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Biomedical subjects

M Kihara

Publications and source records attributed to M Kihara.

At least 127 records · Page 7Linked to original sources

Descriptive epidemiology of HIV/AIDS in Japan, 1985-1994.

The HIV epidemic in Japan appears to be following a unique course, with no predominance of homosexual contact over heterosexual contact in reported cases and relatively little transmission by injection drug users and commercial sex workers. Infection rates are still low compared with those in southeast Asia and Western countries: 404 cases of nonhemophiliac AIDS (287 Japanese, 117 foreigners) and 1,441 cases of nonhemophiliac HIV infection (634 Japanese, 807 foreigners) were reported as of the end of 1994. Nevertheless, the numbers are increasing and the importance of targeted prevention programs is clear, particularly among those at higher risk because of sexual practices, such as homosexual men and commercial sex workers and their clients, or because of injection drug use. More data are needed to assess the impact of HIV/AIDS in Japan. These should include surveillance data as well as results from epidemiologic and behavioral studies.

Acquired Immunodeficiency Syndrome↗

A xanthanolide with potent antibacterial activity against methicillin-resistant Staphylococcus aureus.

This study was conducted to find constituents of an annual herb, Xanthium sibiricum Patr er Widd, with effective antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). By monitoring antibacterial activity against MRSA strains, it was shown that a sesquiterpene lactone, identified as [3aR-(3a alpha, 7 beta,8a beta)]-3,3a,4,7,8,8a-hexahydro-7- methyl-3-methylene-6-(3-oxo-1-butenyl)-2H-cyclohepta[b]furan-2-one, or xanthatin, isolated from leaves of the herb, had outstandingly potent activity against S. aureus species, including MRSA; its activity against MRSA and MSSA strains was similar. Other bacteria, e.g. Staphylococcus epidermidis, Klebsiella pneumoniae, Bacillus cereus, Pseudomonas aeruginosa and Salmonella typhi, were also susceptible at the concentrations tested but the compound had no inhibitory effect on some other bacteria, including Escherichia coli. The results show that xanthatin has outstandingly potent activity against strains of S. aureus but that the activity of the compound is highly species-specific.

Anti-Bacterial Agents↗

[Simple method for typing human immunodeficiency virus type I (B, E) by PCR and chronological change of distribution of subtype (B to E) in Japan].

We analyzed the clade distribution of B and E in HIV-1 isolates in Japan by a nested PCR method using 5'-CCCACAAGATTTAAATATG-3' of the gag gene as clade B primer and 5'-CCCACAAGATTTAAACTCC-3' of the gag gene as clade E primer. Seventy-two anti-HIV-1 confirmatory positive serum samples were collected during a period of 1991-1996 in two hospitals in Yokohama City. Peripheral blood mononuclear cells were obtained from the buffy coat of these samples and extracted DNA were used for nested PCR. The 72 cases comprised of 11 Japanese hemophiliacs, 14 Japanese male homosexuals, 19 Japanese male heterosexuals, 5 Japanese female heterosexuals and 23 Thai female heterosexuals. Of these 36 were clade B and 35 were clade E and one case showed positive PCR results for both B and E primers. Almost all male Japanese hemophiliacs and homosexuals in our sample have clade B, while the female Thai heterosexuals have clade E, irrespective of the year of isolation. As for Japanese male heterosexuals, through 1993, clade B was predominant but since 1994, the predominate clade switched to clade E. Although the number of Japanese female heterosexuals in our sample is small, clade B was isolated in 2 cases even after 1994.

Female↗

The FliO, FliP, FliQ, and FliR proteins of Salmonella typhimurium: putative components for flagellar assembly.

