Biomedical subjects

M Tominaga

Publications and source records attributed to M Tominaga.

At least 55 records · Page 3Linked to original sources

PubMed2001

[Effect of caffeine on microcirculation of human ocular fundus].

PURPOSE: To determine the effect of caffeine on the microcirculation in the human ocular fundus. SUBJECTS AND METHODS: The microcirculation of the ocular fundus in 10 eyes of 10 healthy volunteers was studied using a laser speckle tissue circulation analyser. 100 mg of caffeine or placebo was given orally in a double-blind test. Square blur rate(SBR), a quantitative index of blood flow velocity, was measured in the temporal site of the optic nerve head(ONH) free of surface vessels and in the middle site of the choroid-retina between the ONH and the macula. Intraocular pressure(IOP), blood pressure(BP), pulse rate(PR), and central critical fusion frequency(CFF) were also measured. These parameters were measured before and for 2 hours after administration. The area under curve(AUC), of the SBR was calculated for each area. Ocular perfusion pressure(OPP) was also obtained from blood pressure and intraocular pressure. RESULTS: The time-course change of SBR value showed much individual difference. Caffeine decreased the AUC of the SBR in the ONH as well as in the choroid-retina significantly. IOP, mean BP, PR, OPP and central CFF did not change significantly. CONCLUSIONS: These results suggest that caffeine may increase blood vessel resistance and decrease blood flow in the ONH and choroid-retina in humans.

Adult↗

PubMed2001

[A case of micronodular pneumocyte hyperplasia, lymphangiomyomatosis associated with tuberous sclerosis].

We report a case of tuberous sclerosis (TS) associated with renal angiolipomas, subungual fibroma, adenoma sebaceum, pulmonary lymphangiomyomatosis (LAM), and micronodular pneumocyte hyperplasia (MNPH). A CT scan of the chest demonstrated multiple minute nodules present throughout both lung fields. Histologically, the nodules were well demarcated, and were composed of thickened, fibrotic, alveolar septa lined by pleomorphic, type II pneumocytes. This type of MNPH is extremely rare, and appears to be a hamartomatous proliferation occurring in patients with TS.

Adult↗

PubMed2001

[A case of desmoplastic malignant pleural mesothelioma].

A 71-year-old woman with no history of asbestos exposure was referred to our hospital for evaluation of mediastinal soft tissue density. Six months prior to the admission, she had developed back pain and had been diagnosed as having intercostal neuralgia. Since the symptoms progressed, she was referred to another hospital. While chest radiography revealed no abnormality, chest computed tomography showed the prominence of mediastinal soft tissue, extending to the left hilum and partially destroying the nearby vertebrae. However, no pleural effusion was noted. After admission, a thoracoscopic examination was performed, and a whitish mass was found on the pleural surface partially adhering to the chest wall. Histological examination of the biopsied material showed dense areas of collagenous tissue with small foci of slightly atypical spindle cells. These findings led to the diagnosis of desmoplastic malignant pleural mesothelioma. The patient was treated with combined chemo-radiotherapy, but the response to this treatment was unclear. To date, reports for this subgroup of malignant mesothelioma are still rare.

Aged↗

PubMed2001

[Evaluation of dysmorphic red cells in the urinary sediment].

The usefulness of the morphologic examination of urinary red cells was first described by Birch and Fairley, who reported that the dysmorphic red cells(morphologically variable) were the marker for glomerular bleeding and the isomorphic red cells(morphologically uniform) for non-glomerular bleeding. They also noted that healthy individuals had dysmorphic cells, indicating a glomerular source. The relation between red blood cell morphology and the origin of hematuria has been confirmed subsequently by numerous clinical studies. Although the reports varied on the ratio(10-100%) of dysmorphic cells, their findings have been supported by many investigators. In 1991 Köhler noted that acanthocytes(AC) were the most characteristic red cell type for glomerular bleeding and that acanthocyturia > or = 5% was a good predictive marker for glomerular bleeding. Moreover the red cell was easily recognized. On the other hand, in 1993 Fairley and Birch reported that in glomerulonephritis, erythrocytes varied markedly in size, shape, and hemoglobin content, and that the pattern of morphology indicates the source of bleeding, not the morphology of individual cells. Both observations were confirmed in our in vitro experiments. To clarify the causative mechanism of acanthocyturia, the normal washed erythrocytes were successively exposed to two kinds of solutions simulating conditions in the distal tubules(105 mOsm, pH 5.5, NaCl 37 mmol/l, KH2PO4 1.0 mmol/l, Urea 0.9 g/l) and the collecting tubules(a mixture of NaCl and KH2PO4 solutions with the osmolality between 299 and 1192 mOsm). Various degrees of hemolytic process appeared in the first solution. However, AC appeared only in the second solutions with 9 mmol/l of KH2PO4 and 390 mOsm or more osmolality or with 725 mOsm and 4.1 mmol/l or more of KH2PO4. This result supported the nephron passage theory in the formation of AC in glomerular diseases.

