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Biomedical subjects

K Morimoto

Publications and source records attributed to K Morimoto.

At least 559 records · Page 31Linked to original sources
PubMed1987

[Sister chromatid exchanges and chromosome aberrations as parameters for human risk of cancer development].

Chromosome alterations, which are directly visible changes in the DNA, have close associations to cancer development, non-specific ageing, and heritable genetic status. Human lymphocyte cultures can be used for cytogenetic monitoring of genetic health because many cancers and genetic effects are caused by long-term unhealthy life-styles. We have investigated the sensitivities of lymphocytes from inherited-cancer-prone diseases to the induction of the chromosome alterations by mutagens and carcinogens, and the correlations between the frequency of sister chromatid exchanges (SCEs) in peripheral lymphocytes and life-styles or daily ways of living. Lymphocytes from patients with Down syndrome, Fanconi anemia, xeroderma pigmentosum, ataxia telangiectasia, and Bloom syndromes showed altered (usually enhanced) susceptibilities to the induction of chromosome aberrations and SCEs by mutagens and carcinogens in our environments. Mean frequencies of baseline SCEs in lymphocytes from normal men with poor life-styles have also been shown to be significantly higher than those in cells from men having good life-styles. The former cells have further been shown to have hyper sensitivities to the induction of SCEs by mitomycin-C' treatment compared to latter cells. Unhealthy life-styles also make the lymphocytes to be more sensitive to ara-C's enhancement of radiation-induced chromosome aberrations.

Alcohol Drinking↗
PubMed1987

DNA damage in urinary bladder epithelium of male F344 rats treated with 2-phenyl-1,4-benzoquinone, one of the non-conjugated urinary metabolites of sodium o-phenylphenate.

DNA damage in the urinary bladder epithelium of male F344 rat was tested by alkaline elution assay after an intravesical injection of o-phenylphenol (OPP) or its non-conjugated urinary metabolites. DNA damage, as represented by an increase of the elution rate constant, was induced by the injection of 2-phenyl-1,4-benzoquinone (PBQ) at the concentration of 0.05-0.1%, but was not observed after the injection of either OPP or 2,5-dihydroxyphenyl at 0.05%. Histopathologically, a single intravesical injection of 0.05% or 0.1% PBQ was shown to induce epithelial hyperplasia of the bladder epithelium on day 5 after the treatment.

Animals↗
PubMed1987

[Convexity meningioma associated with Werner's syndrome--histopathological findings with electron microscopical and immunohistochemical findings].

Werner's syndrome is rare and autosomal recessive condition with multiple progeroid features. There is an increased incidence of neoplasm such as meningioma or sarcoma in association with this syndrome. However, the pathogenesis of this subject is still controversial. To date, only two cases have been reported, dealing with surgical operation. Our present case of a 39-year-old woman who had a meningioma associated with Werner's syndrome is the third of such cases. In this rare case we did histopathological examinations including electron microscopic and immunohistochemical studies, which showed intense proliferation of the connective tissue in the tumor tissue. The present morphological study may imply a close relationship between proliferation of collagen fibers in the meningioma and the aberration of connective tissue metabolism in context of theory of the pathogenesis of Werner's syndrome.

Adult↗
PubMed1987

[Rationale of preoperative chemotherapy of osteosarcoma].

The rationale of preoperative chemotherapy for osteosarcoma requires: eradication of microscopic metastatic foci which have already occurred in many patients with osteosarcoma, determination of a more effective form of postoperative adjuvant chemotherapy and easier and safer limb-salvage procedures through clearer marginal definition with reduction of primary lesions. In this paper, chemotherapeutic effects on the 5-year survival rate were analyzed for 49 patients with primary non-metastatic osteosarcoma of the extremities treated with radical surgery. The efficacy of preoperative chemotherapy was assessed in 11 cases of osteosarcomas treated with systemic chemotherapy as a preliminary study. As to the 5-year cumulative survival rate, the systemic group (20 cases) showed a level of 56.7%, which was significantly higher (p less than 0.05) than the figure of 13.8% in a historical retrospective group (29 cases). In assessing the effective tumor response to preoperative chemotherapy, a close correlation between the tumor necrotic ratio and the ratio of decrease of serum alkaline phosphatase was revealed. Seven (63.6%) of 11 cases showed correlation of the tumor necrotic ratio with the ratio of decrease of serum alkaline phosphatase. The tumor necrotic ratios calculated were relatively definite (50-60%) in the CDDP group (3 cases), varied (10-70%) in the HDMTX group (4 cases), and low (less than 40%) in the ADR group (4 cases), regarded as a control group in further studies.

Adult↗
PubMed1987

Specificity of O6-alkylguanine-DNA alkyltransferase.

