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Biomedical subjects

K Hamada

Publications and source records attributed to K Hamada.

At least 577 records · Page 32Linked to original sources
PubMedDate not supplied

Anticonvulsive effect of dapsone (4,4'-diaminodiphenyl sulfone) on amygdala-kindled seizures in rats and cats.

Dapsone (4,4'-diaminodiphenyl sulfone; DDS), an established anti-leprosy drug, showed anticonvulsive effects in the amygdaloid kindling model of epilepsy. Single doses of the drug in rats (6.25-12.5 mg/kg, i.p.) suppressed the kindled seizures in a dose-dependent manner without overt behavioral toxicity. With repeated oral administration in cats, relatively higher initial doses (13-23 mg/kg) were required to obtain seizure suppression, and neurotoxic signs occurred within a few days with serum drug levels of approximately 20 micrograms/ml. Although dapsone showed anticonvulsive effects in both animal species, the effective serum levels overlapped the toxic levels reported in the clinical treatment of leprosy. In the majority of the cats, however, seizure suppression was maintained even after the discontinuation of dapsone with lower serum levels than those observed at the beginning of the seizure suppression. Therefore, dapsone would be useful as an antiepileptic drug only when long-term anticonvulsive efficacy is demonstrated using smaller doses comparable to those used in the treatment of leprosy.

Amygdala↗
PubMedDate not supplied

Role of EP4 prostaglandin E2 receptor in the ischemic liver.

Prostaglandin E(2) (PGE(2)) mediates a variety of both innate and adaptive immunity responses through 4 distinct receptors, EP1-4. Recent studies have suggested the physiological and pathological role of EP4 in various inflammatory diseases. In this study, we investigated the importance of the EP4 receptor, and the efficacy of a selective EP4 agonist to alter hepatic ischemia/reperfusion (I/R) injury, an important cause of damage in liver resection and transplantation. We used an established murine I/R injury model, 70% partial hepatic ischemia for 90 minutes in male C57BL/6 mice. The local expression of EP4 messenger RNA (mRNA) in the naive and the ischemic liver at 2 hours after reperfusion was examined using RT-PCR analysis. Some mice received the EP4 selective agonist during I/R. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured as markers of hepatic injury. EP4 expression in the liver was significantly up-regulated at 2 hours after reperfusion. Furthermore, treatment with EP4 agonist significantly inhibited hepatic injury at 6 hours after reperfusion. Our data suggest an inhibitory role of EP4 PGE(2) receptor in hepatic I/R injury and the therapeutic efficacy of a selective EP4 agonist for liver protection.

Alanine Transaminase↗
PubMedDate not supplied

Physical properties of hemoglobin vesicles as red cell substitutes.

Hemoglobin vesicles (HbV) as red cell substitutes were prepared from a purified carbonylhemoglobin (HbCO) solution and a lipid mixture composed of phospholipids, cholesterol, and alpha-tocopherol. The diameter was controlled to 251 +/- 87 nm using an extrusion method; the vesicles penetrated through the membrane filters with regulated pore sizes. After the ligand exchanging reaction (HbCO-->HbO2), the oxygen affinity (P50) of HbV was 32 Torr, which was controlled with the coencapsulation of pyridoxal 5'-phosphate. The rate of metHb formation in HbV was nonenzymatically reduced with the coencapsulation of DL-homocysteine. The Hb concentration of the HbV suspension, which was dispersed in a phosphate buffered saline solution (pH 7.4), was controlled at 10 g/dL. At this concentration, the total lipid concentration was 6.2 g/dL and the viscosity, 2.6 cP (230 s-1), was lower than that of the blood (4.4 cP). The HbV suspension showed a typical non-Newtonian flow for a particle dispersion and agreed well with the Casson model. The viscosity at shear rates lower than 23 s-1 showed a maximum with increasing the mixing ratio of human blood, plasma, or albumin, while no maximum was observed for the mixture with washed red blood cells. The aggregates of HbV are formed by interaction with plasma proteins, including albumin, while the aggregates reversibly dissociate at higher shear rate.

Blood Substitutes↗
PubMedDate not supplied

Evaluation of cellular immune responses in rhesus monkeys subjected to adenovirus-mediated gene transfer into the cervix.

