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Biomedical subjects

K Goto

Publications and source records attributed to K Goto.

At least 37 records · Page 2Linked to original sources

Effects of heat stress and mechanical stretch on protein expression in cultured skeletal muscle cells.

Effects of heat stress, mechanical stretching or a combination of both on the expression of heat shock proteins (HSPs) and total protein level were studied in a culture system. Rat skeletal muscle cells (L6) were cultured on flexible-bottomed culture plates. They were subjected to one of the four following conditions: (1) 97 h incubation at 37 degrees C, (2) 1 h incubation at 41 degrees C followed by 96 h incubation at 37 degrees C, (3) 1 h incubation at 37 degrees C followed by 96 h cyclic stretching (18% of initial length, 2-s stretch and 4-s release) at 37 degrees C or (4) 1 h incubation at 41 degrees C followed by 96 h cyclic stretching at 37 degrees C. The expression of HSP72 and HSP90 and total protein was determined in the crude homogenates, supernatant and pellets. Cellular protein concentrations in the homogenates and pellets were increased by heat stress and/or mechanical stress (stretch). A cumulative effect of the combination of heating and stretch on the protein concentration in the homogenates and in the pellets was noted. The expressions of HSP72 and HSP90 in the pellets were also increased by heat stress and/or stretch. However, HSP90 in the supernatant did not change following heat stress and/or stretch. The regulation of HSP72 and HSP90 expression in skeletal muscle cells may be closely related to total protein, the abundance of which is also stimulated by mechanical and heat stresses. These observations suggest strongly that heating and passive stretch of muscle may be useful as a means of increasing muscle mass, not only in athletes but also in patients during rehabilitation.

Animals↗

Phase I/II trial of weekly cisplatin, etoposide, and irinotecan chemotherapy for metastatic lung cancer: JCOG 9507.

Combinations of cisplatin-irinotecan and cisplatin-etoposide are active and well tolerated in patients with both small-cell lung cancer (SCLC) and nonsmall-cell lung cancer (NSCLC). To define the recommended dose for phase II trials of irinotecan combined with cisplatin and etoposide in chemonaive patients with stage IV disease, 56 patients (11 having SCLC and 45 NSCLC) received cisplatin 25 mg m(-2) weekly for 9 weeks, etoposide 60 mg m(-2) for 3 days on weeks 1, 3, 5, 7 and 9, and irinotecan 20-100 mg m(-2) (levels 1-8) on weeks 2, 4, 6 and 8, together with a prophylactical granulocyte colony-stimulating factor support (50 microg m(-2) on days 4-7 on weeks 1, 3, 5, 7 and 9, and on days 2-7 on weeks 2, 4, 6 and 8). Grade 3-4 leukocytopenia, neutropenia and thrombocytopenia were noted in 20 (36%), 28 (50%) and nine (16%) patients, respectively. Grade 3 diarrhoea, grade 3 cardiac toxicity, and grade 4 transaminase elevation developed in one (1.8%) patient each. Totally, four of 56 patients were removed from the study because of toxicity and recovered, and two other patients died in situations where drug toxicity might contribute to their death. Dose-limiting toxicity was noted in less than one-third of patients at dose levels 1-7, but in all patients at dose level 8. Thus, the recommended dose was determined to be level 7 (irinotecan 90 mg m(-2)). The response rates for SCLC and NSCLC were 91% (10/11) and 38% (17/45), respectively. The median survival time and 1-year survival rate were 11.9 months and 46% for SCLC and 10.1 months and 40% for NSCLC, respectively. This regimen was considered to be feasible and promising for the treatment of stage IV SCLC and NSCLC.

Adult↗

Tegumentary papillae of Echinostoma caproni cercariae (Trematoda: Echinostomatidae).

Argentophilic staining and scanning electron microscopy were used to study the tegumentary papillae of Echinostoma caproni cercariae. The most abundant tegumentary papillae were uniciliate, but multiciliate papillae were also found, mainly on the ventral aspect of the oral collar. The distribution pattern of the papillae on the body and tail was in general similar to that seen in the cercariae of other 37-collar-spined Echinostoma species. Some differences were noted between E. caproni and the allopatric species, E. trivolvis. E. caproni has a greater number of papillae associated with the collar spines than does E. trivolvis. E. caproni has uniciliate papillae on the acetabulum, whereas E. trivolvis does not. Chaetotaxy is useful to distinguish subtle morphological differences in cercarial species in the 37-collar-spined Echinostoma complex.

