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Biomedical subjects

S Matsubara

Publications and source records attributed to S Matsubara.

At least 91 records · Page 5Linked to original sources

Nicorandil metabolism in rat myocardial mitochondria.

The in vitro study using rats was carried out to clarify the hypothesis that nicorandil is denitrated and then may produce nitric oxide (NO) in myocardial mitochondria. In the presence of a NADPH-generating system, [14C]nicorandil, which was incubated in mitochondrial and microsomal fractions of the lung, heart, or liver, was converted to its main denitrated metabolite, SG-86 and other metabolites. Apparent Km and Vmax for nicorandil in mitochondrial and microsomal fractions of the heart were considerably similar to those of the lung, but completely different from those of the liver. It seems that glutathione-S-transferases (GSTs) are not primarily involved in the conversion of nicorandil to SG-86, because a known GST inhibitor, indomethacin, did not affect the nicorandil degradation in the mitochondrial fraction. Nitrite, the stable metabolite of NO, was measured by the Griess reaction. In the presence of an NADPH-generating system, nicorandil significantly increased nitrite production in myocardial mitochondria, but SG-86 did not. These data strongly indicate that nicorandil is metabolized to SG-86 in myocardial mitochondria, then releasing NO, and that GSTs are not primarily responsible for the conversion of nicorandil to SG-86.

Animals↗

Paradoxical motion of the hemidiaphragm in patients with emphysema.

The authors evaluate paradoxical diaphragmatic motion using magnetic resonance (MR) imaging in patients with emphysema. The subjects were 12 healthy volunteers and 10 male patients with moderate to severe air flow obstruction. With subjects in the supine position, 30 sequential sagittal images of the bilateral lungs were obtained during quiet and forced breathing using a 1.5T MR unit with a body coil. The sequence was single shot fast spin echo (SSFSE) with half Fourier transformation. Subtraction images were made from the original images (by subtracting a given image from the preceding image), which visualized the chest wall motion as white or black bands on the edge of the lung fields. The authors evaluated both the original and subtraction images. MR imaging showed abnormal hemidiaphragmatic motion during forced breathing: the ventral portion of the hemidiaphragm moved downward while the dorsal part moved upward like a seesaw in 6 patients. MR images also revealed abnormal ribcage motion; the ventral ribcage moved anteriorly when the hemidiaphragm moved upward in 7 patients. No abnormal motion was observed in healthy volunteers. MR is a noninvasive and useful tool for evaluating the asynchronous respiratory motion in patients with emphysema.

Adult↗

Chemotactic activity for polymorphonuclear leukocytes: meconium versus meconium-stained amniotic fluid.

PROBLEM: Our previous study indicated that meconium-stained amniotic fluid (turbid AF) possessed a potent chemotactic activity for leukocytes, which may be dependent on interleukin-8. It is not known, however, whether meconium itself possesses this chemotactic activity. METHOD OF STUDY: Meconium samples were collected from mature neonates with and without turbid AF. A 5% meconium suspension in phosphate buffered saline was prepared and measured for its chemotactic activity for leukocytes using the blind well chamber technique. Concentrations of IL-8, TNFalpha and IL-1beta were also measured with ELISA. RESULTS: The number of leukocytes that migrated to the meconium suspension (35 +/- 27) was comparable with that of the clear AF (31 +/- 37), but was significantly lower than that of the turbid AF (184 +/- 62, P < 0.0001). The meconium suspension contained much lower levels of IL-8, TNFalpha and IL-1beta than the turbid AF. CONCLUSIONS: Meconium itself exhibits a lower chemotactic activity for polymorphonuclear leukocytes than turbid AF in vitro. The leukocyte chemotactic activity of turbid AF does not originate from meconium itself.

Amniotic Fluid↗

Analysis of endoglin expression in normal brain tissue and in cerebral arteriovenous malformations.

