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Biomedical subjects

T Oka

Publications and source records attributed to T Oka.

At least 991 records · Page 55Linked to original sources

Increased immunoglobulin E Fc receptor bearing cells in germinal centers of hyperimmunoglobulinemia E patients.

Lymph nodes from 6 patients with hyperimmunoglobulinemia E (hyper-IgE; 4 with Kimura's disease, 1 with atopic dermatitis, and 1 with immunoblastic lymphadenopathy-like T cell lymphoma) and from 7 patients with normal IgE levels were studied to determine the localization of dendritic reticulum cells and of cells bearing Fc epsilon and C3d receptors and immunoglobulin E. The avidin-biotin-glucose oxidase method was used for unfixed biopsy specimens. To identify the above-mentioned cells, H107, a murine monoclonal antibody specific to the Fc epsilon receptor molecule, and corresponding antibodies specific to the other cell types were used. In 5 hyper-IgE patients (4 with Kimura's disease and 1 with atopic dermatitis) all germinal centers of the lymph nodes showed heavy reticular staining with H107, the dendritic reticulum cells being most intensely stained. In contrast, the germinal centers of the lymph nodes in the 7 patients with a normal IgE level only lightly or partially stained with H107. The staining pattern of anti-IgE was similar to that of H107 in the hyper-IgE cases. Likewise, C3d receptor and dendritic reticulum cell-related antigens were demonstrated very intensely in all germinal centers in lymph nodes of patients with hyper-IgE and normal IgE levels. These findings suggest that in a hyper-IgE state increased numbers of dendritic reticulum cells in a germinal center express the Fc epsilon receptor and that such cells may play a role in the differentiation of IgE-producing memory B cells.

Angiolymphoid Hyperplasia with Eosinophilia↗

Epidermal growth factor-like, corneal wound healing substance in mouse tears.

We have identified the presence of a putative corneal wound healing substance in mouse tears, which has a molecular size and immunological properties similar to those of epidermal growth factor (EGF). The substance was capable of binding to EGF receptors in mouse parenchymal cells and this binding was inhibited by anti-EGF serum. The concentration of the EGF-like substance in the tears of male and female mice was estimated to be 79.3 +/- 7.0 (SD) ng/ml and 76.5 +/- 8.1 (SD) ng/ml, respectively, by EGF radioimmunoassay. Removal of the submandibular glands, which produce large amounts of EGF, reduced plasma EGF to an undetectable level and also decreased the concentration of the EGF-like substance in tears to 27.3 +/- 3.9 (SD) ng/ml in male mice and 25.8 +/- 3.7 (SD) ng/ml in female mice. Approximately 50% of sialoadenectomized (submandibular glands removed) male mice with deep corneal wounds developed severe ocular lesions or loss of sight whereas none of normal male mice with similar wounds did. Topical application of EGF to deeply wounded eyes of sialoadenectomized mice eliminated the various complications and restored the healing rate and incidence of recovery to virtually normal levels.

Animals↗

In vitro effects of various heterocyclic thiol compounds and beta-lactam antibiotics on vitamin K-dependent gamma-glutamylcarboxylation activity in liver microsomes.

The in vitro effect of N-methyltetrazolethiol (NMTT), one of the common substituents at the 3'-position of the cephem in various beta-lactam antibiotics, on liver microsomal gamma-glutamylcarboxylation (gamma-carboxylation) activity was examined using solubilized rat liver enzyme. The enzyme activity was inhibited by coexisting with NMTT and NADH, and this inhibitory activity could be suppressed by the addition of a sulfhydryl compound such as dithiothreitol (DTT), glutathione or cysteine. Various five-membered heterocyclic thiol compounds exhibited concentration-dependent inhibition of microsomal gamma-carboxylation activity. These inhibitory actions diminished markedly in the presence of 1 mM DTT. In vitro gamma-carboxylation activity also decreases upon addition of various beta-lactam antibiotics at 1 or 10 mM, depending upon the concentration of the drug. Among the heterocyclic thiol compounds, there is a correlation between their inhibitory activities and hydrophobicities. Thus, the in vitro inhibitory activity of heterocyclic thiol compounds and beta-lactam antibiotics on microsomal gamma-carboxylation activity is not correlated with their molecular structures, but rather depends on their hydrophobicities and with the concentrations in the reaction mixture.

