Biomedical subjects

M Homma

Publications and source records attributed to M Homma.

At least 91 records · Page 5Linked to original sources

PubMed1997

Coexistence of serum anti-DNA topoisomerase I and anti-Sm antibodies: report of 3 cases.

We describe 3 Japanese patients having both serum anti-DNA topoisomerase I and anti-Sm antibodies. All 3 patients had typical features of systemic lupus erythematosus, such as glomerulonephritis, in addition to skin thickening and systemic sclerosis related organ involvement, including pulmonary interstitial fibrosis and renal crisis. This is the first report of the coexistence of these 2 disease specific autoantibodies.

Adolescent↗

PubMed1997

[Phospholipase C inhibitor].

N-Myristoylated PCI peptide, myr-PCI, originally developed based on the PCI sequence of PLC- gamma 2, inhibited activity of purified PLC isoforms in vitro, and external stimuli-dependent IP3 formation in Swiss 3T3 cells. When myr-PCI was added to KMS-8 cells, derived from familial adenomatous polyposis patients, it also suppressed the serum-dependent IP3 formation, DNA synthesis, and cell growth. In order to develop PCI peptides with strong anti-PLC activity, we synthesized the peptides whose N- and/or C-termini were acylated by a variety of compounds, and examined their anti-PLC and anti-proliferative activities. Results would be quite helpful to determine the minimal structure required for PLC inhibition in vivo.

3T3 Cells↗

PubMed1997

[Cerebral infarction due to stenosis of the bilateral internal carotid artery in Turner's syndrome].

A 43-year-old woman was admitted into our hospital because of aphasia and right hemiparesis. Computed tomographic scan demonstrated border zone infarction in the anterior and middle cerebral artery. Magnetic resonance imaging scans showed the borderline area between the terminal branches of the lenticulostriate arteries and the perforating branches of the middle cerebral artery. Digital subtraction ICA angiogram showed severe narrowing of the distal portion of the right and left ICA. A pattern analysis of ambulatory blood pressure monitoring (ABPM) was carried out in this patient, and it was showed "dipper type". Laboratory data was elevated excretion of pituitary gonadotropines and low estrogen excretion. Chromosome analysis revealed the 45, X/46, XX. She was diagnosed with mosaic type of Turner's syndrome. The cerebrovascular abnormality might be due to congenital hypoplasia of arteries, and declining of blood pressure during sleep was possible significant factors in the pathogenesis of cerebral infarction in this patient.

Adult↗

PubMed1996

Signaling by the Escherichia coli aspartate chemoreceptor Tar with a single cytoplasmic domain per dimer.

Many transmembrane receptors are oligomeric proteins. Binding of a ligand may alter the oligomeric state of the receptor, induce structural changes within the oligomer, or both. The bacterial aspartate chemoreceptor Tar forms a homodimer in the presence or absence of ligands. Tar mediates attractant and repellent responses by modulating the activity of the cytoplasmic kinase CheA. In vivo intersubunit suppression was used to show that certain combinations of full-length and truncated mutant Tar proteins complemented each other to restore attractant responses to aspartate. These results suggest that heterodimers with only one intact cytoplasmic domain are functional. The signaling mechanism may require interactions between dimers or conformational changes within a single cytoplasmic domain.

Aspartic Acid↗

PubMed1996

Modulation of the thermosensing profile of the Escherichia coli aspartate receptor tar by covalent modification of its methyl-accepting sites.

The Escherichia coli aspartate receptor Tar is involved in the thermotactic response. We have studied how its thermosensing function is affected by the modification of the four methyl-accepting residues (Gln295, Glu302, Gln309, and Glu491), which play essential roles in adaptation. We found that the primary translational product of tar mediates a chemoresponse, but not a thermoresponse, and that Tar comes to function as a thermoreceptor, once Gln295 or Gln309 is deamidated. This is the first identification of a thermosensing-specific mutant form, suggesting that the methylation sites of Tar constitute at least a part of the region required for thermoreception, signaling, or both. We have also investigated the inverted thermoresponse mediated by Tar in the presence of aspartate. We found that, whereas the deamidated-and-unmethylated form functions as a warm receptor, eliciting a smooth-swimming signal upon increase of temperature, the heavily methylated form functions as a cold receptor, eliciting a smooth-swimming signal upon decrease of temperature. Thus, it is suggested that Tar exists in at least three distinct states, each of which allows it to function as a warm, cold, or null thermoreceptor, depending on the modification patterns of its methylation sites.

