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Biomedical subjects

T Hamada

Publications and source records attributed to T Hamada.

At least 217 records · Page 12Linked to original sources

[Initial symptoms and mode of neurological progression in spinocerebellar ataxia type 6 (SCA6)].

Spinocerebellar ataxia type 6 (SCA6) is genetically defined as a group of SCA characterized by late-onset pure cerebellar ataxia clinically and by a small CAG repeat expansion in the gene encoding the alpha 1A-voltage-dependent-Ca channel subunit (CACNL1A4) on chromosome 19p13.1 genetically. We analyzed the initial symptoms and the mode of progression in this disorder on 25 genetically verified patients. The initial symptoms were recurrent episodes of transient vertigo (72%) or unsteady gait (28%). Neurologically, they showed apparent gaze-evoked nystagmus (92%), transient positional nystagmus (83%), and periodic alternating nystagmus (4%), in addition to cerebellar ataxia. In addition to these episodic symptoms, all patients developed progressive cerebellar ataxia over years. These fluctuating symptoms at the initial stage of the illness were clearly different from those of other SCA, rather overlapping with those of episodic ataxia type 2 (EA2), an allelic disorder of SCA6. The clinical similarity indicates that there might be a common mechanism at least in part causing these two disorders. The mode of progression and their neurological features were also presented.

Adult↗

Neural Network Computer Analysis of Fetal Heart Rate.

> Objective: A nonsubjective evaluation of intrapartum fetal heart rate (FHR) with a neural network (NNW) computer system and its clinical application. Methods: Eight simple FHR data were input into the NNW computer after 16-step normalizations. The computer was composed of 40 units in the input layer, 30 in intermediate layer, and 3 in the output layer, and the probabilities to be normal, suspicious, and pathological were obtained at the output. Before use, the computer was trained 10,000 times by 50-min teacher FHR data of 20 cases with known outcomes. The trained NNW computer was tested by FHRs of another 29 cases. The outcome probabilities in 15 min were calculated every 5 min in another 10 cases, and the bar graphs of the probabilities were displayed in sequence in the trendgrams. Results: The trained NNW computer was 100% accurate in the internal check; in the external check 86% of the results were evaluated correctly with the cardiotocogram, Apgar score, and umbilical arterial pH of the 29 test cases. The FHR scores of our conventional computer FHR analysis were higher in the suspicious and pathological groups than the normal group, and the fetal distress index was high in the pathological group. The trendgrams were simply accurate in typically normal or abnormal cases, transitory abnormal probabilities were shown in intermediate cases, and mixed suspicious and pathological probabilities suggested pathological outcome. Conclusions: The outcome probabilities and their trendgrams in the NNW FHR analysis are promising in objective decision making in the intrapartum stage.

Journal Article↗

Le(y) glycolipid acts as a co-factor for tumor procoagulant activity.

We have generated a monoclonal antibody (MAb), FS01, which inhibits the procoagulant activity (CCA-1) produced by a human squamous cell carcinoma cell line, LK52. Expression of the antigen recognized by FS01 MAb in various cancer cell lines correlated well with the procoagulant activities of the expressing cell lines. Our objective was to characterize the molecule reacting with FS01 MAb and to analyze its involvement in the CCA-1 procoagulant activity. The molecule was identified as a glycolipid and found to be involved in the procoagulant activity because both procoagulant activity and reactivity to FS01 MAb were lost after endoglycoceramidase treatment of CCA-1. Furthermore, FS01 MAb recognized the Lewis Y (Le[y]) antigen. To confirm the involvement of a glycolipid incorporating the Le(y) antigen in the procoagulant activity, we attempted to purify CCA-1 from LK52 culture supernatant. In one of the purification steps, a fraction containing low procoagulant activity (CCA-1p) separated from the Le(y)-positive fraction (CCA-1c). Although CCA-1c alone did not show procoagulant activity, the procoagulant activity of CCA-1p was augmented by CCA-1c and this augmentation was inhibited by FS01 MAb. Furthermore, CCA-1c enhanced the procoagulant activity of 33 cell lines tested as well as CCA-1p. In addition, purified Le(y) glycolipid from canine intestine augmented the procoagulant activity of CCA-1p, and this augmentation also could be inhibited by FS01 MAb. We conclude that Le(y) glycolipid is a co-factor for the procoagulant activity derived from cancer cells.

