Biomedical subjects

T Kodama

Publications and source records attributed to T Kodama.

At least 271 records · Page 15Linked to original sources

PubMed1998

Dynamic behavior of bubbles during extracorporeal shock-wave lithotripsy.

The interaction of air bubbles attached to gelatin surfaces, extirpated livers or abdominal aortas of rats with underwater shock waves was investigated to help clarify the tissue-damage mechanism associated with cavitation bubbles induced during extracorporeal shock-wave lithotripsy. The overpressure of the shock wave was 10.2 +/- 0.5 MPa. The initial bubble radii varied from 0.12 to 3.06 mm. The subsequent collapse of the bubbles was recorded by a high-speed camera. The liver-cell damage was histochemically evaluated. The bubble attached to gelatin or rat's liver surface migrates away from the surface with an oscillatory growth/collapse behavior after the shock-wave interaction. The penetration depth of the liquid jet into the gelatin and the radius of the subsequent damage pit on the surface depend on the initial bubble radius. The elongation and split of the nuclei in the liver parenchymal cells in the direction of the liquid jet and the increase in the cell density within the circumference of the injured region are revealed histologically.

Animals↗

PubMed1998

Innovative technology for tissue disruption by explosive-induced shock waves.

We have developed a novel, less invasive, shock wave source that can be introduced into an arbitrary position in a human body percutaneously. Using this technique we can disrupt cells locally. The shock wave source consists of an explosive, an optical fiber, a balloon catheter, and a Nd:YAG laser, which generates a spherical explosive shock wave. The destructive potential of the present source for injuring tissue was confirmed and the subsequent cell elongation and split in the direction of the shock wave has been observed.

Animals↗

PubMed1998

Search for putative virulence factors of Helicobacter pylori: the low-molecular-weight (33-35 K) antigen.

Early studies suggested that two Helicobacter pylori proteins, CagA and VacA, were virulence factors. Support for that hypothesis has been undermined by geographic differences in prevalence of these antigens. To identify other possible putative virulence factors by establishing a relationship between antigens and different H. pylori diseases, two commercial available immunoblot assay kits, HelicoBlot 2.0 (Genelabs Diagnostics, Singapore) and RIDA Blot Helicobacter (R-Biopharm GmbH, Darmstadt, Germany), were used to investigate the prevalence of various specific antigen seropositivity in 80 H. pylori-infected Japanese (20 each with gastritis, duodenal ulcer, gastric ulcer, or gastric cancer). The production of interleukin-8 (IL-8) in biopsy specimens was also measured by enzyme-linked immunosorbent assay (ELISA). Both assays had 100% sensitivity; specificity was 90% for HB2.0 and 80% for RIDA-BH. With the exception of the 33-35 K antigen, there was no relationship between antigens, endoscopic diagnoses, histological findings, or mucosal IL-8 levels. The 33-35 K antigen was present in 97.5% (39 of 40) patients with gastric or duodenal ulcer compared to 70% (14 of 20) those with chronic gastritis (P < 0.006). The mean IL-8 levels in the corpus was significantly higher in those with antibody to the 33-35 K antigen compared to those without (105.4+/-22 pg/mg vs 10.2+/-8.8 pg/mg) (P=0.015). There was no relationship between other antigens including CagA and production of IL-8. In conclusion, the low-molecular-weight 33-35 K antigen may play an important role in the pathogenesis of H. pylori-related disease.

Antibodies, Bacterial↗

PubMed1998

Kimura's disease of the lacrimal gland.

A 33-year-old Japanese woman had bilateral eyelid swelling and soft tumor of the right orbit. Increased serum IgE and eosinophilia in the peripheral blood was observed. Magnetic resonance imaging of the lesion showed hypointense orbital fat on T1-weighted image and isointense orbital fat on T2-weighted image. Gd-DTPA T1-weighted images demonstrated marked enhancement. The histopathological appearance of the tumor was consistent with Kimura's disease. On a regimen of 60 mg of prednisone per day, the orbital mass reduced in size. A review of the recent literature indicated that corticosteroids rather than surgery might be tried at least initially as treatment.

