PubMed HealthSearch

Biomedical subjects

H Kojima

Publications and source records attributed to H Kojima.

At least 19 recordsLinked to original sources

Suppression of interictal bursting in hippocampus unleashes seizures in entorhinal cortex: a proepileptic effect of lowering [K+]o and raising [Ca2+]o.

The relation between interictal bursts (IIBs) and seizures in epilepsy is obscure. Results from some human and animal studies suggest that IIBs may actually suppress seizure activity. This appears particularly true in the zero magnesium in vitro seizure model. Here we provide new evidence in support of this and new insight into the mechanisms of seizure suppression in this model. Brain slices containing hippocampus and entorhinal cortex were bathed in zero magnesium medium. Electrographic seizures appeared, then were replaced by IIBs. Upon lowering [K+]o and raising [Ca2+]o the IIBs disappeared and the seizures reappeared. Repeated stimuli mimicking IIBs then suppressed seizures again. Selective knife cuts revealed that the IIBs originated in the hippocampus (area CA3) whereas the seizures originated in entorhinal cortex. These results confirm that IIBs suppress seizures in the zero magnesium model. They also show that an important aspect of the interaction between IIBs and seizures in this model is the anatomical segregation of their respective sites of origin. This may apply in other models and in human epilepsy as well. Finally, these results illustrate that one consequence of the anatomical segregation and mutual interaction of IIBs and seizures is that influences which are locally pro- or antiepileptic can have opposite effects in a broader region.

Action Potentials

Increased plasma post-heparin diamine oxidase activity and plant sterol levels in streptozotocin diabetic rat.

Plasma post-heparin diamine oxidase (DAO) activity and plasma levels of plant sterols were examined in streptozotocin diabetic rats fed with chow containing plant sterols, to investigate the enzyme activity in relation to the morphological changes of small intestine as well as sterol absorption in the diabetic rats. Diabetic rats showed increased small intestinal mass and surface area compared with control rats. Plasma post-heparin DAO activity and plant sterol level were also increased more than 2.5-fold in the diabetic rats. Insulin treatment improved these abnormalities. Plasma DAO activity correlated to both the small intestinal hyperplastic change and plasma plant sterol levels. These results indicate that plasma post-heparin DAO activity may be used as a marker of intestinal hypertrophy as well as ability to absorb dietary sterols.

Amine Oxidase (Copper-Containing)

A case of multiple leiomyomatous lesions of the lung: an analysis of flow cytometry and hormone receptors.

A 36 year old woman was admitted to our department because of a chest X-ray which showed multiple developing shadows. She underwent bilateral exploratory thoracotomies and a total 5 tumors were resected and pathologically diagnosed as benign metastasizing leiomyoma, the largest of which was positive for the progesterone receptor and negative for the estrogen receptor. A histogram of this tumor using a flow cytometer showed a diploid pattern and 4.6 percent of the S phase which was not more than that of a leiomyoma of the uterus from another patient. Two months later, she underwent a hysterectomy and bilateral salpingo-oophorectomy for treatment of the positive progesterone receptor in the pulmonary lesions. The resected uterine myoma and normal myometrium showed positive estrogen and progesterone receptors. For the subsequent 28 months she has been free of any further symptoms. Benign metastasizing leiomyoma of the uterus is a rare disease and very interesting because of its histological benignity and hormonal dependency. However, according to the literature, it is often confused in entity due to the fact that normal lung tissue also possesses hormone receptors. Considering our data on hormone receptors, it is rational to think that multiple leiomyomatous lesions in the lung should only be diagnosed as benign metastasizing leiomyomas when they possess positive estrogen and progesterone receptors.

Adult

Effects of nefiracetam, DM-9384 on amnesia and decrease in choline acetyltransferase activity induced by cycloheximide.

The effects of nefiracetam, [N-(2,6-dimethyl-phenyl)-2-(2-oxo-pyrrolidinyl)acetamide, DM-9384], a cyclic derivative of GABA, were investigated in the cycloheximide (CXM)-induced amnesia animal model using the passive avoidance task. Pre-training administration of DM-9384 attenuated the CXM-induced amnesia as indicated by prolongation of step-down latency. It protected against CXM-induced inhibition of choline acetyltransferase activity in the cerebral cortex. These results suggest that DM-9384 attenuates CXM-induced amnesia by interacting with AChergic neuronal system and enhancing protein synthesis in the brain.

Amnesia

Effects of L-ascorbic acid on the mutagenicity of ethyl methanesulfonate in cultured mammalian cells.