Animals↗

Clonal analysis of high-grade squamous intra-epithelial lesions of the uterine cervix.

We previously reported that invasive squamous cell carcinomas of the uterine cervix are of monoclonal composition. In the current study, we extended our previous work to determine the clonal composition of cases of high-grade squamous intra-epithelial lesion (HSIL). Clonal analysis targeting the HUMARA locus was performed on cervical tissue from 9 cases, 8 showing heterozygosity at the HUMARA locus and being, therefore, informative for clonality analysis. Uterine cervices were cut into 12 blocks, fixed with formalin and embedded in paraffin, and DNA was extracted from targeted lesions of each block. A total of 30 samples of cervical intra-epithelial neoplasia 3 (CIN3) (14 samples of carcinoma in situ and 16 samples of severe dysplasia) and 1 sample of CIN2 (moderate dysplasia) were analyzed. Monoclonal composition of the lesions was demonstrated in 30/30 cases of CIN3. Polyclonal composition was seen in the single case of CIN2. In 6 uterine cervices, in which dysplastic lesions were present in more than 3 blocks, the pattern of X-chromosome inactivation was the same in all lesions, suggesting that these individual lesions were derived from a single cell, with intraepithelial extension within the cervical mucosa. By contrast, one uterus contained 2 discontinuous dysplastic foci with different patterns of X-chromosome inactivation, indicating that the 2 lesions developed independently from each other. Our results demonstrate that (i) lesions of CIN3 (severe dysplasia and carcinoma in situ) are composed of a clonal neoplastic population of cells and (ii) most cases of HSIL are unifocal in origin.

Carcinoma in Situ↗

Autosomal dominant spastic paraplegia linked to chromosome 2p: clinical and genetic studies of a large Japanese pedigree.

Autosomal dominant spastic paraplegia (ADSP) is a genetically heterogenous disorder. To date, 3 loci of ADSP have been identified on chromosome 2p, 14q, and 15q, but specific gene mutations remain unknown. To determine the genetic background of ADSP in the Japanese, we studied a large 3-generation pedigree, clinically and genetically. Of the 36 individuals clinically examined, 15 were affected. The main feature in the affected individuals was a slowly progressive spastic paraplegia, associated with upper limb hyperreflexia (58%), reduction of vibration sense (27%) and bladder disturbance (13%). Age at onset ranged from 13 to 50 years with a mean of 30.3 +/- 14.2 (SD). There were 6 parent-child pairs with anticipation and at least 3 others with 'anti-anticipation'. Linkage with 14q and 15q ADSP loci was excluded, and a highly significant lod score was obtained only in the case of the 2p locus (Zmax = 3.53 for D2S400/D2S352, at theta = 0.00). Our study is the first to confirm the existence of 2p-linked ADSP in the Japanese. There is a significant variety in age at onset and disease severity in these 2p-linked families, but the implication for underlying ADSP mutation is not clear.

Adolescent↗

The involvement of calmodulin and Ca2+/calmodulin-dependent protein kinase II in the circadian rhythms controlled by the suprachiasmatic nucleus.

We investigated the involvement of calmodulin and Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the photic entrainment of circadian rhythms using calmodulin inhibitors such as calmidazolium (CMZ) and trifluoperazine (TFP), and a CaMKII inhibitor, KN-62, in rats. Fos expression in the suprachiasmatic nucleus (SCN) of rats induced by photic stimulation (300 lux, 1 h) during the early subjective night of the rats was inhibited by treatment with CMZ (10 mg/kg i.p.) or TFP (20 mg/kg i.p.) 30 min before photic stimulation. With respect to the neuronal firing rate in the rat SCN slice, KN-62 and CMZ application during the early subjective night attenuated the glutamate (10 microM)-induced phase shift. The present results suggest that calmodulin and CaMKII are involved in the photic entrainment mechanism in the rodent SCN.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Dominantly inherited leukodystrophy showing cerebellar deficits and spastic paraparesis: a new entity?