The flagellar genes fliO, fliP, fliQ, and fliR of Salmonella typhimurium are contiguous within the fliLMNOPQR operon. They are needed for flagellation but do not encode any known structural or regulatory components. They may be involved in flagellar protein export, which proceeds by a type III export pathway. The genes have been cloned and sequenced. The sequences predict proteins with molecular masses of 13,068, 26,755, 9,592, and 28,933 Da, respectively. All four gene products were identified experimentally; consistent with their high hydrophobic residue content, they segregated with the membrane fraction. From N-terminal amino acid sequence analysis, we conclude that fliO starts immediately after fliN rather than at a previously proposed site downstream. FliP existed in two forms, a 25-kDa form and a 23-kDa form. N-terminal amino acid analysis of the 23-kDa form demonstrated that it had undergone cleavage of a signal peptide--a rare process for prokaryotic cytoplasmic membrane proteins. Site-directed mutation at the cleavage site resulted in impaired processing, which reduced, but did not eliminate, complementation of a fliP mutant in swarm plate assays. A cloned fragment encoding the mature form of the protein could also complement the fliP mutant but did so even more poorly. Finally, when the first transmembrane span of MotA (a cytoplasmic membrane protein that does not undergo signal peptide cleavage) was fused to the mature form of FliP, the fusion protein complemented very weakly. Higher levels of synthesis of the mutant proteins greatly improved function. We conclude that, for insertion of FliP into the membrane, cleavage is important kinetically but not absolutely required.

Amino Acid Sequence↗

An extreme clockwise switch bias mutation in fliG of Salmonella typhimurium and its suppression by slow-motile mutations in motA and motB.

Pseudorevertants (second-site suppressor mutants) were isolated from a set of parental mutants of Salmonella with defects in the flagellar switch genes fliG and fliM. Most of the suppressing mutations lay in flagellar region IIIb of the chromosome. One fliG mutant, SJW2811, gave rise to a large number of suppressor mutations in the motility genes motA and motB, which are in flagellar region II. SJW2811, which has a three-amino-acid deletion (delta Pro-Ala-Ala) at positions 169 to 171 of FliG, had an extreme clockwise motor bias that produced inverse smooth swimming (i.e., swimming by means of clockwise rotation of a hydrodynamically induced right-handed helical bundle), and formed Mot(-)-like colonies on semisolid medium. Unlike previously reported inverse-swimming mutants, it did not show a chemotactic response to serine, and it remained inverse even in a delta che background; thus, its switch is locked in the clockwise state. The location of the mutation further underscores the conclusion from a previous study of spontaneous missense mutants (V. M. Irikura, M. Kihara, S. Yamaguchi, H. Sockett, and R. M. Macnab, J. Bacteriol. 175:802-810, 1993) that a relatively localized region in the central part of the FliG sequence is critically important for switching. All of the second-site mutations in motA and motB caused some impairment of motility, both in the pseudorevertants and in a wild-type fliG background. The mechanism of suppression of the fliG mutation by the mot mutations is complex, involving destabilization of the right-handed flagellar bundle as a result of reduced motor speed. The mutations in the MotA and MotB sequences were clustered to a considerable degree as follows: in transmembrane helices 3 and 4 of MotA and the sole transmembrane helix of MotB, at helix-membrane interfaces, in the cytoplasmic domains of MotA, and in the vicinity of the peptidoglycan binding region of the periplasmic domain of MotB. The potential importance of Lys28 and Asp33 of the MotB sequence for proton delivery to the site of torque generation is discussed.

Amino Acid Sequence↗

Tissue angiotensinogen gene expression induced by lipopolysaccharide in hypertensive rats.

There is now convincing evidence that various tissues express their own tissue renin-angiotensin system, which may be regulated independently of the systemic renin-angiotensin system. However, little information is available on the regulation of the tissue renin-angiotensin system. We investigated the regulation of tissue angiotensinogen gene expression with respect to the development of hypertension. We measured basal and lipopolysaccharide-stimulated plasma angiotensinogen concentrations by radioimmunoassay and examined the expression of tissue angiotensinogen by Northern blot analysis in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at 4 and 13 weeks of age. Basal plasma angiotensinogen concentration in SHR was comparable to that in WKY at 4 weeks of age and was significantly higher than that in WKY at 13 weeks of age. Lipopolysaccharide induced a significant increase in plasma angiotensinogen concentration in both WKY and SHR at 4 and 13 weeks of age. At 4 weeks of age, the basal levels of angiotensinogen mRNA in the liver, fat, adrenal, and aorta were higher in WKY than in SHR. At 13 weeks of age, the basal levels of angiotensinogen mRNA in the fat, adrenal, aorta, spleen, and kidney were higher in WKY than in SHR, while that in the liver did not differ significantly between the two strains. At 4 weeks of age, pretreatment with lipopolysaccharide increased the angiotensinogen mRNA levels in the liver, fat, adrenal, and aorta in both WKY and SHR. At 13 weeks of age, pretreatment with lipopolysaccharide increased the angiotensinogen mRNA levels in the liver, aorta, and adrenal; decreased those in the spleen; and had no effect in the kidney in both WKY and SHR. Interestingly, lipopolysaccharide increased the angiotensinogen mRNA level in fat only in SHR, with no effect in WKY, at 13 weeks of age. Lipopolysaccharide stimulated tumor necrosis factor-a mRNA expression in fat of WKY and SHR, and the increase in tumor necrosis factor-alpha mRNA level in SHR was significantly greater than that in WKY. Therefore, the increased tumor necrosis factor-alpha mRNA expression may be involved in the increased lipopolysaccharide-induced expression of angiotensinogen gene in fat of SHR at 13 weeks of age. These data suggest that the transcriptional and probably posttranscriptional regulation of angiotensinogen mRNA differs between SHR and WKY, that the regulation of angiotensinogen gene expression is tissue-specific, and that the altered expression of the angiotensinogen gene may be involved in the development of hypertension.

