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Biomedical subjects

K Murakami

Publications and source records attributed to K Murakami.

At least 757 records · Page 42Linked to original sources
PubMed1992

A gender difference in the association between salt sensitivity and family history of hypertension.

We examined 174 subjects (82 men and 92 women) with essential hypertension to determine whether gender played an important role in the association of blood pressure (BP) familial disposition, and hypertension. To evaluate the salt sensitivity of BP, we measured changes in blood pressure after restricting salt intake from about 15 g/day to less than 3 g/day. The familial disposition to hypertension was categorized into four groups according to the presence or absence of hypertension in the father, mother, and siblings. If none, one, two, or three family members had hypertension, they were assigned the FH(-), FH(+), FH(++), and FH( ) groups, respectively. Only in women did the FH(-) group show a significantly smaller blood pressure reduction than that of the other groups. The mean BP reduction in the four groups was 4.1 +/- 1.9, 8.5 +/- 1.1, 10.1 +/- 1.5, and 11.2 +/- 2.8 mm Hg (mean +/- SEM), respectively. This difference in BP reduction was not observed in men. Multiple regression analysis, using percent changes in mean BP as the dependent variable and other factors as independent variables, also showed a significant partial correlation coefficient for familial disposition to hypertension only in women. Thus, the relationship between salt sensitivity and familial disposition to hypertension differed according to gender. This difference may provide an important insight into the hereditary nature of hypertension.

Adult↗
PubMed1991

Identification of a previously unrecognized production site of human renin.

We found expression of the renin gene in the intestine of human, mouse and the transgenic mouse in which the 3' flanking sequences of the human renin gene function as a tissue-specific promoter. A cotransfection analysis showed that the promoter is activated by the product of adenovirus E1A 13S mRNA in cells originated from extrarenal tissues.

Adenoviridae↗
PubMed1991

[Evaluation of renal function by dynamic CT].

Dynamic CT scans of the kidney were conducted in 57 persons with varied renal function. The results of dynamic CT were used to obtain time-density curves for renal cortex, medulla and aorta. Various parameters were calculated from these time-density curves. Among them, CA ratio, the ratio of the area under the renal cortex curve to the area under the aortic curve, showed the best correlation with creatinine clearance. With these parameters, dynamic CT studies are believed to be useful in evaluating renal function.

Adult↗
PubMed1991

The presence of two types of prorenin converting enzymes in the mouse submandibular gland.

We have recently demonstrated, by protein and cDNA sequence analyses, that prorenin converting enzyme (PRECE) in the ICR mouse submandibular gland is identical to the epidermal growth factor-binding protein (EGF-BP) type B, the mGK-13 gene product identified in Balb/c mouse. However, in the course of cDNA cloning, we noticed the presence of the other cDNA type highly homologous but not identical to the PRECE cDNA. The sequence of the newly identified cDNA was identical to that of the pSGP-2 cDNA cloned from NMRI mice, which also encodes EGF-BP type B different at 9 out of 261 amino acids from the mGK-13 product. Although this difference has been explained by strain polymorphism, our results indicate that these two proteins are distinct gene products. The product of the newly identified cDNA also had a prorenin converting activity. Thus, the products of both cDNAs identified in previous and present studies are involved in maturation of two bioactive polypeptides, renin and EGF.

Amino Acid Sequence↗
PubMed1991

Expression of the human angiotensinogen gene in transgenic mice and transfected cells.

We have generated two lines of transgenic mice with integrated copies of a 14-kilobase pair (kb) human DNA fragment containing the angiotensinogen gene, which includes 1.3 kb of 5'- and 3'-flanking regions. In both transgenic lines, a considerable quantity of the correctly initiated and processed angiotensinogen mRNA was detected in the liver and it was detectable in heart. Unexpectedly, mRNA for the transgene was accumulated in the kidney, where is normally the minor source of angiotensinogen, to levels comparable to that in the liver. In addition, an in vitro transfection analysis suggested that the 1.3-kb 5'-flanking sequences are essential for expression of the angiotensinogen gene in hepatic and renal cells and that neither DNA segment within the 14-kb construct contributes significantly to repression of the gene expression in renal cells.

