[Chemotherapy of drugs. I].
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Bacillus subtilis↗
Biomedical subjects
Y Hamada
Publications and source records attributed to Y Hamada.
Synthesis and antifungal activity of 2-chloro-4-amino-5-(p-halogenophenoxy) phenylthiocyanate compounds.
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Antifungal Agents↗
[Quinoline derivatives. 12].
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Antifungal Agents↗
Indication for anti-epileptic drug treatment of benign childhood epilepsy with centro-temporal spikes.
To approach the problem concerning whether or not anti-epileptic treatment of benign childhood epilepsy with centro-temporal spikes (BCECT) is necessary, we retrospectively studied 6 untreated and 39 treated patients with BCECT and compared their clinical findings after 2 years of observation. Then we selected 6 untreated and 28 treated patients from the same series who had been free from attacks for more than 2 years to determine whether the mode of onset (multiple seizures or isolated one for the first month of the illness) was related to the duration of active epilepsy in these two groups. This comparative study of untreated and treated patients followed for 2 years revealed no differences in the interval between first visit and start of attack-free period between the two groups. The mean duration of active epilepsy in those with only isolated seizures at onset was significantly shorter than that in those with multiple seizures at onset. Anti-epileptic medication may be unnecessary in patients with isolated seizure during sleep; it does not affect the natural course of BCECT. Treatment is necessary for a longer period in patients with multiple seizures at onset than in those with isolated seizures at onset.
Anticonvulsants↗
No correlation between glycemic control and an increase in erythrocyte aldose reductase activity in type I and type II diabetic patients.
Aldose reductase, the first enzyme of the polyol pathway, has been related to the pathogenesis of diabetic complications. The regulation of the enzyme in diabetes patients, however, has not yet been clarified. We recently reported that the activity of aldose reductase was increased in erythrocytes of insulin-dependent diabetes mellitus patients but short-term hyperglycemia did not affect the enzyme activity. It is still unclear, however, whether or not the increase in the enzyme activity is caused by long-term hyperglycemia and thus would be seen equally in both type I (insulin-dependent diabetes mellitus) and type 2 (non-insulin-dependent diabetes mellitus) individuals. To further clarify these issues we measured erythrocyte aldose reductase activity in 46 type I patients and 30 type II patients who had variable glucose control and in 16 nondiabetic subjects. We compared the enzyme activity with plasma glucose levels and hemoglobin A1c levels. The results show that erythrocyte aldose reductase activity is increased in both type I and type II patients as compared with nondiabetic subjects (7.1 +/- 0.3 U/L and 6.8 +/- 0.4 U/L erythrocytes versus 5.6 +/- 0.2 U/L erythrocytes, p less than 0.001 and p less than 0.01, respectively), but there were no significant differences between the two groups of diabetic patients. The enzyme activity varied by approximately four times among the diabetic individuals but there was no correlation between the enzyme activity and plasma glucose or hemoglobin A1c levels. We conclude that the increased activity of erythrocyte aldose reductase seen in diabetes is not related to hyperglycemia.
Adult↗
Correlation between erythrocyte aldose reductase activity and the width of skeletal-muscle capillary basement membrane in insulin-dependent diabetes mellitus.
Thickening of capillary basement membrane has been demonstrated in diabetic subjects, and it is considered to be the characteristic pathological lesion of diabetic microvascular disease. There are studies reporting the effects of inhibitors of aldose reductase, the first enzyme of the polyol pathway, on the thickening of the capillary basement membrane. These observations indicate a significant role of the polyol pathway in the development of microvascular disease. However, it is unknown whether or not there is any correlation between the thickness of the capillary basement membrane and the activity of aldose reductase in diabetic patients. To clarify this issue, we measured the width of skeletal-muscle basement membrane and erythrocyte aldose reductase activity in 27 insulin-dependent diabetic and 8 nondiabetic individuals. The results showed that both the aldose reductase activity and the width of capillary basement membrane were increased in diabetic patients as compared to nondiabetic individuals (6.89 +/- 0.38 versus 5.15 +/- 0.60 mL/mU erythrocytes, p < 0.05 and 2257 +/- 166 versus 1136 +/- 69 A, p < 0.0001, respectively) (mean +/- SE), but marked variability was observed in both the enzyme activity and the basement membrane thickness among the diabetic patients. There was a significant correlation between the capillary basement membrane thickness and the activity of erythrocyte aldose reductase (r = 0.51, p < 0.01) in diabetic patients. Our data suggest that the polyol pathway plays an important role in thickening of capillary basement membrane in diabetic individuals, and the variability in aldose reductase activity seen among diabetic patients may result in the varying susceptibility to the development of diabetic microvascular disease.
