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Biomedical subjects

S Tsuda

Publications and source records attributed to S Tsuda.

At least 181 records · Page 10Linked to original sources

Chromosome abnormalities of gastric cancer detected in cancerous effusions.

The chromosomes were examined in cancerous effusions obtained from 7 patients with gastric cancer. In 1 patient, the modal chromosome number was 46 with a normal chromosome complement in the majority of the cells examined. The other 6 patients revealed numerical and structural aberrations. Among the structural rearrangements detected, chromosome 3 was involved in the short arm and in the long arm, each in three patients; bands p25, q21, q23, and q27 were recurrently involved and a band q23 was lost in 3 patients. Rearrangements of chromosome 5 in the long arm and of chromosome 17 at or near the centromere were also observed in three patients each. Gains of chromosome 7 was seen in 5 patients and of chromosome 13 in 4. Some of these alterations may be specific for gastric cancer.

Adult↗

Long arm deletion of chromosome 7 unrelated to original karyotype in recurrent t(8;21) acute myeloblastic leukemia.

We describe a chromosomal abnormality, 7q-, unrelated to the original karyotype in a patient with recurrent t(8;21) acute myeloblastic leukemia. The 7q-, del(7)(q22q34), was seen in otherwise karyotypically normal cells. Cyclophosphamide was administered for 5 months during the maintenance therapy. Our observations indicate that unrelated karyotypes, besides karyotypic evolution, may be implicated in tumor cell heterogeneity and may support the previous documentation of a possibly causal relationship between chemotherapy and development of 7q-. A larger study will be required to elucidate the biologic significance, if any, of the unrelated karyotypes.

Adult↗

Norepinephrine release and neuropeptide Y in medulla oblongata of spontaneously hypertensive rats.

Neuropeptide Y is colocalized with norepinephrine in both central and peripheral noradrenergic neurons. In this study, we examined the regulatory mechanisms of neuropeptide Y on norepinephrine release in the medulla oblongata of rats. Neuropeptide Y inhibited the stimulation-evoked [3H]norepinephrine release in a dose-dependent manner in slices of medulla oblongata of Sprague-Dawley rats (1 Hz, S2/S1 ratio, control, 0.946 +/- 0.040 [+/- SEM], n = 6; neuropeptide Y 1 x 10(-8) M, 0.676 +/- 0.022, n = 6, p less than 0.05; neuropeptide Y 1 x 10(-7) M, 0.589 +/- 0.014, n = 6, p less than 0.05). Neuropeptide Y potentiated inhibition of [3H]norepinephrine release by the alpha 2-agonists UK 14,304 and clonidine. The blockade of alpha 2-adrenergic receptors by RX 781,094 diminished inhibitory effects of neuropeptide Y on norepinephrine release. Pretreatment of pertussis toxin (a toxin that interferes with the coupling of inhibitory receptors to adenylate cyclase) attenuated the suppression of norepinephrine release by neuropeptide Y. In spontaneously hypertensive rats, the inhibitory effect of UK 14,304 and neuropeptide Y on norepinephrine release from the medulla oblongata was significantly less than in age-matched Wistar-Kyoto rats. These results show that neuropeptide Y inhibits norepinephrine release partially mediated by alpha 2-adrenergic receptors and the pertussis toxin-sensitive guanosine triphosphate-binding proteins in rat medulla oblongata. Furthermore, less suppression of norepinephrine release by UK 14,304 and neuropeptide Y in spontaneously hypertensive rats suggests that alpha 2-adrenergic receptors and neuropeptide Y might be involved in the regulation of central sympathetic tone in hypertension.

Adenylate Cyclase Toxin↗

[Solid scintillator "Ready Cap" for measurement with a liquid scintillation counter--spectra and counting efficiencies for 15 different radionuclides].

"Ready Cap", a small plastic container coated with solid scintillator has recently been introduced (Beckman Instruments, Inc.). Pulse height spectra and counting efficiencies obtained with a liquid scintillator and Ready Cap using a liquid scintillator counter were compared for 15 different radionuclides. For radionuclides emitting low-energy beta-rays or characteristic X-rays, the spectra for Ready Cap shifted toward the higher energy side compared with the spectra for the liquid scintillator. This tendency was reversed for the nuclides emitting higher-energy beta-radiations (36Cl and 32P). Generally, counting efficiencies both in Ready Cap and in liquid scintillator increased with increase in the energy of beta- or X-rays. For some nuclides, Ready Cap gave higher counting efficiencies and for others it gave lower values than in the liquid scintillator. However, the differences were not large within each nuclide. The use of Ready Cap is recommended for measurements of radionuclides when liquid scintillation cocktails have no means of waste disposal under the present Japanese radioisotope regulation.

