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Biomedical subjects

W Tanaka

Publications and source records attributed to W Tanaka.

33 records · Page 2Linked to original sources
PubMed1993

High-performance liquid chromatographic determination of PZ-peptidase activity.

A rapid and sensitive assay method for the determination of PZ-peptidase activity is reported. This method is based on the monitoring of the absorption at 320 nm of 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu (PZ-Pro-Leu), enzymatically formed from the substrate 4-phenylazobenzyloxycarbonyl-L-Pro-L-Leu-Gly-L-Pro-D-Arg (PZ-peptide), after separation by high-performance liquid chromatography using a C18 reversed-phase column by isocratic elution. This method is sensitive enough to measure PZ-Pro-Leu at levels as low as 10 pmol, yields highly reproducible results and requires less than 5.5 min per sample for separation and determination. The optimum pH for PZ-peptidase activity was 7.5-8.0. The Km and Vmax values were 166.7 microM and 5.35 pmol/min.microgram protein, respectively, with the use of enzyme extract obtained from mouse whole brain. The approximate molecular mass of this enzyme was estimated to be 64,000 by gel filtration. PZ-peptidase activity was strongly inhibited by Zn2+, Cu2+ and p-chloromercuriphenylsulphonic acid. By using this method, PZ-peptidase activity could be readily detected in a single mouse pituitary gland. Among the tissues examined in various mouse brain regions, the highest specific activity of the enzyme was found in cerebral cortex. The sensitivity and selectivity of this method will aid in efforts to examine the physiological role of this peptidase.

Amino Acid Sequence↗
PubMed1993

Biochemical activity, pharmacokinetics, and tolerability of MK-886, a leukotriene biosynthesis inhibitor, in humans.

MK-886, a leukotriene biosynthesis inhibitor, was evaluated in double-blind, placebo-controlled, randomized single- and multiple-dose studies in 12 and 24 healthy male subjects, respectively. The effects of a single dose (250, 500, and 750 mg) and multiple doses (100 mg and 250 mg every 8 hours) of MK-886 on calcium ionophore stimulated leukotriene B4 synthesis ex vivo in whole blood were evaluated. Inhibition of leukotriene B4 biosynthesis ex vivo occurred in a dose-related manner up to a 500 mg single dose, and 250 mg every 8 hours. A single dose of 500 mg MK-886 significantly inhibited leukotriene B4 biosynthesis by a maximum of 60% at 2 hours after the dose (p < 0.05). Multiple doses of 250 mg significantly inhibited leukotriene B4 biosynthesis by a maximum of 52% at 2 hours after the dose (p < 0.05). The degree of leukotriene B4 inhibition ex vivo in whole blood significantly correlated with plasma MK-886 concentrations (r = 0.78). In conclusion, the single and multiple doses of MK-886 evaluated in this study were well tolerated overall and partially inhibited leukotriene B4 biosynthesis ex vivo in whole blood.

Administration, Oral↗
PubMed1993

Effects of losartan on blood pressure, plasma renin activity, and angiotensin II in volunteers.

Losartan is an orally active, nonpeptide angiotensin II (Ang II) (site-1) receptor antagonist. We conducted a multiple-dose study in healthy male volunteers to investigate the tolerability, blood pressure effects, and changes in plasma renin activity (PRA) and plasma Ang II concentration associated with once-daily administration of 100 mg losartan for a week. Subjects were studied on a standardized sodium diet (24-hour urinary sodium excretion, 98 +/- 37 [SD] mEq per 24 hours on the placebo run-in day). Measurements of blood pressure, heart rate, PRA, Ang II, and aldosterone were taken during a placebo run-in day and after single and multiple (7 days) daily doses of losartan (100 mg, n = 10) or placebo (n = 4). Ang II was measured specifically by high performance liquid chromatography coupled with radioimmunoassay. In subjects given losartan, respective decreases (systolic/diastolic) from run-in in supine blood pressure 6 hours after dosing were (mean +/- SD), compared with the placebo run-in day, first dose: -8.8 +/- 9.6/-6.8 +/- 5.0, last dose: -11.6 +/- 8.9/-7.0 +/- 4.8 mm Hg (p < 0.05 for all changes). At this 6-hour time point, corresponding increases from run-in in PRA were from 1.2 +/- 0.6 to 12.0 +/- 6.3 (first dose) and 9.6 +/- 4.9 (last dose) ng angiotensin I per milliliter per hour and in Ang II were from 4.3 +/- 1.7 to 72.4 +/- 33.3 and 45.7 +/- 14.1 pg/mL. All changes in PRA and Ang II were statistically significant within the losartan-treated group, and the biochemical changes were significantly greater than those in the placebo-treated group. The increment in Ang II was less after the last dose than after the first (p < 0.05). The drug was well tolerated by all subjects. These data indicate that, under the conditions of this study, losartan administration (100 mg/day for eight doses over 9 days) results in treatment-related decreases in blood pressure and increases in PRA and Ang II octapeptide.