Adult↗
Comparative study of population pharmacokinetics upon switching of cyclosporine formulation from Sandimmune to Neoral in stable renal transplant patients.
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Adult↗
Association of erythrocyte aldose reductase activity with diabetic complications in type 1 diabetes mellitus.
Erythrocyte aldose reductase was isolated and its activity measured in 72 Type 1 (insulin dependent) diabetic patients and 21 age and sex matched non-diabetic subjects. The diabetic patients were categorized into two groups in terms of presence (n = 29) or absence (n = 43) of severe diabetic complications. Age, sex, duration of diabetes and HbA1c levels were matched between the diabetic groups. Erythrocyte aldose reductase (mean +/- SEM) was increased in patients with Type 1 diabetes compared to the non-diabetic subjects (7.22 +/- 0.24 vs 5.66 +/- 0.19 Ul-erythrocytes-1, < 0.0001). There was a four-fold variation in its activity among the diabetic patients (3.38-12.23 Ul-erythrocytes-1). The enzyme activity was significantly higher in patients with complications than those without (8.17 +/- 0.39 vs 6.58 +/- 0.26 Ul-erythrocytes-1, p < 0.002). When the patients were stratified by duration of the disease, the enzyme activity was highest in patients who had developed complications with a duration of less than 20 years and lowest in those without complications for 20 years or longer (8.54 +/- 0.48 vs 6.46 +/- p +/- 0.33 Ul-erythrocytes-1, p < 0.002). Patients who had an aldose reductase activity greater than the mean +/- 2SD of that seen in non-diabetic controls were four times more likely to have diabetic complications than those whose enzyme activity fell within 2SD of non-diabetic individuals (p < 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
PEEP therapy for patients with pleurotomy during coronary artery bypass grafting.
Severe pulmonary oxygenation impairment resulting from peripheral lung atelectasis occurred in some patients with pleurotomy during the harvest of the internal mammary artery graft followed by coronary artery bypass grafting (CABG). We studied the efficacy of intraoperative positive end-expiratory airway pressure (PEEP) therapy for the prevention of postoperative pulmonary oxygenation impairment. A total of 66 patients with solitary CABG procedure were included in this study. The pleural cavity was intraoperatively opened in 44 patients and not opened in 22. PEEP therapy was not used in any patient before May 1996 (referred to herein as the former period) and was used more recently in eight patients with pleurotopmy (referred to herein as the latter period). PEEP was initiated immediately after pleurotomy during the harvest of the internal mammary artery graft. Without PEEP therapy, values of PaO2, A-aDO2, and respiratory index (RI) were worse in patients with pleurotomy than in those without pleurotomy. Meanwhile, there were no major differences in these values between patients with or without pleurotomy after the induction of PEEP therapy. Respiratory insufficiency (A-aDO2 > 400 mmHg and RI > 1.5) was detected in six patients with pleurotomy in the former period. Three of these six patients required over 1 week of long-term mechanical respiratory support. No respiratory insufficiency occurred in patients of the latter period. In conclusion, PEEP therapy, which is initiated just after pleurotomy, may prevent oxygen impairment and pulmonary atelectasis after extracorporeal circulation (ECC) and is recommended for patients with pleurotomy, especially for patients with preoperative low respiratory function.
Aged↗
Utility of 3-O-methyl-N-acetyl-D-glucosamine, an N-acetylglucosamine kinase inhibitor, for accurate assay of glucokinase in pancreatic islets and liver.
Glucokinase, an enzyme that catalyzes the phosphorylation of glucose, constitutes the key regulatory step in glucose metabolism in pancreatic islets and liver. We found that 3-O-methyl-N-acetyl-D-glucosamine (3-O-methyl-GlcNAc) potently inhibits glucose phosphorylation by N-acetylglucosamine kinase whereas glucokinase is not at all affected by this hexosamine. The addition of 3-O-methyl-GlcNAc to the assay system for glucokinase in rat liver extracts, which contain a high activity of glucokinase (glucose as substrate) relative to N-acetylglucosamine kinase (N-acetyl-D-glucosamine as substrate), affected neither Km nor Vmax values of glucokinase. On the other hand, both Km and Vmax values of glucokinase in rat pancreatic islet extracts, in which N-acetylglucosamine kinase activity is higher than glucokinase activity, were significantly lowered by the use of 3-O-methyl-GlcNAc as an inhibitor of N-acetylglucosamine kinase.
Acetylglucosamine↗
Human natural tumor necrosis factor alpha induces multiple endocrine and hematologic disorders in rats.
