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Biomedical subjects

M Hirai

Publications and source records attributed to M Hirai.

At least 217 records · Page 12Linked to original sources

Profile of Helicobacter pylori cytotoxin derived from two areas of Japan with different prevalence of atrophic gastritis.

BACKGROUND AND AIM: To clarify the roles of Helicobacter pylori cytotoxin in gastric atrophy, the cytotoxin positive rate and cytotoxin activity in Fukui and Okinawa, where the prevalence of atrophic gastritis and gastric cancer risk are quite different, were studied. MATERIALS: Seventy three strains from Fukui and 51 from Okinawa were examined. METHODS: The validation of atrophy was done by endoscopy, being confirmed with histology. The supernatant of liquid H pylori culture media was concentrated 20-fold, serially diluted, using doubling dilutions, and scored from 1 to 8. The semi-quantitated cytotoxin activity was expressed as the maximum dilution score yielding > 50% A431 cell vacuolation, being standardised with bacterial density. RESULTS: The cytotoxin activity of the strains from Fukui was highly diverse compared with that from Okinawa, although the cytotoxin positive rate was not different. In Fukui strains, the grade of atrophy and the cytotoxin activity were correlated (p < 0.05). In addition, the cytotoxin activity of the strains from all patients in Okinawa, most of whom showed closed-type/mild atrophy, was significantly lower than that of the strains from the patients with open-type/severe atrophy in Fukui (6.46 (5.53) v 9.76 (8.80), p < 0.05), (mean (SEM)). CONCLUSION: The difference in profile of the cytotoxin activity in the two areas was related to the difference in the prevalence of atrophic gastritis.

Adult↗

Transient giant negative T wave in acute anterior myocardial infarction predicts R wave recovery and preservation of left ventricular function.

OBJECTIVE: To investigate the value of a giant negative T wave (> or = 1.0 mV) in precordial leads of 12-lead electrocardiograms in the acute phase of Q wave myocardial infarction as a predictor of myocardial salvage. METHODS: Coronary angiographic and electrocardiographic findings, left ventricular ejection fraction in the chronic stage, and levels of cardiac enzymes were compared in patients with myocardial infarction with (group GNT, n = 31) and without (group N, n = 20) a giant negative T wave. GNT patients were divided into two subgroups according to the presence (GNT:R[+], n = 10) or absence (GNT: R[-], n = 21) of R wave recovery with an amplitude > or = 0.1 mV in at least one lead that had shown Q waves. RESULTS: The maximum level of creatine kinase and the total creatine kinase were lower in group GNT compared with group N (P < 0.05). The left ventricular ejection fraction was higher in group GNT than in group N (P < 0.05). The maximum creatine kinase and total creatine kinase were lower in GNT:R(+) than in GNT:R(-) (P < 0.01). The left ventricular ejection fraction was higher in GNT:R(+) than in GNT:R(-) (P < 0.01). The frequency of R wave recovery was significantly higher when giant negative T waves appeared within 100 h of myocardial infarction or when the maximum potential was > or = 1.4 mV. The appearance of a giant negative T wave > or = 1.4 mV had a sensitivity of 90%, a specificity of 71.4%, a diagnostic accuracy of 77.4%, a positive predictive value of 60%, and a negative predictive value of 93.8% for prediction of R wave recovery. CONCLUSIONS: The appearance of a giant negative T wave, especially within 100 h of the onset of myocardial infarction, with a maximum potential of > or = 1.4 mV, may predict a reappearance of the R wave and a better left ventricular function in patients in the chronic stage of anterior myocardial infarction.

Cardiac Catheterization↗

Effect of a nonpeptide vasopressin V1 antagonist (OPC-21268) on experimental accelerated focal glomerulosclerosis.

The effects of the nonpeptide orally effective vasopressin V1 receptor antagonist OPC-21268 were studied in progressive focal glomerulosclerosis (FGS) which developed in spontaneously hypercholesterolemic (SHC) rats with manifestations of hypercholesterolemia and proteinuria. Unilateral nephrectomy was performed at 7 weeks of age to accelerate spontaneous FGS. After nephrectomy, OPC-administered rats were fed chow containing 1% OPC-21268 for 9 weeks. Treatment with vasopressin V1 antagonist significantly reduced the rate of increase in the levels of triglyceride, systolic blood pressure, serum creatinine and BUN, and prevented a significant deterioration in creatinine clearance. Rats were sacrificed at 16 weeks of age. Histologically, the index of glomerular sclerosis in the OPC group showed a significant decrease compared to that in the control group (2.2 +/- 0.1 vs. 2.6 +/- 0.1, p < 0.01). Relative interstitial volume and glomerular volume in the OPC group showed a tendency to decrease compared to those in the control group. These results indicate that vasopressin plays an important role through V1 receptors in the development of glomerulosclerosis, and vasopressin V1 antagonist may prevent the progression of renal injury in glomerulosclerosis.