Adolescent↗
PubMed1993

Oral leukotriene inhibitor (MK-886) blocks allergen-induced airway responses.

To elucidate the role of leukotrienes (LT) in allergic asthma in humans the effect of MK-886, an LT biosynthesis inhibitor, was evaluated on antigen-induced early (EAR) and late (LAR) asthmatic reactions and bronchial responsiveness to histamine. Eight atopic men participated in a two-part, double-blind, placebo-controlled, crossover trial. MK-886 was administered in two oral doses of 500 mg and 250 mg, 1 h before and 2 h after allergen inhalation, respectively. Biochemical effects of MK-886 were evaluated by the inhibition of urinary LTE4 excretion and calcium ionophore-stimulated LTB4 biosynthesis in whole blood ex vivo. MK-886 significantly inhibited the EAR by 58.4% (AUC0-3 h) and the LAR by 43.6% (AUC3-7 h) when compared with placebo (p < 0.01). There was no difference in PC20 histamine 30 h post allergen challenge between MK-886 and placebo (0.33 and 0.27 doubling doses, p > 0.1). MK-886 inhibited calcium ionophore-stimulated LTB4 production in whole blood (54.2 +/- 25.6%) for up to 6 h post allergen challenge. LTE4 excretion in urine was inhibited by 51.5% during the EAR by as much as 80% during the LAR. This indicates that LT play a role in allergen-induced asthmatic reactions in humans in vivo and that LT synthesis inhibitors such as MK-886 should be further explored for the treatment of asthma.

Administration, Oral↗
PubMed1993

Dynamics of normal and injured human liver regeneration after hepatectomy as assessed on the basis of computed tomography and liver function.

We compared liver volume and function kinetics after partial hepatectomy according to extent of resection and severity of coexisting liver disease in 57 adults with uneventful postoperative courses. Liver volume and massiveness of resection, or resection rate, were estimated on computed tomography. Patients were categorized into three groups on the basis of reaction rate: small (< 30%), medium (30%-50%) and large (> 50%). The regenerative patterns of normal livers in the medium and large groups consisted of three phases: a rapid increase during the first month, some decrease in the second month and a final, slower increase. This contrasted with the pattern of injured livers with chronic hepatitis or cirrhosis, which generally showed a phase of less rapid, gradual increase. The regeneration rate (volume gain, cm3/day) during the first month was found to be proportional to resection rate in the presence or absence of liver disease. Normal livers regenerated at least twice as rapidly as injured livers in patients with comparable resection rates. Normal livers reached plateau levels within 1 to 2 mo regardless of the massiveness of resection, whereas regeneration took 3 to 5 mo in injured livers. Liver function (albumin, bilirubin) recovered concomitantly with liver volume in the medium group, whereas in the large group they generally returned to their initial values behind volume restoration, particularly in cirrhotic patients. In conclusion, human liver regeneration is strongly influenced by the massiveness of the resection and presence of coexisting liver disease. However, we found that some cirrhotic livers can regenerate, albeit more slowly and less completely, as long as the extent of hepatectomy remains within safe functional limits.

Adult↗
PubMed1991

Clinical and biochemical effects of an oral leukotriene biosynthesis inhibitor (MK886) in psoriasis.

