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Biomedical subjects

C Matsumoto

Publications and source records attributed to C Matsumoto.

At least 19 recordsLinked to original sources

Sex- and age-related response to aromatase deficiency in bone.

Deficiency of sex steroids causes osteoporosis, but the relationship between estrogen and androgen is not clear because androgen is converted into estrogen by aromatase. In this study, we characterized bone metabolism in the aromatase-deficient (ArKO) mouse. At 9 weeks old, a marked loss of cancellous bone due to increased bone resorption was observed not only in female ArKO mice but also in males. The degree of bone loss in ArKO males was similar to that in females, and treatment with 17beta-estradiol completely restored the bone mass in both sexes. At 32 weeks old, female ArKO mice showed severe loss of cancellous and cortical bone. Male ArKO mice of this age also showed reduced bone mass, but the degree of bone loss in females was more marked than that in males. Here, we report sex- and age-related responses to aromatase deficiency in bone.

Age Factors↗

Modulation of apolipoprotein E-mediated plasma clearance and cell uptake of emulsion particles by cholesteryl ester.

Cholesteryl ester, along with triglyceride (TG), is the major core component of plasma lipoproteins. We investigated the effect of core composition on the physical state and metabolic behavior of lipid emulsions, as model particles of lipoproteins. Fluorescence studies using 1,6-diphenylhexatriene analogs showed that although cholesteryl oleate (CO) significantly decreased core mobility, the surface rigidity of phosphatidylcholine (PC) monolayers was independent of core composition. When intravenously injected into rats, the increased amount of core CO tended to retard TG emulsion removal from plasma, and the initial clearance rate was correlated with the amount of apolipoprotein E (apoE) bound from plasma. In addition, PC liposomes with a similar emulsion particle size showed negligible binding of apoE and were cleared at a slower rate compared to all emulsions. Furthermore, the effect of CO on the binding behavior of apoE to the emulsion surface and the emulsion uptake by hepatocytes was assessed in vitro. Replacing core TG with CO was found to decrease the apoE binding capacity to emulsions markedly without changing the binding affinity and thereby to reduce the cell uptake of emulsion particles by HepG2 cells. These results indicate that the physical state of core lipids, which can be modulated by CO content, plays a role in emulsion metabolism through the alteration in apoE binding.

Apolipoproteins E↗

Molecular epidemiologic analysis of Vibrio cholerae O1 isolated during the 1997-8 cholera epidemic in southern Thailand.

An unusually high incidence of Vibrio cholerae O1 infection was observed in southern Thailand between late December 1997 and March 1998. Fifty-seven V. cholerae O1 strains were isolated in five provinces during this epidemic and were examined. They were El Tor Ogawa strains exhibiting similar antibiograms. All strains were resistant to tetracycline, which had not been reported in Thailand since 1993. The ribotypes. hybridization patterns with ctx and zot gene probes, arbitrarily primed PCR profiles, and pulsed-field gel electrophoresis profiles of the representative strains were compared with the clinical strains isolated from patients in India and Bangladesh in 1997 and 1998 and from international travellers originating from various Asian countries during the 1992-8 period. All southern Thailand strains and the 1998 international traveller strain of Thai origin showed indistinguishable genetic fingerprinting patterns that were distinct from those of other test strains. The results suggest that a tetracycline-resistant clone newly emerged in late December 1997 caused the large epidemic in southern Thailand and that the variants with a slightly different antibiogram appeared during the course of the spreading epidemic.

Cholera↗

Analysis of HBV infection after blood transfusion in Japan through investigation of a comprehensive donor specimen repository.

