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Biomedical subjects

K Murakami

Publications and source records attributed to K Murakami.

At least 523 records · Page 29Linked to original sources
PubMed1995

Transient decrease in high blood pressure by in vivo transfer of antisense oligodeoxynucleotides against rat angiotensinogen.

The renin-angiotensin system plays an important role in blood pressure regulation. Angiotensinogen, which is mainly produced in the liver, is a unique component of the renin-angiotensin system, because angiotensinogen is only known as a substrate for angiotensin I generation. It is unclear whether circulating angiotensinogen is a rate-limiting step in blood pressure regulation. Recent findings of genetic studies and analyses suggest that the angiotensinogen gene may be a candidate as a determinant of hypertension. To test the hypothesis that angiotensinogen may modulate blood pressure, we transfected antisense oligonucleotides against rat angiotensinogen into the rat liver via the portal vein using liposomes that contain viral agglutinins to promote fusion with target cells, a technique that has been reported to be highly efficient. Transfection of antisense oligonucleotides resulted in a transient decrease in plasma angiotensinogen levels in spontaneously hypertensive rats from day 1 to day 7 after the injection, consistent with the reduction of hepatic angiotensinogen mRNA. Plasma angiotensin II concentration was also decreased in rats transfected with antisense oligonucleotides. Moreover, a transient decrease in blood pressure from day 1 to day 4 was observed, whereas transfection of sense and scrambled oligonucleotides did not result in any changes in plasma angiotensinogen level, blood pressure, or angiotensinogen mRNA level. Overall, our results demonstrate that transfection of antisense oligonucleotides against rat angiotensinogen resulted in a transient decrease in the high blood pressure of spontaneously hypertensive rats, accompanied by a decrease in angiotensinogen and angiotensin II levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1995

Phenotypic analysis of neoplastic cells from calf, thymic, and intermediate forms of bovine leukosis.

Immunohistochemistry and flow cytometric analysis were used with monoclonal antibodies to examine the phenotype of neoplastic cells from cattle with sporadic bovine leukosis (three cases of calf form, two cases of thymic form, and three cases of intermediate form). Three cases of calf form and two cases of intermediate form were positive for B cell lineage in immunohistologic examination and in flow cytometric analysis for B-B2+, sIgM+, and major histocompatibility class II+. Two cases of thymic form and one case of intermediate form were CD2+, CD5+, CD6+, and CD8+ in immunohistologic examination and in flow cytometric analysis. The results show that neoplastic cells develop from B and T cell lineages in sporadic bovine leukosis.

Animals↗
PubMed1995

Immunohistochemical localization of thromboxane receptor and thromboxane synthase in rat testis.

The cellular localization of thromboxane A2 receptor (TXR) and thromboxane synthase (TXS) in rat testes was examined with an antibody against the carboxyl-terminal tail of rat TXR and anti-porcine lung TXS antibody. By light microscopy immunoreactivity for TXR was shown to be present in spermatids, whereas spermatogonia, spermatocytes, and spermatozoa lacked the immunoreactivity. Immunoelectron microscopic analysis revealed that immunostainable TXR was present in acrosomes of spermatids. In contrast, immunoreactivity for TXS was present in all stages of spermatogenic cells; spermatogonia, spermatocytes, spermatids, and spermatozoa. TX system may possibly contribute to the formation of acrosomes or have some unrecognized functions in an autocrine/paracrine fashion.

Amino Acid Sequence↗
PubMed1995

[Studies on attenuation of post-ischemic brain injury by kampo medicines-inhibitory effects of free radical production. II].

It is thought that highly reactive oxygen radicals generated at the ischemia-reperfusion in case of strokes play an important role in damaging the brain. It is well known that lipid peroxidation is propagated by active oxygen radicals, and the the brain is susceptible to the lipid peroxidation. In the previous study, we found that several Chinese herbal medicines and kampo components, which were used for the attenuation of the post-ischemic brain injury, showed a free-radical (OH., O2-. and DPPH) scavenging activity. However, it is not clear whether these Chinese herbal medicines can inhibit the lipid peroxidation reaction or not. In attempting to address this question, we have used three kinds of kampo formulations (Oren-gedoku-to (Huang-Lian-Jie-Du-Tang), Saiko-ka-ryukotsu-borei-to (Chai-Hu-Jia-Long-Gu-Mu-Li-Tang) and Keishi-bukuryo-gan (Gui-Zhi-Fu-Ling-Wan)) to measure the suppressive effect of the lipid peroxidation on the mouse cerebrum using the TBA technique in vitro and in vivo. In vitro experiments, all these Chinese herbal medicines decreased the levels of TBA-reactive substances concentration-dependently. In vivo studies, the levels of the TBA-reactive substance of the cerebrum homogenate of mice treated with these kampo formulations by p.o. for three weeks also decreased. From these results, we suggest that the pharmacological action of Chinese herbal medicines used for the attenuation of the post-ischemic brain damage not only have a free-radical scavenging activity, but also have a suppressive effect on the generation of the lipid peroxidation.

