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Biomedical subjects

K Hirose

Publications and source records attributed to K Hirose.

At least 235 records · Page 13Linked to original sources
PubMed1995

Direct detection and isolation of restriction landmark genomic scanning (RLGS) spot DNA markers tightly linked to a specific trait by using the RLGS spot-bombing method.

We have developed a technique for isolating DNA markers tightly linked to a target region that is based on RLGS, named RLGS spot-bombing (RLGS-SB). RLGS-SB allows us to scan the genome of higher organisms quickly and efficiently to identify loci that are linked to either a target region or gene of interest. The method was initially tested by analyzing a C57BL/6-GusS mouse congenic strain. We identified 33 variant markers out of 10,565 total loci in a 4.2-centimorgan (cM) interval surrounding the Gus locus in 4 days of laboratory work. The validity of RLGS-SB to find DNA markers linked to a target locus was also tested on pooled DNA from segregating backcross progeny by analyzing the spot intensity of already mapped RLGS loci. Finally, we used RLGS-SB to identify DNA markers closely linked to the mouse reeler (rl) locus on chromosome 5 by phenotypic pooling. A total of 31 RLGS loci were identified and mapped to the target region after screening 8856 loci. These 31 loci were mapped within 11.7 cM surrounding rl. The average density of RLGS loci located in the rl region was 0.38 cM. Three loci were closely linked to rl showing a recombination frequency of 0/340, which is < 1 cM from rl. Thus, RLGS-SB provides an efficient and rapid method for the detection and isolation of polymorphic DNA markers linked to a trait or gene of interest.

Animals↗
PubMed1995

Relation of initial infarct size to extent of left ventricular remodeling in the year after acute myocardial infarction.

OBJECTIVES: This study attempted to determine the relation between infarct size after acute myocardial infarction and subsequent left ventricular remodeling using precise clinical measurements. BACKGROUND: Animal studies have demonstrated that the degree of left ventricular remodeling after myocardial infarction is linearly related to infarct size. Clinical studies have not clearly replicated these results because of imprecise measurements and failure to adjust for patency of the infarct-related artery. METHODS: Infarct size was measured from technetium-99m (Tc-99m) sestamibi perfusion images in 14 patients (12 with an anterior, 2 with an inferior infarction) by a threshold method previously described and expressed as percent of the left ventricle (32 +/- 17% left ventricle [mean +/- SD], range 6% to 58%). Absolute end-systolic volume, end-diastolic volume and ejection fraction were determined by electron beam computed tomographic images performed at discharge and at 6 weeks, 6 months and 1 year after myocardial infarction. All patients had documented infarct-related artery patency after reperfusion therapy. RESULTS: At hospital discharge, there was no correlation between infarct size and end-systolic and end-diastolic volumes or ejection fraction. There was significant left ventricular dilation in the study group over the next year. As remodeling progressed, there was closer correlation between infarct size and ejection fraction and end-systolic volume measures (infarct size vs. end-systolic volume, from r = 0.43 at discharge to r = 0.80 at 1 year; infarct size vs. ejection fraction, from r = -0.39 at discharge to r = -0.84 at 1 year). There was a strong inverse correlation between infarct size at discharge and subsequent changes over the next year in end-systolic volume (r = 0.63, p = 0.02) and ejection fraction (r = -0.66, p = 0.01). CONCLUSION: Infarct size as measured by Tc-99m sestamibi at hospital discharge after an index infarction is predictive of subsequent change in left ventricular volume and function in the year after myocardial infarction. Patients with a large infarct demonstrated the greatest degree of dilation in the setting of patency of the infarct-related artery.

Adult↗
PubMed1995

NM23-H1 and NM23-H2 messenger RNA abundance in human hepatocellular carcinoma.