BACKGROUND: To understand the risk of transfusion-transmitted viral infection, it is important to precisely assess cases of infection that follow transfusion. STUDY DESIGN AND METHODS: HBV infections noted after transfusion in 1997, 1998, and 1999 were analyzed. Transfusion in all these cases was performed before NAT was adopted for donor screening. To detect viral infection, PCR and serologic tests for HBV were performed retrospectively on all blood samples from implicated donors that had been stored in a frozen state after each donation. The concentration of HBV genome was measured in HBV-positive blood samples. RESULTS: One hundred three cases of HBV infection were analyzed; of these, only 16, including at least 10 infections due to window-period (HBsAg-positive by reverse particle hemagglutination assay) donations, were confirmed by further testing to be related to transfusion. The concentrations of HBV genome were very low in four blood samples (<50, 400, 500, and 800 genome equivalents/mL of plasma). CONCLUSIONS: The remaining risk of transfusion transmission of HBV infection before the adoption of NAT was mainly due to window-period donations, including one that was made before the HBV genome was detectable by PCR. However, it was determined that transfusion was not responsible in many cases for HBV infection after transfusion.

Blood Donors↗

One hundred nine living donor liver transplants in adults and children: a single-center experience.

OBJECTIVE: To summarize the evolution of a living donor liver transplant program and the authors' experience with 109 cases. SUMMARY BACKGROUND DATA: The authors' institution began to offer living donor liver transplants to children in 1993 and to adults in 1998. METHODS: Donors were healthy, ages 18 to 60 years, related or unrelated, and ABO-compatible (except in one case). Donor evaluation was thorough. Liver biopsy was performed for abnormal lipid profiles or a history of significant alcohol use, a body mass index more than 28, or suspected steatosis. Imaging studies included angiography, computed tomography, endoscopic retrograde cholangiopancreatography, and magnetic resonance imaging. Recipient evaluation and management were the same as for cadaveric transplant. RESULTS: After ABO screening, 136 potential donors were evaluated for 113 recipients; 23 donors withdrew for medical or personal reasons. Four donor surgeries were aborted; 109 transplants were performed. Fifty children (18 years or younger) received 47 left lateral segments and 3 left lobes; 59 adults received 50 right lobes and 9 left lobes. The average donor hospital stay was 6 days. Two donors each required one unit of banked blood. Right lobe donors had three bile leaks from the cut surface of the liver; all resolved. Another right lobe donor had prolonged hyperbilirubinemia. Three donors had small bowel obstructions; two required operation. All donors are alive and well. The most common indications for transplant were biliary atresia in children (56%) and hepatitis C in adults (40%); 35.6% of adults had hepatocellular carcinoma. Biliary reconstructions in all children and 44 adults were with a Roux-en-Y hepaticojejunostomy; 15 adults had duct-to-duct anastomoses. The incidence of major vascular complications was 12% in children and 11.8% in adult recipients. Children had three bile leaks (6%) and six (12%) biliary strictures. Adult patients had 14 (23.7%) bile leaks and 4 (6.8%) biliary strictures. Patient and graft survival rates were 87.6% and 81%, respectively, at 1 year and 75.1% and 69.6% at 5 years. In children, patient and graft survival rates were 89.9% and 85.8%, respectively, at 1 year and 80.9% and 78% at 5 years. In adults, patient and graft survival rates were 85.6% and 77%, respectively, at 1 year. CONCLUSION: Living donor liver transplantation has become an important option for our patients and has dramatically changed our approach to patients with liver failure. The donor surgery is safe and can be done with minimal complications. We expect that living donor liver transplants will represent more than 50% of our transplants within 3 years.

ABO Blood-Group System↗

[Effect of stimulus size on binocular summation within the binocular visual field].

PURPOSE: To study the influence of stimulus sizes on binocular summation using the modified Octopus 201 combined with a space synoptophore. METHODS: Four normal subjects, aged 21 to 26 were tested. Using the SARGON program, we designed a new program to test 37 points in the central 6 degrees visual field. Sensitivity of the central 6 degrees visual field under monocular and binocular conditions was measured while the fusion patterns were displayed on the space synoptophore. The visual fields were measured at stimulus sizes 1, 3, and 5. RESULTS: The visual sensitivity under binocular conditions was higher than under monocular conditions for all the stimulus sizes. Binocular summation for stimulus size 1 was present in a flat form, for stimulus size 3 in a convex form, and for stimulus size 5 in a concave form in the central 6 degrees visual field. CONCLUSION: Binocular summation differed in stimulus size and retinal eccentricity. Binocular summation for stimulus size 3 increased in the fovea and it increased for stimulus size 5 in the peripheral area in the central 6 degrees visual field.