Slc:Wistar male rats treated with human natural tumor necrosis factor alpha (hn TNF-alpha, 3 X 10(5) Japan reference units/kg intravenously) for 3 months showed histologic vacuolation of basophils in the anterior pituitary, hyperplasia of the thyroidal follicular epithelium, and hyperplasia of the testicular interstitial cells. The vacuolated basophils were immunohistochemically shown to be thyrotrophs. In addition, there were decreases in plasma levels of triiodothyronine (T3), thyroxin (T4), and testosterone, and an increase in thyroid-stimulating hormone (TSH). The number of lymphocytes in the marginal zones of lymphoid follicles in spleen and lymph nodes and B-lymphocytes in the peripheral blood decreased. Hyperplasia of hematopoietic cells in the bone marrow and decreases in both leukocytes and erythrocytes in the peripheral blood were prominent. Hyperplasia of bile ductular epithelial cells with periportal mononuclear cell infiltration in the liver and increased cellularity in alveolar walls in the lung were also characteristic. In in vitro studies, hn TNF-alpha inhibited both proliferation and peroxidase activity of thyroid follicular epithelial cells. These findings demonstrate that hn TNF-alpha may induce histologic vacuolation of thyrotrophs by causing a decrease in plasma levels of T3 and T4; hyperplasia of the thyroid follicular epithelium, which may be attributed to the increased plasma level of TSH; hyperplasia of testicular interstitial cells, by lowering the plasma level of testosterone; hyperplasia of bile ductular epithelial cells; hyperplasia of hematopoietic cells in bone marrow; and the increase in cellularity in pulmonary alveolar walls. In addition, hn TNF-alpha may suppress the differentiation of B-lymphocytes.
Animals↗
Multiple hepatoblastomas associated with trisomy 18 in a 3-year-old girl.
A very rare case of full trisomy 18 associated with multiple hepatoblastomas is reported. The patient also had ventricular septal defect and patent ductus arteriosus, which were repaired at 6 months of age. After the cardiac surgery, she was noted to have an abdominal mass and an elevated serum alpha-fetoprotein level. A partial hepatic lobectomy was performed at 7 months of age, and the resected tumor was diagnosed as a fetal-type hepatoblastoma. At 2 years and 4 months of age, a chest radiography disclosed an elevated left diaphragm, and abdominal ultrasonography demonstrated a tumor in the left hepatic lobe. The resected tumor was also diagnosed as a fetal-type hepatoblastoma. Chromosomal analysis demonstrated that the karyotypes of peripheral blood and hepatic tumor cell obtained on two occasions were both 47,XX, +18. She has no evidence of recurrence at 3 years of age without specific therapy.
Abnormalities, Multiple↗
A case of undifferentiated carcinoma of the gallbladder with anomalous arrangement of the pancreaticobiliary ductal system.
Anomalous junction of the pancreaticobiliary duct (AJPBD) is a congenital anomaly associated with gallbladder carcinoma. Especially patients with noncystic dilatation and without dilatation of the biliary tract are at risk of gallbladder carcinoma. A 56-year-old woman with advanced gallbladder cancer associated with AJPBD but without dilatation of the biliary tract was treated at our hospital. Although histologically cancer cells remained in the layer of the proprial mucosa, extensive metastases to lymph nodes including the paraaorta and peripancreas were detected. According to the TNM classification this case was of Stage IVB. The cancer consisted of medullary round cells, and was diagnosed as undifferentiated carcinoma. After surgery poor prognosis was expected, but three years have elapsed with no recurrence. The case is of interest because of two points of discrepancy: the primary cancer did not show deep invasion but demonstrated extensive lymph node metastases; the cancer was histologically malignant but prognosis was relatively good.
Bile Ducts↗
Intravenous nutrition with high-dose fat emulsion and amino acids without glucose provision after hepatic resection.
BACKGROUND/AIMS: Controversy remains regarding the optimal nutrition after hepatic resection. We studied the feasibility and efficacy of an intravenous nutrition with high-dose fat emulsion and amino acids without glucose provision by comparing a glucose-based intravenous nutrition. METHODOLOGY: Twenty-eight patients received either glucose-intravenous nutrition (glucose-IVN group: glucose, 4.2 g; amino acids, 0.8 g/Kg/day) or high-dose fat emulsion and amino acids without glucose provision (HFHA-IVN group: lipids, 2.2 g; amino acids, 1.6 g/Kg/day) for 7 days after hepatic resection (14 patients in each group). Postoperative changes in biochemical tests and plasma levels and arterial-venous concentration differences of amino acids and total ketone bodies across the leg were compared between the two. RESULTS: The 2 groups were comparable regarding perioperative patients' characteristics. None of the patients from either group developed any complications. Postoperative glucose levels showed normal in the HFHA-IVN group, but elevated in the glucose-IVN group. Seven of the glucose-IVN group patients required exogenous insulin administration. Lipid levels were decreased in the glucose-IVN group, but remained normal in the HFHA-IVN group. The HFHA-IVN group showed higher amino acid levels, higher amino acid release, and hyperketonemia and vigorous uptake of ketones by skeletal muscle. CONCLUSIONS: These results indicate that dextrose provision is not essential and the HFHA-IVN provides an alternative to glucose-based intravenous nutrition in patients developing glucose intolerance after hepatic resection.
