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Biomedical subjects

K Shinoda

Publications and source records attributed to K Shinoda.

At least 19 recordsLinked to original sources

On the importance of hydroxyl groups in the polar head-group of nonionic surfactants and membrane lipids.

In this review properties of natural membrane lipids and surfactants synthesized from natural substances, such as paraffin chain alcohols and carbohydrates, are compared with those of synthetic surfactants of the polyoxyethylene type. Special attention is paid to the characteristic solution properties of nonionic surfactants with hydroxyl groups as the hydrophilic moiety, including alkyl glyceryl ethers and alkyl glucosides and maltosides, which are compared with those with oxyethylene groups. The major properties of the hydrophilic moiety are lipophobicity and hydrophilicity. Lipophobicity is an important property of oil-soluble surfactants, in particular for the polyoxyethylene alkyl ether type of surfactants where a too high lipophobicity may result in solubility in water.

Carbohydrate Sequence

Transcriptional activation by the androgen receptor in X-linked spinal and bulbar muscular atrophy.

Polyglutamine tracts encoded by trinucleotide CAG repeats have been found in some transcription factors. Expansion of the polyglutamine tracts in the androgen receptor (AR) has been recognized as a cause of X-linked spinal and bulbar muscular atrophy (SBMA). To study the role of AR as a transcription factor in SBMA, we constructed AR genes encoding expanded polyglutamine tracts (repeat numbers = 52, 92, 132, and 212), and analyzed AR-induced transcriptional activation in NG108-15 cells. We found that AR-induced transcriptional activation gradually decreased with increasing glutamine repeat numbers, and polyglutamine expansion caused a specific reduction in transcription activity in motor neurons. However, the degree of reduction was slight in comparison with the normal AR gene and that of SBMA. Thus, subtle disorders of transcriptional control may occur in SBMA.

Animals

Effect of phenytoin on interleukin-1 beta production in human gingival fibroblasts challenged to tumor necrosis factor alpha in vitro.

Effects and interaction of tumor necrosis factor alpha (TNF alpha) and the antiepileptic drug phenytoin (PHT) on interleukin-1 beta (IL-1 beta) production as well as on prostaglandin E2 (PGE2) formation were studied in gingival fibroblasts in vitro. TNF alpha, in contrast to PHT, dose-dependently stimulated the production of cell-associated IL-1 beta. The stimulatory effect of TNF alpha on IL-1 beta production was accompanied by enhanced PGE2 formation. When PHT and TNF alpha were added simultaneously, the drug potentiated the stimulatory effect of TNF alpha on both IL-1 beta production and PGE2 formation. The major PHT metabolite, p-HPPH, did not affect IL-1 beta production, either alone or in combination with TNF alpha. The production of IL-1 beta induced by TNF alpha and the combination of TNF alpha and PHT was further enhanced in the presence of the prostaglandin endoperoxide (PGH) synthase inhibitors, indomethacin and flurbiprofen. The PHT-mediated enhancement of TNF alpha-induced IL-1 beta production and PGE2 formation in gingival fibroblasts may be an important link in the pathogenesis of gingival overgrowth induced by PHT.

Child

Effects of extracellular matrix macromolecules on the differentiation of plasma membrane structure in cultured astrocytes.

Orthogonal aggregates of small intramembrane particles, termed "assemblies," are concentrated especially in the cell membranes of astrocytic processes that form the glia limitans at the outer surface of the brain and the perivascular sheath surrounding the parenchymal blood vessels. As an initial step to clarifying the totally unknown biochemical nature of this intramembrane structure, we have devised a culture system which enhances the differentiation of assemblies in secondary cultures of astrocytes derived from neonatal mouse neopallium. Since assemblies are most concentrated in the plasma membranes attaching to the basement membrane, we expected that extracellular matrix molecules constituting the basement membrane would be suitable candidates for our aim. We report here that a mixture of type IV collagen, laminin, and fibronectin, major components of the extracellular matrix, has the potency to increase assembly density in cultured astrocytes. We also report that, in freeze-fracture electron microscopy of cultured cells, one can satisfactorily preserve membrane structure and reliably obtain large replicas by inoculating cells on aluminium foil and peeling it from the cells in a freeze-fracture apparatus.