Adult↗

PubMed1998

Microsatellite instability in female non-small-cell lung cancer patients with familial clustering of malignancy.

There is accumulating evidence of an increased risk of familial clustering of cancer in the first-degree relatives of lung cancer probands. However, no explanation has been proposed for these epidemiological data. We reviewed 379 female non-small-cell lung cancer (NSCLC) patients to obtain their family histories of malignancy. Among them, nine female NSCLC patients with three or more relatives diagnosed with malignancy and 28 control patients without a family history of malignancy were selected to be analysed for instability at six different microsatellite loci. We observed microsatellite instability (MSI) more frequently in the patients with three or more family histories of malignancy (six out of nine, 67%) than the control patients (5 out of 28, 18%). The incidence of MSI in the former was significantly higher than that in the control (P=0.011: Fisher's exact test). We detected no significant difference in clinicopathological characteristics between the cases with MSI and those without MSI, except for their family histories of cancer. Our results show that a significantly higher rate of MSI is associated with familial clustering of malignancy. MSI could be one of the underlying mechanisms for familial clustering of malignancy in female NSCLC patients.

Adenocarcinoma↗

PubMed1998

Potent and non-specific inhibition of cytochrome P450 by JM216, a new oral platinum agent.

Bis-acetato-ammine-dichloro-cyclohexylamine-platinum (IV), JM216, is the first antineoplastic platinum compound that can be given to patients orally. Several phase II clinical trials of JM216 monotherapy have already been reported. However, no information on the potential drug interactions caused by JM216 is available. In this study, the capacity of JM216 to inhibit cytochrome P450 (CYP) in human liver microsomes was investigated by measuring the inhibition potential (IC50 and Ki) on prototype reactions. Specific substrates of CYP included testosterone (catalysed by CYP3A4), paclitaxel (CYP2C8), 7-ethoxyresorufin (CYP1A1, CYP1A2), coumarin (CYP2A6), aniline (CYP2E1) and (+/-)-bufuralol (CYP2D6). JM216 inhibited the catalytic activities of CYP isozymes. The IC50 values were between 0.3 microM and 10 microM, indicating strong and non-specific inhibitory effects of JM216. The inhibition occurred in a non-competitive manner, and the Ki value was 1.0 and 0.9 microM for metabolite formation of testosterone and paclitaxel respectively. Therefore, some in vivo studies should be conducted to determine whether or not there is a correlation between in vivo and in vitro results.

Antineoplastic Agents↗

PubMed1998

Kinetics of apoptosis in the lung of mice with allergic airway inflammation.

BACKGROUND: Apoptosis has been suggested as a means to facilitate the resolution of eosinophilic inflammation in bronchial asthma. However, the natural course of apoptosis has not been elucidated in vivo, and there is no direct evidence for eosinophilic apoptosis within lung tissue. OBJECTIVE: The purpose of this study is to clarify whether the apoptosis occurs within the lung tissue, and to define the time-course of change in apoptosis ratio during the resolution of pulmonary eosinophilic inflammation. METHODS: Ovalbumin (OVA)-sensitized Balb/c mice were challenged with aerosolized OVA. We studied apoptotic cells in the lung of OVA-sensitized mice at 1, 3, 7 and 14 days after OVA challenge by in situ detection of DNA fragmentation with deoxynucleotidyl transferase deoxyuridyl triphosphatase nick endlabelling (TUNEL) technique. Apoptotic cells also were identified by electron microscopic analysis in the lung 7 days after OVA challenge. RESULTS: The TUNEL-method revealed that eosinophils localized in the subepithelium of bronchi undergo apoptosis following OVA challenge. Electron microscopy confirmed the presence of apoptotic cells, apoptotic bodies, and macrophages ingesting apoptotic bodies within the lung tissue. The number of apoptotic cells increased concomitantly with the increase in eosinophilic infiltration for 3 days post-challenge. However, both the apoptotic cell counts and the apoptotic ratio continued to increase even after the eosinophil count peaked, indicating rather late induction of apoptosis in the lung. In addition, TUNEL-positive cells were localized in the lung for 14 days post-challenge, indicating prolonged induction of apoptosis after the OVA challenge. CONCLUSION: Our findings constitute direct evidence of eosinophilic apoptosis in situ, and display the kinetics of apoptosis in the lung of the allergic inflammation.