Animals↗

Production of recombinant mite allergen Der fI in insect cells and characterization of products--removal of pro-sequence is essential to IgE-binding activity.

Der fI is a major mite proteinaceous allergen found in house dust. We produced recombinant Der fI (reDer fI) in insect cells using a baculovirus expression system. Based on the molecular mass and N-terminal amino acid (aa) sequence analysis, reDer fI was found to be compromised of a mixture of two proteins, each of which includes a pro-sequence of different length. The reDer fI had IgE-binding activity at only 20% of that of native Der fI. The removal of the pro-sequence in an acidic solution drastically increased IgE-binding activity to almost the same as that of native Der fI, showing that the presence of the pro-sequence is inhibitory to the IgE-binding activity of Der fI.

Allergens↗

[Infection in elderly leukemic patients].

Febrile episodes occurring in 29 elderly patients (mean age 75 years) with leukemia, from 1988 to 1993, were reviewed. A febrile episode was defined as a temperature of 38 degrees C or greater for at least 6 hours. The number of febrile episodes was 64. The average was 2.2 febrile episodes per patient. Seventy-two percent of febrile episodes occurred when the patients had neutropenia below 100/microliters, while 16% occurred with neutropenia of 101/microliters to 500/microliters. Causative microorganisms were identified in 48% of total febrile episodes. The most common infectious site was the urinary tract which accounted for 25% of total episodes. Pneumonia and septicemia accounted for 22% of total episodes, respectively. Gram-positive cocci were responsible for 66% of microbiologically documented febrile episodes, while 21% were caused by gram-negative bacilli. Gram-positive cocci, particularly staphylococcus aureus, coagulae-negative staphylococcus and enterococci increased compared with a decade ago in our department. Granulocyte colony-stimulating factor (G-CSF) was used 12 times for infection. No significant difference in fever amelioration was seen between G-CSF and non-G-CFS cases.

Aged↗

[Diffuse tracheobronchial amyloidosis with airflow limitation and repeated pneumonias].

A 67-year-old man was first admitted to our hospital complaining of a productive cough, and repeated episodes of pneumonia in different sites. Physical examination revealed expiratory wheezing and airflow limitation wlas documented with lung function tests. A chest X-ray film showed patchy pneumonic infiltrates. Chest computed tomography revealed a marked thickening of the tracheal and bronchial wall with linear calcification. Fiberoptic bronchoscopy revealed a diffuse infiltrative process in the tracheobronchial tree, which uniformly reduced the bronchial lumen. Bronchial biopsy specimens showed amyloid deposits with focal calcification, which was confirmed by Congo red and Dylon staining. Extensive examinations including rectal biopsy were negatie for systemic amyloidosis. We suggest that diffuse tracheobronchial amyloidosis should be included in the differential diagnosis of repeated pulmonary infections with airflow obstruction.

Aged↗

[Primary myelofibrosis with severe bone pain].

An 80-year-old man was admitted with bone pain, affecting both lower limbs and the dorsa of the feet, in September, 1991. Primary myelofibrosis was diagnosed. Bilateral x-ray films of the tibia, fibula, femur and vertebra revealed osteoporosis, but this was considered an unlikely source of the bone pain. The bone pain subsequently disappeared, but then became severe in both lower limbs and the dorsa of the feet and was accompanied by leukemic transformations in February, 1992. He died of aspiration pneumonia in July, 1992. Autopsy revealed microfractures with osteoporosis and infiltration of leukemic cells in the periosteum of the left tibia, which may have caused the bone pain. This case provides useful information to analyze the cause of bone pain in patients with myelofibrosis.

Aged↗

Purification, characterization and cDNA cloning of a novel anticoagulant of the intrinsic pathway, (prolixin-S) from salivary glands of the blood sucking bug, Rhodnius prolixus.