We reported previously that direct injection of a recombinant adenovirus (rAd), Ad5CMV-beta-gal, into the cervix of the rhesus monkey resulted in efficient beta-galactosidase expression in the cervix within 3 days. In these studies, we also observed the induction of anti-adenovirus (Ad)-specific immunoglobulin G responses after 22 days. In the continuation of evaluating the anti-Ad-specific immune responses resulting from this approach of gene targeting to the cervix, we measured the cellular immune responses. The introduction of Ad5CMV-beta-gal into the cervix by direct injection, but not by the abrasion technique, resulted in the induction of strong proliferative responses against extracts of cells infected with Ad5CMV-beta-gal but not against control uninfected cells. These responses were initially detected at 22 days postinjection and coincided with the abrogation of transgene expression. Significant levels of proliferative responses were maintained for < or =83 days. Multiple injections of rAds had no significant enhancing effect on either the level or longevity of the proliferative responses. At 3 days after the injection of Ad5CMV-beta-gal, when the transgene expression in the cervix was clearly evident, proliferative responses against the rAd were not detectable. However, the production of low but significant amounts of interleukin-10, a cytokine characteristic of T helper type 2 responses that promote humoral immune responses, was observed at the 3-day point in these animals. These results suggest that significant differences exist between the kinetics of transgene expression and the priming of specific host immune responses, and that these differences may be important for devising alternate strategies to improve techniques for Ad-mediated gene therapy of cervical cancer.

Adenoviridae↗
PubMedDate not supplied

MR imaging of pontine and extrapontine myelinolysis.

Two cases of pontine and extrapontine myelinolysis following electrolyte derangements are presented. One case showed only extrapontine myelinolytic lesions on magnetic resonance (MR) imaging, although both pontine and extrapontine myelinolysis were confirmed at postmortem. Another case made full recovery clinically with resolution of extrapontine lesions on MR imaging.

Adult↗
PubMedDate not supplied

CT and MR findings in tuberculous mediastinitis.

OBJECTIVE: Tuberculous mediastinitis, a rare complication of pulmonary tuberculosis, may simulate a mediastinal tumor on chest radiography. For evaluation and follow-up of the disease, CT and MRI are needed. MATERIALS AND METHODS: Two cases of tuberculous mediastinitis are presented with emphasis on the importance of MRI. In both cases, MRI was performed because the CT appearance was unusual for a mediastinal tumor. RESULTS: The areas of low signal intensity within the anterior mediastinal mass on both T1- and T2-weighted imaging were due to the reactive fibrous tissue and were suggestive of an inflammatory mass. CONCLUSION: When a mediastinal mass would be unusual on CT, MRI should be performed. If there are areas of low signal intensity within the mass on both T1- and T2-weighted imaging, an inflammatory mass such as tuberculous mediastinitis, is one of the possibilities.

Adult↗
PubMedDate not supplied

Hyperintense basal ganglia lesions on T1-weighted images in hereditary hemorrhagic telangiectasia with hepatic involvement.

We present two patients with hereditary hemorrhagic telangiectasia (HHT) accompanied by multiple hepatic arteriovenous malformations (AVMs) whose cranial MRI demonstrated high signal intensity in the basal ganglia on T1-weighted images. Manganese levels in peripheral blood were very high in both patients. These two cases indicate that there may be a significant relationship between high intensity basal ganglia and multiple hepatic AVMs. While the precise mechanism of the signal alternation in the basal ganglia is unproven, high blood levels of manganese in these patients suggest that abnormal intensity in the basal ganglia may be due to deposition of manganese.

Aged↗
PubMedDate not supplied

Adjuvant effect of clarithromycin on chemotherapy for murine lung cancer.

Clarithromycin (CAM) increased the median survival of patients with unresectable non-small-cell lung cancer who had received chemotherapy and/or radiotherapy [Chemotherapy 1997;43:288-296]. The present study was performed to ascertain whether CAM alone exhibits an antitumor effect against Lewis lung carcinoma (LLC) and to analyze the nature of its adjuvant effect on LLC-inoculated C57BL/6 mice. CAM at 10 mg/kg/day retarded the growth of subcutaneously inoculated LLC cells; consequently, the mean survival time of mice with LLC increased. This treatment was also effective in reducing the number of tumor nodules in the lung after intravenous inoculation with LLC cells. When tumor-bearing mice received an intravenous injection of vindesine sulfate (7 mg/kg) and cisplatin (6 mg/kg) 7 days after tumor inoculation, the chemotherapeutic effect was significantly enhanced by CAM treatment when it started 7 days after chemotherapy, but not when it started the day after chemotherapy. The delayed initiation of CAM treatment resulted in the enhancement of natural killer cell activity and CD8+ T cell cytotoxicity and increased the number of interferon-gamma-producing T cells and interleukin-4-producing T cells. These findings indicate that CAM can exhibit an antitumor effect by itself and also induce the well-balanced expansion of helper T cell subsets in tumor-bearing mice recovering from the immunosuppression caused by chemotherapy. CAM may therefore be a promising adjuvant drug in anticancer chemotherapy, and treatment with this macrolide should be initiated at some interval after basic cancer therapy.