Bacterial Proteins↗

PubMed1996

Rotational fluctuation of the sodium-driven flagellar motor of Vibrio alginolyticus induced by binding of inhibitors.

Rotation of the Na(+)-driven flagellar motor of Vibrio alginolyticus was investigated under the influence of inhibitors specific to the motor, amiloride and phenamil. The rotation rate of a single flagellum on a cell stuck to a glass slide was examined using laser dark-field microscopy. In the presence of 50 mM NaCl, the average rotation rate (omega) was about 600 r.p.s. with a standard deviation (sigma omega) of 9% of omega. When omega was decreased to about 200 r.p.s. by the presence of 1.5 mM amiloride, sigma omega increased to 15% of omega. On the other hand, when omega was decreased to about 200 r.p.s. by the addition of 0.6 microM phenamil, a large increase in sigma omega up to 50% of omega, was observed. Similarly large fluctuations were observed at other concentrations of phenamil. These observations suggest that dissociation of phenamil from the motor was much slower than that of amiloride. A very low concentration of phenamil caused a transient but substantial reduction in rotation rate. This might suggest that binding of only a single molecule of phenamil strongly inhibits the torque generation in the flagellar motor.

Amiloride↗

PubMed1996

Chemotactic responses to an attractant and a repellent by the polar and lateral flagellar systems of Vibrio alginolyticus.

Chemotactic responses in Vibrio alginolyticus, which has lateral and polar flagellar systems in one cell, were investigated. A lateral-flagella-defective (Pof+ Laf-) mutant, which has only a polar flagellum, usually swam forward by the pushing action of its flagellum and occasionally changed direction by backward swimming. When the repellent phenol was added, Pof+ Laf- cells moved frequently forward and backward (tumbling state). The tumbling was derived from the frequent changing between counter-clockwise and clockwise (CW) rotation of the flagellar motor, as was confirmed by the tethered-cell method. Furthermore, we found that the tumbling cells did not adapt to the phenol stimulus. When the attractant serine was added, the phenol-treated cells ceased tumbling and swam smoothly, adapting to the attractant stimulus after several minutes. We isolated chemotaxis-defective (Che-) mutants from the Pof+ Laf- mutant; the tumbling mutants were not isolated. One interesting mutant swam backwards continuously, with its flagellum leading the cell and its flagellar motor rotating CW continuously. A polar-flagella-defective mutant (Pof- Laf+) stopped swimming after phenol addition and then recovered swimming ability within 10 min, indicating that lateral flagella can adapt to the repellent stimulus. This may represent a functional difference between the two flagellar systems in Vibrio cells, and between the chemotaxis systems affecting the two types of flagella.

Adaptation, Physiological↗

PubMed1996

The sodium-driven polar flagellar motor of marine Vibrio as the mechanosensor that regulates lateral flagellar expression.

Certain marine Vibrio species swim in sea water, propelled by a polar flagellum, and swarm over surfaces using numerous lateral flagella. The polar and the lateral flagellar motors are powered by sodium- and proton-motive forces, respectively. The lateral flagella are produced in media of high viscosity, and the relevant viscosity sensor is the polar flagellum. The cell might monitor either the rotation rate of the flagellar motor or the mechanical force applied against the flagellum. To test these possibilities, we examined the effects of amiloride and its derivatives, which inhibit the rotation of the sodium-driven motor, on lateral flagellar gene (laf) expression in Vibrio parahaemolyticus. Phenamil, an amiloride analogue that inhibits swimming at micromolar concentrations, induced laf transcription in media devoid of viscous agents in a dose-dependent manner. The relationship between the average swimming speed and laf induction in the presence of various concentrations of phenamil was very similar to that observed when viscosity was changed. These results indicate that marine Vibrio sense a decrease in the rotation rate of (or the sodium influx through) the polar flagellar motor as a trigger for laf induction. Alternative mechanisms for laf induction are also discussed.

Amiloride↗

PubMed1996

Epidemiological analysis of tularemia in Japan (yato-byo).

