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Biomedical subjects

T Okamura

Publications and source records attributed to T Okamura.

At least 415 records · Page 23Linked to original sources

Free testosterone and abortion in early pregnancy.

OBJECTIVES: To investigate the relationship between percentage of free testosterone (% free T) and the abortion rate in early pregnancy. METHODS: Progesterone (P), estradiol (E2), total T, sex hormone binding globulin (SHBG), and % free T were measured in sera obtained from 60 pregnant women with normal pregnancy (n = 38) and missed abortion (n = 22) at between 4 and 12 weeks' gestation. RESULTS: P, E2, total T, and SHBG in 22 patients with missed abortion were significantly lower than those in normal group, whereas % free T was significantly higher. There was a significant negative correlation between % free T and SHBG concentration in the normal group, but not in the missed abortion group. All the subjects in whom % free T was 1.30% and higher subsequently miscarried, but no subject with % free T less than 0.70% had a miscarriage. CONCLUSIONS: The lower the % free T, the lower the rate of subsequent abortion. The value of % free T may be able to predict pregnancy outcome in early pregnancy.

Abortion, Spontaneous↗

A randomized phase II trial of low-dose aclarubicin vs very low-dose cytosine arabinoside for treatment of myelodysplastic syndromes.

We performed a randomized phase II trial comparing low-dose aclarubicin (LC-ACR) with very low-dose cytosine arabinoside (VLD-AC) in 39 consecutive untreated patients with myelodysplastic syndromes (MDS), including refractory anemia (RA), RA with excess of blasts (RAEB) and RAEB in transformation (RAEB-t). Nineteen patients received the VLD-AC therapy; 2 good responses (GR) and 2 partial responses (PR) were obtained in 11 patients with RAEB and RAEB-t, while 2 PR were obtained in 8 RA patients. Eighteen patients received the LD-ACR therapy; 2 GR and 4 PR were obtained in 11 RAEB/RAEB-t patients while 2 PR in 7 RA patients. There was no significant difference in the therapeutic effects and survival between these two groups of patients. These observations suggest that the LD-ACR therapy is effective in some patients with MDS and can be used as an alternative to the low-dose Ara-C therapy.

Aclarubicin↗

Nitric oxide mediates, and acetylcholine modulates, neurally induced relaxation of bovine cerebral arteries.

Helical strips of bovine basilar arteries denuded of the endothelium responded to transmural electrical stimulation with frequency-dependent relaxations that were abolished or markedly attenuated by treatment with tetrodotoxin, oxyhemoglobin and Methylene Blue. Relaxations induced by vasoactive intestinal polypeptide and calcitonin gene-related peptide were not affected by oxyhemoglobin and Methylene Blue. The neurally induced relaxation was not attenuated in the artery made unresponsive to these peptides by successive application. The relaxation caused by nerve stimulation was markedly inhibited by treatment with NG-nitro-L-arginine, a nitric oxide synthase inhibitor, which did not inhibit the relaxation caused by exogenously applied nitric oxide. The inhibition was reversed by L-arginine but not by the D-enantiomer. Exogenously applied acetylcholine did not alter the tone of endothelium-denuded arteries. Neurally induced relaxations were attenuated by treatment with acetylcholine and physostigmine and were significantly potentiated by atropine. It may be concluded that the relaxation induced by nerve stimulation is mediated by nitric oxide, but not by vasoactive intestinal polypeptide or calcitonin gene-related peptide, derived from vasodilator nerves innervating the bovine basilar artery, and the nerve function is inhibited prejunctionally via muscarinic receptor activation by acetylcholine released from cholinergic nerves but is not influenced by vasoactive intestinal polypeptide.

Acetylcholine↗

The photo repair of pyrimidine dimers by DNA photolyase and model systems.

Pyrimidine dimers are eliminated from DNA by a number of different mechanisms known as DNA repair. Photoreactivation, the reversal of the harmful effects of short wavelength radiation by subsequent exposure to longer wavelengths, is one such mechanism. In photoreactivation, the enzyme DNA photolyase utilises light in order to catalyse the cleavage of the cyclobutane ring of the pyrimidine dimer. The results of recent studies of E. coli DNA photolyase and model systems using techniques such as steady state and flash photolysis, time resolved fluorescence and photo CIDNP are surveyed. A mechanism is proposed for the in vitro reaction of E. coli DNA photolyase which involves photoreduction of the FAD radical cofactor followed by electron donation to the dimer from the excited singlet state of reduced FAD.

DNA↗

Angiosarcoma of the chest wall with a gastric metastasis.

