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Biomedical subjects

H Ohmori

Publications and source records attributed to H Ohmori.

At least 145 records · Page 8Linked to original sources
PubMed1996

[Experimental studies on intravesical instillation of SM-5887, a novel anthracycline derivative for treatment of bladder carcinoma].

SM-5887 is a novel anthracycline derivative. Experimental studies of its intravesical chemotherapy were carried out to elucidate its histopathological effect on the normal bladder mucosa and the pharmacokinetics in Beagle dogs. Forty mg (4,000 micrograms/ml), 60 mg (6,000 micrograms/ml) and 80 mg (8,000 micrograms/ml) of SM-5887 dissolved in 10 ml of physiological saline were instilled into the empty bladders of dogs with bilateral cutaneous ureterostomy, respectively. SM-5887 instilled intravesically scarcely passed into the blood. In only one dog of five instilled with 80 mg of SM-5887 intravesically, the serum level of 0.0248 micrograms/ml was detected 2 hours after instillation, but all the others were below the detection limit (0.020 micrograms/ml). Excretion of SM-5887 into the urine was also low. The highest urinary excretion was observed 6 hours after instillation of 80 mg of SM-5887, yet the concentrations of SM-5887 and its metabolites in the urine were extremely low. The urinary concentrations of SM-5887 and its active metabolite, 13-OH derivative, were 0.029 micrograms/ml and 0.131 micrograms/ml, respectively. Other metabolites were not detected. The distribution of SM-5887 in the bladder mucosa and muscular layer was almost equal, but the concentration of its active metabolite, 13-OH derivative, was 5 to 10 times higher in the bladder mucosa than in the bladder muscular layer. The distributions of SM-5887 in the organs other than the bladder, that is, the cortex and medulla of kidney, heart, lung, liver, and spleen, were very low, and those of a 13-OH active metabolite were even lower. In addition, SM-5887 barely affected the normal bladder mucosa. In dogs instilled with 80 mg of SM-5887, no histological change was observed in the bladder mucosa and submucosal layer even after 6-hour retention at the highest concentration of 8,000 micrograms/ml.

Administration, Intravesical↗
PubMed1996

[Relationship of intracellular concentration and duration of contamination of pirarubicin and adriamycin in human bladder cancer cell lines and human bladder normal mucosa cell line].

To establish a method for reasonable clinical use of adriamycin (ADM) and pirarubicin (THP) in the intravesical chemotherapy for superficial bladder cancer, intracellular concentrations of these drugs were examined in culture cell lines (T-24, T-24/ADM and FHS736b1) with variable durations of contamination. The intracellular concentration of THP showed a plateau at 15-30 min. contamination in T-24, and in T-24/ADM, and showed the time dependence of contamination in FHS736b1, human normal bladder mucosa cell line. The intracellular concentration of ADM showed the time dependence of contamination in T-24, T-24/ADM and FHS736b1. And these concentrations of THP were 20 times higher than those of ADM. In conclusion, it seems better that THP was retained for 5-15 min. in the bladder in the intravesical chemotherapy, from the point of view of drug efficacy and preventing side effects. And it seems good that ADM was retained for more than 30 min. in the case with drug sensitive tumors.

Antibiotics, Antineoplastic↗
PubMed1996

[Mucin gene--regulation of the expression of MUC2 and MUC3 mucin gene in the airway].

Mucus hypersecretion is a characteristic feature of several human airway diseases, including chronic bronchitis, cystic fibrosis and asthma. Analysis of rat disease models has suggested that mucin synthesis is up-regulated as part of the disease process. To understand the primary structure of secretory mucins, several cDNAs encoding airway mucin have been isolated. In most cases, full-length sequences have not been obtained. In this review, we focused on the MUC2 and MUC3 mucin gene. MUC2 mucin has been reported to be expressed in the human lung with airway disease and in the rat lung with infection and exposure to irritant such as SO2. MUC3 is also expressed in the bronchus. Less is known about the structure and the expression pattern of the MUC3 mucin gene. Recent findings show that the expression pattern of the MUC2 and MUC3 mucin genes differ strikingly, suggesting that they play distinct functional roles in the airway and intestine. Functional analysis of mucin gene promoter will provide better understanding of the regulation of its expression in the airway under both normal and pathological conditions.

