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Biomedical subjects

S Totsuka

Publications and source records attributed to S Totsuka.

At least 37 records · Page 2Linked to original sources

The binding of basic fibroblast growth factor to Alzheimer's neurofibrillary tangles and senile plaques.

Brain sections from Alzheimer's disease (AD) patients and controls were treated with basic fibroblast growth factor (bFGF) and then immunostained with anti-bFGF. Additional sections were treated with biotinylated bFGF without using the anti-bFGF. Labelling was visualized by the ABC method. Both protocols above intensely labelled neurofibrillary tangles, senile plaques and amyloidotic vessels in AD brains. Omission of the bFGF treatment abolished the staining of the AD lesions. The pretreatment of sections with heparitinase also reduced their staining. These results indicate that AD lesions contain bFGF-binding sites and that the chemical substrate for bFGF binding to AD lesions was heparan sulfate.

Alzheimer Disease↗

Acetylcholinesterase activities and monoamine metabolite levels in the cerebrospinal fluid of patients with Alzheimer's disease.

We measured cholinesterase (ChE) activity and monoamine metabolite levels in the cerebrospinal fluid (CSF) of 22 patients with early-onset Alzheimer type dementia (Alzheimer's disease; AD) and of 32 controls. Acetylcholinesterase (AChE) activity, 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) levels were significantly lower in AD patients than in controls. However, there was an overlap in values of each CSF parameter. The measurement of various CSF parameters rather than one alone was more useful as a diagnostic aid. CSF ChE activities correlated with scores on the GBS rating scale, Hasegawa dementia scale, and Wechsler Adult Intelligence Scale, but the monoamine metabolite levels did not. Although cholinergic and monoaminergic deficits may coexist in AD patients, cholinergic deficits tend to be more often associated with cognitive decline than the monoaminergic deficits.

Acetylcholinesterase↗

[Study on the repeated oral administration method in infant rats].

The purpose of this study was to establish a new technique for repeated oral administration to infant rats. To determine the maximum volume which could be administered to infant rats the following amounts of the Chinese ink were given by metal gastric zonde for mice: 0.01, 0.04 and 0.08ml/g B. W. General conditions and the arrival distance of the Chinese ink in the gastro-intestinal tract were also observed in infant rats. The best way of administration to infant rats was decided as follows: infant rats were isolated from the dums for one hour before administration and held tenderly by their neck to sustain their mouth upward, then a metal gastric zonde for mice 2 cm long was inserted to their mouth and drug solution was injected slowly. From the observation of general conditions and pathological examination, the maximum volumes for single or repeated administration were considered to be 0.04ml/g B. W. and 0.01 ml/g B. W. respectively. Daily oral administration of 0.1ml/g B. W. of distilled water, 1% CMC solution or 1% tragacantha gum suspension for 44 days caused no effects in infant rats when administration was begun 4 days after birth. These results show that the new method for administration to infant rats is useful to evaluate the toxicity or pharmacological activity of drugs.

Administration, Oral↗

[A case of advanced gastric cancer responsive to intratumoral OK-432 injection].

An 83-year-old patient with advanced gastric cancer was given repeated endoscopic administration of OK-432 combined with systemic immunochemotherapy. The cancerous lesion gradually regressed following the treatment, and remarkable degeneration was observed in many tumor cells. Detailed immunohistochemical examination revealed that Leu 7-positive cells had markedly infiltrated the cancerous tissue. This finding suggests that NK cells may play an important role in tumor regression induced by intratumoral OK-432 therapy.

Adenocarcinoma↗

Noradrenergic function and the dexamethasone suppression test in depression.

We measured the plasma free 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and the serum cortisol levels before and after the oral administration of dexamethasone. There was not a significant difference in the plasma free MHPG levels between the patients with major depression and normal subjects. There was a significant positive correlation between the plasma MHPG levels and postdexamethasone cortisol levels in patients with major depression. This indicates that there exists a certain relation between abnormalities of the central noradrenergic systems and hypothalamic-pituitary-adrenal axis in patients with major depression. The mean total scores of the Hamilton Rating Scale for Depression of the first (MHPG less than 5 ng/ml) and third (10 ng/ml less than or equal to MHPG) groups were significantly higher than those of the second (5 less than or equal to MHPG less than 10 ng/ml) group.

Depressive Disorder↗

Molecular cloning of human ornithine aminotransferase mRNA.

The isolation and characterization of a cDNA clone for the mRNA of human ornithine aminotransferase (OATase; ornithine-oxo-acid aminotransferase; L-ornithine:2-oxo-acid aminotransferase, EC 2.6.1.13), a nonabundant mitochondrial matrix enzyme that is severely deficient in a hereditary chorioretinal degenerative disease (gyrate atrophy), is described. Human liver, retina, and retinoblastoma (Y79) mRNAs were prepared and tested for the OATase mRNA content by in vitro translation, immunoprecipitation, and NaDodSO4/PAGE. The retinoblastoma cells were found to be expressing this enzyme at a relatively high level. The primary translation product of the OATase mRNA is larger than the pure OATase protein on NaDodSO4/PAGE by approximately equal to 4 kDa, suggesting a precursor protein. lambda gt11 cDNA libraries were prepared from the human mRNAs, and the recombinant clones were immunoscreened as plaques with two different preparations of rabbit anti-human OATase antibodies. A clone (lambda gtRB315) was isolated from the retinoblastoma library that reacts with both of the antibody preparations, and the DNA sequence of its 2.1-kilobase-pair cDNA insert was obtained. An open reading frame consisting of 1371 nucleotides is present in the sequence, and a putative translational initiation methionine codon is identified at position 55. A putative leader sequence consisting of 32 amino acid residues is identified, resulting in a precursor protein of 439 amino acid residues and a molecular mass of 48,534 Da and a mature protein of 407 residues and 45,136 Da. The amino acid sequences of seven tryptic peptides (115 amino acid residues) of the pure human OATase were obtained by microsequencing. When the tryptic peptide and cDNA-derived amino acid sequences were compared, homologies in 111 of 115 residues, including a match of 20 consecutive residues, were observed. An RNA blot hybridization of 32P-labeled OATase cDNA to normal human retina and retinoblastoma mRNAs demonstrated an OATase mRNA species of approximately equal to 2.2 kilobases. The level of OATase mRNA in the normal human retina is approximately equal to 1/100th the level of rhodopsin mRNA and 1/5th to 1/10th the level present in the retinoblastoma cells.