The salivary glands of the blood sucking insect, Rhodnius prolixus, have an anticoagulant, prolixin-S, which was reported as a specific inhibitor of intrinsic coagulant pathway. Prolixin-S was purified from the salivary glands extract of Rhodnius prolixus by gel filtration and anion exchange HPLC by assaying prolongation of activated partial thromboplastin time (APTT). The isolated protein specifically inhibited factor IXa-catalyzed activation of factor X in the presence of Ca2+ and phospholipids irrespective of the presence or absence of factor VIIIa. The anticoagulant factor had red color and a specific absorbance peak at 402 nm and thus it was identified as a heme protein. A Rhodnius prolixus salivary gland cDNA library was prepared, screened with an antibody against prolixin-S and its complete cDNA sequence was determined. cDNA and deduced amino acid sequences showed that prolixin-S is a novel anticoagulant of 19,922 Da, which has no sequence homology with any other anticoagulant reported so far.

Amino Acid Sequence↗

[Effect of prolonged intravenous ritodrine tocolysis on diurnal glucose profiles in pregnant women with normal carbohydrate tolerance].

Our purpose was to investigate an effect of prolonged intravenous ritodrine tocolysis on maternal carbohydrate metabolism in women with normal glucose tolerance. In patients with preterm labor, diurnal plasma glucose levels were measured both during the 24 hours after beginning the therapy (phase 1) and each day during over five days of continuous ritodrine tocolysis (phase 2). We also measured diurnal plasma glucose levels in normal pregnant women without any therapy (control group). In phase 1, in comparison with before therapy, a significant increase in the plasma glucose levels was observed with the highest level at 9 hours after starting ritodrine (146.4 +/- 31.6mg/dl). The higher plasma glucose levels persisted during phase 1. Although infusion rates were similar in both phases, maternal plasma glucose levels in phase 1 were significantly higher than in phase 2 (mean plasma glucose level, 128.1 +/- 21.3mg/dl vs. 92.7 +/- 11.6 mg/dl, p < 0.05; maximum plasma glucose level, 159.5 +/- 25.2mg/dl vs. 106.6 +/- 14.5mg/dl, p < 0.05). Diurnal glucose levels in phase 2 were similar to those in the control group. In phase 1, there seemed to be a dose-dependent relation between the ritodrine infusion rates and plasma glucose levels, but we did not find any relationship between them in phase 2. In conclusion, although hyperglycemia occurs during the initial phase of continuous ritodrine therapy (at least 24 hours), prolonged ritodrine infusion leads to normalization of the maternal plasma glucose levels.

Blood Glucose↗

[A case report of a successful Redo Bentall operation].

An initial Bentall operation was performed on a patient aged 38 years with annuloaortic ectasia and aortic regurgitation. An echocardiogram and RI angiogram revealed a perigraft aortic aneurysm on the same patient aged 45 years. The aneurysm gradually developed and the maximum diameter reached 90 mm in size. The Redo-Bentall operation (Piehler modification) was successfully done once again on the same patient aged 56 years. The anastmosis between the right coronary orifice and the graft was detached on all sides. The anastmosis between the left coronary orifice and the graft was detached two thirds of all sides.

Aneurysm, False↗

[Long-term results of cardiac valve replacement with a Delrin-disk model of the Björk-Shiley valve prosthesis--comparative analysis with the Spherical-disk model].

Records from 99 patients who received the Delrin-disk model (Group D) of the Björk-Shiley (BS) prosthesis between December, 1971 and November, 1974 were reviewed and compared to those from 248 patients who received the Spherical-disk model BS between January, 1975 and June, 1981 (Group S). Complete follow-up was obtained in 98.8% of the patients. The follow-up was over 1302.3 patient-years (mean 13.2 years per patient) in Group D and 2967.5 patient-years (mean 12.0 years per patient) in Group S. Early mortality was not significantly different (Group D: 18.2%, Group S: 10.5%). Of 15 late deaths in Group D, 12 (60%) were valve related and of 58 late deaths in Group S, 34 (58.6%) were valve related. The survival proportion based on Kaplan-Meier analysis, and which included early deaths, was equivalent in both groups (Group D: 65.7% at 21 years, Group S: 64.8% at 18 years). The freedom from reoperation was 74.3% at 21 years for Group D and 95% at 18 years for Group S (p < 0.005). The incidence of prosthetic valve dysfunction in Group D was significantly higher than that in Group S during 15 years after insertion of the valve. The freedoms from thromboembolism and valve-related events were not significant in both groups. Gross examination of the explanted Delrin disk found wear indentations and excessive clearance between the disk and the prosthetic ring. Therefore, disk wear was the primary cause of prosthetic valve dysfunction for the Delrin model. These results suggest that patients with the Delrin-disk model of the Björk-Shiley prosthesis should receive close follow-up for structural integrity of the valve. Further, reoperation might be needed due to significant valve dysfunction in this group of patients.

