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Biomedical subjects

K Wada

Publications and source records attributed to K Wada.

At least 397 records · Page 22Linked to original sources
PubMed1995

Proteoglycan synthesis by corneal explants from developing embryonic chicken.

Proteoglycan biosynthesis in developing chicken corneas was studied. Corneas free of scleral rims were prepared from 5- to 18-day-old chick embryos and labeled in vitro with [3H]glucosamine and [35S]sulfate. Then, the labeled medium and corneal proteoglycans were analyzed. Day 5 corneas synthesized mainly chondroitin sulfate/dermatan sulfate proteoglycan and a sudden increase in keratan sulfate proteoglycan synthesis was found on Day 7. Keratan sulfate proteoglycan in Day 7 cornea appeared to be synthesized by fibroblasts which invaded the stroma between Day 5 and Day 7. The proportion of keratan sulfate proteoglycan synthesis increased with advancing embryonic age until Day 14 and declined a little on Day 18. The relative proportion of chondroitin sulfate/dermatan sulfate proteoglycan synthesis changed in a reverse curve during Day 7 to Day 18. Because embryonic cornea begins to become transparent on Day 14, this change in proteoglycan synthesis may be correlated with the onset of transparency. The labeled glycosaminoglycans were isolated from cultured embryonic corneas by pronase digestion, and then digested with chondroitinase ABC or keratanase II. Disaccharides in the enzymatic digests were analyzed by HPLC, and the extents and positions of sulfation of proteoglycans were determined. Sulfation of keratan sulfate proteoglycan continued to increase with advancing age until Day 18. Moreover, it has been shown by HPLC of unsaturated disaccharides of chondroitinase ABC digests that, whereas a comparable amount of non-sulfated "chondroitin sulfate/dermatan sulfate" was synthesized during Day 7 to Day 9, its amount declined during late development (Day 12 to Day 18). Such increases in sulfation of proteoglycans with advancing age may be correlated with progress of corneal transparency, which begins on Day 14 and continues until hatching. Analysis of proteoglycans of the culture medium has shown that most of the medium proteoglycans were keratan sulfate proteoglycan and free keratan sulfate chain (or keratan sulfate chain with a short peptide) during all ages after Day 7, although the major proteoglycan of Day 5 medium was chondroitin sulfate/dermatan sulfate proteoglycan. Sulfation of medium keratan sulfate also increased with advancing age. In addition, the proportion of free keratan sulfate chain in the medium increased during late corneal development, suggesting that catabolism of keratan sulfate proteoglycan might be preferentially accelerated during those times.

Animals↗
PubMed1995

Changes in c-Kit expression and effects of SCF during differentiation of human erythroid progenitor cells.

We analysed c-Kit expression during erythroid differentiation using immunocytochemical staining and flow cytometric analysis. Burst-forming units-erythroid (BFU-E)-derived cell aggregates were identified in methylcellulose cultures containing human umbilical cord blood CD34+ cells and were stained by the indirect immunoalkaline phosphatase method. To investigate the changes in levels of cell-surface c-Kit expression, we subjected progenitor cells in liquid culture to flow cytometric analysis. In addition, the effects of stem cell factor (SCF) on cell-surface c-Kit expression were analysed in these two culture systems and the effects of SCF on erythroid colony formation were studied in a methylcellulose culture. c-Kit was expressed on the cell surface from BFU-E to erythroid precursors recognized morphologically as basophilic erythroblasts. Flow cytometric analysis showed that c-Kit expression increased until 6 d in liquid culture, and that decreased expression of c-Kit was associated with the increased expression of glycophorin A. Moreover, SCF increased the size of erythroid colonies when added at days 0, 4 and 8 in methylcellulose cultures. These results indicate that the c-Kit/SCF system still plays in proliferation of erythroid progenitor cells at the colony-forming units-erythroid stage. Finally, expression of c-Kit in erythroid progenitor cells cultured without SCF showed a diffuse pattern on the cell surface, whereas we observed positive c-Kit immunoreactivity in the region of the Golgi apparatus of these cells cultured with SCF. Flow cytometric analysis also showed that the levels of cell-surface c-Kit expression decreased in the presence of SCF. These results suggest that SCF induced down-modulation of cell-surface c-Kit expression, despite continuous synthesis of c-Kit protein.

Cell Adhesion Molecules↗
PubMed1995

Antithrombotic effect of a novel recombinant hirudin analogue, CX-397, in a rat arterial thrombosis model.

