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Biomedical subjects

T Matsubara

Publications and source records attributed to T Matsubara.

At least 253 records · Page 14Linked to original sources

Cultured osteoblast synthesize nitric oxide in response to cytokines and lipopolysaccharide.

Nitric oxide (NO) is generated from L-arginine by NO synthase. NO has been reported to be produced by a variety of cell types such as vascular endothelial cells, macrophages, neutrophils and articular chondrocytes. A recent report demonstrated that NO inhibits osteoclast (OC) function and, in this way, is critically associated with bone metabolism. In the present study we have studied NO synthesis by osteoblasts (OBs). OB cell line, MC3T3-E1, was cultured with the various cytokines for 72 hrs. Nitrite, a stable endproduct of cell-generated NO, in the culture supernatant was then determined by using a spectrophotometric method based on Griess reaction. IL-1 alpha increased nitrite release in a dose-dependent fashion and a significant enhancement (p < 0.01) was attained at 10 U/ml. OBs released 14.2 nmol/4.0 x 10(4) cells of nitrite after 72 hrs stimulation by 100 U/ml IL-1 alpha. In contrast IL-1 beta, TNF-alpha and INF-gamma failed to affect NO synthesis by MC3T3-E1. The results suggest that OBs produce NO in response to IL-1 alpha and OB-induced NO may play a role in OB-OC interaction in the inflammatory process.

Animals↗

Myocardial metabolic markers of total ischemia in vitro.

The influence of total ischemia on the formation of products of anaerobic metabolism was investigated in canine hearts in vitro. Contents of organic acids were quantitatively analyzed by gas chromatography-mass spectrometry, and high energy phosphate compounds were determined using the luciferin-luciferase enzyme system. During a 10-min period of total ischemia, myocardial creatine phosphate significantly decreased, while ATP remained unchanged as compared with preischemic values. Both 10 min and 60 min of ischemia induced significant increase in tissue succinic acid levels. In contrast, a significant increase in myocardial lactic acid content was only induced with 60 min of ischemia. The data obtained indicate that the accumulation of succinic acid may be regarded as a potential metabolic marker of myocardial total ischemia.

Animals↗

Correlation between myocardial blood flow and tissue succinate during acute ischemia.

This study was performed to clarify the relationship between degree plus duration of myocardial ischemia and tissue succinate or lactate contents, and to assess whether their accumulation might be a metabolic marker of ischemic myocardium. Regional myocardial blood flow (MBF) was measured using the hydrogen gas clearance method in anesthetized open-chest dogs subjected to 10 min or 60 min of myocardial ischemia by coronary ligation. The contents of succinic acid and lactic acid in myocardium corresponding to locations of MBF measurement were quantitatively analyzed by gas chromatography-mass spectrometry. In severely ischemic areas with MBF less than 20 ml/min/100g, significant increases in both succinic and lactic acids were observed 10 min after coronary occlusion. Sixty min of ischemia induced significant increase in the myocardial succinic acid content not only in severely but also in moderately ischemic areas. In contrast, lactic acid was significantly increased only in the severely ischemic area 60 min after coronary occlusion. These results indicate a good correlation between degree plus duration of myocardial ischemia and tissue succinic acid content, suggesting that its accumulation in myocardium may be a reliable and sensitive metabolic marker of coronary ligation ischemia.

Acute Disease↗

[Indocyanine green fluorescence angiography in Harada disease].

Indocyanine green fluorescence angiography (ICG angiography) can reveal choroidal circulation, and so it is used to observe uveitis. We examined 29 eyes of 15 patients with Harada disease using ICG angiography. In the early phase, filling delay of choroidal circulation was the most remarkable finding in cases with flat retinal detachment in the posterior pole. In the early to late phase choroidal vessels were indistinct, and speckled hypofluorescence on the diffuse background fluorescence was seen. Leakage from the choroid into the subretinal space was seen in ICG angiography at the same leak points seen in fluorescein angiography. In 3 patients, the area of retinal detachment showed hypofluoresence in the late phase. Areas of Dalen-Fuchs spots showed hypofluorescence. ICG angiography clearly revealed severe disturbance of choroidal circulation in Harada disease, and filling delay of the choroidal circulation and indistinct choroidal vessels correlated with the severity of this disease. ICG angiography helps to evaluate the pathology of Harada disease clinically.

