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Biomedical subjects

M Ohtani

Publications and source records attributed to M Ohtani.

At least 37 records · Page 2Linked to original sources

The cooperative action of angiotensin II with subluteolytic administration of PGF2alpha in inducing luteolysis and oestrus in the cow.

There is evidence that the potent vasoconstrictor angiotensin II (Ang II) regulates luteal functions. In the present study, the effect of an intraluteal injection of Ang II alone or in combination with pretreatment with a subluteolytic i.m. dose of PGF(2alpha) on the concentration of plasma progesterone, corpus luteum regression and duration of the oestrous cycle was investigated. Cows were assigned randomly to receive an intraluteal injection of either: (i) 500 microl saline 30 min after i.m. administration of saline (control, n = 7); (ii) 500 microl saline 30 min after i.m. administration of a subluteolytic dose (125 microg) of a PGF(2alpha) analogue (1/4 PGF(2alpha), n = 5); (iii) 2 mg Ang II in 500 microl saline 30 min after i.m. administration of saline (Ang II, n = 5); or (iv) 2 mg Ang II in 500 microl saline 30 min after i.m. administration of a subluteolytic dose (125 microg) of the PGF(2alpha) analogue (1/4 PGF(2alpha)/Ang II, n = 6) on day 12 of the oestrous cycle. There were no significant changes in plasma progesterone concentrations in the control, 1/4 PGF(2alpha) or Ang II treatment groups. Treatment with 1/4 PGF(2alpha)/Ang II decreased plasma progesterone concentration, and induced luteolysis and oestrus. The onset of oestrus in cows treated with full-dose (500 microg) PGF(2alpha) (3.1 +/- 0.2 (mean +/- SEM) days after treatment) was significantly earlier than that in cows treated with 1/4 PGF(2alpha)/Ang II (4.8 +/- 0.2 days after treatment) (P < 0.05). The results from the present study demonstrate that an intraluteal injection of Ang II after i.m. administration of a subluteolytic dose of PGF(2alpha) analogue induces luteolysis and oestrus. Thus, these results support the contention that Ang II is directly correlated with the process of luteal regression in cows.

Angiotensin II↗

Successful laparoscopic fundoplication in children with ventriculoperitoneal shunts.

We reported successful laparoscopic fundoplication in 2 pediatric cases with VPS and discuss the safety and feasibility of the procedure. Case 1: A 13-year-old girl with VPS underwent laparoscopic fundoplication. Case 2: a 9-year-old boy with VPS underwent laparoscopic fundoplication. In both cases, laparoscopic Nissen fundoplication was performed with a standard five-port technique with a low pressure of a pneumoperitoneum. The VPS system had no effect on port layout and intraabdominal manipulation and no adverse complications were observed in either case. The effect of a pneumoperitoneum in the VPS system remains controversial, however, the author emphasized that advanced laparoscopic surgery can be performed safely with creating a low pressure of a pneumoperitoneum.

Adolescent↗

Immunohistochemical localization of inducible nitric oxide synthase in synovial tissue of human temporomandibular joints with internal derangement.

The expression and distribution of inducible nitric oxide synthase (iNOS) was examined in 12 samples of human temporomandibular joint (TMJ) with internal derangement (ID) and four control specimens. In the diseased joints, strong or definite iNOS reactivity was expressed in synovial lining and endothelial cells; weaker activity was present in synovial fibroblasts. In contrast, although there was weak expression of iNOS in synovial fibroblasts and endothelial cells in the two control specimens, there was no iNOS staining in the synovial lining cell layers. This original report that iNOS is expressed in the synovial tissue of the temporomandibular joint indicates that nitric oxide is produced locally at least in the synovial lining in these joints when affected by internal derangement.

Adolescent↗

Effects of CYP2C19 gene polymorphism on cure rates for Helicobacter pylori infection by triple therapy with proton pump inhibitor (omeprazole or rabeprazole), amoxycillin and clarithromycin in Japan.