Animals

Developmental defects of the ventromedial hypothalamic nucleus and pituitary gonadotroph in the Ftz-F1 disrupted mice.

Ad4BP (or SF-1) has been identified as a transcription factor which regulates all the steroidogenic P450 genes in the peripheral organs, and is encoded by the mammalian homologue of Drosophila FTZ-F1 gene. mRNA coding for Ad4BP was detected in the hypothalamus and pituitary of rats by RT-PCR. Immunohistochemical analyses using an antiserum to Ad4BP in the brain and pituitary revealed that the transcription factor is expressed in nuclei of the dorsomedial part of the ventromedial hypothalamus (dmVMH) and in some subpopulation of the adenohypophysial cells. Double immunostaining of the pituitary for Ad4BP and trophic peptide hormones, FSH, TSH, and ACTH, indicated a restricted localization of Ad4BP to the gonadotroph. Disruption of the mouse Ftz-F1 gene was clarified to induce severe defects in the organization of the dmVMH and the function of the pituitary gonadotroph. However, some of the dm VMH neurons and pituitary gonadotrophs persisted, which provided a sharp contrast to complete agenesis of the peripheral steroidogenic tissues (adrenal and gonads) in the mutant mouse. Additional abnormalities were seen in the ventrolateral part of VMH and dorsomedial hypothalamic nucleus, both of which do not express Ad4BP but have strong reciprocal fiber-connections with the dmVMH. Aromatase P450-containing cells in the medial preoptico-amygdaloid region, which were devoid of Ad4BP, persisted even in the brain of the gene disrupted mice. The present results clearly showed that the hypothalamic and pituitary Ad4BPs are essential to normal development of the functional VMH and gonadotroph through some mechanism distinct from that in the peripheral steroidogenic tissues.

Animals

Serial MRI in early Creutzfeldt-Jacob disease with a point mutation of prion protein at codon 180.

We report a 66-year-old woman with histologically diagnosed Creutzfeldt-Jacob disease (CJD), followed with MRI from an early clinical stage. MRI demonstrated expansion of the high cortical signal on T2-weighted images, which differs from previous MRI reports of CJD. This patient followed an atypical clinical course: 16 months had passed before she developed akinetic mutism, and periodic sharp waves had not been detected on EEG after 2 years in spite of her akinetic mutism. Brain biopsy showed primary spongiform changes in the grey matter, and a point mutation of the prion protein gene at codon 180 was discovered using polymerase chain reaction direct sequencing and Tth 111 I cutting. This is the first case with the point mutation of the codon 180 variant with an atypical clinical course and characteristic MRI findings.

Aged

Electron microscopic finding of eccrine sweat gland epithelial cells in a patient with Krabbe disease.

A 13 month old boy was found to have severely reduced beta-galactocerebrosidase activity suggesting infantile Krabbe disease. Clinically, the patient showed a progressive neurological deterioration with white-matter disease on radiological study. Axillary skin biopsy was performed to support the diagnosis. On electron microscopy, needle-like inclusions, which are the typical finding seen in the cytoplasm of astrocytes and Schwann cells in the classic infantile form, were present in eccrine sweat gland epithelial cells. This method is useful for diagnosis when nerve biopsy and biochemical analysis are not readily available.

Eccrine Glands

Lymphocytapheresis in combination with immunosuppressive drugs for refractory myasthenia gravis: two-color flow cytometric analysis of changes in peripheral blood lymphocyte subsets.

