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Y Tone

Publications and source records attributed to Y Tone.

53 records · Page 3Linked to original sources
PubMed1992

Functional properties of a novel mutant thyroid hormone receptor in a family with generalized thyroid hormone resistance syndrome.

OBJECTIVE: We wished to ascertain whether a mutation in the thyroid hormone receptor beta gene was present in a family with generalized thyroid hormone resistance syndrome and to characterize the functional properties of this mutant receptor. DESIGN: Blood samples were obtained from family members for hormone assays and genomic DNA was isolated from leucocytes for genetic analyses. PATIENTS: Three members (B,C,E) of a family with possible thyroid hormone resistance and two normal family members (A,D) were studied. MEASUREMENTS: Basal thyroid function tests together with serum sex hormone binding globulin (SHBG) levels were measured. The thyroid hormone receptor beta gene was amplified using the polymerase chain reaction and the receptor mutation identified by sequence analysis. The ability of mutant receptor to bind T3, interact with a specific DNA sequence and to modulate target gene expression was tested. The effects of mutant receptor on co-expressed wild type receptor action were determined. RESULTS: Patients with resistance had raised levels of T4 and T3 together with inappropriately normal serum TSH and SHBG whereas unaffected individuals had a normal hormone profile. A single nucleotide substitution corresponding to a glycine to serine mutation at codon 340 (G340S) in the hormone binding domain was identified in one of the two beta receptor gene alleles in patients with resistance, but not in the normal family members. When expressed in vitro, this receptor protein (G340S), as well as a related (G340R) mutant identified in another family, retained the ability to bind to a specific DNA sequence but were unable to bind ligand or to activate or repress target gene expression. In addition both receptor mutants were capable of inhibiting the function of wild type thyroid hormone receptor in a co-expression assay but differed in their inhibitory potential. CONCLUSIONS: We report a second type of mutation (Gly to Ser) in codon 340 of hTR beta in a family with generalized thyroid hormone resistance. Mutations at this site eliminate T3 binding, causing a loss of hormone-stimulated receptor function. However, the mutant receptors retain the ability to block normal receptor action. The occurrence of different mutations at the same site suggests that alterations in this region of the receptor may be important for generating the clinical phenotype of this disorder.

DNA Mutational Analysis↗
PubMed1992

Prevention of aortic calcification in patients on hemodialysis by long-term administration of vitamin E.

The effects of vitamin E on the progress of atherosclerosis in patients on hemodialysis was investigated clinically using ACI. There was a significant suppression of the increase in ACI in group A, compared to group B, at the time of observation in each year. On the other hand, no significant changes were noted in BWD, CTR, BP and blood chemical examination, except that the level of MDA was significantly decreased in group A as compared with that in group B 4 years later. Since ACI is an index representing atherosclerosis, the results of this study seemed to suggest that the progress of atherosclerosis was suppressed by long-term administration of vitamin E in patients on hemodialysis.

Aortic Diseases↗
PubMed1992

Study on the inhibitory effect of uremic plasma on lipoprotein lipase.

An investigation was undertaken to determine which plasma factors from normal controls and patients with chronic renal failure (CRF) exert have inhibitory effects on the activity of lipoprotein lipase (LPL) purified from heparinized human plasma by using an accurate LPL assay system. Inhibitors of LPL were found to be present in the plasma. The inhibition of the LPL activity was significantly greater in CRF patients than in normal controls. Following hemodialysis (HD), the same concentration of uremic plasma led to less inhibition. The inhibitors existed only in lipoprotein deficient plasma (LPDS), which demonstrated an LPL-inhibitory activity at extremely high concentrations with a significant difference between the patients and normal controls. There was no difference between the two groups at low concentrations. A specific inhibitory effect on LPL in LPDS was noted in the 7S and 4S fractions separated by gel filtration employing Sephacryl S-200 column chromatography. The inhibitory effect of the 7S fraction was found to be dependent on the concentration, and the difference between the two groups was similar to that for LPDS. The results obtained in the present study suggest that the plasma from CRF patients exhibited a strong inhibitory action on the LPL activity as compared to the plasma from normal controls, and the inhibitory action was due primarily due to poor excretion of dialyzable inhibitors.