A total of 1372 cases of tularemia observed in Japan since 1924 were analysed. More than 90% of the cases were reported in the north-eastern part of the main island of Japan. After World War II, more than 40 cases were reported yearly for 20 years. Since 1966, however, there have been less than 10 cases per year. Ninety-three % of the cases were caused by contact with infected wild rabbits. The pattern of monthly distribution showed a peak in December and also a lower peak in May. The number of patients older than 40 years of age and the proportion of cases in females have gradually increased. In the earlier survey periods almost 70% of the cases were engaged in agriculture but at present this rate is less than 50%. The changes in the occurrence of tularemia in Japan is thought to be related to the change of life style caused by the rapid growth of the Japanese economy after World War II.

Adolescent↗

PubMed1996

Characterization of the flagellar hook length control protein fliK of Salmonella typhimurium and Escherichia coli.

During flagellar morphogenesis in Salmonella typhimurium and Escherichia coli, the fliK gene product is responsible for hook length control. A previous study (M. Homma, T. Iino, and R. M. Macnab, J. Bacteriol. 170:2221-2228, 1988) had suggested that the fliK gene may generate two products; we have confirmed that both proteins are products of the fliK gene and have eliminated several possible explanations for the two forms. We have determined the DNA sequence of the fliK gene in both bacterial species. The deduced amino acid sequences of the wild-type FliK proteins of S. typhimurium and E. coli correspond to molecular masses of 41,748 and 39,246 Da, respectively, and are fairly hydrophilic. Alignment of the sequences gives an identity level of 50%, which is low for homologous flagellar proteins from S. typhimurium and E. coli; the C-terminal sequence is the most highly conserved part (71% identity in the last 154 amino acids). The central and C-terminal regions are rich in proline and glutamine residues, respectively. Linker insertion mutagenesis of the conserved C-terminal region completely abolished motility, whereas disruption of the less conserved N-terminal and central regions had little or no effect. We suggest that the N-terminal (or N-terminal and central) and C-terminal regions may constitute domains. For several reasons, we consider it unlikely that FliK is functioning as a molecular ruler for determining hook length and conclude that it is probably employing a novel mechanism.

Amino Acid Sequence↗

PubMed1996

Effect of viscosity on swimming by the lateral and polar flagella of Vibrio alginolyticus.

By using mutants of Vibrio alginolyticus with only a polar flagellum (Pof+ Laf-) or only lateral flagella (Pof- Laf+), we examined the relationship between swimming speed and the viscosity of the medium for each flagellar system. Pof+ Laf- cells could not swim in the high-viscosity environment (ca. 200 cP) in which Pof- Laf+ cells swam at 20 microns/s. The Pof- Laf+ cells swam at about 20 microns/s at normal viscosity (1 cP) without the viscous agent, and the speed increased to 40 microns/s at about 5 cP and then decreased gradually as the viscosity was increased further. These results show the functional difference between polar and lateral flagella in viscous environments.

Cell Movement↗

PubMed1996

Cloning and characterization of motY, a gene coding for a component of the sodium-driven flagellar motor in Vibrio alginolyticus.

The bacterial flagellar motor is a molecular machine that couples proton or sodium influx to force generation for driving rotation of the helical flagellar filament. In this study, we cloned a gene (motY) encoding a component of the sodium-driven polar flagellar motor in Vibrio alginolyticus. Nucleotide sequence analysis revealed that the gene encodes a 293-amino-acid polypeptide with a single putative transmembrane segment that is very similar (94.5% identity) to the recently described MotY of V. parahaemolyticus. Their C-terminal domains were similar to the C-terminal domains of many peptidoglycan-interacting proteins, e.g., Escherichia coli MotB and OmpA, suggesting that MotY may interact with peptidoglycan for anchoring the motor. By using the lac promoter-repressor system, motY expression was controlled in V. alginolyticus cells. Swimming ability increased with increasing concentrations of the inducer isopropyl-beta-D-thiogalactopyranoside, and the swimming fraction increased after induction. These results are consistent with the notion that MotY is a component of the force-generating unit. V. alginolyticus motY complemented the motY mutation of V. parahaemolyticus. However, motY appeared to lack a region corresponding to the proposed motY promoter of V. parahaemolyticus. Instead, sequences similar to the sigma54 consensus were found in the upstream regions of both species. We propose that they are transcribed from the sigma54 -specific promoters.

