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Biomedical subjects

K Murakami

Publications and source records attributed to K Murakami.

At least 451 records · Page 25Linked to original sources
PubMed1996

Valproate metabolites in high-dose valproate plus phenytoin therapy.

PURPOSE: We wished to determine the relation between liver function, beta-, and omega-, and omega-1-oxidation metabolites and 4-en-valproate (VPA). METHODS: We measured the serum levels of VPA and its metabolites in children and adolescent receiving high-dose VPA plus phenytoin (PHT) therapy using gas chromatography-mass spectrometry with selected ion monitoring (GC/MS/ SIM). RESULTS: In high-dose VPA plus PHT polytherapy, the total VPA serum concentration was distinctly low, the concentrations of total beta-oxidation metabolites were decreased, the percentage values of VPA (percent of VPA) of total beta-oxidation metabolites were increased, and the E-2-en-VPA/3-keto-VPA ratios were decreased, as compared with those in high-dose VPA monotherapy. In high-dose VPA plus PHT polytherapy, 4-en-VPA (microM) was decreased and the concentrations of [omega + (omega-1)]-oxidation metabolites (microM) were decreased as compared with those in high-dose VPA monotherapy. In high-dose VPA plus PHT, serum glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and lactic dehydrogenase (LDH) did not correlate significantly with the ¿beta/omega + (omega-1)¿ metabolites ratio and 4-en-VPA levels, but serum GOT, GPT, and LDH were increased as compared with those in high-dose VPA therapy. We were not able to establish a significant relation between the formation of metabolites of VPA metabolites and liver dysfunction in patients receiving high-dose VPA and PHT concurrently. CONCLUSIONS: Metabolic levels do not appear to be a reliable predictor of hepatotoxicity in children receiving pharmacological antiepileptic drug (AED) therapy.

Adolescent↗
PubMed1996

Effect of L-carnitine supplementation on acute valproate intoxication.

We analyzed urinary valproate (VPA) metabolites and carnitine concentrations in a child who accidentally ingested 400 mg/kg VPA. The concentration of 4-en VPA, the presumed major factor in VPA-induced hepatotoxicity, was markedly increased, without liver dysfunction or hyperammonemia. The other major abnormality was decreased beta-oxidation and markedly increased omega-oxidation. After L-carnitine supplementation, VPA metabolism returned to normal. The level of valproylcarnitine was not increased and therefore was not affected by L-carnitine. L-Carnitine may be useful in treating patients with coma after VPA overdose.

Ammonia↗
PubMed1996

Upstream interactions at the lambda pRM promoter are sequence nonspecific and activate the promoter to a lesser extent than an introduced UP element of an rRNA promoter.

The rightward regulatory region of bacteriophage lambda contains two promoters, pRM and pR, which direct the synthesis of nonoverlapping divergent transcripts from start sites 82 bp apart. Each of the two promoters has an upstream (A+T)-rich region (ATR) within the sequence from -40 to -60 where in the rrnB P1 promoter a stretch of 20 (A+T) bp greatly stimulates promoter function. Here we present an investigation of the possible functional significance of pRM's ATR. We determined the effects on RNA polymerase-pRM promoter interaction both of (G+C) substitutions in the ATR and of amino acid substitutions in the alpha subunit, known to affect the upstream interaction. We find small (two- to threefold) effects of selected mutations in the alpha subunit on open complex formation at pRM. However, the (presumably upstream) interactions underlying these effects are sequence nonspecific, as they are not affected by (G+C) substitutions in the ATR. Substitution of the 20-bp UP element of the rrnB P1 promoter between positions -40 and -60 at pRM stimulates open complex formation to a considerably greater extent (5- to 10-fold). Results from kinetic studies indicate that on this construct the UP element mainly accelerates a step subsequent to the binding of RNA polymerase, although it may also facilitate the binding event itself. Less extensive studies likewise provide evidence for a two- to threefold activation of pR by upstream interactions. The possible involvement of the alpha subunit in the previously characterized (e.g., B. C. Mita, Y. Tang, and P. L. deHaseth, J. Biol. Chem. 270:30428-30433, 1995) interference of pR-bound RNA polymerase with open complex formation at pRM is discussed.

Amino Acid Sequence↗
PubMed1996

Attenuation of endotoxin-induced pulmonary vascular injury by antithrombin III.