A rare case of chest-wall angiosarcoma with high tendency of local recurrence and with a solitary gastric metastasis is reported. The patient was an 84-year-old man who had a left lateral thoracic mass with a colic pain. The histological diagnosis of a biopsied specimen suggested an angiosarcoma. The first resection was performed, the resected specimen consisted of the 8th, 9th and 10th ribs including the tumor. However the tumor recurred around the primary site and the second resection was undertaken eight months after the first resection. Only three months after the second resection a second chest-wall recurrence together with a solitary gastric metastasis was found. Progressive emaciation, anemia and thrombocytopenia became evident, and the patient died the 40th day after the gastrectomy. Primarily a wide resection of the chest wall beyond the pathologically negative region around the tumor is thought to be necessary.

Aged↗

Responses to perivascular nerve stimulation of distal temporal arteries from dogs and monkeys.

In helical strips of dog distal superficial temporal artery denuded of endothelium and partially contracted with prostaglandin F2 alpha (PGF2 alpha), nicotine produced a moderate relaxation preceded by no contraction or a slight contraction. The contraction was less than that observed in proximal arterial strips obtained from the same dogs and was abolished by alpha-adrenoceptor antagonists. Relaxations under alpha-receptor blockade were greater in the distal than in the proximal arteries. Treatment with NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor, abolished the relaxation caused by nicotine and transmural electrical stimulation (5 Hz for 40 s), the response being reversed by L- but not by D-arginine. In monkey temporal arteries of the distal and proximal portions treated with alpha-antagonists, nicotine produced similar magnitudes of relaxation, which were abolished by treatment with the NO synthase inhibitor. Vasodilator nerves appear to play an important role in regulation of small arterial tone; noradrenergic vasoconstrictor function is less and vasodilator nerve function is more evident in dog distal arteries than in dog proximal arteries. The neurally induced relaxation in dog and monkey distal temporal arteries is postulated to be mediated by NO derived from nerves.

Adrenergic alpha-Antagonists↗

Evaluation of leukaemic contamination in peripheral blood stem cell harvests by reverse transcriptase polymerase chain reaction.

A major issue in autologous blood stem cell transplantation (ABSCT) for leukaemia is whether peripheral blood stem cell (PBSC) harvests are less contaminated with leukaemic cells than bone marrow mononuclear cells (BMMNC). We compared leukaemic contamination in PBSC harvests and BMMNC, obtained simultaneously, by using reverse transcriptase polymerase chain reaction (RT-PCR) of leukaemia-specific chimaeric messenger RNA (mRNA), in three patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukaemia (ALL), one with Ph-positive acute myelogenous leukaemia (AML), and two with acute promyelocytic leukaemia (APL). Our two-step PCR method employed 'nested primers' in the second step and can detect one leukaemic blast diluted into 10(6) HL-60 cells. In three of four patients with Ph-positive ALL and AML we detected leukaemic contamination in both PBSC harvests and BMMNC. In the remaining patient with ALL, both PBSC harvests and BMMNC were PCR-negative. Both PBSC harvests and BMMNC from one patient with APL were PCR-positive. In contrast, PBSC harvests from another patient with APL, whose BMMNC could not be obtained because of bone marrow necrosis, were PCR-positive after the first course of consolidation chemotherapy, but became PCR-negative after the second course. The present study does not support the hypothesis that PBSC harvests are less contaminated by leukaemic cells than BMMNC, but suggests that PBSC harvests are contaminated when BMMNC are contaminated.

Adult↗

Clinicopathologic, enzyme and histochemical studies of centrocytic (mantle cell) lymphoma: comparison with other types of low-grade B cell lymphoma based on the updated Kiel classification.

Lymph nodes from 21 cases of malignant lymphoma of a centrocytic (mantle cell) type, (ML, cc (mc)) were examined. All the cases had monoclonal surface immunoglobulin (sig) M and/or D, but were negative for CD10 (CALLA), and CD11c (LeuM5). Lymphoma cells with CD25 (anti-Tac)+, CD5 (Leu1)+, and alkaline phosphatase (ALPase)- in eight cases showed bone marrow involvement (10-66% of the nucleated cells; mean 32 +/- 18%) but with no leukemic changes. These eight cases had a similar phenotype and were distributed by the lymphoma cells to the examined B-chronic lymphocytic leukemia. Seven cases showed an infiltration of CD25-, CD5+, and ALPase- lymphoma cells, in which only two cases showed focal bone marrow involvement. There was a close relationship between CD25 expression and bone marrow invasion by the lymphoma cells in ML, cc (mc). Three of the six CD25- and CD5- cases presented zonal proliferation of ALPase+ lymphoma cells with round nuclei and a high anti-proliferating cell nuclear antigen/cyclin (PCNA/c) rate in the mantle zone and paracortex, accompanied by a prominent interdigitating dendritic and histiocytic cell reaction. Examined CD25-, CD5- and ALPase+ lymphoma showed a neoplastic counterpart of so-called marginal zone lymphocytes, which was different from other cases of ML, cc (mc). Lymphoma cells in ML, cc (mc), except for those of the so-called marginal zone lymphoma, might be derived from slgM+, D+/-, CD25+/-, CD5+/-, ALPase-, CD10- and CD11c- lymphocytes present in the mantle zone and primary lymph follicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