Animals↗

Inactivation of dynorphin-(1-8) in isolated preparations by three peptidases.

Inactivation of dynorphin-(1-8) in three in vitro isolated preparations, guinea-pig ileum, mouse vas deferens and rabbit vas deferens, was estimated by employing the relatively specific inhibitors of enkephalin-hydrolyzing enzymes. All three enzyme inhibitors, amastatin, captopril and phosphoramidon, significantly enhanced the inhibitory potency of dynorphin-(1-8) in the three isolated preparations. The magnitude of the enhancement of the dynorphin potency by captopril was significantly higher than that by either amastatin or phosphoramidon in guinea-pig ileum; that by amastatin was significantly higher than that by either captopril or phosphoramidon in rabbit vas deferens; and that by amastatin was similar to that by captopril, but significantly higher than that by phosphoramidon in mouse vas deferens. The Ke values of three antagonists, naloxone, Mr 2266 and ICI 154129, against dynorphin-(1-8) in the presence of the three peptidase inhibitors indicated that dynorphin-(1-8) acted on kappa receptors in guinea-pig ileum and on both kappa and delta receptors in mouse vas deferens. Since amastatin, captopril and phosphoramidon produced the naloxone-reversible inhibition of contractions of guinea-pig ileum in the presence of dynorphin-(1-8), all three dynorphin-inactivating enzymes were indicated to be located very close to kappa receptors.

Aminopeptidases↗

Effects of flunarizine on induced nystagmus and cochlear blood flow.

The effects of flunarizine on induced nystagmus and cochlear blood flow were compared with those of cinnarizine and diphenidol. Flunarizine significantly inhibited caloric (cool water)-induced nystagmus frequency and duration of nystagmus in rabbits at 5 mg/kg i.v., whereas cinnarizine and diphenidol only slightly decreased the frequency of nystagmus at 5 mg/kg, i.v. As for optokinetic stimuli-induced nystagmus in rabbits, flunarizine significantly decreased the amplitude of nystagmus at 2.5 mg/kg i.v., and cinnarizine and diphenidol inhibited nystagmus at 5 mg/kg, i.v. Flunarizine had no effect on nystagmus induced by electrical stimulation of the lateral geniculate body in rabbits at doses up to 5 mg/kg, i.v. Flunarizine increased the cochlear blood flow in anesthetized guinea pigs dose-dependently (0.312-1.25 mg/kg i.v.) On the other hand, cinnarizine (0.625-2.5 mg/kg i.v.) and diphenidol (0.625-2.5 mg/kg i.v.) increased cochlear blood flow, but the duration of action of both cinnarizine and diphenidol was shorter than that of flunarizine at the same dose. As stated above, flunarizine inhibited nystagmus experimentally induced by caloric or optokinetic stimuli. Increased cochlear blood flow suggested that the enhancement of vestibular blood flow might play an important role in the treatment of vestibular dysfunctions with this drug.

Animals↗

Effect of cycloheximide on the levels of nuclear HMG proteins in rat liver.

Within 30 minutes of administration of cycloheximide to rats, rRNA synthesis in isolated liver nuclei was inhibited by approximately 50%. The nuclear contents of high mobility group (HMG) proteins, including HMG 1, 2 and 14, were found to be decreased in parallel with the inhibition of RNA synthesis while the contents of the total cellular HMG proteins remained unchanged. The role of HMG proteins in the regulation of RNA synthesis is discussed.

Amanitins↗

Receptor binding properties of the new calcium antagonist benidipine hydrochloride.