Adolescent↗

[Sympathetic ophthalmia in an elderly man].

A 78-years-old man suffered from sympathetic ophthalmia. He had been treated with 5-fluorouracil (5-FU) for metastasis of colon cancer in the liver. He received a perforating eye injury in the left eye thereafter the eye became phthisic. Two months after the injury, he noticed visual disturbance in the right eye. He was treated with large doses of systemic corticosteroid after a diagnosis of uveitis of the right eye, but the visual acuity of the right eye became worse. The eye showed non-specific diffuse uveitis. A diagnosis of sympathetic ophthalmia was made from previous history and ocular findings. We enucleated the injured eye and continued the systemic corticosteroid. Then the right eye improved. Histopathological examination of the enucleated eye revealed the choroid was infiltrated with a granulomatous lesion of lymphocytes and epithelioid cells. HLA typing showed DR4, DR8, DR52, DR53, and DQ1, and we made a final diagnosis of sympathetic ophthalmia. It is probable that the clinical findings were modified by the 5-FU treatment and the patient's advanced age.

Aged↗

How extensive should lymph node dissection be for cancer of the thoracic esophagus?

From 1985 to 1992, 171 patients with cancer of the thoracic esophagus underwent esophagectomy with systematic dissection of regional lymph nodes including cervical nodes. The hospital mortality rate was 5.3%. The dissected nodes were classified into four groups: the deep cervical (C), upper mediastinal and cervical paratracheal (U), middle and lower mediastinal (L), and upper perigastric (G) groups. The U group mainly consisted of nodes beside the recurrent laryngeal nerves. The phase of cancer infiltration of lymph nodes was evaluated by the total number and the distribution of involved nodes. Of cases with nodal involvement, only 37% were in the late phase, in which more than seven nodes or in which the U, L, and G groups were all involved. Of cases in the earliest phase in which only one node was involved, 93% had either the U or G group involved. The C group of nodes was infrequently involved until the late phase. Cancer had metastasized to the U and G groups across a considerable anatomic distance even in earlier phases. Outcomes of the cases with nodal involvement not in the late phase were satisfactory; the cumulative survival was 60% at 3 years and 54% at 5 years. Systematic nodal dissection would benefit even cases with nodal involvement, unless the disease is in the late phase. Nodes beside the recurrent nerves and upper perigastric nodes should be dissected with higher priority, though they are located anatomically distant.

Carcinoma, Squamous Cell↗

Neurosteroids in cerebrospinal fluid in neurologic disorders.

In order to investigate the role of "neurosteroids" in the central nervous system (CNS), cerebrospinal fluid (CSF) levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) were determined by radioimmunoassay in 57 patients with various neurologic disorders and 26 patients with non-neurologic disorders. The content of CSF DHEA and DHEAS in patients with Guillain-Barré syndrome (GBS), and the content of CSF DHEAS in patients with carcinomatous meningitis were significantly higher as compared to non-neurological control patients. These changes may be explained by the breakdown of blood-nerve barrier in these disorders. A significant positive correlation was observed between DHEAS and total protein in CSF. In males but not females, a negative correlation was observed between CSF DHEAS and aging. The level of CSF DHEAS, but not DHEA, was significantly higher in males than in females.

Adult↗

Occurrence of phosphonotetraglycosyl ceramide in the sea hare Dolabella auricularia.

