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Biomedical subjects

M Nasu

Publications and source records attributed to M Nasu.

At least 91 records · Page 5Linked to original sources

Analysis of p53 gene mutations in Helicobacter pylori-associated gastritis mucosa in endoscopic biopsy specimens.

BACKGROUND: No previous report has shown the relationship between Helicobacter pylori infection and a direct sequence analysis of p53 gene mutation in a biopsy sample of human gastric mucosa. METHODS: A total of 60 endoscopic biopsies samples (21 patients with H. pylori-positive gastritis and 9 patients with H. pylori-negative gastritis), including antral mucosa and corpus mucosa, were used in this study. Direct DNA sequencing of exons 5, 6, 7, and 8 of the p53 gene was performed by the dyedeoxy terminator method. RESULTS: Mutations in the p53 gene were identified in non-hot spot codons in exon 7 and 8 in 11 of 21 samples (52.4%) from H. pylori-positive gastritis patients. There was no mutation in H. pylori-negative gastritis patients. CONCLUSIONS: This finding shows that H. pylori infection can induce p53 point mutations and appears to be involved in the pathway leading to dysplasia or carcinoma.

Adult↗

Effect of Helicobacter pylori infection on the N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in mongolian gerbils.

The effect of Helicobacter pylori infection on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastric cancer was studied using a Mongolian gerbil model. Five-week-old male Mongolian gerbils were divided into four groups of 25-30 animals each and challenged for 20 weeks with H.pylori, MNNG, a combination of H.pylori and MNNG, or neither of them. Four to 20 animals from each group were killed at 16, 24 and 52 weeks after H.pylori inoculation, and histopathological changes in their stomachs were examined. A well-differentiated adenocarcinoma was first observed 24 weeks after inoculation in the combination group. At 52 weeks, only six of 15 animals were colonized with H.pylori persistently, and four of them showed well-differentiated adenocarcinomas; on the other hand, neither of the animals with disappearance of H.pylori from the combination group showed adenocarcinoma. At the same observation time, three of 17 animals from MNNG group showed poorly differentiated adenocarcinomas. The incidence of gastric carcinoma in the combination group was significantly higher than that in the MNNG group (P < 0.05). However, no tumors were seen in the control and H.pylori groups. The present findings demonstrate that H.pylori infection enhances the carcinogenic action of MNNG.

Adenocarcinoma↗

Effect of bepridil on intracellular calcium concentration and contraction in cultured rat ventricular myocytes.

We studied the effects of a new antiarrhythmic and antianginal agent, bepridil, on the intracellular calcium transient and contraction of cultured neonatal rat ventricular cells, and compared the effects with those caused by an authentic Ca2+ -entry blocker, D600 (methoxyverapamil). The Ca2+ transient was measured by using dual-wavelength microfluorometry of fura-2. The contraction was measured as a shortening of cell aggregates with the use of a video image-analyzing system. Both bepridil (1-30 microM) and D600 (1-30 microM) decreased the peak systolic amplitude of the Ca2+ transient in a concentration- and frequency-dependent manner. Bepridil, but not D600, significantly shortened the half-decay time of the Ca2+ transient and prolonged the time course of the contraction. D600 decreased the contraction in parallel with the decrease in the peak Ca2+ transient, whereas bepridil exerted no significant effect on the contraction. Bepridil (10 microM) induced a leftward shift (to lower amplitude of peak systolic Ca2+ transient) of the relation between the magnitude of contraction and the peak systolic Ca2+ transient, which was obtained by changing external Ca2+ concentration. In contrast, D600 (10 microM) did not affect the relation. The results suggest that the negative inotropic effect of bepridil (caused by its Ca2+ channel-blocking effect) is offset by its simultaneous increase in the sensitivity of contractile protein(s) to intracellular Ca2+, which may be a unique characteristic of this antiarrhythmic agent in a clinical setting.

Animals↗

Clindamycin suppresses endotoxin released by ceftazidime-treated Escherichia coli O55:B5 and subsequent production of tumor necrosis factor alpha and interleukin-1 beta.

