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Biomedical subjects

K Yazawa

Publications and source records attributed to K Yazawa.

At least 55 records · Page 3Linked to original sources
PubMed1999

ADP-ribosylation as an intermediate step in inactivation of rifampin by a mycobacterial gene.

Mycobacterium smegmatis DSM43756 inactivates rifampin, and the inactivated antibiotic product recovered from culture medium was ribosylated on the 23-OH group. To study this process, the gene responsible for the inactivation was expressed at high levels by the lac promoter in Escherichia coli conferring resistance to >500 microg of antibiotic per ml. Cell homogenates generated a novel derivative designated RIP-TAs; in this study, we determined that RIP-TAs is 23-(O-ADP-ribosyl)rifampin. Our results indicated that RIP-TAs is an intermediate in the pathway leading to ribosylated rifampin and that the previously characterized gene encodes a mono(ADP-ribosyl)transferase which, however, shows no sequence similarity to other enzymes of this class.

ADP Ribose Transferases↗
PubMed1999

Protective effect of quinaprilat, an active metabolite of quinapril, on Ca2+-overload induced by lysophosphatidylcholine in isolated rat cardiomyocytes.

We examined the effects of quinaprilat, an active metabolite of quinapril (an angiotensin converting enzyme (ACE) inhibitor) on the increase in intracellular concentration of Ca2+ ([Ca2+]i) (Ca2+-overload) induced by lysophosphatidylcholine (LPC) in isolated rat cardiomyocytes. LPC (15 microM) produced Ca2+-overload with a change in cell-shape from rod to round. Quinaprilat but not quinapril at 20 or 50 microM attenuated the LPC-induced increase in [Ca2+]i and the change in cell-shape in a concentration-dependent manner. Since quinaprilat has an inhibitory action on ACE and quinapril has practically no inhibitory action on ACE, it is likely that the inhibitory action of quinaprilat on ACE is necessary for the protective effect of the drug against LPC-induced changes. We therefore examined the effects of enalapril (another ACE inhibitor with the weak inhibitory action on ACE) and enalaprilat (an active metabolite of enalapril with an inhibitory action on ACE) on the LPC-induced changes. Both enalapril and enalaprilat attenuated the LPC-induced Ca2+-overload, suggesting that the inhibitory action on ACE may not mainly contribute to the protective effect of ACE inhibitors against LPC-induced Ca2+-overload. This suggestion was supported by the fact that neither ACE (0.2 U/ml) nor angiotensin II (0.1-100 microM) increased [Ca2+]i in isolated cardiomyocytes. Furthermore, application of bradykinin (0.01-10 microM) did not enhance the protective effect of quinaprilat against LPC-induced changes. LPC also increased release of creatine kinase (CK) from the myocyte markedly, and quinaprilat but not quinapril attenuated the LPC-induced CK release. Unexpectedly, both enalapril and enalaprilat did not attenuate the LPC-induced CK release. Neither quinapril nor quinaprilat changed the critical micelle concentration of LPC, suggesting that these drugs do not directly bind to LPC. We conclude that quinaprilat attenuates the LPC-induced increase in [Ca2+]i, and that the protective effect of quinaprilat on the LPC-induced change may not be related to a decrease in angiotensin II production or an increase in bradykinin production.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Dietary effect of EPA-rich and DHA-rich fish oils on the immune function of Sprague-Dawley rats.

The dietary effect of fish oils (FOs) rich in eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on the immune function of Sprague-Dawley rats was compared with that of safflower oil. After 3 weeks of feeding at the 10% level of a dietary fat, the IgG and IgM production by splenocytes and IgG production by mesenteric lymph node (MLN) lymphocytes were significantly higher in the FO-fed rats, while no significant difference was found in IgA or IgE productivity by both the spleen and MLN lymphocytes. In the FO-fed rats, peritoneal exudate cells released a lower amount of LTB4, reflecting their lower arachidonic acid level, and a higher amount of LTB5, reflecting their higher EPA level in phospholipids. On these EPA-rich FO exerted a stronger effect than DHA-rich FO immune functions.

Adjuvants, Immunologic↗
PubMed1999

The effect of docosahexaenoic acid on plasma catecholamine concentrations and glucose tolerance during long-lasting psychological stress: a double-blind placebo-controlled study.

