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Biomedical subjects

T Hamada

Publications and source records attributed to T Hamada.

At least 127 records · Page 7Linked to original sources

Suppression of adjuvant arthritis of rats by a novel matrix metalloproteinase-inhibitor.

BAY 12-9566 (4-[4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) is a newly developed, synthetic matrix metalloproteinase (MMP) inhibitor (MMPI) that selectively inhibits MMP-2, MMP-3 and MMP-9 isozymes. We study the effect of BAY 12-9566 on inflammation and cartilage destruction in adjuvant-induced arthritis (AA) in rats. Rats were injected with adjuvant and treated for 21 days with vehicle, Indomethacin or BAY 12-9566. AA was assessed: by measuring arthritic index, paw volume, urinary pyridinoline (Pyr) and deoxypyridinoline (Dpyr); by examining joint inflammation; and by microscopic morphometry of articular cartilages. Oral treatment of rats for 22 days with 50 mg kg(-1) body weight/d BAY 12-9566 showed decreased AA as determined by improvement in body weight gain (P<0.01), arthritic index (P<0.05) and swelling of paws contralateral to the adjuvant injection site (P<0.05). Neutrophil infiltration and collagen degradation were also significantly lower (P<0.01) in this treatment group. Cartilage destruction was successfully suppressed (P<0.01) in rats treated with either 50 mg kg(-1) body weight/d BAY 12-9566 or 1 mg kg(-1) body weight/d Indomethacin. These results indicate that BAY 12-9566 successfully suppressed inflammation and cartilage destruction in rats with AA. Moreover, these results also suggested that MMP-2, MMP-3 and MMP-9 are involved in arthritic diseases such as rheumatoid arthritis.

Amino Acids↗

Combined cutaneous hamartoma encompassing benign melanocytic naevus, vellus hair cyst and epidermoid cyst.

We describe a combined cutaneous hamartoma in a 57-year-old man, which comprised a vellus hair cyst, an epidermoid cyst and an intradermal melanocytic naevus in a single facial tumour. The vellus hair cyst was filled with keratinous material with unusual slit-like lacunae. While numerous cases of epidermoid cyst have been reported in association with an intradermal melanocytic naevus, our case is a rare example of a lesion combining several hamartomatous elements.

Cysts↗

Chemotherapy-induced acral erythema: report of a case and immunohistochemical findings.

Chemotherapy-induced acral erythema (CAE) is an uncommon and distinct reaction seen in patients receiving high-dose chemotherapy. The exact pathogenic mechanisms of this disorder are still unknown. We report a 27-year-old woman who presented with red, swollen and painful macules on both palms, clinically consistent with this disease. Histological examination demonstrated vacuolar degeneration of the basal cell layer and spongiotic blisters in the epidermis, especially in the atrophied eccrine ducts and papillary oedema with mild perivascular infiltration of mononuclear and hypersegmented neutrophils. Immunohistochemistry showed that the infiltrating mononuclear cells were CD3-CD16+CD56+ leucocyte function antigen-1+, possibly natural killer cells. The eccrine ducts expressed HLA-DR and intracellular adhesion molecule-1 (ICAM-1). Our findings suggest that cell-to-cell interaction between NK cells and keratinocytes in the eccrine apparatus may induce CAE and may be involved in the pathogenesis of the skin reaction in our patient and possibly in this disease.

Adrenal Cortex Hormones↗

Interactions between thermal cycled resilient denture lining materials, salivary and serum pellicles and Candida albicans in vitro. Part I. Effects on fungal growth.

In the present study, the growth of a single isolate of Candida albicans on seven saliva-, serum-coated or protein free (uncoated), thermocycled (4-70 degrees C for 1 min, respectively; 0, 1000 and 10 000 times) commercial resilient lining materials was investigated by monitoring pH changes in growth media. The inhibitory effect of the tissue conditioners on fungal growth was observed using three parameters, i.e. (i) the delay in the onset of the rapid decline in pH, (ii) the reduction in the rate of pH change and (iii) the pH minima reached. In the case of control soft liners (not thermocycled and uncoated), the antifungal effect appeared to depend upon the type of commercial soft liner used. Thus, an initial delay in pH decline and a very high pH minima were observed with fluoric and heat-cured silicone materials. High pH minima were also observed with cold-cured acrylic soft liners, whereas cold-cured silicone materials did not significantly differ from heat-cured acrylic resin (P>0.05). However, the antifungal effect of the materials was significantly reduced both by thermal cycling (ANOVA, P<0.01) and a layer of protein coating (saliva, P<0.05; serum, P<0.01). These results, taken together, suggest that the ageing of the materials and the biological fluids of the host, particularly serum, promote yeast growth on soft lining materials.