A clinical study of hypergraphia in epilepsy.

Fifteen patients with epilepsy and hypergraphia were compared with 32 patients with epilepsy but without hypergraphia. The number of previous psychiatric episodes, the number of Washington Psychosocial Seizure Inventory (WPSI) items indicating emotional maladjustment, and the number of CT scan abnormalities were significantly greater in the hypergraphic patients than in the non-hypergraphic patients. Cognitive performance, EEG laterality and the scores of WPSI items related to the psychological stress of seizures did not differ significantly between the two groups. Hypergraphia reflects changes in emotional responsiveness secondary to organic temporal lobe lesions.

Adult↗

Neural mechanism underlying basilar arterial constriction by intracisternal L-NNA in anesthetized dogs.

Basilar arterial diameters were angiographically measured in anesthetized dogs in which systemic blood pressure and heart rate were also monitored. Injections of NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor, into the cisterna magna produced a significant, persistent decrease in arterial diameter, the effect being reversed by intracisternal injections of L-arginine. The vasoconstrictor effect of L-NNA was diminished in dogs treated with hexamethonium. On the other hand, treatment with phentolamine in a dose sufficient to lower blood pressure to a level similar to that attained with hexamethonium did not inhibit, but rather potentiated, the effect of intracisternal L-NNA. Nicotine injected into the vertebral artery significantly dilated the basilar artery. The effect was abolished by treatment with L-NNA applied intracisternally, the inhibition being reversed by the addition of L-arginine. Systemic blood pressure and heart rate were not altered by intracisternally applied L-NNA and L-arginine. These findings support the hypothesis that basilar arterial constriction caused by intracisternal L-NNA is associated with a suppression of NO synthesis in nitroxidergic nerves innervating the cerebroarterial wall rather than an elimination of basal release of NO from the endothelium. Functional importance of nitroxidergic vasodilator innervation in cerebral arteries in vivo is thus clarified.

Anesthesia↗

Monkey cerebral arterial relaxation caused by hypercapnic acidosis and hypertonic bicarbonate.

In helical strips of Japanese monkey cerebral arteries contracted with vasoconstrictors, applications of high CO2 (15% compared with 5% CO2 in control media) and hypertonic NaHCO3 (50 mM) produced relaxations. Similar relaxations were also obtained in human cerebral arterial strips. Hypercapnia increased PCO2 and resulted in acidosis in the bathing media, and the addition of NaHCO3 restored the pH to normal with high PCO2 and increased the osmotic pressure. The relaxant responses were not influenced by endothelium denudation and treatment with indomethacin. The hypercapnia-induced relaxation was suppressed by ouabain but was unaffected by amiloride. On the other hand, hypertonic bicarbonate-induced relaxations were inhibited by ouabain as well as by amiloride. Removal of Na+ from the bathing media abolished the hypercapnia-induced relaxation but did not alter the hyperosmolar relaxation. In contrast to hypertonic NaHCO3, isotonic bicarbonate solutions contracted the arterial strips by neutralizing the pH under hypercapnia. It may be concluded that relaxations elicited by hypercapnic acidosis are associated with a fall of extracellular pH and an activation of the electrogenic Na+ pump, and those caused by hyperosmolarity are due to stimulation of the Na(+)-H+ exchange and the Na+ pump. Endothelium-derived vasoactive substances and cyclooxygenase products do not appear to be involved in these relaxations of monkey cerebral arteries under the experimental conditions used.

Acidosis↗

Treatment of disseminated intravascular coagulation and its prodromal stage with gabaxate mesilate (FOY): a multi-center trial.

