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Biomedical subjects

M Matsuo

Publications and source records attributed to M Matsuo.

At least 289 records · Page 16Linked to original sources

[Epidemic of Salmonella enteritidis infection of childhood in the northern area of Nagasaki].

Salmonella Enteritidis infections were a local epidemic in the northern area of Nagasaki, Japan, during August to September in 1992. Out patients (142) visited our hospital because of diarrhea and-or abdominal pain and 96 patients had stool cultures and 51 patients were diagnosed as Salmonella infection. Of the 51 patients it was found that the Salmonella serogroups were 09, 07, 08 and the number of patients were 42, 8, 1, respectively. Phage type 1 was identified in all of the S. Enteritidis infected 38 patients who were examined. About 90% of the patients were under 10 years old. Namely, this Salmonella Enteritidis epidemic in childhood. The peak epidemic period was consistent with the local summer festival and the etiology of infection was thought to be caused by polluted handmade ice cream. S. enteritidis was identified from the ice cream which was also phage type 1. The latent period was 87 hrs.

Child↗

Luminal dilution caused by certain mild irritants and capsaicin contributes to their gastric mucosal protection.

We have recently shown that certain mild irritants caused the increase in fluid volume in the rat stomach. The present study was conducted to investigate 1) whether standing fluid in the gastric cavity can prevent gastric mucosal injury caused by 0.6 N HCl and 2) the mechanisms by which certain mild irritants increase the gastric fluid volume. One milliliter of water administered immediately before irritants greatly inhibited gastric lesion formation. Sodium chloride and capsaicin induced a profound enhancement of gastric fluid volume, as acid mild irritants did also. Sensory denervation completely abolished the volume increase caused by capsaicin but hardly influenced that caused by mild irritants. Capsaicin increased the amount of Evans blue in the gastric fluid, but mild irritants did not. On the other hand, HCl and capsaicin significantly inhibited the emptying of phenol red. From these results, we conclude that mild irritants and capsaicin can induce volume increase that by itself is enough to afford protection through luminal dilution. Capsaicin but not mild irritants requires sensory neurons to increase the gastric fluid volume. Certain mild irritants may provide a fluid pooling effect partly by inhibiting gastric emptying.

Animals↗

Activation of tissue factor-induced coagulation and endothelial cell dysfunction in non-insulin-dependent diabetic patients with microalbuminuria.

We studied the relationships between albuminuria, tissue factor-induced coagulation, and endothelial cell dysfunction in 67 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were divided into three groups on the basis of their urinary albumin excretion rate (AER). To assess the early phase of tissue factor-induced coagulation, activated factor VII (FVIIa) levels in plasma were measured by a direct fluorogenic assay. As markers of endothelial cell dysfunction, levels of von Willebrand factor (vWF), tissue-type plasminogen activator-plasminogen activator inhibitor-1 (TPA-PAI-1) complex, PAI-1, and tissue factor pathway inhibitor (TFPI) were measured. FVIIa levels were increased in normoalbuminuric NIDDM patients (AER < 15 micrograms/min) when compared with normal control subjects. This FVIIa increase was accompanied by an increase in thrombin-antithrombin III complex (TAT) levels, indicating increased activation of coagulation even in normoalbuminuric patients. In NIDDM patients with microalbuminuria (AER = 15-200 micrograms/min), the FVIIa level, the FVIIa-FVII antigen (Ag) ratio (an indicator of activation of FVII zymogen to FVIIa), and the TAT level were further increased. This group also had higher levels of endothelial cell-derived factors (vWF, TPA-PAI-1 complex, and PAI-1) than the control group. The levels of endothelial cell-derived factors (including TFPI) were highest in the NIDDM patients with overt albuminuria (AER > 200 micrograms/min). In all 67 diabetic patients, AER showed a strong positive correlation with FVIIa (r = .574, P < .0001) and a weakly but still significant correlation with FVIIa-FVII:Ag (r = .365, P = .01), vWF (r = .315, P < .01), and TAT (r = .323, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Modulation of in vitro splicing of the upstream intron by modifying an intra-exon sequence which is deleted from the dystrophin gene in dystrophin Kobe.

