Biomedical subjects

M Tagawa

Publications and source records attributed to M Tagawa.

At least 145 records · Page 8Linked to original sources

PubMed1995

Sedative effect of medetomidine and its reversal by atipamezole in house musk shrews (Suncus murinus).

This study was undertaken to evaluate the sedative effect of medetomidine, an alpha 2-adrenoceptor agonist, and the counteractive effect of atipamezole, an antagonist to medetomidine, in house musk shrews (Suncus murinus). Two hundred, 300, 400, or 600 micrograms/kg of medetomidine was intraperitoneal injected into 89 house musk shrews. A sedative effect was produced in one to two minutes after injection. The dose-dependent prolongation of the sedative duration and the dose-dependent appearance of a hypothermic effect were demonstrated. With 200 micrograms/kg of medetomidine, the sedative effect obtained was not adequate in some of the animals. With 300 micrograms/kg and above, a stable sedative state was induced in all the animals. The duration of sedation in the house musk shrews was much longer (p < 0.01) in males than in females. This suggested the higher susceptibility of male house musk shrews to this drug. The sedative effect and hypothermia obtained with 400 micrograms/kg of medetomidine were completely counteracted by more than 2.0 mg/kg of atipamezole. With 0.5 and 1.0 mg/kg of atipamezole, only a partial antagonistic action was produced. Transient vomiting appeared in 4.5% of the house musk shrews at approximately one minute after injection of medetomidine. This side-effect had occurred before the sedative effect was obtained, and was not serious enough to be a problem. None of the 89 house musk shrews died in this experiment. The above results show that the combination of medetomidine and atipamezole is a highly effective and safe anesthetic treatment which permits easy handling of house musk shrews.

Adrenergic alpha-Antagonists↗

PubMed1995

Incidence of hepatocellular carcinoma in chronic hepatitis B and C: a prospective study of 251 patients.

The incidence of hepatocellular carcinoma (HCC) was prospectively studied in 251 chronic hepatitis patients, and was compared between the 127 cases of hepatitis B and 124 cases of hepatitis C. All patients were diagnosed by needle biopsy on entering the study, and the cases consisted of chronic persistent hepatitis (CPH), chronic active hepatitis (CAH)2a, and CAH2b (cirrhosis was not included). Of the cases of chronic hepatitis B, 5 cases of HCC (3.9%) were detected; among the chronic hepatitis C cases, 13 cases (10.4%) were detected. Thus, although the mean follow-up periods were in the same range, the incidence of hepatocellular carcinoma was 2.7 times higher in hepatitis C than in hepatitis B (chi 2 = 3.116, P < .05). Using the Kaplan-Meier method, the incidence of HCC was significantly higher in chronic hepatitis C (P = .0194, generalized Wilcoxon test). In hepatitis C, the incubation period until HCC was detected was shorter when the liver disease was more advanced. Such a tendency was not observed in hepatitis B. In the 13 cases of HCC occurring in chronic hepatitis C, noncirrhotic liver was seen in only 1 case (7.7%), whereas 2 of the 5 cases of HCC (40%) in chronic hepatitis B were noncirrhotic. The prevalence of hepatitis C virus (HCV) genotypes II and III was the same in the total followed cases and HCC cases.

Adult↗

PubMed1994

Effects of neuropeptide analogues on calcium flux and proliferation in lung cancer cell lines.

