Biomedical subjects
Publications and source records attributed to M Tominaga.
Pain is initiated when noxious stimuli excite the peripheral terminals of specialized primary afferent neurons called nociceptors. Many molecules are involved in conversion of the noxious stimuli to the electrical signals in the nociceptor endings. Among them, TRP channels play important roles in detecting noxious stimuli.
PURPOSE: Recent years, CT on rail system was reported to be useful as a tool for image-guided radiotherapy (IGRT). This system was clinically developed with the aim of stereotactic irradiation (STI) for brain, lung, liver, prostate and other sites. Quality assurance and quality control (QC) is an important issue in CT on rail system to assure geometric accuracies. The purpose of this study is to estimate the geometric accuracies of our CT on rail system using a detachable micro-multi leaf collimator (mMLC) with new type radiochromic films. Carrying out our original QC program, translational errors, setup reproducibility, beam misalignment and beam characteristics were evaluated. METHODS AND MATERIALS: We have studied with CT on rail system (FOCAL unit, Toshiba Medical systems, Tokyo, Japan) and mMLC unit (Accuknife, Direx Inc., Tokyo, Japan). We have developed original alignment phantom and small steel markers (2 mm phi) were implanted on its surface at certain intervals. Firstly, we have evaluated the accuracy of self-moving CT gantry and CT resolutions for cranio-caudal directions by changing slice thickness. And then using the phantom, we have measured the accuracy and reproducibility of geometric isocenter of the linac side and the CT gantry side by scanning the phantom. We have also measured the geometric changes of the common treatment couch by weight-loaded test (up to 135 kgw). To estimate dosimetric and geometric accuracies with the mMLC unit, the misalignment of the beam axes (gantry, collimator and couch rotation axis), mMLC leaf positions, and dose distributions for the verification plan were measured with new type GafChromic films (GafChromic-RTQA, ISP Inc., USA) and cylindrical phantom. The dose characteristics of the GafChromic film were also evaluated. RESULTS: The reproducibility of the self-moving CT gantry have a good agreement within 1 mm. Weight-load test have shown a good reliability within 2 mm at the common treatment couch. The translational precision of the common treatment couch was 0.0 +/- 0.1 mm at linac side and -0.2 +/- 0.5 mm at CT gantry side. The misalignments of beam axes have been kept within 0.4 mm at maximum. Gap test have shown the accuracies of the mMLC leaf positions, which is needed to keep within 1 mm by a routine calibration. CONCLUSIONS: To practice quality control program for the FOCAL unit and the mMLC unit is essential for a regular interval to reduce systematic errors. New type radiochromic film would be useful for a verification tool as alternative to conventional film.
BACKGROUND: This study aims to demonstrate the relevance of temperament to job stress. METHOD: The subjects were 848 male and 366 female Japanese company employees. Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire version (TEMPS-A) and Munich Personality Test (MPT) were administered to assess temperaments, and the NIOSH Generic Job Stress Questionnaire (GJSQ) to assess job stress. We used hierarchical multiple linear regression analysis in order to demonstrate whether temperament variables added any unique variance after controlling the effects of other predictors such as gender, age and job rank. RESULTS: In all subscales of the GJSQ, temperament predicted a large share of the variance in job stress. Remarkably, for interpersonal relationship stressors, the temperament variables added greater variance than that predicted by gender, age and job rank. Summary of the hierarchical linear regression analysis showed that the irritable temperament was associated with the most prominent vulnerability, followed by cyclothymic and anxious temperaments. The schizoid temperament had difficulty in the area of social support. On the other hand, the hyperthymic temperament displayed significant robustness in facing most job stressors; the melancholic type showed a similar pattern to a lesser degree. LIMITATION: The findings may be different in a clinical Japanese sample, or a cohort of healthy employees from a different cultural background. CONCLUSIONS: Temperament influences job stress significantly-indeed, it impacts on such stress with greater magnitude than age, gender and job rank in most areas examined. Temperament influences interpersonal relationship stressors more than workload-related stressors. Interestingly, in line with previous clinical and theoretical formulations, the hyperthymic and melancholic types actually appear to be "hyper-adapted" to the workplace.