Angiotensinogen↗

Essential hypertension and 5' upstream core promoter region of human angiotensinogen gene.

The angiotensinogen (AGT) gene M235T variant is associated with essential hypertension and elevated plasma AGT concentrations, although the underlying mechanisms are unknown. Recent studies have suggested that AGCE 1 (human AGT gene core promoter element 1) located in the 5' upstream core promoter region (position -25 to -1) of the human AGT gene has an important part in the expression of AGT mRNA by binding with transcription factor AGCF 1 (human AGT gene core promoter element binding factor 1), and a mutation at -20 from adenine to cytosine (A-20C) increases the level of expression of this transcript. We therefore examined subjects with this mutation to study the association with increased plasma AGT concentrations and with essential hypertension. One hundred eighty-eight subjects receiving no antihypertensive medication were examined with regard to the correlation between A-20C and plasma AGT concentrations, and 234 subjects were studied with respect to the association between A-20C and essential hypertension. A-20C was determined by polymerase chain reaction-restriction fragment length polymorphism analysis with EcoOR 109I. Multiple regression analysis showed a weak but significant correlation between A-20C and plasma AGT concentrations (P=.047) and essential hypertension (P=.049). The results suggest that A-20C may underlie the increase in plasma AGT concentrations and be involved in the development of essential hypertension.

Angiotensinogen↗

Extraction and purification of effective antimicrobial constituents of Terminalia chebula RETS. against methicillin-resistant Staphylococcus aureus.

Examination of the EtOH extract of the fruiting bodies of Terminalia chebula RETZ. led to the isolation of two potent antimicrobial substances against even methicillin-resistant strains of Staphylococcus aureus. On the basis of spectroscopic evidence, the two isolates have been identified as gallic acid and its ethyl ester.

Anti-Bacterial Agents↗

Synthesis and biological evaluation of 7-hydroxy-3,4-diphenyl-1,2-dihydroisoquinolines as new 4-hydroxytamoxifen analogues.

A phenolic 3,4-diphenyl-1,2-dihydroisoquinoline derivative (4a) as a new 4-hydroxytamoxifen analogue and a related compound (4c) were synthesized from 3,4-diphenyl-1,2,3,4-tetrahydroisoquinolin-4-ols (5a, c), which were prepared by intramolecular Barbier reaction of N-(2-iodobenzyl)phenacylamines. Anti-proliferative activities of 4a,c and 5a,c, as well as 4b and 5b prepared previously, against human mammary carcinoma MCF-7 cell line and human nasopharyngeal carcinoma KB cell line were evaluated. The 3,4-diphenyl-1,2-dihydroisoquinoline derivatives (4a,c) and isoquinolin-4-ols (5a,b) were active against MCF-7 cells and were nearly equipotent to the corresponding nonphenolic compound (1a). The mechanism of the anti-proliferative activity of 4a-c against MCF-7 cells is discussed.

Animals↗

The neuronal isoform of constitutive nitric oxide synthase is up-regulated in the macula densa of angiotensinogen gene-knockout mice.