Small cell lung cancers (SCLC) and some non-small cell lung cancers (NSCLC) have neuroendocrine features which include production of a variety of neuropeptides, cell surface expression of the receptors for these peptides, and autocrine stimulation by the peptides. Previous studies showed that some peptide antagonists and anti-peptide antibodies inhibited the growth of SCLC cell lines which expressed receptors for the specific peptide. We and others showed that the heterogeneity of peptide receptor expression and responsiveness was a major potential obstacle for developing therapeutic uses of peptide antagonists. In this manuscript we evaluated the effects of 11 peptide antagonists (3 bombesin-specific, 2 cholecystokinin-specific, 1 arginine vasopressin (AVP)-specific, and 5 substance P derivatives with broad specificity) on peptide-induced calcium mobilization and growth of SCLC and NSCLC cell lines. For each antagonist, we determined the dose-response effects, specificity of peptide antagonism, and biological stability in serum using Indo-1AM-based flow cytometric assays. We found that the three bombesin antagonists, S30, SC196, and L336,175, varied in potency from 10 nM to 10 microM, varied in serum stability from 6 h to more than 24 h, and had no effect on the calcium response elicited by other peptides. None of these compounds effectively inhibited the growth of SCLC cell lines in [3H]dThd and cell growth assays in vitro. Similarly, the three cholecystokinin and AVP antagonists were highly specific for cholecystokinin and AVP, respectively, had widely varying potency, but had little inhibitory effect on SCLC growth in vitro. In contrast, the five substance P derivatives inhibited the calcium response to bombesin, AVP, bradykinin, and fetal bovine serum. None of these five antagonists were as potent as the six specific antagonists described above, but they were more effective in inhibiting the growth of SCLC cell lines in vitro. These substance P derivatives inhibited the growth of peptide-sensitive SCLC cell lines more efficiently than their inhibition of peptide-insensitive NSCLC or breast cancer cell lines. Relatively high concentrations of these substance P derivatives were required to inhibit in vitro growth, even in the absence of added peptide. It is likely that more potent broad spectrum antagonists, toxins, or radiolabeled stable antagonists will need to be developed for maximal clinical development of this type of anti-growth factor therapy.

Amino Acid Sequence↗

PubMed1994

Prostaglandin E2/parathyroid hormone-induced suppression of alkaline phosphatase activity is mediated by protein kinase C.

1. Bone resorptive factors, prostaglandin E2 and parathyroid hormone are shown to suppress alkaline phosphatase activity in a rat osteoblastic cell line. 2. Phorbol myristate acetate, but not dibutyryl cAMP or calcium ionophore can suppress alkaline phosphatase activity. 3. The protein kinase C inhibitors (H89, staurosporine) are able to block the suppression of alkaline phosphatase activity induced by prostaglandin E2 and parathyroid hormone. 4. These data suggest that protein kinase C is involved in the inhibition of alkaline phosphatase activity induced by prostaglandin E2 and parathyroid hormone.

Alkaline Phosphatase↗

PubMed1994

A newly designed radioimmunoconjugate releasing a hippurate-like radiometal chelate for enhanced target/non-target radioactivity.

Target-to-non-target ratio of radioactivity can be enhanced by the injection of monoclonal antibodies (MoAbs) labeled with metallic radionuclides, if some modality to accelerate the urinary excretion of radioactivity accumulated in non-target tissues could be introduced. In this study, a radioimmunoconjugate chemically designed to release a hippurate-like radiometal chelate was synthesized and tested in vivo. A 67Ga chelate of succinyldeferoxamine (SDF) was conjugated with a MoAb against osteogenic sarcoma (OST7, IgG1) through an ester bond using a new metabolizable MESS linker, N-[I4-(maleimidoethoxy)succinyl]oxy]succinimide (67Ga-DFO-MESS-OST7). When injected into normal mice, 67Ga-DFO-MESS-OST7 exhibited faster clearance of radioactivity from circulation with less accumulation in the liver, kidney and spleen than those observed with 67Ga-DFO-EMCS-OST7, which was prepared under identical conditions to 67Ga-DFO-MESS-OST7 except for using a non-metabolizable linker holding no ester bond to release 67Ga-SDF. Size exclusion HPLC analysis of the liver homogenate obtained from mice 24 h after injection of 67Ga-DFO-MESS-OST7 indicated that all the radioactivity was eluted in the high molecular weight fraction with most of it being present as the 67Ga-DFO-MESS-OST7 fraction. Reverse-phase HPLC analysis of urine sample from the same mice showed a single radioactivity peak at the same retention time as that of 67Ga-SDF. In athymic mice bearing osteogenic sarcoma, 67Ga-DFO-MESS-OST7 exhibited higher tumor-to-blood and tumor-to-organ ratio of radioactivity when compared with 67Ga-DFO-EMCS-OST7. These results indicated that 67Ga-DFO-MESS-OST7 achieved enhanced target-to-non-target ratio of the radioactivity, due to preferential cleavage of the ester bond in non-target tissues, followed by rapid urinary excretion of the resulting chelate (probably as 57Ga-SDF). These results also suggest that the present design would become an applicable modality for enhancing the target-to-non-target ratio of radioactivity by MoAbs.