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Uterine expression of the epidermal growth factor (EGF) family of growth factors has not been studied in the dog. The present study looks at the presence of mRNA transcripts and immunohistochemical localization for transforming growth factor-alpha (TGF-alpha), which is the potent EGF family member, and for EGF receptor (EGF-R) in the canine uterus during the estrous cycle. The reverse transcriptase-polymerase chain reaction together with sequencing of the products confirmed the presence of their mRNA transcripts in the endometrium throughout the estrous cycle. Immunohistochemical analysis found clear positive staining for TGF-alpha and EGF-R in the luminal and glandular epithelia at proestrus and estrus. Immunoreactivity decreased at the early stage of diestrus. In the mid stage of diestrus, clear staining for TGF-alpha was again found in the glands of the luminal region, and staining for EGF-R was observed in all glands. Very little staining was seen at anestrus for either TGF-alpha or EGF-R. These results suggest that TGF-alpha expressed in the uterus may be involved in regulating growth, differentiation and regression in the endometrial epithelial cells during the estrous cycle in the dog.
Use of combination anti-retroviral drug regimens including protease inhibitors dramatically decreased morbidity and mortality rates in HIV-1 infected individuals. However, such combination therapies appear to have many side effects, in addition to the emergence of resistant HIV-1 strains. Therefore, in this study we sought to elucidate novel therapeutic principles against HIV-1 infection. We examined the effects of electrical stimulation on both chronically HIV-1(LAI) infected HeLa cells (P6 HeLa/HIV-1(LAI)) and uninfected cells (P6 HeLa). Cells were cultured on an optically transparent electrode and application of potential at 1.0 V vs Ag/AgCl was performed over time periods ranging from 10 min to 60 min. Both P6 HeLa/HIV-1(LAI) and P6 HeLa cells were progressively damaged as the duration of electrical stimulation increased. However, P6 HeLa/HIV-1(LAl) cells were much more influenced by electrical stimulation than P6 HeLa cells. The difference in damage rate was most obvious at 30 min of electrical stimulation, with damaged cells accounting for about 87% and 4% of P6 HeLa/HIV-1(LAI) and P6 HeLa cells, respectively. After the application of potential for 20 min, the proliferation of P6 HeLa/HIV-1(LAI) cells was markedly inhibited, while the P6 HeLa cells proliferated to an extent similar to that of uninfected cells without application of potential. These results indicate that sensitivity to electrical stimulation is much higher in chronically HIV-1 infected cells than in uninfected cells. This could be considered as a useful new approach against HIV-1 infection.
Acquired immunodeficiency syndrome (AIDS) is a disease caused by infection with the human immunodeficiency virus (HIV). Although drug therapy for AIDS is available, problems such as side effects associated with drug therapy and the appearance of resistant HIV strains have arisen. Therefore, therapies based on new principles other than drug treatment are required. In the present study, the effect of electrical stimulation on HIV-1(LAI) chronically infected HeLa (P6 HeLa/HIV-1(LAI)) cells cultured on an electrode surface was examined. The results indicated that sensitivity to electrical stimulation was much higher in P6 HeLa/HIV-1(LAI) cells than in uninfected P6 HeLa cells. When electrical stimulation was applied at 1.0 V (vs. Ag/AgCl) for 20 min, the proportion of damage to cell membrane among P6 HeLa/HIV-1(LAI) cells, as evaluated by Trypan blue staining, was approximately 4 times higher than that for uninfected P6 HeLa cells. Furthermore, in comparison with uninfected P6 HeLa cells, the proliferation of P6 HeLa/HIV-1(LAI) cells was significantly suppressed after electrical stimulation. This technique was proven to selectively kill P6 HeLa/HIV-1(LAI) cells, when compared with uninfected control cells.
BACKGROUND: Compromised patients subjected to major digestive surgery frequently develop infective complications caused by methicillin-resistant Staphylococcus aureus (MRSA), which may have dangerous consequences. This was a prospective randomized study to determine whether intranasal mupirocin could reduce postoperative infective complications in patients having digestive surgery. METHODS: A total of 395 patients who underwent abdominal digestive surgery were assigned randomly into two groups: a treated group (193 patients) and controls (202). Patients in the treated group were given 30 mg mupirocin calcium hydrate ointment topically to each nostril three times a day on each of the 3 days before operation. The untreated group received no mupirocin treatment. RESULTS: Most infections were due to Gram-negative bacteria in both groups. There were 21 Gram-positive infections detected at the surgical site, ten in the treated group and 11 in control patients. The incidence of pneumonia was significantly different between the groups (none in the treated group and five in control patients; P = 0.028). Four of five patients with pneumonia had a sputum culture containing MRSA. CONCLUSION: Intranasal mupirocin treatment had no significant impact on surgical-site infection after digestive surgery.