The effects of L-ascorbic acid (AsA) on the mutations induced by ethyl methanesulfonate (EMS) were examined by means of the 6-thioguanine (6TG)-resistant mutation assay and chromosome aberration assay in cultured Chinese hamster V79 cells. When cells were treated with EMS at various concentrations in the presence of 100 micrograms/ml AsA, EMS-induced 6TG-resistant mutations were reduced about one third or one fourth. EMS-induced chromosome aberrations were also reduced by AsA. These reductions in the mutagenicity of EMS were also found when cells were treated with mixtures of AsA and EMS which had previously been incubated at 37.0 degrees C for 2 h. In pre- and post-treatments with AsA, however, the frequencies of EMS-induced mutations were not reduced, but rather increased markedly.

Animals

Combined mutagenicity of methyl methanesulfonate and ethyl methanesulfonate in Chinese hamster V79 cells.

The combined effects of methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) on the induction of 6-thioguanine (6TG)-resistant mutants and chromosome aberrations were examined in Chinese hamster V79 cells. Cells were simultaneously treated with EMS at a concentration of D20 and MMS at various concentrations for 3, 6 or 9 h. In other experiments cells were simultaneously treated with MMS at a concentration of D20 and EMS at various concentrations for 3, 6 or 9 h. The mathematical analysis of the combined effects of both chemicals for cell killing (cytotoxicity) and 6TG-resistant mutations indicates that synergistic interactions were observed for both cell killing and mutations induced by MMS and EMS. The frequency of chromosome aberrations induced by simultaneous treatment with MMS at a concentration of D20 and EMS at various concentrations for 3 h was additive. However, the frequency of chromosome aberrations induced by EMS at a concentration of D20 and MMS at various concentrations for 3 h was not significantly different from those induced by MMS alone.

Animals

Effects of DM-9384, a pyrrolidone derivative, on ischemia-induced changes in the central monoamine systems.

Alterations in brain tissue levels of monoamines and monoamine metabolites were studied in gerbils 60 min after cerebral ischemia induced by 10 min carotid ligation after pretreatment with the antiischemic drug DM-9384 (1, 3, 10, 30 mg/kg, PO). The DA levels decreased in striatum after the ischemia, while cortical and hippocampal DA levels increased. The DOPAC levels increased in cortex, but were essentially unaffected in other regions. The HVA levels increased in all forebrain regions studied. NA levels decreased in hippocampus and superior colliculus, while a general increase in MHPG levels was seen. Decreases in 5-HT levels were seen in all forebrain regions except cortex. The 10 mg/kg and 30 mg/kg doses of DM-9384 counteracted the decrease in striatal 5-HT and hypothalamic MHPG/NA ratio, respectively. Thus pretreatment with DM-9384 exerted minor protective effects on the alterations induced in monoamine systems by transient forebrain ischemia.

3,4-Dihydroxyphenylacetic Acid

Hyperlipidemia and atherosclerosis in experimental insulinopenic diabetic monkeys.

Chronic insulinopenic diabetes was induced by i.v. streptozotocin in the non-human primate Macaca fuscata. Five diabetic monkeys were kept for 8-19 months and nine for 24-48 months without any insulin treatment. Hyperglycemia (241 +/- 22 mg/dl, M +/- SE less than or equal to 1 year) progressed to 376 +/- 34 mg/dl (greater than 2 years) and ketosis to 3.5 mM (greater than 2 years) during the course of diabetes; this was roughly inversely proportional to hypoinsulinemia (3.4 microU/ml, 2 years). Serum cholesterol increased from 184 +/- 11 (less than or equal to 1 year) to 328 +/- 66 mg/dl (greater than 2 years) with the major increase in LDL-cholesterol (2.7-fold over control, greater than 2 years). HDL-cholesterol did not change at all throughout the experimental period. TG increased from 144 +/- 25 (less than or equal to 1 year) to 676 +/- 116 (greater than 2 years) with a major increase in the VLDL fraction (15-fold over control, greater than 2 years). Serum levels of apo B increased to 141 +/- 16 (less than or equal to 2 years) and 223 +/- 8 mg/dl (greater than 2 years) in contrast to control, 73 +/- 2. Morphologically, lipid deposition in the intima and fatty streaks have been observed in the abdominal aorta of all the diabetic monkeys with duration of more than 2 years. In six of the diabetic monkeys atheromatous changes such as intimal and medial thickening with smooth muscle cell proliferation were observed with foam cell formation. Similar atherosclerotic lesions were observed in renal and coronary arteries in at least six of these monkeys. In diabetic monkeys with duration of less than 2 years, mild atherosclerotic lesions were observed in two out of five. The results indicate that long standing insulinopenia leads to metabolic derangements characterized by hyperglycemia, ketonemia and hyperlipidemia. Elevation of LDL-cholesterol and VLDL TG with an increase of apo B is a characteristic of lipoprotein disorder. Morphologically, early to moderately advanced lesions of atherosclerosis were observed in aorta, renal and coronary arteries as a result of metabolic derangement due to insulin deficiency.