Amino Acid Sequence↗

An autopsy case of adult neuronal ceroid lipofuscinosis.

This is a report of an autopsy case (45-year-old woman) of adult neuronal ceroid lipofuscinosis with a long-lasting course of 25 years. In the course of her illness, gait disturbance, bulbar palsy and dementia were observed. Pathologically severe neuronal loss and hemosiderin-like granules were found in the cortex, basal nuclei, thalamus and others. The residual cells of these tissues were swollen with lipofuscin-like pigments. The extremely swollen nerve cells were found in the anterior horn of the spinal cord. Electron microscopically, numerous curvilinear bodies, myelin figures and fingerprint profiles were seen in those cytoplasms. Ceroid and lipofuscin were proven by a histochemical examination.

Brain↗

[Clinical studies on the transference of cephem-type antibiotics into bile and gallbladder tissues with special reference to cefotiam and cefmenoxime].

Cefotiam (CTM) and cefmenoxime (CMX) were studied for their serum concentrations and transference into bile in patients with PTCD or T-tube. One gram of CTM or either 1 g or 2 g of CMX was administered by an intravenous drip infusion for over 30 minutes. These drugs were also studied for their serum concentrations, bile concentrations, and tissue concentrations in the walls of the gallbladder of patients operated on for cholelithiasis. Intravenous drip infusion (over 30 minutes) was used to administer 1 g of CTM or 1 g or 2 g CMX immediately before surgery. Both CTM and CMX were readily transferred into bile. Their bile concentrations, however, varied greatly among patients, and extremely low levels were detected in some patients. A crossover analysis of concentrations of CMX in bile of patients given doses of 1 g and 2 g revealed a dose-response relationship. The crossover analysis of drug concentrations in bile of patients given CTM and CMX showed that CMX is transferred more readily to bile. The relationship between liver functions and drug transfer to bile was examined by plotting the total bilirubin level against drug concentrations in bile. The plots formed an exponential curve with a correlation coefficient (r) being -0.52 in cases when each subjects received 1 g of CTM and -0.72 in cases when each subjects received 1 g of CMX. A study of 3 patients given CMX at a dose of 1 g suggested that bile levels of CMX may be correlated to ICG. Concentrations of CTM and CMX in tissues of the gallbladder wall were fairly high, with unexpectedly small variance among patients. Even in patients with low bile concentrations of these drugs, drug levels in the tissues of the gallbladder wall were high. Drug levels in the noninflammatory tissues were higher than those in inflammatory lesions. The above findings suggest that CTM should be the antibiotic of choice for patients with ordinary biliary tract infections and after the surgery of the liver and biliary tract system, while CMX should be the antibiotic of choice for patients with severe biliary tract infections, and for compromised hosts after the surgery of the liver and biliary tract system.

Aged↗

Clinicopathologic studies on neuro-Behçet's disease.

Nine cases of neuro-Behcet's disease were investigated clinicopathologically. Pathological pictures of the central nervous system were characterized as follows: the site of predilection was the brain stem, followed by the spinal cord, cerebrum and cerebellum. The pathognomonic changes were recurrent inflammations around small vessels, causing a softening of the tissue. Lesions were composed of a perivascular infiltration of lymphocytes, histiocytes and microglias and, moreover, diapedesis, degenerated nerve cells and oligodendroglias, glial nodule, breakdown of myelin and axon, fatty granule cells and glio-mesenchymal proliferation were present occasionally. Electron microscopic studies on the neurons revealed no evidence of viral particles except for some accumulations of electron dense bodies.

Adult↗

Radiation effects on retinoblastoma successively transplanted into nude mouse eyes.

27 surgical specimens of retinoblastoma were transplanted into the anterior chamber of athymic nude mice (BALB/cA nu/nu), and 8 of them proliferated progressively filling the eyes. Among 7 specimens originally showing the rosette type, 1 case exhibited a typical Flexner-Wintersteiner rosette but the other 6 showed only an incomplete rosette after transplantation. One specimen originally showing the undifferentiated type exhibited the same cell type after transplantation. After the 2nd and 7th passage in the nude mouse, a chromosome analysis of the tumor cells confirmed that the cells were from the original human retinoblastoma. After the 7th passage the effects of radiation on the ultrastructure of the transplanted retinoblastoma cells were studies. The Linac beta-ray was radiated at single doses from 300 to 1500 rad, and the eyes were fixed on the 11th day and examined by light and electron microscopy. With 300 and 450 rad, no apparent change was found, but over 600 rad, degenerating cells being polygonal in shape and stained heavily with toluidine blue, were seen; they increased in number by increasing the dose of radiation. These degenerating cells contained vacuoles, dilated endoplasmic reticulum, myelinated figures, laminated and dense particles and empty mitochondria. They also showed partial disappearance of the cell membrane and karyorrhexis. By increasing the dose of radiation, the mitotic figures decreased, but even with 1500 rad, a few mitotic figures were still encountered.

Animals↗