Capsiate is a capsaicin-like ingredient of a non-pungent cultivar of red pepper, CH-19 sweet. To elucidate the mechanisms underlying the non-pungency of capsiate, we investigated whether capsiate activates the cloned capsaicin receptor, TRPV1 (VR1). In patch-clamp experiments, capsiate was found to activate TRPV1 expressed transiently in HEK293 cells with a similar potency as capsaicin. Capsiate induced nociceptive responses in mice when injected subcutaneously into their hindpaws with a similar dose dependency as capsaicin. These data indicate that the non-pungent capsiate is an agonist for TRPV1 and could excite peripheral nociceptors. In contrast to this, capsiate did not induce any significant responses when applied to the skin surface, eye or oral cavity of mice, suggesting that capsiate requires direct access to nerve endings to exhibit its effects. Capsiate was proved to have high lipophilicity and to be easily broken down in normal aqueous conditions, leading to less accessibility to nociceptors. Another highly lipophilic capsaicin analogue, olvanil, was similar to capsiate in that it did not produce irritant responses when applied to the skin surface, although it could activate TRPV1. Taken together, high lipophilicity and instability might be critical determinants for pungency and so help in understanding the effects of capsaicin-related compounds.
14-membered ring macrolides have been reported to have anti-inflammatory effects and to decrease neutrophil infiltration into the airways in chronic lower respiratory tract diseases. This study investigated the potential inhibitory effects of macrolide antibiotics on bleomycin-induced acute lung injury. Four drugs were studied: two 14-membered ring macrolides, clarithromycin (CAM) and roxithromycin (RXM); a 15-membered ring macrolide, azithromycin (AZM); and a 16-membered ring macrolide, josamycin (JM). Their effects were compared with macrolide untreated, pretreated, and post-treated groups. An acute lung injury was inhibited by pretreatment with CAM or RXM, which significantly ameliorated the bleomycin-induced increases in the total cell and neutrophil counts in bronchoalveolar lavage (BAL) fluids and the wet lung weight. The pretreatment with CAM or RXM also suppressed inflammatory cell infiltration and interstitial lung edema in the histopathological study. These inhibitory effects were associated with a decreased KC concentration in the BAL fluid and a decreased number of apoptotic cells in the lungs. Posttreatment with CAM or RXM had no marked inhibitory effects. Pretreatment with AZM was much less effective, and JM showed no inhibitory effects. These findings suggest that 14-membered ring macrolides have different effects on inflammatory lung disease than 15- and 16-membered ring macrolides and may be therapeutic agents for acute lung injury and pulmonary fibrosis.
BACKGROUND: Liver resection of segments VII and/or VIII sometimes requires segmental resection of the right hepatic vein in patients with liver tumours invading or located close to the hepatic vein. In this situation, hepatic vein reconstruction is thought to have an important role in the postoperative function of segment VI. This study investigated whether preoperative embolization of the major hepatic vein could obviate the need for hepatic vein reconstruction after cranial partial resection of the liver including the major hepatic vein trunk in a preclinical model. METHODS: Sixteen beagles were divided into two groups of eight: control group (hepatectomy alone) and hepatic venous embolization (HVE) group (hepatectomy after HVE). HVE was performed 2 weeks before hepatectomy. All dogs underwent resection of the cranial third of the left lateral liver lobe together with the major trunk of the left hepatic vein. Following hepatectomy, survival, histological features, portal venous pressure and serum aspartate aminotransferase (AST) levels were determined. RESULTS: Six control animals and seven in the HVE group were alive 1 week after hepatectomy. Immediately after hepatectomy, portal venous pressure was significantly higher in the control group compared with the HVE group (mean(s.d.) 14.0(1.1) versus 8.1(1.0) mmHg; P < 0.01). Histological examination of the remnant left lateral lobe demonstrated patchy parenchymal haemorrhage in the control group and normal parenchymal architecture in the HVE group. Peak AST levels were observed on day 1 in both groups and were significantly higher in the control group (mean(s.d.) 182(42) versus 67(40) units/l; P < 0.01). CONCLUSION: In this model, preoperative HVE facilitated interlobar venous collateral formation and minimized the untoward effects of segmental hepatic vein resection. This procedure may obviate the need for hepatic vein reconstruction after cranial partial liver resection including the major hepatic vein.