Amino Acid Sequence↗
PubMed1996

[Patch clamp].

Patch clamp technique was applied to variety of cells for variety of purposes. There are several modifications made for the technique and we can now record not only from the single channel but also from the whole cell membrane. The application of the patch recording technique was expanded and recordings were made recently from brain slice preparations. We have summarized technical aspects and several applications of patch clamp in this short review.

Animals↗
PubMed1996

[Potentiation of procaine-induced local sensory block by verapamil in rats].

We have studied the effects of calcium-channel blocker, verapamil, on procaine-induced local sensory block. Standardized tail-flick (TF) test was used to investigate the duration and intensity of procaine-induced local conduction block in rats. After obtaining baseline TF latencies (mean; 3.3 sec), two 100 microliters of 0.4% procaine alone, a combination of 0.4% procaine and verapamil (100 micrograms, or 200 micrograms), or a large dose of verapamil (200 micrograms) were injected to the opposite sites of the tail base and TF test was performed every five minutes for 45 minutes. A large dose of verapamil showed no prolongation of TF latencies. The administration of 0.4% procaine alone produced a significant increase of TF latencies and the peak effect of % MPE (percent maximum possible effect) was demonstrated at 4 minutes after the drug injection (mean % MPE; 37.0%). Coadministration of 0.4% procaine and two doses of verapamil produced significant increases of % MPE in a dose-dependent fashion. It was concluded that sensory block by procaine of the peripheral nerves is potentiated by coadministration of calcium-channel blocker, verapamil.

Anesthetics, Local↗
PubMed1995

Analysis of an insertional operator mutation (gntOi) that affects the expression level of the Bacillus subtilis gnt operon, and characterization of gntOi suppressor mutations.

The Bacillus subtilis gnt operon is negatively regulated via interaction of the gnt repressor (GntR) with an operator upstream of gntR, which is antagonized by gluconate. An 8 bp insertional operator mutation (gntOi) of the gnt operon was constructed which affected the expression level of this operon. Two suppressors of this gntOi mutation, exhibiting normal expression, were also isolated; one involved a threonine substitution for the Ala-48 residue (gntR48T) within the helix-turn-helix DNA-binding motif of GntR, and the other an adenine substitution for the guanine at nucleotide -4 within the gntOi operator (gntOiM4A) (+ 1 is the transcription initiation site). The gntR48T mutation by itself rendered the gnt operon partially constitutive. When the gntR43L mutation, which renders the gnt operon fully constitutive, was introduced into the gntOi or gntOiM4A mutant, the operator mutations were found not to affect the promoter activity of the gnt operon. These in vivo results indicate that the gntOi mutation affects the operator interaction with GntR, causing a low expression level even in the presence of gluconate. In vitro gel retardation and DNase I footprint analyses demonstrated that even when gluconate was present, GntR still bound to the gntOi operator region.

Amino Acid Sequence↗
PubMed1995

Expansion of methylmercury poisoning outside of Minamata: an epidemiological study on chronic methylmercury poisoning outside of Minamata.

The first methylmercury poisoning by consumption of fish arose in Minamata, Japan, in 1953. Methylmercury dispersed from Minamata to the Shiranui Sea until 1968. Mercury concentration in the hair of residents on the coast of the Shiranui Sea was 10 to 20 times higher than that in nonpolluted people in Kumamoto Prefecture in 1960. People on the coast of the Shiranui Sea have consumed fish containing low-dose methylmercury without a ban over decades until 1968. We studied the effect of long-term consumption of methylmercury on those people 10 years later after the end of methylmercury dispersion. Our epidemiological study clarified that people in a fishing village (Ooura) on the coast of the Shiranui Sea showed a significantly higher frequency of neurological signs characteristic of methylmercury poisoning (hypoesthesia, ataxia, impairment of hearing, visual change, and dysarthria) in comparison with people in a nonpolluted fishing village (Ichiburi). The neurological disorders were still detected 10 years later in Ooura after the end of methylmercury dispersion from Minamata; hypoesthesia showed the highest frequency in Ooura. These results suggest that people on the coast of the Shiranui Sea were afected by long-term dietary exposure to methylmercury.