Animals↗

PubMed1998

A Bacillus subtilis gene-encoding protein homologous to eukaryotic SMC motor protein is necessary for chromosome partition.

We have analysed the function of a gene of Bacillus subtilis, the product of which shows significant homology with eukaryotic SMC proteins essential for chromosome condensation and segregation. Two mutant strains were constructed; in one, the expression was under the control of the inducible spac promoter (conditional null) and, in the other, the gene was disrupted by insertion (disrupted null). Both could form colonies at 23 degree C but not at 37 degree C in the absence of the expression of the Smc protein, indicating that the B. subtilis smc gene was essential for cell growth at higher temperatures. Microscopic examination revealed the formation of anucleate and elongated cells and diffusion of nucleoids within the elongated cells in the disrupted null mutant grown at 23 degree C and in the conditional null mutant grown in low concentrations of IPTG at 37 degree C. In addition, immunofluorescence microscopy showed that subcellular localization of the SpoOJ partition protein was irregular in the smc disrupted null mutant, compared with bipolar localization in wild-type cells. These results indicate that the B. subtilis smc gene is essential for chromosome partition. The role of B. subtilis Smc protein in chromosome partition is discussed.

Bacillus subtilis↗

PubMed1998

Relationship of vacA genotypes of Helicobacter pylori to cagA status, cytotoxin production, and clinical outcome.

BACKGROUND: Mosaicism in vacA alleles with three distinct families of vacA signal sequences (s1a, s1b and s2) and two distinct families of middle region alleles (m1 and m2) has been reported. It was suggested that the vacA s1a genotype was closely associated with duodenal ulcer disease and with high cytotoxin production. The aim of this study was to evaluate the role of vacA genotyping with respect to gastric inflammation and injury, cytotoxin activity, and clinical presentation. METHODS: H. pylori from patients with gastritis, peptic ulcer disease, or gastric cancer were characterized by vacA typing by polymerase chain reaction (PCR) and DNA sequencing. In vitro cytotoxin activity was assessed by vacuolation assay using Vero cells as well as with Hela cells. RESULTS: Four hundred ninety-one strains were tested. vacA genotype s1a/m1 was present in more than 95% of strains independent of presentation with gastritis, peptic ulcer, or gastric cancer. No vacA genotype was associated with high average cytotoxin activity. The s2/m2 isolates had low or absent cytotoxin activity. All cagA negative strains (n = 18) were s1a strains and both s2/m2 strains were cagA positive. One strain that was a recombinant of m1 and m2 strains was identified and had low cytotoxin activity. The nucleotide and amino acid sequences between original m1 strains and Japanese m1 strains (new m1 strains) were about 85% and 81%, respectively. Strains with the new m1 genotype had nucleotide and amino acid sequences similarity of more than 96%. There was no difference in cytotoxin activity between strains with the Western type m1 and the new type m1 genotype. CONCLUSION: In this as in other reported studies ( approximately 1500 patients overall) vacA genotype was strongly but not exclusively associated with the presence of cagA. Overall, the studies did not support a role for vacA genotyping in relation to cytotoxin activity, virulence, histologic finding, or risk of a particular H. pylori disease. vacA genotype s1 is likely to be a surrogate marker for the presence of the cag pathogenicity island.

Adult↗

PubMed1998

A case of microphthalmos with cyst and partial trisomy 22.

A 13-day-old girl was referred for evaluation of a right orbital mass. Ophthalmic examinations revealed microphthalmia with cyst in the right eye and microphthalmia in the left eye. She had lowset ears, auricular fistula, micrognathia, and muscular hypotonia. Chromosomal analysis using fluorescence in-situ hybridization (FISH) showed partial trisomy 22. To our knowledge, microphthalmos with cyst associated with partial trisomy 22 has not been described previously in the English literature. Repeated aspiration resulted in a decrease in size of the cyst.