We studied a dominant hereditary disorder showing progressive spastic paraparesis. The symptoms began in early childhood, with cerebellar deficits and mild mental deterioration, and the subsequent appearance of limb spasticity resulted in severe disability in the 3rd-4th decades of life. None of the patients were associated with any somatic abnormalities. Brain MRI showed diffuse white-matter involvement in all affected patients, but not in unaffected siblings. Although dominant, recessive, or X-linked leukodystrophies cause similar clinical features, our family did not show any known biochemical or gene deficits characteristic of these disorders. The clinical, radiological, and biochemical findings of this family are reported and suggest a possible novel genetic disorder.

Adult↗

Anti-nuclear antibodies and the optic-spinal form of multiple sclerosis.

We found anti-nuclear antibodies (ANA) (1:20 or higher) in sera from 11 of 16 patients with a diagnosis of the optic-spinal form of multiple sclerosis (OpS-MS) and 13 of 59 patients with other forms of MS (other MS), both rates being significant (P = 0.0004). Six of the OpS-MS patients had a high level of ANA (1:80 or higher), while levels were high in only three of the other MS patients, showing a significant difference (P = 0.0022). Titres of ANA were significantly higher in OpS-MS patients than in other MS patients (P < 0.0001). There was no relationship between the presence of ANA and age in OpS-MS patients, while patients with were older than those without high ANA levels among other MS patients. ANA-positive rate and titres were significantly higher in OpS-MS patients than in sex- and age-matched other MS patients. These results support the concept that OpS-MS constitutes a distinct subgroup among patients with a clinical diagnosis of MS and may indicate that systemic dysregulation of the inflammatory or immune response is more common in OpS-MS patients; the possible pathogenetic relevance of ANA-associated vasculopathy to some patients with a clinical diagnosis of OpS-MS should be considered.

Adult↗

Facial palsy in multiple sclerosis.

Facial palsy occurred in 21 (19.6%) of 107 Japanese patients with multiple sclerosis (MS) during a mean follow-up period of 4.3 years. We observed residual signs of facial palsy in five other patients in whom acute onset was confirmed from medical records. Facial palsy began on average 7.6 years after the onset of MS but in five patients (4.7%) was the first symptom of MS, preceding the next MS symptom by 0.5-3 years. Facial palsy was usually associated with other brainstem signs, while two patients showed only facial palsy 1 and 3 years after the onset of MS. Twenty-one (84.0%) of the 25 patients who underwent brain magnetic resonance imaging (MRI) showed brainstem lesions in the pontine tegmentum ipsilateral to the facial palsy. However, the two patients without other symptoms or signs had no apparent causal lesion on MRI, which suggests difficulty in differentiating idiopathic Bell's palsy from MS- associated facial palsy by MRI, although it has an excellent capacity to detect causal lesions of facial palsy associated with MS.

Adult↗

A ring model for spatiotemporal properties of simple cells in the visual cortex.

A neural model is proposed for the spatiotemporal properties of simple cells in the visual cortex. In the model, several cortical cells are arranged on a ring, with mutual excitatory or inhibitory connections. The cells also receive excitatory inputs either from lagged and nonlagged cells of the lateral geniculate nucleus in one setting or from nonlagged cells in the other. Computer simulation shows that the cortical cells have spatiotemporally inseparable receptive fields in the former setting and separable fields in the latter; spatial profiles at a given time in the spatiotemporal fields are described with a Gabor function whose phase parameter varies regularly from 0 to 2 pi with rotation along the ring; the inseparable cells have directional selectivity as observed physiologically.

Membrane Potentials↗

Risk factors for methicillin-resistant Staphylococcus aureus (MRSA) infection in a Japanese geriatric hospital.