Analysis of Variance↗

Interactions between thermal cycled resilient denture lining materials, salivary and serum pellicles and Candida albicans in vitro. Part II. Effects on fungal colonization.

In the present study, the growth of a single isolate of Candida albicans on saliva-, serum-coated or protein free (uncoated), thermocycled (4-70 degrees C for 1 min, respectively; 0, 1000 and 10 000 times) seven commercial soft lining materials were investigated, by adenosine triphosphate (ATP) analysis. In the case of control resilient liners (not thermocycled and uncoated), the fungal colonization appeared to depend upon the type of commercial resilient liner used. Thus, the lowest colonization was observed with fluoric and heat-cured silicone materials, cold-cured silicone materials, except for one product, and heat-cured acrylic resin exhibited the highest colonization capacity, and cold-cured acrylic resilient liners exhibited the intermediate. However, the fungal colonization on the materials was significantly promoted both by thermal cycling (ANOVA, P<0.01) and a layer of protein coating (saliva, P<0.01; serum, P<0.01). These results, taken together, suggest that the ageing of the materials and the biological fluids of the host promote yeast colonization on resilient lining materials.

Acrylic Resins↗

Effect of serum concentration on Candida biofilm formation on acrylic surfaces.

The biofilm formation of the oral fungal pathogen Candida on denture acrylic strips coated with saliva, serum and, saliva-serum pellicle were examined in vitro using Candida albicans (four isolates), Candida glabrata (three isolates) and Candida tropicalis (three isolates). The degree of biofilm activity varied depending upon both the isolate and the pellicle. Significantly increased biofilm activity on the pellicle (particularly serum)-coated strips was observed with three isolates of C. albicans and another of C. glabrata on protein-coated acrylics, with increasing concentration of serum in the pellicle. Similar trends were observed with one isolate of C. albicans and C. glabrata, although the effects of pellicles were not significant. In contrast, with all three isolates of C. tropicalis and a single isolate of C. glabrata, although the biofilm activity on the protein-free control strips was significantly higher than that of saliva-coated strips, the increase in activity of pellicle-admixed biofilm depended upon the serum concentration. Candidal biofilm formation on acrylic surfaces is essentially promoted with increasing concentration of serum in the pellicle. This suggests that inflammation in the oral environment would facilitate fungal colonization on denture acrylic.

Acrylic Resins↗

Ovarian yolk sac tumor with virilization during pregnancy: immunohistochemical demonstration of Leydig cells as functioning stroma.

A case is reported of yolk sac tumor occurring in the left ovary and complicated by pregnancy. The 22-year-old patient presented at 28 weeks gestation with virilization and elevated serum levels of testosterone and alpha-fetoprotein. The tumor showed the typical features of yolk sac tumor with a mixture of islands of Leydig cells. The accumulations of Leydig cells were well demarcated from the cellular components of the yolk sac tumor and were distributed throughout the tumor, although with predominant localization at the periphery. By immunohistochemistry the Leydig cells were intensely positive for vimentin and negative for cytokeratins, allowing clear distinction from the cell components of the yolk sac tumor, which were positive for cytokeratins and negative for vimentin. Testosterone was also identified in the cytoplasm of the Leydig cells. After tumor resection the testosterone and alpha-fetoprotein levels declined simultaneously; this, together with the immunohistochemical demonstration of testosterone, indicates that the Leydig cells were responsible for the endocrine manifestations. Furthermore, antibodies against inhibin alpha-subunit and calretinin could be used to detect the Leydig cells. The present case, a combination of yolk sac tumor and Leydig cells acting as a functioning stroma and causing virilization during pregnancy, is very rare.

Adult↗

Synaptotagmin IV is present at the Golgi and distal parts of neurites.

Synaptotagmin IV (SytIV) is an immediate early gene induced by membrane depolarization in PC12 cells and in rat brain. However, little is known about the function of SytIV or the functional relationship between SytIV and SytI, because SytIV has yet to be localized. Here we show that SytIV was localized at the Golgi and distal part of neurites in nerve growth factor-differentiated PC12 cells and cultured hippocampal neurons by immunocytochemistry using an isoform-specific antibody (anti-SytIV). These SytIV signals were not colocalized well with SytI signals. Upon membrane depolarization, SytIV signals were increased at both the Golgi and distal part of neurites within several hours in both types of cells. We further show that the increase of SytIV protein levels results from protein kinase A-dependent gene up-regulation. In hippocampal neurons, SytIV was developmentally regulated. These results suggest that SytIV may play a role at the Golgi and tips of neurites during development and synaptic plasticity.