Evaluation Studies as Topic↗

Chemical synthesis of oligoribonucleotides for structural studies.

Large-scale synthesis of oligoribonucleotides has been performed successfully on a solid support by the phosphoramidite approach using levulinyl and tetrahydrofuranyl protection for the 5'- and 2'-hydroxyl groups respectively. A hexamer containing inosine and four fragments of a hammerhead-type ribozyme have been synthesized on a 10 mumol scale for structural studies by NMR spectroscopy and X-ray crystallography.

Base Sequence↗

[A case of Borrmann type 4 gastric carcinoma which disappeared by intraaortic infusion chemotherapy with ADM and MMC].

A 64-year-old woman with Borrmann type 4 gastric cancer was treated by intraaortic (celiac artery) one-shot infusion chemotherapy with adriamycin (ADM) and mitomycin C (MMC). One month after the first administration of 30 mg ADM and 20 mg MMC, the second administration of 50 mg ADM and 20 mg MMC was done. The third administration of 50 mg ADM and 20 mg MMC was performed one month after the second administration. Clinical symptoms of back pain, lumbago and anorexia had almost disappeared soon after the third administration. Although the findings of the X-ray examination of stomach, gastroscopy and celiac angiography showed marked improvement, total gastrectomy with lymphadenectomy was performed 2 months after the third administration because residual cancer cell nests were highly suspect. Histological examination of the resected stomach and lymphnodes revealed no cancer cells. The patient has been in good health without any recurrent signs for 16 months after operation.

Antineoplastic Combined Chemotherapy Protocols↗

[Clinical evaluation of cefuzonam of severe infections in leukemia and related disorders].

Cefuzonam (CZON) which has a broad spectrum on both Gram-negative and Gram-positive bacteria including methicillin-resistant Staphylococcus aureus was evaluated in severe infections associated with hematological disorders. Sixty five patients were treated with CZON. Among them, 56 patients were evaluable for effectiveness. Nine patients were not evaluable because 3 patients were treated with combination of other antibiotics such as ceftizoxime, norfloxacin, ofloxacin, 1 patient was subjected to additional therapy of G-CSF and gamma-globulin, 4 were the patients with other disease than hematologic disorder (3 malignant mesotheliomas, 1 ovarian cancer), and the remaining one was prophylactically treated. Excellent responses were observed in 21 (37.5%) patients, good responses in 11 (19.6%) patients, with an overall efficacy rate of 57.1%. The efficacy rate in septic patients was 80% (4/5), and that in patient whose peripheral granulocytes were continuously below 100/microliters was 60% (3/5). Three patients who suffered from malignant mesothelioma, one patient who suffered from ovarian cancer, one patient who was treated prophylactically were included in the final evaluation of side effects. Side effects were observed in 2 patients (2/61, 3.3%). In a patient of 7 years, mild liver disfunction (GOT/GPT, 46/55) was found in 10 days after CZON treatment was started. In a patient of 65 years, mild appetite loss was identified in 2 days after CZON administration was begun. The liver disfunction was improved soon after the cessation of the treatment. The mild appetite loss disappeared while the treatment was continued. These results showed that CZON was an effective and safe antibiotic for the treatment of severe infections in patients with hematological disorders.

Adult↗

Increase in permeability of human endothelial cell monolayer by recombinant human lymphotoxin.

The effect of lymphotoxin (LT) on transendothelial permeability was examined using in vitro human endothelial cell (EC) culture system. To assess permeability, we measured the movement of human IgG labeled with horseradish peroxidase (HRP-huIgG) across an EC monolayer cultured on a fibronectin and collagen-coated membrane. LT increases the permeability dose dependently within 16 hours. Similar results were obtained with tumor necrosis factor (TNF)-alpha. The results suggest that increase in vascular permeability by LT and TNF-alpha plays an important role in initiating hemorrhagic necrosis of tumors in vivo.

Cell Membrane Permeability↗

Distribution of breakpoint within the breakpoint cluster region (bcr) in chronic myelogenous leukemia with a complex Philadelphia chromosome translocation.