Adult↗
PubMed1990

Dose-dependent pharmacokinetics and first-pass metabolism of acetaminophen in rats.

In order to investigate the in vivo first-pass metabolism of acetaminophen (AAP) following the oral and intraduodenal administration in rats, a pharmacokinetic compartment model including absorption process was developed. Using the parameters for the disposition kinetics of AAP and its metabolites, sulfate and glucuronide, which were determined in the separate study, the extent of the first-pass metabolism and the contribution of sulfation and glucuronidation to the total first-pass metabolism in vivo were quantitatively estimated. As for the results, the first-pass metabolism of AAP following the oral and intraduodenal administration was mainly attributable to the sulfo-conjugation pathway in rats. The sulfation of AAP in the intestine and/or in the liver during the first-pass was proved to be a saturable process. Then, the sulfation in the first-pass metabolism showed the dose- and absorption rate-dependent kinetics. Thus, the pharmacokinetic model including the absorption process proposed in the present study was proved to be valid and useful for the estimation of in vivo first-pass metabolism of AAP in rats.

Acetaminophen↗
PubMed1989

Selective killing of carcinoembryonic-antigen (CEA)-producing cells in vitro by the immunoconjugate cytorhodin-S and CEA-reactive cytorhodin-S antibody CA208.

Cytorhodin-S, an anthracycline derivative, was covalently coupled to a monoclonal antibody (mAb) CA208, against carcinoembryonic antigen (CEA) in order to achieve selective killing of a CEA-producing colon carcinoma cell line, COLO 205. The conjugate (15 molecules of drugs/antibody) retained substantial antibody activity as well as drug activity as assessed by enzyme-linked immunosorbent assay and 24-h L1210 proliferation assay, respectively. Furthermore, the conjugate inhibited the growth of COLO 205 cells in a short-term cytostatic assay. This cytostatic effect of the immunoconjugate on COLO 205 cells was inhibited in a dose-dependent manner by pretreatment of the cells with unconjugated CA208 mAb. In addition, chloroquine, a lysosomotropic agent, inhibited the cytostatic effect of the immunoconjugate, indicating the involvement of lysosomal enzymes in releasing drugs from the immunoconjugate. The antibody (CA208) was significantly incorporated into the cytoplasm of COLO 205 cells as demonstrated by immuno-electron microscopy. These in vitro results indicate that cytorhodin-S may be a good partner in immunoconjugates. However, in vivo animal experiments with the immunoconjugate revealed that the immunoconjugate was not so effective in prolonging survival. Thus, in vivo efficacy of this immunoconjugate remains to be further improved in application to cancer immunotherapy.

Animals↗
PubMed1989

[Clinical efficacy of sulbactam/ampicillin in the field of pediatrics].

Sulbactam (SBT) is a new derivative of the basic penicillin nucleus. It effectively and irreversibly inhibits several important bacterial beta-lactamases and displays synergistic effects against the resistant organisms when co-administered with ampicillin (ABPC). SBT/ABPC, which is a fixed combination of SBT and ABPC in a 1:2 ratio, was studied for clinical efficacy in the field of pediatrics. Patients treated were infants and children ranging from 12 days to 13 years and 2 months old suffering from acute tonsillitis in 2 cases, acute bronchitis in 2 cases, septicemia in 2 cases, acute enteritis, acute pyelonephritis and osteomyelitis in 1 case each, a total of 9 cases. SBT/ABPC was administered 100-300 mg/kg in daily doses and durations of treatment ranged from 4 to 17 days. Clinical results were "excellent" in 6 and "good" in 2: the efficacy rate was 88.9% or 8 cases out of 9. Neither clinical side effects nor abnormal laboratory findings obviously attributable to SBT/ABPC were observed in any cases.

Adolescent↗
PubMed1988

[Pharmacokinetics and clinical effects of sultamicillin fine granules in pediatrics].