Adult↗

Case of the Month. Giant multiple intraductal papilloma of the breast: a case report and review of the literature.

A case is described of multiple intraductal papilloma of the breast in a 39 year old Micronesian female who presented to our institution with a 2 year history of spontaneous bloody nipple discharge with an associated giant cystic breast mass. This case report illustrates an unusual presentation of a rare benign breast lesion. The clinical, radiographic, and pathologic features of this disease process are discussed; the literature is reviewed; and management options are discussed.

Adult↗

A high-throughput screening utilizing intramolecular fluorescence resonance energy transfer for the discovery of the molecules that bind HIV-1 TAR RNA specifically.

A 16-residue peptide, including the Tat(49-57) sequence was labeled with a fluorescein and a tetramethylrhodamine at its N- and C-terminus, respectively. This double dye-labeled peptide was prepared as a tracer for high-throughput screening utilizing intramolecular fluorescence resonance energy transfer (FRET). The binding of the competitor molecules for HIV-1 TAR RNA were monitored and dissociation constants of those molecule were determined by using this tracer. This novel screening system might be useful to discover the drug for HIV-1 TAR RNA.

Drug Evaluation, Preclinical↗

Effects of pneumoperitoneum on cardiac autonomic nervous activity evaluated by heart rate variability analysis during sevoflurane, isoflurane, or propofol anesthesia.

BACKGROUND: The effects of pneumoperitoneum on the activity of the cardiac autonomic nervous system have not been completely understood. METHODS: In this study, 45 unpremedicated adult patients who underwent laparoscopic cholecystectomy were anesthetized with either 3.5% sevoflurane, 2% isoflurane, or 8 mg/kg/h propofol (15 patients in each group). The status of cardiac autonomic nervous activity was evaluated by heart rate variability analysis three times: once when the patient was awake, once after induction of general anesthesia, and once after insufflation for pneumoperitoneum. Intra-abdominal pressure was maintained automatically at 10 mm Hg by a carbon dioxide (CO(2)) insufflator. For each measurement, electrocardiogram was recorded for 256 s and played back offline to detect R-R intervals. Power spectral analysis of heart rate variability was applied, and the low-frequency (LF, 0.04-0.15 Hz) and high-frequency (HF, 0.15-0. 40 Hz) bands of the spectral density of the heart rate variability were obtained from a power spectra of R-R intervals using the fast-Fourier transform algorithm. The HF/LF ratio also was analyzed. RESULTS: Measurements of heart rate variability in the three groups showed similar change. Although the power of HF, which represents parasympathetic nervous activity, did not change, the power of LF, which represents both sympathetic and parasympathetic nervous activity, decreased during the anesthetized stage and increased during the insufflated stage. The HF/LF ratio, which represents the balance of parasympathetic and sympathetic activity, increased after induction of general anesthesia, and decreased after insufflation. CONCLUSIONS: Our results suggest that pneumoperitoneum increases sympathetic cardiac activity. The choice of general anesthetic did not seem to have a major influence on the change in the cardiac autonomic nervous system after induction of pneumoperitoneum for laparoscopic cholecystectomy.

Adult↗

Isolation of a pandemic O3:K6 clone of a Vibrio parahaemolyticus strain from environmental and clinical sources in Thailand.

Application of an immunomagnetic enrichment method selective for Vibrio parahaemolyticus serovar K6 allowed isolation of a strain belonging to the pandemic O3:K6 clone of V. parahaemolyticus from fresh shellfish not implicated in a clinical case in southern Thailand. Arbitrarily primed PCR profiles of this strain, clinical O3:K6 strains isolated from sporadic diarrhea cases in the same area, and a standard pandemic O3:K6 strain were indistinguishable.

