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Biomedical subjects

S Sakamoto

Publications and source records attributed to S Sakamoto.

At least 343 records · Page 19Linked to original sources

Suppression by kampo medicines in preneoplastic mammary hyperplastic alveolar nodules of SHN virgin mice.

Sho-saiko-to (SST), Keishi-bukuryo-gan (KBG), and Shakuyaku-kanzo-to (SKT) are Japanese modified traditional Chinese herbal medicines (Kampo medicines) consisting of 7, 5, and 2 medical plants, respectively. It is known that the hyperplastic alveolar nodule (HAN) is a representative preneoplastic state in the mammary glands of mice. We examined the effects of SST, KBG, and SKT on the formation and growth of HAN in a high-mammary-tumor strain of SHN virgin mice. Oral administration of SST for 60 days beginning at 90 days of age reduced the number and area of HAN and mammary thymidylate synthetase activity with a reduction of serum prolactin level. There was little difference between the other experimental groups and the control in the formation and growth of HAN and the enzyme activities. These results indicate that SST may have a preventive effect on malignant mammary transformations.

Animals↗

Reactive lymphoid hyperplasia of the liver.

A patient with reactive lymphoid hyperplasia of the liver was symptom free and had no underlying disease except for diabetes mellitus. The hepatic tumor was found by ultrasound examination at routine checkup. The preoperative diagnosis of the tumor was unsuccessful despite various radiological examinations. Histological examination of the resected tumor showed that it was composed of benign-appearing lymphocytic proliferations forming lymphoid follicles that included numerous germinal centers. The germinal center was mainly composed of B-cell marker, L26-positive lymphocytes, but a few T cells were also found. Lymphocytes surrounding germinal centers were mainly T-cell marker, UCHL1-positive T-cells, and a small number of B cells. The B cells in the lymphoid follicles were stained for both kappa and lambda light chains at equal frequency, indicating polyclonal and benign nature. A diagnosis of reactive lymphoid hyperplasia of the liver seems justified.

B-Lymphocytes↗

Cloning and sequencing of two new Verotoxin 2 variant genes of Escherichia coli isolated from cases of human and bovine diarrhea.

We cloned and sequenced two new Verotoxin 2 (VT2) variant genes: one from an Escherichia coli strain from a case of bovine diarrhea and the other from an E. coli strain from a patient with diarrhea. The nucleotide and amino acid sequences of these two genes were highly homologous with, but distinct from those of the VT2, VT2vha, VT2vhb, SLT-IIv (VT2vp1) and SLT-IIva (VT2vp2) genes. Their nucleotide sequences were much more closely homologous to that of VT2vh than to that of VT2vp. Search for these two new genes in other Verocytotoxin-producing E. coli strains resulted in the isolation of 2 strains carrying one of the new VT2 variant genes, one strain from Tokyo and the other from Canada.

Animals↗

Improved survival from fungaemia in patients with haematological malignancies: analysis of risk factors for death and usefulness of early antifungal therapy.

Fourty-three episodes of fungaemia encountered from 1978 to 1991 in 43 patients with haematological malignancies are reviewed here to analyse the risk factors for death and to evaluate the efficacy of early antifungal therapy. Low serum cholinesterase and elevated serum blood urea nitrogen were significantly associated with fungaemic death, defined as death occurring within 2 weeks after documentation of fungaemia. Overall death rate from fungaemia was 62.8%. Before the introduction of early antifungal therapy in 1986, however, fungaemic mortality was 85.7%; it was reduced to 51.7% thereafter (p = 0.01). Determination of plasma (1-->3)-beta-D-glucan was helpful in detecting deep fungal infections and initiating antifungal therapy early.

Adolescent↗

Effect of inhaled procaterol on cough receptor sensitivity to capsaicin in patients with asthma or chronic bronchitis and in normal subjects.

BACKGROUND: To evaluate the effect of inhaled beta 2 adrenergic agonists on the sensitivity of airway cough receptors, the effect of inhaled procaterol on cough induced by aerosolised capsaicin, a stimulant of C fibres, was studied in patients with asthma or chronic bronchitis and in normal subjects. METHOD: Eleven patients with asthma and 10 with chronic bronchitis and 14 normal subjects participated. Increasing concentrations of capsaicin solution were inhaled for 15 seconds by tidal breathing through the mouth at one minute intervals until five or more coughs were elicited, before and 30 minutes after inhalation of 20 micrograms procaterol or placebo (freon gas alone) through a metered dose inhaler. Cough threshold was defined as the lowest concentration of capsaicin that elicited five or more coughs. To evaluate the bronchodilator effect of procaterol and the bronchoconstrictor effect of inhaled capsaicin, forced expiratory volume in one second (FEV1) was measured before and one minute after a capsaicin provocation test. This test was carried out both before and 30 minutes after treatment with procaterol or placebo. RESULTS: The geometric mean value of cough threshold to capsaicin was significantly increased by procaterol and placebo in both groups of patients but not in the control subjects. The increment in the cough threshold was not significantly different between the treatments with procaterol and placebo in each group. FEV1 was significantly increased by procaterol but not by placebo in all three groups. CONCLUSIONS: Inhaled procaterol has no effect on airway cough receptor sensitivity to capsaicin. The attenuation of the cough sensitivity seen after inhalation of procaterol in patients with asthma and bronchitis may result from tachyphylaxis to capsaicin.