This study investigates the effects of candesartan, an angiotensin II type 1 receptor blockade, on carotid arterial intimal thickening and glucose tolerance in balloon-injured male Wistar fatty rats and their littermates (Wistar lean rats). Candesartan was orally administered to 12-week-old rats for 21 days, and age-matched rats without the agent were used as the respective controls. Balloon catheterization in the left common carotid artery was performed on day 7, and the artery was removed on day 14 for histological analysis. Compared with the area ratios of the neointima/media in fatty rats without treatment, the ratios in fatty rats treated with candesartan at 1 mg. kg(-1). d(-1) and lean rats without treatment were significantly decreased to 65%; on the other hand, the ratios of fatty rats treated with candesartan at 10 mg. kg(-1). d(-1) and lean rats treated with 1 mg. kg(-1). d(-1) were reduced to 35%, and those of lean rats treated with 10 mg. kg(-1). d(-1) were reduced to 28%. The administration of candesartan also decreased the level of plasma glucose time- and dose-dependently in fatty rats. In an intragastric glucose load, the levels of both glucose and insulin at 30 and 60 minutes were significantly decreased when fatty rats were treated with candesartan at 10 mg. kg(-1). d(-1). In cultured vascular smooth muscle cells from fatty rats, insulin-stimulated Akt (New England Biolabs) phosphorylation and 2-deoxy-D-glucose uptake were inhibited to 59% and 68%, respectively, by angiotensin II, but the effects were ameliorated by the addition of 10(-7) mol/L candesartan. We conclude that candesartan could be effective for the suppression of vascular smooth muscle cell growth dose-dependently in Wistar fatty and lean rats. Furthermore, the agent could improve insulin resistance in Wistar fatty rats.
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. It has been proposed that ATP, released from different cell types, initiates the sensation of pain by acting predominantly on nociceptive ionotropic purinoceptors located on sensory nerve terminals. In this study, we examined the effects of extracellular ATP on VR1. In cells expressing VR1, ATP increased the currents evoked by capsaicin or protons through activation of metabotropic P2Y(1) receptors in a protein kinase C-dependent pathway. The involvement of G(q/11)-coupled metabotropic receptors in the potentiation of VR1 response was confirmed in cells expressing both VR1 and M1 muscarinic acetylcholine receptors. In the presence of ATP, the temperature threshold for VR1 activation was reduced from 42 degrees C to 35 degrees C, such that normally nonpainful thermal stimuli (i.e., normal body temperature) were capable of activating VR1. This represents a novel mechanism through which the large amounts of ATP released from damaged cells in response to tissue trauma might trigger the sensation of pain.
To clarify the role of nitric oxide (NO) in the pathogenesis of seizures in susceptible EL mice, we investigated effects of three drugs potentially related to NO production, MK-801, dantrolene, and FK506, on convulsive seizures and brain NO metabolites (NOx). MK-801 or dantrolene, but not FK506, suppressed convulsive seizures in EL mice; only MK-801 reduced NOx in the brain. Our results suggested involvement of the N-methyl-D-aspartate receptor-channel complex and intracellular calcium mobilization, but not calcineurin, in the convulsions of EL mice.