Animals↗

Analysis of gyrB and toxR gene sequences of Vibrio hollisae and development of gyrB- and toxR-targeted PCR methods for isolation of V. hollisae from the environment and its identification.

Isolation of Vibrio hollisae strains, particularly from the environment, is rare. This may be due, in part, to the difficulty encountered when using conventional biochemical tests to identify the microorganism. In this study, we evaluated whether two particular genes may be useful for the identification of V. hollisae. The two genes are presumed to be conserved among the bacterial species (gyrB) or among the species of the genus Vibrio (toxR). A portion of the gyrB sequence of V. hollisae was cloned by PCR using a set of degenerate primers. The sequence showed 80% identity with the corresponding Vibrio parahaemolyticus gyrB sequence. The toxR gene of V. hollisae was cloned utilizing a htpG gene probe derived from the V. parahaemolyticus htpG gene, which is known to be linked to the toxR gene in V. hollisae. The coding sequence of the cloned V. hollisae toxR gene had 59% identity with the V. parahaemolyticus toxR coding sequence. The results of DNA colony hybridization tests using the DNA probes derived from the two genes of V. hollisae indicated that these gene sequences could be utilized for differentiation of V. hollisae from other Vibrio species and from microorganisms found in marine fish. PCR methods targeting the two gene sequences were established. Both PCR methods were shown to specifically detect the respective target sequences of V. hollisae but not other organisms. A strain of V. hollisae added at a concentration of 1 to 10(2) CFU/ml to alkaline peptone water containing a seafood sample could be detected by a 4-h enrichment incubation in alkaline peptone water at 37 degrees C followed by quick DNA extraction with an extraction kit and 35-cycle PCR specific for the V. hollisae toxR gene. We conclude that screening of seafood samples by this 35-cycle, V. hollisae toxR-specific PCR, followed by isolation on a differential medium and identification by the above htpG- and toxR-targeted PCR methods, can be useful for isolation from the environment and identification of V. hollisae.

Animals↗

Pandemic spread of an O3:K6 clone of Vibrio parahaemolyticus and emergence of related strains evidenced by arbitrarily primed PCR and toxRS sequence analyses.

Vibrio parahaemolyticus O3:K6 strains responsible for the increase in the number of cases of diarrhea in Calcutta, India, beginning in February 1996 and those isolated from Southeast Asian travelers beginning in 1995 were shown to belong to a unique clone characterized by possession of the tdh gene but not the trh gene and by unique arbitrarily primed PCR (AP-PCR) profiles (J. Okuda, M. Ishibashi, E. Hayakawa, T. Nishino, Y. Takeda, A. K. Mukhopadhyay, S. Garg, S. K. Bhattacharya, G. B. Nair, and M. Nishibuchi, J. Clin. Microbiol. 35:3150-3155, 1997). Evidence supporting a hypothesis that this clone emerged only recently and is spreading to many countries was obtained in this study. Of 227 strains isolated in a hospital in Bangladesh between 1977 and 1998, only 22 strains isolated between 1996 and 1998 belonged to the new O3:K6 clone (defined by the serovar, the tdh and trh typing, and AP-PCR profiles). The O3:K6 strains isolated from clinical sources in Taiwan, Laos, Japan, Thailand, Korea, and the United States between 1997 and 1998 were also shown to belong to the new O3:K6 clone. The clonality of the new O3:K6 strains was also confirmed by analysis of the toxRS sequence, which has been shown to be useful for phylogenetic analysis of the members of the genus Vibrio. The toxRS sequences of the representative strains of the new O3:K6 clone differed from those of the O3:K6 strains isolated before 1995 at least at 7 base positions within a 1,346-bp region. A new PCR method targeted to 2 of the base positions unique to the new O3:K6 clone was developed. This PCR method could clearly differentiate all 172 strains belonging to the new O3:K6 clone from other O3:K6 strains isolated earlier. One hundred sixty-six strains belonging to 28 serovars other than O3:K6 were also examined by the new PCR method. The tdh-positive and trh-lacking strains that belonged to the O4:K68 and O1:K untypeable serovars and were isolated in three countries and from international travelers beginning in 1997 gave positive results. The AP-PCR profiles of these strains were nearly identical to those of the new O3:K6 clone, and their toxRS sequences were 100% identical to that of the new O3:K6 clone. The results suggest that these strains may have diverged from the new O3:K6 clone by alteration of the O:K antigens. In conclusion, this study presents strong evidence for the first pandemicity in the history of V. parahaemolyticus and reports a novel toxRS-targeted PCR method that will be useful in epidemiological investigation of the cases associated with the current pandemic spread.