We carried out lymphocytapheresis (LCP) in combination with the administration of immunosuppressive drugs in patients with myasthenia gravis (MG), who were resistant to conventional immunosuppressive therapy, and examined its efficacy and effects on peripheral blood lymphocyte subsets. LCP was carried out once a week for 1 month (one course, 4 times) using a continuous-flow blood cell separator. Immunosuppressive medication (prednisolone or prednisolone and azathioprine) was continued during the course of treatment. After LCP, clinical improvement was noted in 5 of 6 patients. Anti-AChR antibody titers and the number of lymphocytes were significantly reduced in all patients. A significant decrease in CD4+CD45RA- (memory) T cell level and significant increase in CD4+CD45RA+ (naive) T cell level were also observed. In the patients having good response to LCP, follow-up evaluation showed long-term clinical improvements, as well as the memory T cell level staying at the decreased level. Our study suggests that LCP in combination with the administration of immunosuppressive drugs can suppress the disease activity of MG.

Autoantibodies

Physical status and dementia risk: a three-year prospective study in urban Japan.

A three-year prospective study of 3,180 non-dementia persons in Sendai City, Japan was conducted to examine the effects of physical status and diseases diagnosed on dementia incidence. This cohort had been made at the initial survey in 1988 and the evaluation for incident dementia was performed on 2,461 respondents (77.4%) in a follow-up survey in 1991. Regarding physical status, the logistic regression including sex, age, health status, ambulatory activity and activities of daily living indicated that the poor health status and the limitation of ambulatory activity were significantly associated with an increased risk of dementia. The significant positive association with dementia was observed on stroke, respiratory disease and depression. This study identified the high risk population for dementia in the aspect of physical status.

Activities of Daily Living

Multivariate analysis of limb long bone growth during the human prenatal period.

Prenatal development of the human limb bones (humerus, ulna, radius, femur, tibia, fibula) was studied. Cross-sectional data, consisting of 21 anthropometric measures of these bones were collected from 122 Japanese fetuses between the gestational ages of 18 and 40 weeks. Principal component analysis was applied to the data to provide multivariate assessments of morphological patterning among the variables. Three orthogonal components that accounted for 94.2% of the overall sample variation were extracted. The first component accounted for 88.2% of the variation and represented an axis of overall body size that was dependent on gestational age. The second and third components both reflected a trend in shape involving the cartilaginous parts of the humerus and femur. The findings indicated that different growth factors existed between the ossified and cartilaginous parts of fetal long bones. Multivariate allometric coefficients were extracted from the first principal component. The variables that were related to the construction of the articulate showed positive allometry, and the central widths of the diaphysis showed negative allometry compared with total size. In prenatal skeleton, certain shape changes are functionally linked to and required by changes in body size. A comparison among the coefficients of long bone length revealed that lower limb bones grew faster than upper limb bones during the period under study here. Allometric coefficients were equivalent among bones within a limb, whereas homologous bones in the upper and lower limb grew at different rates.

Bone and Bones

Dementia and physical disability as competing risks for mortality in a community-based sample of the elderly Japanese.

To examine whether an excess mortality due to dementia is independent of coexisting physical disability, a probability-sample of the non-institutionalized elderly (n = 3,308) living in Sendai City, Japan was followed between 1988 and 1991. Of those, 128 were diagnosed as dementia in 1988 by psychiatrists, using Diagnostic and Statistical Manual of Mental Disorders, Third Edition-Revised as a diagnostic standard. Information on the ability to perform activities of daily living (ADL) was collected by self-report of the study subjects in 1988 baseline survey. The survival status was investigated three years later. The risks of dementia and co-existing ADL disability for mortality was examined by Cox proportional hazard models. The results indicated that the relation between dementia and mortality was two-fold, depending upon the physical functions. Dementia increased the risk for mortality among those without ADL disability, but it did not so among those with ADL disability, rather ADL function was a stronger predictor for mortality among the latter individuals. Prevention and treatment of physical disability would be important for improving the survival of the demented people.