Treatment of septicemia caused by Escherichia coli with ceftazidime (CAZ) may be associated with the development of septic shock due to the release of bacterial lipopolysaccharide. We examined the suppressive effect of clindamycin (CLDM) on CAZ-induced release of endotoxin by cultured E. coli and the subsequent production of inflammatory cytokines (tumor necrosis factor alpha [TNF-alpha] and interleukin-1 beta [IL-1 beta]). E. coli ATCC 12014 was incubated in inactivated horse serum with or without CLDM for 1, 4, or 18 h, followed by the addition of CAZ and collection of the culture supernatant at 0, 1, and 2 h. The concentration of endotoxin in each sample was measured by a chromogenic Limulus test. Another portion of the culture supernatant was added to THP-1 cell culture and incubated for 4 h, and the concentrations of TNF-alpha and IL-1 beta in the supernatant were measured by an enzyme-linked immunosorbent assay. In the control group (no CLDM), CAZ administration resulted in significant increases in endotoxin, TNF-alpha, and IL-1 beta concentrations. Pretreatment of E. coli with CLDM for 4 or 18 h before the addition of CAZ significantly suppressed the concentrations of endotoxin, TNF-alpha, and IL-1 beta in a time-dependent manner. In addition, CAZ treatment transformed E. coli from rodshaped bacteria to filament-like structures, as determined by electron microscopy, while pretreatment with CLDM prevented these morphological changes. Our in vitro studies showed that CAZ-induced release of large quantities of endotoxin by E. coli could be suppressed by prior administration of CLDM.

Anti-Bacterial Agents↗

Local secretory immunoglobulin A and postimmunization gastritis correlate with protection against Helicobacter pylori infection after oral vaccination of mice.

C57BL/6 mice were orally immunized with five weekly doses of 2 mg, 200 microgram, or 2 microgram of Helicobacter pylori (Sydney strain) whole-cell sonicate combined with cholera toxin. One week after the last vaccination, mice were challenged with 5 x 10(7) CFU of live H. pylori three times at 2-day intervals. At 6 or 18 weeks after the challenge, mice were sacrificed and bacterial cultures and histological studies of the stomach were performed. Vaccination with 2 mg/session or 200 microgram/session inhibited H. pylori colonization by 90 and 100%, respectively. These mice were considered protected. Lower levels of H. pylori-specific immunoglobulin A (IgA) were detected in fecal and saliva samples before challenge. However, a significant increase in IgA secretion in mucosal tissue and a higher labeling index for IgA-positive lumina of pyloric glands were noted in these mice in response to challenge and in a vaccine dose-dependent manner. In protected mice, however, severe gastritis characterized by marked infiltration of inflammation mononuclear cells was noted at 6 weeks after challenge, compared with the gastritis seen in unprotected mice or nonvaccinated, ordinarily infected mice. Marked expression of gamma interferon mRNA was detected in the stomach of all protected mice, and 50% of these mice expressed interleukin 4 (IL-4) or IL-5 mRNA. Our findings suggest that local secretory IgA antibody and severe postimmunization gastritis correlate well with protection of mice against H. pylori infection.

Administration, Oral↗

PCR detection of DNA specific for Trichosporon species in serum of patients with disseminated trichosporonosis.

Deep-seated trichosporonosis is a lethal opportunistic infection that disseminates rapidly and widely in immunocompromised patients, and early diagnosis is crucial for the treatment of this infection. We developed a novel nested-PCR assay that detects DNA specific for clinically important strains of Trichosporon in serum samples from patients with disseminated trichosporonosis. In this assay, two sets of oligonucleotide primers were derived from the sequence of 26S rRNA genes of Trichosporon asahii. The specific fragment was amplified from T. asahii and T. mucoides, but not from other microorganisms, including some other basidiomycetous fungi (Cryptococcus, Malassezia, Rhodotorula, and Sporobolomyces). Target DNA was detected by the nested PCR with as little as 5 fg of the extracted DNA of T. asahii. In a study using 11 clinical samples, the specific fragment was detected by the nested PCR in 64% (7 of 11) of sera from patients with histologically diagnosed disseminated trichosporonosis, while glucuronoxylomannan antigen was detected in only 54% (6 of 11) of the samples. Our new nested-PCR assay using serum samples can be performed repeatedly throughout the course of the disease. In addition, not only can it be used for early diagnosis of trichosporonosis, but it may also be beneficial for monitoring its progress or response to therapy.

Aged↗

Angiographic and clinical significance of 'transient' ST-segment depression in the lateral chest leads in anterior wall acute myocardial infarction.