Animals↗

Cardiac and plasma catecholamine responses to exercise in patients with type 2 diabetes: prognostic implications for cardiac-cerebrovascular events.

BACKGROUND: Patients with diabetes mellitus have an altered exercise plasma catecholamine response, which may be related to the abnormal sympathoadrenal function and autonomic neuropathy. Presence of autonomic neuropathy is associated with poor prognosis, but relationship between exercise plasma catecholamine and prognosis has not been investigated. This study determined if altered plasma catecholamine response to exercise was associated with cardiac-cerebrovascular events. METHODS: Forty patients with type 2 diabetes without apparent macrovascular complications and 30 control subjects performed treadmill exercise with serial measurements of plasma norepinephrine and epinephrine. Clinical, exercise, and catecholaminergic variables considered relevant to the cardiac-cerebrovascular events were examined by Cox regression model. Analysis of 24-hour heart rate variability was performed in a subgroup of patients. RESULTS: During 7.2 years, 8 patients, but no control subjects, had events (3 myocardial and 5 cerebral infarctions). Compared with Event(-) patients, Event(+) patients had: (1) orthostatic hypotension; (2) lower peak exercise heart rate; (3) lower plasma norepinephrine immediately after exercise; and (4) lower plasma epinephrine at peak exercise. High frequency components in heart rate variability analysis were diminished in Event(+) patients. Multivariate analysis showed that peak heart rate (P = 0.04) and plasma epinephrine at peak exercise (P = 0.03) were independent predictors of subsequent events. CONCLUSIONS: These data suggest that chronotropic incompetence and lower plasma epinephrine response to exercise are associated with high risk of cardiac-cerebrovascular events in patients with type 2 diabetes.

Catecholamines↗

Postactivation potentiation in endurance-trained male athletes.

PURPOSE: The purpose of the study was to determine whether postactivation potentiation (PAP) was enhanced in the trained muscles of male endurance athletes. METHODS: Triathletes (TRI), distance runners (RUN), active controls (AC), and sedentary control subjects (SED) (N = 10 per group) performed 10-s maximal isometric contractions (MVC) of the elbow extensor and ankle plantarflexor muscles. Maximal twitch contractions were evoked (percutaneous stimulation) before and during a 5-min period after the MVC. PAP was measured as the percentage change in peak twitch torque post-MVC. RESULTS: TRI, who train both upper and lower limb muscles, had enhanced (relative to SED) PAP in both elbow extensor and plantarflexor muscles. In RUN, who train only the lower limbs, enhanced PAP was restricted to the plantarflexors. AC, whose main activity was upper and lower limb weight training, also had enhanced PAP in both muscle groups, although the enhancement in the plantarflexors was not as great as in TRI and RUN. CONCLUSION: PAP is enhanced in endurance athletes. Enhanced PAP may counteract fatigue during endurance exercise. The mechanism(s) responsible for the enhanced PAP remain to be determined.

Adult↗

Molecular cloning, sequencing, and expression in Escherichia coli of the gene encoding a novel 5-oxoprolinase without ATP-hydrolyzing activity from Alcaligenes faecalis N-38A.

The gene encoding a novel 5-oxoprolinase without ATP-hydrolyzing activity from Alcaligenes faecalis N-38A was cloned and characterized. The coding region of this gene is 1,299 bp long. The predicted primary protein is composed of 433 amino acid residues, with a 31-amino-acid signal peptide. The mature protein is composed of 402 amino acid residues with a molecular mass of 46,163 Da. The derived amino acid sequence of the enzyme showed no significant sequence similarity to any other proteins reported so far. The 5-oxoprolinase gene was expressed in Escherichia coli by using a regulatory expression system with an isopropyl-beta-D-thiogalactopyranoside-inducible tac promoter, and its expression level was approximately 16 mg per liter. The purified enzyme has the same characteristics as the authentic enzyme, except for the amino terminus, which has three additional amino acids. The enzyme was markedly inhibited by p-chloromercuribenzoic acid, EDTA, o-phenanthroline, HgCl(2), and CuSO(4). The EDTA-inactivated enzyme was completely restored by the addition of Zn(2+) or Co(2+). In addition, the enzyme was found to contain 1 g-atom of zinc per mol of protein. These results suggest that the 5-oxoprolinase produced by A. faecalis N-38A is a zinc metalloenzyme.