We previously found that docosahexaenoic acid (DHA) intake prevented aggression from increasing at times of mental stress. In the present study, we investigated whether DHA intake modified the plasma catecholamines and cortisol of medical students during a 9-wk period of final exams. We also investigated the effects of DHA intake on a 75 g oral glucose tolerance test (oGTT). Fourteen medical students participated in the present study. They were randomly allocated to either control or DHA group in a double-blind manner. Subjects in the control group (4 males and 3 females) took 10 control capsules/d, each capsule containing 280 mg of mixed plant oil, and those in the DHA group (4 males and 3 females) took 10 DHA capsules/d containing 1.5 g DHA for 9 wk, during which subjects underwent more than 20 stressful final exams. At the start and end of the study, plasma catecholamines (epinephrine, norepinephrine (NE) and dopamine) and cortisol were measured; a 75 g oGTT was also performed. There were no intra- or intergroup differences in plasma glucose concentrations. However, NE concentrations were significantly reduced after DHA administration (-31%, p < 0.03). The other catecholamines and cortisol did not change significantly. The plasma ratio of epinephrine to NE increased in every DHA subject (+78%, p < 0.02), and intergroup differences were significant (p < 0.03). We conclude that these effects of DHA may be applied to people under long-lasting psychological stress to prevent stress-related diseases.

Adult↗
PubMed1999

Brasilicardin A, a new terpenoid antibiotic from pathogenic Nocardia brasiliensis: fermentation, isolation and biological activity.

A novel tricyclic diterpenoid antibiotic, brasilicardin A, was isolated from the culture broth of Nocardia brasiliensis IFM 0406. The antibiotic exhibited immunosuppressive activity in a mouse mixed lymphocyte reaction (MLR) assay system and its IC50 value was 0.057 microg/ml. Although the inhibitory activity of cyclosporin A (CyA) against IL-2 production was confirmed in the MLR assay system, brasilicardin A did not have the activity. The results of in vitro toxicity testing of brasilicardin A against various human cell lines were compared with those of CyA.

Aminoglycosides↗
PubMed1999

[Long-term immunological study on postoperative adjuvant treatment with interferon-gamma in patients with renal cell carcinoma who underwent nephrectomy].

Previously, we reported the short-term immunological effects of postoperative adjuvant interferon-gamma (IFN-gamma) administration to renal cell carcinoma patients as determined by three-color flow cytometry. We now report the results of a long-term study on a larger number of subjects. Thirty-three patients with renal cell carcinoma received a prophylactic intramuscular injection of IFN-gamma (300 x 10(4) units per week) after nephrectomy. We evaluated immunological changes by measuring peripheral blood lymphocyte subsets including activated cytotoxic T lymphocytes (ACTL), cytotoxic T lymphocytes (CTL), activated suppressor T lymphocytes (ASTL), helper T lymphocytes (HTL), activated suppressor-inducer T lymphocytes (AITL), and suppressor-inducer T lymphocytes (SITL). We also estimated the natural killer (NK) activity by a cytolytic test. All 33 patients were examined for at least 12 months after the start of IFN-gamma injection, and 18 patients were examined for 30 months including the 6-month period following discontinuation of IFN-gamma injection. We found significant enhancement of the ACTL subset from the second week to the sixth month after the start of IFN-gamma injection. On the other hand, we found a significant decrease in the percentage of the HTL and SITL subsets for a long time after the start of injection. NK activity significantly increased throughout the period of administration, and it continued to increase for six months after discontinuation of IFN-gamma injection.

Adult↗
PubMed1999

[A case of juvenile retinoschisis diagnosed by analysis of the XLRS 1 gene].

BACKGROUND: We report on a 3 year-old boy who was first diagnosed with retinal detachment and macular hole and received surgical treatment. X-linked juvenile retinoschisis was determined by DNA analysis. CASE: Past or family history was not recognized. There was left macular hole but no typical spoke-like foveal retinoschisis was observed in either eye. We could not diagnose the case as X-linked juvenile retinoschisis because there was no family history of it, central foveal reflex was observed in right eye with corrected visual acuity of 1.2, and no abnormality was recorded in the electroretinogram. High molecular weight DNA was extracted from peripheral leukocytes, and the XLRS 1 gene was analyzed. Hemizygous missense mutation, Arg102Gln, was detected. We diagnosed the disease as X-linked juvenile retinoschisis because the Arg102Gln mutation was detected in a family in Germany, two families in the United Kingdom, and two families in the USA. CONCLUSION: XLRS 1 gene analysis is useful if the diagnosis is difficult clinically due to atypical clinical findings.