1. The antithrombotic effect of a new specific thrombin inhibitor, CX-397, was examined in a photochemically-induced arterial thrombosis model in the rat femoral artery and compared with that of heparin. 2. Pretreatment with CX-397 (10, 20 and 40 micrograms kg-1 min-1, i.v.) from 15 min before the experiment prolonged the time required for thrombotic occlusion of the artery in a dose-dependent manner. The antithrombotic efficacy of CX-397 was associated with modest increases in activated partial thromboplastin time (APTT) and template bleeding time. 3. On the other hand, heparin at a dose of 450 micrograms kg-1 markedly prolonged APTT and the bleeding time, but did not inhibit thrombo-occlusion. 4. CX-397 selectively inhibited platelet aggregation and concurrent secretion of 5-hydroxytryptamine (5-HT) and thromboxane A2 (TXA2) production from platelets in response to thrombin, but not to collagen and ADP, in a dose-dependent manner (5-100 ng ml-1). 5. CX-397 at 10 micrograms kg-1 combined with vapiprost, a TXA2 receptor antagonist, at 0.1 mg kg-1 significantly prevented occlusion, whereas, at these doses, neither drug alone had much effect. 6. These results demonstrate that CX-397 may prove to be more efficient for preventing platelet-rich thrombosis than heparin. Thrombin may play an important role in the rat thrombosis model. 7. The additive antithrombotic effect of the combination of thrombin inhibitor and TXA2 receptor antagonist at low doses suggests that thrombin and TXA2 may work in concert to produce thrombosis.

Animals↗
PubMed1995

[A trial of clinical application of sparfloxacin for treating mycobacterial infections].

Sparfloxacin seems to be a good candidate for antimycobacterial treatment. However, there have been no clinical studies. We experienced 2 SPFX-treated cases, who could not use other antimycobacterial agents because of side effect, we tried SPFX-treatment on these cases. Good results were obtained, however, for long time use to prevent side effects, we tried SPFX every second day and monitored the serum levels of SPFX. SPFX-every second day treatment gave good clinical results and adequate serum levels of SPFX were observed.

Aged↗
PubMed1995

Differential effects of geometrical isomers of octadecadienoic acids on ketogenesis and lipid secretion in the livers from rats fed a cholesterol-enriched diet.

The effect of cis,cis (cc)- and trans,trans (tt)-9,12-octadecadienoic (18:2) acids on ketogenesis and lipid secretion was compared in isolated perfused livers from cholesterol-fed rats. The hepatic uptake of 18:2 acids was comparable in both isomers. The livers perfused with cc-18:2 acid in comparison with those perfused without fatty acid substrate produced approximately 4-fold more ketone bodies accompanying the rise of the beta-hydroxybutyrate:acetoacetate ratio, while the tt-acid isomer further increased these parameters. The hepatic secretion rates of triglyceride and phospholipid as well as cholesterol were all elevated on perfusing the cc-18:2 acid as compared to without fatty acid. In contrast, the rates observed with the tt-18:2 acid isomer except for phospholipid were intermediate, indicating a reciprocal response in ketogenesis and lipid secretion by the trans isomer. The rate of incorporation of trans-fatty acid into perfusate triglyceride and cholesterol ester were lower than cis-acid, but vice versa into perfusate phospholipids. On the other hand, the effects of trans-fatty acid on the concentration and composition of hepatic lipids were less clear. These results emphasize the differential effect of geometrical isomers of the 18:2 acids on oxidation and esterification even in the livers containing a high level of cholesterol.

3-Hydroxybutyric Acid↗
PubMed1995

Columbin isolated from calumbae radix affects the sleeping time of anesthetized mice.

In a screening series of bioactive components in edible and medicinal plants, we found that Calumbae Radix (Colombo root, 1% powdered feed, for 5 d) and its component, columbin (20-40 mg/kg/d, for 5 d, orally), shortened the sleeping time induced by a urethane and alpha-chloralose mixture and prolonged the sleeping time induced by hexobarbital in mice.

Anesthesia↗
PubMed1995

Thromboxane A2 synthetase inhibitors with histamine H1-blocking activity: synthesis and evaluation of a new series of indole derivatives.

A novel series of N-substituted 3-(1H-imidazol-1-ylmethyl)indole carboxylic acid derivatives were prepared and evaluated for thromboxane A2 (TXA2) synthetase-inhibitory and histaminergic H1-blocking activity. Among the compounds synthesized, indole-6-carboxylic acid derivatives showed higher activities than the other positional isomers of carboxylic acid. 1-[3-(4-Benzhydryl-1-piperazinyl)propyl]-3-(1H-imidazol-1-ylmethyl )-1H-indole-6-carboxylic acid (12) had the strongest thromboxane synthetase inhibitory activity (IC50 = 5 x 10(-8) M) and H1-blocking activity (IC50 = 8 x 10(-9) M).

Animals↗
PubMed1995

Selective use of L-valine and L-isoleucine for the biosynthesis of branched-chain fatty acids in rat skin.