Aged↗
Isolation of tumor associated antigens from Lewis lung carcinoma by affinity chromatography on peanut agglutinin-agarose.
Receptors for peanut agglutinin (PNA) were isolated from Lewis lung carcinoma cells (3LL) by detergent solubilization and affinity chromatography on PNA-agarose. The isolated receptors showed heterogeneous yet distinct molecular species when they were analyzed by SDS gel electrophoresis. In vivo inoculation of the isolated receptors could induce potent cytotoxic effector cells against 3LL cells, which were detected by Winn's tumor neutralization assay. The PNA receptors were also effective in preventing the settlement of the intravenously injected 3LL tumors in the lung. These findings suggest that PNA receptors can be used for immunological therapy of certain cancers.
Animals↗
Effect of intracellular unstirred layer on apparent reflection coefficient for urea in inner medullary collecting duct: a computer simulation.
In the vasopressin-stimulated inner medullary collecting duct (IMCD), urea is transported through a pathway which is distinct from a water channel. Therefore, no frictional interaction between urea and water should occur at the membrane level, and the reflection coefficient for urea must be close to unity. However, the presence of unstirred layers in the vicinity of membranes causes solute concentration polarization, leading to an underestimation of the reflection coefficient (apparent reflection coefficient). When the value is determined across the perfused renal tubular wall, the intracellular space also constitutes an unstirred layer. The profile of solute and water transport across the system consisting of two membranes and the interposed intracellular space was simulated by a computer to examine the effect of unstirred layer on the value of apparent reflection coefficient. The model demonstrated that the imposed osmotic gradient across the tubular epithelial is decreased at each membrane interface. Under conditions of minimal unstirred layers in the bathing fluid, the existence of the intracellular constraints to diffusion cause considerable underestimation of the reflection coefficient. The higher the membrane permeability of urea and the smaller the diffusion coefficient of urea in the intracellular space, the greater becomes the magnitude of the underestimation. Thus, the measured apparent reflection coefficient for urea may become significantly less than the estimated value, leading to a reduction of the effective transmural osmotic driving force.
Animals↗
Immunohistochemical expression of tyrosine kinase (Trk) receptor proteins in mature neuronal cell tumors of the central nervous system.
The interactions of neurotrophins with the Trk family of tyrosine kinase receptors result in growth and maturational changes in neuronal cells. Although the histogenesis of brain tumors composed of mature neuronal cells is still not completely understood, neurotrophins and Trk receptors may be involved in the evolution, maturation, and persistence of these tumors. The clinical and anatomic pathological features of 8 primary neuronal cell tumors (ganglioglioma: 3 cases, cerebral neurocytoma: 3 cases, intraventricular neurocytoma: 2 cases) occurring in the central nervous system (CNS) have been examined. In addition to routine histological examinations, immunohistochemistry was used to evaluate the expression of neurotrophin receptors (TrkA, TrkB) and of neuronal differentiation markers such as neuron-specific enolase, neurofilament, synaptophysin, and chromogranin A. While neither TrkA nor TrkB expression was demonstrated in 2 intraventricular neurocytomas, the remaining 6 tumors did show positive immunohistochemical staining for TrkA and/or TrkB proteins; for TrkA protein, ganglionic cells showed membraneous or cytoplasmic staining, while small non-ganglionic neuronal cells with scant cytoplasm occasionally showed positive cytoplasmic immunoreactivity. For TrkB protein, small non-ganglionic neuronal cells showed a more intense immunoreaction than ganglionic cells. Gangliogliomas with high TrkA and TrkB expression showed higher levels of neuronal differentiation, as demonstrated by the neuron-specific enolase and neurofilament immunoreactivity. The existence of neurotrophin receptors in the tumor cells thus suggests that neurotrophic influence are involved in the evolution and subsequent cellular maturation in neuronal cell tumors of the CNS.
Adult↗