We evaluated the effects of antithrombin III (AT III) on the pulmonary vascular injury induced by injecting rats with lipopolysaccharide (LPS) to investigate the possible usefulness of AT III as a treatment for acute respiratory distress syndrome. The intravenous administration of AT III prevented the pulmonary accumulation of leukocytes (as evaluated by myeloperoxidase activity) and the increase in pulmonary vascular permeability to 125I-bovine serum albumin induced by LPS. The increase in pulmonary vascular permeability induced by LPS administration was unaffected by various anticoagulants but was inhibited by the leukocytopenia induced by nitrogen mustard or by the administration of a granulocyte elastase inhibitor, ONO-5046. AT III given alone, but not heparin plus AT III or Trp49-modified AT III, which lacks affinity for heparin, significantly increased the plasma concentration of 6-keto-prostaglandin F1alpha, suggesting that the interaction of AT III with heparin-like substances at the endothelial cell surface promotes the release of prostacyclin from endothelial cells in vivo. Trp49-modified AT III failed to prevent the LPS-induced accumulation of leukocytes and vascular injury. The pulmonary accumulation of leukocytes and vascular injury induced by LPS were not prevented by administering AT III to rats that were pretreated with indomethacin. The continuous intravenous infusion of prostacyclin prevented the LPS-induced pulmonary accumulation of leukocytes and vascular injury. Findings suggest that AT III depends on its ability to promote the release of prostacyclin, a potent inhibitor of leukocyte activation, from endothelial cells to prevent pulmonary vascular injury induced by LPS.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Recombinant thrombomodulin prevents endotoxin-induced lung injury in rats by inhibiting leukocyte activation.

Acute respiratory distress syndrome (ARDS) is a serious complication of sepsis. Thrombomodulin, an important endothelial anticoagulant, binds thrombin to generate activated protein C (APC). We have previously demonstrated that APC prevents endotoxin (ET)-induced pulmonary vascular injury by inhibiting activated leukocytes. We therefore examined whether recombinant human soluble thrombomodulin (rhs-TM) prevents activated leukocyte-induced pulmonary vascular injury in rats receiving ET. Intravenous administration of rhs-TM prevented ET-induced pulmonary accumulation of leukocytes and increase in pulmonary vascular permeability, as well as ET-induced histological changes, such as leukocyte infiltration and pulmonary interstitial edema. Dansyl-Glu-Gly-Arg-chloromethyl ketone-treated factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, did not prevent these effects of ET. rhs-TM did not prevent ET-induced pulmonary accumulation of leukocytes and pulmonary vascular injury in rats pretreated with DEGR-Xa. These results suggest that rhs-TM prevents ET-induced pulmonary vascular injury by inhibiting pulmonary accumulation of leukocytes and that this effect may be mediated primarily by APC generation.

Animals↗
PubMed1996

Role of transcriptional cis-elements, angiotensinogen gene-activating elements, of angiotensinogen gene in blood pressure regulation.

Results of recent genetic studies suggest that the angiotensinogen gene is a possible determinant of hypertension. Using antisense technology, we demonstrated that generation of circulating angiotensinogen is a rate-limiting step in blood pressure regulation. In the present study, we examined how the angiotensinogen gene is regulated in vivo. The transcriptional cis-elements, angiotensinogen gene-activating elements (AGE) 2 and 3, have been reported to regulate angiotensinogen production in human hepatocytes in vitro. To determine the critical transcriptional regulator of angiotensinogen production in vivo, we used synthetic double-stranded oligodeoxynucleotides (ODN) as "decoy" cis-elements to block the binding of nuclear factors to promoter regions of the targeted gene, resulting in the inhibition of gene transactivation. Here we examined whether AGE 2 and AGE 3 in the promoter region of the angiotensinogen gene have a pivotal role in hepatic angiotensinogen production in vivo. Hepatic angiotensinogen mRNA was decreased by the transfection of AGE 2 but not mismatched decoy ODN. Transfection of decoy but not mismatched ODN against AGE 2 resulted in a transient decrease in blood pressure of spontaneously hypertensive rats (SHR), accompanied by a reduction in plasma angiotensinogen and angiotensin II levels. In contrast, transfection of AGE 3 decoy ODN had little effect on blood pressure. Overall, our results demonstrate that transfection of decoy ODN against AGE 2, but not against AGE 3, of the angiotensinogen gene resulted in a transient decrease in high blood pressure of SHR, suggesting that the transcriptional cis-element AGE 2, rather than AGE 3, has an important role in blood pressure regulation through the control of circulating angiotensinogen.

Angiotensinogen↗
PubMed1996

Tissue-specific regulation of angiotensinogen gene expression in spontaneously hypertensive rats.