nm23 was originally identified as an antimetastatic gene, the expression of which was inversely correlated with tumor metastatic potential in rodent model systems. Subsequently, two related human nm23 genes, nm23-H1 and nm23-H2, were identified. The relationship between expression of nm23-H1 and nm23-H2 in hepatocellular carcinoma specimens from 30 patients and metastatic potential was investigated with the use of a quantitative reverse transcription-PCR procedure. The abundance of nm23-H1 and nm23-H2 mRNA was compared with serum alpha-fetoprotein concentration, tumor size (maximum diameter), and histopathological parameters such as portal vein tumor thrombus, intrahepatic metastasis, capsular formation, capsular infiltration, differentiation of tumor cells, and TNM stage. The abundance of nm23-H1 mRNA showed a significant inverse correlation with intrahepatic metastasis and TNM stage. Furthermore, we confirmed that reduced expression of nm23-H1 mRNA was in accordance with a reduced amount of NM23-H1 protein using Western blot analysis. No correlation was apparent between nm23-H2 mRNA abundance and intrahepatic metastasis. These data support the conclusion that nm23-H1 may play a more important role than nm23-H2 in intrahepatic metastasis in hepatocellular carcinoma. Furthermore, nm23-H1 mRNA abundance may be a predictor of intrahepatic metastasis, the most important factor correlated with the metastatic potential of hepatocellular carcinoma.

Age Factors↗
PubMed1995

Accessibility to tissue-specific genes from methylation profiles of mouse brain genomic DNA.

The DNA methylation status of a large number of genomic loci is visualized simultaneously and quantitatively as two-dimensional gel spots in the newly developed restriction landmark genomic scanning with a methylation-sensitive restriction enzyme (RLGS-M). Here, we demonstrate that RLGS-M using NorI as a methylation-sensitive enzyme could also scan gene loci of mammalian genomes, since almost all of the NotI loci corresponding to randomly chosen RLGS-M spots were located near or in transcriptional units (6 out of 7 NotI-linking clones) when mouse brain genomic DNA was used. This supports the previous prediction that most NotI sites are located in CpG islands (Lindsay and Bird, Nature 1987, 327, 336-338). Furthermore, beginning with RLGS-M spots we examined how to approach their corresponding RNA messages, whose expression may be associated with methylation. We compared RLGS-M patterns among various developmental stages of the mouse brain from embryonic day 9.5 to postnatal 8 weeks or among in vitro cell lines, and detected alterations of RLGS-M spots which were due to methylation of NotI sites. Two experiments using NotI-linking clones or polymerase chain reaction (PCR) were carried out to approach to their corresponding RNA messages. Consequently, we isolated two PCR-amplified clones (# 15 and # 91) which corresponded to methylatable loci and gave positive signals to mRNA from the adult brain. Furthermore, we identified two NotI-linking clones (C211 and C198) whose corresponding NotI loci localized near or at transcriptional units and were methylated in cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Subsite-specific risk factors for colorectal cancer: a hospital-based case-control study in Japan.

To investigate the subsite-specific risk factors for colorectal cancer, we conducted a case-control study, using a common questionnaire which inquired about general lifestyles over the past five years (1988-92), at the Aichi Cancer Center Hospital, Nagoya, Japan. This study compared 432 patients with histopathologically diagnosed colorectal cancer (94 proximal colon [cecum, ascending colon, transverse colon]; 137 distal colon [descending colon, sigmoid colon]; 201 rectum [rectosigmoid, rectum]); and 31,782 first-visit outpatient controls who were free from cancer. In both genders, habitual smoking selectively increased the risk for rectum cancer. Soft or loose feces increased the risk for all subsites of colorectal cancer, particularly in female rectum cancer (odds ratio [OR] = 4.5). Among female dietary habits, Japanese-style foods decreased the risk for distal colon cancer, but increased the risk for proximal colon cancer. These results suggested that the risk factors for colorectal cancer differ by subsite among such a low-risk population as the Japanese. It is suggested also that 'irritable bowel' (soft or loose feces) might be associated with distal subsites of colorectal cancer, independently or combined with habitual smoking.

Adult↗
PubMed1995

Induction of gene expression for immunomodulating cytokines in peripheral blood mononuclear cells in response to orally administered PSK, an immunomodulating protein-bound polysaccharide.

The protein-bound polysaccharide extracted from a fungus, PSK, has been used as a biological response modifier in the treatment of cancer patients in Japan for over 16 years. The administration of PSK to tumor-bearing rodents inhibited tumor growth and modulated immune responses. Recently, an in vitro study has revealed that PSK is a strong inducer of cytokine gene expression and production in human peripheral blood mononuclear cells (PBMC). To establish whether PSK has cytokine-inducing activities in vivo, we have orally administered PSK (1 g, the clinical dose) to 12 healthy volunteers and 9 gastric cancer patients who had undergone gastrectomy, and assessed the gene expression for cytokines in PBMC of each subject. As determined by the reverse-transcribed polymerase chain reaction method, the induction of gene expression for both tumor necrosis factor alpha and interleukin-8 (IL-8) was detected in PBMC from 5 of the 12 healthy volunteers (42%) and 4 of the 9 patients (44%). Furthermore, the concentration of serum IL-8 was elevated in 5 healthy volunteers given PSK orally, who had shown induction of IL-8 gene expression, as detected by enzyme-linked immunosorbent assay. These findings indicate that responsiveness of PBMC to PSK, in terms of gene expression and production of cytokines, varies among individuals. Thus, when using PSK to treat cancer patients, it seems advisable to select patients on the basis of their responsiveness to PSK. We speculate that the cytokines induced by PSK might mediate the immunoenhancing action of this agent in vivo.