Molecular analysis of dystrophin Kobe showed that exon 19 of the dystrophin gene bearing 52-bp deletion was skipped during splicing, although the known consensus sequences at the 5' and 3' splice sites of exon 19 were maintained (Matsuo, M., T. Masumura, H. Nishio, T. Nakajima, Y. Kitoh, T. Takumi, J. Koga, and H. Nakamura. 1991. J. Clin. Invest. 87:2127-2131). These data suggest that the deleted sequence of exon 19 may function as a cis-acting element for exact splicing for the upstream and downstream introns. To investigate this potential role of exon 19, an in vitro splicing system using artificial dystrophin mRNA precursors (pre-mRNAs) was established. Pre-mRNA containing exon 18, truncated intron 18, and exon 19 was spliced precisely in vitro, whereas splicing of intron 18 was almost completely abolished when the wild-type exon 19 was replaced by the dystrophin Kobe exon 19. Splicing of intron 18 was not fully reactivated when dystrophin Kobe exon 19 was restored to nearly normal length by inserting other sequences into the deleted site. These results suggest that the presence of the exon 19 sequence which is lost in dystrophin Kobe is more critical for splicing of intron 18 than the length of the exon 19 sequence. Characteristically, the efficiency of splicing of this intron seemed to correlate with the presence of polypurine tracks within the downstream exon 19. Moreover, an antisense 31-mer 2'-O-methyl ribonucleotide complementary to the 5' half of the deleted sequence in dystrophin Kobe exon 19 inhibited splicing of wild-type pre-mRNA in a dose- and time-dependent manner. This first in vitro evidence that dystrophin pre-mRNA splicing can be modulated by an antisense oligonucleotide raises the possibility of a new therapeutic approach for Duchenne muscular dystrophy.

Base Sequence↗

[Stereoselective synthesis and pharmacological properties of metabolites of new antiinflammatory agent. 4'-Acetyl-2'-(2,4-difluorophenoxy)methanesulfonanilide (FK3311)].

Asymmetric reduction of acetophenone (FK3311: 1) and ethyl phenylglyoxylate (7) with various chiral reducing agents was investigated in an attempt to synthesize both optical isomers of the two metabolites (2 and 5) of 1. The treatment of 1 with 3,3-diphenyl-1-methyltetrahydro-1H,3H-pyrrolo[1,2-c]-[1,3,2]- oxazaborolidine-borane complex (reductants B, C) gave chiral alcohol 2 in a high optical purity. On the other hand, reduction of 7 by B-chlorodiisopinocamphenylborane (reductants E, F) gave the best result among the tested reagents. Each isomer of 2 and 5 was examined for in vitro activity to inhibit zymosan-induced prostaglandine E2 production, adjuvant-induced arthritis for antiinflammatory activity, and acetic acid-induced writhing for analgesic activity in comparison with the racemic mixture.

Analgesics↗

Collaborative assessment of optimal administration period and parameters to detect effects on male fertility in the rat: effects of cyclophosphamide on the male reproductive system.

As part of a collaborative project to determine optimal administration period and parameters to detect compound effects on male fertility in the rat, adult male rats were administered cyclophosphamide daily at 5, 10, 20 and 40 mg/kg for 2 weeks, or at 2.5, 5 and 10 mg/kg for 4 or 9 weeks. After the pre-pairing administration period, each male was paired with an untreated female. After mating, testes and epididymides were removed and examined for organ weights, sperm head counts, sperm morphology and histopathology. Mated females were caesarean-sectioned on Day 13 of gestation. Although atrophy of epithelia in the cauda epididymides and decreases of spermatogenic cells in the testes were observed in the higher dose groups in the 2w study, no other effects on the male reproductive system were noted in any of the studies. There were clear effects on pregnancy outcome; implantation efficiency was decreased in the highest dosage groups and postimplantation losses increased in all the dosage groups in all studies. These results suggest that a fertility study with females is needed particularly in the case of mutagenic agents, together with a detailed histopathological evaluation for reliable detection of toxicity on the male reproductive system.