Angiotensinogen is expressed in many tissues besides the liver. Recent studies have suggested that abnormalities in the regulation of angiotensinogen gene expression may be involved in the development of hypertension. However, little information is available concerning the functional significance of tissue angiotensinogen. In this study, we measured plasma angiotensinogen concentration by radioimmunoassay and examined the expression of tissue angiotensinogen by Northern blot analysis in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Although plasma angiotensinogen concentration in SHR was comparable to that in WKY at 6 weeks of age, it was increased significantly at 14 weeks of age in SHR and became higher than that in WKY. The levels of hepatic angiotensinogen mRNA were similar in SHR and WKY, and the levels of aortic, adrenal, and renal angiotensinogen mRNAs were lower in SHR than in WKY at both 6 and 14 weeks of age. Brain angiotensinogen expression in SHR was higher than in WKY at 6 weeks of age and was comparable to that in WKY at 14 weeks of age. On the other hand, cardiac and fat angiotensinogen mRNA levels were significantly increased at 14 weeks of age in SHR. These results demonstrate that the expression of tissue angiotensinogen is regulated differently in SHR and WKY and indicate that the development of hypertension is accompanied at least temporally with increases in plasma angiotensinogen concentration as well as cardiac and adipogenic angiotensinogen mRNA in SHR.

Angiotensinogen↗
PubMed1996

Double cancer in a 74-year-old woman: a case report with genetic findings.

An autopsy case of double cancer is reported. The patient had undergone right hemicolectomy for colon carcinoma in 1982, and the second cancer was detected in the pancreas in April 1989, which was diagnosed as intraductal papillary adenocarcinoma that is known for its favorable prognosis after surgical resection. However, as the patient did not consent to the operation, she died in August 1994, five years after the diagnosis of the second cancer. Histopathological study revealed neither recurrence nor metastasis of colon carcinoma. The pancreatic carcinoma metastasized to the lung, liver, and peritoneum. DNAs were extracted from paraffin-embedded tissue for molecular pathological examinations. Different mutations were found at codon 12 of the K-ras gene by nucleotide sequencing analysis: one in the colon and the other in the pancreas and lung. Over-expression of p53 protein was also detected in the colon by immunostaining. Replication error was not observed in these three tumors suggesting that a factor(s) other than genetic instability was playing a role in the development of double cancer in this patient.

Aged↗
PubMed1996

Liver involvement in Tsutsugamushi disease.

Tsutsugamushi disease, one of the rickettsiosis, is known to be occasionally accompanied by elevation of hepatic enzyme levels. However, there are only a few reports on histopathological findings of the liver. We presented a case of Tsutsugamushi disease with liver involvement. A 51-year-old man suffered from eruptions and a high fever with a mild transaminasemia. He was diagnosed as Tsutsugamushi disease by detection of IgM class antibody against Rickettsia tsutsugamushi. Laparoscopic examination showed a dark-brown liver with diffuse whitish markings. Microscopic findings were consistent with the features of non-specific reactive hepatitis: sinusoidal small lymphocyte infiltrations, mild disarray of hepatocytes and aggregation of T lymphocytes and macrophages in the lobule.

Humans↗
PubMed1996

Exercise-induced change in beta-adrenergic receptor number in lymphocytes from trained and untrained men.

This study was undertaken to clarify whether beta-adrenergic receptor (beta-AR) translocation from intracellular sites to the cell surface contributes to an increase in the number of beta-AR in lymphocytes from trained and untrained men after exercise. Nine trained and 9 untrained subjects performed exercise on a bicycle ergometer until exhaustion. The number of beta-AR in the cell surface (beta-AR(surface)) and intracellular sites (beta-AR(intra)) was determined at rest and after maximal exercise by measuring the binding of the radioligand 125I-iodocyanopindolol in the presence or absence of hydrophilic (CGP-12177A) or lipophilic (propranolol) unlabeled ligands. The number of beta-AR(surface) increased after exercise from 1,524.4 +/- 321.4 to 3,432.6 +/- 503.3 sites/cell (p < 0.01), whereas that of beta-AR(intra) decreased from 356.2 +/- 85.7 to 190.3 +/- 60.2 sites/cell (p < 0.05). The isoproterenol-stimulated cAMP production per 1 x 10(6) lymphocytes after exercise was significantly higher than that at rest. However, the cAMP production per single beta-AR(surface) tended to be lower after exercise. No differences between the trained and untrained subjects were found in beta-AR numbers or intracellular cAMP levels. These findings demonstrate that maximal exercise induces the translocation of beta-AR from intracellular sites to the cell surface in human lymphocytes. However, this translocation accounts for only 10% of the increase in total cellular beta-AR, suggesting that other mechanisms are predominant and contribute substantially to the increase in beta-AR(surface).

Adult↗
PubMed1996

Immunohistochemical characterization of monoclonal antibodies (PDs) as markers of the periderm in the developing chicken embryo.

The outermost surface cell layer of the developing embryo, the periderm, arises from the initial single layer of ectoderm and is eventually exfoliated from the stratified epidermis, which has the same ectodermal origin. In this study, monoclonal antibodies against chicken limb bud ectoderm were generated and screened for those which stained the periderm. Four separate antibodies termed PD2, 3, 7 and 9 were obtained from 180 mixed hybridomas. These PD antibodies stained the periderm selectively at all stages examined (stage 20-42). By correlating the results of immunohistochemistry with observations made by transmission electron microscopy, it was revealed that PD antibodies stained both the squamous periderm at an early stage and rounded bulging peridermal cells just before exfoliation. Therefore we feel that PD antibodies may be useful in further systematic investigations of the development and function of the chicken embryonic periderm.