A case control study on MRSA infection was carried out, with the purpose of evaluating the effect of age, gender, hypoalbuminemia, the limitation of activities of daily living (ADL), the administration of antibiotics and the use of the new cephems which include third generation cephalosporins and monobactam and carbapenems, on the occurrence of MRSA infection among the inpatients in a geriatric hospital. From April 1991 to March 1994, 285 patients underwent a bacterial culture in the various clinical aspects. 118 patients were positive for MRSA, who were then used as cases while 167 patients who were negative for MRSA were used as controls. The level of serum albumin and the ADL score were lower in the MRSA group than in the non-MRSA group (P < 0.01) while the number of antibiotics administered before bacterial culture was greater in the MRSA group than in the non-MRSA group (P < 0.01). The third generation cephems were more commonly used in the MRSA positive patients than the negative patients (P < 0.01). Even after controlling for the other factors, hypoalbuminemia (OR = 1.73, 95% CI = 1.27-2.36), the limited ADL (partially limited vs without limitation: OR = 1.88, 95% CI = 1.19-2.96, completely limited vs without limitation: OR = 2.50, 95% CI = 1.64-3.82), the use of antibiotics other than the third generation cephems (vs without antibiotics: OR = 1.73, 95% CI = 1.20-2.50) and the administration of the third generation cephems (vs without antibiotics: OR = 3.12, 95% CI = 2.16-4.50) increased the risk of MRSA infection.

Aged↗

The determination of working time and gelation time of temporary soft lining materials.

OBJECTIVE: The purpose of this study was to establish a new method for the determination of working time and gelation time of temporary soft lining materials using a displacement rheometer. METHOD: A displacement rheometer (The Dental School, University of Newcastle, Newcastle upon Tyne, UK) was used to apply a rapid displacement of 0.25 mm held for 1 s at intervals of 60 s to samples of four temporary soft lining materials. Material displacement and elastic recovery at each test time was recorded. The test procedure was repeated three times at 23 degrees C and at 37 degrees C for each material. For one material, the displacement time was varied (1, 5, 10 s). The working time was defined as the time corresponding to the initial observation of elastic recovery at 23 degrees C. Gelation time was the time when a material achieved 95% of its maximum elastic recovery at 37 degrees C. Values were compared between materials using one-way analysis of variance and Student-Newman-Keuls test at the 5% level of significance. RESULTS: The gelation rate of all materials increased with increasing temperature although the extent of this influence varied between materials. The development of elastic recovery in the materials during gelation accurately fitted asymmetric sigmoids. The correlation coefficient (r) ranged from 0.982 to 0.999. Statistically significant variations in both the working and gelation times of the test materials were established. The time of displacement affected both the rate of development of elasticity and the value of elastic recovery but this effect was only statistically significant when the displacement time was increased to 10 s. SIGNIFICANCE: The displacement rheometer may be suited for use as a standard test method for the determination of the working time, gelation time and elastic behavior of temporary soft lining materials.

Acrylic Resins↗

Cell density-dependent mitogenic effect and -independent cellular handling of epidermal growth factor in primary cultured rat hepatocytes.

AIMS: Mitogenic effect and cellular handling of epidermal growth factor (EGF) were analyzed in primary cultured rat hepatocytes at several cell densities. METHODS/RESULTS: DNA synthesis, assessed by the incorporation of 125I-deoxyuridine, was accelerated by EGF at a low cell density while that stimulated by EGF was relatively low at the highest cell density, suggesting a cell density-dependent regulation of mitogenic response to EGF. An equilibrium binding study of 125I-EGF in the presence of various concentrations of unlabeled EGF at 0 degree C revealed that the dissociation constant (Kd) was 0.47-0.88 nM while the specific binding capacity (n) was 86-96 fmol/mg protein at each cell density. No significant difference was observed in the time profiles of the surface-bound, internalized, and degradation products of 125I-EGF, assessed per mg protein, between different cell densities. Based on a kinetic analysis of the time-profiles, the internalization rate constant and the degradation rate constant were found to be independent of cell density. CONCLUSIONS: These results indicate that the cellular binding and disposition of EGF are not regulated by cell density, and that the cell density-dependence of the mitogenic effect cannot be attributed to differences in the affinity or capacity of the EGF receptor, internalization, or degradation of EGF. We speculate that the cell density-dependent mitogenic response may be accounted for by the difference in other factors such as the signal transduction processes induced by the receptor binding of EGF, or the translocation of a small fraction of the total EGF to hepatocyte nuclei.