Animals↗

PubMed1994

Morphine-isoflurane interaction in dogs, swine and rhesus monkeys.

In monkeys, dogs and swine (six each) we tested the reduction of the isoflurane MAC (minimal alveolar concentration) produced by 2 mg.kg-1 morphine intravenously (i.v.) and the concurrent effect on PCO2 with spontaneous ventilation. MAC fell to a minimum of 55% of control at 53 min in monkeys, 50% at 38 min in dogs and 13% at 33 min in swine. PaCO2 rose at constant MAC with morphine to 55-60 mmHg, but did not fall over the next several hours despite the decline of plasma morphine concentration, and the resulting needed rise in isoflurane concentration to keep the anaesthesia depth at 1 MAC. After isoflurane concentration had returned to pre-morphine control levels, naloxone immediately reduced PaCO2 to or below control level. Morphine pharmacokinetics in the three species studied conformed to a two-compartment model.

Anesthesia↗

PubMed1994

Clinical evaluation of uniaxially oriented poly-L-lactide rod for fixation of experimental femoral diaphyseal fracture in immature cats.

Transverse diaphyseal fractures of the femur were experimentally made in immature cats, and were fixed by an intramedullary pinning technique using an uniaxially oriented poly-L-lactide (PLLA) rod, a biodegradable polymer. The healing process was evaluated radiographically and histologically. Formation of bony callus was completed in 8 weeks, and cortical bony union followed. The remodeling process was then observed form 12 to 16 weeks. The healing process was almost the same as when a metallic implant was used. Abundant periosteal callus formation may be attributable to the lower elasticity of the PLLA rod compared with metallic implants. Since no other abnormalities such as growth deformities were detected, it was concluded that the combined use of a uniaxially oriented PLLA rod and an external splint is clinically useful for the repair of diaphyseal fractures in immature cats.

Animals↗

PubMed1994

Effect of change in body position on cardiopulmonary function and plasma cortisol in cattle.

The aim of these studies was to investigate the effect of body posture on circulatory and respiratory system function in unmediated cattle. The plasma cortisol concentration was also measured and served as an indication of the level of stress imposed by animal handling and positional manipulation. Six mature, healthy Holstein cows were physically restrained and studied in standing, supine and right lateral postures. The plasma cortisol concentration increased with the change in body position. In a supine position, the value was increased to more than three times the control value (p < 0.001). The arterial oxygen tension and oxygen saturation were significantly decreased (p < 0.001) with changes in body position. The decrease was most pronounced when cattle were restrained in a supine position. Arterial carbon dioxide tension, heart rate, mean arterial pressure and central venous pressure did not change significantly with changes in body posture. Restraining of cattle in a lateral recumbent or supine position without introducing anesthesia was found to exert a strong stress which affected the respiratory function and increased the plasma cortisol level.

Animals↗

PubMed1994

A therapeutic effect of ulinastatin on endotoxin-induced shock in dogs--comparison with methylprednisolone.

The therapeutic effect of ulinastatin (25,000 U/kg, i.v.) on endotoxin-induced shock was compared with that of methylprednisolone (30 mg/kg, i.v.) in 17 anesthetized dogs. Both of these drugs had almost the same tendency to improve the hemodynamics, arachidonate cascade metabolites and pulmonary surface activity. There was little difference between the effectiveness of ulinastatin and that of methylprednisolone. It was newly confirmed that the release of 6-keto-PGF1 alpha, thromboxane B2 and leukotriene B4, arachidonate cascade metabolites and chemical mediators associated with endotoxin-induced shock, were significantly (p < 0.01 and p < 0.05) decreased by ulinastatin in the same way as methylprednisolone. These results suggest that ulinastatin is as useful as methylprednisolone for the treatment of endotoxin-induced shock.

6-Ketoprostaglandin F1 alpha↗

PubMed1994

Prophylactic efficacy of milbemycin oxime against multiple infection of dogs with Dirofilaria immitis.

In order to examine the prophylactic effects of milbemycin oxime (MO) against Dirofilaria immitis infection, experiments were carried out under multiple infection with D. immitis. Ten filaria-free beagles of age 4 to 8 months were each inoculated with a total number of 480 larvae 12 times at intervals of 15 days over a period of 6 months, and MO was given monthly for the 6 months at a dose of 0.25 mg/kg. The infection rate in the medicated group of dogs was nil, this suggesting complete protection of the infection, while in the non-medicated control group it ranged from 6.5 to 14.8% (mean, 11.4%).