One hundred and ninety-one patients with disseminated intravascular coagulation syndrome (DIC) or its prodromal stage (preDIC) were treated with only gabaxate mesilate (FOY) (group G) or a combination of gabaxate and unfractionated heparin (group GH), and the efficacy of gabaxate was evaluated in a multicenter study. Following the treatment, the mean DIC score, which was evaluated on the basis of clinical symptoms and hemostatic parameters, decreased significantly to 5.58 +/- 3.48 from 6.75 +/- 3.14 in group G (p < 0.001) and to 6.34 +/- 3.33 from 7.31 +/- 3.00 in group GH (p < 0.05). In patients with overt DIC, the mean score decreased to 6.71 +/- 3.54 from 8.42 +/- 2.84 (p < 0.001). In DIC, the rate of overall efficacy was 46.2% in group G and 35.1% in group GH. In preDIC, it was 41.5% in group G and 27.3% in group GH. No side effects, including severe bleeding, were found in this study. The results indicate that gabaxate mesilate is clinically effective for patients with DIC and preDIC.

Adolescent↗

One-shot intravesical instillation of the mucous adhesive anticancer agent hydroxypropylcellulose-doxorubicin for the treatment of superficial bladder carcinoma is sufficient to determine antitumor effects.

A 20 mg/20 ml dose of the membrane adhesive anticancer preparation, hydroxypropylcellulose-doxorubicin (HPC-doxorubicin), was instilled into urinary bladders through a catheter for the treatment of superficial bladder carcinomas (Ta-T1). After 14-30 days, the effects of the drug on tumors was examined by cystoscopy, and the residual tumor tissue where reduction in size was observed was resected by transurethral resection (TUR). Therapeutic effects were as follows: a complete response (CR) was found in 6 cases (37.5%), a reduction in size of more than 50% (partial response = PR) in 4 cases (25%), and a less than 25% reduction (no change = NC) in 6 cases (37.5%). In no case was progression of the disease noted. In CR cases, cold cup punch biopsy revealed no tumor cells remaining at the site where the tumor was present before the instillation. Side effects such as bladder irritation were found in 4 cases, but they were only temporary in nature. The one-dose HPC-doxorubicin approach developed by ourselves allowed detection of antitumor effects between 14 and 30 days after the instillation and therefore determination of sensitivities at an earlier stage than with instillation of the conventional water-soluble type of doxorubicin hydrochloride.

Administration, Intravesical↗

Neural mechanism of hypertension by nitric oxide synthase inhibitor in dogs.

This study aimed to determine the mechanism of hypertension associated with nitric oxide synthase inhibition. Intravenous injections of NG-nitro-L-arginine, a nitric oxide synthase inhibitor, produced a sustained increase in systemic blood pressure and a decrease in heart rate in anesthetized dogs, whereas NG-nitro-D-arginine had no effect. L-Arginine reversed the pressor response. NG-Nitro-L-arginine-induced hypertension was markedly attenuated or abolished by treatment with hexamethonium; this inhibition was still observed when the blood pressure fall caused by the ganglionic blocking agent was compensated by continuous infusion of angiotensin II. In dogs treated with phentolamine in a dose sufficient to lower blood pressure to the level similar to that elicited by hexamethonium and to suppress the pressor response to norepinephrine, the hypertensive effect of NG-nitro-L-arginine was not attenuated. We conclude that hypertension caused by the nitric oxide synthase inhibitor is associated with an elimination of nitroxidergic neural function rather than an impairment of the basal release of nitric oxide from the endothelium.

Amino Acid Oxidoreductases↗

Impairment by damage of the pterygopalatine ganglion of nitroxidergic vasodilator nerve function in canine cerebral and retinal arteries.

Histochemical study revealed that transcutaneous injection of ethanol into the vicinity of the pterygopalatine ganglion greatly decreased the positive staining for NADPH diaphorase activity after 1 week in the ipsilateral ganglion of a dog and abolished the staining of perivascular nerves in the middle and posterior cerebral arteries. Transmural electrical stimulation or nicotine produced a relaxation in middle and posterior cerebral arteries isolated from the side with the nontreated ganglion (control side), whereas the relaxation was abolished or reversed to a contraction in the arteries from the side with the ethanol-treated ganglion. Nitric oxide-induced relaxations did not differ in the arteries from both sides. The response to nerve stimulation of the control arteries was suppressed by treatment with NG-nitro-L-arginine (L-NA), an inhibitor of nitric oxide synthase, and the inhibition was reversed by L-arginine. Nicotine produced a contraction followed by a relaxation in central retinal arterial strips obtained from the control side; the relaxation was abolished and the contraction was potentiated in the arteries from the treated side. The nicotine-induced relaxation was abolished by L-NA, and the contraction was suppressed by phentolamine. On the other hand, the nicotine-induced relaxation in superficial temporal arteries, susceptible to L-NA, was not attenuated by treatment with ethanol. The findings obtained so far support our hypothesis that nitric oxide released from the vasodilator nerve acts as a transmitter to produce arterial smooth muscle relaxation and suggest that the nerve fibers to the cerebral and retinal arteries arise from the pterygopalatine ganglion.