Animals↗

Cardiac involvement in a family with Becker muscular dystrophy.

We report a family with Becker muscular dystrophy (BMD) presenting with cardiac involvement. The proband was a 41-year-old Japanese man who was hospitalized with exertional dyspnea and muscle weakness. Cardiac examination showed findings consistent with dilated cardiomyopathy. Dystrophin immunohistochemical analysis showed a discontinuous patchy staining pattern in cardiac and skeletal muscles biopsied from the proband. His brothers had high creatine kinase (CK) activity and abnormal electrocardiogram. Dystrophin gene analysis revealed that the proband and his brothers had G-to-T transversion at the terminal nucleotide of exon13. We conclude that the mutated dystrophin gene may cause cardiac involvement as a symptom precedent to skeletal muscle involvement.

Adult↗

Effects of oxygen inhalation on the antioxidant capacity of lungs, livers, and brains in normal and vitamin E-deficient rats at various ages.

The effects of oxygen inhalation for 48 h on the antioxidant capacity of lungs, livers, and brains in normal and vitamin E-deficient rats at various ages were examined. The activity levels of catalase, glutathione peroxidase, and superoxide dismutase, and the level of vitamin E in tissue homogenates were assayed as the indices of antioxidant capacity. Oxygen inhalation mostly decreased antioxidant enzyme activity in lungs. In particular, the catalase activity was much decreased. The glutathione peroxidase activity tended to be decreased. The superoxide dismutase activity was decreased in 32-month-old rats. Vitamin E deficiency did not augment oxidative damage due to oxygen inhalation. There appears to be no age effect on the oxygen-induced decrease in the antioxidant enzyme activities of lungs, except the superoxide dismutase activity in very old rats. Oxygen inhalation had some effects on the antioxidant capacity of livers and brains. For example, oxygen inhalation decreased the vitamin E concentration of livers in 32-month-old, normal rats. These results suggest that the antioxidant capacity of lungs is directly damaged by oxygen inhalation and that the antioxidant capacity of livers and brains is indirectly affected through lung damage. Antioxidant capacity may be maintained without large variation during young and middle ages, but its redundancy for emergency use may be diminished in old age.

Administration, Inhalation↗

Marked increase of activated factor VII in uremic patients.

We investigated plasma activated factor VII (FVIIa) levels in uremic patients (nondialysis group: n = 38; dialysis group: n = 36) and healthy controls (n = 32). We also measured the plasma levels of thrombomodulin (an indicator of endothelial cell injury) and tissue factor. Plasma FVIIa showed a marked increase in the nondialysis group (mean [95% confidence interval]: 4.6 [4.1-5.1] ng/ml, p < 0.0001) with the progressive impairment of renal function, as indicated by the serum creatinine level, when compared with the 32 controls (2.8 [2.5-3.1] ng/ml), and was further increased in the dialysis group (6.1 [5.5-6.8] ng/ml, p < 0.001 vs. nondialysis group). Plasma levels of thrombomodulin and tissue factor were also higher in the nondialysis group than the control group, and were further increased in the dialysis group. Plasma tissue factor levels did not show any correlation with FVIIa or thrombomodulin in both the nondialysis and dialysis groups. Thus, circulating tissue factor appears to be released by a different mechanism from thrombomodulin and may not contribute to the direct activation of factor VII in uremic patients. On the other hand, the plasma level of thrombomodulin was positively correlated with that of FVIIa in the nondialysis group, and this correlation was independent of renal function. Thus, enhanced conversion of factor VII zymogen to FVIIa, probably related to endothelial cell injury, may be a risk factor for cardiovascular events in uremic patients.

Aged↗

Genetic determinants of plasma factor VII activity in the Japanese.