Two kinds of phosphonoglycolipids were isolated from the sea hare Dolabella auricularia. One was phosphonopentaglycosyl ceramide with the same structure as that of the phosphonoglycolipid obtained from the sea hare Aplysia kurodai. The other, phosphonotetraglycosyl ceramide, was discovered in this study. Its structure was determined to be 3-O-Me-Gal alpha 1-3(AEP-6Gal alpha 1-2)Gal beta 1-4Glc beta 1-1-ceramide. The presence of tetraglycosyl and pentaglycosyl ceramides, the backbone structures of phosphonoglycolipids in the neutral glycolipid fraction, indicate that these neutral glycolipids are precursors of the phosphonoglycolipids.

Animals↗

cDNA cloning and characterization of a novel member of steroid-induced cytochrome P450 3A in rats.

A unique cDNA clone, termed cDEX, coding for dexamethasone-inducible novel rat cytochrome P450 was isolated and characterized. The restriction enzyme map of the cDEX was slightly different from the reported two CYP3A1 sequences, and several nucleotide substitutions were found. Compared to the CYP3A1 sequence reported as P450pcn1 by F. Gonzalez et al. (J. Biol. Chem. 1985, 260, 7435-7441), there were 26 substitutions of nucleotides leading to 11 amino acid changes and a six-base (two amino acid)-long deletion in the open reading frame. Comparison with the sequence of pP450IGC2 reported by V. Ribeiro and M. C. Lechner (Arch. Biochem. Biophys., 1992, 293, 147-152) showed 18 nucleotide changes resulting in eight amino acid substitutions and the six-base-long deletion in the coding region. cDEX and these clones shared 97.8 and 98.4% similarity in deduced amino acid sequences, respectively, while only 86.3% similarity with P450pcn2 (CYP3A2). RNA blot hybridization analysis indicated that the mRNA corresponding to cDEX was mainly induced in rat liver by the administration of steroidal agents.

Amino Acid Sequence↗

Effects of diabetes on cardiac glycogen metabolism in rats.

The effects of diabetes on myocardial glycogen metabolism in rats were examined and compared with those of fasting. Male Wistar rats were divided into three groups: controls, streptozotocin-induced diabetics, and one-week fasted. Isolated rat hearts were subjected to substrate-free 30-min Langendorff perfusion followed by 60-min working heart perfusion with glucose alone or in combination with insulin or insulin plus beta-hydroxybutyrate (BHB). Myocardial glycogen contents were determined before or 30 min after Langendorff perfusion, or 60 min after working heart perfusion. Before Langendorff perfusion, tissue glycogen concentrations in control, diabetic, and fasted hearts were 3.3 +/- 0.2, 10.0 +/- 0.9, and 5.7 +/- 0.5 (mg/g wet weight), respectively. In diabetic rats, the myocardial glycogen concentration was markedly decreased after working heart perfusion of any of the substrate combinations, even those with insulin and BHB. In contrast, myocardial glycogen in control or fasted rats was not reduced after the addition of glucose with insulin, and/or glucose with insulin and BHB. These results suggest that degradation of tissue glycogen occurs in isolated perfused hearts from diabetic rats, while a clearly different response is shown by fasted hearts.

3-Hydroxybutyric Acid↗

Repeat angiography and magnetic resonance imaging (MRI) of dissecting aneurysms of the intracranial vertebral artery. Report of four cases.

We here present 4 cases with dissecting aneurysm (DA) of the intracranial vertebral artery, who were followed up by repeat cerebral angiography and MRI. The patients consisted of 2 males and 2 females, and the mean age was 43 years. Two cases were associated with polyarteritis nodosa (PN) and hypertension, respectively. Three of the cases developed subarachnoid haemorrhage (SAH), while the other one suffered from lateral medullary syndrome. In cerebral angiography, "pearl and string" signs were revealed in all cases, while a "double lumen" indicating a true diagnostic sign of DA was demonstrated in only one case. Repeat angiography showed that a bleb formation with a bulging of the aneurysmal sac was seen in 2 cases, and an irregularity of the wall in one case. On the other hand in one case, the ectatic part shrank, while the stenotic part was restored. In magnetic resonance imaging (MRI), a hyperintensity mass on T 1-weighted image (T 1-WI) adjacent to flow void suggesting either an intramural haematoma or a linear shape hyperintensity on T 1-WI were demonstrated in 3 cases. In the follow up MRI done in 2 cases, a serial change in the intensity from iso-intensity to hyperintensity on T 1-WI was observed in one case suggesting intramural haemorrhage, while an enlargement of the ectasic flow void was seen in the other case. Three of 4 cases were operated on by trapping of the aneurysms. One, who had systemic vascular diseases due to PN, and repeat angiography showed a regression of the aneurysm, was conservatively treated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Assessment of area at risk and efficacy of treatment in patients with acute coronary syndrome using 99mTc tetrofosmin imaging in humans.