Child, Preschool↗
PubMed1999

[Relationship between hippocampal arachidonic acid content and induction of LTP in aged rats].

There are several lines of evidence indicating that membrane AA correlates with the ability of aged rats to sustain LTP. The age-related decrease in membrane AA seems to be triggered by increased lipid peroxidation, which is involved with the decline of LTP. The chronic treatment of DHA could decrease membrane AA without an increase in lipid peroxidation. We have thus investigated the effect of chronic treatment of DHA on hippocampal LTP to assess whether the decrease in membrane AA could directly affect the induction of LTP. The effects of daily supplementation of DHA for 3 months on membrane AA, LTP, and Ca2+ response were evaluated using hippocampal slices from 26-month-old Wistar rats. Chronic treatment of DHA reduced the hippocampal AA significantly, but did not change the amplitude of LTP. Neither 30 mM K+ nor 500 microM NMDA-induced Ca2+ response was affected by chronic treatment of DHA, while the 500 microM carbachol-induced Ca2+ response was reduced. From these results, the reduction of membrane AA might suppress the carbachol-induced Ca2+ response by inhibiting the muscarinic receptor function, IP3 formation and/or Ca2+ release from Ca2+ stores by IP3. However, the reduction of membrane AA is not likely to be a main causal factor of the decline of LTP.

Aging↗
PubMed1998

New platelet fibrinogen receptor glycoprotein IIb-IIIa antagonists: orally active series of N-alkylated amidines with a 6,6-bicyclic template.

The design, synthesis, and pharmacological evaluation of (S)-(-)-ethyl [6-[4-(morpholinoformimidoyl)benzamido]-3, 4-dihydro-2H-1-benzopyran-3-yl]acetate hydrochloride ((S)-4.HCl, MS-180), an orally active glycoprotein IIb-IIIa (GPIIb-IIIa) antagonist, are reported. Pharmacophore mapping of amidino and carboxyl groups of already known GPIIb-IIIa antagonists led to the synthesis of nine amidino acids containing 6,6-bicyclic ring skeletons (10a-i). Among them, the compounds 10a,c,e having an amide bond and 1,2,3,4-tetrahydronaphthalene or 3, 4-dihydro-2H-1-benzopyran skeleton showed marked inhibitions with IC50 values of 46-57 nM in human platelet aggregation assay in vitro, but low oral activities. N-Alkylation of the amidino group coupled with the ester prodrug approach afforded MS-180 ((S)-4.HCl), which generates in vivo the corresponding carboxylic acid (S)-3 as an active species. In vitro, (S)-3 inhibited ADP-induced aggregation of guinea pig, dog, and human platelets (IC50 = 110, 253, and 35 nM, respectively) and inhibited the binding of fibrinogen to immobilized GPIIb-IIIa of human platelets (IC50 = 0.12 nM). After oral administration of MS-180 ((S)-4.HCl) to fasted beagle dog, ex vivo inhibition of platelet aggregation was observed. The maximal inhibitions were observed 2-4 h after dosing with dose dependency (60% inhibition at a dose of 1 mg/kg, 85% at 3 mg/kg, and 100% at 10 mg/kg, respectively) and the extent of the inhibitions paralleled the plasma concentration of the active species (S)-3. On the basis of these studies, we selected MS-180 ((S)-4.HCl) as a candidate for clinical evaluation as a drug for the treatment and prevention of thrombosis in patients.

Acetates↗
PubMed1998

1a-docosahexaenoyl mitomycin C: a novel inhibitor of protein tyrosine kinase.