This study aimed to clarify the significance of ST-segment depression in the lateral chest leads in anterior wall acute myocardial infarction (AMI) with ST-segment elevation. A total of 196 patients with their first anterior wall AMI (< or =6h) were divided into 2 groups according to the presence (group A, n=39) or absence (group B, n=157) of ST-segment depression > or =0.1 mV in V5 and/or V6 on the admission electrocardiogram. Patients with electrocardiographic confounding factors were excluded. No patients had persistent ST-segment depression in the lateral chest leads. Emergency coronary angiography revealed that group A had higher incidences of occlusion of the left anterior descending coronary artery (LAD) proximal to its first septal branch (77% vs 51%, p<0.01) and good collateral circulation than group B (46% vs 25%, p<0.05). Peak creatine kinase levels were significantly lower in group A than in group B (2060+/-1099 vs 2873+/-2077 IU/L, p<0.01). Left ventricular ejection fraction in the chronic phase was significantly greater in group A than in group B. Regional wall motion in the infarct region in the chronic phase was better in group A than in group B. These results indicate that patients with 'transient' ST-segment depression in the lateral chest leads in anterior wall AMI had a relatively smaller infarct size, despite their higher incidence of occlusion of the LAD proximal to its first septal branch, because of their higher incidence of good collateral circulation.

Aged↗

Clinical usefulness of the proximal isovelocity surface area method using echocardiography in patients with eccentric aortic regurgitation.

BACKGROUND AND AIM OF THE STUDY: The Doppler color flow mapping techniques of the distal jet are influenced by the eccentricity of aortic regurgitation (AR). The aim of this study was to clarify screening variables for assessing AR severity in patients with an eccentric jet. METHODS: Fifty-four patients with eccentric AR were studied. Values of the radius and effective regurgitant orifice area (EROA) determined by the proximal isovelocity surface area (PISA) method using transthoracic echocardiography (TTE) were compared with measurements by multiplane transesophageal echocardiography (m-TEE), aortic angiography and regurgitant fraction. RESULTS: In patients with eccentric AR, values of PISA radius and EROA by TTE correlated well with values made by m-TEE (r = 0.87, p<0.001 and r = 0.86, p<0.001, respectively), angiographic grade (rs = 0.87, p<0.001 and rs = 0.88, p<0.001, respectively) and regurgitant fraction (r = 0.88, p<0.001 and r = 0.84, p<0.001, respectively). Values of PISA radius > or =0.70 cm and EROA > or =0.25 cm2 were always associated with a regurgitant fraction > or =0.40, while PISA radius <0.70 cm and EROA <0.25 cm2 were always associated with a regurgitant fraction <0.40. CONCLUSIONS: Measurements determined by the PISA method, using either TTE or m-TEE, are reliable for assessing the severity of eccentric AR. PISA radius is easy to obtain and therefore widely applicable in clinical practice as a screening tool for evaluating eccentric AR severity.

Adult↗

[Epstein-Barr virus associated Richter's syndrome accompanied by interstitial pneumonia].

A 65-year-old man who had an 8-year history of chronic lymphocytic leukemia was admitted to our hospital on February 19, 1998 because of high fever, dry cough, and weight loss. Laboratory data on admission included serum lactate dehydrogenase at 980 IU/l, CRP at 21.8 mg/dl, and soluble interleukin-2 receptor at 7,280 U/ml. The results of serological tests for Epstein-Barr virus (EBV) antibodies were as follows: EBV capsid antigen IgG 1:2560, EBV early antigen IgG 1:640, and EBV nuclear antigens 1:20. Computed tomography revealed diffuse interstitial pneumonia in both lungs, hepatosplenomegaly with multiple nodules, and enlarged intra-abdominal lymph nodes. In addition, Gallium-67 scintigraphy demonstrated abnormal accumulations. Although the patient initially responded well to combination chemotherapy, he eventually deteriorated and died on November 2, 1988, despite salvage chemotherapy. Postmortem needle biopsy specimens from the liver and spleen revealed diffuse proliferation of polymorphic large lymphoma cells. The lymphoma cells were positive for L-26, latent membrane protein 1, and EBV nuclear antigen, but negative for UCHL-1 and CD3, 5, 10, and 30. In situ hybridization procedures disclosed the presence of EBV-encoded small RNA in lymphoma cells. These findings suggested the possibility of association with EBV infection in some cases of Richter's syndrome.

Aged↗

[Efficacy of combination with granisetron and methylprednisolone for nausea, vomiting and appetite loss in remission induction chemotherapy of acute myeloid leukemia--a randomized comparative trial between granisetron alone and granisetron plus methylprednisolone].

