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M Kihara

Publications and source records attributed to M Kihara.

At least 181 records · Page 10Linked to original sources

Identification and characterization of adenosine A1 receptor-cAMP system in human glomeruli.

Although adenosine is known to affect renal function through stimulating adenosine receptors, little is known about A1 receptors in human glomeruli. Thus, we attempted to identify the adenosine A1 receptor-cyclic AMP (cAMP) system in human glomeruli. Normal renal cortical tissues were obtained at nephrectomy of patients with renal cell carcinoma. Glomeruli were isolated using a graded sieving method or dissected manually under a stereomicroscope. Radioligand binding assay using 2-chloro-N-[3H] cyclopentyl adenosine ([3H]CCPA, an A1 agonist ligand) was performed at 30 degrees C for 90 minutes. Cyclic AMP (cAMP) produced in glomeruli was measured after incubation with different concentrations of N6-cyclohexyladenosine (CHA; A1 agonist) and a phosphodiesterase inhibitor. The specific binding was saturated within 60 minutes and reversible by adding 1 mM of theophylline. Scatchard plot analysis revealed a single class of binding site (Kd = 1.78 +/- 0.21 nM, Bmax = 271.7 +/- 35.8 fmol/mg protein). The specific binding was inhibited dose-dependently by various agents in an order suggesting A1 receptor specificity. CHA inhibited the production of cAMP in microdissected human glomeruli. This inhibitory effect was antagonized by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; A1 antagonist). This is the first study revealing the presence of the A1 receptor-cAMP system in human glomeruli using a radioligand binding assay method and by measuring the cAMP production.

Adenosine↗

Organization of the Escherichia coli and Salmonella typhimurium chromosomes between flagellar regions IIIa and IIIb, including a large non-coding region.

Flagellar regions IIIa and IIIb of the Escherichia coli and Salmonella typhimurium chromosomes (at 40 min and 42-43 min, respectively) has been shown to be separated by DNA unrelated to flagellar function, with region IIIa being immediately followed by a gene, amyA, that encodes a cytoplasmic alpha-amylase. The chromosome between amyA and flagellar region IIIb has now been investigated. The high level of DNA similarity between the E. coli and S. typhimurium sequences that exists in flagellar region IIIa and in amyA continues initially, with three genes of unknown function; in E. coli, there may be a fourth gene. The remainder of the region, up to the start of flagellar region IIIb, lacks any obvious open reading frames, scores poorly on an algorithm for coding probability, has a high A+T content, and is totally dissimilar in the two species. We conclude that it is non-coding. In E. coli this region extends for 2.7 kb and in S. typhimurium for 0.8 kb. These values are unusually large for prokaryotes, where the non-coding regions between operons are generally quite short. The data, which are discussed in the context of a hypothesized disruption of a contiguous ancestral flagellar region, may give new insight into the organization and evolution of the bacterial chromosome.

Amino Acid Sequence↗

Salmonella typhimurium fliG and fliN mutations causing defects in assembly, rotation, and switching of the flagellar motor.

FliG, FliM, and FliN are three proteins of Salmonella typhimurium that affect the rotation and switching of direction of the flagellar motor. An analysis of mutant alleles of FliM has been described recently (H. Sockett, S. Yamaguchi, M. Kihara, V. M. Irikura, and R. M. Macnab, J. Bacteriol. 174:793-806, 1992). We have now analyzed a large number of mutations in the fliG and fliN genes that are responsible for four different types of defects: failure to assembly flagella (nonflagellate phenotype), failure to rotate flagella (paralyzed phenotype), and failure to display normal chemotaxis as a result of an abnormally high bias to clockwise (CW) or counterclockwise (CCW) rotation (CW-bias and CCW-bias phenotypes, respectively). The null phenotype for fliG, caused by nonsense or frameshift mutations, was nonflagellate. However, a considerable part of the FliG amino acid sequence was not needed for flagellation, with several substantial in-frame deletions preventing motor rotation but not flagellar assembly. Missense mutations in fliG causing paralysis or abnormal switching occurred at a number of positions, almost all within the middle one-third of the gene. CW-bias and CCW-bias mutations tended to segregate into separate subclusters. The null phenotype of fliN is uncertain, since frameshift and nonsense mutations gave in some cases the nonflagellate phenotype and in other cases the paralyzed phenotype; in none of these cases was the phenotype a consequence of polar effects on downstream flagellar genes. Few positions in FliN were found to affect switching: only one gave rise to the CW mutant bias and only four gave rise to the CCW mutant bias. The different properties of the FliM, FliG, and FliN proteins with respect to the processes of assembly, rotation, and switching are discussed.