Adjuvants, Immunologic↗
PubMed1995

Protective activity and antigenic analysis of fractions of culture filtrates of Erysipelothrix rhusiopathiae.

The protective activity in mice and antigenic composition of the culture filtrate of 11 strains of Erysipelothrix rhusiopathiae were compared. Protective activity was found in the first (P-1) fraction obtained by Sephadex G-200 gel filtration of the culture filtrate of each strain. Comparing the 50% protective dose (PD50) of the P-1 fraction of the 11 strains by active immunization, highly protective activity was shown by 5 strains, such as Agata, Fujisawa, Shizuoka-63, Koganei 65-0.15 and SE-9. For the 50% effective dose (ED50) determined by passive protective studies, the four strains, Agata, Fujisawa, Koganei 65-0.15 and SE-9 were shown to be highly protective. However, strains 2179 and 2553 showed low activities in both PD50 and ED50. The highly and weakly protective strains were compared by western blot analysis for the protein components. In most strains tested, there were two protein bands of molecular weight of 64 kDa and 43 kDa. Therefore, these two structural proteins were common to the strains and were associated with stimulation of a protective effect in mice.

Animals↗
PubMed1995

Serial changes in left and right ventricular systolic and diastolic dynamics during the first year after an index left ventricular Q wave myocardial infarction.

OBJECTIVES: This study quantified serially biventricular emptying and filling after infarction and related these to changes in volume, muscle mass, wall stress and contractility. BACKGROUND: There are limited data on serial changes in ventricular dynamics after infarction. METHODS: Forty patients had serial electron beam computed tomographic examinations during the first year after index Q wave infarction (21 anterior, 19 inferior), and global biventricular volumes, peak rates of emptying and filling and left ventricular muscle masses were quantified. Mean mid-left ventricular end-systolic wall stresses, rate-corrected velocities of circumferential shortening and two indexes of left ventricular contractility--the end-systolic wall stress/volume ratio and the end-systolic wall stress/rate-corrected velocity of circumferential shortening relation--were estimated in each instance. RESULTS: Patients with anterior infarction had an increase in biventricular chamber volume of 15% to 35% by 1 year. Global biventricular peak rates of emptying and filling were decreased by 20% to 30% from hospital discharge to 6 weeks but thereafter remained unchanged. Despite a significant increase in mean wall stresses, the end-systolic wall stress/volume ratio remained unchanged during the year. The rate-corrected velocities of circumferential shortening declined serially after anterior infarction but did so in proportion to the increase in mean wall stresses, consistent with no net change in left ventricular contractility. Patients with inferior infarction showed a trend toward similar changes, but the magnitudes did not reach significance. CONCLUSIONS: Left (and right) ventricular global peak rates of emptying and filling during the first year after infarction can be altered in the absence of additional ischemic injury but are more consistent with responses to changes in left ventricular afterload than changes in intrinsic ventricular performance or contractility. Serial changes in left ventricular afterload after infarction are largely due to progressive chamber enlargement and limited development of compensatory hypertrophy during the first year. Intrinsic global left ventricular contractile performance was not altered by postinfarction cardiac remodeling in the patients examined.

Coronary Circulation↗
PubMed1995

Serial changes in regional right ventricular free wall and left ventricular septal wall lengths during the first 4 to 5 years after index anterior wall myocardial infarction.