BACKGROUND: Omeprazole is mainly metabolized by cytochrome P450 2C19 (CYP2C19) in the liver. Rabeprazole, on the other hand, is mainly metabolized to thioether-rabeprazole via a non-enzymatic pathway and partially metabolized to demethylated-rabeprazole by CYP2C19 in liver CYP2C19 status may affect cure rate for Helicobacter pylori infection with proton pump inhibitor triple therapy. AIM: To investigate whether genetic polymorphism of CYP2C19 and selected proton pump inhibitors (omeprazole or rabeprazole) were associated with cure rate for Helicobacter pylori infection using triple therapy with omeprazole or rabeprazole, amoxicillin, and clarithromycin. METHODS: A total of 170 Helicobacter pylori-positive patients with chronic gastritis were randomized to receive one of the following Helicobacter pylori eradication regimens; OAC (omeprazole 20 mg bd, amoxycillin 750 mg bd and clarithromycin 400 mg bd for 1 week) and RAC (rabeprazole 20 mg bd, amoxycillin 750 mg bd and clarithromycin 400 mg bd for 1 week). The CYP2C19 genotype; wild-type or two mutant genes (ml in exon 5 and m2 in exon 4), or both, were identified by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: In DAC regimen, cure rate (per protocol analysis) was 73.3% in homozygous extensive metabolizers, 86.1% in heterozygous extensive metabolizers, and 85.0% in poor metabolizers. In RAC regimen, the cure rate was 81.0% in homozygous extensive metabolizers, 82.9% in heterozygous extensive metabolizers, and 87.5% in poor metabolizers. Cure rate was not significantly different between the CYP2C19 genotypes in both regimens. CONCLUSION: Triple therapy with proton pump inhibitor (omeprazole or rabeprazole), amoxycillin, and clarithromycin is sufficiently effective in cure of Helicobacter pylori infection regardless of CYP2C19 status.

2-Pyridinylmethylsulfinylbenzimidazoles↗

The effect of Helicobacter pylori eradication therapy on dyspepsia symptoms in industrial workers in Japan.

BACKGROUND: The relationship between Helicobacter pylori infection and non-ulcer dyspepsia is still controversial. The potential benefits and risks of the treatment could depend on local conditions, such as the prevalence of the infection and the local rates of gastric cancer. AIM: To evaluate the effects of H. pylori eradication therapy on non-ulcer dyspepsia symptoms in industrial workers in Japan. METHODS: A total of 615 employees of an industrial corporation were examined for H. pylori infection and symptom scores; 215 H. pylori-positive non-ulcer dyspepsia cases underwent eradication therapy. Symptom scores were also analysed 12 months after the eradication therapy. Serum pepsinogen A and pepsinogen C levels were analysed and chronic atrophic gastritis was serologically diagnosed on the basis of the criteria of a pepsinogen A < 70 ng/mL and pepsinogen A : pepsinogen C ratio < 3.0. RESULTS: The symptom score improved significantly in the cured cases, but not in the non-cured cases. The effect of the cure of H. pylori infection on symptoms was analysed according to the serological diagnosis of chronic atrophic gastritis. In both groups, cases with atrophic gastritis and cases with chronic gastritis only, the cure of infection was effective in improving symptoms. CONCLUSION: The cure of H. pylori infection was effective in reducing non-ulcer dyspepsia symptoms in industrial workers in Japan.

Adult↗

Identification and cloning of genes associated with the guinea pig skin delayed-type hypersensitivity reaction.

Although the cellular and molecular mechanisms underlying the delayed-type hypersensitivity (DTH) reaction have been investigated, the functions of infiltrating leukocytes and skin resident cells in the elicitation phase of the DTH reaction are not completely understood. To gain more insight into the role of these cells in the DTH reaction, we identified about 250 cDNA fragments showing elevated expression during the DNCB-induced guinea pig skin DTH reaction by differential display analysis. Characterization of 50 of them led to the identification of 28 genes whose expression was elevated in the DNCB-induced DTH reactive tissue. Sequencing of the 28 cDNA fragments and homology search analysis demonstrated that 10 of them represented known genes, some of which, in particular elafin (an elastase inhibitor) and ferritin, are considered to play roles in the DTH reaction. The other 18 fragments are probably derived from unknown genes. Cloning of the cDNAs of one of these genes indicated that it is that for guinea pig tryptophanyl-tRNA synthetase (WRS), a protein found to be induced by interferon-gamma and upregulated during the late stages of mononuclear phagocyte maturation in vitro. Strong induction of the WRS gene during the DTH reaction suggests its involvement in the in vivo immune response.