Adolescent↗

[A case report on graft replacement of ruptured aneurysm of the arch and the descending thoracic aorta associated with dense pulmonary adhesion].

A 73-year-old patient had been followed for aortic arch aneurysm of 54 mm in diameter. He was hospitalized complaining of chest and back pain. A chest CT scan showed ruptured aortic arch aneurysm extending to mid-descending thoracic aorta, and an emergent operation was decided. The trachea was intubated with a univent tube providing a movable blocker (System Corporation) which was directed to the left bronchus for differential lung ventilation. The descending thoracic aorta was exposed through the left 4th intercostal thoracotomy just at the site intending to anastomose a prosthetic graft because of dense pulmonary adhesion. The ascending and arch aorta was approached via median sternotomy. Under deep hypothermia and retrograde cerebral perfusion, total arch and descending aortic replacement was performed using an arch graft providing four branch grafts for neck vessels reconstruction and pump perfusion. The patient showed moderate pulmonary bleeding during and after cardiopulmonary bypass, but improved gradually. He was weaned from the respirator on the 13th post-operative day. During extensive thoracic aortic surgery using left thoracotomy combined with median sternotomy, left lung deflation using a univent tracheal tube with a blocker, and circulatory arrest during distal aortic anastomosis, are useful in preventing lethal pulmonary bleeding caused by lung injury under the fully heparinized condition. However, in cases associated with dense pulmonary adhesion, it is important to dissect carefully just a small area necessary to anastomose a graft, and to take elaborate assistant measures.

Aged↗

Identification and characterization of a novel family of serine/threonine kinases containing two N-terminal LIM motifs.

We previously isolated human cDNA coding for LIMK1 (LIM motif-containing protein kinase-1), a putative protein kinase containing two LIM motifs at the N terminus and an unusual protein kinase domain at the C terminus. In the present study, we isolated human cDNA encoding LIMK2, a second member of a LIMK family, with a domain structure similar to LIMK1 and 50% overall amino acid identity with LIMK1. The protein kinase domains of LIMK1 and LIMK2 are unique in that they contain an unusual sequence motif Asp-Leu-Asn-Ser-His-Asn in subdomain VIB and a highly basic insert between subdomains VII and VIII. Expression patterns of LIMK1 and LIMK2 mRNAs in human tissues differ significantly. Chromosomal localization of human LIMK1 and LIMK2 genes was assigned to 7q11.23 and 22q12, respectively, by fluorescence in situ hybridization. The Myc epitope-tagged LIMK1 and LIMK2 proteins transiently expressed in COS cells exhibited serine/threonine-specific kinase activity toward myelin basic protein and histone in in vitro kinase assay. Immunofluorescence and subcellular fractionation analysis revealed that Myc-tagged LIMK1 and LIMK2 were localized mainly in the cytoplasm. The "native" LIMK1 protein endogenously expressed in A431 epidermoid carcinoma cells also exhibited serine/threonine kinase activity. The specific activity of native LIMK1 from A431 cells was apparently much higher than that of "recombinant" LIMK1 ectopically expressed in COS cells, hence, it is likely that there is a mechanism, by which native LIMK1 is activated. A 140-kDa tyrosine-phosphorylated protein (pp140) was co-immunoprecipitated with native LIMK1 form A431 cell lysates; therefore, pp140 may be a LIMK1-associated protein involved in the regulation of LIMK1 function.

Amino Acid Sequence↗

Identification and characterization of a novel protein kinase, TESK1, specifically expressed in testicular germ cells.

We have isolated cDNA clones encoding the rat and human forms of a novel protein kinase, termed TESK1 (testis-specific protein kinase 1). Sequence analysis indicates that rat TESK1 contains 628 amino acid residues, composed of an N-terminal protein kinase consensus sequence followed by a C-terminal proline-rich region. Human TESK1 contains 626 amino acids, sharing 92% amino acid identity with its rat counterpart. The protein kinase domain of TESK1 is structurally similar to those of LIMK (LIM motif-containing protein kinase)-1 and LIMK2, with 49-50% sequence identity. Phylogenetic analysis of the protein kinase domains revealed that TESK1 is most closely related to a LIMK subfamily. Chromosomal localization of human TESK1 gene was assigned to 9p13. Anti-TESK1 antibody raised against the C-terminal peptide of TESK1 recognized two polypeptides of 68 and 80 kDa in cell lysates of COS cells transfected with human TESK1 cDNA expression plasmid. TESK1 protein expressed in COS cells exhibited serine/threonine kinase activity, when myelin basic protein was used as a substrate. Northern blot analysis revealed that TESK1 mRNA was specifically expressed in rat and mouse testicular germ cells. The TESK1 mRNA in the testis was detectable only after the 18th day of postnatal development of mice and was mainly expressed in the round spermatids. These observations suggest that TESK1 has a specific function in spermatogenesis.