Alleles↗

Assessment of sudomotor dysfunction in early Parkinson's disease.

We performed a quantitative sudomotor function test on 10 patients with early Parkinson's disease (PD) and 11 age-matched control subjects. Thermal warming increased the sweat rate in both PD and controls. There was no difference in sweat rate between the forearm and the thigh in either PD or controls. In PD, thyrotropin-releasing hormone (TRH) did not increase the sweat rate, whereas it did so in the controls. These results suggest that sudomotor dysfunction in early PD is minor but that there may be an impairment of TRH-induced sympathetic response in the early stages of PD.

Forearm↗

[Recent trends in human immunodeficiency virus (HIV) infection and anti-HIV testing in foreign residents in Japan].

To explore the recent situation of the human immunodeficiency virus (HIV) epidemic in foreign residents in Japan, a survey of medical records between 1989-1992 was performed in a clinic located in a small district of Tokyo metropolitan area where foreign prostitutes were relatively concentrated. From medical records results of laboratory tests for HIV, syphilis, gonorrhea and chlamydial infection were collected. The present study revealed (1) that more than 1000 foreigners, of whom the majority were Thai, with a female to male ratio over 10, visited the clinic during the 4 years with a marked increase from 1990 to 1991, (2) that among the laboratory tests only anti-HIV testing rate markedly increased by 2-3 fold from 1990 to 1991 in both sexes (3) that anti-HIV seropositives were 41 in total (F = 39, M = 2), around 4% in both sexes, with a slight increasing trend in females and particularly high infection rate (14.0%) in females aged < 20 and (4) that no significant correlation was observed between HIV infection and other sexually transmitted diseases. These results suggest that the remarkable increase witnessed by the recent AIDS surveillance in Japan could have been influenced at least in part by the sudden increase in the testing rate for anti-HIV as well as by the increase in the number of foreigners visiting clinics. It also suggests the critical importance of targeting foreign females of high risk behaviour in the AIDS prevention strategies in Japan since HIV infection rates were high among foreign females, especially in teenagers.

AIDS Serodiagnosis↗

[On the recent abrupt rise in the number of foreign females in the AIDS surveillance in Japan].

AIDS surveillance in Japan has recently witnessed an abrupt increase in the number of foreign females infected with HIV, which soared from 2 in 1989 to 274 in 1992. To clarify underlying causes for such a phenomenon anti-HIV seropositive rates and anti-HIV testing rates of foreign females who visited hospitals or clinics were investigated either by a retrospective medical records survey or by direct serological tests in several districts in the Tokyo metropolitan area. These studies revealed that seropositive rates of foreign females, mostly from Thailand, ranged between 1.0-5.0% during Jan. 1990-Apr. 1993, varying between districts and with a slight increase over the period. The proportion of foreign females who underwent anti-HIV test was found to have markedly increased from around 10% in 1990 to 75% in 1991 in spite of testing rates for syphilis or gonorrheal infection remaining unchanged during the same period. Their sexual behaviour was also studied and found that most of them were engaged in sex activities without using condom. These results suggest (1) The number of foreign females with HIV infection could have been considerably underestimated by the surveillance because in 1991, when the surveillance detected only 105 foreign females, around 600 or more foreign female infectees may have existed in Japan as estimated by multiplying the 3% infection rate with 20,000, the estimated female Thai population illegally residing in Japan by the end of 1991.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗

[Prevalence of hepatitis C virus and human immunodeficiency virus infection among Japanese female prostitutes].

To investigate the incidence of hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection in Japanese sexual workers, 191 out of 194 female prostitutes working in a certain district of the Tokyo metropolitan area were tested for anti-HCV, anti-hepatitis B virus (HBV), anti-HIV and anti-Treponema pallidum (TP). They were also interviewed with regard to their past history of blood transfusion, vaccination against HBV, liver diseases and repeated skin piercing treatments such as tattooing, acupuncture and intravenous drug use. Sera from 300 female blood donors (aged 20 s-40 s), of the same district, collected during the same year, were assessed for comparison. Incidence of seropositives for anti-HCV and anti-TP were found to be significantly high in the prostitute group (11.0% and 16.2%, respectively) compared to the control (0% for both). Anti-HBV seropositives were 14.1% in the prostitute group and 12.7% in the control group without significant difference and none of our subjects were found to be anti-HIV positive. Among HCV infected only 5 experienced repeated skin-piercing treatment and none underwent blood transfusion. From these results it is concluded that HCV has a potential for being transmitted by heterosexual contact, although the exact risk for infection needs to be determined by further investigation.