Adult↗
PubMed1995

Nonuniform changes in fibre types in the soleus muscle of the developing rat.

Muscle fibre composition among the proximal (25%), middle (50%) and distal (75%) regions of the rat soleus muscle at various ages were compared to investigate whether the region-specific changes in fibre types known to occur under nonphysiological conditions (i.e. electrical stimulation along with immobilization in a lengthened position) also occur in the developing muscle. In addition, we attempted to detect fibres with nonuniform histochemical properties in the different segments, processing with myofibrillar actomyosin adenosine triphosphatase after pre-incubation at pH 10.3 against successive cryosections (200 microns apart). Samples were obtained from 66 Wistar rats of both sexes ranging in age from 13 to 85 days and subdivided into age groups of 2, 3, 4, 5 and 12 weeks. The mass and length of the soleus muscle increased most significantly at age 3-4 and 2-4 weeks, respectively. The distal region had a significantly lower percentage of type I fibres than the middle region at age 3 weeks, than the proximal and middle regions at age 4 weeks. In addition, some fibres [0.7 (SD 0.5)% n = 19 +/- 13] possessing nonuniform histochemical properties in different segments were observed from the middle and distal region at age 4 weeks. These findings would suggest that transformations from type II to type I fibres in the soleus muscle of the developing rat occur from the proximal or middle segments.

Aging↗
PubMed1995

dinP, a new gene in Escherichia coli, whose product shows similarities to UmuC and its homologues.

A new gene, designated dinP, was found during E. coli genomic sequencing around the 5.5 min region. Its coding region is preceded by a sequence similar to the consensus binding sequence for LexA, the so-called SOS box sequence. The amino acid sequence of DinP (351 amino acid residues) has a strong similarity to the C. elegans hypothetical protein F22B7.6 and weaker similarities to the UmuC homologues in E. coli and Salmonella typhimurium and also to REV1 of Saccharomyces cerevisiae. Another SOS operon (dinJ1 and dinJ2 genes) found in this region is also described.

Amino Acid Sequence↗
PubMed1995

Induction of heat shock protein 70 and nucleolin and their intracellular distribution during early stage of liver regeneration.

Our previous work demonstrated a simultaneous induction of Hsp70 and nucleolin mRNA during the prereplicative stage of hepatocytes after partial hepatectomy [Ohmori, H. et al. (1990) Exp. Cell Res. 189, 227-232]. In the present study, changes of intracellular localization of these proteins were examined. Nucleolin, which mainly localized in the nucleus, increased with time and accumulated in the nucleolus around 12-18 h after partial hepatectomy. Hsp70 protein also increased slightly around 6-12 h after the operation. In accordance with this increase, immunohistochemical staining revealed that almost all nuclei of hepatocytes became Hsp70-positive, although Hsp70 was seen to be dispersed throughout the nucleoplasm and nucleolus at all times examined. Next, we isolated a cDNA clone of ribosomal protein (S-17) and examined its behavior. Induction of S-17 mRNA was observed to be essentially similar to that of nucleolin mRNA in regenerating rat liver, although inductions of histone H2A and H4 occurred at a later time, that is, in parallel with DNA synthesis. Furthermore, we observed a simultaneous induction of Hsp70 and nucleolin mRNA by serum-stimulation after serum-depletion in HeLa and IAR-20 (rat) culture cells. These results suggest that the induction of Hsp70, in addition to nucleolin, was not fortuitous but may be involved in the early events of liver regeneration.

Animals↗
PubMed1995

Nuclear accumulation of p53 in normal human fibroblasts is induced by various cellular stresses which evoke the heat shock response, independently of the cell cycle.