Animals↗

PubMed1994

Usefulness of computed tomography after myelography for surgery on dogs with cervical intervertebral disc protrusion.

Computed tomography after myelography (CTM) was performed pre- and postoperatively on four dogs diagnosed as having cervical intervertebral disc protrusion. The surgery was performed by ventral slot technique in all the cases. The direction of the ventral slot was precisely adjusted according to the location of the protruded discs as seen on CTM. Postoperative values for the transversal area of the spinal cord were greater than those measured preoperatively, suggesting effective decompression of the cord. The prognosis for these patients was excellent. In view of these results, it was considered that preoperative confirmation of the positional relationship between the spinal cord and the protruded disc by CTM was quite useful in planning the surgical technique for disc disease in the dog.

Animals↗

PubMed1994

Application of oriented poly-L-lactide screws for experimental Salter-Harris type 4 fracture in distal femoral condyle of the dog.

The clinical usefulness of biodegradable oriented poly-L-lactide (PLLA) screws for experimental Salter-Harris type 4 fracture in the distal femoral condyle of dogs was evaluated. Bony union of the osteotomized fragment of the condyle was almost completed radiographically and histologically within 1 to 2 months after surgery, suggesting that PLLA screws maintained strength long enough to fix the fragment until bone healing. At 4 to 6 months after surgery, minute fissures were histologically confirmed on the surface of the screw thread, suggesting the early stage of biodegradation and absorption of the polymer. During the observational period, no significant difference between the treated femur and the contralateral non-treated femur in either total femoral length or maximum condyle width was observed, indicating no growth disturbance in the treated femur. From these results it was concluded that the PLLA screw might be an ideal implant for the reduction and fixation of epiphyseal plate fractures such as Salter-Harris type 3 or type 4 fractures.

Animals↗

PubMed1994

Identification of a rat protein tyrosine phosphatase gene preferentially expressed in the embryonal brain.

We have identified a novel protein tyrosine phosphatase gene from an embryonal rat brain by reverse transcription-based polymerase chain reaction. Its transcription is specific to brain and is developmentally regulated, as it is expressed at high levels in embryonal and neonatal stages but scarcely in an adult. Southern blot analysis indicates that the gene exists as a single copy and is conserved among various species. Homology search of the deduced amino acid sequence suggests that this gene belongs to the same family of the membrane-type tyrosine phosphatase gene of Drosophila (DPTP10D), whose expression is specific to an central nervous system of fly embryo.

Aging↗

PubMed1994

Expression of protein tyrosine phosphatase genes in the developing brain of mouse and rat.

We have examined the expression of protein tyrosine phosphatase genes in the embryonic brain of mouse and rat with reverse transcription-polymerase chain reaction. Several receptor and cytoplasmic types of tyrosine phosphatase genes were detected. Among them a novel gene was identified from mouse and rat brain, respectively. The partial amino acid sequences reveal that the new genes found in the developing brain of mouse and rat are homologous each other. Since they retain conserved phosphatase sequences, they may represent a family of protein tyrosine phosphatase gene that is commonly expressed in rodent brain.

Amino Acid Sequence↗

PubMed1994

Absorption, distribution, metabolism and excretion of [14C]ebastine after repeated oral administration in rats.

Absorption, distribution, metabolism and excretion of ebastine (4'-tert-butyl-4-[4-(diphenylmethoxy)piperidino]butyrophenone, LAS-90, CAS 90729-43-4), a new potent histamine H1-receptor antagonist, were studied with 14C-labeled compound in male rats during and after 21 consecutive daily oral administrations at a dose of 2 mg/kg/d. Plasma levels at 2 h after each administration were virtually constant in the range of 81-166 ng eq./ml for 21 days. The plasma levels at 24 h following each administration were lower than the reliable limit of radioactivity measurements during the course of the experiment. Plasma level reached the maximum (Cmax) of 109 ng eq./ml at 2 h after the 21st administration and decreased monophasically with a half-life (t1/2) of 2.5 h, which was similar to the results in the previous single dose study. [14C]Ebastine radioactivity was distributed to the liver, kidney, submaxillary gland, hypophysis, adrenal, lung and pancreas twice as high or more, and to others including brain similarly as or lower than in plasma, at 1 h after the last administration. At 168 h, radioactivity was detected at low levels in several tissues such as liver, kidney, submaxillary gland, etc. and not in other examined tissues. About 2-3% and more than 90% of the daily dose were excreted in urine and feces, respectively, within 24 h after each administration and radioactivity was virtually completely excreted within 120 h after the last administration. The analysis by thin-layer chromatography revealed that the composition of radioactive metabolites in plasma, urine and feces after repeated administration was similar to that in the single dose study.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1994