Acanthocytes↗

PubMed2001

[Standard material for measurement of hemoglobin A1c].

In Japan, the standardization of measurement of hemoglobin A1c(HbA1c) has been successfully achieved using the standard material(JDS Lot 1, lyophilized, two levels) produced and distributed by the former Shima Committee of the Japan Diabetes Society(JDS). However, methods for measurement of HbA1c other than the HPLC method, for example immunoassay, have been commonly used in the laboratory. Peptide mapping, a candidate method of analytical chemistry for determination of HbA1c, cannot be applied to a lyophilized sample. The present JDS Committee, which continues the work of the Shima Committee, recently certified a deeply-frozen material as the primary standard reference material(five levels) and named it JDS Lot 2. The Lot 2 value of HbA1c is the same as Lot 1, and is different from the National Glycohemoglobin Standardization Program(NGSP) value by -0.3%. It is likely that the standardization of measurement of HbA1c in the future in Japan will be continued using with JDS Lot 2.

Chromatography, High Pressure Liquid↗

PubMed2000

Novel design of nonpeptide AVP V(2) receptor agonists: structural requirements for an agonist having 1-(4-aminobenzoyl)-2,3,4, 5-tetrahydro-1H-1-benzazepine as a template.

The discovery of a series of nonpeptide arginine vasopressin V(2) receptor agonists is described. After identifying the aniline derivative 8 as our lead compound from the metabolites of compound 7 that showed antidiuretic activity by po administration to Brattleboro rats, improvements in the in vitro potency involving evaluations of the structural requirements for agonist action and optimizing the structure of the benzoyl moiety have been intensively undertaken. These studies led to compounds 16g, 19a, and 23b,h,i that show potent agonist activity for the V(2) receptor.

Administration, Oral↗

PubMed2000

Effects of combined administration of zonisamide and valproic acid or phenytoin to nitric oxide production, monoamines and zonisamide concentrations in the brain of seizure-susceptible EL mice.

This study was undertaken to elucidate the anticonvulsive effects of zonisamide (ZNS: 25, 50, and 75 mg/kg, intraperitoneal [i.p.]), which was coadministered with valproic acid (VPA: 25, 50, and 100 mg/kg, i.p.), or phenytoin (PHT: 10, 25, and 50 mg/kg, i.p.) to ZNS concentration, nitric oxide metabolites (NOx levels), and monoamines in the brain of the EL mouse, a strain highly susceptible to seizures. NOx levels were obtained from measuring of combined level of nitrite plus nitrate. Coadministration of ZNS with VPA or PHT suppressed convulsive seizures more effectively than with treatment of ZNS alone. Both serum and brain concentrations of ZNS tended to increase as the dose of VPA or PHT was increased. While coadministrations of ZNS (75 mg/kg) and VPA or PHT at any dose did not change brain and serum NOx levels, those altered brain monoamine contents. These results suggested that anticonvulsive effect of coadministrations of ZNS and VPA or PHT were caused by changes of monoamines rather than changes of NO metabolites.

Animals↗

PubMed2000

Acid potentiation of the capsaicin receptor determined by a key extracellular site.

The capsaicin (vanilloid) receptor, VR1, is a sensory neuron-specific ion channel that serves as a polymodal detector of pain-producing chemical and physical stimuli. The response of VR1 to capsaicin or noxious heat is dynamically potentiated by extracellular protons within a pH range encountered during tissue acidosis, such as that associated with arthritis, infarction, tumor growth, and other forms of injury. A molecular determinant for this important physiological activity was localized to an extracellular Glu residue (E600) in the region linking the fifth transmembrane domain with the putative pore-forming region of the channel. We suggest that this residue serves as a key regulatory site of the receptor by setting sensitivity to other noxious stimuli in response to changes in extracellular proton concentration. We also demonstrate that protons, vanilloids, and heat promote channel opening through distinct pathways, because mutations at a second site (E648) selectively abrogate proton-evoked channel activation without diminishing responses to other noxious stimuli. Our findings provide molecular evidence for stimulus-specific steps in VR1 activation and offer strategies for the development of novel analgesic agents.