The prevention of nausea, vomiting and appetite loss induced by remission induction chemotherapy for acute myeloid leukemia was compared by randomization between granisetron alone and combination with granisetron plus methylprednisolone. Granisetron was administered at 40 micrograms/kg during chemotherapy, and methylprednisolone was administered concomitantly at 125 mg/body for 3 days or more in the combination group. The single and combination groups comprised 14 and 13 patients, respectively, and there was no significant difference between the background of both groups. To evaluate the effect they were scored according to 4 grades, and evaluated every 24 hours from the start of chemotherapy to 5 days after its completion. The complete inhibition rate of vomiting was as high as 71.4% and 92.3% in the single and combination groups, respectively, showing no significant difference. The grade of vomiting was mild in both groups. Nausea was noted in 71.4% and 46.2%, respectively, and the inhibitory effect tended to be higher in the combination group. Appetite loss developed in 92.9% and 41.7%, respectively, and the prevention effect was clearly higher in the combination group. The prevention effects on nausea 7, 8 and 10 days after the start of chemotherapy, on appetite loss 2-10 days after it, and 2-5 days after its completion, were higher in the combination group. Granisetron revealed an excellent inhibitory effect on vomiting induced by remission induction chemotherapy for acute myeloid leukemia, but combination with granisetron and methylprednisolone was considered useful for nausea in the latter half of the treatment period and for appetite loss during the whole period.

Acute Disease↗

A rapid method for determination of the relative copy number of HTLV-I proviral genome in HTLV-I carriers and adult T-cell leukemia patients by polymerase chain reaction.

Ten adult T-cell leukemia (ATL) patients and 11 asymptomatic human T-cell leukemia virus type I (HTLV-I) carriers were examined by polymerase chain reaction (PCR) assay with a reduced sensitivity to evaluate its utility in detecting the relative copy number of the HTLV-I genome in clinical samples. Differences in the intensities of the PCR products were observed between the acute type ATL patients and ATL patients in remission or carriers. Intense bands were found in all acute type ATL patients (6/6, 100%), while specific bands were seen in only 2 carriers (2/11, 18.2%). The bands found in one of the two patients in remission were weak. One patient, who had acute type ATL, had achieved a remission but later relapsed. Using this technique, we examined the differences in the intensities of the bands of the PCR products in a patient with acute type ATL who had achieved remission but later relapsed. Thus, this technique may be of clinical importance in diagnosing acute ATL and assessing the effect of therapy.

Adult↗

Endpoint colorimetric method for assaying total cholesterol in serum with cholesterol dehydrogenase.

BACKGROUND: Various methods are available to measure serum cholesterol concentrations. Of these, the cholesterol ester hydrolase (CEH)-cholesterol oxidase-peroxidase chromogenic method is widely used. However, this method has the disadvantage of interference by reducing substances. We developed and evaluated an endpoint assay for serum cholesterol, based on a CEH-cholesterol dehydrogenase (CDH)-ultraviolet method. METHODS: Cholesterol esters are first hydrolyzed to free cholesterol by CEH. The free cholesterol is then reduced by CDH to cholest-4-ene-3-one with the simultaneous production of beta-NADH from beta-NAD(+). At equilibrium, the CDH reaction gives incomplete conversion of cholesterol to cholest-4-ene-3-one. To overcome this disadvantage, we added hydrazine monohydrate to the reaction mixture to remove cholest-4-ene-3-one, which allowed the reaction to proceed to completion and gave stoichiometric production of beta-NADH from the reaction of beta-NAD(+) with cholesterol. RESULTS: We tested whether the amount of cholesterol added was equivalent to the absorbance change of NADH at 340 nm with six aqueous samples. Recoveries were 97.1-100.3%. The reaction was linear up to 20.28 mmol/L. The mean within-day (n = 20) and between-day (n = 10) imprecision (CV) was 0. 29-0.43% and 0.22-0.61%, respectively. No interference by bilirubin, hemoglobin, ascorbic acid, and other reducing agents was observed. The equation obtained in comparison with the modified Abell-Levy-Brodie-Kendall method was: y = 0.992x - 0.0058 mmol/L; r = 0.997; S(y|x) = 0.117 mmol/L; n = 50. CONCLUSION: This method is an accurate, reliable method for serum cholesterol analysis and is amenable to automation.

Cholesterol↗

[Aortic valve papillary fibroelastoma in a patient with mitral valve regurgitation].

Papillary fibroelastoma is a rare cardiac tumour. We describe a patient with mitral valve regurgitation and aortic valve papillary fibroelastoma. The patient was 62-year-old woman. She was referred to us for surgical treatment of mitral valve. Preoperative echocardiography showed rheumatic mitral valve regurgitation (Sellers grade III) and it also demonstrated mobile masses of the aortic valve. At operation, mitral valve was repaired by a posterior annuloplasty. Through the aortotomy, small tumors were found to be attached to each cusps of the aortic valve and they were successfully removed. The histopathologic diagnosis was papillary fibroelastoma of the aortic valve. The postoperative course was uneventful.