Amino Acid Sequence↗

Detection and cloning of a protein recognized by anti-human prostate-specific antigen (PSA) antibody in the rat ventral prostate.

Prostate-specific antigen (PSA), a 33 kDa glycoprotein produced in the epithelium of the human prostate, has become established as a useful tumor marker for prostate cancer in man. Since reports of homologous proteins in animals other than primates have been lacking, the present investigation was carried out to identify any PSA-like protein in rats. Immunoblot analysis using a specific monoclonal anti-human PSA antibody detected a 32 kDa immunoreactive protein in the ventral lobe of the rat prostate, but not in other lobes or in other tissues. Positive immunostaining was observed only for the luminal surface of the glandular epithelium and the intraductal fluid in the ventral prostate. Sequence analysis of a cDNA for the rat PSA-like protein, cloned by immunoscreening of an expression cDNA library prepared from the ventral lobe, revealed identity to the rat submaxillary gland S3 kallikrein. Human PSA also belongs to the kallikrein family. Thus, this protein produced in the rat ventral prostate was suggested to be a possible counterpart of human PSA.

Amino Acid Sequence↗

Helicobacter pylori infection induces hyperammonaemia in Mongolian gerbils with liver cirrhosis.

BACKGROUND AND AIMS: We previously reported the effect of Helicobacter pylori eradication on hyperammonaemia in patients with liver cirrhosis. However, the role of H pylori as a cause of hyperammonaemia is controversial. We developed an animal model with liver cirrhosis and investigated the effect of H pylori infection on hyperammonaemia. MATERIALS AND METHODS: Five week old male Mongolian gerbils were inoculated orally with broth culture of H pylori. Forty eight gerbils were divided into four groups. Gerbils not inoculated with H pylori were fed a commercial rodent diet (group A) or a choline deficient diet (group C). Gerbils inoculated with H pylori were fed the commercial rodent diet (group B) or the choline deficient diet (group D). Blood ammonia levels of the femoral vein and portal vein were measured 30 weeks later. RESULTS: All gerbils fed the choline deficient diet developed liver cirrhosis with fatty metamorphosis. The survival rate of group D was significantly lower than that of the other groups. Systemic and portal blood ammonia levels in group D were significantly higher than those in the other groups. CONCLUSIONS: H pylori infection induces hyperammonaemia in gerbils with liver cirrhosis.

Animals↗

Gastric leptin and Helicobacter pylori infection.

BACKGROUND: Leptin regulates feeding behaviour and therefore may be a mediator of anorexia associated with acute and chronic inflammation. Recently, leptin mRNA and leptin protein were found in the gastric epithelium. AIM: The aim of the present study was to examine the effect of Helicobacter pylori infection on gastric leptin expression to investigate the pathophysiological role of gastric leptin. METHODS: Surgically resected human stomach tissues were subjected to immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) to check for the presence of leptin in the human gastric epithelium. A total of 201 H pylori positive patients with chronic gastritis underwent eradication therapy for H pylori and were examined for the effect of infection cure in terms of body mass index (BMI) and serum leptin levels. Biopsy specimens from the gastric fundic mucosa were obtained from 40 of the 201 patients before and three months after eradication therapy. These samples were subjected to quantitative RT-PCR to examine the effect of eradication therapy on leptin expression in the gastric fundic mucosa. RESULTS: Leptin immunoreactive cells were detected in the lower half of the gastric fundic glands and a leptin PCR product was also found in the gastric fundic mucosa. H pylori infection significantly increased gastric leptin expression. In addition, cure of H pylori infection significantly reduced gastric leptin expression, with a concomitant increase in BMI. In contrast, serum leptin levels did not change significantly after cure of H pylori infection. CONCLUSION: Leptin is present in the human gastric mucosa. Gastric leptin may play a role in weight gain after eradication of H pylori infection. Gastric leptin may have a local rather than systemic action.