Antipsoriatic agents have been shown to decrease skin levels of arachidonic acid and its metabolites including 12-monohydroxy-eicosatetranoic acid (12-HETE), and leukotriene B4 (LTB4). In addition, specific systemic and topical lipoxygenase inhibitors have been reported to be effective in the treatment of psoriasis. The objective of this study was to investigate the effect of a potent oral leukotriene biosynthesis inhibitor (MK886) in patients with chronic plaque psoriasis. Clinical response together with the changes of LTB4 levels in lesional skin biopsy specimens, and urinary leukotriene E4 (LTE4) excretion were evaluated. In addition, markers of inflammation, proliferation and keratinization were studied immunohistochemically. No change in clinical scores or lesional LTB4 levels were observed with a 10 1/3-day course of MK886. A statistically significant reduction in urinary LTE4 excretion was observed: mean LTE4 (ng/h) were 5.14 before treatment and 1.51 on day 11 with MK886; and 7.55 before treatment and 6.57 on day 11 with placebo treatment. Epidermal accumulation of polymorphonuclear leukocytes (PMN) tended to diminish in the MK886 treatment group. These results indicate that although a reduction (greater than 70%) in urinary LTE4 excretion was found, and a slight decrease of epidermal PMN accumulation was observed, no correlative changes in clinical scores or LTB4 levels in skin lesion were found with a short course of MK886.

Administration, Oral↗
PubMed1986

Assay of plasma leupeptin using the reversible binding of leupeptin to bovine pancreatic trypsin.

A competitive binding radioassay for leupeptin has been developed utilizing the reversible binding of leupeptin to bovine pancreatic trypsin. An ethanol precipitation step was introduced to separate trypsin-bound leupeptin from its free form. Advantages of this method are simplicity of the procedure and avoidance of the preparation of antiserum. The possible metabolites of leupeptin exhibit no significant inhibitory effect on leupeptin-trypsin binding in this system. This method was applied to the determination of plasma leupeptin levels in dogs after oral administration of the peptide.

Animals↗
PubMed1985

Mitogenic potentials of bestatin, amastatin, arphamenines A and B, FK-156 and FK-565 on spleen lymphocytes.

The following aminopeptidase (AP) activities were found to be associated with the surface of mouse spleen cells: Leu-AP (138 pmol/10(5) cells X minute) and AP-B (16 pmol/10(5) cells X minute with Lys-beta-naphthylamide as substrate and 21 pmol/10(5) cells X minute with Arg-beta-naphthylamide substrate); AP-A activity was not detected by the assay system applied. The immunoactive peptide bestatin inhibited the Leu-AP, while AP-B activity decreased in the presence of both arphamenines A and B and bestatin. No effects on these enzymes were caused by amastatin (an AP-A inhibitor), FK-156, FK-565 and Bu-2743E; the latter peptide turned out to be not an inhibitor of cell surface associated microsomal Leu-AP but an inhibitor of cytosolic Leu-AP. The immunoactive peptides bestatin, arphamenines A and B, and amastatin increased [3H]thymidine incorporation into spleen cells containing lymphocytes and macrophages. These mitogenic actions were not observed when macrophages were removed from the cultures or the cells had been stimulated with ConA or LPS. The lactoyl- and heptanoyl peptides FK-156 and FK-565 caused a mitogenic action on lymphocytes independently of the presence of macrophages. The inhibitor of cytosolic Leu-AP did not change the incorporation into lymphocytes.

Adjuvants, Immunologic↗
PubMed1981

On the mutagenicity and immunogenicity of a beta-propiolactone-treated therapeutic IgG-preparation.

During the production of Intraglobin, an i.v. tolerable IgG-immunoglobulin preparation, fraction Cohn II is treated with beta-propiolactone. Thereby the IgG-molecules are chemically modified thus preventing an increase in secondary aggregates which could give rise to adverse reactions in the patients treated with the IgG-preparation. The safety tests described here neither showed any evidence for the presence of unhydrolysed mutagenic-beta-propiolactone in the final product nor that neoantigenic determinants had been created by the reaction of beta-propiolactone with the protein molecules.

Animals↗
PubMedDate not supplied

Topical cooling assisted hepatic resection of segment 7 and 8 oriented by en-bloc interruption of the targeted portal pedicles.