Adult↗

Comparative study of various genetic hypertensive rat strains: blood pressure, body weight, growth and organ weights.

In an attempt to compare various genetic strains of hypertensive rats, representative hypertensive strains and associated controls (male, 1-month-old, 6-10 of each strain and 18 strains in total) were collected at a single center (National Institutes of Health; NIH, United States), maintained under the same experimental conditions with normal sodium NIH open formula diet and studied by a single investigator using standard techniques. Animals were measured for blood pressure (BP) by a tail-cuff method without anesthesia and body weight (BW) at 10 and 12 weeks of age and killed to measure organ weights. Hypertension was severe (> 190 mmHg) in spontaneously hypertensive rats (SHR) and their stroke-prone substrains at 12 weeks of age but mild to moderate (145-160 mmHg) in the rest of the hypertensive strains (Dahl's, Milan, Lyon, Sabra, and New Zealand Strains). Regarding organ size, partial correlation analysis showed that organ weights, except for brain and adrenal glands, are good functions of BW and that weight of the left ventricle (LV) was the only one significantly linked to BP levels. A bivariate regression model for LV weight was obtained as follows: LV(mg) = 1.478 BW(g) + 2.13BP(mmHg) - 51(R = 0.878, P < 0.001). The presence of some genetic factor regulating relative organ size independently of BW and BP was suggested in LV weight as well as in the weight of the other organs. Among the strains, MHS was found to be unique for the smallest kidney size and New Zealand strains for the greatest relative LV size when adjusted to allow for the influence of BP.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

In vivo studies on receptor pharmacology of the human eccrine sweat gland.

The receptor pharmacology of the human sweat gland was studied in vivo. The axon-reflex response was mediated by nicotinic receptors which were activated by nicotine and acetylcholine, but not pilocarpine, and inhibited by hexamethonium. The direct response was mainly muscarinic, responding to pilocarpine and acetylcholine. A component of the direct response was nicotinic, since it was activated by nicotine and blocked by hexamethonium in a dose-dependent manner. The axon-reflex response to nicotine and acetylcholine was partially blocked by pilocarpine, especially when application of pilocarpine preceded the procedure. The inhibition of the nicotinic response may be secondary to M1 antagonism since pilocarpine is an M2 agonist and M1 antagonist and pirenzepine, a specific M1 antagonist, caused similar effects as pilocarpine.

Acetylcholine↗

Effect of long-term calcitonin therapy by injection and nasal spray on the incidence of fractures in osteogenesis imperfecta.

The effect of calcitonin therapy by injection or nasal spray on the incidence of bone fractures was studied in patients with osteogenesis imperfecta. In contrast to injection of calcitonin, intranasal administration of calcitonin twice a week for 2 weeks, followed by 2 weeks of no therapy, was simple and seemed beneficial for decreasing bone fractures in patients with osteogenesis imperfecta.

Administration, Intranasal↗

Effect of dietary sodium on platelet alpha 2-adrenoceptors in young normotensive men with or without a family history of hypertension.

OBJECTIVE: To study the effects of genetics on the response of platelet alpha 2-adrenoceptors to a change in salt intake. METHODS: Biochemical measurements and radioligand binding assays in platelets were performed in 11 normotensive male university students with a family history of essential hypertension (FH+) and in 17 students without a family history of hypertension (FH-). The 28 students were fed a high-sodium diet for 7 days and a low-sodium diet for 7 days. RESULTS: In FH+ subjects the number of alpha 2-adrenergic receptors on platelet membrane fractions increased significantly from the high-sodium diet to the low-sodium diet, even though plasma noradrenaline concentrations tended to increase with the low-sodium diet. There was no change in the number of alpha 2-adrenoceptors in the FH--group. In both groups the radioligand binding affinity was decreased during a low-sodium period compared with in a high-sodium period. CONCLUSION: In the FH+ subjects the change in platelet alpha 2-adrenoceptors associated with altered sodium status was similar to that seen in patients with salt-sensitive hypertension, suggesting that there is a genetic susceptibility to sodium.

Adult↗

Escherichia coli produces a cytoplasmic alpha-amylase, AmyA.

