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Biomedical subjects

T Saitoh

Publications and source records attributed to T Saitoh.

At least 235 records · Page 13Linked to original sources
PubMed1994

The survival of rat cerebral cortical neurons in the presence of trophic APP peptides.

One function of Alzheimer amyloid protein precursor (APP) is the regulation of growth and differentiation in several types of cells, including fibroblasts, PC12 cells, and neurons. This activity is represented by a small stretch of amino acids in the center of the molecule around RERMS. The APP 17-mer peptide containing the RERMS domain supported survival and neurite extension of rat cortical neurons in a dose-dependent and sequence-specific manner. The APP fragment synthesized in Escherichia coli supported the survival and neurite extension of rat cortical neurons, whereas the mutant APP fragment lacking the 30 amino acids around the RERMS domain had drastically reduced activity to support the survival and neurite extension. The current study established APP as a neuron survival factor and determined that the sequence around RERMS is important for this function.

Alzheimer Disease↗
PubMed1994

Reduction of neurological damage by a peptide segment of the amyloid beta/A4 protein precursor in a rabbit spinal cord ischemia model.

Although found as a precursor of Alzheimer amyloid, substantial evidence suggests that beta/A4 protein precursor (APP) is involved in regulation of neuronal growth and survival. Recently, we have obtained evidence that the trophic properties of APP are fully preserved in a 17-amino acid sequence. If APP is neurotrophic, then it would be anticipated that administration of the growth-promoting segment of the APP 17-mer peptide might attenuate the neuronal dysfunction or loss or behavioral deficits associated with neuronal injury, such as that accompanying central nervous system ischemia. We evaluated this 17-mer peptide in a rabbit spinal cord ischemia model and found that this peptide alleviates paraplegia resulting from ischemia/reperfusion. Ischemia of the distal lumbar cord was produced by temporary occlusion of the abdominal aorta. Saline, 17-mer APP peptide, or a control peptide (200, 500, or 1000 nM) was administered intrathecally 20 min prior to ischemia and once daily for 3 days thereafter. The neurologic and morphologic outcomes were evaluated after 4 days. Durations of ischemia encompassing all grades of neurologic function were included. The 500 nM dose of 17-mer APP peptide significantly reduced neurologic damage. The average ischemia duration necessary to produce permanent neurologic damage increased from 27.9 +/- 1.9 min in saline-injected controls and 27.7 +/- 2.0 in scrambled sequence peptide-injected controls to 40.2 +/- 4.0 min in the 500 nM 17-mer APP-injected group. The 200 nM dose produced a nonsignificant trend toward reduced neurologic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Cytokine gene expression on glioma cell lines and specimens.

Expression of the cytokine genes in human glioma cell lines and specimens was studied. Primers for 7 different human cytokine, IL-1 beta, IL-6, IL-8, GM-CSF, TGF-beta 1, TNF-alpha and IFN-gamma were used to analyze messenger RNA transcripts by polymerase chain reaction (PCR). Messenger RNA encoding for IL-1 beta, IL-6, IL-8, GM-CSF and TGF-beta 1 was found to be expressed in some of glioma cell lines. And those showed a proliferative response to IL-1 beta. IL-8 mRNA was found in 2 of 5 low grade gliomas, in 8 of 9 high grade gliomas. TGF-beta 1 mRNA was found in all gliomas, in 1 of 2 normal brains. IL-1 beta mRNA was only found in normal brains. TNF-alpha and IFN-gamma were not found in glioma cell lines and specimens. IL-8 mRNA was apt to be found more frequently among high grade glioma specimens.

Adolescent↗
PubMed1994

Biological behaviour and morphological characteristics of a transplantable tumour (MM-KMY) derived from a malignant meningioma in an F344 rat.

A subcutaneously transplantable meningeal tumour (MM-KMY) was derived from a spontaneous malignant meningioma which developed in the cerebellar meninges of a female F344 rat. MM-KMY was subjected to 25 serial passages in syngeneic male and female rats. The transplants grew in 8 weeks into a nodule with an average diameter of 5.7 cm and average weight of 125.2 g. MM-KMY possessed large cysts containing fluid and necrotic tissue. Metastases frequently occurred in the lungs of MM-KMY-bearing rats. Histologically, both the original tumour and MM-KMY consisted of round to fusiform neoplastic cells of varying size, with nuclear pleomorphism. Mitotic figures occurred frequently. MM-KMY cells were positive for vimentin. Ultrastructurally, the cells showed desmosome-like structures, interdigitating processes and cytoplasmic intermediate filaments, suggesting an arachnoid cell origin. Abnormal accumulations of hyaline droplets in renal tubular epithelial cells were frequently observed in MM-KMY-bearing rats, suggesting overload of low molecular proteins in the renal tubules. The droplets gave a faint immunoreaction for lysozyme. The relation between the appearance of renal tubular hyaline droplets and the growth of MM-KMY remains to be determined. MM-KMY may prove useful for studying the biological behaviour and morphogenesis of meningeal tumours.