Animals↗

Quantification of thigmotropism (contact sensing) of Candida albicans and Candida tropicalis.

To quantify the thigmotropism, we adapted the our previous method using a chemotaxifilter system in combination with a bioluminescent adenosine triphosphate (ATP) assay based on firefly luciferase-luciferin system and analyzed the relationship between the ability of germ tube formation and thigmotropism of C. albicans and C. tropicalis. Both the ability to form germ tube and the amount of hyphae exhibiting thigmotropism varied depending upon both the species and strains of Candida. C. albicans formed more germ tubes than C. tropicalis. A good correlation was observed between the ability to form a germ tube and the capacity for thigmotropism, and the results gave a level of significance (p < 0.05). Further, SEM observation revealed that relatively long hyphae of C. tropicalis with penetrated through the pores of filter membrane. This phenomenon may be of importance in the development of pathogenesis of C. tropicalis as well as C. albicans.

Candida↗

Effects of dietary sugars and, saliva and serum on Candida bioflim formation on acrylic surfaces.

The effect of two dietary sugars, glucose and galactose, on biofilm formation of the oral fungal pathogen Candida on denture acrylic strips coated with saliva and serum pellicles was examined in vitro using Candida albicans (3 isolates), C. glabrata (2 isolates) and C. tropicalis (2 isolates). The degree of biofilm activity was affected by both the dietary sugar and the nature of the pellicle (ANOVA, p < 0.01). With most isolates the glucose grown yeasts demonstrated significantly more bioflim activity than the galactose grown fungi, in the presence of pellicles (ANOVA, p < 0.01 or P < 0.01). In contrast, one isolate of galactose-grown yeast elicited significantly higher biofilm activity than glucose-grown yeasts on the control strips (ANOVA, p < 0.01). Taken together, these results imply that a saliva or a serum pellicle, and the carbon source in the environment, act a complex manner modulating Candida bioflim formation.

Acrylic Resins↗

Apoptosis induced by cadmium.

Cell death resulting from cadmium (Cd) intoxication has been confirmed to occur through apoptosis by morphological and biochemical studies. However it is still not clear whether Cd itself or metallothionein (MT) induced by Cd is the major factor responsible for the apoptosis. Although apoptosis is inducible by exposure of cells to various stimuli, the common pathway involved is generally accepted to be activation of endonucleases that induce internucleosomal cleavage of DNA, resulting in the 'ladder' formation observed upon agarose gel electrophoresis and the chromatin condensation seen by electron microscopy. Cd does not seem to activate the endonuclease in vitro. However, Cd itself can be associated with apoptosis through indirect oxidative stress by inhibition of antioxidant enzymes and possible interaction with zinc finger protein. In addition to the direct effect of Cd, MT appears to play dual roles in apoptosis induction: one as a Cd carrier by which Cd accumulates in the nucleus, and the other as an inhibitor of zinc finger proteins, which include transcriptional factors related to apoptosis such as the product of the apoptosis resistance gene A20. In this review, we demonstrated that the mode of cell death following Cd exposure is associated with intracellular movement of Cd and MT. A possible mechanism for Cd-induced apoptosis is also discussed.

Journal Article↗

Effects of salivary or serum pellicles on the Candida albicans growth and biofilm formation on soft lining materials in vitro.

The effects of salivary or serum pellicle on Candida albicans growth, biofilm formation and cavitation on the soft lining materials were examined. Both saliva and serum pellicles reduced the antifungal effects of soft liners. The fungal biofilm formation on these materials varied depending upon both the materials tested and protein-coats, and the pellicles which significantly enhanced the biofilm formation. Similarly, the pellicles enhanced the firm colonization and hyphal invasion of the yeasts on the specimens, although the cavitation appeared to be regulated by the plasticizer used. These results suggest that the interactions between proteinaceous pellicle, tissue conditioners and fungi are complex. They also suggest that denture pellicles facilitate fungal plaque formation onto soft lining materials through several mechanisms such as reduction of the antifungal effects of soft liners, facilitation of biofilm formation, firm colonization and hyphal invasion. In addition, the composition of the materials is also involved in the susceptibility to the fungi.

Biofilms↗