We analyzed, by Southern blot hybridization, the site of breakpoint within the breakpoint cluster region (bcr) in six patients with a complex Philadelphia chromosome (Ph) translocation and in 23 unselected patients with a standard Ph. The breakpoint was found within the 5.8 kb bcr in all 29 patients. When the bcr was subdivided into four parts, fragments I-IV, based on the restriction enzyme sites, among the six patients with a complex Ph, two had a breakpoint at fragment I, three at fragment II, and one at fragment III. This distribution of breakpoints in patients with a complex Ph did not differ significantly from that in patients with a standard Ph. A deletion of an allele within the bcr was found in three patients (50%) with a complex Ph and in three (13%) with a standard Ph. The internal bcr deletion may be more common in patients with a complex Ph.

Alleles↗

Alteration in the density, morphology, and biological properties of eosinophils produced by bullous pemphigoid blister fluid.

Bullous pemphigoid blister fluid (BP-BF) was examined for its effects on the density, morphology, and biological properties of eosinophils. Normodense eosinophils (NEo) were prepared from guinea pig peritoneal exudates by Nycodenz density gradient centrifugation. After culturing with BP-BF, NEo were converted into hypodense eosinophils (HEo) in a time-dependent manner. HEo were morphologically different from NEo in that HEo had spheroidal granules each with a lytic crystalloid core and a significantly increased cell volume. These HEo showed an enhanced antibody- and/or complement-dependent helminthotoxic activity to Schistosoma mansoni larvae, amplified chemiluminescence response to opsonized zymosan, and augmented expression of both FcR+ and CR+. These results suggest that BP-BF contains an activity that may not only induce an eosinophil hypodensity as a consequence of increasing cell volume, but simultaneously enhance an eosinophil cytotoxic potential through augmenting cell-surface receptors and receptor-linked oxidative metabolism. In addition, observed tissue accumulation of this activity suggests that eosinophils may be regulated by their phenotypic change in the skin lesions of bullous pemphigoid and be involved in blister formation.

Animals↗

A case of incomplete DiGeorge syndrome associated with partial monosomy 22q11.1 due to maternal 14;22 translocation.

We report a boy with some clinical symptoms compatible with a diagnosis of incomplete DiGeorge syndrome. He had a dismorphic face, micrognathia, cleft palate, and heart anomalies similar to DiGeorge syndrome, but lacked aplasia of the thymus or hypoparathyroidism typical of the syndrome. High-resolution banding analysis revealed that his karyotype was 45,XY,-14,-22, +der(14)(14pter----14q32.32::22q11.21----22qter), the consequence of a maternal reciprocal translocation between chromosomes 14 and 22. Precise localization of the gene responsible for the present DiGeorge syndrome was assigned to subband 22q11.1.

Adult↗

Greater calmodulin-dependent regulation of neurotransmitter release and vascular responsiveness in chronic Doca-salt hypertension.

The present study was carried out to investigate the role of calmodulin in the adrenergic transmission of deoxycorticosterone acetate (DOCA)-salt hypertension. In perfused mesenteric vasculatures prepared from DOCA-salt hypertensive rats (seven to eight weeks after operation) and age-matched normotensive control rats, the effects of a specific calmodulin antagonist (W-7: N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide) on the norepinephrine release and vascular responsiveness were examined. Endogenous norepinephrine overflow during electrical nerve stimulation was significantly greater in the mesenteric vasculatures of DOCA-salt hypertensive rats both at low (5 Hz) and high (15 Hz) frequencies than in those of the normotensive controls. Vasoconstrictor responses to electrical nerve stimulation or exogenous norepinephrine were also enhanced in the DOCA-salt hypertension compared to those in the controls. The calmodulin antagonist (W-7) inhibited the stimulation-evoked norepinephrine overflow and pressor responses in a dose-dependent manner. The suppressive magnitudes in these responses by W-7 were significantly greater in the mesenteric vasculatures of the DOCA-salt hypertension than in those of the control rats. These results demonstrate that the vascular adrenergic neurotransmission might be enhanced in the mesenteric vasculatures of the DOCA-salt hypertensive rats. Further, it is suggested that the marked reduction in stimulation-evoked norepinephrine overflow and vasoconstrictor responses by W-7 showed the greater calmodulin-dependent regulation in the vascular adrenergic activity of DOCA-salt hypertension.

Animals↗

Facilitatory effects of ouabain and digitalis-like substance on adrenergic transmission in hypertension.