Chromosomes, Human, Pair 22↗

PubMed1998

Characteristic changes of large granular lymphocytes that strongly express CD56 in endometrium during the menstrual cycle and early pregnancy.

Large granular lymphocytes that strongly express CD56 (CD56++ LGL) constitute a major population of leukocytes in the secretory endometrium and pregnancy decidua and are considered to be involved in reproductive immunity and in maintaining the pregnancy. The present study aimed to reveal the relationship between the characteristic changes of CD56++ LGL and altered hormonal environment and/or trophoblast invasion in the endometrium. Cell surface markers of CD56++ LGL obtained from the endometrium during the menstrual cycle and early pregnancy were analysed using flow cytometry. The percentages of both CD56++ LGL that express activation antigens (CD69, HLA-DR) and those that express lymphocyte function associated antigen-1 (LFA-1) (CD11a/CD18) were highest in the proliferative phase and decreased gradually throughout the menstrual cycle. Expression of these antigens was further suppressed in the late secretory phase, as well as in the early stage of pregnancy. However, the percentage of CD56++ LGL that express these antigens was significantly higher in spontaneous abortions than in normal pregnancies. On the other hand, the percentage of CD56++ LGL that express CD45RA was lower during normal pregnancy than during the menstrual cycle. The present results suggest that characteristics alterations of CD56++ LGL are regulated by altered hormonal environment and by trophoblast invasion.

Abortion, Spontaneous↗

PubMed1998

Factors that influence the eligibility of cases for inclusion in clinical trials. The Lung Cancer Chemotherapy Study Group of the Japan Clinical Oncology Group.

BACKGROUND: It is important to minimize the incidence of ineligible cases to improve the quality of clinical trials. To determine factors which may influence the incidence of ineligible cases, the incidence of and reasons for ineligibility in clinical trials were retrospectively analyzed. METHODS: We retrospectively examined the incidence of and reasons for ineligibility for inclusion in eight clinical trials conducted by the Lung Cancer Chemotherapy Study Group of the Japan Clinical Oncology Group and four trials financed by trust funds from a pharmaceutical company. RESULTS: In these 12 clinical studies, the incidence of ineligibility was 4.2% (32/762) (range 0-10.6%). Specific factors that might influence the incidence of ineligible cases were then analyzed. There was a significant difference in the incidence of ineligibility between the methods of registration (P < 0.05). The incidences using a central registration and without using a central registration system were 2.8% (9/322) and 5.2% (23/440) respectively. We also analyzed ineligible cases in clinical studies published in the Journal of Clinical Oncology. In clinical studies published in the Journal of Clinical Oncology recently and 10 years ago, the incidences of ineligible cases were 5.0% (942/18 878) and 4.1% (206/4995) respectively. In clinical studies on lung cancer published in the Journal of Clinical Oncology from 1984 to 1995, the incidence of ineligible cases was 4.7% (900/19,116). There was no significant difference in the incidence of ineligible cases between our 12 studies and the Journal of Clinical Oncology clinical studies by the chi 2 test (P > 0.05). CONCLUSIONS: We conclude that the incidence of ineligible cases in our studies is similar to that in clinical trials published in the Journal of Clinical Oncology. Central registration systems are useful for checking for ineligibility, and to increase the quality of clinical trials.

Clinical Trials as Topic↗

PubMed1998

Primary unknown cancer in pulmonary hilar lymph node with spontaneous transient regression: report of a case.