In the gap between two closely linked flagellar gene clusters on the Escherichia coli and Salmonella typhimurium chromosomes (at about 42 to 43 min on the E. coli map), we found an open reading frame whose sequence suggested that it encoded an alpha-amylase; the deduced amino acid sequences in the two species were 87% identical. The strongest similarities to other alpha-amylases were to the excreted liquefying alpha-amylases of bacilli, with > 40% amino acid identity; the N-terminal sequence of the mature bacillar protein (after signal peptide cleavage) aligned with the N-terminal sequence of the E. coli or S. typhimurium protein (without assuming signal peptide cleavage). Minicell experiments identified the product of the E. coli gene as a 56-kDa protein, in agreement with the size predicted from the sequence. The protein was retained by spheroplasts rather than being released with the periplasmic fraction; cells transformed with plasmids containing the gene did not digest extracellular starch unless they were lysed; and the protein, when overproduced, was found in the soluble fraction. We conclude that the protein is cytoplasmic, as predicted by its sequence. The purified protein rapidly digested amylose, starch, amylopectin, and maltodextrins of size G6 or larger; it also digested glycogen, but much more slowly. It was specific for the alpha-anomeric linkage, being unable to digest cellulose. The principal products of starch digestion included maltotriose and maltotetraose as well as maltose, verifying that the protein was an alpha-amylase rather than a beta-amylase. The newly discovered gene has been named amyA. The natural physiological role of the AmyA protein is not yet evident.

Amino Acid Sequence↗

Molecular analysis of the flagellar switch protein FliM of Salmonella typhimurium.

Defects in the chemotaxis proteins CheY and CheZ of Salmonella typhimurium can be suppressed by mutations in the flagellar switch, such that swarming of a pseudorevertant on semisolid plates is significantly better than that of its parent. cheY suppressors contribute to a clockwise switch bias, and cheZ suppressors contribute to a counterclockwise bias. Among the three known switch genes, fliM contributes most examples of such suppressor mutations. We have investigated the changes in FliM that are responsible for suppression, as well as the changes in CheY or CheZ that are being compensated for. Ten independently isolated parental cheY mutations represented nine distinct mutations, one an amino acid duplication and the rest missense mutations. Several of the altered amino acids lie on one face of the three-dimensional structure of CheY (A. M. Stock, J. M. Mottonen, J. B. Stock, and C. E. Schutt, Nature (London) 337:745-749, 1989; K. Volz and P. Matsumura, J. Biol. Chem. 266:15511-15519, 1991); this face may constitute the binding site for the switch. All 10 cheZ mutations were distinct, with several of them resulting in premature termination. cheY and cheZ suppressors in FliM occurred in clusters, which in general did not overlap. A few cheZ suppressors and one cheY suppressor involved changes near the N terminus of FliM, but neither cheY nor cheZ suppressors involved changes near the C terminus. Among the strongest cheY suppressors were changes from Arg to a neutral amino acid or from Val to Glu, suggesting that electrostatic interactions may play an important role in switching. A given cheY or cheZ mutation could be suppressed by many different fliM mutations; conversely, a given fliM mutation was often encountered as a suppressor of more than one cheY or cheZ mutation. The data suggest that an important factor in suppression is a balancing of the shift in switch bias introduced by alteration of CheY or CheZ with an appropriate opposing shift introduced by alteration of FliM. For strains with a severe parental mutation, such as the cheZ null mutations, adjustment of switch bias is essentially the only factor in suppression, since the attractant L-aspartate caused at most a slight further enhancement of the swarming rate over that occurring in the absence of a chemotactic stimulus. We discuss a model for switching in which there are distinct interactions for the counterclockwise and clockwise states, with suppression occurring by impairment of one of the states and hence by relative enhancement of the other state. FliM can also undergo amino acid changes that result in a paralyzed (Mot-) phenotype; these changes were confined to a very few residues in the protein.

Amino Acid Sequence↗

International cooperative study on the relationship between dietary factors and blood pressure: a preliminary report from the Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. The CARDIAC Cooperative Study Research Group.

1. To investigate the epidemiological relationship of dietary factors to blood pressure (BP) and major cardiovascular diseases, we carried out the international cooperative Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study, which so far involves 48 centers in 20 countries as of August 1991. From each population, 100 men and 100 women aged 50-54 years were randomly selected for BP measurement, 24-h urine collection, blood tests, and medical interview. Various biological markers of diets from urine and blood were analyzed centrally in the Izumo CARDIAC center. 2. Cross center analysis using simple linear regression revealed strong significant correlations of body mass index (BMI) to systolic BP (SBP; p < 0.01) and diastolic BP (DBP; p < 0.001) in men. 24-h urinary sodium (Na) excretion in men also showed significant correlations with SBP (p < 0.05) and DBP p < 0.05) even after controlling for the effect of BMI (SBP; p < 0.05, DBP; p < 0.05). 3. Within center analysis using multiple linear regression implied that BMI and Na strongly adversely affect BP, whereas magnesium may have beneficial influence on BP. 4. Multicolinearities among 24h urinary sodium, calcium, and urea nitrogen were noted in men.

Body Mass Index↗