BACKGROUND AND PURPOSE: A high incidence of arteriovenous malformations (AVMs) is associated with hereditary hemorrhagic telangiectasia type 1. Endoglin, the gene mutated in this disorder, is expressed at reduced levels on blood vessels of these patients. Since endoglin is a component of the transforming growth factor-beta receptor complex critical for vascular development and homeostasis, we determined its expression in sporadic cerebral AVMs and in normal brain vessels. METHODS: Twenty cerebral AVMs and 10 normal brain samples were analyzed for endoglin, platelet endothelial cell adhesion molecule 1 (PECAM-1), alpha-smooth muscle cell actin, vimentin, and desmin by immunohistochemistry. RESULTS: In normal brain, endoglin was found not only on the endothelium of all vessels but also on the adventitial layer of arteries and arterioles. In cerebral AVMs, the numerous vessels present expressed endoglin on both endothelium and adventitia. Arterialized veins, identified by lack of elastin and uneven thickness of smooth muscle cells, revealed endoglin-positive mesenchymal cells in the adventitia and perivascular connective tissue. These cells were fibroblasts since they expressed vimentin but not actin and/or desmin. CONCLUSIONS: This is the first report of endoglin expression on adventitia of normal brain arteries and on arterialized veins in cerebral AVMs. Increasing numbers of endoglin-positive endothelial and adventitial cells were seen in sporadic cerebral AVMs, but endoglin density was normal. Thus, it is not involved in the generation of these lesions. However, the presence of endoglin on fibroblasts in the perivascular stroma suggests an active role for this protein in vascular remodeling in response to increased blood flow and shear stress.

Actins↗

Evidence for the AT1 subtype of the angiotensin II receptor in the rat submandibular gland.

We have characterized angiotensin II (Ang II) receptor subtypes on rat submandibular gland membranes using a radioligand binding assay. [3H]Ang II binding to the membrane fractions exhibited both high (Kd =0.08 nm, Bmax =2.19 fmol/mg protein) and low (Kd =4.19 nm, Bmax = 13.7 fmol/mg protein) affinity. Ang 11, Ang III and saralasin completely displaced the [3H]Ang II binding, whereas CV-11974, an AT1 receptor antagonist and PD123319, an AT2 receptor antagonist maximally displaced up to approximately 87 and 13% of the total binding, respectively. [3H]DuP753 binding to the membrane fractions exhibited a single population of binding site with a Kd of 4.22 nM and Bmax of 3.77 pmol/mg protein. Ang II, Ang III and CV-11974 completely displaced the [3H]DuP753 binding with slope factors near unity, but PD123319 did not. These findings suggest that rat submandibular gland membranes contain predominantly the AT1 receptor subtype.

Angiotensin Receptor Antagonists↗

Hypotensive interaction of sildenafil and nicorandil in rats through the cGMP pathway but not by K(ATP) channel activation.

The possibility that sildenafil citrate can potentiate nicorandil-induced hypotension by increasing cGMP levels of vascular smooth muscle cells was examined using anesthetized rats and isolated aortas. In pentobarbital-anesthetized rats, more than 0.3 mg/kg of sildenafil (i.v.) potentiated intra-aortic (i.Ao.) administration of nitroglycerin-induced hypotension. Hypotension due to nicorandil (100 microg/kg, i.Ao.) was potentiated by sildenafil (1 mg/kg, i.v.), even after glibenclamide treatment, although pinacidil-induced hypotension was not reinforced. Hypotensive responses to neither nitroglycerin (3 microg/kg, i.v.) nor nicorandil (100 microg/kg, i.v.) were potentiated by sildenafil, however. Increases in femoral blood flow due to nitroglycerin (0.1-3 microg, i.a.) were potentiated significantly by sildenafil, but those due to nicorandil (1-30 microg, i.a.) were not. Isolated rat aortas precontracted with phenylephrine were dilated dose-dependently using nicorandil, nitroglycerin, pinacidil or sildenafil. The relaxant effect due to nicorandil and nitroglycerin was reinforced significantly by pretreatment with an ineffective concentration of sildenafil (10(-8) M), but pinacidil was not. After ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) completely blocked relaxation by nicorandil, sildenafil did not increase relaxation. These findings suggest that combination of sildenafil with nicorandil, as well as with nitroglycerin, potentiates the hypotensive response by augmentation of vasodilatation. Synergism of vasodilatation may be linked with NO action, but not with K(ATP) channel-activation.

3',5'-Cyclic-GMP Phosphodiesterases↗

The value of plain radiographs in the prediction of outcome in pelvic fractures treated with embolisation therapy.