Animals↗

Hyperkeratosis and leukocytosis in transgenic mice carrying MHC class I chain-related gene B (MICB).

Major histocompatibility complex (MHC) class I chain-related gene A and B (MICA and MICB) are located very close to HLA-B. MICA is reported to be strongly associated with Behçet's disease (BD), a multisysytemic inflammation disorder characterized by oral apthous ulcers, skin lesions and genital ulcers. These two molecules are highly conserved at the amino acid levels. To determine the function of MICB in vivo and the relationship between the expression of MICB and BD experimentally, we produced several transgenic mouse lines (termed CAG-MICB) expressing human MICB cDNA under a ubiquitous promoter. They exhibited a 50% increase in the number of white blood cells compared with their non-transgenic littermates, and also exhibited a 10-20% reduction in body weight compared with non-transgenic littermates. Exfoliation of the skin first appeared around 7 days after birth and disappeared after 2 weeks of age. This was repeatedly observed in the transgenic offspring of two independent CAG-MICB lines examined. Histopathological analysis of skin of young mice exhibiting skin abnormalities revealed hyperkeratosis of the epidermis and thickening of the granular layer with slight infiltration of inflammatory cells in the dermis without any vasculitis. Other remarkable abnormalities associated with BD have not been observed in the CAG-MICB lines. Furthermore, fluorescein angiography of eyes of the CAG-MICB lines was performed, but there were no marked changes of BD-related uveitis in the ocular fundus. These findings suggest that (i) MICB expression is related to temporary skin inflammation, and (ii) expression of MICB is not directly associated with BD.

Animals↗

Cervical dystonia in dentatorubral-pallidoluysian atrophy.

Hereditary dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal-dominant neurodegenerative disease characterized by variable clinical phenotypes. Its characteristic clinical manifestations include ataxia, choreoathetotic movements, seizures, myoclonus and dementia, but cervical dystonia has been rarely reported. Here we report a family with DRPLA who presented with cervical dystonia. The proband was a 66-year-old woman. Cervical dystonia was the initial and the most prominent symptom, and mild cerebellar signs and choreic movements were also observed. DNA analysis revealed expanded trinucleotide repeats within the DRPLA gene. The daughter of the proband, a 29-year-old woman, also had cervical dystonia for 3 years. Cranial magnetic resonance imaging showed a mild atrophy of the brainstem and the cerebellum in both of these patients. DRPLA should be considered in the differential diagnosis of patients presenting with cervical dystonia.

Adult↗

A single set of low intensity resistance exercise immediately following high intensity resistance exercise stimulates growth hormone secretion in men.

AIM: The purpose of the present study was to examine the effects of an additional set immediately following high intensity resistance exercise on growth hormone (GH) response. METHODS: Subjects (n=8) performed 4 resistance exercise protocols (bilateral knee extension exercise) on separate days. The protocols were categorized into 2 types of protocol, namely "Strength-up type (S-type)" and "Combination type (Combi-type)". The S-type was resistance exercise which consisted of 5 sets at 90% of 1 repetition maximum (RM) with 3-min rest periods between sets, whereas the Combi-type is a training protocol which adds an additional set (either 50% of 1 RM [C50-type], 70% of 1 RM [C70-type] or 90% of 1 RM [C90-type]) to the S-type. Serum GH concentration and blood lactate concentration were determined pre-exercise and at 0-60 min postexercise. Relative changes in thigh girth and maximal unilateral isometric strength were determined pre-exercise and immediately postexercise. RESULTS: The increasing values of GH concentration (DGH) in the S-type was the lowest of all protocols. On the other hand, DGH in the C50-type showed a significantly (p<0.05) higher increase than in the S-type and C90-type, and a relatively higher increase than in the C70-type. CONCLUSION: These results suggests that a high intensity, low volume training protocol to induce neural adaptation resulted in little GH response, but GH secretion was increased by performing a single set of low intensity resistance exercise at the end of a series of high intensity resistance sets.

Adult↗

Triplet chemotherapy with vinorelbine, gemcitabine, and cisplatin for advanced non-small cell lung cancer: a phase II study.