Animals↗
PubMed1996

[Isolated angiitis of the central nervous system presenting as subcortical hemorrhage--a case report of benign type].

A 47-year-old woman had an episode of severe headache for a few days. She suddenly experienced right leg weakness and sensory loss. A CT scan revealed subcortical hematoma at the left parietal lobe on admission. Cerebral angiography showed multiple vascular irregularities such as segmentally narrow or sausage-like dialatated areas. Her laboratory studies were entirely normal including antinuclear antibody and coagulation tests. The diagnosis of isolated angiitis of the CNS was made and she responded well to the low dose corticosteroid therapy. Repeated cerebral angiography two months after the onset demonstrated most of the areas of segmental irregularity had improved with a few unchanged areas. Some cerebral angiitis do exist that respond well to corticosteroid therapy, therefore, early diagnosis and treatment are suggested in cases of angiitis.

Cerebral Arterial Diseases↗
PubMed1996

Expression of tenascin in normal and diseased human kidneys.

Expression of tenascin was studied in normal human adult and fetal kidney specimens, and in renal tissues biopsied from patients with several types of glomerulonephritis. Immunofluorescent staining of the normal kidneys showed that tenascin was present weakly in the mesangial area and interstitium, but was absent from the glomerular capillaries. In the fetal kidney, tenascin was detected in the interstitium, but not in the immature glomeruli. In kidney tissues biopsied from patients with various renal diseases, expression of tenascin was associated with increased mesangial expansion and tubulointerstitial changes. In situ hybridization showed that tenascin mRNA was expressed in the renal tissues, but tenascin mRNA and tenascin protein were occasionally dissociated. These findings indicate that expression of tenascin is associated with mesangial expansion and also with tubulointerstitial changes in human glomerulonephritis. Tenascin expression may contribute to repair of injured glomeruli and interstitium.

Adult↗
PubMed1996

Follow-up study on F-wave in patients with lumbosacral radiculopathy. Comparison between before and after surgery.

The aim of this study is to explore the clinical value of follow-up examinations of F-wave in patients with lumbosacral radiculopathy. Postoperative changes in the initial abnormalities and their relationship with improvement in clinical findings were examined. Results from conventional motor nerve conduction study at knee-ankle segment are also discussed. The subjects were 30 patients with unilateral lumbosacral radiculopathy caused by herniated disc. F-waves were obtained from abductor hallucis and extensor digitorum brevis by supramaximal stimulation to tibial and peroneal nerves, respectively, at the ankle. Minimal latency (Fmin), maximal latency (Fmax), chronodispersion (Fdif) and duration (Fdur) were used as the parameters. No subject had abnormal motor nerve conduction velocity (MCV) throughout the course of this study, and there was no significant difference between preoperative and postoperative levels. Peroneal Fmin, Fmax, Fdif and tibial Fdur all showed significant (p < 0.05 in Wicoxon signed-rank test) improvement after surgery. Moreover, these overall improvements significantly (p < 0.05 in chi 2 test) correlated with recovery in muscle weakness. However, normalization of F-wave was not always associated with full recovery in muscle weakness at that time. These findings suggested that follow-up examination of F-wave was of value for objective assessment after operation.

Adult↗
PubMed1996

A novel platelet activating factor antagonist, SM-12502, attenuates endotoxin-induced disseminated intravascular coagulation and acute pulmonary vascular injury by inhibiting TNF production in rats.

Adult respiratory distress syndrome and disseminated intravascular coagulation are important pathologic conditions affecting the outcome of patients with sepsis. To elucidate the possible therapeutic efficacy of SM-12502, a novel platelet activating factor antagonist, on acute lung injury and disseminated intravascular coagulation in sepsis, we investigated the effect of SM-12502 on an endotoxin (ET)-induced septic model in rats. SM-12502 prevented ET-induced increases in pulmonary vascular permeability and ET-induced histologic changes, such as leukocyte infiltration and pulmonary interstitial edema, 6 h following the administration of ET (5 mg/kg). SM-12502 also inhibited the decrease in fibrinogen and the increase in fibrin and fibrinogen degradation products observed following ET administration. SM-12502 prevented increases in the serum concentration of tumor necrosis factor (TNF) 90 min following ET administration in vivo, and significantly inhibited the production of TNF-alpha by ET-stimulated monocytes in vitro. These findings suggest that SM-12502 attenuates the actions of endotoxin by the inhibition of TNF production.

Animals↗