40 haemodynamically unstable patients with pelvic injuries were studied to assess the ability of plain radiographs to detect haemorrhagic sites. Pelvic radiographs and bilateral angiograms were reviewed separately for detection of haemorrhagic sites in both anterior and posterior segments. Sensitivity and specificity of pelvic radiographs for the detection of haemorrhagic sites were obtained by analysis of angiographic findings. Angiography demonstrated arterial injury in 106 divisions: 26 right anterior, 22 right posterior, 33 left anterior and 25 left posterior. Sensitivities of the radiographs for predicting haemorrhagic sites were higher in the anterior segment (right, 96%; left, 100%) than in the posterior segment (right, 73%; left, 83%). However, specificities were lower in the anterior segment (right, 79%; left, 78%) than in the posterior segment (right, 100%; left, 100%). In 15 (58%) of 26 patients with in-dwelling Foley catheters, including those with catheter deviation, the severity of anterior injury indicated on plain radiographs was correlated with angiographic findings. Plain radiographs of the pelvis proved useful for predicting haemorrhagic sites in haemodynamically unstable patients with pelvic fractures, especially in those with anterior fractures.

Adolescent↗

Placenta of discordant twins: lack of change in histochemically detectable enzyme activities.

We localised three important enzymes histochemically in placental trophoblasts from women who gave birth to dichorionic discordant twins, in which the co-twin was affected by foetal growth restriction (FGR). The enzymes studied were adenosine diphosphate-degrading enzyme (ADP-degrading enzyme, plasma membrane enzyme), cytochrome c oxidase (mitochondrial enzyme), and glucose-6-phosphatase (endoplasmic reticular enzyme). We compared these enzyme activities and their distribution patterns among placentas of the smaller (FGR) co-twin, larger co-twin, pre-eclamptic singleton with FGR, and normal singletons with birth weight of appropriate for their gestational ages. In FGR co-twin placentas, the intensity and localisation pattern of these three enzymes did not differ from those seen in the larger co-twin and normal singleton placentas. Decreased ADP-degrading activity and cytochrome c oxidase negative mitochondria, which were characteristic features of pre-eclamptic trophoblasts, were not observed in FGR co-twin placentas. These observations indicated that, in the FGR co-twin, enzyme-histochemically detectable trophoblastic cell dysfunction may be absent, or if present, less prominent, compared with pre-eclamptic FGR. We previously reported that placental trophoblasts from singleton idiopathic FGR also showed no reduction in these enzyme activities. In mechanism and pathophysiology, FGR in dichorionic discordant twins may be quite different from pre-eclamptic FGR, but somewhat resembles idiopathic FGR, though all three disorders lead to placental insufficiency, resulting in limited foetal growth.

Apyrase↗

Large goiter and multiple rib tumors.

We report an interesting case of a 47-yr-old who had a large goiter and multiple rib tumors. The patient was initially suspected of having thyroid cancer, which had metastasized on the ribs, based on imaging studies. However, laboratory tests revealed a high level of ionized calcium and parathyroid hormone (PTH). The large goiter was diagnosed as having parathyroid tumors owing to the high level of PTH in the tissue fluid. The biopsy specimen from a rib tumor was diagnosed as containing brown tumors associated with primary hyperparathyroidism (PHP). The patient also had prolactinoma and pancreatic gastrinoma. Her daughter had both prolactinoma and PHP, and her brother and her father had PHP. Thus, the patient was diagnosed as having multiple endocrine neoplasia type 1.

Adult↗

Different phenotypes of multiple endocrine neoplasia type 1 (MEN1) in monozygotic twins found in a Japanese MEN1 family with MEN1 gene mutation.

We report monozygotic twins who showed different MEN1 phenotypes. The proband (28 y.o., female) had both primary hyperparathyroidism (PHP) and insulinoma, and genetic analysis revealed a point mutation (569del1, exon 3) of the MEN1 gene. This mutation causes a frameshift and produces a stop codon at codon 184. Restriction digestion (HinfI) analysis confirmed the same mutation of the MEN1 gene in six of the affected members including her two sisters, the monozygotic twins, and no such mutation in two unaffected members. In two generations of this family, eight of eleven family members had PHP and four of them were found to have other MEN1-related lesions. Both of the monozygotic twins had PHP. Interestingly, one had pancreatic tumor but the other had no evidence of it. Pituitary MRI showed no pituitary lesion in either of them. This is the first Japanese case of monozygotic twins with different MEN1 phenotypes.

Adult↗

Effects of a thyromimetic on apolipoprotein B-100 in rats.