Extensive investigations of the specificity of O6-alkylguanine-DNA alkyltransferase (AAT) have been carried out. These studies have shown that: (i) the mammalian protein differs from that of Escherichia coli in lacking the ability to remove methyl groups from O4-methylthymine; (ii) the protein can remove longer alkyl groups from the O6 position but the rate of repair declines as the chain length increases; (iii) O6-methylguanine in RNA is much less active as a substrate for the protein than O6-methylguanine in double-stranded DNA; (iv) the free-base O6-alkylguanine is a very weak substrate for the protein so that reaction with it leads to the loss of alkyltransferase activity. (This property can be used to deplete AAT in cultured cells and in tissues and tumours after administration of O6-methylguanine); and (v) oligodeoxynucleotides containing O6-methylguanine are substrates for AAT. Such oligodeoxynucleotides can be labelled with 32P at very high specific activity and can be used in an ultrasensitive assay for AAT activity.

Alkylation↗
PubMed1987

[Therapeutic results in recurrent breast cancer with the use of Bestrabucil (KM2210)].

We administered Bestrabucil, a benzoate ester of a complex of beta-estradiol and chlorambucil, continuously to six patients with breast cancer recurrent to local and regional lymph nodes, at a dose level of 200 mg/day. Of these six cases, one achieved CR, two PR, one MR, and two were NC. The drug was thus effective in 50% of the cases, with mild side effects. At the same time, since the concentration transfer to lymph nodes was satisfactory, Bestrabucil was thought to be an effective drug for the treatment of locally recurrent breast cancer.

Adult↗
PubMed1987

[Cerebrospinal fluid concentrations of creatinine and purine metabolites determined by high performance liquid chromatography: preliminary report on head injury and stroke patients].

A prospective high performance liquid chromatography (HPLC) study was performed in eighteen patients with head injury and stroke and four control volunteers to evaluate creatinine and purine metabolites concentration (adenosine, inosine, hypoxanthine, uric acid) in cerebrospinal fluid (CSF). The present HPLC method is rapid, accurate and sensitive in the same isocratic run and no specimen pretreatment of 0.02 ml CSF is necessary. The creatinine level in CSF was increased from 122 to 169 mumol/l in some patients, and was found unrelated to that of serum. The uric acid levels varied between 5.8 and 121 mumol/l and were associated with decrease in Glasgow Coma Scale score and had a critical point of 30 mumol/l. We present initial results in application of HPLC method to measure the creatinine and purine metabolites in CSF. This preliminary report presents that these high levels in CSF of head injury and stroke patients probably reflect tissue damage and an increased tissue catabolism.

Adenosine↗
PubMed1986

Cerebral ischemia in the gerbil: transmission electron microscopic and immunoelectron microscopic investigation.

Progression of cerebral ischemia from 5 min to 3 h after occlusion of a common carotid artery was investigated in the subiculum-CA1 region of the hippocampus of the gerbil by transmission electron microscopic and immunoelectron microscopic technique. The earliest change was found after 5 min in the periphery of the apical dendrites in the stratum moleculare, where mitochondrial swelling and disintegration of microtubules were clearly seen inside swollen dendritic processes. After ischemia for 10 min, similar abnormalities were observed in the more proximal part of the apical dendrites, and the basal dendrites also became similarly affected. After ischemia for 30 min to 1 h, the pyramidal cell bodies showed mitochondrial swelling, distension of endoplasmic reticulum and disaggregation of polyribosomes. The immunoelectron microscopic procedure for tubulin revealed irregularity of reaction products associated with microtubules after ischemia for 5 min in the dendritic terminals in the stratum moleculare and in the stratum radiatum after ischemia for 10 min. Reaction products in the pyramidal cell bodies became sparse after ischemia for 30 min to 1 h. The present investigation revealed early onset of ischemic damage in the dendritic terminals and subsequent proximal extension, with disintegration of microtubules and mitochondrial swelling.

Animals↗
PubMed1986

Interrelationship between secretion, protein phosphorylation and intracellular Ca2+ concentration in platelets stimulated by thrombin or thromboxane A2 analogue.

The interrelationship between ATP-secretion, protein phosphorylation and intracellular Ca2+ concentration ([Ca2+]i) was studied in both 32P and quin 2 loaded human platelets stimulated by thrombin or thromboxane A2 analogue (STA2). In platelets stimulated by thrombin, the degree of 47,000 dalton polypeptides (P47) phosphorylation was observed in completely dose-related manner, regardless of the amount of [Ca2+]i. In the same condition, the degree of myosin light chain (P20) phosphorylation, however, was well correlated with ATP secretion and [Ca2+]i, when platelets were stimulated by lower dose of thrombin. The similar results were obtained in platelets stimulated by STA2. These findings suggested that P20, but not P47, phosphorylation in activated platelets is mediated by a rise of [Ca2+]i and is well correlated with the secretory reaction. It was unlikely that P47 phosphorylation plays any role in promoting platelet activation.