We conducted a phase II trial of triplet chemotherapy consisting of vinorelbine, gemcitabine, and cisplatin in patients with advanced non-small cell lung cancer to assess its efficacy and toxicity. Thirty-three patients with chemotherapy-naïve stage IIIB disease (n=8), stage IV disease (n=23), or recurrence after surgical resection (n=2) were given intravenous infusions of vinorelbine 25 mg m(-2), gemcitabine 1000 mg m(-2), and cisplatin 40 mg m(-2) on days 1 and 8 at 3-week intervals. There were 16 partial responses, and the objective response rate was 48% (95% confidence interval: 31-66%). The median survival time was 13.5 months (95% confidence interval: 10.6-16.4 months), and the one-year survival rate was 61%. Grade 4 haematologic toxicity consisted of neutropenia in 72% of patients, and febrile neutropenia occurred in 42% of the patients. There was one toxic death, and it was attributed to neutropenic fever and haemoptysis. Autopsy revealed diffuse pulmonary haemorrhage secondary to bacterial abscesses and vasculitis in both lungs. The common nonhaematologic toxicities included grade 2-3 nausea (39%) and vomiting (18%). Triplet chemotherapy containing vinorelbine, gemcitabine, and cisplatin is effective in the treatment of chemo-näive patients with advanced non-small cell lung cancer, but produces unacceptable frequent febrile neutropenia.

Adult↗

Orexin-mediated feeding behavior involves both leptin-sensitive and -insensitive pathways.

Orexin-A and -B are neuropeptides that are implicated in the regulation of vigilance states and energy homeostasis. Orexins are specifically produced by neurons located within the lateral hypothalamic area (LHA), a region implicated in the regulation of feeding behavior. Here, we examined the functional interactions between orexins and anorectic factors [leptin, alpha-melanocyte-stimulating hormone (alpha-MSH) and glucagon-like peptide-1 (GLP-1)] in rats. Intracerebroventricular injection of orexin-A (10 nmol) potently augmented food intake in rats. Neuropeptide Y (NPY) (0.3 nmol) and galanin (3 nmol) also induced a transient increase in food intake. Both NPY- and galanin-induced feeding behaviors were completely inhibited by preadministration of leptin (3 microg), while the same or a higher dose (10 microg) of leptin only partially inhibited orexin-A or -B-induced increase of food intake. Preadministration of anorectic peptides (alpha-MSH and GLP-1), which are shown to be regulated by leptin, abolished NPY-induced feeding; however, orexin-induced feeding was only partially inhibited by these anorectic peptides. These observations suggest that NPY- and galanin-induced increases of feeding involve a leptin-sensitive pathway, while orexin-induced feeding involves both leptin-sensitive and -insensitive pathways.

Animals↗

Okadaic acid stimulates apoptosis through expression of Fas receptor and Fas ligand in human oral squamous carcinoma cells.

Fas receptor is a member of a superfamily of receptors characterized by cysteine-rich motifs in the extracellular domain of the molecule. Binding of Fas ligand to Fas receptor leads to activation of the latter and the induction of intracellular signals that result in apoptotic cell death. In the present study, we used reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis to examine the expression of mRNAs and proteins of Fas receptor and Fas ligand in human oral squamous carcinoma SCC-25 cells treated with okadaic acid. The PCR product of Fas receptor mRNA was detected in the cells and a protein with an estimated molecular weight of 35,000 was also expressed in them. Expression of Fas receptor mRNA stimulated by okadaic acid was elevated in dose- and time-dependent manners as judged by semiquantitative RT-PCR analysis, with the maximum expression level at 50 nM and 8 h treatment. Fas ligand mRNA expression was also stimulated by okadaic acid in SCC-25 cells in dose- and time-dependent manners. Okadaic acid also stimulated the expression of Fas ligand protein in the cells. Okadaic acid in serum-free medium induced apoptosis in SCC-25 cells in a time-dependent manner up to 24 h as determined by nuclear condensation and fragmentation of chromatin and DNA ladder formation. The present results indicate that the expression of Fas receptor and Fas ligand is negatively regulated by a protein phosphatase(s) sensitive to okadaic acid and is involved in okadaic acid-induced apoptosis in SCC-25 cells. Our results also suggest that Fas receptor and Fas ligand system might regulate apoptosis in SCC-25 cells in an autocrine fashion.

Apoptosis↗

Head tremor in dentatorubral-pallidoluysian atrophy.