We have studied the effects of a cardiac sparing thyromimetic, CGS 23425, on postprandial levels of triglycerides, abundance of apolipoprotein B (apo B) protein and hepatic apo B mRNA expression in rats. When compared with control rats, triglyceride clearance was significantly accelerated by treatment with CGS 23425. A full return to baseline values was achieved within 8 h after ingesting a large quantity of fat, as compared to >24 h in control animals. The abundance of apo B-100 protein in CGS 23425-treated hyperlipidemic rats decreased in a dose-dependent manner, but levels of apo B-48 were not significantly affected. Like L-tri-iodothyronine (L-T(3)), treatment with 30 microg/kg CGS 23425 for 6 or 9 days decreased the levels of apo B-100 protein by 80% and 40% respectively. This change was paralleled by a 27% reduction in hepatic apo B-100 mRNA. To investigate a potential mechanism of CGS 23425 action, we measured in vitro apo B mRNA editing activity in hepatocellular extract from control or CGS 23425-treated rats. Treatment with CGS 23425 increased activity of the hepatic apo B-100 editosome, apobec-1. In human hepatoma cells which lack apobec-1 activity, apo B-100 mRNA levels remained the same in cells treated with or without the agent. In summary, these observations show that CGS 23425 decreases the levels of apo B-100 in rats. This action of CGS 23425 involves apo B-100 mRNA editing activity.

APOBEC-1 Deaminase↗

Effect of soy milk and bifidobacterium-fermented soy milk on plasma and liver lipids in ovariectomized Syrian hamsters.

The effects of soy milk and fermented soy milk on lipid metabolism were studied in ovariectomized Syrian hamsters. Five mo-old Syrian hamsters were randomly assigned to four treatment groups: ovariectomized (OVX)+control diet (OVX-C); OVX+soy milk diet (OVX-SM); OVX+fermented soy milk diet (OVX-FSM); and sham-operated+control diet (Sham-C). The hamsters were fed on these diets for 4 wk. The atherogenic index value of the OVX-FSM group was lower than that of the OVX-C group. The plasma triglyceride level of the OVX-FSM group was significantly lower than that of the OVX-C group. The liver total cholesterol contents in the OVX-SM and OVX-FSM groups were significantly lower than that in the OVX-C group. Thus, these results demonstrate that bifidobacterium-fermented soy milk had a hypolipidemic effect in ovariectomized hamsters.

Animals↗

Computerized tomographic ureteroscopy for diagnosing ureteral tumors.

PURPOSE: Helical computerized tomography (CT) image acquisition has led to the availability of improved data sets for CT endoscopic imaging that represent virtual endoscopy using CT. We assessed the usefulness of CT ureteroscopic imaging for diagnosing ureteral tumors. MATERIALS AND METHODS: A total of 16 patients with ureteral stenosis underwent surface rendering CT ureteroscopy after the intravenous administration of contrast material and furosemide. To distinguish ureteral tumors from ureteral strictures 2 observers blinded to other patient history and evaluation data independently and prospectively evaluated CT ureteroscopy with reformatted CT ureterograms in these 16 patients. CT ureteroscopic images were then correlated with surgical and pathological findings, which served as the gold standard. RESULTS: Surgical and pathological findings in the 16 patients revealed 16 ureteral tumors, including carcinoma in 10 (carcinoma in situ in 1, fibroepithelial polyps in 2 and hyperplastic polypoids in 4), inflammatory intrinsic stricture in 2 and extrinsic stricture in 4 caused by retroperitoneal fibrosis in 2 and lymph node metastasis in 2. CT ureteroscopy correctly detected all lesions except 1 carcinoma in situ, 1 polypoid carcinoma and 1 hyperplastic polypoid. The sensitivity and specificity of CT ureteroscopy for detecting ureteral tumors and carcinoma were 81% and 100%, and 80% and 75%, respectively, when tumors without stalks were considered carcinoma. CONCLUSIONS: CT ureteroscopy is useful for visualizing the complex morphology of ureteral tumors and distinguishing tumor from ureteral stricture.

Adult↗

[A case of Guillain-Barré syndrome (GBS) following human parvovirus B19 infection].

