CIT) and with seven normal controls. After 3 wk of CSII treatment, mean daily blood glucose and HbA1 decreased to mean (+/- SE) values of 129 +/- 6 mg/dl and 8.0 +/- 0.1%, respectively. Plasma free-insulin levels in IDDM patients 30 min before a meal during CSII were significantly higher than those during CIT or in normal controls. Fasting mean plasma IRS levels of the IDDM patients during CSII (7.3 +/- 1.4 pg/ml) were not different from those during CIT (8.4 +/- 1.3 pg/ml) and in normal controls (5.9 +/- 0.8 pg/ml). Arginine elicited a rise in plasma IRS during CIT in all seven IDDM patients during CIT and in the normal controls, with peak values of 18.2 +/- 4.1 and 12.5 +/- 1.8 pg/ml, respectively. However, no significant increase in plasma IRS was observed in all seven IDDM patients during CSII. The integrated values of plasma IRS during the arginine-infusion study of the IDDM patients treated with CIT were significantly higher than those of the normal controls. The increased integrated values of plasma immunoreactive glucagon response to arginine observed during CIT became normalized after CSII. These results suggest that glycemic control with CSII in IDDM patients suppresses the increased plasma IRS response to arginine that occurs during CIT.(ABSTRACT TRUNCATED AT 250 WORDS)
The frequencies of retinopathy, proteinuria, hypertension, and electrocardiographic (ECG) abnormalities in 2025 diabetic subjects new to our clinic in Tokyo were analyzed in relation to status at initial visit with respect to age, estimated duration of diabetes, and fasting blood glucose. Frequency and severity of retinopathy increased markedly with duration of diabetes. A relationship was found between retinopathy at first visit and level of blood glucose at that time. Proteinuria also clearly increased with duration; its frequency was generally higher in older age groups. Frequency of hypertension increased with age up to 60 yr, but there was no association between prevalence of hypertension and duration of diabetes. ECG abnormalities also increased with age, although serious abnormalities were rare even in older subjects. Hypertension and ECG abnormalities were not more common in those with higher initial blood glucose values, and the frequencies of these aberrations did not increase with the duration of diabetes. ECG abnormalities were more common among hypertensives, especially in younger age groups. Despite the clear effect of degree and duration of hyperglycemia on microvascular complications, there was no evidence of a direct effect of hyperglycemia on macrovascular abnormalities in this study.
The serum insulin, fractional absorption, serum human C-peptide, and plasma glucose responses of normal fasting subjects were compared after the subcutaneous and intravenous administration of human insulin (recombinant DNA) and Novo Actrapid insulin. While no statistical difference at each time point was observed between the two insulins, for each time point after 0.05 and 0.1 U/kg s.c., the 0-6 h area under curve (AUC) after the 0.05 U/kg dose was greater for human insulin than for pork insulin. There was no difference in the 0-6 h AUC after the 0.1 U/kg s.c. dose. The serum human C-peptide responses to the two insulins were virtually identical. With the 0.05 U/kg s.c. dose, hypoglycemic effect of human insulin was greater than for Actrapid. This difference did not occur after 0.1 U/kg s.c. Following intravenous administration using 0.05 U/kg, the serum IRI, serum C-peptide, and glucose responses were the same. These data indicate only slight differences between human insulin and Actrapid insulin.
In 9 of the 14 national samples of diabetic patients assembled for the WHO Multinational Study of Vascular Disease in Diabetes additional laboratory data made it possible to relate manifestations of macrovascular disease to blood glucose concentrations as well as to diabetes duration and to other potential determinants. In five of the samples, serum triglyceride concentrations were also measured and were included in simple and multivariate analyses. Ischemic heart disease defined from Minnesota-coded EKGs and standardized WHO questionnaires was more strongly associated with serum triglyceride concentrations than with serum cholesterol concentrations, an association less notable in non-insulin-dependent diabetic patients. Ischemic heart disease was not related to the single fasting plasma glucose estimated for this study. Stroke and amputation were much more strongly related to the known duration of diabetes than was ischemic heart disease, and they were both related to blood glucose concentration measured at the time of study. Despite major variation in arterial disease prevalence rates between collaborating centers, risk for diabetic women appeared to equal that for diabetic men. The major variation in arterial disease prevalence between national groups could be accounted for only in part by the risk factors studied. Other factors, genetic or more likely environmental, are likely to contribute to the variation in arterial disease susceptibility and, if definable, may be potentially preventable.
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The present study concerns an autopsied case of dementia with Lewy bodies (DLB) showing advanced Lewy pathology but minimal Alzheimer pathology. The patient was a 50-year-old Japanese male without inheritance. His initial symptoms at the age of 43 suggested the diagnosis ofjuvenile idiopathic Parkinson's disease (PD), but were followed by memory disturbance 1 year later. He showed parkinsonism, dementia, personality change, fluctuating cognition and visual hallucinations 3 years later. Neuroradiological examination revealed moderate brain atrophy, predominantly in the frontal and temporal lobes. Neuropathological examination demonstrated a widespread occurrence of Lewy bodies (LB) with LB-related neurites not only in the brainstem but also in the cerebrum. The present case showed Lewy pathology which corresponded to stage IV by our staging and was parallel to neuronal loss. There was marked neuronal loss with many LB-related neurites in the CA2 of the hippocampus. Neurofibrillary tangles (NFT) were almost restricted to the entorhinal cortex, while senile plaques were absent. Consequently, the present case was pathologically diagnosed as having DLB of the neocortical type, pure form. In the present study, we suggest that Lewy pathology in the cerebral cortex could be responsible for progressive dementia.