A series of derivatives of mitomycin C conjugated with various fatty acids at position 1a was synthesized and the effect of these compounds on protein kinase activities was evaluated. 1a-Docosahexaenoyl mitomycin C (DMMC) selectively inhibited protein tyrosine kinase (PTK) activity in the postnuclear fraction of v-src-transformed NIH 3T3 cells although neither derivatives conjugated with other fatty acids or docosahexaenoic acid or mitomycin C did not. DMMC inhibited the activity of calmodulin-dependent kinase III and protein kinase A very weakly, and only barely affected protein kinase C activity. DMMC also attenuated autophosphorylation of immunoprecipitated p60v-src irreversibly. The addition of thiol compounds to the reaction mixture reversed the inhibition by DMMC, suggesting that some thiol moiety of PTK protein might be involved. DMMC also inhibited kinase activity of p210bcr-abl immunoprecipitated from the lysate of K562 cells. These results indicate that DMMC is a novel inhibitor of PTK.

3T3 Cells↗
PubMed1998

Multiple carcinoids of the duodenum accompanied by type I familial multiple endocrine neoplasia.

A case of multiple carcinoid tumors of the duodenum accompanied by familial multiple endocrine neoplasia is reported. A 46-year-old man with duodenal polyps discovered during a mass screening was followed up for 5 years. In August 1994, a histological examination revealed carcinoid tumors, and he was thus referred to our hospital for surgery. He underwent a parathyroidectomy and cholecystectomy for primary hyperparathyroidism and cholecystolithiasis, respectively. The patient's sister had also undergone a parathyroidectomy and distal pancreatectomy for primary hyperparathyroidism and insulinoma of the pancreas. In addition, his two children were also followed up for hypercalcemia. A serum examination of the patient revealed high levels of somatostatin and pancreatic polypeptide, but normal levels of gastrin and serotonin. In November 1994, a pancreaticoduodenectomy with a D2 lymph node dissection was performed. The macroscopic findings of the resected specimen showed multiple polypoid lesions with delles on the top, measuring 3 to 15 mm in size throughout the duodenum. A microscopic examination revealed the tumor to have infiltrated into the submucosa extensively, and an immunohistochemical analysis also demonstrated the tumor cells to be positive for somatostatin, but not for pancreatic polypeptide. After surgery, the serum level of somatostatin returned to normal but the pancreatic polypeptide remained high. The post-operative course was uneventful, and the patient remains in good health.

Carcinoid Tumor↗
PubMed1998

Docosahexaenoic acid does not affect aggression of normal volunteers under nonstressful conditions. A randomized, placebo-controlled, double-blind study.

We previously found that docosahexaenoic acid (DHA) intake prevents aggression enhancement at times of mental stress. In the present study we investigated changes in aggression under nonstressful conditions. Forty-six students of two universities took either DHA-rich fish oil capsules containing 1.5 g DHA (DHA group: 13 males and 9 females) or control oil capsules containing 97% soybean oil plus 3% of another fish oil (control group: 11 males and 13 females) for 3 mon in a double-blind fashion. At the start and end of the study they took an aggression-estimating test (P-F Study) without a stressor component. DHA (5.9 to 8.5%, P < 0.001) and eicosapentaenoic acid (0.7 to 1.5%, P < 0.001) increased in red blood cell phospholipids in the DHA group, while linoleic acid increased slightly (8.3 to 9.1%, P < 0.002) in the soybean oil control group. In the control group, measured aggression levels decreased from 34.8 to 29.4% (P < 0.005), whereas they remained stable in the DHA group (33.5 to 33.8%). The intergroup differences (-5.4 vs. 0.3%) were marginally significant (P < or = 0.05). Aggression levels were stable in the DHA group whether there was stressor (as previously shown) or not. This effect of DHA appears to be interesting, considering the reported association between a low intake of n-3 fatty acids and depression.

Adult↗
PubMed1998

A new approach to the development of anti-ischemic drugs: protective drugs against cell injury induced by lysophosphatidylcholine.

Recent studies have revealed that lysophosphatidylcholine (LPC) produces mechanical and metabolic derangements in perfused working rat hearts and Ca2+-overload in isolated cardiac myocytes. Thus, LPC possesses an ischemia-like effect on the heart. Therefore, a drug that possesses an anti-LPC action would protect or improve ischemia/reperfusion damage. We examined the effects of various anti-ischemic drugs on the Ca2+ overload induced by LPC. Our data suggest that a drug with high lipophilicity possesses a protective effect on cell injury induced by LPC, probably because of preservation of membrane integrity.

Adrenergic beta-Antagonists↗