Animals↗
PubMed1995

Role of cathepsin B as prorenin processing enzyme in human kidney.

Renin is synthesized from an inactive precursor, prorenin, through cleavage at a pair of basic amino acids catalyzed by prorenin processing enzyme (PPE). A lysosomal protease, cathepsin B, has been suggested to be a strong candidate for PPE. However, there still remains a possibility that other protease(s) can also catalyze prorenin processing. We studied the subcellular distribution of PPE in human renal cortex using pure recombinant prorenin as a PPE assay substrate. PPE and renin activities, and cathepsin B activity and protein were colocalized in the lysosomal fraction. The PPE activity was completely inhibited by a cathepsin B specific inhibitor, CA074. Taken together with the immunohistochemical data showing that cathepsin B and PPE are colocalized in dense secretory granules of juxtaglomerular cells of kidney, we conclude that cathepsin B is the authentic PPE in human kidney.

Catalysis↗
PubMed1995

Recent advances in the study of renin and angiotensinogen genes: from molecules to the whole body.

The renin-angiotensin system (RAS) plays a key role in the regulation of the circulation and is critically involved in the pathogenesis of several diseases, including hypertension. Renin is synthesized mainly in the kidney and is secreted into the bloodstream. It catalyzes the rate-limiting cleavage of substrate angiotensinogen, which is derived mainly from the liver, to generate angiotensin I. Renin and angiotensinogen genes have been isolated and their structure has been determined by the methods of molecular biology. Renin and angiotensinogen genes are expressed in many tissues, and the tissue-specific regulation of these genes has been studied. The existence of local RASs in contrast to the classical circulating RAS has been suggested, although their exact functional role remains to be determined. Recent molecular analyses have led to a detailed description of the transcriptional mechanism of the renin and angiotensinogen genes, and have made it possible to study the regulation of the expression of these genes in several physiological and pathological states. In addition, several types of transgenic animals have been developed to study the functional importance of the RAS in vivo. Transgenic mice with human renin and human angiotensinogen genes may be a good model of human hypertension. In such mice, the human genes are expressed in the normal tissue-specific pattern, the circulating RAS is activated, and blood pressure is high. Finally, angiotensinogen-deficient mice have also been developed by homologous recombination in mouse embryonic stem cells. These mice do not produce angiotensinogen in the liver. As a result, they have no plasma immunoreactive angiotensin I and are hypotensive. The profound hypotension in these mice indicates the importance of the RAS in maintaining pressure.

Angiotensinogen↗
PubMed1995

Development of oligodendrocyte and myelination in the central nervous system.

We demonstrated the cell lineage of oligodendrocytes from the glial precursor cells to mature oligodendrocytes forming myelin sheath around the axon. There are several different stages of oligodendrocyte development in vito. So far there are no precise data about their morphological changes during oligodendrocyte development, but by the analysis using SEM and immunostaining, the characteristic morphological changes with serial expression of cell markers were observed in each developmental steps of oligodendrocyte. We have also clearly demonstrated how oligodendrocytes wrap around the axon by using video time-lapse movies. These results will be useful for understanding the exact cellular mechanism of myelination in the CNS.