Adult↗

[No relation between angiotensin-converting enzyme (ACE) inhibitor-induced cough and ACE gene polymorphism, plasma bradykinin, substance P and ACE inhibitor concentration in Japanese patients].

Persistent dry cough is well known as the most common side-effect of angiotensin-converting enzyme (ACE) inhibitors. We examined the relationship between a cough and ACE gene polymorphism, plasma bradykinin (BK), substance P (SP) and ACE inhibitor concentrations in patients with hypertension or chronic nephritis. First, ACE genotyping was carried out in 96 patients, 42 with coughs and 54 without coughs, which had been treated with various kinds of ACE inhibitors. However, no significant difference in the ACE genotypes was observed between the two groups. Second, the plasma concentrations of BK, SP and ACE inhibitor were measured in 12 patients, which were treated with trandolapril at a daily dose of 1 mg for 4-33 weeks. In 3 patients, the cough was induced during the trandolapril therapy, while it was induced not in 9 patients. The plasma levels of BK and SP did not significantly change after trandolapril administration in the patients with and without coughs. Between the two groups, there were no significant differences in the plasma levels of BK and SP either before or after the trandolapril therapy. Also the plasma concentrations of trandolapril and trandolaprilat, the active metabolite of trandolapril, did not significantly differ between the two groups. These results suggest that there is no significant relationship between the ACE inhibitor-induced cough and ACE gene polymorphism, plasma BK, SP and ACE inhibitor concentrations in patients with hypertension or chronic nephritis.

Aged↗

Amino acid supplementation affects hematological and biochemical parameters in elite rugby players.

Individual amino acid supplementation affects various types of athletic performance. However, little information on combinations of amino acids is currently available. This study evaluated an amino acid mixture containing L-leucine, L-isoleucine, L-valine, L-arginine, and L-glutamine to 3.6 g of total amino acids per dose. Twenty-three rugby players were given 3.6 g, twice, daily of the amino acid mixture for 90 days (June-August 1994) and blood samples were collected for analyses in September 1993, March 1994, September 1994, and September 1995. After 90 days of supplementation, almost all of the athletes reported improvement in vigor and earlier recovery from fatigue. Significant increases (P<0.05) were observed in hemoglobin, RBC count, hematocrit, and serum iron by amino acid supplementation. Significant increases (P<0.05) were also noted in total cholesterol and low-density lipoprotein along with decreased (P<0.05) alkaline phosphatase. All values reverted to original levels when measured after one year of continued training without supplementation.

Adult↗

Changes in hematological parameters of athletes after receiving daily dose of a mixture of 12 amino acids for one month during the middle- and long-distance running training.

Previous studies have shown that a mixture of amino acids, consisting of 9 essential amino acids and 3 non-essential amino acids was effective in facilitating muscle recovery from athletic activities. In this study, the objective was to determine whether this amino acid mixture improved the physical condition and associated blood parameters of athletes in training when administered for a prolonged period. Thirteen college middle- and long-distance runners were placed in a 6-month experiment and received the amino acid mixture at the dose of 2.2 g/day for one month, 4.4 g/day for one month, and 6.6 g/day for one month with washout periods between test periods. The physical condition was scored and blood samples were collected before and after each test period. When the subjects received 2.2 g of the amino acid mixture three times a day, the physical condition was significantly improved along with increases in red blood cell count, hemoglobin, hematocrit, serum albumin, and fasting glucose, and a decrease in creatine phophokinase (p<0.05), suggesting increased hematopoiesis and glycogenesis, and rapid alleviation of muscle inflammation by the amino acid mixture.

Adult↗

Phagocytic response of bovine polymorphonuclear leukocytes to different incubation conditions and following exposure to some effectors of phagocytosis and different anticoagulants in vitro.