Angiotensinogen gene-knockout (Atg -/-) mice lacking angiotensin II exhibit chronic hypotension and an increase in renal renin gene expression. The present study was designed to provide evidence for the possible involvement of neuronal type nitric oxide synthase (N-NOS) at the macula densa in the increased renin production in Atg -/- mice. The enzyme activity of N-NOS was histochemically detected by NADPH diaphorase (NADPHd) reaction combined with N-NOS immunohistochemistry. N-NOS mRNA expression in the renal cortical tissue was determined using reverse transcription-PCR in a semiquantitative manner. The levels of renal renin mRNA were evaluated by Northern blot analysis. In the kidneys of wild-type (Atg +/+) mice, N-NOS activity was localized to the macula densa as reported previously. On the other hand, N-NOS-positive macula densa cells of Atg -/- mice were distributed beyond the original location of the macula densa. They often occupy the entire cross-sectional profiles of the tubules. In addition, Atg -/- mice showed a stronger signal intensity for the enzyme reaction than Atg +/+ mice. The mean total number of N-NOS-positive cells per 100 glomeruli was 6 times higher in Atg -/- mice than in Atg +/+ mice. Semiquantitative reverse transcription-PCR revealed an increase in the N-NOS mRNA level in renal cortical tissue of Atg -/- mice compared with Atg +/+ mice. Furthermore, the selective inhibition of N-NOS activity by 7-nitrondazole significantly decreased the level of renal renin mRNA in Atg -/- mice. These results suggest that increased N-NOS activity at the macula densa is involved a renal renin overproduction in Atg -/- mice.

Angiotensinogen↗

Analysis of molecular heterogeneity of Dahl/Iwai salt-sensitive rats and salt-resistant rats.

Molecular evidence, using DNA fingerprint analyses, of extensive genetic heterogeneity between spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and even within some of the WKY colonies has been reported. Thus we investigated the genetic relations between Dahl S and R rats newly inbred by Dr. Iwai. Genomic DNA was isolated from the liver of four Dahl S and four Dahl R rats, digested with the restriction enzyme HinfI or AluI, and separated in 1.2% agarose gel by electrophoresis. Then, DNA fingerprinting was performed by Southern blot analysis using the human myoglobin 33.6 minisatellite probe. Bands were detected in an alkaline phosphatase reaction system. Within the same strains, there was no heterogeneity of these fingerprinting patterns. The S and R rats shared 82% of the bands in the HinfI-digested DNA and 93% of those in the AluI-digested DNA. These shared values were much greater than the reported value (54%) between SHR and WKY from Charles River Laboratories. These newly inbred Dahl S and R rats may be appropriate, although still limited, experimental animals for investigating the pathophysiology of salt-sensitive hypertension.

Animals↗

[A case of nephrotic syndrome after bone marrow transplantation].

We reported a 27-year-old man who developed nephrotic syndrome 12 months after a bone marrow transplantation from his HLA-identical sister for chronic myelocytic leukemia. Anti-nuclear antibodies had been serially investigated after the bone marrow transplantation. They were detected in his serum 5 months before the appearance of proteinuria, but he tested negative at the onset of nephrotic syndrome. Histological analysis of the renal biopsy revealed subepithelial and subendothelial immune deposits in the glomerular basement membrane with increased mesangial matrix and cells. These findings suggested immune complex glomerulonephritis due to chronic graft-versus-host disease (GVHD) after bone marrow transplantation. In murine experimental chronic GVHD, anti-nuclear antibodies, which generate immune complexes that deposit or form in the kidney have been detected.

Adult↗

[HIV/AIDS counseling services for foreigners at the Shinjuku Public Health Center].

Since October 1994, the Shinjuku Public Health Center in collaboration with an NGO, has offered AIDS counseling services for foreigners. Although the NGO operated with volunteers before July 1995, the Center began budgeted HIV/AIDS counseling for foreigners from July 1995. The pre-HIV test counseling and post-test counseling sessions were held twice a month, in English, Thai, Spanish and Portuguese. Counselors who speak those languages worked in coordination with staff members of the Center. Starting July 1995, counseling by telephone was also offered. During the 1 1/2 years, from October 1994 to March 1996, 600 people visited the Center for HIV tests and AIDS counseling, of whom 103 (17%) were foreigners. Among the 103 foreigners, one person was detected as seropositive. The 103 foreigners included 56 Thai speakers, 20 English speakers, 8 Portuguese speakers, 7 Spanish speakers and 12 people who speak other native languages (Chinese, Korean, Burmese, Iranian). From July 1995 to March 1996, (about 8 months), 39 foreigners utilized the telephoned service for HIV test information: these 39 included 5 seropositive persons and AIDS patients. The number of foreigners visiting the Center for AIDS counseling and the number of foreigners utilizing the telephone service has increased each year. It is expected that the demand for these services will increase continuously in future.