Angiotensinogen↗
PubMed1991

Mouse submandibular gland prorenin-converting enzyme is a member of glandular kallikrein family.

Mouse submandibular gland prorenin-converting enzyme (PRECE) consists of the two polypeptide chains of 17 and 10 kDa and cleaves mouse Ren-2 prorenin at a dibasic site to yield mature renin. Western blot analysis using an antiserum against this enzyme gave rise to multiple bands in mouse submandibular glands, suggesting that PRECE is a member of a protease family. Partial amino acid sequence analysis of purified PRECE and cloning and sequence analyses of its cDNA indicated that it is identical to the mGK-13 gene product, epidermal growth factor-binding protein type B, which is a member of the glandular kallikrein family and is involved in maturation of epidermal growth factor. Conditioned medium from Chinese hamster ovary cells transfected with an expression plasmid for PRECE had prorenin converting activity. These results indicate that PRECE is involved in the maturation of two bioactive polypeptides expressed in mouse submandibular glands, Ren-2 renin and epidermal growth factor.

Amino Acid Sequence↗
PubMed1991

Decay of mammalian hexokinase: characterization of the specific proteolytic activity.

Hexokinase-degrading activity (HKDA) is associated with hexokinase throughout purification. It is not ubiquitin-dependent. With glucose present, HKDA requires MgATP. It is triggered by removal (or ATP-dependent consumption) of glucose, and masked when glucose is restored. PCMB, TLCK and TPCK suppress hexokinase and activate HKDA. Glucose removal and active-site blockage appear to induce HKDA.

Adenosine Triphosphate↗
PubMed1991

Human renin in transgenic mouse kidney is localized to juxtaglomerular cells.

To examine whether expression of human renin in the transgenic mouse kidney is regulated in a cell-specific manner, we have characterized monoclonal antibodies against human renin and determined the renin-production site by immunohistochemistry. By using a monoclonal antibody specific for human renin, A6-11-6, we demonstrated that human renin in the transgenic mouse kidney is localized to the juxtaglomerular cells of afferent arterioles.

Animals↗
PubMed1991

[Depiction of the normal adrenal gland evaluation with 0.5 tesla MRI].

MR studies of the abdomen in 128 patients were reviewed in order to evaluate the normal adrenal glands. The studies were performed on a 0.5-Tesla superconducting unit. T1-weighted spin-echo (T1WI), T2-weighted spin-echo (T2WI) and T2*-weighted gradient-echo (T2*-WI) images were obtained. T1WI demonstrated the normal adrenal glands in 90% of the patients. T2*WI identified the glands in 86%, a higher rate than the 73% for T2WI. On both T1WI and T2WI, the right adrenal gland was demonstrated of a lower rate than the left adrenal gland, because the right retroperitoneal fat layer was narrow in patients with hepatic tumors. T2*WI depicted both adrenal glands equally, because the intensity of the left adrenal gland was the same as that of collateral veins from portal hypertension. It is suggested that both T1WI and T2WI with a gradient echo pulse sequence are more useful in depicting the adrenal glands than both T1WI and T2WI.

Adrenal Glands↗
PubMed1991

[The clinical application of multi-voxel 1H-CSI (chemical shift imaging) in brain tumors].

The 1H-Chemical shift imaging (CSI) method was developed and applied to reveal the metabolic changes in brain tumors. In the tumor, the decrease of NAA and the increase of lactate were observed by the CSI. These changes were more remarkable in the malignant tumors than in the benign tumors. The lactate was also observed in the tissue surrounding the tumors, which was supposed to be produced in the brain with hypoperfusion condition or to be leaked out from the tumor. The 1H-CSI has an advantage to demonstrate the pathophysiological changes in a wide area of the brain.