We have evaluated sultamicillin (SBTPC) fine granules for pharmacokinetics and therapeutic effectiveness in children. The results are summarized as follows. 1. Pharmacokinetic parameters after the oral administration of single dose of 5.0 mg per kg body weight in 1 child were as follows: The peak serum concentrations of ampicillin (ABPC) and sulbactam (SBT) were 1.92 micrograms/ml at 1 hour and 1.85 micrograms/ml at 1 hour, respectively. The half-lives in serum and urinary excretion rate for ABPC and SBT were similar. 2. A clinical study was performed on 15 children with infections, including 4 with tonsillitis, 5 with pharyngitis, 2 each with bronchitis, cystitis, and urinary tract infections. Doses ranging from 6.7 to 18.2 mg/kg body weight were given tid. or qid. Lengths of treatment ranged from 5 to 10 days. The therapeutic responses were considered "excellent" in 6 and "good" in 9, with an effectiveness rate of 100%. 3. As to side effects of the drug, diarrhea was observed in 1 patient. It was concluded that SBTPC was a promising drug for the treatment of bacterial infections in children.

Administration, Oral↗
PubMed1986

Pharmaceutical evaluation of hollow type suppositories. V. Preparation of valproic acid suppository and rectal absorption of valproic acid in rabbits.

Seven kinds of suppositories were constructed with oleaginous base materials (Witepsol H-15 (H-15) and E-85 (E-85]: a conventional type suppository containing valproic acid (VPA) mixed with E-85 (I), a conventional type suppository containing sodium salt of VPA (sodium valproate) (S-VPA) mixed with H-15 (II), hollow type suppositories containing VPA in the forms of oily liquid (free acid) (III), macrogol 1000 or 6000 mixture (IV or V), powder (S-VPA) (VI) and aqueous solution (S-VPA was dissolved in 0.9% NaCl solution) (VII) in each cavity. The content of VPA in type I was decreased considerably by volatility and type II was found to be hygroscopic. Therefore conventional type suppositories containing VPA or S-VPA were not of practical use, whereas III and VI prevented volatility of VPA and minimized the hygroscopic property of S-VPA. Plasma concentration of VPA was measured in rabbits after rectal administrations of III, IV, VI and VII. By using VI, the highest values of the mean of the peak plasma VPA concentration (Cmax) (49.8 +/- 2.6 micrograms/ml) and the mean of the area under the plasma concentration-time curve (AUC) (90.0 +/- 3.7 h X micrograms/ml) were obtained. The Cmax and the AUC estimated after administration of VII were not significantly different from those of VI. The Cmax and the AUC were lower with III than with IV, VI or VII but the extent of bioavailability (EBA) of III was about 80%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Suppressive effect of indazole adenine dinucleotides on proliferation of normal and malignant cells.

The suppressive effects of newly synthesized NAD-analogs, indazole adenine dinucleotides (IAD), on the cellular proliferation of normal and L5178Y cells were investigated in connection with their inhibitory activity on inosine 5'-monophosphate dehydrogenase (IMPD). All the dinucleotides, except compounds VIII and IX, were observed to show a certain extent of suppression at a concentration of 100 micrograms/ml. In particular, some compounds (II, VII, X and XI) among them showed a strong suppression (70-90%) in the leukemic cell system. The suppression seemed to be roughly correlative with the degree of IMPD inhibition of the dinucleotide.

Adenine Nucleotides↗
PubMed1985

Adjuvant activity of chitin derivatives in mice and guinea-pigs.

Adjuvant activity of chitin derivatives was examined in guinea-pigs and mice. Among derivatives of chitin tested, 30 and 70% deacetylated chitin (DAC-30 and DAC-70), were active as adjuvants for the circulating-antibody formation to bacterial alpha-amylase and for the induction of delayed-type hypersensitivity to azobenzenearsonate-N-acetyl-L-tyrosine. DAC-70 enhanced the helper T cell function, the generation of alloreactive cytotoxic T lymphocytes, and the activity of natural killer cells in mice, however, it was inactive as mitogen. Other derivatives of chitin showed weaker or no adjuvant activity compared with DAC-70. Carboxymethyl-, hydroxyethyl and dihydroxypropyl-chitin showed weak mitogenic activities on normal spleen cells.