Acquired Immunodeficiency Syndrome↗

[The HIV/AIDS Epidemic in Cambodia].

In December 1995 and March 1996, we visited institutes which were conducting epidemiological studied of HIV/AIDS in Cambodia, and obtained data for further collaborative study between Japan and Cambodia. Data included information on AIDS patients and HIV infected persons, and behavioral epidemiology of CSWs (Commercial Sex Workers). The cumulative reported number of AIDS patients and HIV infected persons in Cambodia was 86 and 2,536 cases respectively in 1995. The cause of infection was mostly heterosexual contact with very few cases from injecting drug use (IDU) and other causes. The seroprevalence rate of HIV antibody among donated blood rapidly increased from 0.08% in 1991 to 4.47% in 1995, and those among CSWs and pregnant women were 37.9% and 2.6%, respectively, in 1995. The average rate of condom use among CSWs was 66%, but the rate of usual usage was only 14%. These results indicate that the HIV/AIDS epidemic had spread rapidly through CSWs, that it had been spread among peoples in communities, and that usage of condoms among CSWs was insufficient in Cambodia. Without strong countermeasures against HIV/AIDS in this country, HIV/AIDS epidemic may spread significantly to not only peoples in this country but also those in neighbouring countries in the future.

Acquired Immunodeficiency Syndrome↗

[A case of polyneuropathy with B-CLL and HTLV-I associated myelopathy (HAM)].

We report a case of polyneuropathy associated with chronic B lymphoid leukemia (B-CLL) and HAM. A 65-year-old man had an initial onset with polyneuropathy, then myelopathy appeared. High HTLV-I antibody and anti-ganglioside antibodies were observed. The biopsy examination of the sural nerve showed mainly demyelinated changes. Muscle weakness gradually improved after cyclophosphamide therapy. Anti-ganglioside antibodies were also decreased in titer. This case suggested that the production of antiganglioside antibodies and the occurrence of polyneuropathy might be caused by both factors of HTLV-I infected T cells and B cell tumors.

Aged↗

Regulation of cardiac angiotensinogen mRNA in vivo and in vitro.

In this study, to investigate the mechanism of hypertension-associated induction of cardiac angiotensinogen in vivo and in vitro, we studied the regulation of angiotensinogen mRNA in the hearts of genetically hypertensive rats and in the rat cardiomyocytes. Levels of cardiac angiotensinogen mRNA were significantly increased in the hypertensive rats. Steady state mRNA levels for angiotensinogen mRNA in cardiomyocytes were increased by angiotensin II and mechanical stretch. The addition of an angiotensin II type 1 receptor antagonist (CV11974) and a transcriptional inhibitor (actinomycin D) completely blocked the induction of angiotensinogen mRNA by angiotensin II in cardiomyocytes. The addition of CV11974 significantly, but not completely, inhibited the induction of angiotensinogen mRNA by mechanical stretch. Actinomycin D completely blocked the induction of angiotensinogen mRNA by stretch in cardiomyocytes. An angiotensin II type 2 receptor antagonist (PD123319) and a protein synthesis inhibitor (cycloheximide) did not affect the induction. These results indicate that the expression of cardiac angiotensinogen mRNA is activated by the development of hypertensive cardiac hypertrophy, and that angiotensin II and mechanical stretch activates the angiotensinogen gene via the angiotensin II type 1 receptor-pathway in cardiomyocytes.

Angiotensinogen↗

HIV prevention in developed countries.

HIV prevention in developed countries is marked by impressive successes and dismal failures. The successes point the way to what works; the failures highlight obstacles that must be overcome. Successes include important behavioural changes among gay and bisexual men, antiviral use to prevent vertical transmission, and securing the safety of the blood supply. New strategies are needed to reach the residual of individuals continuing with unsafe practices (a special hazard in high-prevalence areas); to reach young people who are beginning to engage in sexual relations and injection drug use; and to overcome political opposition to prevention strategies.

Acquired Immunodeficiency Syndrome↗