BACKGROUND/AIMS: The crucial points of hepatic segmentectomy include an accurate mapping of proposed segment(s) to be resected and minimization of intra-operative blood loss. This study reports a surgical technique of hepatic resection for segment 7 and 8, and a benefit of supplemental use of topical cooling during consecutive right hepatic inflow occlusion. METHODOLOGY: From January 1993 to December 1996, ten hepatocellular carcinoma patients with pathologic livers underwent hepatic segmentectomy for segment 7 and 8. The mapping of the target segments was guided by en-bloc test occlusion of the relevant portal pedicles and subsequent discoloration, often after the opening hilum method. Of these, five tumors were resected with topical cooling by ice slush seeding during consecutive right inflow occlusion (cooling group) and the remainder without cooling (Normothermic group). In the normothermic group, inflow occlusion was carried out by cyclic clamping and unclamping method. RESULTS: The inflow occlusion time was 54 +/- 9.4 min in the cooling group, much longer than in the normothermic group. Although the post-operative peak transaminase values were twice as high as those in the normothermic group, the blood loss was significantly less, and there was no detrimental effect of prolonged, consecutive ischemia on the other intra- and post-operative data. CONCLUSIONS: En-bloc taping of the target portal pedicles with or without the opening hilum method is useful in the mapping of segments, and the use of topical cooling is beneficial in prolonged inflow occlusion during complicated right-sided segmentectomy.

Adult↗
PubMedDate not supplied

Selective cytotoxic activity of grape peel and seed extracts against oral tumor cell lines.

Grape seed extracts were more cytotoxic than grape peel extracts. Methanol and 70% methanol extracts of grape seed selectively killed two human oral tumor cell lines, more efficiently than human gingival fibroblasts. ESR spectroscopy revealed that these extracts produced radicals under alkaline conditions and enhanced the radical intensity of sodium ascorbate at higher concentrations. On the other hand, lower concentration of these extracts slightly reduced the radical intensity of sodium ascorbate, and scavenged superoxide anion, generated by hypoxanthine and xanthine oxidase reaction. These properties of grape seed extracts suggest their possible application for cancer prevention.

Anticarcinogenic Agents↗
PubMedDate not supplied

Adverse effect of perioperative blood transfusions on survival after hepatic resection for hepatocellular carcinoma.

BACKGROUND/AIMS: Experimental and clinical studies have found a relationship between blood transfusion and altered immune function. We estimated the risk of transfusions for shorter survival on patients with hepatocellular carcinoma who underwent hepatic resection. METHODOLOGY: The impact of perioperative blood transfusions on 235 patients with hepatocellular carcinoma who had resections from January 1981 to December 1988 was retrospectively examined. All patients underwent hepatic resection and received no additional chemotherapy. RESULTS: Using the Cox proportional hazard model, the number of perioperative blood transfusions was found to be a significant prognostic factor for patient outcome (p = 0.03). Overall, patients who received less than 12 transfused units had a significantly better 5-year survival rate than those who received more than 13 transfused units (46.3% vs. 24.5%, p < 0.001). This result was also seen when the patients were subdivided by stage: 5-year survival in the early stage group (57.2% vs. 35.5%, p < 0.01) and in the advanced stage group (30.0% vs. 18.2%, p < 0.05). The number of perioperative blood transfusions also influenced the survival of patients who underwent a curative resection (66.2% vs. 38.5%, p < 0.01), but did not affect the survival of those who received a non-curative resection (7.9% vs. 7.4%). CONCLUSION: This study suggests that the number of perioperative blood transfusions is a significant prognostic factor in patients with hepatocellular carcinoma who undergo hepatic resection.

Carcinoma, Hepatocellular↗
PubMedDate not supplied

Laparoscopic partial hepatectomy.

This article describes the surgical techniques and indications of laparoscopic partial hepatectomy, which is not as widely available as laparoscopic cholecystectomy. Three patients with hepatocellular carcinoma and associated severe liver cirrhosis were candidates for this technique from July 1993 to August 1994. The tumor size was 4 cm or less and all the tumors were located in segment 5 or 8 which had grown nodularly and protruded from the liver surface. A microwave tissue coagulator was used for parenchymal dissection under ultrasonographic guidance in a gas-less method with or without low-pressure pneumoperitoteum of 4 mmHg. The principle of dissection consists of tissue coagulation and fragmentation with dissecting forceps. Three hepatectomies were performed uneventfully without blood transfusion and the patients rapidly returned to their preoperative conditions. The laparoscopic partial hepatectomy can be an option of treatment in selected cases where the tumor can be removed by minor, superficial resection.

Carcinoma, Hepatocellular↗