Animals↗
PubMed1994

Secreted form of amyloid beta/A4 protein precursor (APP) binds to two distinct APP binding sites on rat B103 neuron-like cells through two different domains, but only one site is involved in neuritotropic activity.

Recent studies have identified the Alzheimer's disease amyloid beta/A4 protein precursor (APP) as a trophic and/or tropic protein on several types of cells, including fibroblasts, primary culture neurons, PC12 cells, and B103 neuron-like cells. Many trophic proteins bind heparin, and it is believed that the heparin-binding domain is crucial for the trophic activity of these proteins. APP also binds heparin. The current studies were undertaken to examine the hypothesis that the neuritotropic activity of APP requires heparin binding. It was found that APP produced in E. coli bound B103 cells through detergent-extractable molecules. Approximately 50% of the binding sites were heparinase-sensitive, and heparin and heparan sulfate competed for APP binding to these sites. The heparinase-insensitive sites were recognized by a stretch of 17 amino acids of APP (residues 319-335) that contains the neuritotropic activity of APP. A mutant APP with a deletion at this site was capable of binding to the heparinase-sensitive sites, although this molecule was not neuritotropic to B103 neuron-like cells. Therefore, the neuritotropic site and the heparin-binding site are distinct in APP, and the neuritotropic effect of APP is produced through its binding to detergent-extractable and heparinase-insensitive sites.

Amyloid beta-Protein Precursor↗
PubMed1994

Nucleolar organizer regions and PCNA expression in prostatic cancers.

Argyrophilic nucleolar organizer regions (AgNOR) of 79 prostatic adenocarcinomas, and an immunohistochemical stain using a monoclonal antibody against proliferating cell nuclear antigen (PCNA) of 54 prostatic adenocarcinomas, obtained by needle biopsy and transurethral resection of the prostate between 1986 and 1989, were investigated. A morphological classification was devised to count silver dots based on the relations between intra- and extra-nucleolar AgNOR (type A, B, C and D). Total AgNOR counts were significantly higher in carcinoma (4.2 +/- 1.57) than in the benign prostatic lesions (1.90 +/- 0.24). Count differences of AgNOR were evident in histological differentiation, nuclear anaplasia, and presence of nucleoli, mitosis, lymphatic invasion and vascular invasion. Higher total AgNOR counts were almost always associated with type B and C AgNOR (intranucleolar AgNOR), but were not associated with type A (nucleolus without small dot) nor type D (extra-nucleolar AgNOR). This study shows the diagnostic value of AgNOR in prostatic cancer, and the importance of morphological classification of AgNOR. The survival of patients with higher AgNOR counts (> or = 4.3) was significantly poorer than survival of those with lower AgNOR counts (< 4.3). Significantly more PCNA positive cells were identified in cancer by immunohistochemical stain and correlated with the presence of mitosis, but there was no significant difference in survival rate groups classified by PCNA positivity. It is also suggested that PCNA can be a useful marker of cell proliferation in prostatic lesions, but the AgNOR counts were diagnostically and prognostically more valuable than immunohistochemical PCNA in prostatic lesions. The correlation between AgNOR and PCNA immunoreactivity was not significant.

Adenocarcinoma↗
PubMed1994

A novel antagonist, phenylbenzene omega-phosphono-alpha-amino acid, for strychnine-sensitive glycine receptors in the rat spinal cord.

1. 3-[2'-Phosphonomethyl[1,1'-biphenyl]-3-yl]alanine (PMBA) is a novel glycine antagonist at strychnine-sensitive receptors. The chemical structure of PMBA, possessing both a glycine moiety and a phosphono group, is quite different from that of strychnine. 2. In the spinal motoneurone of newborn rats, glycine (100 microM-1 mM) induced depolarizing responses in a concentration-dependent manner. PMBA effectively inhibited depolarizing responses to glycine and other agonists, such as taurine and beta-alanine. The dose-response curves for glycine were shifted to the right in an almost parallel manner (pA2 value: 5.30 +/- 0.23, n = 5) by PMBA which was about 60 times less potent than strychnine (pA2 value: 7.08 +/- 0.21, n = 5) as a glycine antagonist. 3. PMBA (1-100 microM) did not interact with modulatory glycine sites on N-methyl-D-aspartate (NMDA) receptors, which suggests a high selectivity of PMBA for strychnine-sensitive glycine receptors. At considerably high concentrations (0.1 mM-1 mM), PMBA depressed responses to GABA (pA2 value: 3.57 +/- 0.24, n = 3). 4. PMBA inhibited the binding of [3H]-strychnine to synaptosomes from adult rat spinal cords; the IC50 values of PMBA, glycine and strychnine were 8 +/- 2, 9 +/- 3 and 0.08 +/- 0.04 microM, respectively (n = 5) for [3H]-strychnine (4.8 nM). 5. PMBA is a central excitant drug with relatively high potency and selectivity and should be useful as a pharmacological probe for analysing the mechanisms underlying physiological functions of glycine receptors.