Acids↗

PubMed2000

Successful rescue of severe recurrent hepatitis C with interferon and ribavirin in a liver transplant patient.

BACKGROUND: Rapid graft dysfunction caused by hepatitis C virus (HCV) reinfection, although uncommon, is a disastrous complication in liver transplant patients. Finding an effective therapy for this subgroup of patients with severe recurrent HCV is a priority. METHOD: We describe a successful rescue of a 46-year-old man with recurrent hepatitis C (HCV genotype 1b) using long-term interferon (IFN) and ribavirin. The patient had a very aggressive type of posttransplantation HCV infection, as judged by biochemical and histologic findings. RESULTS: Despite high pretreatment values of serum alanine aminotransferase (ALT; peak value of 901 IU/L) and HCV-RNA (2.3 x 10(6) copies/ml), the combination therapy with IFN and ribavirin produced a rapid normalization of the serum ALT values, accompanied by the clearance of serum HCV-RNA. Although HCV-RNA reappeared in the serum at 3 months, the patient had continued ALT normalization and histological improvement with follow-up of over 26 months to date after the initiation of the combination therapy. CONCLUSION: This observation suggests that IFN in combination with ribavirin may offer an effective therapeutic option for liver transplant patients with severe recurrent hepatitis C.

Alanine Transaminase↗

PubMed2000

The effect of alcohol on convulsions and nitric oxide levels in seizure-susceptible el mice.

To evaluate the influences of ethanol intake on convulsive seizures and brain nitric oxide (NO) production, EL mice, a strain highly susceptible to seizures, were given a 10% ethanol solution ad libitum. In mice consuming ethanol for 4, 8, and 12 weeks, seizures were not suppressed by zonisamide (75 mg/kg ip). Brain NO metabolite levels in mice after 12 weeks of consumption were significantly lower than those in control mice and those consuming ethanol for 4 weeks. Numbers of NADPH diaphorase-positive neurons in the hippocampal formation and parietal cortex of mice consuming for 4 and 12 weeks were significantly higher than in controls. These results suggested that increasing of numbers of NADPH diaphorase-positive neurons in the hippocampal formation and parietal cortex were assumed to develop in compensation for reduction in whole-brain NO metabolite levels of EL mice exposed to ethanol.

Journal Article↗

PubMed2000

Successful treatments of lung injury and skin burn due to hydrofluoric acid exposure.

Recent growth in the electronics and chemical industries has brought about a progressive increase in the use of hydrofluoric acid (HF), along with the concomitant risk of acute poisoning among HF workers. We report severe cases of inhalation exposure and skin injury which were successfully treated by administering a 5% calcium gluconate solution with a nebulizer and applying 2.5% calcium gluconate jelly, respectively. Case 1: A 52-year old worker used HF for surface treatment after welding stainless steel, and was hospitalized with rapid onset of severe dyspnea. On admission to the critical care medical center he had widespread wheezing and crackles in his lungs. Chest radiograph showed a fine diffuse veiling over both lower pulmonary fields. Severe hypocalcemia with high concentrations of F in serum and urine were disclosed. He was immediately given 5% calcium gluconate solution by intermittent positive-pressure breathing (IPPB), utilizing a nebulizer. On the 21st hospital day, chest film and CT scan did not demonstrate any abnormality. He was discharged very much improved on the 22nd hospital day. Case 2: A 35-year old worker at an electronics factory was admitted to his local hospital with severe skin burn on his face and neck after exposure to 100% HF. Treatment began with immediate copious washing with water for 20 min. Calcium gluconate 2.5% gel (HF burn jelly) was applied to the area as a first-aid measure. Persistent high concentrations of serum and urinary F were disclosed for 2 weeks. After treatment with applications of HF burn jelly, he was confirmed as being completely recovered. The present cases and a review of published data suggest that an adequate method of emergency treatment for accidental HF poisoning is necessary.

Administration, Topical↗

PubMed2000

The role of plant villin in the organization of the actin cytoskeleton, cytoplasmic streaming and the architecture of the transvacuolar strand in root hair cells of Hydrocharis.