Animals↗
PubMedDate not supplied

Antitumor effect of erythromycin in mice.

Oral administration of erythromycin in the dose range of 1-10 mg/kg increased the survival times of tumor-bearing mice in both allogeneic and syngeneic mouse systems by two- to three-fold as compared with those of vehicle control mice, with the maximum effect at a dose of 5 mg/kg/day. During the early phase of tumor transplantation, tumoricidal macrophages and natural killer cells were active in the antitumor resistance of erythromycin-treated mice. Thereafter, the tumoricidal activity of macrophages became stronger as serum levels of interleukin-4 (IL-4) rose. Furthermore, treatment of mice with anti-IL-4 monoclonal antibody abolished the antitumor resistance conferred by erythromycin. These results indicate that erythromycin exhibits an indirect antineoplastic activity by enhancing the production of IL-4 which augments the tumoricidal activity of macrophages.

Administration, Oral↗
PubMedDate not supplied

Significant survival benefit to patients with advanced non-small-cell lung cancer from treatment with clarithromycin.

We carried out a randomized study of 49 consecutive patients with unresectable primary lung cancer to determine whether clarithromycin (CAM), a 14-membered ring macrolide, can improve outcome. A total of 49 patients (42 patients with non-small-cell lung cancer and 7 patients with small-cell lung cancer) had received prior chemotherapy, radiotherapy or both during their hospital stay. They were randomly allocated into two study groups on the first visit after discharge: 25 patients (22 patients with non-small-cell lung cancer, 3 patients with small-cell lung cancer) were assigned to receive CAM (400 mg/day, orally), and 24 patients (20 patients with non-small-cell lung cancer, 4 patients with small-cell lung cancer) did not receive CAM. CAM treatment after randomization was open and the treatment was to be continued as long as the patients could tolerate CAM. There was no significant difference in the median survival time for small-cell lung cancer between the CAM group and the non-CAM group. However, CAM treatment significantly increased the median survival time for non-small-cell lung cancer patients, the median survival for the CAM group was 535 days and that for the non-CAM group was 277 days. Analyses of prognostic factors showed that only treatment with CAM was predictive of longer survival for non-small-cell lung cancer, and other tested covariates had no effects on the prognosis. There were no remarkable side effects observed in the CAM group throughout treatment. We conclude that long-term treatment using CAM is beneficial for unresectable non-small-cell lung cancer patients and that it can increase the median survival of patients with advanced disease.

Aged↗
PubMedDate not supplied

Resistance training alters cytokine gene expression in skeletal muscle of adults with type 2 diabetes.

Resistance training results in muscle hypertrophy and improves glycemic control in patients with type 2 diabetes. Whether resistance training modulates inflammation in muscles of diabetic patients remains unknown. We examined the expression of genes encoding the cytokines, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and transforming growth factor-beta1 (TGF-beta1) as well as the pan-leukocyte marker CD18. Thirty men and women (67+/-7 years) were randomized to either 16 weeks of resistance training and usual diabetes care (EX) or to usual diabetes care only (CON). Muscle biopsies were obtained from the vastus lateralis muscle prior to the 16-week intervention, and 72 h following the maximal strength test post-intervention. Fiber cross-sectional area (CSA) was determined following ATPase staining. Cytokine and CD18 transcript levels were assessed by real-time PCR. Resistance training increased CSA of type I and II fibers (both P <0.05) and IL-1beta transcript levels (P = 0.05). TNF-alpha (P<0.05) and TGF-beta1 transcripts (P<0.05) increased over time in the EX group, but these increases did not differ from those in the CON group. In both groups, the increase in CD18 transcripts remained minimal. The two groups differ by the relationship between changes in CD18 and changes in cytokine transcripts, suggesting that resistance training affects the source of cytokines in muscle. Our studies establish that resistance training in older adults with type 2 diabetes results in muscle fiber hypertrophy, despite a greater accumulation of inflammatory cytokine transcripts in muscle.

Aged↗
PubMedDate not supplied

Expression of E-cadherin and beta-catenin in primary and peritoneal metastatic ovarian carcinoma.