Adenosine Triphosphate↗
PubMed1986

Effects of a new thyrotropin-releasing hormone analogue (DN-1417) on evoked responses and long-term potentiation in the dentate gyrus of rat.

The effects of a recently synthesized analogue, thyrotropin-releasing hormone (TRH) analogue, DN-1417, on evoked responses and long-term potentiation (LTP) of the perforant path input to the dentate gyrus were examined in normal rats and after hypophysectomy. Eighty micrograms of DN-1417 injected i.c.v. reduced granule cell excitability with a small increase in the excitatory postsynaptic potential (EPSP) and reduced LTP of the EPSP. However, DN-1417 slightly increased the potentiation of the population spike. Similar results were obtained in a rat 7 days post-hypophysectomy. It is concluded that the effects of DN-1417 on LTP are similar to those of TRH and may be unrelated to its endocrine actions.

Animals↗
PubMed1986

Effect of kallikrein-kinin system on calcium-vitamin D3 metabolism.

Kallikrein has been reported to stimulate callus formation and cell proliferation. It is well-known that vitamin D3 play an role on the metabolism of calcium. However, the relation between vitamin D3 and kallikrein are still poorly understood. We have studied the effect of kallikrein on calcium and vitamin D3 with canine kidney. Mongrel dogs were anesthetized with sodium pentobarbital and prepared by the method of Nakanishi et al. Drugs were infused into renal artery for 60 minutes under three different serum calcium concentrations (Exp. I, Exp. II, Exp. III). Blood samples were collected at the midpoint of the 60 minutes urine collection period. Plasma vitamin D3 concentrations were measured by the metabolites of 25-hydroxyvitamin D3 and 1 alpha,25-dihydroxyvitamin D3. 25-hydroxyvitamin D3 was estimated by competitive protein binding assay and 1 alpha,25-dihydroxyvitamin D3 was determined by radioreceptor assay after separated using HPLC. Electrolytes of sodium, potassium, chloride, calcium and phosphorus in serum and urine, plasma cyclic AMP, glomerular filtration rate, renal blood flow and blood pressure were also measured respectively. Plasma 1 alpha,25-dihydroxyvitamin D3 concentration was found to be decreased by the infusion of kallikrein (0.02 KU/kg/min) in three experimental conditions, especially in Exp. II. Bradykinin (0.02 microgram/kg/min) also caused to kallikrein-like changes of vitamin D3. It is suggested that kallikrein-kinin system is related to inhibit the mechanism of vitamin D3 activation system on kidney.

Animals↗
PubMed1986

Adaptation-like response to the chemical induction of sister chromatid exchanges in human lymphocytes.

Experiments have been performed to determine whether human lymphocytes in primary cultures can show an "adaptive" response to the induction of cellular lesions (manifested as a production of sister chromatid exchanges, SCEs) as previously found in bacteria and established human and mammalian cell lines. Human lymphocytes were pretreated with various subtoxic concentrations (5-50 ng/ml) of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) once every 6h for 72 h, and subsequently challenged by a high dose (4 micrograms/ml) of MNNG. The lymphocytes in MNNG-challenged cultures had the lowest frequency of SCEs when pretreated with 10 ng/ml MNNG. Further cross-resistance study revealed that repeated pretreatments of lymphocytes with 10 ng/ml MNNG for 72 h can render the cells resistant to the induction of SCEs by the following challenge with a high dose of MNNG, but not of mitomycin C or ethyl nitrosourea. The data also suggest variations in the degree of the adaptation-like response among individuals.

Adaptation, Biological↗
PubMed1986

Kindling induced changes in EEG recorded during stimulation from the site of stimulation: collapse of GABA-mediated inhibition and onset of rhythmic synchronous burst.

As a new approach to the functional alteration of kindled epileptogenic foci, we have demonstrated electroencephalographic (EEG) changes at the site of stimulation at the times when the kindling stimulation is applied in freely moving rats. In the kindled amygdala, three components of response were observed: an initial evoked potential, a subsequent EEG suppression, and an eventual burst of rhythmic spiking. The three components were a common feature also in the kindled hippocampus and prepyriform region. The duration of component 2, EEG suppression, progressively increased with each day of kindling (40 to 50 days), but dramatically shortened again after a rest period of 1 month. It was sensitive to pharmacological manipulations of gamma-aminobutyric acid (GABA). The amplitude of component 3, rhythmic spiking, increased during kindling, and was relatively insensitive to current intensities. The increased amplitude was long-lasting, independent of GABAergic, monoaminergic, and cholinergic manipulations, but sensitive to a benzodiazepine. It is suggested that component 3 is the outbreak of synchronous excitatory action which may be related to the basic mechanism of kindling.

Action Potentials↗