Iso- and anteiso-fatty acids are detected in more than trace amounts in rat skin surface lipid. The terminal portion of even carbon number iso- and anteiso-fatty acids are synthesized respectively from valine (Val) and isoleucine (Ile) by essentially the same reaction sequences established for straight chain fatty acids. This paper describes the stereospecific biosynthesis of these branched chain fatty acids (BCFAs) and alcohols (BCFALs) in rat skin. Dependence of the concentration of these BCFAs on dietary L-Val and L-Ile was studied. Concentrations of even carbon number iso- and anteiso-fatty acid increased respectively with dietary L-Val and L-Ile. The saturation dose appeared to be 2% for L-Val and 1% for L-Ile. Supplementation of the diet with 2% D-Val, however, did not affect the concentration of even carbon number iso-fatty acid in rat skin surface lipid despite a comparable serum Val level to that of the 2% L-Val group. A similar experiment using 1% DL-Ile found that L-isomer, but not D-isomer, in the circulation was used for the biosynthesis of anteiso-fatty acids. This view was applicable to the incorporation of D-Val and DL-Ile into related BCFALs.

Absorption↗
PubMed1995

Isolation of Salmonella typhimurium from zebra finches (Poephila guttata).

Salmonella Typhimurium was isolated from a fresh fecal sample of zebra finches (Poephila guttata) in December 1992 on an aviary where a large scale outbreak of S. Typhimurium infection among bengalees (a variety of Lonchura striata) in 1991 had been recorded. The isolates from zebra finches were examined for antibiotic sensitivity and plasmids, which were 60 Mdal, then they showed the same pattern as those of S. Typhimurium isolated at the previous outbreak. This is the first report of S. Typhimurium isolation from zebra finches.

Animals↗
PubMed1995

Pneumatosis cystoides intestinalis after chemotherapy for hematological malignancies: report of 4 cases.

Pneumatosis cystoides intestinalis (PCI) is known to be a relatively rare condition which is characterized by gas cysts in the gastrointestinal mucosa. We treated four cases of PCI accompanied by hematological malignancies during chemotherapy treatment. All cases suffered from abdominal discomfort. Abdominal X-ray films revealed gas cysts in the intestine. PCI was observed during leukocytopenic states, and three cases had septicemia. Etoposide was administered to three cases, and prednisolone to all cases. It is considered that PCI sometimes occurs in patients with hematological malignancies during a period of leukocytopenia, and may be caused by intestinal mucosal damage due to myelosuppressive agents and immunosuppression from prednisolone.

Adult↗
PubMed1995

Comparison of antithrombotic effects of GPIIb-IIIa receptor antagonist and TXA2 receptor antagonist in the guinea-pig thrombosis model: possible role of TXA2 in reocclusion after thrombolysis.

The effects of Ro 44-9883, a new specific antagonist of platelet glycoprotein IIb-IIIa receptor, on thrombus formation and reocclusion after thrombolysis induced by tissue-type plasminogen activator (t-PA) were compared with those of vapiprost, a thromboxane (TX) A2 receptor antagonist, using a photochemically-induced thrombosis model in the guinea-pig femoral artery. Pretreatment with Ro 44-9883 (5, 10 and 20 micrograms/kg/min, i.v.) prolonged the time required to occlude the artery in a dose-dependent manner. Ro 44-9883 at 10 and 20 micrograms/kg/min significantly inhibited ex vivo platelet aggregation in whole blood induced by collagen, ADP or U46619. Vapiprost 0.3 mg/kg inhibited thrombus formation and platelet aggregation induced by collagen or U46619, to the same extent as Ro 44-9883 at the higher doses. In the thrombolysis study, Ro 44-9883 at the higher doses given as comedication with t-PA reduced the time to achieve reperfusion and increased the vascular patency after successful reperfusion. Vapiprost also significantly reduced the time to reperfusion and prevented reocclusion. However, the vascular patency after thrombolysis by t-PA with vapiprost was significantly increased compared with Ro 44-9883. Ro 44-9883 inhibited platelet aggregation, but did not prevent TXA2 formation in platelets. Thus, vascular contraction mediated by platelet-derived TXA2 may be responsible for lower efficacy of Ro 44-9883 against reocclusion compared with vapiprost. These results indicate that not only platelet aggregation but also vasoconstriction may contribute to reocclusion after t-PA-induced thrombolysis in the guinea-pig.

Acetates↗
PubMed1995

Effects of the novel water-soluble calcium antagonist (+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride on the responses of isolated canine arteries.