In many types of plant cell, bundles of actin filaments (AFs) are generally involved in cytoplasmic streaming and the organization of transvacuolar strands. Actin cross-linking proteins are believed to arrange AFs into the bundles. In root hair cells of Hydrocharis dubia (Blume) Baker, a 135-kDa polypeptide cross-reacted with an antiserum against a 135-kDa actin-bundling protein (135-ABP), a villin homologue, isolated from lily pollen tubes. Immunofluorescence microscopy revealed that the 135-kDa polypeptide co-localized with AF bundles in the transvacuolar strand and in the sub-cortical region of the cells. Microinjection of antiserum against 135-ABP into living root hair cells induced the disappearance of the transvacuolar strand. Concomitantly, thick AF bundles in the transvacuolar strand dispersed into thin bundles. In the root hair cells, AFs showed uniform polarity in the bundles, which is consistent with the in-vitro activity of 135-ABP. These results suggest that villin is a factor responsible for bundling AFs in root hair cells as well as in pollen tubes, and that it plays a key role in determining the direction of cytoplasmic streaming in these cells.

Actins↗

PubMed2000

Chairpersons' opinions regarding quality control of surgical faculty performance in Japanese academic surgery departments.

BACKGROUND: The governance and power structure of the department of surgery depends to a large extent on the chairperson's decisions in Japanese medical schools. This paper reports the current collective opinions of surgery department chairpersons regarding the quality assessment of surgical faculty performance. METHODS: Surveyed were 78 chairpersons of general surgery departments from 72 Japanese medical schools. Chairpersons were questioned about administrative and organizational decision making: rank order requirements for full-time surgical faculties, coordination of staff for surgical operations, and performance outcome measures. RESULTS: In all, 68 (87%) chairpersons responded. When selecting surgical faculties, publishing competence (45%) and collaborative personality (44%) were the two foremost concerns of chairpersons. Teaching experience (0%) and board certification (2%) showed the lowest rate for the first priority among the 6 elements listed. The operator was mainly decided by the chairperson (63%) whereas the rest of the operative team members were decided by either the chairperson (28%), a specialty team (38%), or attending surgeons (32%). Thirty-three chairpersons (49%) of 68 respondents used the morbidity and mortality conference as the only available approach for assessing surgical performance on a regular basis, whereas the remaining half did not have routine outcome measures. CONCLUSIONS: The results of this study indicate that surgery department chairpersons deemed collaborative personality and publishing competence the two major requirements for candidates of surgical faculties. Although the morbidity and mortality conference is currently the only available approach for assessing surgical performance, the majority of chairpersons felt that outcome measures should be based on more objective and structured criteria.

Academic Medical Centers↗

PubMed2000

Age-related alterations of nitric oxide production in the brains of seizure-susceptible EL mice.

We evaluated age-related changes in nitric oxide (NO) production in the brains of EL mice, a strain highly susceptible to seizures. A group of EL(s) mice were tossed up weekly to induce convulsive seizures, while in a nonstimulated EL(ns) group induction of convulsive seizures was avoided. Brain levels of nitrite plus nitrate (NOx) in EL(ns) mice were significantly higher than in nonstimulated mice at 10 days, and also higher than levels at 15 and 50 weeks in either EL(s) or EL(ns) mice. A significantly higher number of NO-producing cells were demonstrated in the hippocampus and parietal cortex by staining for nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase in EL(s) mice at the ages of 15 and 50 weeks than in EL(ns) mice at the age of 6 weeks. In EL(ns) mice, significantly fewer neurons showed NADPH-diaphorase staining in the hippocampus, striatum and parietal cortex at the age of 50 weeks than at 6 weeks. The present results suggest that whole-brain NOx levels in EL(ns) and EL(s) mice and numbers of NADPH-diaphorase-positive neurons in EL(ns) mice decreased with aging, while increasing of numbers of such neurons in EL(s) mice were assumed to develop in compensation for reduction in whole-brain NOx levels.

Aging↗

PubMed2000

Venodilatory effect of pranidipine, a calcium channel blocker, monitored with perfluorocarbon in vivo (19)F-NMR spectroscopy.

We previously reported that the (19)F-NMR signal intensity of perfluorocarbon was increased by a venodilator, nitroglycerine, and decreased by an arteriodilator, hydralazine. In the present study, we demonstrated that pranidipine, a calcium channel blocker, increased the intensity of the FC-43 signal, while nifedipine, a prototype of calcium channel blockers, did not. These results suggest that pranidipine dilates the venous system in contrast to nifedipine.

Animals↗

PubMed2000

Characterization of a novel nonpeptide vasopressin V(2)-agonist, OPC-51803, in cells transfected human vasopressin receptor subtypes.