Administration, Inhalation↗

Suppression of spontaneous development of uterine adenomyosis and mammary hyperplastic alveolar nodules by Chinese herbal medicines in mice.

The effects of traditional Chinese herbal remedies, Shakuyaku-kanzo-to (SKT) and Hachimijiou-gan (HJG), on the spontaneous development of uterine adenomyosis and mammary hyperplastic alveolar nodules (HAN) were examined in an experimental animal model using SHN strain of mice. Female mice were provided with the chow containing 1% of SKT or HJG during 25-150 days of age. At 150 days of age, SKT treatment showed significantly lower incidence of adenomyosis, and HJG treatment resulted in a significantly lower incidence of HAN when compared to a control chow containing no medicines. Long-term exposure to these herbal medicines affected little serum prolactin (PRL) level, estrous cycle, food intake and body growth. Thus, the present mouse data suggest that the oral administration of these herbal medicines is a useful tool for the treatment of uterine adenomyosis or mammary disorder such as cystic mastitis.

Adenomyoma↗

Reductions of myocardial Na-K-ATPase activity and ouabain binding sites in heart failure: prevention by nadolol.

To study the changes in myocardial digitalis binding sites in heart failure, we measured myocardial ouabain binding sites, Na-K-adenosinetriphosphatase (ATPase) activity, and ventricular muscle mechanical responses to acetylstrophanthidin in dogs with right-heart failure (RHF) produced by tricuspid avulsion and pulmonary artery constriction. Sham-operated dogs were studied as the control. RHF produced a significant decrease in ouabain binding sites in the right and left ventricular myocardium, which was accompanied by a proportional decrease in Na-K-ATPase activity. However, RHF and sham-operated dogs did not differ in systemic hemodynamic or right ventricular trabeculate muscle isometric contractile responses to acetylstrophanthidin. To determine whether chronic beta-adrenergic stimulation contributed to the development of Na-K-ATPase downregulation, we administered nadolol (40 mg/day) to a separate group of dogs during an early stage of RHF development. Nadolol effectively prevented the reduction of myocardial ouabain binding sites that occurred in RHF. Thus we conclude that myocardial ouabain binding sites and Na-K-ATPase activity are reduced in dogs with experimental heart failure and that these changes probably occur as a result of the attendant heightened sympathetic activity.

Animals↗

Structural analysis of a low-sulfated chondroitin sulfate chain in human urinary trypsin inhibitor.

The low-sulfated chondroitin 4-sulfate(LSC) chain from human urinary trypsin inhibitor was purified and the structure was characterized. After hyaluronidase SD digestion of LSC, an oligosaccharide which contains the linkage region could be obtained. The structure of oligosaccharide was analyzed by HPLC and 500 MHz 1H-NMR spectroscopy. The analytical results revealed that 4-O-sulfo GalNAc residues were located in the neighborhood of the linkage region.

Carbohydrate Conformation↗

Studies on novel bone resorption inhibitors. I. Synthesis and pharmacological activities of aminomethylenebisphosphonate derivatives.

A series of aminomethylenebisphosphonate derivatives was synthesized and evaluated for their antiresorptive activities using a parathyroid hormone (PTH)-induced hypercalcemia model in rats (PIH model). Among these compounds, (cycloheptylamino)methylenebis(phosphonic acid) (3j) was finally selected for further investigation, proving 10-fold as potent as pamidronate in the PIH model and an immobilization bone atrophy model in rats (DA model). The structure-activity relationships of this series of bisphosphonates are discussed.

Animals↗

The similar mammary tumour potentials in virgins and breeders of SHN mice.

Spontaneous mammary tumour potential was compared between virgins and breeders of a high mammary tumour strain of SHN mice. Virgins were essentially similar to breeders in both the cumulative and the monthly incidences of mammary tumours. DNA synthesizing enzyme activities and the number and the weight of mammary tumours also differed little between groups. While the number of preneoplastic mammary hyperplastic alveolar nodules (HAN) was significantly higher in breeders than in virgins, little difference was observed between groups in the end-bud formation and the duct growth of normal glands and the growth of HAN. These results indicate that in SHN mice virgins have similar mammary tumour potential to breeders, which is much advantageous for practical use of this strain as an animal model for human breast and other types of cancers.

Animals↗

Inhibitory effects of insulin-like growth factor (IGF)-binding proteins-1 and -3 on IGF-activated glucose consumption in mouse BALB/c 3T3 fibroblasts.

We have examined the biological effects of insulin-like growth factor-binding proteins (IGFBPs) on insulin-like growth factor (IGF)-activated glucose consumption in a BALB/c 3T3 subline. The method employed was a colorimetric measurement of glucose consumption, allowing the detection of changes from the initial glucose concentration in conditioned medium, following the addition of IGFs and IGFBPs. Human IGFBP-1, purified from amniotic fluid, inhibited IGF-activated glucose consumption, although it had no effect on insulin-activated glucose consumption. The median effective dose (ED50) of IGFBP-1 to cause inhibitory effects on IGF-activated glucose consumption was 100-200 micrograms/l and was similar for both IGF-I and IGF-II at a concentration of 1.0 microgram IGF/l. Therefore, at IGF concentrations of comparable activity, the inhibitory effects of IGFBP-1 were greater for IGF-I than for IGF-II, because of the higher activity of IGF-I in this assay. Recombinant human IGFBP-3 also inhibited IGF-activated glucose consumption, without affecting insulin-stimulated glucose consumption. The inhibitory effects of IGFBP-3 were greater for IGF-II than for IGF-I when IGFBP-3 was coincubated with either of the IGFs, at both IGF concentrations of comparable activity and equivalent molar concentrations. Thus, it became clear that the inhibitory effects of these IGFBPs on IGF biological action depended primarily upon their affinity for the specific IGF ligand and molar ratio of IGFBP/IGF peptide. Interestingly, when cells were pretreated with IGFBP-3, prior to the simultaneous addition of IGFs and IGFBP-3, the inhibitory effect was higher for IGF-I than for IGF-II. Either no effect or a minor inhibitory effect on IGF-activated glucose consumption was detected with IGFBP pretreatment alone. When the ED50 for inhibition of IGF action by IGFBPs in this in-vitro assay was compared with the physiological concentrations of IGFs and IGFBPs in normal human serum and in amniotic fluid, it was estimated that the IGFBP-1 concentration present in serum was not sufficient to modulate IGF action effectively while the concentration in amniotic fluid was enough for effective suppression. IGFBP-3 exhibited an ED50 low enough to suppress IGF-II and possibly IGF-I action when cells were pretreated with IGFBP-3. Thus, our data suggested that IGFBP-1 in amniotic fluid and IGFBP-3 in serum could be a potent inhibitor for IGF action. IGFBP-1 in serum, however, may not be able to function as a direct inhibitor under physiological conditions but, rather, may modulate IGF action together with other IGFBPs.

Animals↗

Protein kinase C activation and calcium mobilization decrease prolactin release from human decidual cells in early pregnancy.

The present study was undertaken to investigate the effects of protein kinase C (PKC) activation and calcium mobilization on the release of prolactin from human decidual cells in early pregnancy. Decidua obtained from patients in early pregnancy was enzymatically dispersed and cultured with phorbol myristate acetate (PMA) and calcium ionophore A23187 in a cell culture system. Prolactin in the medium was measured by enzyme-immunoassay. PMA, a PKC activator, dose-dependently attenuated the release of prolactin from cultured decidual cells, while a PKC inhibitor, H7, significantly (P < 0.001) diminished the effect of PMA on prolactin release. PMA had no effect on cell numbers or DNA synthesis in the decidual cells during culture. It did not significantly increase the generation of inositol phosphate in decidual cells prelabelled with myo-[3H]inositol and it had no effect on intracellular calcium concentration ([Ca2+]i). Calcium ionophore A23187, a Ca(2+)-mobilizing agent, also significantly (P < 0.001) attenuated the release of prolactin and potentiated the PMA-induced suppression of prolactin release from decidual cells. These findings suggest that activation of PKC and mobilization of Ca2+ may be involved in regulating prolactin release from human decidual cells. The PMA-induced suppression of prolactin release is not triggered by phosphoinositide hydrolysis nor by the increase in [Ca2+]i in decidual cells.

Calcimycin↗

Bleeding tendency caused by the deposit of amyloid substance in the perivascular region.

A 55-year-old woman, who had systemic amyloidosis associated with multiple myeloma, had sudden development of hematomas of her lip and upper eye lid. There was no evidence of deterioration of multiple myeloma, thrombocytopenia nor deficiency of coagulation factors. Biopsy specimen showed the deposit of amyloid substance in the dermis and perivascular region. The bleeding tendency in this patient with myeloma was likely due to the deposit of amyloid substance in the vascular wall; improvement was achieved with administration of hemostatic agents.

Adrenochrome↗

Intracranial cavernous angioma manifesting as subarachnoid hemorrhage--case report.

A 56-year-old male presented with a posterior fossa cavernous angioma manifesting as persistent headache with mild neck stiffness. Lumbar puncture revealed subarachnoid hemorrhage (SAH). Repeated four-vessel angiography failed to identify the source of the SAH. Magnetic resonance (MR) imaging demonstrated multiple small lesions in the posterior fossa and cerebral hemispheres, and the SAH. A mass arising from the biventral lobule of the right cerebellar hemisphere extended exophytically into the cisterna magna with intratumoral hemorrhage. These findings were compatible with the presumptive diagnosis of SAH from the mass at the right biventral lobule. The lesion was totally removed through a suboccipital craniectomy without sequelae. The histological diagnosis was cavernous angioma. Intracranial cavernous angioma presenting only as SAH has never been reported before. The use of MR imaging in establishing the diagnosis of vascular malformations is emphasized, particularly when neither computed tomography nor angiography can adequately visualize the origin of SAH.

Cerebellar Neoplasms↗