The in vitro receptor binding affinity of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-diyhydropyridine-3, 5-dicarboxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) to 3H-nitrendipine, alpha 1-adrenergic, alpha 2-adrenergic, beta-adrenergic, muscarinic cholinergic, H1-histaminergic, D2-dopaminergic, S2-serotonergic, A1 adenosine and A2 adenosine receptors was compared with that of nifedipine, nitrendipine and nicardipine. KW-3049 bound stereospecifically to 3H-nitrendipine binding sites of rat myocardium with high affinity (Ki = 0.13 nmol/l) and to the rat brain alpha 1-receptor (Ki = 1.2 mumol/l). KW-3049 exhibited no remarkable binding affinity to alpha 2, beta-, D2-, H1-, S2-, A1-, A2- and muscarinic cholinergic receptors at 100 mumol/l. KW-3049 showed competitive inhibition against 3H-nitrendipine binding when it was added simultaneously with the ligand and rat heart membranes. KW-3049 did not affect the dissociation of 3H-nitrendipine from the receptor sites. The inhibitory activity of various isomers of KW-3049 at the 3H-nitrendipine binding sites was shown in the order of S-S-(+) greater than KW-3049 (racemate, S-S-(+), R-R-(-] greater than R-R-(-) greater than S-R-(-) greater than racemate (R-S-(+), S-R-(-] greater than R-S-(+). S-S-(+)isomer was 12 times more potent than R-R-(-)isomer on Ki basis, whereas alpha 1-adrenoceptors followed the order of S-S-(+), R-S-(+), KW-3049, racemate (R-S-(+), S-R-(-], S-R-(-) and R-R-(-).

Animals↗

[Clinical efficacy and pharmacokinetic evaluation of ceftizoxime in neonates and young infants].

Thirteen neonates and young infants, including 5 infants with very low birth weight, were treated with ceftizoxime (CZX) and its clinical efficacy and side effects were evaluated. The ages of the patients ranged from 0 to 96 days, and their body weights ranged from 580 to 5,050 g. Doses given were 20-54 mg/kg every 6 to 12 hours for 2.5 to 7.5 days. Two infants with sepsis, one with urinary tract infection, one with sepsis and urinary tract infection, and 1 with fetal infection were considered to have responded satisfactorily to the CZX treatment. The drug was well tolerated and side effects was not apparent. Pharmacokinetic studies were done on CZX in 8 patients including 4 infants with very low birth weight. Their ages ranged from 2 to 91 days, and body weights from 545 to 5,050 g. Serum concentrations at 2 hours after single 20 mg/kg intravenous bolus injections were 19.2 to 44.2 micrograms/ml and the levels were 2.11 to 26.3 micrograms/ml at 8 hours. Elimination half-lives of CZX ranged 1.90 to 9.57 hours in these patients. In 2 infants with very low birth weights with ages 7 and 91 days, half-lives were as long as 9.57 and 8.24 hours, respectively. Urinary recovery in 6 hours was 31.9-66.9% in 5 patients. Urine concentrations of the drug in 24 samples collected at various time from the 7 patients ranged from 130 to 3,219 micrograms/ml. Influence of CZX on the fecal flora was studied in 1 patient given 20 mg/kg X 4/day of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Ceftizoxime↗

[Citrate (CG-120) therapy for urolithiasis. 1. Clinical effects].

Urinary citrate is an important determinant for crystallization of calcium salts, and recently oral administration of citrate has been suggested to be clinically useful in the management of renal stone disease. The effect of CG-120, a citrate compound (potassium citrate, sodium citrate and citric acid) produced by Dr. Madaus (Germany), on upper urinary tract stones was investigated in 398 patients in this study group. The patients were treated with 3 or 4 g CG-120 daily. Two hundred thirty-one of them were treated accurately according to the protocol of the study for more than 32 weeks. The cumulative percentage of positive clinical effect for the stone (disappearance, passage or decrease in size) was 30.3% (70/231). There were no differences in the clinical effect between the group of 3 g/day and the group of 4 g/day. CG-120 seemed to be more effective in the cases of ureteral stone, young patients and females, but was less effective in the recurrent stone formers. Although there were 45 episodes of side effects in 38 patients in this study, no serious side effects attributed to CG-120 were experienced. CG-120 was proved as a useful drug in the treatment of upper urinary tract calculi as well as its prevention.