A 69-year-old man was referred to our hospital in December 1993 because an abnormal mass had been detected in the right pulmonary hilum. Computed tomography (CT) of the chest revealed a swollen hilar lymph node between the right middle and lower lobe bronchi, and an adherent tumor in the right ventrobasal segment (S8). Chest roentgenogram in February 1994, however, showed no evident tumor in the right lung field. In March 1996, the mass in the right pulmonary hilum reappeared on chest roentgenogram. Chest CT revealed a swollen hilar lymph node between the right middle and lower lobe bronchi, but there was no tumor in right S8. The patient underwent video-assisted thoracoscopy on 17 May 1996. Intraoperative needle biopsy of the node revealed cancer cells. We performed right middle and lower bilobectomy with mediastinal dissection. Histological diagnosis revealed a large cell carcinoma almost completely occupying a hilar lymph node. The resected middle and lower lobes showed no tumors, except for a coagulation necrosis measuring 1.5 cm in diameter in S8b, corresponding to the site where a tumor shadow had been depicted on the CT image in December 1993. We concluded that the coagulation necrosis might have been the primary site of the tumor, which had spontaneously regressed and then appeared in the metastatic interlobar node.

Aged↗

PubMed1998

Hypocholesterolemic effects of the LDL receptor gene transcriptional upregulator CP-230821.

CP-230821 is a novel, potent LDL receptor gene transcriptional upregulator which decreases total plasma cholesterol level. Interestingly, this plasma LDL decrease does not alter hepatic lipid contents. A series of experiments was undertaken to study the molecular biology of this phenomenon. Twelve hours after CP-230821 treatment, the transcriptional activity and mRNA level of the LDL receptor gene in HepG2 cells were increased by 264% and 426%, respectively. Although treatment with the HMG-CoA reductase inhibitor compactin also increased LDL receptor gene transcription and mRNA, CP-230821 did not increase the level of HMG-CoA reductase gene transcription or mRNA. These results indicate that LDL receptor gene activity may play an important role in the decrease of plasma LDL level. These results further suggest that the LDL receptor gene and the HMG-CoA reductase gene are not strictly coordinately controlled.

Animals↗

PubMed1998

Glycolaldehyde-modified low density lipoprotein leads macrophages to foam cells via the macrophage scavenger receptor.

It was shown that proteins modified with advanced glycation end products (AGE) are effectively endocytosed by macrophages or macrophage-derived cells in vitro, and immunohistochemical studies involving anti-AGE antibodies demonstrated the accumulation of AGE-modified proteins (AGE-proteins) in macrophage-derived foam cells in human atherosclerotic lesions in situ, suggesting the involvement of AGE-modified LDL in the atherogenic process in vivo. To examine this suggestion, LDL was modified with glycolaldehyde, a highly reactive intermediate of the Maillard reaction. Physicochemically, glycolaldehyde-modified LDL (GA-LDL) was characterized by increases in negative charge, fluorescence intensity, and reactivity to anti-AGE antibodies, properties highly similar to those of AGE-proteins. The cellular interaction of GA-LDL with mouse peritoneal macrophages showed that GA-LDL was specifically recognized and endocytosed, followed by lysosomal degradation. The endocytic uptake of GA-LDL by these cells was competitively inhibited by acetylated LDL (acetyl-LDL), and the endocytic degradation of acetyl-LDL was also competed for by GA-LDL. Furthermore, incubation of GA-LDL with these macrophages and Chinese hamster ovary cells overexpressing the macrophage scavenger receptor (MSR), but not with peritoneal macrophages from MSR-knockout mice, led to the intracellular accumulation of cholesteryl esters (CE). These results raised the possibility that AGE-modified LDL, if available in situ, is taken up by macrophages mainly via MSR and then contributes to foam cell formation in early atherosclerotic lesions.

Acetaldehyde↗

PubMed1998

A new deleted allele in the human cytochrome P450 2A6 (CYP2A6) gene found in individuals showing poor metabolic capacity to coumarin and (+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502).