Animals↗
PubMed1995

delta-Aminolevulinic acid dehydratase deficiency porphyria (ADP) with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in a 69-year-old woman.

delta-Aminolevulinic acid dehydratase deficiency porphyria (ALAD porphyria, ADP) with syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in a 69-year-old woman is reported. The patient was admitted to our hospital complaining of slight cough with low-grade fever, and treated with piperacillin sodium, resulting in complete resolution of the symptoms, following a diagnosis of bronchopneumonia. Thereafter, however, she began to complain of vomiting, abdominal pain, facial numbness and paresis of the extremities with gait disturbance, and became comatose with hyponatremia (serum Na concentration 119 mEq/L) in a few days. Laboratory tests revealed an antidiuretic hormone (ADH) level of 13.5 pg/mL, plasma osmolality 218 mOsm/KgH2O, urinary osmolality 429 mOsm/KgH20, urinary Na concentration > 20 mEq/L, and no abnormalities of thyroid, adrenal or renal function. Neither edema nor dehydration was evident. These data indicated the presence of SIADH. No abnormalities suggestive of malignant or infectious diseases such as lung cancer, pneumonia and Guillain-Barré syndrome were evident from laboratory and roentgenographic findings. As the cause of SIADH, therefore, porphyria was suspected. Metabolites and activities of enzymes in the heme biosynthetic pathway were examined, and very low activity of delta-aminolevulinic acid dehydratase (ALA-D) (0.14 mumol PBG/mL RBC/h) was found. The patient was neither an alcoholic nor a heavy smoker, and she had no past history of heavy metal intoxication, photosensitivity or tyrosinemia. On the basis of these data and clinical features, she was diagnosed as having ADP. We consider this to be the first case of ADP reported in Japan.

Abdominal Pain↗
PubMed1995

Establishment of a new human cell line, LI90, exhibiting characteristics of hepatic Ito (fat-storing) cells.

BACKGROUND: Thus far, human hepatic Ito (fat-storing) cell lines have not been established. Therefore, functional characteristics of Ito cells have not been fully investigated. EXPERIMENTAL DESIGN: We established a new cell line, LI90, that exhibited characteristics compatible with those of Ito cells from a human hepatic mesenchymal tumor. LI90 cells were examined with phase-contrast microscopy, immunohistochemistry, and cytogenetics, and their vitamin A-storing activity was analyzed. To obtain a marker specific for Ito cells for immunohistochemical analyses, we raised mAb against LI90 cells and clarified the molecular nature of the Ag recognized with the new Ab using an expression cloning approach. RESULTS: LI90 cells showed polygonal shape and had well developed alpha-smooth muscle actin filaments in their cytoplasm. In an overconfluent culture condition, LI90 cells aggregated to form a typical hills-and-valleys structure, LI90 cells produced various connective tissue components, such as collagen types I, III, IV, V, and VI, laminin, and fibronectin. In culture media containing vitamin A, LI90 cells formed many fat droplets in their cytoplasm, and fluorescence characteristic of vitamin A was observed in the droplets. By immunizing mice with LI90 cells, three separate mAb specifically reacting with Ito cells in human liver sections were established, and the Ag recognized with all three Ab were identified as extracellular matrix tenascin. CONCLUSIONS: The above-described morphologic and functional characteristics, including vitamin A-storage and biosynthesis of tenascin, are compatible with those of Ito cells. Therefore, LI90 cells will be useful for in vitro studies of functions of human Ito cells.

Antibodies, Monoclonal↗
PubMed1995

[A possible mechanism of interstitial pneumonia during interferon therapy with sho-saiko-to].

Interstitial pneumonia has been reported to be a side effect of treatment with interferon, and Sho-saiko-to (Xiao-Chai-Hu-Tang) may enhance this side effect. It is well known that activated neutrophils are important mediators of pulmonary fibrosis, so we studied the effects of interferon and Sho-saiko-to on neutrophil activation. Homogenized lung myeloperoxidase (MPO) activity was assayed after intraperitoneal injection of interferon with or without pretreatment with Sho-saiko-to. Although Sho-saiko-to alone did not change the lung MPO content, MPO in the lung was significantly increased by interferon administration. The increase was enhanced further by pretreatment with Sho-saiko-to. When the accumulated neutrophils are activated by some cytokines, such as TNF alpha or IL-1 beta from monocytes/macrophages, they may damage lung tissue. We therefore studied the effects of Sho-saiko-to and interferon on TNF alpha production in freshly isolated human monocytes. Sho-saiko-to increased the production of TNF alpha, but interferon did not. In addition, Sho-saiko-to significantly increased the production of TNF alpha by monocytes stimulated by lipopolysaccharide. Taken together, these data indicate that interferon causes neutrophils to accumulate in the lung. Sho-saiko-to alone may not injure lung tissue, but it increases the effect of interferon. When stimulated by some antigen, Sho-saiko-to may overstimulate the neutrophils. Granulocytes elastase and oxygen radicals released from activated neutrophils may damage lung tissue. The fibroblasts that repair the damaged tissue may increase the risk of pulmonary fibrosis.