OBJECTIVES: This study investigated serial changes in regional right ventricular free wall and interventricular septal wall lengths during the first 4 to 5 years after an index anterior wall myocardial infarction. BACKGROUND: We previously demonstrated that remodeling after anterior wall myocardial infarction was a biventricular process; however, regional changes in biventricular topology were not investigated. METHODS: Serial electron beam computed tomographic scanning was performed in 19 patients at five times (hospital discharge and at 6 weeks, 6 months, 1 year and 4 to 5 years) after an index anterior wall myocardial infarction, and global and regional right ventricular free wall and interventricular septal wall lengths were quantified. RESULTS: At a mean (+/- SD) of 1,642 +/- 171 days (4 to 5 years) after infarction, global end-diastolic and end-systolic right ventricular free wall and interventricular septal wall lengths increased in parallel by 13% to 23% as global left and right ventricular volumes increased 22% to 29% from hospital discharge to 4 to 5 years after infarction. When global right ventricular free wall was compared with interventricular septal wall lengths, percent increases at end-diastole and end-systole were not statistically different at any time during the study period. Distinct regional changes in both right ventricular free wall and interventricular septal wall lengths after infarction were most dramatic during the first 6 weeks and primarily confined to the most apical levels. However, further and significant increases in both were observed by 4 to 5 years after infarction. CONCLUSIONS: Changes in both right ventricular free wall and interventricular septal wall lengths were apparent during the 4 to 5 years after the index anterior wall infarction, and the combination of both contributed to global increases in right and left ventricular chamber volumes. Regional changes in both right ventricular free wall and interventricular septal wall lengths were almost exclusively confined to their respective apices and progressed generally in parallel; however, the cause-and-effect relation remains speculative at the present time.

Adult↗
PubMed1995

Surgical strategy for pheochromocytoma: emphasis on the pledge of flank extraperitoneal approach in selected patients.

BACKGROUND: Anterior transabdominal exploration has traditionally been advocated as the standard procedure for pheochromocytoma. However, some authors claim that a flank extraperitoneal approach with accurate unilateral localization is justifiable. METHODS: Retrospective analysis was performed on 87 patients with pheochromocytoma to determine the appropriateness of extraperitoneal exploration. RESULTS: There were 45 men and 42 women with a mean age of 44.7 years (range, 16 to 83 years). Fifteen patients (17.5%) had pheochromocytoma as a part of multiple endocrine neoplasia (MEN) type 2A, and four had familial pheochromocytoma, von Hippel-Lindau disease, or von Recklinghausen's disease. All tumors detected by preoperative localization studies were correctly identified and were resected through flank extraperitoneal (45 patients), transabdominal (28), thoracoabdominal (13), and posterior (1) approaches. Tumors were extraadrenal in 14, multiple in 22, bilateral in 12, and unequivocally malignant in 2 patients at the initial operation. Two patients died during the immediate postoperative period, giving an operative mortality of 2.3%. Two patients had persistent disease. During follow-up within a mean period of 5 years (range, 1 month to 13.7 years) 8 patients (9.1%) experienced recurrence or metastasis. Other than the patients with MEN 2, recurrence was not attributable to the operative approach. CONCLUSIONS: If a preoperative localization study is accurate, an extraperitoneal approach is justifiable for many patients with pheochromocytomas.

Adolescent↗
PubMed1995

Chemokine gene transfection into tumour cells reduced tumorigenicity in nude mice in association with neutrophilic infiltration.

To study the effect of localised secretion of chemokines on tumour growth, the genes for human (hu) interleukin 8 (IL-8), hu-MCP-1 (MCAF), hu-MIP-1 alpha (LD78), murine (mu)-MCP-1 (JE), mu-MIP-1 alpha or mu-MIP-2 were introduced, via mammalian expression vectors, into Chinese hamster ovary (CHO) cells, and the ability of transfected cells to form tumours in vivo was evaluated. The production of hu-IL-8, hu-MIP-1 alpha or mu-MIP-1 alpha by transfected clones did not influence the growth rate in vitro, but drastically suppressed tumour growth when injected subcutaneously (s.c.) into nude mice. However, clones transfected with hu-MCP-1, mu-MCP-1 or mu-MIP-2 did not show any significant difference in growth rate in vivo compared with clones transfected with vector alone. Histological examination of the site of injection of CHO clones transfected with hu-IL-8, hu-MIP-1 alpha or mu-MIP-1 alpha showed predominantly neutrophilic infiltration. These results indicate that chemokines have potent anti-tumour activity when released, even at low doses, at the tumour site, which may be mediated by recruitment and targeting of neutrophilic granulocytes to chemokine-releasing cells. Our studies highlight the potential usefulness of localised chemokine secretion in inducing potent host anti-tumour defensive responses.