The ability of bovine polymorphonuclear leukocytes (PMN) to phagocytose fluorescent beads in vitro was studied using flow cytometry. The effects of varying laboratory conditions (bead:PMN ratio, length of incubation, and temperature) were first determined, then the effects of lipopolysaccharide (LPS), phorbol myristate acetate (PMA), cytochalasin B, and formyl-met-leu-phe (fMLP) on phagocytosis were evaluated. The recommended bead:PMN ratio, incubation period, and incubation temperature are 20:1, 30 min, and 38.5 degrees C, respectively. Lipopolysaccharide increased phagocytosis at a relatively high minimum dose; PMA increased phagocytosis even at low doses; cytochalasin B increased and decreased phagocytosis at low and high doses, respectively; and fMLP had no significant effect on phagocytosis. Also, the effects of ethylene diamine tetraacetic acid (EDTA) and acid citrate dextrose (ACD) as anticoagulants were compared with heparin-treated blood PMNs. Both EDTA and ACD decreased phagocytosis. Although there are reports that demonstrated that heparin reduced PMN phagocytosis, at least among the 3 anticoagulants used, heparin remains to be the standard anticoagulant for the study of PMN phagocytosis.

Animals↗

Characteristic magnetic resonance imaging for neurological assessment in HELLP syndrome with eclampsia: a case report.

HELLP syndrome is a complication of pregnancy characterized by hemolytic anemia, elevated liver enzymes, and low platelets. We describe a patient who suffered a generalized tonic seizure as a clinical onset. Magnetic resonance imaging (MRI) of the brain showed high intensity lesions on T2-weighted images and low- and iso- intensity on T1-weighed images. The patient fully recovered and on follow-up MRI the abnormal lesions were almost totally resolved. The sensitivity and specificity of MRI is useful in distinguishing this complication of pregnancy from cerebral apoplexy, brain tumor, epilepsy and other causes.

Adult↗

Involvement of CYP2B6 in n-demethylation of ketamine in human liver microsomes.

Ketamine is metabolized by cytochrome P450 (CYP) leading to production of pharmacologically active products and contributing to drug excretion. We identified the CYP enzymes involved in the N-demethylation of ketamine enantiomers using pooled human liver microsomes and microsomes from human B-lymphoblastoid cells that expressed CYP enzymes. The kinetic data in human liver microsomes for the (R)- and (S)-ketamine N-demethylase activities could be analyzed as two-enzyme systems. The K(m) values were 31 and 496 microM for (R)-ketamine, and 24 and 444 microM for (S)-ketamine. Among the 12 cDNA-expressed CYP enzymes examined, CYP2B6, CYP2C9, and CYP3A4 showed high activities for the N-demethylation of both enantiomers at the substrate concentration of 1 mM. CYP2B6 had the lowest K(m) value for the N-demethylation of (R)- and (S)-ketamine (74 and 44 microM, respectively). Also, the intrinsic clearance (CL(int): V(max)/K(m)) of CYP2B6 for the N-demethylation of both enantiomers were 7 to 13 times higher than those of CYP2C9 and CYP3A4. Orphenadrine (CYP2B6 inhibitor, 500 microM) and sulfaphenazole (CYP2C9 inhibitor, 100 microM) inhibited the N-demethylase activities for both enantiomers (5 microM) in human liver microsomes by 60 to 70%, whereas cyclosporin A (CYP3A4 inhibitor, 100 microM) failed to inhibit these activities. In addition, the anti-CYP2B6 antibody inhibited these activities in human liver microsomes by 80%, whereas anti-CYP2C antibody and anti-CYP3A4 antibody failed to inhibit these activities. These results suggest that the high affinity/low capacity enzyme in human liver microsomes is mediated by CYP2B6, and the low affinity/high capacity enzyme is mediated by CYP2C9 and CYP3A4. CYP2B6 mainly mediates the N-demethylation of (R)- and (S)-ketamine in human liver microsomes at therapeutic concentrations (5 microM).

Aryl Hydrocarbon Hydroxylases↗

Prevention of allergic inflammation by a novel prostaglandin receptor antagonist, S-5751.