Effects of a solvent mixture commonly used to dissolve antiepileptic drugs on the anticonvulsive effect as well as serum and brain concentrations of zonisamide (ZNS), a sulfonamide derivative, were investigated. The solvent mixture consisted of propylene glycol (PG, 40%) and ethanol (10.5%) in saline (PES). Intraperitoneal administration of ZNS at 25, 50, and 75 mg/kg dissolved in PES suppressed seizures in the EL strain of mice more effectively than the same doses of ZNS in saline. Serum and brain concentrations of the drug were significantly higher with PES than with saline as the vehicle for administration. At a dose of 75 mg/kg ip, both serum and brain ZNS concentrations in mice treated with ZNS in PES remained significantly higher than concentrations in mice treated with ZNS in saline from 1 to 6 hours after injection. PES mixtures including PG may not be suitable solvents for antiepileptic drugs in experiments investigating anticonvulsive effects.
BACKGROUND: Complete hepatic venous isolation and extracorporeal charcoal hemoperfusion (HVI.CHP) can limit systemic exposure to high-dose chemotherapeutic agents when given by hepatic arterial infusion (HAI). The purpose of this study was to determine if the concomitant use of sodium thiosulfate (STS) could further expand the advantages of pharmacologic delivery of HVI.CHP for cisplatin (CDDP) during HAI chemotherapy. METHODS: CDDP (4mg/kg) was administered over 20 minutes via HAI under conditions of HVI.CHP in 14 mongrel dogs. HVI.CHP was performed for 30 minutes after initiation of HAI. During CDDP infusion, 7 dogs each received 400 mg/kg STS (a 100-fold molar ratio to CDDP) over 20 minutes via the prefilter (STS group) circuit line, while the remaining 7 dogs (controls) received no STS. Blood samples were taken serially from the prefilter circuit line (hepatic venous blood), postfilter line, and the left carotid artery (systemic blood). The free and total CDDP concentrations in these samples were determined by flameless atomic absorption spectrophotometry. RESULTS: During 20 minutes HAI of CDDP, the mean CDDP extraction ratios (ER) by CHP filter were always higher in the STS group than in the control group, regardless of the form (free or total) of CDDP. The differences between the STS and control groups in the extraction ratios of free and total CDDP were significant at all time points measured (P < .05). Consequently, systemic exposure to CDDP, as assessed by area under the time-concentration curve of total CDDP, was significantly lower in the STS group than in the control group (P < .05). CONCLUSIONS: These results indicated that concomitant STS infusion could further increase the effect of HVI.CHP on CDDP removal after HAI.
We studied the difference in glucose levels between capillary and venous whole blood during 75-g oral glucose tolerance test (OGTT) in 75 healthy subjects. Capillary and venous whole blood glucose values were measured by HK-G6PD method after deproteinization. The post-loaded glucose levels in capillary blood were significantly higher than those in venous blood, and the mean values of capillary and venous difference at 30, 60, 90, 120 and 180 min were 1.37, 1.40, 1.07, 0.95 and 0.52 mmol/l, respectively, with the maximum difference at 60 min. No correlation was found in the magnitude of the differences in glucose between capillary and venous blood specimens. We determined the inaccuracy of six self-monitoring blood glucose devices relative to the reference method using venous plasma, venous whole blood and capillary whole blood from 31 diabetic patients. The differences of mean values of venous whole blood and capillary whole blood, and venous whole blood and venous plasma, and capillary whole blood and venous plasma were 9.6%, 11.3% and -3.2%, respectively. The range of bias and Sy/x were 0.31-1.06 mmol/l and 0.71-1.07 mmol/l, respectively, compared to the reference method using venous plasma.
Nociceptin (orphanin FQ) may act on primary afferents and be involved in the regulation of nociceptive processing. We have shown, using reverse transcription-polymerase chain reaction (RT-PCR), that carrageenan-produced peripheral inflammation induces the expression of prepronociceptin (PPN) mRNA in the dorsal root ganglia (DRG). The present experiments were conducted to determine the localization of PPN mRNA in primary sensory neurons after peripheral inflammation, using in situ hybridization. An intraplantar injection of carrageenan induced the expression of PPN mRNA in small and medium sized neurons in the DRG; the effect peaked 0.5 h after carrageenan and subsided by 6 h. All neurons positive for PPN mRNA were positive for vanilloid receptor subtype 1 (VR1)-like immunoreactivity and some VR1-immunoreactive neurons were negative for PPN mRNA. The results suggest that peripheral inflammation induces the production of nociceptin in a sub-population of VR1-positive primary sensory neurons and support the idea that nociceptin produced there is involved in the regulation of nociceptive processing.