Nuclear accumulation of p53 is induced by various DNA damaging agents (the p53 response). Induction of nuclear accumulation of p53 after various cellular stresses, mostly other than DNA damage, including heat shock, was examined in normal human fibroblasts by immunostaining and flow cytometry using a mouse anti-p53 monoclonal antibody. Immunostaining revealed nuclear accumulation of p53 within 6 h after various stresses [heat shock, osmotic shock, heavy metal (Cd), blockers of the cellular respiratory system (NaN3), amino acid analogues (azetidine and canavanine), an inhibitor of protein synthesis (puromycin), and oxygen free radicals (H2O2)]. Heat shock proved to be one of the most effective inducers among these stresses. FACScan analysis revealed that this induction of p53 occurred regardless of the stage in the cell cycle and that accumulation of cells in G2/M occurred. As all of these stresses are known to induce the heat shock response, the mechanism of p53 induction after stresses and that of heat shock response may share, at least partly, some common signaling pathway(s).

Cell Cycle↗
PubMed1995

[Drug sensitivity and expression of beta-lactamase in enterococci isolated at Okayama University Hospital].

The following results were obtained from a study of Enterococci isolated at the Okayama University Hospital from 1990 to 1994. 1) The isolation frequency of Enterococci was about 6% for each year. 2) The percentage of Enterococcus faecalis (E. faecalis) among Enterococci decreased each year, but the percentage of Enterococcus faecium (E. faecium), and Enterococcus avium (E. avium) increased each year. 3) Results of drug sensitivity tests revealed that the incidence of ofloxacin (OFLX) resistant E. faecalis and E. avium increased each year. Also, the resistance of E. faecalis to ampicillin (ABPC), the primary medication choice for treating E. faecalis, increased each year. 4) A few vancomycin (VCM) non-sensitive Enterococci were isolated. These bacteria showed low-sensitivity toward ABPC, imipenem (IPM), gentamicin (GM), and OFLX, and the extent of multiple drug resistance increased each year. 5) One hundred strains of Enterococci were selected to examine the expression of beta-lactamase using the broth method and the iodine-starch method. However, beta-lactamase producing strains were not detected.

Anti-Bacterial Agents↗
PubMed1995

The pcsA gene is identical to dinD in Escherichia coli.

The pcsA68 mutant of Escherichia coli is a cold-sensitive mutant which forms long filaments with a large nucleoid in the central region at 20 degrees C. We here show that (i) the coding region for the pcsA gene is identical with orfY located upstream of pyrE and can be deleted without loss of viability; (ii) pcsA is also identical to dinD, a DNA damage-inducible gene, whose expression is regulated by the LexA-RecA system; (iii) the cold-sensitive phenotype of the pcsA68 mutation is suppressed by delta recA or lexA1 (Ind-) mutation, but not by sulA inactivation; (iv) overproduction of PcsA68 leads to inhibition of cell growth in recA+ and delta recA strains at 20 and 37 degrees C, but PcsA+ does not show such an effect at any temperature; (v) SOS response is induced in the pcsA68 mutant cells at 20 degrees C. We discuss the possible function of the pcsA gene, comparing it with the sulA or the dif-xerCD function. We also describe a new method for gene disruption with positive and negative selection.

Bacterial Proteins↗
PubMed1995

Bacillus subtilis gnt repressor mutants that diminish gluconate-binding ability.

The Bacillus subtilis gnt operon is negatively regulated by GntR, which is antagonized by gluconate. Three GntR mutants with diminished gluconate-binding ability were obtained. Two were missense mutants (Met-209 to Ile and Ser-230 to Leu), whereas the third had a deletion of the C-terminal 23 amino acids. The mutant GntR proteins were unable to become properly detached from the gnt operator even in the presence of gluconate.

Amino Acid Sequence↗
PubMed1994

Molecular cloning of the amino-terminal region of a rat MUC 2 mucin gene homologue. Evidence for expression in both intestine and airway.