Animals

Suppressive effect of vasopressin on ketosis in diabetic rats.

In order to clarify if vasopressin (VP) plays a role in the pathophysiology of hyperosmolar nonketotic diabetic coma (HNDC), VP has been infused to diabetic rats and plasma levels of glucose (PG), ketone bodies, FFA and glucagon were determined. High-dose VP infusion (1.2 U/kg/h) caused gradual elevation of PG (60%) and glucagon levels (600%), while ketone bodies showed transient decrease (20%) at 30 min. Under the suppression of endogenous glucagon secretion by constant infusion of somatostatin (100 micrograms/kg/h), high dose VP showed 25% increase in PG levels and 30% reduction of ketone body levels for the subsequent VP infusion for 1.5 hour. Low-dose VP infusion (0.06 U/kg/h) had no hyperglycemic effect, but suppressed ketosis (20%) in the same condition. There were no changes in plasma FFA concentrations, indicating no significant effect of VP on lipolysis. The results indicate that VP often elevated in HNDC may play an important role for the pathophysiology of HNDC through suppression of hepatic ketogenesis.

Animals

Increased ketogenesis related to insulin deficiency in isolated hepatocytes from NIDDM model rats.

To investigate the hepatic ketone body metabolism in NIDDM, we studied the ketone body production rates in hepatocytes from newly developed non-obese NIDDM model rats. NIDDM model rats were prepared by intraperitoneal injection of streptozotocin at 2 or 5 days of age (STZ2, STZ5 respectively). After 10-15 weeks, ketone body production rates in hepatocytes isolated from these rats were compared with those from control rats as well as ketotic rats made by intravenous injection of streptozotocin into adult rats. Basal ketone body production rates from 0.3 mM [U-14C] palmitate in hepatocytes from control, STZ 2, STZ 5 and ketotic rats were 11.7 +/- 0.98, 14.9 +/- 0.72, 16.0 +/- 0.45, 22.8 +/- 2.32 nmole.palmitate/mg.prot/hr, respectively. These rates were stimulated by 1 microgram/ml of glucagon in control, STZ 2 and STZ 5 rats (14.1 +/- 0.99, 18.6 +/- 1.36, 18.7 +/- 0.69 nmole.palmitate/mg.prot/hr, respectively), but not in ketotic rats (22.8 +/- 2.07 nmole.palmitate/mg.prot/hr). The similar effects were observed by 1 microgram/ml of epinephrine. The basal ketone body production rates were negatively correlated to both hepatic glycogen contents and plasma IRI levels. Considering these parameters together, the extent of metabolic derangement in STZ 2 and STZ 5 rats was between that in control and ketotic rats. These results indicate that the derangements of hepatic ketone body production are related to the severity of insulin deficiency and suggest that the enhanced hepatic ketogenesis contributes in part to the elevated plasma ketone body levels in non-obese NIDDM.

Animals

The effect of hypoxia on the epileptiform activities induced by magnesium-free medium in rat brain slices.

In order to understand the mechanisms underlying the seizure generation, the present study has investigated the effect of hypoxia on the transition between seizure and interictal bursting. Bathing rat brain slices of the hippocampus and entorhinal cortex in magnesium-free medium elicits electrographic seizures. However, they are eventually replaced by the interictal bursts. It has previously been shown that the interictal bursts, arising in the hippocampal area CA3, are propagated to and disrupt the seizure generation in the entorhinal cortex. In this report we demonstrate that hypoxia promotes the seizure reappearance in the entorhinal cortex by suppressing the interictal bursts in CA3.

Animals

In vivo biotinylation of fusion proteins expressed in Escherichia coli with a sequence of Propionibacterium freudenreichii transcarboxylase 1.3S biotin subunit.

Biotinylation of fusion proteins in E. coli was studied using a sequence of Propionibacterium freudenreichii transcarboxylase 1.3S biotin subunit. As the biotinylation sequence, we examined two sequences: one was of amino acid residues [84-123] of 1.3S, a partial sequence containing a region from a conserved tetrapeptide (Ala-Met-Bct-Met) around the biotinyl lysine (Bct) to the carboxyl terminal; the other was of an almost entire sequence [18-123]. We constructed recombinant plasmids for fusion proteins of beta-galactosidase, of chloramphenicol acetyltransferase, and of alkaline phosphatase. We found the biotinylation in the [18-123] sequence fused to alkaline phosphatase.

Amino Acid Sequence

Chronic active Epstein-Barr virus infection in an adult.