Amino Acid Sequence↗
PubMed1995

The reeler gene encodes a protein with an EGF-like motif expressed by pioneer neurons.

We have identified a strong candidate cDNA for the mouse reeler gene. This 5 kb transcript encodes a 99.4 kD protein consisting of 881 amino acids and possessing two EGF-like motifs. We assayed two independent mutant alleles--'Jackson reeler', which has a deletion of the entire gene, and 'Orleans reeler' which exhibits a 220 bp deletion in the open reading frame, including the second EGF-like motif and resulting in a frame shift. In situ hybridization reveals that the transcript is detected exclusively in the pioneer neurons which guide neuronal cell migration along the radial array. Our findings offer an explanation for how the reeler mutant phenotype causes a disturbance of the complex architecture of the neuronal network.

Amino Acid Sequence↗
PubMed1995

Cytokine mRNA expression patterns in human esophageal cancer cell lines.

The mRNA expression for 21 kinds of cytokines was measured in six human esophageal cancer cell lines using RT-PCR. More than moderate levels of RNA for IL-1 alpha were expressed in six of six cell lines, IL-1 beta in four, IL-6 in six, IL-7 in five, IL-10 in six, G-CSF in six, GM-CSF in six, SCF in six, MIP-2 beta in two, and LIF in six. None of the tumors expressed detectable message for IL-2, 3, 4, 5, 8, 11, 13, or IRAP after 30 cycles of PCR amplification. IL-1 alpha, IL-6, M-CSF, and GM-CSF levels in the culture supernatants were detectable using ELISA in three of six, four of six, one of six, and six of six ECCs, respectively. IL-1 beta, IL-2, TNF-alpha, and G-CSF were not detectable in all ECCs. There was no correlation between cytokine mRNA expression and production. These results suggest the existence of a complicated cytokine network around esophageal carcinomas that may affect their growth and proliferation.

Base Sequence↗
PubMed1995

A large-scale, hospital-based case-control study of risk factors of breast cancer according to menopausal status.

We conducted a large-scale, hospital-based case-control study to evaluate differences and similarities in the risk factors of female breast cancer according to menopausal status. This study is based on a questionnaire survey on life style routinely obtained from outpatients who first visited the Aichi Cancer Center Hospital between January 1, 1988 and December 31, 1992. Among 36,944 outpatients, 1,186 women with breast cancer detected by histological examination were taken as the case group (607 premenopausal women and 445 postmenopausal women) and 23,163 women confirmed to be free of cancer were selected as the control group. New findings and reconfirmed factors of breast cancer were as follows. 1) The risk of at least one breast cancer history among subjects' first-degree relatives was relatively high among pre- as well as post-menopausal women. 2) A protective effect of physical activity against breast cancer was observed among both pre- and post-menopausal women. 3) Dietary control decreased the risk of premenopausal breast cancer. 4) Current smoking and drinking elevated the risk of breast cancer in premenopausal women. 5) Decreasing trends of breast cancer risk were associated with intake of bean curd, green-yellow vegetables, potato or sweet potato, chicken and ham or sausage in premenopausal women, while in postmenopausal women a risk reduction was associated with a more frequent intake of boiled, broiled and/or raw fish (sashimi). Further study will be needed to clarify the age group- and/or birth cohort-specific risk factors for breast cancer among the young generation in Japan.

Adult↗
PubMed1995

Expression of CD44 variant exons 8-10 in gastric cancer.

The expression of CD44 variant containing variant exons 8-10 product (CD44v8-10) was studied by western blot analysis and immunohistochemistry in gastric cancers using a monoclonal antibody, 44-1V. On western blots, a single band of 130 kD was recognized in stomach cancer cell lines. CD44v8-10 expression, with reactivity localized in the cell membrane, was found in 65 (33.5%) of the 194 advanced gastric cancers. There was no correlation between CD44v8-10 immunoreactivity and serosal, lymphatic, or lymph node invasion. However, there was significant correlation with CD44v8-10 immunoreactivity and venous invasion. CD44v8-10-positive cancers were more frequently associated with hematogenous metastasis than those which were immunonegative. There was an inverse association between CD44v8-10 immunoreactivity and peritoneal dissemination, especially in diffuse type adenocarcinomas. These observations indicate that CD44v8-10 may play a role in the metastasis of gastric cancer.

Adenocarcinoma↗