The determination of the myocardium at risk before intervention and the change in that region after intervention constitute a promising measurement tool for the assessment of acute therapy. A new 99mTc labeled myocardial blood flow tracer, 99mTc tetrofosmin, is expected to enable the evaluation of myocardium at risk because of the absence of redistribution. This preliminary study was performed in 9 patients with acute coronary syndrome (4 unstable angina and 5 acute myocardial infarction) to investigate whether recovery of perfusion by tetrofosmin imaging parallels mechanical improvement. Tetrofosmin imaging was performed acutely and 3-30 days later. Visual analysis of defect severity was assessed in both studies. Segments with improvement in perfusion were accompanied by significant wall motion recovery compared with normal and unimproved segments (delta WMI: normal segments 0.40 +/- 0.67, improved segments 1.79 +/- 0.68, unimproved segments -0.15 +/- 0.16, p < 0.01 for improved segments compared with other groups), suggesting the efficacy of this tracer for the assessment of the acute therapy. These data suggest that 99mTc tetrofosmin imaging is a useful method for the assessment of the myocardial area at risk and the efficacy of acute therapy in acute myocardial infarction and unstable angina.

Aged↗

Increased CYP1A2 content and capacity to activate Glu-P-1 and Trp-P-2 in liver microsomes of scorbutic ODS rats.

Osteogenic Disorder Shionogi (ODS) rats, which cannot synthesize ascorbic acid due to a deficiency of L-gulonolactone oxidase, become scorbutic when not supplied with dietary ascorbic acid. We used the deficient rats to study the effects of ascorbic acid on the amount of cytochrome P450 enzymes in liver microsomes. The total amount of hepatic cytochrome P450 in ODS rats deprived of ascorbic acid was lower by approximately 40%, whereas ODS rats fed with ascorbic acid and the wild strain had the same level of total hepatic cytochrome P450. Western blot analysis for various forms of cytochrome P450 in liver microsomes indicated that the amount of CYP1A2 was significantly higher in ascorbic acid deficient rats. On the other hand, amounts of CYP2B2 and 3A were lower, and those of CYP2E1 and CYP2C6/11 were unaffected. In accordance with the higher amount of CYP1A2, Northern blot analysis showed increased expression of CYP1A2 mRNA. The capacity of microsomes to produce mutagens from 2-amino-6-methyl-dipyrido[1,2-a:3',2'-d]imidazole acetate (Glu-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole acetate (Trp-P-2) was higher in scorbutic ODS rats by the Ames test. These results indicate that the effects of ascorbic acid deficiency on the expression of cytochrome P450 in ODS rat livers are form-specific and that the increased CYP1A2 is associated with increased metabolic activation of promutagens in the scorbutic state.

Animals↗

Circadian blood pressure variation in diabetic patients with autonomic neuropathy.