We report a rare adult case of chronic active Epstein-Barr virus (EBV) infection. A 54-year-old woman was admitted to our hospital with intermittent fever, weight loss, hepatosplenomegaly, pancytopenia and liver disturbance. In serological tests for EBV, anti-virus capsid antigen (VCA)-IgG antibody and anti-early antigen (EA)-IgG antibody were markedly elevated and anti-EBV nuclear antigen (EBNA) antibody was negative. EBV genome was detected in the bone marrow nucleated cells and peripheral lymphocytes by Southern blot hybridization. The patient developed left facial edema, bilateral breast tumor and pneumonia. She died one year after admission in spite of the administration of prednisolone, interferon and acyclovir.

Acyclovir

[Ablative and prophylactic effects of BCG Tokyo 172 strain for intravesical treatment in patients with superficial bladder cancer and carcinoma in situ of the bladder. Bladder cancer BCG Study Group].

We investigated the effects of intravesical instillation of BCG Tokyo 172 strain on patients with superficial bladder cancer and CIS of the bladder for tumor ablation and prophylaxis. This is the first controlled multicenter study for governmental approval of BCG Tokyo 172 strain for the treatment of superficial bladder cancer and CIS of the bladder. One hundred-fifty-seven patients (125 with Ta or T1, and 32 with CIS) were treated by 80 mg of BCG diluted in 40 ml of saline, once a week for 8 weeks. The dose and interval adopted in this multicenter study was determined by the previous Phase II study conducted by the same Study Group. Out of 125 superficial tumor Ta, T1, 83 (66.4%) showed complete disappearance of the tumor (CR) and 26 (20.8%) partial disappearance (PR), and out of 32 CIS, 27 (84.4%) showed CR and 2 (6.3%) PR. Among those patients showing CR, and PR who were treated with additional TUR-Bt, 98 patients were randomised for a controlled study of prophylactic BCG instillation. Prophylactic treatment consisted of 40 mg of BCG diluted in 40 ml of saline, monthly for 12 months. Forty-two patients were assigned to the treatment group, whereas the remaining 56 to the control group without any prophylactic instillation. Three cases showed tumor recurrence during the prophylactic phase. Twenty-five cases could not be treated for the whole course of prophylactic instillation mainly due to bladder irritable symptoms. Recurrent free curves were compared till 1050 days after the initiation of the study. However, there was no significant difference between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intravesical

[Anorexia nervosa with neutropenia--response of neutrophils to G-CSF].

A 50-year-old woman with anorexia nervosa was admitted for evaluation of neutropenia (WBC 1,600/microliters). Her bone marrow was gelatinous, and myeloid cells had decreased. Homogeneous substance deposited in the marrow, stained by alcian blue (pH 2.5), indicative of acid mucopolysaccharides. CFU-G and CFU-GM were decreased in number and myeloid pool in the bone marrow also decreased. Anti-neutrophilic antibody was negative. Neutropenia may be related to myeloid hypoplasia, due to increase of acid mucopolysaccharides replacing adipose cells in the bone marrow under long-term mal-nutritional state. Neutrophils markedly increased by administration of rhG-CSF 5.0 micrograms/kg/day for 14 days without the first peak. Serum G-CSF level did not increase (less than 60 pg/ml). It is effective to administer G-CSF to anorexia nervosa with neutropenia.

Anorexia Nervosa

Characteristic distribution of glycolipids in gadoid fish nerve tissues and its bearing on phylogeny.

Glycolipids were isolated from nerve tissues of gadoid fishes including Alaskan pollack and Pacific cod. Their chemical structures were determined by gas-liquid chromatography and gas chromatography-mass spectrometry, and their constituents were analyzed in detail and compared with those of glycolipids from other fish groups. The results revealed that gadoid fish nerve membranes contain peculiar glycolipid molecular species that are distinctly different from those in other teleostean fishes and higher vertebrates. The mole percentage ratio of the four major glycolipids (cerebroside-sulfatide-galactosylglyceride-sulfogalactosylglyce ride) was 48:12:25:15, indicating profound accumulation of glycoglycerolipids. Galactosylglyceride and sulfogalactosylglyceride were primarily of the diacyl type (greater than 90%), the major fatty acids being 16:0 and 18:1. An abundance of glucocerebroside (25 to 55% of cerebroside) and its fatty acid ester (37 to 47% of ester cerebroside) was noted. Cerebroside and sulfatide were characterized by the absence of hydroxy and odd numbered fatty acids, and 24:1 acid was a predominant component of both glucocerebroside and galactocerebroside. Subcellular fractionation revealed that myelin membranes comprised such unusual glycolipid constituents as those seen in whole nerve tissues. A vertebrate whose nerve membranes consist of such peculiar glycolipid molecules has not previously been reported. The characteristics of the glycolipid composition in gadoid fishes are discussed in relation to myelin functions, physicochemical properties of nerve membranes, and the phylogenic significance of this fish group.

Animals