Dentatorubral-pallidoluysian atrophy (DRPLA) is a rare autosomal-dominant neurodegenerative disorder characterized by variable combination of clinical manifestations including ataxia, myoclonus, seizures, dementia, and choreic movements. Head tremor has been rarely reported. We report a 66-year-old-woman with genetically determined DRPLA who presented with head tremor. A "no-no" type head tremor was the initial and the most prominent symptom, and mild cerebellar signs and choreic movements were also observed later. Neither hand tremor nor dystonia was noted. The patient did not show dementia, myoclonus, or seizures. Surface electromyogram (EMG) revealed 3.5-4 Hz rhythmic EMG bursts in both sternocleidomastoid muscles. DNA analysis disclosed expanded trinucleotide repeats (n = 54) in the DRPLA gene. We suggest that isolated head tremor can be a clinical manifestation of DRPLA.

Aged↗

Spontaneous recurrence of methamphetamine-induced paranoid-hallucinatory states in female subjects: susceptibility to psychotic states and implications for relapse of schizophrenia.

In this study, we examined the relationship between increased sensitivity to stress associated with noradrenergic hyperactivity and dopaminergic changes, and susceptibility to subsequent spontaneous recurrences of methamphetamine (MAP) psychosis (i.e., flashbacks). The subjects were 81 physically healthy females. Plasma monoamine metabolite levels were assayed in: 19 flashbackers, of whom 11 experienced a single flashback and 8 exhibited subsequent flashbacks; 20 non-flashbackers with a history of MAP psychosis; 8 subjects with persistent MAP psychosis; and 23 MAP users and 11 non-user controls. All 19 flashbackers had undergone frightening and stressful experiences during previous MAP use. Mild psychosocial stressors then triggered their flashbacks. During flashbacks, plasma norepinephrine levels increased, with a small increase in plasma levels of 3-methoxytyramine, which is an index of dopamine release. Among the 19 flashbackers, the 8 with subsequent episodes had increased NE levels and slightly increased 3-methoxytyramine levels, while the 11 with a single episode displayed small increases in norepinephrine and 3-methoxytyramine levels. Thus, noradrenergic hyperactivity and increased dopamine release in response to mild psychosocial stressors may be responsible for the development of flashbacks. Robust noradrenergic hyperactivity with slightly increased DA release in response to mild stress may induce susceptibility to subsequent flashbacks. Flashbacks and schizophrenia may share the pathophysiology of susceptibility to recurrence of paranoid-hallucinatory states such as stress sensitization, and also noradrenergic hyperactivity and enhanced DA release. Thus, flashbacks may provide an appropriate model of susceptibility to paranoid-hallucinatory states of schizophrenia. The model psychosis is a potential tool for validating basic neurobiological concepts thought to be related to the schizophrenia. A better understanding of the neurobiological mechanisms of susceptibility to recurrence could provide useful information in the development of strategies for preventing relapse.

Adult↗

Optical filters inhibiting television-induced photosensitive seizures.

OBJECTIVE: Televised images are the most common stimulus for provoking photosensitive seizures in photosensitive persons. To inhibit photosensitive seizures in photosensitive persons who do or do not have epilepsy, the authors sought nonpharmacologic methods for reducing the levels of photic stimulation of televised images. BACKGROUND: The authors found two types of pathophysiologic mechanisms (wavelength-dependent and quantity of light-dependent mechanisms) for photoparoxysmal responses (PPR). METHODS: The authors tested two different types of optical filters, one reflecting long-wavelength red light selectively, which stimulates a wavelength-dependent mechanism, and the other absorbing light in the visible spectrum evenly (neutral density filters). Inhibiting effects of optical filters were studied by conventional intermittent photic stimulation (IPS) using strobe light and novel photic stimulation using flashing cathode ray tubes (CRT). RESULTS: Both filters individually inhibited PPR insufficiently (less than 50%). Compound optical filters, composed of both types of filters, can inhibit the PPR, approximately 90% for IPS and 95% for photic stimulation with CRT. These compound optical filters do not destroy chromaticity of emissions from the television's CRT. CONCLUSIONS: These compound filters may be useful to prevent seizures induced by television in photosensitive persons.

Adolescent↗

Tributyltin or triphenyltin inhibits aromatase activity in the human granulosa-like tumor cell line KGN.