Aged

Longitudinal study of serum and cerebrospinal fluid (CSF) class-specific antibodies against Campylobacter jejuni and GM1 ganglioside in Guillain-Barré syndrome.

We report two Guillain-Barré Syndrome (GBS) patients with culture-proven Campylobacter jejuni (Penner19/Lior 7). Elevated anti-C.jejuni IgA antibody declined to the normal range within one month, elevation of anti-C.jejuni IgM antibody lasted for 3 months and the titers of anti-C.jejuni IgG antibody were still elevated at one year after the neurologic onset. Serological criteria for antecedent C.jejuni infection in GBS patients should require 1) high titer of serum IgA and/or IgM antibody against C.jejuni followed by seroconversion of the IgA and/or IgM and 2) a 4-fold decline of IgG serum dilution against C.jejuni. Anti-C.jejuni antibodies in cerebrospinal fluid (CSF) reached the maximum value at one month after their neurologic onset which may not be responsible for the main pathological mechanism in the development of GBS. Anti-GM1 antibodies in serum and CSF were parallel with those of anti-C.jejuni antibodies during the course of the disease.

Adult

Herpes simplex virus type 2 infections presenting as brainstem encephalitis and recurrent myelitis.

We describe here 3 patients with central nervous system infection caused by herpes simplex virus type 2 (HSV-2); one patient with brainstem encephalitis and two with recurrent transverse thoracic myelitis. All three patients showed increased IgG antibodies to HSV in the cerebrospinal fluid (CSF). HSV-2 DNA was demonstrated in the CSF by polymerase chain reaction (PCR) amplification. Upon treatment with acyclovir, one patient with myelitis partially recovered and the others completely recovered. It is important to recognize the wide spectrum of clinical manifestations of HSV-2 infection in the central nervous system (CNS).

Adult

A case of osteoporosis with bilateral defects in the mandibular processes.

We carried out a detailed total body examination of a 62-year-old woman with osteoporosis who had bilateral defects in the mandibular processes. It was inferred that the defects in both articular heads were caused by resorption of small bone fragments following fracture. The quantity of bone salt was determined by microdensitometry, and a diagnosis of osteoporosis was then established. An improved bite was obtained by treatment consisting of tooth extraction and the preparation of partial dentures.

Absorptiometry, Photon

RES-1214-1 and -2, novel non-peptidic endothelin type A receptor antagonists produced by Pestalotiopsis sp.

RES-1214-1 and -2, novel and non-peptidic endothelin antagonists, were isolated from the cultured broth of a fungus, Pestalotiopsis sp. RE-1214. RES-1214-1 and -2 selectivity inhibited the ET-1 binding to endothelin type A receptor (ETA receptor) with IC50 values of 1.5 microM and 10 microM, respectively. RES-1214-1 and -2 inhibited the increase in intracellular Ca2+ concentration elicited by 1 nM ET-1 in A10 cells. Taxonomy of producing strains, fermentation, isolation, structural determination, and biochemical properties of RES-1214-1 and-2 are described.

Animals

[Giant cell interstitial pneumonia in a metal grinder with an abnormally high level of serum CA19-9].

Interstitial pneumonia and recurrent pneumothorax developed in a 48-year-old man who had worked as a metal grinder. He died of respiratory failure despite having received antibiotics and steroids, and despite having undergone pleural sclerosis therapy. Giant cell interstitial pneumonia was diagnosed; innumerable bizarre giant cells engulfing black granules were found within the alveoli. The results of high-energy dispersion X-ray microanalysis indicated that the patient had hard metal pneumoconiosis associated with tungsten in the black granules. When he was admitted to the hospital, his serum CA19-9 and SLEX concentrations were abnormally high (2600 and 200 ng/ml, respectively). Immunohistochemical analysis of lung tissue was done with anti-CA19-9 and SLEX antibodies. CA19-9 staining revealed strong bronchialization and squamous metaplasia in contrast to type II hyperplasia. SLEX staining showed strong type II hyperplasia. Further investigations will be needed to determine the mechanism of elevated tumor-associated carbohydrate antigens in serum.