Aspartic Acid↗
PubMed1991

Formation of beta-amyloid protein deposits in brains of transgenic mice.

Deposits of beta-amyloid are one of the main pathological characteristics of Alzheimer's disease. The beta-amyloid peptide constituent (relative molecular mass 4,200) of the deposits is derived from the beta-amyloid precursor protein (beta-APP) which is expressed in several different isoforms. The two most prevalent beta-APP isoforms are distinguished by either the presence (beta-APP751) or absence (beta-APP695) of a Kunitz serine protease inhibitor domain. Changes in the abundance of different beta-APP messenger RNAs in brains of Alzheimer's disease victims have been widely reported. Although these results have been controversial, most evidence favours an increase in the mRNAs encoding protease inhibitor-containing isoforms of beta-APP and it is proposed that this change contributes to beta-amyloid formation. We have now produced an imbalance in the normal neuronal ratio of beta-APP isoforms by preparing transgenic mice expressing additional beta-APP751 under the control of a neural-specific promoter. The cortical and hippocampal brain regions of the transgenic mice display extracellular beta-amyloid immunoreactive deposits varying in size (less than 5-50 microns) and abundance. These results suggest that one mechanism of beta-amyloid formation may involve a disruption of the normal ratio of neuronal beta-APP isoform expression and support a direct relationship between increased expression of Kunitz inhibitor-bearing beta-APP isoforms and beta-amyloid deposition.

Alzheimer Disease↗
PubMed1991

Arg-X-Lys/Arg-Arg motif as a signal for precursor cleavage catalyzed by furin within the constitutive secretory pathway.

Many peptide hormones are produced from larger precursors by endoproteolysis at pairs of basic amino acids (e.g. Lys-Arg and Arg-Arg) within the regulated secretory pathway in endocrine cells. However, many other secretory and membrane proteins appear to be produced from precursors through cleavage at multiple, rather than paired, basic residues within the constitutive secretory pathway in non-endocrine cells. By surveying various precursors processed constitutively, we noticed that most of them have the consensus sequence, Arg-X-Lys/Arg-Arg (RXK/RR), at the cleavage site. When expressed in endocrine and non-endocrine cells, a precursor with the RXKR sequence was cleaved in both types of cells, whereas that with the Lys-Arg pair was cleaved only in the endocrine cells. When the RXKR precursor was coexpressed with furin and PC3, both of which are mammalian homologues of the yeast precursor-processing endoprotease Kex2, in non-endocrine cells, enhancement of the precursor cleavage by furin but not by PC3 was observed. By contrast, when the Lys-Arg precursor was coexpressed with the two mammalian proteases in endocrine cells with no endogenous processing activity at dibasic sites, it was cleaved only by PC3. These results indicate that the basic pair and the RXK/RR sequence are the signals for precursor cleavages catalyzed by PC3 within the regulated secretory pathway and by furin within the constitutive pathway, respectively.

Amino Acid Sequence↗
PubMed1991

Similarity between physicochemical properties of recombinant rat prorenin and native inactive renin.

Rat prorenin was synthesized by Chinese-hamster ovary cells transfected with an expression vector containing rat preprorenin cDNA sequences, then purified by concanavalin A-Sepharose chromatography and h.p.l.c. on G3000SW. The molecular mass of purified prorenin was 46,000 Da, as determined by h.p.l.c. on G3000SW. Immunoblot analysis indicated that recombinant prorenin cross-reacted with anti-(mature renin) antibody and two kinds of antibodies recognizing the N-terminus and C-terminus of the prosegment of rat prorenin. Recombinant prorenin was bound to a Cibacron Blue-Sepharose column and eluted with 1.4 M-NaCl, but was not retained by an octapeptide renin inhibitor (H-77)-Sepharose column. Trypsin activation of prorenin increased the renin activity 110-fold, caused binding to an H-77-Sepharose column and nullified the reactivity to the above two kinds of anti-prosegment antibodies, findings indicating that the activation of prorenin with trypsin is due to the cleavage of the prosegment. Rat plasma inactive renin, partially purified by h.p.l.c. on G3000SW, had much the same physicochemical characteristics as the recombinant prorenin. These results provide evidence that rat plasma inactive renin is prorenin. Recombinant prorenin is a useful material for examining the physiological role of circulating prorenin.

Animals↗
PubMed1991

Sequence requirements for prohormone processing in mouse pituitary AtT-20 cells. Analysis using prorenins as model substrates.

Although cleavage of peptides at sites marked by paired basic amino acids is a common feature of prohormone processing, little is known about the properties of endoprotease(s) responsible for cleavage of the precursor. To examine the cleavage specificity of a processing endoprotease, we have altered the Lys-Arg cleavage site of human prorenin to Arg-Arg, Lys-Lys and Arg-Lys by site-directed mutagenesis, and expressed the native and mutated precursors in mouse pituitary AtT-20 cells which are known to process foreign prohormones, including prorenin, at paired basic sites during the regulated secretory process. All native and mutated human prorenins were sorted into the regulated secretory pathway. The mutated precursor with Arg-Arg instead of the Lys-Arg native pair was processed at about half the efficiency of the native one, while the Lys-Lys and Arg-Lys mutants were not processed. Rat prorenin, which naturally has a Lys-Lys pair, was not processed in the cells. In addition, mouse Ren2 prorenin, which has a Ser residue next to the Lys-Arg pair, but not mouse Ren1 prorenin, which has a Pro residue next to the pair, was processed. These results suggest that the Arg residue at the COOH side of the basic pair is essential for cleavage of prorenins by a processing enzyme during the regulated secretory process in AtT-20 cells, although the NH2-side Lys residue also plays a role. The results also demonstrate that the processing enzyme cannot cleave the Arg-Pro peptide bond.

Amino Acid Sequence↗
PubMed1991

[Detection of A-P shunt by MR angiography].

Magnetic Resonance Angiography using a time-of-flight method was performed on two cases with arterial-portal shunting (A-P shunt). Each case was examined both with and without presaturation applied above the diaphragms. Signal intensity in the portal vein on these cases decreased with presaturation. This presaturation normally eliminates signal from inflowing spins in the artery but never effect on that in portal vein. Therefore the decrease of signal intensity in the portal vein with presaturation indicates the arterial inflow to the portal vein.

Arteriovenous Fistula↗
PubMed1991

Effects of novel aldose reductase inhibitors, M16209 and M16287, on streptozotocin-induced diabetic neuropathy in rats.

We investigated the effects of novel aldose reductase inhibitors, M16209 (1-(3-bromobenzo[b]furan-2-ylsulfonyl)hydantoin) and M16287 (1-(3-chlorobenzo[b]furan-2-ylsulfonyl)hydantoin), on neuropathy in streptozotocin-induced (STZ) diabetic rats. Both compounds (3-100 mg/kg per day, p.o.) dose dependently improved the decreased motor nerve conduction velocity in the sciatic nerve during a 14-day treatment period. These compounds also partially ameliorated the diabetes-induced histological changes in the sciatic nerve. A distinct increase in sorbitol content and a slight decrease in myo-inositol content was observed in the sciatic nerve of STZ diabetic rats, and the sorbitol accumulation was dose dependently suppressed by treatment with M16209 and M16287. Treatment started at an earlier period was more effective in the suppression of sorbitol accumulation. There was a significant correlation between motor nerve conduction velocity and nerve sorbitol content, whereas there was none between motor nerve conduction velocity and myo-inositol content. The present study indicates that M16209 and M16287 are potent aldose reductase inhibitors expected to be useful for the treatment of diabetic complications.

Aldehyde Reductase↗