The effects of NKY-722 ((+/-)-3-(4-allyl-1-piperazinyl)-2,2-dimethylpropyl methyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate dihydrochloride, CAS 117241-46-0), a new water soluble dihydropyridine derivative on the responses of isolated canine arteries were examined. NKY-722 (IC50: 5-16 x 10(-10) mol/l), nicardipine (IC50: 5-10 x 10(-10) mol/l) and nifedipine (IC50: 44-195 x 10(-10) mol/l) relaxed four arteries in the potency order of basilar > coronary > mesenteric > intrarenal arteries. NKY-722 was nearly equipotent to nicardipine and about 10 times more potent than nifedipine. [3H]NKY-722 was accumulated in the four arteries in the same order of amount as the vasoinhibitory effect. All three drugs inhibited the contraction induced by Ca2+ and methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylophenyl)-p yri dine-5- carboxylate (Bay K 8644) in the mesenteric arteries, indicating their Ca2+ antagonistic actions. NKY-722 and nicardipine were nearly equipotent and about 100 times more potent than nifedipine on the Ca(2+)-induced contraction and was about 4 times more potent than nicardipine and 400 times more potent than nifedipine on the Bay K 8644-induced contraction. NKY-722, nicardipine and nifedipine relaxed the mesenteric arteries precontracted with KCl by more than 90%, while they relaxed the arteries contracted with PGF2 alpha, 9,11-dideoxy-9 alpha, 11 alpha-methanoepoxy-PGF2 alpha (U-46619) and endothelin-1 only by 40-70%. The IC50 values of NKY-722 and nicardipine were similar and much smaller than that of nifedipine for all four contracting agents.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

[Allogenic bone marrow transplantation for Fanconi's anemia with leukemic transformation from an HLA identical father].

We report a case of a 19-year-old male with congenital aplastic anemia and multiple abnormalities; short stature, hypoplastic thumb, skin pigmentation and mental retardation. He was admitted to our hospital because of severe pancytopenia. Bone marrow aspiration showed markedly hypocellular marrow with 42% myeloblasts. He was diagnosed as AML (M2) transformed from Fanconi's anemia and underwent allo-BMT from an HLA-identical father. The conditioning regimen consisted of high dose Ara-C, high dose etoposide and 12Gy fractionated total body irradiation. Severe toxicity associated with the conditioning regimen was not observed. Cyclosporin A and short-term methotrexate were administered for prophylaxis of acute GVHD. Neither acute nor chronic GVHD were observed. He is well and free of disease for 15 months since BMT. Very few cases of Fanconi's anemia with leukemic transformation treated by BMT have been reported. Long-term observation will be necessary to evaluate our conditioning regimen for Fanconi's anemia with leukemic transformation.

Adult↗
PubMed1995

[Usefulness of adjuvant chemotherapy with antimetabolites for cervical invasive cancer].

A series of 584 patients with cervical invasive cancer were included in the retrospective study on the efficacy of long-term oral maintenance chemotherapy with antimetabolites (Fluorouracil or Tegaful). The patients were histologically classified into the squamous cell carcinoma (SCC) group and the adenocarcinoma (AD) group. In the SCC group (n = 518), 163 patients were given more than 300 mg/day of antimetabolite tablets for one year or more after the main therapy (hysterectomy or pelvic irradiation). In the AD group (n = 66), 36 patients were treated with the same dose of antimetabolites. The Kaplan-Meier overall and cancer specific survival analysis estimates that the chronic administration of antimetabolites did not improve the cumulative 5-year survival in the SCC group. In contrast, the cumulative 5-year survival rate in the AD group treated with antimetabolites (88%) was significantly higher than that without chemotherapy (64%) by Kaplan-Meier analysis. This significant improvement in the survival rate in the AD group due to antimetabolites was notable in patients in FIGO stage I or II treated with radical or semiradical hysterectomy, these results indicate that oral adjuvant chemotherapy with antimetabolites is useful for cervical adenocarcinoma, but not for squamous cell carcinoma.

Adenocarcinoma↗
PubMed1995

[Chemosensitivity test with endoscopic biopsy specimens].

In SDI test using tetrazolium salt, we compared MTT with XTT, which has been recently developed and is more sensitive than MTT. Further, a chemosensitivity test with endoscopic biopsy specimens using XTT was conducted. The reproducibility of the MTT assay was assessed under various conditions. The I.I of MTT assay did not vary according to type or concentration of anticancer drugs and the biopsy site of specimens. Then MTT and XTT assay were compared, revealing the results of these 2 assays were significantly correlated. Thus, XTT assay was performed with tissues from surgical specimens using biotome. Of the 16 specimens subjected to XTT assay, 6 showed an OD value of 0.100 or more, which was well within assessment. XTT assay was also performed in biopsy specimens from patients using a biotome manipulated under endoscopic guidance before operation. Three among 6 specimens showed an OD value of 0.100 or more. Our findings have demonstrated that the SDI test using XTT can be used for the chemosensitivity test, even when these specimens contain a relatively small number of cells collected using a biotome.

Animals↗