Protein expression levels of E-cadherin and beta-catenin were examined in 39 primary and 10 metastatic ovarian carcinoma to elucidate the role of these molecules in the extension of ovarian carcinoma by immunohistochemistry. Twenty-two of 39 (56%) ovarian carcinomas were preserved type and 17 of 39 (44%) were reduced type of E-cadherin. In contrast, 36 of 39 (92%) ovarian carcinomas were preserved type and 3 of 39 (8%) were reduced type of beta-catenin. E-cadherin expression in well-differentiated carcinoma was higher than that in moderately/poorly-differentiated carcinoma (p<0.05). Interestingly, 6 of 10 (60%) peritoneal metastatic lesions resulted in the reduced expression of E-cadherin compared with primary lesions. In contrast, only 2 of 10 (20%) metastatic lesions showed reduced expression of beta-catenin compared with primary lesions. Mutation of exon 3 of beta-catenin gene was rare (3%, 1/39) in carcinoma. These results suggested that the cell adhesion molecule E-cadherin might play an important role in the formation of peritoneal metastasis. In contrast, beta-catenin is not a good indicator of metastasis in human ovarian carcinoma.

Amino Acid Sequence↗
PubMedDate not supplied

Gene expression of human squamous cell carcinoma antigens 1 and 2 in human cell lines.

The squamous cell carcinoma antigen (SCCA) serves as a serological marker for squamous cell carcinomas. Molecular cloning of the SCCA genomic region has revealed the presence of two tandemly arrayed genes, SCCA1 and SCCA2. SCCA1 is a papain-like cysteine proteinase inhibitor, while SCCA2 is a chymotrypsin-like serine proteinase inhibitor. Little is known concerning how expression of the SCCA1 and SCCA2 genes is regulated in human cell lines. The purpose of this study was to determine whether the SCCA1 gene or SCCA2 gene is more strongly expressed in human cell lines. Squamous cell carcinoma cell lines secreted respectively 4 times and 50 times as much SCCA proteins into medium as normal human keratinocyte and non-squamous cell carcinoma cell lines, as measured by enzyme-linked immunosorbent assay. Quantitative RT-PCR ELISA digoxigenin-labeling assay demonstrated that SCCA1 mRNA expression in squamous cell carcinoma cell lines was respectively 2.8 times and 42 times that in keratinocyte and non-squamous cell carcinoma cell lines. The ratio of SCCA1 to SCCA2 mRNA expression differed distinctly among squamous cell carcinoma, keratinocyte and non-squamous cell carcinoma cell lines (2.8, squamous; 24.1, keratinocyte; 11.0, non-squamous). These findings suggest that SCCA1 is mainly expressed in squamous cell carcinoma, keratinocyte and non-squamous cell carcinoma cell lines and that the ratio of SCCA1 to SCCA2 expression might be a novel marker for the detection of squamous cell carcinoma.

Adenocarcinoma↗
PubMedDate not supplied

Do androgens influence hair growth by altering the paracrine factors secreted by dermal papilla cells?

Androgens regulate many aspects of human hair growth in both sexes. After puberty they transform tiny vellus follicles in many areas, e.g. the face, to terminal ones producing long, thick, pigmented hairs. In genetically predisposed individuals, androgens also cause the reverse transformation of terminal scalp follicles into vellus ones, causing balding. In the current hypothesis for androgen action, androgens control most follicular cells indirectly acting via the mesenchyme-derived dermal papilla which regulates many aspects of follicular activity. In this model androgens binding to androgen receptors in dermal papilla cells alter their production of regulatory molecules which influence other follicular components; these molecules may be soluble paracrine factors and/or extracellular matrix proteins. This hypothesis is supported by immunohistochemical localisation of androgen receptors in dermal papilla cell nuclei and the demonstrations that androgen receptor content and testosterone metabolism patterns of cultured dermal papilla cells from various body sites reflect hair growth in androgen-insensitivity syndromes. The next question is whether androgens alter the paracrine factors secreted by dermal papilla cells. Cultured dermal papilla cells do release soluble, proteinaceous factors into their media which stimulate the growth of keratinocytes and other dermal papilla cells. This mitogenic potential can cross species from humans to rodents. Importantly, testosterone in vitro stimulates the mitogenic potential of beard cells, but in contrast inhibits production by balding scalp cells reflecting their in vivo androgenic responses. Since androgens in vitro do alter the secretion of paracrine factors the current focus lies in identifying specific factors produced, e.g. IGF-I and stem cell factor (SCF), using ELISA and RT-PCR, and comparing their expression in cells from follicles with varying responses to androgens in vivo or under androgen stimulation in vitro. This should lead to greater understanding of androgen action and enable the development of better treatment for androgen-potentiated disorders.

Androgens↗
PubMedDate not supplied

Effects of aging and cytokine blockade on inflammatory cachexia.