The S-oxidation of (4)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) and the 7-hydroxylation of coumarin are primarily catalyzed by cytochrome P450 2A6 (CYP2A6). The activities of SM-12502 S-oxidase and coumarin 7-hydroxylase were investigated with liver microsomes from 20 human individuals. Liver microsomes from individual H16 showed the lowest activities of both enzymes. The expression of CYP2A6 protein was not detectable in liver microsomes from individuals H4, H5, H7, H8, H12 and H16. CYP2A6 mRNA was hardly detectable in the liver of the individual H16. A new SacI-restriction fragment length polymorphism showing the lack of a 2.6 kb fragment was found in two of forty genomic DNA preparations from individuals H16 and No. 594, using CYP2A6 cDNA as a probe. This deletional 2.6 kb fragment was isolated from a genomic library prepared from one individuals showing normal coumarin 7-hydroxylase activity and was sequenced. This fragment contained a CYP2A6 gene region from 319 bp upstream of a putative exon 6 to a SacI site in exon 9, indicating that this region was deleted in the two individuals in this study. We also demonstrated by polymerase chain reaction analysis that the exon 8 of CYP2A6 gene was deleted in individuals H16 and No. 594. These results indicate that the reduced activity of SM-12502 S-oxidase and no activity of coumarin 7-hydroxylase are caused by the lack of CYP2A6 mRNA and CYP2A6 protein caused by the CYP2A6 gene deletion.

Aryl Hydrocarbon Hydroxylases↗

PubMed1998

Characterization of anti-histone antibodies in patients with type 1 autoimmune hepatitis.

We have recently found that antibodies to total histones are common in a group of American patients with type 1 autoimmune hepatitis (AIH). In an attempt to determine the profile and clinical association of anti-histone antibody (AHA), 45 Japanese AIH patients were studied for serum isotypic reactivity with individual histones (H1, H2A, H2B, H3, H4) by enzyme-linked immunosorbent assay and western blotting. The results revealed that 40% of sera had reactivities with at least one of individual histones and that the antibodies were detected in all three classes of immunoglobulins (IgG, IgM, IgA). Immunoglobulin G type anti-H3 showed the dominant reactivity and it characterized 72% of sera with AHA. The titre of anti-H3 decreased significantly (P < 0.0075) after steroid therapy and the index of decrease for anti-H3 was correlated in individuals with that for serum aminotransferase. In general, patients with AHA showed higher serum level of alanine aminotransferase (P < 0.05), immunoglobulin G (P < 0.025), and higher frequency of A2-DR4 haplotype (53 vs 17%) than their seronegative counterparts. However, the titre of AHA was low in this disease condition and histone class-specific antibodies did not distinguish patients with distinctive clinical features, although patients with anti-H3 tended to be younger than those without AHA.

Adolescent↗

PubMed1998

Analysis of the 13C-urea breath test for detection of Helicobacter pylori infection based on the kinetics of delta-13CO2 using laser spectroscopy.

We have previously reported on laser spectroscopy as a simple alternative to mass spectrometry. To validate a simplified 13C-urea breath test (UBT) with laser spectroscopy for the detection of Helicobacter pylori in clinical use, we evaluated the optimal time of breath sample collection. The 13C-UBT was carried out on each of 102 infected and 70 non-infected subjects (32 without eradication and 38 after eradication therapy). Breath samples were taken at five time points within 60 min followed by 100 mg of 13C-urea administration. The ratio of 13CO2 to 12CO2 was measured using laser spectroscopy and the recovery of tracer in the exhaled breath was calculated. Results were compared with histological and culture examinations of gastric biopsies to establish the infection status. For statistical evaluation of 13C-UBT, the optimal timing of breath sample collection was examined on the basis of the kinetics of delta-13CO2. In 32 H. pylori-negative patients (without therapy), the mean +/- 2SD of delta-13CO2 was at its minimum 20 min after urea ingestion whereas in H. pylori-positive patients, the mean +/- SD delta-13CO2 was maximum at 20 min. In addition, receiver operating characteristic (ROC) curve analysis showed that the cut-off value was estimated between 2.5-3.0 per mil (%0) at 20 min before therapy. Based on the histology and culture results, the sensitivity, specificity and positive and negative predictive values were 98.0%, 100%, and 94.1%, respectively. In conclusion, 13C-UBT with laser spectroscopy is a non-invasive, simple, sensitive and specific test to determine H. pylori status. Our findings suggest that in clinical use, measurements made at 20 min after substrate administration could be recommended for most sensitive and specific 13C-UBT results.

2-Pyridinylmethylsulfinylbenzimidazoles↗