Prostaglandin (PG) D2, the major cyclooxygenase metabolite generated from immunologically stimulated mast cells, is thought to contribute to the pathogenesis of allergic diseases due to its various inflammatory effects. However, since no DP receptor antagonist has been developed as an antiallergic drug, the role of PGD2 in the pathogenesis of allergic diseases remains uncertain. Here, we report the in vivo efficacy of our newly established DP receptor antagonist, S-5751 [((Z)-7-[(1R,2R,3S,5S)-2-(5-hydroxy benzo[b]thiophen-3-ylcarbonylamino)-10-norpinan-3-yl]hept-5- enoic acid)], using various allergic inflammation guinea pig models. In allergic rhinitis models, oral administration of S-5751 dramatically inhibited not only early nasal responses, as assessed by sneezing, mucosal plasma exudation, and nasal blockage, but also late responses such as mucosal plasma exudation and eosinophil infiltration. Even when S-5751 was administered after recovery from the early responses, these late phase responses were almost completely suppressed. In addition, S-5751 alleviated allergen-induced plasma exudation in the conjunctiva in an allergic conjunctivitis model and antigen-induced eosinophil infiltration into the lung in an asthma model. These findings provide evidence for the crucial role of PGD2 as a mediator of allergic inflammation in guinea pigs and suggest that DP receptor antagonists may be useful in the treatment of allergic diseases triggered by mast cell activation.

Animals↗

The volume limit in fluid resuscitation to prevent respiratory failure in massively burned children without inhalation injury.

We evaluated the accurate fluid requirement to prevent respiratory failure during the postresuscitation period in the resuscitation of massively burned children without inhalation injury. Forty-nine children were treated by similar fluid resuscitation and physiologic support protocols. Using a retrospective chart review, the children were divided into three groups as follows: Group N (no lung injury, n = 33, 41.4+/-18.7%TBSA burned), Group M (mild-to-moderate lung injury, n = 11, 73.7+/-17.1%TBSA burned) and Group S (severe lung injury, n = 5, 67.2+/-16.6%TBSA burned). Information about fluid resuscitation during the first 24 hr post-injury was collected and compared among the three groups. There was no significant difference in the hourly urine output and the resuscitation volume estimated by body weight and burn size among the groups. The volumes estimated by ml/kg/%TBSA burned were 7.0 ml/kg/%TBSA burned, 8.0 ml/kg/%TBSA burned, and 9.4 ml/kg/%TBSA burned in Groups N, M, and S, respectively. According to the fluid volume estimated by the burn index (BI; 1/2 of % second-degree burns plus % third-degree burns), the volumes were 13.8+/-4.0 ml/kg/BI, 14.4+/-4.4 ml/kg/BI, 18.8+/-3.7ml/kg/BI in Groups N, M, and S, respectively (Group N < Group S, p < 0.05). There was a significant positive correlation between the maximum respiratory index (AaDO2/PaO2) during the first week and the initial total volume administered (ml/kg/BI). These findings indicated that the fluid requirements to prevent postresuscitation respiratory failure in massively burned children might be estimated according to the depth of burned area in addition to body weight and burn size.

Blood Proteins↗

[Urinary tumor marker for urothelial cancer].

The urinary tumor markers BTA, BFP and NMP22 used for urothelial cancer in Japan are reviewed briefly. We also evaluate and compare the sensitivity and specificity of BTA, BFP and NMP22 with urine cytology in detecting bladder cancer in 24 of our patients. The results showed that the sensitivity with urine cytology, BTA, BFP and NMP22 was 37, 54, 66 and 62% respectively. The specificity of BTA, BFP and NMP22 with urine cytology was 100, 65, 60 and 70% respectively. The sensitivity with BTA, BFP and NMP22 for urothelial cancer was higher than that with urine cytology. However, all except for urine cytology showed high false positive rates (83-90%) for urinary tract infection. These markers may thus complement urine cytology, which has a low sensitivity for urothelial cancer. Quite possibly they could act as low-cost and useful tumor markers, which could in turn reduce the number of invasive cystoscopic examinations. However, considering their high false positive rates for benign disease such as urinary tract infection, we must acknowledge that an ideal urothelial tumor marker, which is simple, non-invasive, inexpensive and accurate with high sensitivity and specificity has yet to be developed.

Antigens, Neoplasm↗