Animals↗
PubMed1994

Gm haplotypes in chronic inflammatory demyelinating polyradiculoneuropathy in Japanese patients.

We studied the serum Gm allotype of 58 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and 236 nonrelated normal controls in Japan. The incidences of the Gm phenotype and haplotype in the patients were not significantly different from those in the normal controls. When CIDP was classified into two subgroups in terms of clinical course, the chronic relapsing (CR) and chronic nonrelapsing type (CNR), the distribution of all Gm haplotypes was significantly different between CR and CNR (total chi 2 = 8.319; corrected p < 0.05). Our findings suggest that the clinical course of CIDP may be associated with the Gm haplotype.

Chronic Disease↗
PubMed1994

Development of a sensitive two-site immunoradiometric assay for parathyroid hormone-related peptide: evidence for elevated levels in plasma from patients with adult T-cell leukemia/lymphoma and B-cell lymphoma.

We have developed a sensitive immunoradiometric assay for PTH-related peptide (PTHrP) using a monoclonal antibody against PTHrP(1-34) and a polyclonal antibody against PTHrP(50-83), with recombinant human PTHrP(1-87) as the standard. The detection limit of the immunoradiometric assay was 0.5 pmol/L, and plasma PTHrP(1-87) concentrations in 110 healthy subjects were 0.8 +/- 0.01 pmol/L, with the upper limit of the normal range being 1.1 pmol/L. Increased circulating PTHrP(1-87) concentrations were demonstrated in all 46 cancer patients with hypercalcemia, but not in patients with primary hyperparathyroidism, chronic renal failure, or hypoparathyroidism. Normalization of serum calcium levels after resection of tumors was shown to correlate well with that of plasma PTHrP(1-87) concentrations in 2 cancer patients. High circulating PTHrP(1-87) levels were also demonstrated in 12 out of 13 hypercalcemic patients with adult T-cell leukemia/lymphoma and in 7 out of 8 hypercalcemic patients with non-Hodgkin's lymphoma especially of B-cell type. These results suggest that PTHrP is a major humoral factor responsible for the hypercalcemia frequently associated with adult T-cell leukemia/lymphoma and also with B-cell lymphoma.

Adult↗
PubMed1994

The apolipoprotein E allele epsilon 4 is overrepresented in patients with the Lewy body variant of Alzheimer's disease.

We determined apolipoprotein E (ApoE) genotypes in 122 autopsied demented patients. The frequency of the ApoE epsilon 4 allele was 39.6% in Alzheimer's disease (AD), 29.0% in the Lewy body variant of AD (LBV), and 6.25% in diffuse Lewy body disease. For AD and LBV patients, the epsilon 4 frequency was significantly higher than that reported in nondemented controls (10 to 15%). Therefore, LBV and AD share ApoE epsilon 4 as a genetic risk factor, providing further evidence that these conditions overlap.

Aged↗
PubMed1994

[Ultrastructural consequence of shock wave exposure on VX2 cancer implanted to the urinary bladder].

In order to clarify the ultrastructural consequence of the VX2 cancer cell exposed to underwater shock waves. The VX2 cancer implanted to the urinary bladder of rabbit was received the shock waves (1000 shots, 100 MPa, 5/sec.) generated by the piezo-ceramics. Damage to the cancer cell were manifested by the three kind of findings: the one was the cell junction failure which caused the isolated cells; the second was the destruction of organelle which seemed to form the vacuole in cytoplasm; and the last finding was the emergence of moth eaten appearance in the exposed cell. We conclude that underwater shock wave exposure induces lethal injury in VX2 implanted cancer.

Animals↗
PubMed1994

[Clinical usefulness of serum assay of EIA-CYFRA 21-1 in lung cancer].

Enzyme immunoassay CYFRA 21-1, a novel lung tumor marker presented in serum (upper limit of normal values: 3.5 ng/ml) was measured in 84 patients with lung cancer and 141 patients with benign respiratory diseases. The positive rate for CYFRA 21-1 in primary lung cancer was 70.3% and the false positive rate in respiratory diseases was 24.1%. In respect to the histological types of lung cancer, CYFRA 21-1 was elevated in 85.0% of squamous cell carcinoma and in 64.8% of other cell types of primary lung cancer. Elevated CYFRA 21-1 levels were found in 40% of Stage I-II, in 80.0% of Stage IIIA-B, and in 73.5% of Stage IV. The overall diagnostic efficiency was 53.4% for CYFRA 21-1 and 44.5% for CEA, respectively. Receiver operating characteristic (ROC) curve analysis suggested that CYFRA 21-1 test has an advantage over CEA. From the results of this study, CYFRA 21-1 was more efficient than CEA as primary diagnostic marker in lung cancer.