To obtain cDNAs for analysis of mucin gene transcription in rat models of human disease, we screened a rat intestinal cDNA library in lambda ZAPII using an upstream non-tandem repeat cDNA fragment of the human MUC 2 gene (Gum, J., Hicks, J., Toribara, N., Rothe, E., Lagace, R., and Y., K. (1992) J. Biol. Chem. 267, 21375-21383). Three cDNAs, 1-1, 8-1, and 21-1, were isolated. A translation start site was found in cDNA 21-1. Combined nucleotide sequence for the three cDNAs contained an open reading frame spanning 4546 base pairs. This amino-terminal sequence contains a non-tandem repeat domain enriched in cysteine (1391 residues) followed by an irregular tandem repeat domain (122 residues). Identity with the human gene is about 80% in the non-tandem repeat domain and about 38% in the irregular tandem repeat domain. Primer extension and S1 nuclease protection analysis indicate a transcription start site at 28 base pairs upstream of translation initiation. Northern analysis showed expression of cognate RNA in the intestine and airway but not heart and spleen. The cDNAs have been used to isolate the gene promoter, the structure of which should yield clues to the regulation of mucin expression in rat models of human disease.

Amino Acid Sequence↗
PubMed1994

Activation of glutamate receptors in response to membrane depolarization of hair cells isolated from chick cochlea.

1. Experiments were performed to identify the neurotransmitter released from hair cells of chick cochlea. An isolated hair cell was closely apposed to a cultured granule cell of the rat cerebellum, and both cells were whole-cell voltage clamped by utilizing a nystatin perforated patch technique. 2. Depolarization of hair cells to potentials more positive than -20 mV induced currents in the granule cell in a 10 mM Ca2+ extracellular medium. Amplitudes of induced currents were dependent on the membrane potential of granule cells and showed an outward-going rectification. The induced current in granule cells was reversibly suppressed by a local application of 2-amino-5-phosphonovalerate (APV), which indicates that the current was generated through the activation of an NMDA subtype of the glutamate receptor expressed on the granule cell. 3. The current amplitude of the granule cell was dependent on the size of hair cell depolarization. The size of current induced in a granule cell held at +55 mV was progressively increased with hair cell depolarization from -20 to +10 mV. At more positive potentials, the current amplitude was decreased. This voltage dependence was similar to but did not exactly match that of Ca2+ currents in the hair cell. The granule cell current appeared at more positive membrane potentials than the Ca2+ current in hair cells. 4. When intracellular Ca2+ concentration was increased by UV irradiation of the hair cell loaded with a caged Ca2+ compound, nitr-5, the closely apposed granule cell generated an outward current when voltage clamped at +55 mV. 5. These observations (paragraphs 2-4) imply that the most likely neurotransmitter released from the hair cell at its synapse with the afferent nerve terminal is glutamate.

2-Amino-5-phosphonovalerate↗
PubMed1994

The role of inositol trisphosphate on ACh-induced outward currents in bullfrog saccular hair cells.

Acetylcholine (ACh) is considered as the most likely candidate for a neurotransmitter of the efferent synapse onto hair cell. In this paper, the nature of this cholinergic receptor mechanism on dissociated bullfrog saccular hair cell was examined by using whole cell recording and Ca2+ sensitive fluorophotometric technique. Both the ACh-induced current and the increase of [Ca2+]i were observed in an oscillatory manner, and were the largest around the basal part of the cell where the efferent synapse is thought to make a contact with the membrane. The reversal potential of ACh-induced current indicated that ACh activated a K+ conductance. The ACh-induced current was reversibly blocked by atropine, d-tubocurarine (dTC), apamin, tetraethylammonium (TEA) and quinine. Neither muscarine nor nicotine mimicked the ACh-induced current. When GTP gamma S was injected into a hair cell, the first ACh application induced an outward current of transient kinetics, but in subsequent trials ACh-induced current lost its decay phase. Intracellularly injected D-myo-inositol 1,4,5-trisphosphate (InsP3) generated outward currents. Intracellularly injected heparin suppressed ACh-induced currents, and lithium (Li+) increased ACh-induced currents. These results indicate that ACh activates a receptor coupled with a guanine nucleotide binding protein (G-protein) which triggers metabolic cascades of InsP3 and Ca2+ leading to the activation of the Ca(2+)-activated K+ channel.

Acetylcholine↗