Adenosine Triphosphate↗

Postactivation potentiation, fiber type, and twitch contraction time in human knee extensor muscles.

In small mammals, muscles with shorter twitch contraction times and a predominance of fast-twitch, type II fibers exhibit greater posttetanic twitch force potentiation than muscles with longer twitch contraction times and a predominance of slow-twitch, type I fibers. In humans, the correlation between potentiation and fiber-type distribution has not been found consistently. In the present study, postactivation potentiation (PAP) was induced in the knee extensors of 20 young men by a 10-s maximum voluntary isometric contraction (MVC). Maximal twitch contractions of the knee extensors were evoked before and after the MVC. A negative correlation (r = -0. 73, P < 0.001) was found between PAP and pre-MVC twitch time to peak torque (TPT). The four men with the highest (HPAP, 104 +/- 11%) and lowest (LPAP, 43 +/- 7%) PAP values (P < 0.0001) underwent needle biopsies of vastus lateralis. HPAP had a greater percentage of type II fibers (72 +/- 9 vs. 39 +/- 7%, P < 0.001) and shorter pre-MVC twitch TPT (61 +/- 12 vs. 86 +/- 7 ms, P < 0.05) than LPAP. These data indicate that, similar to the muscles of small mammals, human muscles with shorter twitch contraction times and a higher percentage of type II fibers exhibit greater PAP.

Adult↗

Chemotaxis of primitive hematopoietic cells in response to stromal cell-derived factor-1.

Stromal cell-derived factor-1 (SDF-1) provides a potent chemotactic stimulus for CD34(+) hematopoietic cells. We cultured mobilized peripheral blood (PB) and umbilical cord blood (CB) for up to 5 weeks and examined the migratory activity of cobblestone area-forming cells (CAFCs) and long-term culture-initiating cells (LTC-ICs) in a transwell assay. In this system, SDF-1 or MS-5 marrow stromal cells placed in the lower chamber induced transmembrane and transendothelial migration by 2- and 5-week-old CAFCs and LTC-ICs in 3 hours. Transmigration was blocked by preincubation of input CD34(+) cells with antibody to CXCR4. Transendothelial migration of CB CAFCs and LTC-ICs was higher than that of PB. We expanded CD34(+) cells from CB in serum-free medium with thrombopoietin, flk-2 ligand, and c-kit ligand, with or without IL-3 and found that CAFCs cultured in the absence of IL-3 had a chemotactic response equivalent to noncultured cells, even after 5 weeks. However, addition of IL-3 to the culture reduced this response by 20-50%. These data indicate that SDF-1 induces chemotaxis of primitive hematopoietic cells signaling through CXCR4 and that the chemoattraction could be downmodulated by culture ex vivo.

Animals↗

Calsequestrin, a calcium sequestering protein localized at the sarcoplasmic reticulum, is not essential for body-wall muscle function in Caenorhabditis elegans.

Calsequestrin is the major calcium-binding protein of cardiac and skeletal muscles whose function is to sequester Ca(2+ )in the lumen of the sarcoplasmic reticulum (SR). Here we describe the identification and functional characterization of a C. elegans calsequestrin gene (csq-1). CSQ-1 shows moderate similarity (50% similarity, 30% identity) to rabbit skeletal calsequestrin. Unlike mammals, which have two different genes encoding cardiac and fast-twitch skeletal muscle isoforms, csq-1 is the only calsequestrin gene in the C. elegans genome. We show that csq-1 is highly expressed in the body-wall muscles, beginning in mid-embryogenesis and maintained through the adult stage. In body-wall muscle cells, CSQ-1 is localized to sarcoplasmic membranes surrounding sarcomeric structures, in the regions where ryanodine receptors (UNC-68) are located. Mutation in UNC-68 affects CSQ-1 localization, suggesting that the two possibly interact in vivo. Genetic analyses of chromosomal deficiency mutants deleting csq-1 show that CSQ-1 is not essential for initiation of embryonic muscle formation and contraction. Furthermore, double-stranded RNA injection resulted in animals completely lacking CSQ-1 in body-wall muscles with no observable defects in locomotion. These findings suggest that although CSQ-1 is one of the major calcium-binding proteins in the body-wall muscles of C. elegans, it is not essential for body-wall muscle formation and contraction.