Biomarkers, Tumor

Clinical features of Japanese Leber's hereditary optic neuropathy with 11778 mutation of mitochondrial DNA.

The G to A transition of nucleotide position (nt) 11778 of mitochondrial DNA (mtDNA) has been frequently observed in Japanese Leber's hereditary optic neuropathy (LHON) cases. Therefore, we performed a multi-institutional study in Japan of LHON cases with this 11778 mutation of the mtDNA. Genetic and clinical data on 108 cases (90 affected and 18 carriers) in 79 unrelated families were obtained from 64 Japanese institutions. Detection of the nt11778 mutation was performed using restriction enzymes (74 cases) or dot blot with allele specific oligonucleotide (34 cases). Heteroplasmy was observed in 13 of the 90 affected cases and in 8 of the 18 carrier cases. Forty-five families had family history of LHON (44 maternal inheritance, 1 undetermined), and in 28 families (35.9%) there were isolated cases. The male-to-female ratio in the affected was 82:7 (92.1% male). The age at onset of visual loss ranged from 7 to 59 years (average: 23.4 years). All cases had bilateral involvement except one case with a blind eye resulting from ocular infection during childhood. Onset interval between the two eyes ranged from simultaneous to 17 months (average: 2.5 months), in 91.3% of cases being under 6 months. Visual acuity was 0.1 or worse in 152 (85.9%) of 177 eyes, only 6 eyes showing over 0.5. Progression of visual loss ranged from 0 to 48 months (average: 6.2 months). Central visual field abnormality was observed in 162 eyes (96.4%) of 168 eyes. Nonsuspect fundus in the ophthalmoscopic examination constituted 22.8% of eyes. Systemic corticosteroid was given to 45 (52.9%) of 85 cases and visual acuity was improved in only 2 cases (4.4%). Arrhythmia, neurological and muscular abnormality were observed as rare general complications. The present survey indicates that the male-to-female ratio is higher than the previous Japanese LHON statistics and that the visual outcome is better than in American LHON cases with the 11778 mutation.

Adolescent

[Intracranial tuberculoma with spontaneous recovery].

A 57-year-old man was admitted because of headache, nausea, and fever up (38 degrees C). He showed nuchal rigidity slightly. CSF analysis showed 833 white blood cells (WBC) (80% monocyte), protein value of 68 mg/dl, glucose level of 36 mg/dl and ADA level of 11.8 IU/l. Brain pre-contrast CT indicated high density area in right parietal lobe, and it showed slightly homogeneously enhancement with contrast medium. MRI on T2 WI demonstrated hypointense lesion with bright central core in right parietal lobe. The lesion showed isointense on T1WI, and indicated homogeneous enhancement with Gd-DTPA. He was sent to our hospital after one week. With only antibiotics the symptoms were relieved and the CSF findings improved during the previous hospital. However, Mycobacterium tuberculosis (M. tuberculosis) DNA was detected in CSF by PCR amplification, and he recovered completely with anti-tuberculous treatment. This case was interesting to reveal atypical features of spontaneous recovery. Since Shankar's study using polymerase chain reaction (PCR) for detection of M. tuberculosis in cerebrospinal fluid (CSF), the PCR assay have been recognized to be a rapid method for diagnosis of tuberculous meningitis (TBM). But there are problems of PCR sensitivity when dealing with CSF samples containing small amount of M. tuberculosis DNA. Comparing direct PCR with nested PCR, we studied on the evaluation of PCR for diagnosis of TBM. In this study the nested PCR was positive in all CSF specimens from 4 patients with TBM, but we could not detect M. tuberculosis DNA by only the direct PCR. Nested PCR amplification improved the sensitivity and specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged