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Biomedical subjects

H Gotoh

Publications and source records attributed to H Gotoh.

At least 73 records · Page 4Linked to original sources

Involvement of phosphoinositide turnover in ouabain inotropism.

We examined whether ouabain activities phospholipases and reinforces contraction force of papillary muscles through resultant second messengers. 2-Nitro-4-carboxyphenyl-N,N-diphenylcarbamate (NCDC), the inhibitor of phospholipase C (PLC), abolished the ouabain inotropy in rabbit papillary muscles. Calphostin C, the specific inhibitor of protein kinase C (PKC), also depressed the ouabain inotropy. 12-O-Tetradecanoylphorbor-13-acetate (TPA), the specific activator of PKC, enhanced the beat-to-beat phasic contractility at low concentrations. Radioenzymatic assay revealed that ouabain treatment doubled diacylglycerol (DG) content in excised papillary muscles. We concluded that ouabain activates PLC, and the resultant second messenger, DG, augments the cardiac contraction force through activation of PKC.

Animals↗

Mechanism of inhibitory action of capsaicin on particulate axoplasmic transport in sensory neurons in culture.

The inhibitory effect of capsaicin on axoplasmic transport in cultured dorsal root ganglion cells was analyzed by video-enhanced contrast microscopy. Capsaicin inhibited particle transports in a dose-dependent manner, irrespective of the diameter of axons. The effect of capsaicin was reversible at low concentrations. Capsaicin affected both the anterograde and retrograde transport. Large organelles were more sensitive to capsaicin than small ones in the retrograde transport. An experiment using calcium-sensitive dye, Fura 2, indicated that capsaicin raised the intraneuronal free calcium concentration preceding the inhibition of the transport. Electron microscopy revealed that microtubules and neurofilaments are disorganized and disoriented by capsaicin. We reached a conclusion that capsaicin inhibits fast axoplasmic transport of both anterograde and retrograde directions in all types of somatosensory neurons in culture by disorganizing intraaxonal cytoskeletal structures, through the elevated intracellular Ca2+ concentration.

Animals↗

Purification and characterization of zinc-dependent acid phosphatase from bovine brain.

Zn(2+)-Dependent acid phosphatase (Zn(2+)-APase) was purified to homogeneity from bovine brain. The apparent molecular weight of the enzyme was estimated to be about 62000 by gel filtration and 31000 by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The enzyme exhibited an isoelectric point of approximately 4.8. The enzyme required Zn2+ ions for catalytic activity, but other cations had little or no effect. The maximum enzyme activity was obtained in the presence of about 5 mM of Zn2+ at pH 5.5 in 50 mM 2-(N-morpholino)ethanesulfonic acid-NaOH buffer. The enzyme significantly catalyzed the hydrolysis of p-nitrophenyl phosphate, phenyl phosphate, and phosphotyrosine. The enzyme was also active for myo-inositol-2-monophosphate and adenosine 2'-monophosphate of the other common phosphate esters tested, though significantly less active than for p-nitrophenyl phosphate. The optimum activity pH of the enzyme was around 5.5 with p-nitrophenyl phosphate and myo-inositol-2-monophosphate. The enzyme was resistant to fluoride ions. Two types of Zn(2+)-APases, a high molecular weight (molecular weight, M(r)., about 110,000) and a low molecular weight (M(r), about 62,000) type, were found to exist in various tissues of rat. Brain, lung, spleen, stomach, heart, skeletal muscle, and erythrocytes contained only the lower molecular weight type. On the other hand, liver and kidney contained mainly the higher molecular weight type, and the small intestine contained significant quantities of the both types.

Acid Phosphatase↗

How neurotransmitters affect axoplasmic transport?

The effects of acetylcholine (ACh) and adrenaline on fast axoplasmic transport of cultured superior cervical ganglion cells were analyzed with a computer-assisted video-enhanced differential interference contrast microscopic system. ACh suppressed the transport reversibly in both anterograde and retrograde directions, and adrenaline increased the transport reversibly. These effects are related to the amount of c-AMP. This amount of c-AMP in connection with neurotransmitters controls the axoplasmic transport, which in turn is related to the activity of the neuron.

Acetylcholine↗

Effect of neurotransmitters on axoplasmic transport: acetylcholine effect on superior cervical ganglion cells.

The effect of acetylcholine (ACh) on particle movements along axons of cultured superior cervical ganglion cells was analyzed with a computer-assisted video-enhanced differential interference contrast microscope system. ACh suppressed the axoplasmic transport reversibly in both anterograde and retrograde directions. A muscarinic agonist, arecoline, mimicked the ACh effect, but nicotine did not. An experiment with the Ca(2+)-indicator dye, fura-2, revealed that ACh suppressed the transport without any change of intracellular Ca2+ concentration. ACh also suppressed the axoplasmic transport in Ca(2+)-free medium. Islet-activating protein (IAP), pertussis toxin, blocked the ACh effect. These results indicate that ACh activates muscarinic receptors and suppresses fast axoplasmic transport through the activation of IAP-sensitive GTP-binding protein, irrespective of Ca2+ ions.

Acetylcholine↗

Immunophenotype and DNA content of myeloma cells in primary plasma cell leukemia.

To clarify the biological characteristics of the myeloma cells in primary plasma cell leukemia (PCL), we studied the immunological phenotype and DNA content of cells from five patients with primary PCL as compared to those from the patients with typical multiple myeloma (MM). In two of five patients with PCL myeloma cells had B-cell-associated antigens (B1, J5) and surface immunoglobulin in addition to plasma cell associated antigens, suggesting that these cells are immunologically immature as compared to mature plasma cells. Concerning the DNA content of myeloma cells, two of four patients had hypodiploid while two had diploid myeloma cells. In contrast, 24 of the 37 (65%) patients with typical MM had hyperdiploid and 1 had hypodiploid myeloma cells. These observations suggest that the myeloma cells in PCL are immunologically heterogeneous. The increased incidence of hypodiploidy in PCL may explain its relatively poor prognosis as previously shown in those with typical MM and hypodiploid DNA content.

Adult↗

Novel type of clonally involved cytoplasmic immunoglobulin-negative cells in multiple myeloma: flow cytometric study.

In order to identify myeloma cells and their precursor cells, we studied bone marrow samples from 39 patients with multiple myeloma, including 2 with plasma cell leukemia, using dual parameter cytometry of both DNA and cytoplasmic immunoglobulin (Cyt-Ig). Myeloma cells from 25 patients (64.1%) were aneuploid and those from the remaining 14 patients were diploid. In 25 patients with aneuploid myeloma, we found a small component of cells which had aneuploid DNA content without Cyt-Ig in addition to myeloma cells showing aneuploidy with Cyt-Ig. These aneuploid Cyt-Ig-negative cells were considered to be clonally involved because they were aneuploid, and detected predominantly in patients with stage III myeloma. This suggests that these cells may contribute to disease progression. The characteristics of these cells are described and the relationship between these cells and myeloma precursor cells is discussed.

Aneuploidy↗

Fungemia caused by Hansenula anomala: successful treatment with fluconazole.

Fungemia, due to Hansenula anomala, developed in an adult patient with small cell lung cancer who received anti-cancer chemotherapy and plasmapheresis for a sensori-motor neuropathy complication. Treatment with intravenous infusion of fluconazole in addition to the removal of the central venous catheter was successful in treating the fungemia. Pathogenic Hansenula anomala infections are rare, but reports of this infection have been increasing. The use of fluconazole treatment for this infection has not been reported in the literature, and this is the first case of an adult infection of Hansenula anomala in Japan.

Carcinoma, Small Cell↗

[Auer rods-positive neutrophils observed at diagnosis increased after remission induction in patient with acute promyelocytic leukemia].

50-year-old male was admitted to our hospital because of gingival bleeding and fever in August 1987. The leukocyte count was 13,300/microliters with 80.5% leukemic promyelocytes and bone marrow was hypercellular with 86.4% leukemic promyelocytes. A small number of mature neutrophils containing Auer rods were seen in bone marrow. On a diagnosis of acute promyelocytic leukemia and treated with induction chemotherapy consisting of behenoyl-arabinofuranosyl cytosine (BHAC), daunorubicin, 6-mercaptopurine (6-MP) and prednisolone (PSL) was reformed. After cytoreduction, leukemic cells reappeared in the peripheral blood, concomitant with mature neutrophils having Auer rods. Vitamin D3 was not effective as a differentiation inducing agent. Complete remission was obtained in November 1987 by the reinduction chemotherapy consisting of BHAC, aclarubicin, 6-MP and PSL. In this case, neutrophils with Auer rods might have been derived from the leukemic clone and differentiation of leukemic promyelocytes by intensive chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

Genetic control of sex-dependent meiotic recombination in the major histocompatibility complex of the mouse.

Meiotic recombination within the proximal region of the major histocompatibility complex (MHC) of the mouse is not random but occurs in clusters at certain restricted sites, so-called recombinational hotspots. The wm7 haplotype of the MHC, derived from the wild mouse, enhances recombination specifically during female meiosis within a fragment of 1.3 kb of DNA located between the A beta 3 and A beta 2 genes in genetic crosses with laboratory haplotypes. Previous studies revealed no significant strain differences in nucleotide sequences around the hotspot, irrespective of the ability of the strain to enhance the recombination. It appeared that a distant genetic element might, therefore, control the rate of recombination. In the present study, original recombinants whose breakpoints were defined by direct sequencing of PCR-amplified DNAs were tested for the rate of secondary recombination in the crosses with laboratory strains in order to determine the location of such a genetic element. The results clearly demonstrated that the chromosomal segment proximal to the hotspot is essential for enhancement of recombination. Moreover, the male recombination is suppressed by a segment distal to the hotspot.

Alleles↗

Detection of minimal residual myeloma cells by dual parameter analysis of DNA and cytoplasmic immunoglobulin.

We demonstrated the utility of dual parameter analysis of DNA and cytoplasmic immunoglobulin for the detection of minimal residual myeloma cells in bone marrow and peripheral blood. This method is sensitive: even 0.1% of contaminating myeloma cells could be detected in peripheral blood of myeloma patients and in the model experiments using cell lines. This method is useful for the selection of patients undergoing high-dose chemotherapy and autologous blood stem cell transplantation.

Bone Marrow↗

[Chronic lymphocytic leukemia with bilateral exophthalmos and visual disturbance].

A 61-year-old male was admitted to our hospital because of progressive bilateral exophthalmos and visual disturbance. He was diagnosed as chronic lymphocytic leukemia (CLL) with stage I of Rai system. Ophthalmologic examinations suggested that CLL cells might have invaded diffusely to bilateral orbits. Radiation to orbital lesions might result in other ophthalmologic complications such as cataract, therefore we tried to treat him with chemotherapy alone. As a result, combination chemotherapy consisting of vincristine, cyclophosphamide, prednisolone and doxorubicin (VEPA) and additional daily oral administration of cyclophosphamide were effective enough for his ophthalmologic recovery.

Exophthalmos↗

Philadelphia chromosome positive precursor B-cell acute lymphoblastic leukemia with a translocation t(2;14)(p13;q32).

A female patient with precursor B-cell acute lymphoblastic leukemia (precursor B-ALL) was analyzed cytogenetically. Karyotyping of the leukemic cells showed a Philadelphia chromosome (Ph1), and also showed a translocation between 2p13 and 14q32, which is thought to be specific for children with B-cell chronic lymphocytic leukemia. DNA analysis with both conventional and pulsed-field gel electrophoresis revealed the rearrangement of the c-abl gene, the BCR gene outside the 5.8 kb breakpoint cluster region (bcr or M-BCR), and the comigration of an abnormal Not I pHabl 5' and 3'-bcr fragment, indicating the presence of BCR/c-abl recombination. The JH gene was rearranged, but the JK gene showed a germline configuration, as with previously reported cases with a t(2;14). This case is the first report of a patient with Ph1-positive precursor B-ALL, in whom a specific translocation t(2;14)(p13;q32) is found simultaneously.

Adult↗

[Differentiation of intestinal candidial colonization from invasive candidiasis by measuring serum level of D-arabinitol in combination with oral administration of low dose amphotericin B].

The measurement of D-arabinitol in serum has been reported to be useful for the diagnosis of invasive candidiasis. However, excessive proliferation of Candida species in intestinal tract often leads false positive result of serum D-arabinitol. Based on the evidence that amphotericin B (AMPH) is scarcely absorbed from intestinal tract and inhibits the proliferation of Candida species only in intestinal tract, we have developed a simple differentiation method of intestinal candida colonization from invasive candidiasis by measuring serum level of D-arabinitol in combination with oral administration of low dose AMPH. AMPH, 600 mg/day for 2 days was orally administered to five patients with hematological malignancies who showed more than 1.7 mumol/mg of D-arabinitol/creatinine ratio (D/C ratio) in serum without any evidence of invasive candidiasis. D/C ratios were markedly decreased and normalized after the oral administration of low dose AMPH. While, in a patient with invasive candidiasis in whom Candida species was detected by blood cultures, D/C ratio remained unchanged in spite of oral administration of AMPH. These observations suggest that this method is a simple and reliable diagnostic method to distinguish intestinal candida colonization from true invasive candidiasis.

Administration, Oral↗