Amino Acid Sequence↗

Ultrasonography improves diagnostic accuracy of acute appendicitis and provides cost savings to hospitals in Japan.

A cost analysis based on changes in patient care was used to evaluate the utility of abdominal ultrasonography in both the clinical management of patients clinically suspected of having acute appendicitis and in reducing expenditure of hospital resources. Among the 200 patients suspected of having acute appendicitis, 57 actually had acute appendicitis. Interpretation of appendiceal ultrasonographic results was 98.5% accurate. The ultrasonographic result led to changes in the treatment of 103 patients. Moreover, ultrasonography led to the prevention of unnecessary appendectomy in 25 patients, providing a savings to the hospital of about Yen 8,013,450 ($65,150), and prevented unnecessary hospital admission for 78 patient-days, thus saving the hospital approximately Yen 1,199,250 ($9750). The cost of performing the 200 ultrasonographic examinations was about Yen 1,096,176 ($8912), and thus the overall savings to the hospital was approximately Yen 40,590 ($330) per patient. Ultrasonography performed in patients with suspected acute appendicitis improves patient diagnostic accuracy, thus leading to more appropriate selection of patient treatment and reduced hospital expenditure.

Acute Disease↗

Efficacy of cholesterol-lowering treatment in Japanese elderly patients with coronary artery disease and normal cholesterol level using 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor.

The clinical benefit of cholesterol-lowering treatment is unknown in the Japanese elderly in whom the prevalence of morbidity and mortality related to coronary artery disease are known to be low. To evaluate the efficacy of cholesterol-lowering treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor in Japanese elderly patients with documented coronary artery disease, 121 patients with serum cholesterol > or = 150 mg/dl prospectively received HMG-CoA reductase inhibitor, and 271 patients undergoing cholesterol-lowering treatment based on dietary therapy alone served as historical controls. The 143 elderly patients age > or = 65 years in the 2 groups had similar baseline serum total cholesterol level (201 +/- 30 vs 202 +/- 31 mg/dl), age (71 +/- 4 vs 70 +/- 4 years), proportion of men (37/53 vs 64/90), number of diseased vessels (1.7 +/- 0.9 vs 1.5 +/- 1.0), and incidences of other classical coronary risk factors, including hypertension, diabetes mellitus, smoking, obesity and family history of coronary artery disease. In all 392 patients, similar trends were observed, including serum total cholesterol level (208 +/- 33 vs 201 +/- 34 mg/dl). With HMG-CoA reductase inhibitors, serum total cholesterol level was reduced by 14% in the elderly subjects and by 13% in all patients. During the follow-up of approximately 3 years, cardiac events occurred in 5 patients (one elderly) in the treatment group and 38 patients (12 elderly) in the control group. Kaplan-Meier survival estimates revealed a higher event-free survival rate with HMG-CoA reductase inhibitors in the elderly subjects (98% vs 85%, p < 0.05) and in all patients (94% vs 86%, p < 0.05). Cox proportional hazard modeling also demonstrated a significant reduction in risk for cardiac events with drug therapy (relative risk 0.32, p < 0.05), in addition to the number of diseased vessels (relative risk 1.8, p < 0.01). In contrast, no additional risk was observed with advancing age. Cholesterol-lowering treatment with HMG-CoA reductase inhibitors is effective to improve the prognosis of Japanese elderly patients, including those with normal serum cholesterol level.

Anticholesteremic Agents↗

The novel drug CS-891 inhibits 5alpha-reductase activity in freshly isolated dermal papilla of human hair follicles.

The local conversion of testosterone (T) to the more potent androgen dihydrotestosterone (DHT) by 5alpha-reductase (5aR) is implicated in the pathogenesis of androgenetic alopecia (AGA). Recently, the clinical effectiveness of finasteride, a selective type II 5aR inhibitor, in treating AGA has been documented, and these clinical studies have shown that circulating DHT is lowered by 60-70% in men taking finasteride. The source of the residual circulating DHT is presumed to be due to type I 5aR activity which is not affected by finasteride. Several novel compounds with potent dual inhibitory activity on both isoenzymes have been described and CS-891 is one of them. This compound may be likewise effective in the prevention or treatment of AGA. As a prerequisite for such an action CS-891 should be able to inhibit 5aR activity in its target tissue: the hair follicles (HF). Here we report on the capability of CS-891 to inhibit 5aR activity in dermal papillae (DP) of human HF.

Adult↗