We discovered the first nonpeptide arginine-vasopressin (AVP) V(2)-receptor agonist, OPC-51803. Pharmacological properties of OPC-51803 were elucidated using HeLa cells expressing human AVP receptor subtypes (V(2), V(1a) and V(1b)) and compared with those of 1-desamino-8-D-arginine vasopressin (dDAVP), a peptide V(2)-receptor agonist. OPC-51803 and dDAVP displaced [(3)H]-AVP binding to human V(2)- and V(1a)-receptors with K(i) values of 91.9+/-10.8 nM (n = 6) and 3.12+/-0.38 nM (n = 6) for V(2)-receptors, and 819+/-39 nM (n = 6) and 41.5+/-9.9 nM (n = 6) for V(1a)-receptors, indicating that OPC-51803 was about nine times more selective for V(2)-receptors, similar to the selectivity of dDAVP. OPC-51803 scarcely displaced [(3)H]-AVP binding to human V(1b)-receptors even at 10(-4) M, while dDAVP showed potent affinity to human V(1b)-receptors with the K(i) value of 13.7+/-3.2 nM (n = 4). OPC-51803 concentration-dependently increased cyclic adenosine 3', 5'-monophosphate (cyclic AMP) production in HeLa cells expressing human V(2)-receptors with an EC(50) value of 189+/-14 nM (n = 6). The concentration-response curve for cyclic AMP production induced by OPC-51803 was shifted to the right in the presence of a V(2)-antagonist, OPC-31260. At 10(-5) M, OPC-51803 did not increase the intracellular Ca(2+) concentration ([Ca(2+)](i)) in HeLa cells expressing human V(1a)-receptors. On the other hand, dDAVP increased [Ca(2+)](i) in HeLa cells expressing human V(1a)- and V(1b)-receptors in a concentration-dependent fashion. From these results, OPC-51803 has been confirmed to be the first nonpeptide agonist for human AVP V(2)-receptors without agonistic activities for V(1a)- and V(1b)-receptors. OPC-51803 may be useful for the treatment of AVP-deficient pathophysiological states and as a tool for AVP researches.

Arginine Vasopressin↗

PubMed2000

Nifedipine suppresses neointimal thickening by its inhibitory effect on vascular smooth muscle cell growth via a MEK-ERK pathway coupling with Pyk2.

The aim of this study was to determine whether nifedipine could suppress an atherogenic process such as balloon-injured intimal thickening in vivo and the proliferation of vascular smooth muscle cells (VSMC) in vitro. First, we examined the in vivo effect of nifedipine to determine whether it could suppress intimal thickening induced by balloon catheterization. Sprague-Dawley (SD) rats were divided into three groups (L, nifedipine 0.3 mg kg(-1) day(-1); H, nifedipine 3 mg kg(-1) day(-1); C, no nifedipine), and Alzet((R)) osmotic pumps were implanted in their backs for continuous administration. The neointimal layers were completely occupied by proliferated VSMC, and the area ratios of neointima/media treated with nifedipine significantly decreased dose-dependently compared to those of the control. Neither blood pressure nor lipid levels changed among the three groups. We next evaluated the in vitro effect of nifedipine on the proliferation of cultured rat VSMC. Nifedipine decreased the values of [(3)H]-thymidine incorporation and total cellular protein content as well as the levels of phosphorylated extracellular signal-regulated protein kinase (ERK) 1/2, mitogen-activated protein kinase kinase (MEK) 1/2, and even the phosphorylation of Pyk2, in dose-dependent fashions. In addition, nifedipine suppressed the levels of proliferative cell nuclear antigen (PCNA) dose-dependently in both VSMC and balloon-injured thoracic aortae. These results indicate that nifedipine has an inhibitory effect on intimal thickening by attenuating intimal VSMC proliferation, suggesting that nifedipine could be effective for preventing the progression of atherosclerotic plaque as in restenosis after angioplasty.

Actins↗

PubMed2000

Expression of cyclooxygenase-1 (COX-1) in labial salivary glands of Sjögren's syndrome.

COX plays an important role in inflammatory diseases such as rheumatoid arthritis. To determine the role of COX in Sjögren's syndrome (SS), we examined COX expression in the salivary glands of SS patients. We examined 15 patients with SS and two normal subjects. Labial salivary gland tissue samples were analysed immunohistochemically using anti-COX-1 and COX-2 antibodies. All biopsy samples from 15 patients with SS were stained for COX-1. In contrast, COX-1 immunostaining was not detected in normal salivary gland tissues. Co-expression of COX-1 and CD68 was confirmed by mirror section technique and double antibody immunostaining. This finding indicated that COX-1-expressing cells in SS salivary glands were infiltrating macrophages. In contrast to COX-1 staining, only a little COX-2 immunostaining was observed in salivary gland tissues from SS patients. These data suggest that COX-1 expression on infiltrating macrophages may contribute to the inflammatory process of salivary glands in SS.

Adult↗