OBJECTIVE: To evaluate the role of aging and specific cytokine blockade in the etiology of cachexia caused by adjuvant arthritis (AA), a model of cytokine-associated cachexia. METHODS: AA was induced in Lewis rats using CFA. In Experiment 1, severity of AA and inflammatory cachexia was assessed in young (Y, age 2-6 months, n = 132) and old rats (O, age 18-22 months, n = 40). In Experiment 2, young rats were divided into 5 different intervention groups: Saline-injected (n = 66); CFA-injected (n = 78); CFA-injected and treated with IL-1 receptor antagonist (IL-1Ra, n = 18); CFA-injected and treated with soluble TNF receptor type I (sTNFrI, n = 27); and CFA-injected and treated with both IL-1Ra and sTNFrI (both treatments, n = 8). RESULTS: In Experiment 1, young Lewis rats developed more severe arthritis (mean joint score on day 21 = 5.1 +/- 0.3) compared to the old group (0.6 +/- 0.6, p < 0.0001). The young group with AA lost 2.1% of baseline total body weight loss compared to 13.8% total body weight gain in controls (p < 0.0001). In contrast, old rats injected with CFA lost as much weight (-11%) as age-matched saline injected controls (-13%, p > 0.05, n = 18, age 18-22 months). In Experiment 2, mean joint scores in rats treated with IL-1Ra, sTNFrI or both were higher then untreated rats injected with CFA (p < 0.0001). Despite this, rats given both IL-1Ra and sTNFrI lost less weight on day 16 (p < 0.01) and 21 (p < 0.002) than untreated rats or those rats treated with either IL-1Ra or sTNFrI. CONCLUSION: Lewis rats aged 2-6 months are more susceptible to developing AA than older rats (age range 18-22 months). Inhibition of both IL-1 and TNF is needed to mitigate AA-associated weight loss, and this effect is dissociated from the effect of such inhibition on joint inflammation.

Aging↗
PubMedDate not supplied

Dementia with ALS features and diffuse Pick body-like inclusions (atypical Pick's disease?).

An autopsy case of dementia beginning with right hand muscle atrophy was reported. A 42-year-old woman with no family history of neurologic disease developed weakness of the right hand at age 30, and was diagnosed as having amyotrophic lateral sclerosis (ALS). The weakness and atrophy spread to the four extremities subsequently. At age 36, she could not walk without assistance. At age 38, she was first noted as having dementia with forced crying, and she also showed generalized muscle weakness and atrophy. She rapidly developed akinetic mutism, and died of respiratory failure at age 42, 12 years after the onset of the symptoms. Macroscopically, the brain showed fronto-temporal atrophy. Microscopic examination revealed numerous intracytoplasmic inclusions throughout the central nervous system (CNS) including anterior horn of the spinal cord. The inclusions were stained moderate to dark brown with silver stain. Electron microscopically, they consisted of fibrils covered along most of the length with granular and fuzzy materials. This case was thought to be difficult to categorize in any known neuro-degenerative diseases. We proposed the case to be "atypical Pick's disease" with ALS features. This case might be a new entity of neuro-degenerative disease.

Adult↗
PubMedDate not supplied

Antihypertensive effects of a new transdermal delivery system for clonidine (M-5041T) in spontaneously hypertensive rats.

The antihypertensive effects of a new transdermal delivery system for clonidine (clonidine tape; M-5041T) were investigated in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. In spontaneously hypertensive rats, M-5041T, at doses of 0.5-4.5 mg/kg (1.25-11.25 cm2/kg), produced a dose-dependent decrease of both systolic blood pressure and heart rate for 24 hr during transdermal application. These significant hypotensive effects lasted for 24 hr following the patching of M-5041T on the back of the animals at a dose of 4.5 mg/kg. In normotensive Wistar-Kyoto rats, the hypotensive and bradycardic effects of M-5041T were weak compared with those in spontaneously hypertensive rats. In both rat strains, M-5041T (4.5 mg/kg) caused behavioral changes such as sedation, piloerection and exophthalmos, accompanied by hypotensive effects. Both M-5041T (1.5 mg/kg) and clonidine (50 micrograms/kg, subcutaneously and 100 micrograms/kg, orally) induced similar hypotensive effects, accompanied by sedation. The hypotensive effects following transdermal M-5041T or systemic clonidine administrations were correlated with the time courses of the plasma clonidine concentration. In contrast to clonidine administered subcutaneously or orally, M-5041T produced a gradual increase in the plasma clonidine concentration, which persisted at a consistent level for at least 12 hr thereafter. Significant hypotensive effects lasted for 12 and 24 hr following M-5041T patching at 1.5 and 4.5 mg/kg, respectively. The present findings suggest that M-5041T can serve as an efficient and useful antihypertensive transdermal delivery system to achieve persistent blood pressure control.

Administration, Cutaneous↗