The purpose of the present study was to examine the role of Na+,K+-ATPase activity in vascular adrenergic transmission of hypertension. In isolated perfused mesenteric vasculatures of spontaneously hypertensive rats (SHR, Okamoto and Aoki strain, seven- to ten-weeks-old) and age-matched Wistar Kyoto rats (WKY), the effects of ouabain, a potent Na+,K+-ATPase inhibitor, or partially purified plasma obtained from salt-induced hypertension on pressor responses and norepinephrine overflow were investigated. Pressor responses and norepinephrine overflow during electrical nerve stimulation were significantly greater in SHR than in WKY. Ouabain increased the stimulation-evoked pressor responses and norepinephrine overflow. This facilitation was more prominent in SHR than in WKY. Partially purified plasma obtained from reduced renal mass-salt hypertensive rats, which had a crossimmunoreactivity with digoxin, also increased the pressor responses and norepinephrine overflow during electrical nerve stimulation, and the effects were greater in SHR than in WKY. These results suggest that Na+,K+-ATPase on vascular adrenergic neurons has an important role in the regulation of neurotransmitter release, and that its activity might be enhanced in SHR.

Animals↗

Myelodysplastic syndrome preceding acute myelomonocytic leukemia with dysplastic marrow eosinophilia and inv(16).

A 44-year-old Japanese male having refractory anemia with excess of blasts (RAEB) preceding acute myelomonocytic leukemia (AMMoL) with dysplastic marrow eosinophilia (M4Eo in the FAB classification) is reported. Sequential cytogenetic studies revealed a specific chromosomal abnormality, inv(16) (p13q22), when RAEB was first diagnosed and again when overt leukemic transformation compatible with M4Eo was manifested. However, during the interval between the RAEB and AMMoL, an unrelated abnormal karyotype without inv(16), 47,XY,+9, was seen, when hematological data revealed remission after a low dose of cytosine arabinoside was administered. In this patient eosinophils in the marrow were involved in the leukemic process cytogenetically, because a few metaphases overlaid with eosinophilic granules had the inv(16) with other numerical abnormalities.

Adult↗

Inhibition of norepinephrine release by presynaptic alpha 2-adrenoceptors in mesenteric vasculature preparations from chronic DOCA-salt hypertensive rats.

This study investigated norepinephrine release during electrical nerve stimulation and inhibitory characteristics of presynaptic alpha 2-adrenoceptors in perfused mesenteric vasculature from deoxycorticosterone acetate (DOCA)-salt hypertensive rats (7-8 weeks after surgery). Electrical stimulation of sympathetic innervation caused a significantly greater release of endogenous norepinephrine into the mesenteric vasculature of DOCA-salt hypertensive rats than in age-matched normotensive controls. Pressor responses to electrical nerve stimulation were also enhanced in DOCA-salt hypertension. Yohimbine, a potent alpha 2-adrenoceptor blocking agent, potentiated the stimulation-evoked release of norepinephrine into the vasculature in normotensive rats. This effect was blunted in DOCA-salt hypertension. These results suggest that increased norepinephrine release from the sympathetic nerve endings in DOCA-salt hypertension might partly reflect an impaired presynaptic alpha 2-adrenoceptor-mediated inhibition, which could enhance vascular sympathetic tone in this model of hypertension.

Animals↗

Neurotransmitter release and vascular responsiveness in mesenteric vasculatures from two-kidney, one-clip Goldblatt hypertensive rats.

In order to investigate the peripheral neuroeffector functions of renal hypertension, norepinephrine release from the sympathetic nerve endings and vascular responsiveness were evaluated in the mesenteric vasculatures from two-kidney, one-clip Goldblatt hypertensive rats (2K, 1C-HT). Norepinephrine release and pressor responses during periarterial nerve stimulation (40 V, 5 msec rectangular pulses for 1 min, 5, 10 and 15 Hz) were unchanged during the acute phase (3 weeks after surgery), and were rather reduced during the chronic phase (7-8 weeks after surgery) in 2K, 1C-HT compared to sham-operated normotensive control rats. By contrast, the vasoconstrictor responses to exogenously applied norepinephrine were significantly greater in 2K, 1C-HT than in the normotensive controls. From these observations, it seems unlikely that peripheral adrenergic function in the blood vessels plays an important role in the pathogenesis of 2K, 1C-HT. However, the increased sensitivity of vascular smooth muscle cells to norepinephrine may contribute to the maintenance of high blood pressure in the face of reduced vascular sympathetic tone in this form of hypertension.

Animals↗