Adjuvants, Immunologic↗
PubMed1985

[Therapeutic effects of cefminox in the treatment of various infections of infants and children].

The therapeutic effects of cefminox (CMNX, MT-141), a new synthetic cephalosporin antibiotic, were examined in the treatment of various pediatric infections. Patients treated were infants and children ranging from 12 days after birth to 12 years old suffering from bronchopneumonia in 10 cases, urinary tract infection in 6 cases, pharyngitis in 2 cases, cervical lymphadenitis in 2 cases, suppurative meningitis, cervical abscess, mastoiditis, peritonitis, bronchitis in 1 case each, total of 25 cases. As regards method of administration, CMNX from a vial was dissolved in physiological saline or distilled water for injection, and the solution was administered by 3 to 5 minutes one shot intravenous injection (15 cases), or CMNX was diluted with large volume parenteral product and administered by 30 to 60 minutes drip infusion (10 cases). The dosage of the drug was 21.3 to 165.5 mg/kg/day. The administration was continued for 3 to 13 days except 1 case. As regards clinical efficacy, good or excellent results were obtained in all cases except 3 cases, 1 case was urinary tract infection with cerebral palsy and vesicoureteral reflux, and 1 case was bronchopneumonia with Down syndrome and endocardial cushion defect, the other was suppurative meningitis. Total effective rate was 88%. No clinical side effects nor abnormal laboratory findings obviously attributable to CMNX were observed.

Anti-Bacterial Agents↗
PubMed1985

[The therapeutic effects of aspoxicillin on various infectious diseases in children].

Clinical application to ascertain the effects of aspoxicillin (ASPC), a new semisynthetic penicillin antibiotic, upon several infectious diseases of children was performed in 7 cases with pneumonia, 5 cases with acute bronchitis, each case with tonsillitis, enterocolitis, urinary tract infection and suspected sepsis. ASPC was injected by drip infusion and the dosage was 63-117 mg/kg/day in 3 and 4 times a day. Clinical efficacy obtained as "excellent" was in 7 cases, "good" in 8 cases "poor" in 1 case, and efficacy rate was 93.8%. From the bacteriological point of view, eliminated in each of H. influenzae, H. parainfluenzae, group A beta-Streptococcus and unchanged in a case of E. coli. There were transient thrombocytopenia in 2 cases and eosinophilia in 3 cases.

Adolescent↗
PubMed1983

[Therapeutic effects of an ampicillin suppository KS-R1) on infections in children].

Clinical and bacteriological effects of ampicillin suppository (KS-R1) were determined in 9 cases with urinary tract infection and 13 cases with upper respiratory tract infection in children. Clinical effects were excellent in 1 case, good in 18 cases, fair in 2 cases and poor in 1 case. Bacteriological effects were eradication in 6 cases, decrease in 1 case, persistance in 3 cases and replacement in 1 case among 11 cases which were measured the pathogens before and after treatment. As to the side effects, one patient showed watery diarrhea, and another one showed the elevation of GOT. KS-R1 is considered to be a useful drug for the treatment of infection in children both clinically and bacteriologically.

Age Factors↗
PubMed1983

[Clinical efficacy of T-1982 (cefbuperazone) for infections of children].

T-1982 (cefbuperazone) was given at a daily dose of 42-80 mg/kg to 7 children with bacterial infections; 3 with bacterial intestinitis, 1 with bronchitis, 1 with tonsillitis and 2 with urinary tract infections. Clinical effectiveness was obtained in 6 cases, and the rate was 85.7%. Bacteriological responses were "disappeared" in 4 cases, "decreased" in 1 case and "unknown" in 2 cases. No noticeable side effects were observed except elevation of eosinophil in 1 case.

Anti-Bacterial Agents↗