Amiloride↗

PubMed1996

The Sendai paramyxovirus accessory C proteins inhibit viral genome amplification in a promoter-specific fashion.

Many paramyxoviruses express small basic C proteins, from an alternate, overlapping open reading frame of the P gene mRNA, which were previously found to inhibit mRNA synthesis. During recent experiments in which infectious Sendai virus (SeV) was recovered from cDNA via the initial expression of the viral N, P, and L genes from plasmids, the abrogation of C protein expression from the plasmid P gene was found to be necessary for virus recovery. We have investigated the effect of C coexpression on the amplification of an internally deleted defective interfering (DI) genome directly in the transfected cell, for which, in contrast to virus recovery experiments, genome amplification is independent of mRNA synthesis carried out by the SeV polymerase. We find that C protein coexpression also strongly inhibits the amplification of this DI genome but has little or no effect on that of a copy-back DI genome (DI-H4). We have also characterized the C protein from a mutant SeV and found that (i) it had lost most of its inhibitory activity on internally deleted DI genome amplification and (ii) its coexpression no longer prevented the recovery of SeV from DNA. However, consistent with the insensitivity of copy-back DI genomes to C protein inhibition, C coexpression did not prevent the recovery of copy-back nondefective viruses from DNA. The inhibitory effects of C coexpression thus appear to be promoter specific.

Gene Amplification↗

PubMed1996

Abnormal prostanoid metabolism in lupus nephritis and the effects of a thromboxane A2 synthetase inhibitor, DP-1904.

Abnormalities of prostanoid metabolism, which may affect renal function, were studied in lupus nephritis. The subjects were 31 patients with lupus nephritis, ten with non-renal SLE, and four with renal, non-SLE collagen disease. Urinary levels of various prostanoids, thromboxane B2(TXB2), 11-dehydro-TXB2, 6-keto-PGF1 alpha,2,3-dinor-6-keto-PGF1 alpha and PGE2, and plasma level of 11-dehydro-TXB2, were determined. The effects of four days' dosing of a selective thromboxane A2 (TXA2) synthetase inhibitor, DP-1904 (DP), on prostanoid metabolism, were also studied. Urinary excretion of TXB2, which reflects the renal production of TXA2, was significantly increased in patients with lupus nephritis as compared with non-renal SLE (p < 0.05). The urinary TXB2/6-keto-PGF1 alpha ratio was also increased in lupus nephritis as compared with non-renal SLE or healthy controls (p < 0.01), indicating a prostanoid imbalance, which may lead to impaired renal function and subsequent pathology. The urinary TXB2/6-keto-PGF1 alpha ratio in these lupus nephritis patients showed negative correlations with Ccr and positive correlations with anti-DNA antibody titer (p < 0.001). DP was administered orally (400 mg/day, given in two divided doses) for four days to eight lupus nephritis patients. The urinary excretion of TXB2 and urinary TXB2/6-keto-PGF1 alpha ratio were decreased after one to two days of treatment in all patients. An increase in creatinine clearance used as a measure of renal function was observed in four of eight patients. Furthermore, no side effects were elicited during the four days of treatment. The conclusion reached were that the abnormal prostanoid metabolism observed in lupus nephritis could aggravate renal function through hemodynamic mediation, and that the deviated metabolism was reversible and, at least partially, corrected by a TXA2 synthetase inhibitor.

6-Ketoprostaglandin F1 alpha↗

PubMed1996

Late development of anti-La/SS-B antibodies in a patient with Sjogren's syndrome and high titer anti-Ro/SS-A antibodies.

The frequent coexistence of anti-Ro and anti-La autoantibodies is well described, however, there is little evidence of sequential development of these two autoantibodies. We report a case of typical Sjogren's syndrome with high titer anti-Ro antibodies, who subsequently developed anti-La antibodies later in the course. This case suggests that the anti-La antibodies may actually follow the anti-Ro antibodies in some cases as hypothesized in the concept of linked set of autoantibodies, analogous to development of anti-Sm in certain anti-nRNP antibody positive SLE patients and animal models.