The superimposition of male sex organs (penis and vas deferens) in a female gastropod, called imposex, is widely attributed to the exposure to tributyltin (TBT) compounds, used world-wide in antifouling paints for ships. It has been hypothesized that the TBT-induced imposex is mediated by an increasing androgen level relative to the estrogen level, namely a decreased conversion of androgens to estrogens (i.e., aromatization). In the present study, we tested this hypothesis by examining the effects of TBT or triphenyltin (TPT) on the aromatase activity in a cultured human granulosa-like tumor cell line, KGN, which was recently established by our group. Treatment with more than 1000 ng/ml TBT compounds was very toxic to the cells and caused immediate cell death within 24 h, while 200 ng/ml was found to cause apoptosis of the cells. Treatment of the KGN cells for more than 48 h with 20 ng/ml TBT or TPT, which is a concentration level reported to cause imposex in marine species, did not affect cell proliferation but significantly suppressed the aromatase activity determined by a [(3)H]H(2)O release assay. Treatment with 20 ng/ml TBT compounds for 7 days also resulted in a reduction of the E2 production from Delta 4-androstenedione stimulated by db-cAMP. The changes in the aromatase activity by TBT compounds were associated with comparable changes in P450arom mRNA assessed by RT-PCR. The luciferase activity of the P450arom promoter II (1 kb) decreased after the addition of 20 ng/ml TBT compounds in transfected KGN cells either in a basic state or in states stimulated by db-cAMP. The Ad4BP-dependent increase in the luciferase activity of P450arom promoter II was also downregulated by such treatments. These results indicate that TBT compounds inhibited the aromatase activity and also decreased the P450arom mRNA level at the transcriptional level in KGN cells. The direct inhibitory effect of TBT compounds on the aromatase activity may therefore partly explain the induction of imposex by these compounds in female species.

Androstenedione↗

Possible involvement of p38 mitogen-activated protein kinase in decidual function in parturition.

We designed the present study to elucidate the molecular mechanism for parturition, focusing on p38 mitogen-activated protein kinase (p38). The kinase activity of p38 in mouse uterus was gestation stage-dependent, and was markedly increased on day 19 of gestation and during labor. Immunohistochemical examination with anti-phospho p38 antibody revealed that activated p38 was predominantly localized in decidual stromal cells stained with anti-prolactin antibody. In human primary cultured decidual cells, a p38 inhibitor, SB202190, significantly inhibited both prostaglandin F(2alpha) production and COX-2 expression induced by stimulation with IL-1beta. These results suggest that the p38 signaling pathway is involved in decidual function at the late stage of gestation and may contribute to parturition.

Animals↗

The first direct oxidative conversion of a selenol to a stable selenenic acid: experimental demonstration of three processes included in the catalytic cycle of glutathione peroxidase.

[structure: see text]. A stable selenenic acid was synthesized by direct oxidation of a selenol bearing a novel bowl-type substituent with H2O2, and its structure was established by X-ray crystallographic analysis. Selenenyl sulfides obtained by the reaction of the selenenic acid with 1,4-dithiols were reduced to the corresponding selenol by treatment with a tertiary amine, thus achieving the experimental demonstration of three processes included in the catalytic cycle of glutathione peroxidase.

Catalysis↗

Susceptibility to subsequent episodes of spontaneous recurrence of methamphetamine psychosis.

We examine susceptibility to subsequent spontaneous recurrences of methamphetamine psychosis (i.e. flashbacks) in 11 flashbackers with a single episode and in nine flashbackers with subsequent episodes. All had undergone frightening stressful experiences during previous MAP use. Mild psychosocial stressors then triggered flashbacks. During flashbacks, the nine flashbackers with subsequent episodes had more markedly increased norepinephrine levels, with slightly increased 3-methoxytyramine levels. The duration of imprisonment in this subgroup approached significantly long levels than in the 11 flashbackers with a single episode. Robust noradrenergic hyperactivity with slightly increased dopamine release may therefore predict subsequent flashbacks. Longer exposure to distressing situations may also contribute to robust noradrenergic hyperactivity.

3,4-Dihydroxyphenylacetic Acid↗

Tongue atrophy in facioscapulohumeral muscular dystrophy.

Involvement of the lingual muscle is considered one of the exclusion criteria of facioscapulohumeral muscular dystrophy (FSHD). In a series of 151 Japanese patients with 4q35-FSHD, seven patients (4.6%) had tongue atrophy with abnormal MRI findings and typical myogenic patterns of electromyography. All seven patients belong to a group of early-onset FSHD with large gene deletions on chromosome 4q35. Our result suggests that the patients with 4q35-FSHD could have myopathic tongue atrophy.

Adolescent↗