Bacterial Proteins↗

Identification of quantitative trait loci for serum cholesterol levels in stroke-prone spontaneously hypertensive rats.

The stroke-prone spontaneously hypertensive rat (SHRSP) has been reported to show significantly lower levels of serum total cholesterol than the normotensive control strain Wistar-Kyoto rat (WKY). Because selective inbreeding was conducted for stroke proneness, this concomitantly inherited characteristic of SHRSP may play some pathophysiological role in stroke. We evaluated the genetic determinants of the cholesterol trait by estimating heritability and subsequently by undertaking a genome-wide screen with 161 genetic markers in F(2) progeny involving SHRSP and WKY (104 male and 106 female rats). Three quantitative trait loci (QTLs) were detected on rat chromosomes 5, 7, and 15. Markers from the linked region on chromosome 15 indicated significant evidence of linkage with a maximal log of the odds (LOD) score of 7.7, whereas those on chromosomes 5 and 7 cosegregated with the trait in a sex-specific manner (the QTL close to genetic marker D5 Mit5 reached an LOD score of 7.3 in males, and that close to D7 Mit10 reached an LOD score of 3.2 in females). The male-specific QTL on chromosome 5 appeared to overlap with previously reported QTLs for stroke-associated phenotypes, but an identical gene (or genes) appeared unlikely to control these and the cholesterol traits simultaneously. In the present study, serum cholesterol levels were shown to be highly genetically determined in SHRSP (the heritability estimates are 76% in males and 83% in females), and 3 QTLs with substantial effects were identified. Further work, however, is required to clarify whether the cholesterol trait is related to the etiology of stroke or has been retained by chance through the inbreeding process in SHRSP.

Alleles↗

Perioperative temporal profile of cognitive function in elderly patients undergoing hip surgery.

To test the hypothesis that elderly patients who have surgery for femoral neck fractures may have delirium not only after surgery but before surgery, we prospectively investigated the perioperative temporal profile of cognitive function in such patients. We performed the Abbreviated Mental Test (AMT) six times in each patient (on the day of admission, 3 days after admission, on the day before surgery, 2 days after surgery, 7 days after surgery, and on the day of discharge). Patients were given no premedication and were anesthetized with spinal anesthesia using 0.2% hypobaric tetracaine. Of the 68 patients who were admitted because of a diagnosis of fractured neck of the femur and were scheduled to have surgery, 27 patients were subjected to analysis. Four and three patients showed a significant decrease (3 or more points) in AMT score 2 and 7 days after surgery, respectively. We conclude that surgery may have a stronger impact on cognitive function than environmental change shortly after admission in elderly patients with femoral neck fractures.

Aged↗

Mapping of four simple sequence repeat (SSR) markers on rat chromosome 4.

We previously reported that several markers on rat chromosome (Chr) 4 cosegregated with the occurrence of cerebral stroke and brain edema in stroke-prone spontaneously hypertensive rats (SHRSP). To obtain insights into the positional candidate genes for stroke susceptibility in this region, we mapped four genes, Taurine transporter (Tau), tumor necrosis factor receptor (Tnfr), GABA transporter (Gat1) and glucose transporter-3 (Glut3) genes, using newly developed simple sequence repeat (SSR) markers on rat Chr 4. We isolated the SSRs for the genes either by screening a rat genomic library or by searching the GenBank database. By linkage analysis using two sets of backcrosses, Gat1 and Tnfr were mapped in the region associated with stroke, while Taut was located distant from the region. The Glut3 locus was also assigned to rat Chr 4 using a rat x mouse hybrid clone panel. These results indicated that the Tnfr, Gat1 and Glut3 genes were good positional candidates for the stroke susceptibility in SHRSP, suggesting that further evaluation of these genes by functional studies could prove useful.