We investigated the frequency of the factor VII Gln353 (FVII Gln353) allele in Japan, where coronary artery disease is much less common and factor VII coagulant activity (FVIIc) is lower than in Western countries. Japanese males (n = 144) aged 40-59 years living in 2 different districts were studied, and the FVIIc and activated factor VII (FVIIa) levels were measured with human (FVIIa Hum) and bovine soluble tissue factor (FVIIa Bov). The frequency of the FVII Gln353 allele in the 2 districts was 0.026 and 0.052 (combined: 0.034), which was about one third of that in a European population. Thus, the lower FVIIc level in Japanese is not due to the effect of FVII Gln353 allele. Ten individuals with the Gln353 allele showed a 39% decrease of FVIIa Hum levels and a 29% decrease of the FVIIa Bov level compared with 134 individuals homozygous for the FVII Arg353 allele. These decreases of FVIIa were greater than the decrease of FVIIc (17%), suggesting that FVII Gln353 may be difficult to activate in vivo. The marked decrease of FVIIa levels in individuals with the FVII Gln353 allele suggests that they are genetically protected against cardiovascular disease irrespective of ethnic background, by virtue of their decreased FVIIa level.

Adult↗

[A case of histological complete remission by preoperative intraarterial infusion chemotherapy].

We experienced a case of histological complete remission by preoperative intraarterial infusion chemotherapy in the treatment of histologically diagnosed endometrial cancer of well differentiated type. MRI demonstrated invasion of the myometrium to a depth of more than 1/2 and left partial parametrium. This patient was given intra-uterine arterial infusion chemotherapy twice (CDDP & ADM ia, CPA iv). Radical hysterectomy was done 3 weeks after intraarterial infusion chemotherapy. The extirpated uterus was histologically complete remission. Thus, in this case shows that intraarterial infusion chemotherapy is effective for neo-adjuvant chemotherapy of endometrial cancer.

Adenocarcinoma↗

Effect of the angiotensinogen gene Met235-->Thr variant on blood pressure and other cardiovascular risk factors in two Japanese populations.

OBJECTIVE: To investigate the gene frequency of the T235 allele and its relationship with hypertension in two Japanese populations. METHODS: T235 was investigated by restriction fragment length polymorphism using the polymerase chain reaction technique in 213 Japanese males aged 40-59 years, who were randomly selected from participants in the Jichi Medical School Cohort Study (Awaji-Hokudan population, n = 157; Niigata-Yamato population, n = 56). RESULTS: The gene frequency of the T235 allele in the two populations was very similar (Awaji-Hokudan 0.65, Niigata-Yamato 0.62; mean 0.64). The T235 frequency was 0.60 in normotensive males, approximately 1.2- to 1.7-fold that in Caucasians. Hypertension, in particular that associated with a positive family history of hypertension, was more common in individuals homozygous for the T235 allele. The levels of total cholesterol, blood glucose and fibrinogen showed a weak and non-significant relationship with the angiotensinogen genotype. CONCLUSION: The T235 angiotensinogen allele was more common in Japanese than in Caucasians, and was a predisposing factor for hypertension.

Adult↗

[Mutation detection by PCR-TGGE].

The variants in enterotoxigenic Escherichia coli (ETEC) heat-labile toxin (LT) gene were detected by temperature gradient gel electrophoresis (TGGE). 15 clinical strains isolated from patients and a wild type strain (B2C) were analyzed after the conventional PCR. Although all PCR products (707bp) corresponded to A-subunit of LT, three strains were the different electrophoretic patterns after silver staining as compared to the wild type. For further electrophoretic analyses, the 707bp region was divided into 4 parts. The different ones were localized in the downstream part (183bp), but each those DNA bands was not so clear than DNA bands in 707bp. The clearer patterns were obtained by using a primer attached GC-clamp. The hetero-duplex assays in TGGE were proceeded by a series of procedures in mixing with the equal quantity of PCR products derived from a variant and a wild type, heat-denaturation and then annealing. TGGE of those mixed samples had 4 bands that were 2 front bands as homo-duplex and 2 slower migration bands as hetero-duplex. To Confirm the site of the mutations, the nucleotide sequences in each 183bp PCR products were decided by dideoxynucleotide-fluorescent dye method. Indeed, two variants were recognized four one-base substitutions without deletions and the one was five. Thus, the difference of migration in TGGE depended on the number and the localization in mutation sites.