Alternative Splicing↗

Diagnostic usefulness of postexercise systolic blood pressure response for detection of coronary artery disease in patients with electrocardiographic left ventricular hypertrophy.

Patients with left ventricular (LV) hypertrophy often have a positive result on exercise testing despite a normal coronary arteriogram. This indicates that exercise-induced ST depression is not always an accurate indicator of the presence of coronary artery disease (CAD) in such patients. We evaluated the usefulness of the postexercise systolic blood pressure (BP) response for detection of CAD in 51 patients with both electrocardiographic evidence of LV hypertrophy and positive ST depression on treadmill exercise testing. Coronary cineangiograms showed normal coronary arteries in 23 patients (45%) (group 1) and significant CAD in 28 patients (55%) (group 2). The systolic BP ratio (systolic BP at 3 minutes of recovery divided by systolic BP at peak exercise) was significantly higher in group 2 than in group 1 (1.01 +/- 0.19 vs 0.80 +/- 0.09; p < 0.001). Analysis of the relative cumulative frequency revealed that a systolic BP ratio of 0.86 was the cutoff point for distinguishing a patient with CAD from one with normal coronary arteries. The sensitivity, specificity, and accuracy of a systolic BP ratio > or = 0.86 for detection of CAD in patients with LV hypertrophy were 79%, 83%, and 82%, respectively. Our results suggest that the use of an abnormal BP ratio, in combination with ST depression, improves the accuracy of treadmill exercise testing for detecting CAD in patients with electrocardiographic evidence of LV hypertrophy.

Adult↗

c-Myc and cyclin D3 (CcnD3) genes are independent targets for glucocorticoid inhibition of lymphoid cell proliferation.

Glucocorticoids inhibit the expression of critical cell cycle-regulatory genes. The G1 cyclin gene CcnD3, which encodes cyclin D3, is inhibited by dexamethasone in P1798 murine T lymphoma cells. Glucocorticoids also inhibit expression of the catalytic partner of cyclin D3, Cdk4. Inhibition of these two genes results in a decrease in the ability to phosphorylate the Rb-1 tumor suppressor gene product. Stable transformation with SV40 T antigen expression vectors prevents glucocorticoid-mediated cell cycle arrest, which is consistent with the conclusion that glucocorticoids inhibit Rb-1 phosphorylation. Overexpression of cyclin D3 suffices to restore Rb-kinase activity in glucocorticoid-treated cells. Nevertheless, overexpression of cyclin D3 does not prevent glucocorticoid inhibition of cell proliferation. Cells transformed with Cdk4 expression vectors, with or without cyclin D3 expression vectors, also undergo G0 arrest in the presence of dexamethasone. Glucocorticoids inhibit c-Myc expression in lymphoid cells, and transient expression of c-Myc protein attenuates the lytic response in glucocorticoid-treated human leukemia cells (R. Thulasi, D. V. Harbour, and E. B. Thompson, J. Biol. Chem., 268: 18306-16312, 1993). However, P1798 cells stably transfected with c-Myc expression vectors are sensitive to glucocorticoid-mediated G0 arrest. Such transformants withdraw from the cell cycle when treated with dexamethasone. P1798 cells were transformed so as to express both c-Myc protein and cyclin D3 in the presence of glucocorticoids. These Myc/D3 cells continue to proliferate in the presence of dexamethasone, and virtually all of these cells are capable of entering S phase in the presence of the steroid. Rapid apoptotic cell death occurs when wild-type P1798 cells are treated with dexamethasone in serum-free medium. Myc-transformed and cyclin D3-transformed cells also die rapidly when treated with glucocorticoids in the absence of serum. T antigen transformants are resistant to glucocorticoid-mediated apoptosis in serum-free medium. Double transformants that express both cyclin D3 and c-Myc are also resistant to apoptosis in the presence of dexamethasone. We conclude that inhibition of both CcnD3 and c-Myc genes is critical to glucocorticoid-mediated G0 arrest. Furthermore, those genes that convey resistance to growth arrest also convey resistance to cell death.

Animals↗