Aortic Valve↗

Divergence of virulence factors of Helicobacter pylori among clinical isolates does not correlate with disease specificity.

The aim of this study was to examine the relation between disease specificity and the virulence factors of Helicobacter pylori isolated from patients with gastric cancer (GC), duodenal ulcer (DU), and gastritis (GS). Altogether 18 isolates obtained from patients with GC, 28 isolates from DU patients, and 13 isolates from GS patients were analyzed. All isolates were tested for the presence of the cagA gene, and genotyping of the vacA gene was done by the polymerase chain reaction. Production of VacA protein and expression of vacuolating cytotoxic activity in the H. pylori culture supernatant were examined. The serum antibody titers against purified VacA and CagA proteins were determined by enzyme-linked immunosorbent assay (ELISA). Interleukin-8 (IL-8) production by AGS cells in response to H. pylori isolates was measured by an hIL-8 ELISA kit. Genetic analysis of vacA revealed that most of the clinical isolates were classified into the S1a type by signal sequence typing. There were no differences in cagA detection rates, vacuolating cytotoxin activity, or mean antibody titers against VacA and CagA protein among the three groups. The mean IL-8 concentrations in the supernatants of AGS cells were similar in the three groups. In this study, there was no difference in virulence factors of H. pylori among isolates from GC, DU, and GS.

Antigens, Bacterial↗

Evidence for viability of coccoid forms of Helicobacter pylori.

It is an open question whether the coccoid form of Helicobacter pylori is alive in the dormant state or is degenerative and in the process of cell death. We studied the viability of the coccoid form of H. pylori to explore the possibility of infectivity to the host by evaluating its protein synthesis and acid response. Coccoid H. pylori conserved the capability to produce proteins for at least 100 days when stored at 4 degrees C in either phosphate-buffered saline (PBS) or distilled water. After 20 days of storage in distilled water exposure of the coccoids obtained to acidic pH induced expression of the several proteins but inhibited those induced after 20 days of storage in PBS. However, after extending the incubation of the coccoid forms in PBS up to 100 days, the organisms acquired the ability to induce the proteins in response to acid stress. The induction of protein expression may be involved in the biological event of transformation into the spiral form. Furthermore, this altered response of the coccoids to acid shock may determine the potential for morphological reversion during incubation.

Bacterial Proteins↗

What are the predictors of restoration of sinus rhythm after combined treatment with surgical repair for organic heart disease and the Maze procedure for atrial fibrillation?

BACKGROUND: Recently, combined treatment using the Maze procedure for organic heart disease and atrial fibrillation has been reported, but there have been few studies of cardiac rhythm after combined treatment. Predictors of cardiac rhythm after combined surgical treatment have been unknown. METHODS: Thirty patients who underwent cardiac surgery with the Maze procedure were retrospectively enrolled in this study. Two groups consisted of the patients with restoration of sinus rhythm after surgery (SR: n=15, 6 males and 9 females, mean age of 64 years), and the patients with maintenance of atrial fibrillation (AF; n=15, 5 males and 10 females, mean age of 61 years). Before cardiac surgery, all patients underwent exercise testing with measurement of atrial natriuretic peptide (ANP) before and after exercise testing, two-dimensional echocardiography, and right and left heart catheterization. RESULTS: The mean maximal heart rate and the ANP level after exercise testing in SR were significantly higher than those in AF. The left atrial dimension and right atrial and pulmonary capillary wedge pressures were significantly higher in AF than in SR. These findings indicate that subjects in SR exhibited less impaired atrial function which were evaluated by exercise testing with measurement of ANP, echocardiography, and cardiac catheterization. CONCLUSIONS: The atrial function of patients with sinus rhythm after the Maze procedure may be less impaired than that of patients remaining in atrial fibrillation.

Aged↗

Anisotropic neural interaction in the primary auditory cortex of guinea pigs with sound stimulation.

Neural interaction in the primary auditory cortex of guinea pigs anesthetized with sodium pentobarbital was studied using a single line multi-electrode (4 x 1) aligned across and along the isofrequency band. Under the spontaneous condition, the neural interaction was isotropic; the amplitude of cross-correlogram peaks decreased as the electrode separation increased both across and along the isofrequency band. Under tone stimulation, the neural interaction was anisotropic; the amplitude of peaks was decreased rapidly beyond 400 microm across the isofrequency band, while it decreased little up to 700 microm along the isofrequency band. This anisotropic interaction was dependent on the stimulus intensity.

Acoustic Stimulation↗