Base Sequence↗

The antitumor effect of hyperthermia combined with fluorouracil and its analogues.

The effectiveness of 5-fluorouracil (5-FU), FT-207 and FT-207 + uracil in combination with two repetitions of 43 degrees C hyperthermia in the treatment of the Meth-A-Fibrosarcoma and Sarcoma-180 was examined in vivo in BALB/c mice. The antitumor effect was evaluated in terms of inhibition of tumor growth by measuring the tumor for 7 days. The 5-FU concentration in each tumor was also monitored. Hyperthermia combined with FT-207 or FT-207 + uracil showed a synergistic effect for the inhibition of growth of both tumors which was not observed with 5-FU. There were no significant differences in the intratumoral concentration of 5-FU in unheated or heated Sarcoma-180 for any drug treatment after the first hyperthermia treatment, except for significant decreases in the group given 5-FU with the first hyperthermia treatment. After the second hyperthermia treatment, significant decreases in the concentration of 5-FU and FT-207 + uracil were observed. In the Meth-A-Fibrosarcoma, the intratumoral concentration of 5-FU decreased significantly in the group given 5-FU and increased significantly in the group given FT-207 + uracil after the first hyperthermia treatment, while there were significant decreases in 5-FU, FT-207 and FT-207 + uracil administered with the second hyperthermia treatment. Hyperthermia combined with FT-207 or FT-207 + uracil is considered to be effective.

Animals↗

High lipoprotein (a) levels in chronic hemodialysis patients are closely related to the acute phase reaction.

To study the mechanism underlying the high lipoprotein (a) [Lp(a)] level in uremic patients on chronic hemodialysis, we investigated the levels of Lp(a), acute phase reactants (C-reactive protein and sialic acid), and interleukin-6 (IL-6) in 54 dialysis patients. The mean [95% CI] Lp(a) level was increased in the hemodialysis patients compared with the 30 controls (30 [25-36] vs. 18 [14-23] mg/dl, p < 0.005). Among dialysis patients, 46% had an Lp(a) level > 30 mg/dl, which was significantly higher than the percentage in the control group (17%). The levels of C-reactive protein, sialic acid, and IL-6 were also increased in dialysis subjects compared with controls (200 [134-299] vs. 37 [24-58] micrograms/dl, p < 0.0001; 63 [59-66] vs. 54 [52-56] mg/dl, p < 0.002; and 9.2 [7.8-11] vs. 5.5 [5.0-6.1] pg/ml, p < 0.0005, respectively). The Lp(a) level was positively correlated with that of C-reactive protein (r = 0.415, p < 0.002), sialic acid (r = 0.426, p < 0.002), and IL-6 (r = 0.298, p < 0.05) in the hemodialysis patients, but not in the controls or non-dialysis uremic patients. The Lp(a) level in the dialysis patients was also positively correlated with activation markers of coagulation (thrombin-antithrombin III complex and plasmin-alpha 2-plasmin inhibitor complex, p < 0.005). These results indicate that the Lp(a) level is closely related to the acute phase reaction and hypercoagulability in chronic hemodialysis patients.

Acute-Phase Reaction↗

Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a common inherited disease with a worldwide incidence of 1 in 3,500 male births. Recent molecular study on the DMD gene identified a 14-kb mRNA encoded by 79 exons distributed over 2.5 million bp of the X-chromosome. The protein named dystrophin contains 3,685 amino acids. Most of the genetic events (mutations) that inactivate the dystrophin gene have been shown to be deletions, with over 65% of patients exhibiting the loss of one or more of the exons at the genomic DNA level. The mechanism of the inactivation of the dystrophin gene in one third of patients with DMD/BMD is unknown.

Dystrophin↗

Medical genetics in Japan.

In Japan genetic diseases are getting more popular in medicine, because of increased awareness of the role of genetic determinants of diseases. Care for patients with inherited disease is one of the current big problems. In this review, programs developed to support Duchenne muscular dystrophy patients are described as an example of medical services available for genetic diseases in Japan.

Female↗