Animals↗
PubMed1995

[Serum pepsinogen response to therapy for Helicobacter pylori associated gastro-duodenal disease].

We investigated the effect of H. pylori therapy on serum concentrations of pepsinogens on 87 patients of gastro-duodenal disease. In addition, we intended to see whether serum pepsinogen can serve as markers of response to H. pylori eradication. In 48 successfully eradicated cases, there was a significant decrease in gastritis score, and was a significant fall in serum pepsinogen II (PG II) level, and was a significant increase in pepsinogen I/II ratio (PG I/II ratio). In contrast, no change in gastritis score, PG II, and PG I/II ratio were observed in 39 unsuccessfully eradicated patients. No change in serum pepsinogen I (PG I) level was observed in both groups. In provisional successfully eradicated cases in PG II of decrease greater than 30% in after treatment, there was a sensitivity of 83.3% and a specificity of 89.7%. For the PG I/II ratio of increased greater than 30% in after treatment, the sensitivity was 95.8%, and the specificity was 94.9%. These findings suggest that PG II, PG I/II ratio can be useful for clinical evaluation of eradication therapy.

Adolescent↗
PubMed1995

Peptic ulcer recurrence after Helicobacter pylori eradication: a 5-year follow-up study.

OBJECTIVE: To investigate whether eradication of Helicobacter pylori prevents peptic ulcer recurrence in the long term. PATIENTS AND METHODS: We treated 81 patients with endoscopically proven H. pylori-related peptic ulcers (39 with gastric ulcers and 42 with duodenal ulcers) with either amoxycillin or clarithromycin in combination with a proton-pump inhibitor or a histamine H2-receptor antagonist. The patients were followed for a recurrence of peptic ulcers for at least 5 years. Recurrence was assessed by endoscopy and the status of H. pylori was evaluated by culture, a rapid urease test and a histological examination. RESULTS: After 5 years of follow-up, the rate of recurrence of H. pylori-related duodenal ulcers decreased significantly (P < 0.0001) in the H. pylori-eradicated patients compared with non-eradicated patients. However, in the gastric ulcer group, there was no significant reduction in the recurrence rate. CONCLUSIONS: Our findings suggest that eradication of H. pylori significantly reduces the rate of duodenal ulcer relapse and that this relapse is associated with the presence of H. pylori. Therefore, H. pylori eradication may be considered a definitive cure for duodenal ulcers.

Adolescent↗
PubMed1995

Influence of Helicobacter pylori infection and the effects of its eradication on gastric emptying in non-ulcerative dyspepsia.

AIM: The aim of the present study was to clarify the effects of Helicobacter pylori infection and its eradication on gastric emptying. SUBJECTS AND METHODS: Out of a total of 52 patients with non-ulcerative dyspepsia, 34 H.pylori-positive patients were enrolled. Antimicrobial drugs for the eradication of H. pylori were administered to 19 out of the 34 H. pylori-positive patients. Gastric emptying was evaluated according to the acetaminophen method. Inflammatory changes and intracellular periodic acid-Schiff-positive substances in the antral mucosa were examined in biopsy specimens. RESULTS: Although gastric emptying was significantly prolonged in the patients with non-ulcerative dyspepsia compared with the control group (P < 0.01), there was no difference in gastric emptying between H. pylori-positive and -negative patients, with all patients showing significantly less gastric emptying than the control group. The H. pylori eradication rate was 58% (11 out of 19) and gastric emptying improved significantly in seven patients whose infection was eradicated and whose dyspeptic symptoms disappeared. The ammonia concentration in gastric juice, inflammatory changes in the gastric mucosa and the index of periodic acid-Schiff-positive substances improved significantly when H. pylori was successfully eradicated compared with patients in whom eradication was unsuccessful. As gut hormones may affect gastroduodenal motility associated with H. pylori infection, we also studied the levels of serum gastrin and cholecystokinin. In the patients whose infection was eradicated, serum gastrin decreased significantly, but the cholecystokinin level did not change significantly, although there was a non-significant trend for cholecystokinin to increase. CONCLUSIONS: These results suggest that delayed gastric emptying is partly associated with H. pylori infection and that the infection may contribute to the development of non-ulcerative dyspepsia.

Adult↗