Biomarkers, Tumor↗
PubMed1994

[A case of Swyer-James syndrome--a morphological study with inflated fixed lung].

Morphological features of Swyer-James syndrome were studied in a specimen obtained during left pneumonectomy. A 67-year-old woman was admitted because her left lung was hyperlucent and contained a solitary nodule. Primary lung adenocarcinoma complicated with Swyer-James syndrome was diagnosed, and left pneumonectomy done. The left upper lobe was inflated and fixed for morphological study. The volume of the specimen was obviously lower than normal but the bronchial branching was normal. Macroscopically, the specimen had irregular bronchial walls, bronchiectatic changes, and dilation of distal air spaces, similar to panlobular emphysema. Microscopically, there was scarring in periarteriolar regions that suggested bronchiolitis obliterans, enlargement of distal airspaces, and an abnormally low number of capillaries. These findings suggest hypoplasia of the lung due to abnormal lung growth after birth.

Aged↗
PubMed1994

[Intracranial extracerebral glioma].

A case of solitary leptomeningeal extracerebral glioma is reported. A 75-year-old man was admitted to our hospital because of headache and right hemiparesis. CT scan and carotid angiography revealed a tumor in the left convexity. At operation, the tumor was located between the dura mater and the arachnoid membrane and adhered to the brain surface only in a limited area. Histological study including immunostain and electron microscopy showed the tumor as anaplastic oligo-astrocytoma. We speculate that our case may originate from a heterotopic glial nest in the dural border cell layer of dura mater. This explanation seems likely because the tumor was located mostly in the subdural space.

Aged↗
PubMed1994

Expression of histamine H2 receptor in Chinese hamster ovary cells: a probe to study the desensitization mechanism.

Canine histamine H2 receptor DNA, cloned by polymenase chain reaction (PCR), was transfected into Chinese hamster ovary cells using an expression vector. The expression of H2 receptors was demonstrated by immunoblotting with specific antibodies and the binding of tiotidine, an H2 receptor antagonist. H2 receptor-specific cAMP production was observed only in cells expressing canine H2 receptors. Preincubation of transfected cells with 10 microM histamine for 10 or 60 min at 37 degrees C decreased both the maximal response and the sensitivity of the subsequent histamine-stimulated cAMP production, showing desensitization. Under these circumstances, decreases in tiotidine binding without changes in affinity in intact cells and also in the membrane were observed, whereas there was no decrease in total H2 receptor number. Thus, desensitization of histamine H2 receptor was associated with the sequetration of receptors.

Animals↗
PubMed1994

Peptides containing the RERMS sequence of amyloid beta/A4 protein precursor bind cell surface and promote neurite extension.

Amyloid beta/A4 protein precursor (APP) is secreted into medium by most cultured cells and can function as an autocrine factor. To study the biological function of secreted forms of APP (sAPP) on neurons, we used a clonal CNS neuronal line, B103, which does not synthesize detectable levels of APP. B103 cells transfected with APP construct developed neurites faster than the parent B103 cells when plated in a serum-free defined medium. Neurite outgrowth of B103 cells was promoted by the conditioned medium of APP-695-over-producing cells or by the bacteria-produced sAPP-695 (named KB75). A series of peptides having sequences between Ala-319 and Met-335 of APP-695 also stimulated neurite outgrowth of B103 cells. The sequence of five amino acids, RERMS (APP 328-332), within this stretch of sequence, was the shortest active peptide, although the concentration required for the neuritotropic activity was higher than that of KB75. Binding assay using 125I-labeled APP 17-mer peptide corresponding to Ala-319 to Met-335 of APP-695 as a ligand demonstrated specific and saturable cell-surface binding sites. The predicted KD value was 20 +/- 5 nM and the Bmax value was 80 +/- 8 fmol/10(6) cells. The binding could be displaced with KB75. A 17-mer peptide with reverse sequence neither induced neurite outgrowth nor competed for the binding. A bacteria-produced sAPP fragment lacking the active 17-mer sequence (named KB75 delta) did not compete with 125I-labeled 17-mer for binding or stimulate neurite extension. A peptide of sequence RMSQ (APP 330-333), which partially overlaps the active sequence RERMS, could block the neuritotropic effects of both KB75 and the 17-mer at higher concentrations. APP 17-mer was also found to induce the accumulation of inositol polyphosphates, suggesting that the APP 17-mer effects involve activation of inositol phospholipid signal transduction systems. These data indicate that sAPP induces neurite extension through cell-surface binding and that the domain containing the RERMS sequence (APP 328-332) represents the active site responsible for this function.

Amino Acid Sequence↗