Adolescent↗

[Citrate (CG-120) therapy in urolithiasis. 2. Effect on urinary and serum biochemistry ].

The long-term effects of citrate therapy (CG-120, 3 g/day or 4 g/day) were examined in 398 patients with upper urinary tract calculi. We studied the influence of citrate therapy on urinary and blood biochemistry in 353 of them. CG-120 caused a sustained increase in urinary citrate, urinary pH and potassium, but no substantial or significant changes in other urinary parameters (uric acid, phosphate, oxalate, sodium, chloride and urine volume). Although urinary calcium decreased significantly up to the 24th week, it did not change significantly there after and it tended to increase at the 54th week. Urinary creatinine excretion decreased after 34 weeks of administration, but this phenomenon could not be explained, because the level of blood urea nitrogen and serum creatinine was not elevated in any case before administration. There were no changes in the serum calcium, magnesium, phosphate, uric acid, sodium, potassium or chloride level.

Blood Chemical Analysis↗

Antihypertensive effects of the new calcium antagonist benidipine hydrochloride in rats.

Using spontaneously hypertensive rats (SHR), DOCA-NaCl hypertensive rats (DHR) and normotensive rats (NTR), the antihypertensive action of (+/-)-(R*)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dic arb oxylic acid (R*)-1-benzyl-3-piperidinyl ester, methyl ester hydrochloride (benidipine hydrochloride, KW-3049) was comparatively evaluated with those of nicardipine and hydralazine. Administration of KW-3049 at 0.5, 1 and 3 mg/kg (p.o.) showed dose-dependent antihypertensive action. This action appeared gradually and it lasted longer than those of nicardipine and hydralazine. The administration of KW-3049 at 0.5 mg/kg (p.o.) did not show any effect on the blood pressure of NTR, but a long-lasting blood pressure lowering action was observed by the administration at 1 and 3 mg/kg (p.o.). This antihypertensive action specific to the hypertensive animals was similar to that of nicardipine, however, it was different from that of hydralazine, with which the blood pressure in SHR, DHR and NTR was lowered in similar degrees. Also, administration of KW-3049 caused tachycardia concomitant with the fall of blood pressure, however, it was mild as compared with those of nicardipine and hydralazine. When KW-3049 at doses of 3 and 10 mg/kg (p.o.) once a day was continuously administered to SHR for 31 days and changes of the antihypertensive action were observed, no tolerance developed and rebound hypertension following the discontinuation of medication did not occur. When the effect on the urinary volume and electrolyte excretion was evaluated in rats loaded with physiological saline solution, a natriuretic effect was observed by the administration of KW-3049 at 0.5, 1 and 3 mg/kg (p.o.).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Menstrual abnormality in patients with breast cancer receiving adjuvant endocrine-chemotherapy].

Menstrual status and ovarian function were studied in 24 premenopausal breast cancer patients receiving adjuvant therapy with chemotherapy and tamoxifen or chemotherapy alone. In 13 of 24 patients (54.1%), abnormal menses, including amenorrhea in 12 cases and oligomenorrhea in 1 case, developed during adjuvant therapy. In patients with abnormal menses, serum estradiol was significantly lower, and the levels of gonadotropins were significantly higher than in patients with normal menses. Among 13 patients with abnormal menses, 4 patients treated with cyclophosphamide revealed persistent amenorrhea during the whole period with adjuvant therapy, and the levels of serum estradiol and progesterone were extremely low. Furthermore, in these patients normal menses has not recovered and the levels of serum estradiol and progesterone remained low 4 to 5 months after cessation of cyclophosphamide administration. Thus, adjuvant chemotherapy caused depression of ovarian function, and cyclophosphamide induced ovarian failure, resulting in complete amenorrhea.

Adult↗