OBJECTIVE: To elucidate distinctive patterns of circadian variation of blood pressure in diabetic patients. DESIGN: Circadian variations and indices of blood pressure variability were examined by non-invasive ambulatory blood pressure monitoring. The indices were assessed for a correlation with various possible signs of autonomic neuropathy, including the coefficient of variation of the RR interval and orthostatic hypotension. METHODS: The study was conducted on 38 normotensive diabetics and 15 age- and sex-matched non-diabetic controls, all of whom were outpatients at the Third Department of Internal Medicine in Nagoya University Hospital. Ambulatory blood pressure measurements were taken in all subjects and the coefficients of variation in the RR interval and postural changes in blood pressure were determined. RESULTS: The diabetic patients demonstrated a different pattern of circadian variation in blood pressure from that of the non-diabetics. Diurnal-nocturnal differences were significantly smaller in diabetics than in non-diabetic controls. Statistically significant correlations were found between diurnal-nocturnal differences in blood pressure and the duration of diabetes, glycaemic control, the coefficient of variation in the RR interval and the change in blood pressure on standing. A subgroup of diabetic patients with severe autonomic neuropathy showed the lowest diurnal-nocturnal differences. CONCLUSIONS: In diabetic patients with autonomic neuropathy circadian variations in blood pressure are blunted. Ambulatory blood pressure monitoring can detect these abnormal variations and therefore may be useful in evaluating diabetic autonomic neuropathy.

Adult↗

Transient depletion of T cells with bright CD11a/CD18 expression from peripheral circulation during acute Kawasaki disease.

To clarify the activation of peripheral blood T cells in Kawasaki disease (KD) patients, we investigated whether expression of lymphocyte function-associated antigen-1 (LFA-1, CD11a/CD18) and/or intercellular adhesion molecule-1 (ICAM-1, CD54) on peripheral blood T cells increases during the acute stage. Expression of cellular adhesion molecules was measured using flow cytometry. There was a decrease in the percentage of CD3+ T cells in the bright LFA-1 alpha and LFA-1 beta population and a concomitant increase in the dim population of LFA-1 alpha and LFA-1 beta during the acute stage, in comparison with those of the convalescent stage. In addition, we observed no significant differences in ICAM-1 expression during the acute stage compared with that of the convalescent stage. In our view the present data, in conjunction with previous reports on T-cell function during acute KD, suggest that activated T cells are temporarily withdrawn from peripheral circulation during acute KD.

Acute Disease↗

Time-dependent blockade of neurogenic plasma extravasation in dura mater by 5-HT1B/D agonists and endopeptidase 24.11.

1. The delayed effects of stimulating the trigeminal ganglion unilaterally in rats and guinea-pigs were assessed by measuring the leakage of radiolabelled albumin from blood into the dura mater at intervals for up to 120 min after a 5 min stimulation period (5 Hz, 0.6 mA, 5 ms). 2. [125I]-albumin (50 microCi kg-1) was injected i.v. as a tracer 0, 20, 50, 80 or 110 min after stimulation and the animals were killed 10 min later. Extravasation of plasma protein developed for up to 90 min poststimulation. 3. To examine the mechanism underlying delayed plasma protein extravasation, CP-93,129 (5-HT1B receptor agonist, 460 nmol.kg-1), sumatriptan (5-HT1B/D receptor agonist, 24 nmol kg-1), or neutral endopeptidase 24.11 (1 nmol kg-1) were administered 45 or 75 min after trigeminal stimulation and 5 min before radiolabelled albumin. The extravasation response was reduced at 45 min. CP-23,129 also blocked extravasation when injected 25 min after capsaicin administration (1 mumol kg-1). 4. If the tracer was injected 5 min prior to electrical trigeminal stimulation, endopeptidase 24.11 (1 nmol kg-1) given 10 min before stimulation blocked the leakage (as reported previously for CP-93,129 or sumatriptan). All three compounds blocked the leakage when administered 30 min (but not 60 min) poststimulation in this paradigm. 5. The data support the previously made contention that neuropeptide release from sensory fibres mediates the plasma extravasation response following trigeminal ganglion stimulation, and that release and plasma leakage continue many minutes beyond the stimulation period. Hence, drugs that inhibit neuropeptide release (CP-93,129, sumatriptan), or enhance breakdown of neuropeptide mediators(endopeptidase 24.11) block the delayed extravasation response. Extravasation developing later than 45 min poststimulation was not neurogenically mediated.

Animals↗