Antibodies, Antinuclear↗

PubMed1996

Vertebral body shape as a predictor of spinal deformity in osteogenesis imperfecta.

We analyzed forty-four patients who had osteogenesis imperfecta, in order to determine the prevalence of spinal deformities. At the time of the most recent follow-up scoliosis was present in thirty patients (68 per cent) and kyphosis, in eighteen (41 per cent). According to the classification system of Falvo et al., scoliosis progressed rapidly with growth in twelve of fifteen patients who had the congenita type of osteogenesis imperfecta and in four of thirteen who had the tarda-I type. Curves that progressed before puberty did not always continue to progress after cessation of growth. Lateral roentgenograms made at the initial examination revealed four types of vertebral body deformities: biconcave, flattened, wedged, and unclassifiable vertebrae:Biconcave vertebrae were seen characteristically in patients who had the congenita type of osteogenesis imperfecta. The presence of six biconcave vertebrae or more before puberty indicated that severe scoliosis (more than 50 degrees) was likely to develop. Biconcave vertebrae did not appear to affect the severity of kyphosis. The other types of vertebral deformities were not useful for predicting progression of spinal deformity.

Adolescent↗

PubMed1996

Restricted heterogeneity and changing spectrotypes in autoantibodies to La/SS-B.

Isoelectric focusing (IEF) spectrotype of specific immunoglobulins has been studied as a marker for B-cell clonality. In the present study, the spectrotype of anti-La antibodies in human autoimmune sera were analyzed by newly developed IEF sandwich assay in which focused total immunoglobulin on filter papers are incubated with crude antigen followed by horse-radish peroxidase-labeled anti-La antibodies. The anti-La spectrotypes contained oligoclonal bands, the positions and patterns of which are different in each patient, suggesting the preferential expansion of limited numbers of anti-La producing B-cell clones unique to individual patients. Furthermore, the bands on anti-La spectrotype in sequentially obtained sera changed continuously, suggesting alteration in the expanding anti-La producing clones. These may reflect affinity maturation and/or diversification of the B-cell epitopes involving somatic mutation.

Antibodies, Antinuclear↗

PubMed1996

Improvement of renal function with a selective thromboxane A2 synthetase inhibitor, DP-1904, in lupus nephritis.

OBJECTIVE: To examine abnormalities of prostanoid metabolism in lupus nephritis, which may affect renal function, and the effects of 4 day dosing of a selective thromboxane A2 (TXA2) synthetase inhibitor, DP-1904, on prostanoid metabolism. METHODS: Urinary levels of various prostanoids, thromboxane B2(TXB2), 11-dehydro-TXB2, 6-keto-prostaglandin F1 alpha, 2,3-dinor-6-keto-PGF1 alpha, and prostaglandin E2 were determined. In a randomized crossover study, 8 patients with biopsy proven lupus nephritis were given 4 days' oral administration of DP-1904 (400 mg/day bid) or indomethacin (50 mg/day bid). The effects of DP-1904 on prostanoid metabolism were studied. RESULTS: Urinary excretion of TXB2, which reflects the renal production of TXA2, was significantly increased in patients with lupus nephritis compared with non-renal systemic lupus erythematosus (SLE)(p < 0.05); enhanced production of TXA2 was also estimated in patients with lupus nephritis. The urinary TXB2/6-keto-PGF1 alpha ratio was also increased in lupus nephritis compared with non-renal SLE (p < 0.01), indicating a prostanoid imbalance that may lead to impaired renal function and subsequent pathology. During administration of DP-1904, the urinary excretion of TXB2 was significantly decreased after 1 to 2 days. An increase in creatinine clearance as a measure of renal function was observed. In contrast, during the administration of indomethacin, urinary excretion of both TXB2 and 6-keto-PGF1 alpha decreased and there were no significant changes in the urinary TXB2/6-keto-PGF1 alpha ratio or creatinine clearance. Hemodynamic changes were associated with a slight increase in sodium excretion, but with no change in arterial blood pressure. No side effects were elicited during the 4 days of treatments. CONCLUSION: The abnormal prostanoid metabolism observed in lupus nephritis could aggravate renal function, which was mediated hemodynamically, and the altered metabolism was reversible and at least partially corrected by a TXA2 synthetase inhibitor, DP-1904.

Adult↗