Human parvovirus B19 (HPV-B19) infection is recently known to produce variable clinical manifestations, but neurological disorder associated with this infection is uncommon. We reported a case of GBS associated with transient lupus-like status following HPV-B19 infection. This is the first report describing an adult case of GBS following HPV-B19 infection. A healthy female, aged 33, developed erythema infectiosum simultaneously with her 5-year-old daughter. On the same day, she noticed leg fatigue, which worsened in the following days. On the day 11th, she became unable to walk. Mild pancytopenia, liver injury, proteinuria, hypocomplementemia, and increased anti-nuclear antibody (ANA) were revealed at a hospital. Polymerase chain reaction detected HPV-B19 DNA in the serum. On the day 17th, she was admitted to our hospital because of moderate generalized weakness and mild sensory disturbance, which were symmetrical and distal-dominant. The deep tendon reflexes were absent. Analysis of cerebrospinal fluid showed albuminocytologic dissociation. Other laboratory data were normal except positive ANA. Enzyme-linked immunosorbent assay (ELISA) showed high titer of the serum IgM antibody to GM1 and GD1b. Serum anti HPV-B19 IgM and IgG tested by ELISA were also positive. She improved gradually after 2 courses of double filtrated plasma pheresis.

Adult↗

[The frequency of Streptococcus pneumoniae strains and sensitivity surveillance for several antibiotics in Gifu Prefecture].

The frequency and the antibacterial sensitivity of Streptococcus pneumoniae strains isolated from 6 key hospitals (in 5 areas) and 1 otorhinolaryngology clinic in Gifu Prefecture from February to March, 1999, were investigated with several antibiotics. A total of 128 strains of Streptococcus pneumoniae were isolated throughout the study: 47 strains (36.7%) of penicillin-susceptible S. pneumoniae (PSSP), 51 strains (39.8%) of penicillin-intermediate S. pneumoniae (PISP), and 30 strains (23.4%) of penicillin-resistant S. pneumoniae (PRSP); the resistant bacteria being relatively prominent. In these hospitals, PSSP was isolated by 38.8% in all the key hospitals and by 30% in the otolaryngology clinic with almost no discernible difference. PISP was isolated by 63.3%, higher in the otolaryngology clinic and PRSP by 28.6%, higher in the key hospitals conversely. The MIC90s in PISP and PRSP were determined with the antibiotics. In result, only cefditoren (CDTR) showed favorable antibacterial activities with the MIC90 of 0.78 microgram/ml among penicillins or oral cephems. The MIC90s of carbapenems such as imipenem (IPM), meropenem (MEPM), and panipenem (PAPM) were less than 0.39 microgram/ml; particularly, PAPM showed the highest antibacterial activities. Among new quinolones such as tosufloxacin (TFLX), levofloxacin (LVFX), sparfloxacin (SPFX), and ciprofloxacin (CPFX), TFLX showed the highest antibacterial activities with the MIC90 of 0.39 microgram/ml. Other agents showed very low antibacterial activities as the MIC90s were 25 micrograms/ml in minocycline (MINO) and more than 100 micrograms/ml in clarithromycin (CAM) and clindamycin (CLDM).

Amoxicillin↗

Relation between viability of vaginal polymorphonuclear leukocytes and presence of histologic chorioamnionitis.

BACKGROUND: The number and percentage of viable vaginal polymorphonuclear leukocytes (vPMNs) are known to be increased in women who experience preterm labor. Whether those parameters may be associated with the presence of histologic chorioamnionitis (CAM) is not known. METHODS: We investigated prospectively 39 women at 26.3 +/- 6.2 weeks of gestation. The following were determined in vaginal washings: total number of vPMNs and the percent that were viable, the pH, and the concentrations of granulocyte elastase and interleukin-8 (IL-8). In addition, the white blood cell count and the serum level of C-reactive protein were determined in peripheral blood. The placenta and the umbilical cord were examined histologically with special reference to the presence of CAM. The optimal cutoff value for prediction of histologic CAM was obtained for each variable using receiver operating characteristic curves. A multivariate logistic-regression model was used to determine the independent risk factors for this disorder. RESULTS: Histologic CAM was present in ten women (37.1 +/- 3.8 weeks) and absent in 29 women (38.2 +/- 1.5 weeks). The total number of vPMNs, the percent of viable vPMNs, and the IL-8 level were all significantly increased in the women with CAM, in contrast to those without CAM. When the optimal cutoff value for each of seven covariates was entered into the model, only the percent of viable vPMNs, > or = 11%, demonstrated a significant relationship with histologic CAM (odds ratio 26.9; 95% confidence interval 1.3 to 545; p < 0.05). CONCLUSIONS: Women with a % viability of vPMNs of > or = 11% were at a significantly higher risk for histologic CAM. Data suggest that an influx of PMNs into the vagina occurs continuously in patients with histologic CAM.

Adult↗