Animals↗

Endothelial modulation of contractions caused by oxyhemoglobin and NG-nitro-L-arginine in isolated dog and monkey cerebral arteries.

BACKGROUND AND PURPOSE: Oxyhemoglobin is a key substance in provoking cerebral vasospasm and a scavenger of nitric oxide. The present study was designed to determine whether suppression of the action of endothelium-derived nitric oxide is involved in oxyhemoglobin-induced cerebroarterial contraction. METHODS: Dog and monkey cerebral artery strips with and without endothelium were immersed for isometric tension recording in modified Ringer-Locke solution aerated with 95% oxygen and 5% carbon dioxide. RESULTS: NG-nitro-L-arginine, a nitric oxide synthase inhibitor, produced concentration-related contraction that was greater in the strips with intact endothelium than in those denuded of endothelium. The D-enantiomer caused no or only a slight contraction. In the presence of NG-nitro-L-arginine, oxyhemoglobin elicited additional contraction that is comparable to or even greater than that obtained in the absence of the inhibitor. The oxyhemoglobin-induced contraction was attenuated by endothelium denudation. CONCLUSIONS: Inhibition of the basal release of nitric oxide from endothelium results in dog and monkey cerebral arterial contraction. However, the inhibition of nitric oxide action is not a major mechanism involved in oxyhemoglobin-induced contraction; other mechanisms, such as the release of prostanoids, appear to be important.

Animals↗

Potentiation by hypoxia of contractions caused by angiotensin II in dog and monkey cerebral arteries.

BACKGROUND AND PURPOSE: Hypoxia alters the responsiveness to endogenous substances of cerebral arteries, possibly resulting in the modulation of blood supply to ischemic brain regions. The present study was undertaken to analyze the mechanism of potentiation by hypoxia of angiotensin II-induced cerebroarterial contractions. METHODS: Monkey and dog cerebral arterial strips with endothelium were suspended for isometric tension recording in Ringer-Locke solution aerated with 95% O2-5% CO2 (partial pressure, 570-600 mm Hg) or 95% N2-5% CO2 (approximately 10 mm Hg). RESULTS: Contractions induced by angiotensin II and substance P were potentiated by exposure to hypoxia, whereas contractile responses to prostaglandin F2 alpha were not influenced. Treatment with cyclooxygenase inhibitors abolished the peptide-induced contraction but did not alter the prostaglandin F2 alpha-induced contraction. Relaxations induced by arachidonic acid were suppressed by indomethacin and hypoxia, whereas those caused by a prostaglandin I2 analogue were unaffected. CONCLUSIONS: The potentiation by hypoxia of cerebroarterial contractions caused by angiotensin II and substance P appears to be due to an interference with the synthesis of prostaglandin I2 from arachidonic acid and a resultant increase in the production of vasoconstrictor prostaglandins.

Angiotensin II↗

Identification of a functional receptor for granulocyte colony-stimulating factor on platelets.

Since granulocyte colony-stimulating factor (G-CSF) is thought to be a granulocyte lineage-specific cytokine, G-CSF receptors on blood cells other than those of granulocyte or monocyte lineage have not been well investigated. We now report that G-CSF receptors are present on platelets. The expression of G-CSF receptors on platelets was demonstrated by flow cytometry and radioreceptor assay. The mean number of G-CSF-binding sites per cell was 41 and the binding affinity was high (Kd 300 pM), similar to the affinity observed on granulocytes. Cross-linking assay revealed that G-CSF receptors were present on a single subunit protein of approximately 150 kD on the platelets. To clarify whether or not G-CSF might produce some direct functional influence on platelet response, the effects on platelet aggregation were studied. Although G-CSF itself did not affect platelet aggregation in vitro, preincubation with G-CSF augmented a secondary aggregation of platelets induced by low concentrations of adenosine diphosphate (ADP). There was a dose-response relationship for this G-CSF activity at concentrations of up to 10 ng/ml. Furthermore, the augmented ADP-induced secondary aggregation of platelets on G-CSF receptors was completely abrogated in the presence of anti-G-CSF polyclonal antibodies. These results indicate that platelets possess functional G-CSF receptors.

Adenosine Diphosphate↗