Animals↗

Activation of monocytes in vivo causes intracellular accumulation of lipoprotein-derived lipids and marked hypocholesterolemia--a possible pathogenesis of necrobiotic xanthogranuloma.

Necrobiotic xanthogranuloma (NXG) is a rare histiocytic disease with generalized xanthomatosis. However, most cases with NXG are normolipidemic or hypolipidemic. The mechanism for the formation of xanthoma in NXG has not yet been clarified. We observed a case of NXG with severe hypocholesterolemia (total cholesterol: 1.69 mmol/l) and analyzed the function of monocytes in this case. Histological examinations by light microscopy revealed a large amount of lipid deposition in the patient's freshly isolated monocytes. The patient's monocytes showed a 3-fold increase in cholesteryl ester content and a 3-fold enhancement of acetyl low density lipoprotein (LDL) uptake compared with the control monocytes. However, no significant difference was noted in the expression of CD36 protein and the mRNA levels of scavenger receptor-class A (SR-A) between the monocytes of the patient and the control. The phagocytotic ability of the patient's monocytes was enhanced 1.5-fold compared with that of the control monocytes. These findings suggest that the activated monocytes may have degraded the modified LDL via a pathway other than CD36 or SR-A, and accumulated a great amount of lipids in vivo. In conclusion, the present study has demonstrated a possible pathogenesis of NXG that the activation of monocytes in vivo may contribute to the intracellular accumulation of lipoprotein-derived lipids leading to non-inherited xanthomatosis and the marked hypocholesterolemia.

Aged↗

Aging and salt-loading modulate blood pressure QTLs in rats.

To evaluate the effects of nongenetic factors, aging, and salt-loading on the quantitative trait loci (QTLs) for blood pressure (BP), we conducted a genome-wide linkage analysis using multiple sets of BP measurements in 125 male F2 generation cross derived from stroke-prone spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. The experiment was arranged in two stages. In the first stage, corresponding to the developing period of the rats, BP was measured repeatedly without loading of salt; this continued until the rats were 5 months of age. In the second stage, after the baseline BP leveled off, 1% salt water was given to the rats and BP was monitored for the subsequent 7 months. Genome scanning was performed using 201 markers. In the developing period, three QTLs were identified on chromosomes 1, 3, and 4 (logarithmic odds [LOD] scores of 5.6, 3.1, and 3.2, respectively), which had peaks at 8 or 10 weeks of age. In the latter salt-loading stage, QTLs for BP were detected on chromosomes 1 and 10 (LOD scores 4.6 and 4.5, respectively). When the BP increase during salt-loading was analyzed as a phenotype, however, only the region on chromosome 10 showed linkage at a suggestive level (LOD score 3.2). The present study provides experimental evidence that QTLs for BP could be modulated by nongenetic factors, such as aging and salt-loading.

Aging↗

Analysis in spontaneously hypertensive rats.

1. Linkage analysis is performed between basal or salt-sensitive high blood pressure and several loci on chromosomes in F2 progenies obtained from crossing stroke-prone spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats. 2. Basal hypertensive genes are mapped to a region near the D1Mit2 locus on chromosome 1 and near the D3Mgh8 locus on chromosome 3 in the male and female F2 progenies. 3. Salt-sensitive hypertensive gene is mapped to a region near RR1023 locus on chromosome 10 in the male F2 progenies. 4. Salt-sensitive hypertensive gene is mapped to a region near D3Mgh12 locus on chromosome 3 in the female F2 progenies.

Animals↗