New immunocapture enzyme (ICE) assay for quantification of cancer procoagulant activity: studies of inhibitors.

A new, sensitive and specific immunocapture enzyme (ICE) assay for quantitation of the enzymatic activity of cancer procoagulant (CP) has been developed. The assay had good reproducibility (inter- and intra-assay CV were 6.4% and 5.7% respectively) and was linear for concentrations of CP from 0.5 microgram/ml to 10 micrograms/ml (r2 = 0.995). Using this assay the inhibition of CP by iodoacetamide, mercuric chloride, E-64, leupeptin and antipain was demonstrated. There was no significant effect of cystatin and natural plasma proteinase inhibitors alpha 1-antitrypsin, alpha 1-antichymotrypsin, alpha 2-macroglobulin and antithrombin-III/heparin, on the activity of the CP.

Biomarkers, Tumor↗

PubMed1993

Effects of acclimation to hypertonic environment on plasma and pituitary levels of two prolactins and growth hormone in two species of tilapia, Oreochromis mossambicus and Oreochromis niloticus.

Specific radioimmunoassays (RIAs) for the pair of tilapia prolactins (tPRLs) and growth hormone (tGH) were developed using antisera raised in rabbits. Anti-tPRL177 did not cross-react with tPRL188 and tGH. Anti-tPRL188 did not cross-react with tPRL177 and showed slight cross-reaction (3.1%) with tGH. Anti-tGH showed negligible cross-reactions with tPRL177 (0.4%) and tPRL188 (1.6%). Pituitary homogenates and plasma from Oreochromis niloticus exhibited displacement curves parallel to the standards in the three RIAs. Plasma from hypophysectomized O. niloticus showed no cross-reaction in any of the three RIAs. Plasma and pituitary levels of the two PRLs in O. mossambicus in freshwater did not differ significantly from each other, whereas in O. niloticus, the levels of PRL177 were significantly greater than those of PRL188 in both plasma and pituitary. After acclimation for 3-4 weeks in seawater (O. mossambicus) or 50% seawater (O. niloticus), the levels of both PRLs decreased significantly compared to their levels in freshwater. Acclimation to a hypertonic environment did not affect plasma and pituitary GH levels in either species. Immunocytochemical staining of the pituitary of O. niloticus revealed colocalization of both PRLs in rostral pars distalis. Our findings suggest that the synthesis and secretion of the two tPRLs could be independently regulated in the same cells.

Adaptation, Physiological↗

PubMed1993

Effect of dibutyryl cyclic AMP on hemodynamics and chemical mediators in dogs with experimentally-induced endotoxic shock.

The therapeutic effect of dibutyryl cyclic AMP (DBcAMP) in endotoxic shock was evaluated, using 11 dogs with experimentally-induced endotoxic shock (5 in DBcAMP group and 6 in control group) under general anesthesia. The DBcAMP group was treated by single intravenous injection of DBcAMP (10 mg/kg) at 15 min before inoculation with endotoxin (3 mg/kg). After the inoculation of endotoxin, this group was given drip infusion of DBcAMP at a rate of 0.1 mg/kg/min over 180 min. Hemodynamic parameters and chemical mediators were measured until 360 min after endotoxin inoculation. The cardiac output and urinary volume, which were decreased in the control group, were significantly inhibited to decrease in the DBcAMP group (p < 0.01). The increases in 6-keto-PGF1 alpha and thromboxane B2, chemical mediators released in endotoxic shock, were significantly inhibited (P < 0.05 and p < 0.01, respectively). These results suggested that DBcAMP is useful for the treatment of endotoxic shock.

6-Ketoprostaglandin F1 alpha↗