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Biomedical subjects

M Tsuji

Publications and source records attributed to M Tsuji.

At least 289 records · Page 16Linked to original sources

The Bo-RBC-SCID mouse model for evaluating the efficacy of anti-theilerial drugs.

We have previously developed a mouse model which allowed the proliferation of Theileria sergenti in severe combined immunodeficiency (SCID) mice with circulating bovine erythrocytes (Bo-RBC). In the present study, this model was utilized to test the efficacy of anti-theilerial drugs. Bo-RBC-SCID mice were created by giving periodic transfusions of T. sergenti-free Bo-RBC, and subsequently infecting with T. sergenti. Three anti-protozoal compounds, Pamaquine (Yamanouchi Pharmaceutical Co. Ltd), Ganaseg (Japan CIBA-GEIGY Ltd) and Buparvaquone (Coopers Animal Health Ltd), were subcutaneously administered into the mice at doses recommended for cattle therapy. Blood examinations demonstrated that all three drugs significantly reduced the level of parasitemia although Ganaseg was effective only at a dose five times higher than that recommended for cattle therapy. Administration of the drugs neither caused any sign of acute toxicity nor changed the rate of Bo-RBC in the SCID mice's circulating blood cells. The results indicate that the Bo-RBC-SCID mouse model may offer a useful in vivo system for evaluating the efficacy of anti-protozoal drugs against T. sergenti.

Aminoquinolines↗

Anti-viral activity of sulfated chitin derivatives against Friend murine leukaemia and herpes simplex type-1 viruses.

Sulfated chitin derivatives, selected for their low toxicity and high inhibitory activity of melanoma metastasis, were examined for anti-viral activity against Friend murine leukaemia, herpes simplex type-1 (HSV) and Sendai viruses. Carboxymethyl chitin with a 7.66% degree of sulfation (SCM-chitin III) showed a significant inhibition of Friend murine leukaemia helper virus (F-MuLV) and HSV, but not of Sendai virus growth in vitro. Sulfated N-deacetylated chitin had a significant but weak activity against F-MuLV and HSV infections. Carboxymethyl chitin showed no effect on these infections in vitro. SCM-chitin III also exhibited anti-viral activity in vivo by suppressing the splenomegaly which was caused by prior infection of mice with FV, a complex of F-MuLV and spleen focus-forming virus.

Animals↗

Reduction of thyroxine-induced necrotic foci and thrombi in the mouse liver by androgen, oestrogen and glucocorticoid but not by progesterone.

Injections of thyroxine (T4) at a dose of 10 micrograms/mouse/day into castrated adult female or male C57BL/6 mice for 3 weeks induced multiple necrotic foci and portal thrombi in the liver at high incidences. However, injections of T4 into intact female or male mice resulted in the marked decrease in their incidences. Furthermore, injections of 5 alpha-dihydrotestosterone at doses more than 50 micrograms/mouse/day, oestradiol-17 beta at doses of 0.2 and 1 micrograms/mouse/day or dexamethasone at doses more than 20 micrograms/mouse/day into castrated female mice markedly reduced incidences of necrotic foci and thrombi induced by T4, while injections of progesterone did not show any effects on them. The present results indicate that an excess of thyroid hormone causes the hepatic impairment in castrated mice and that androgen and oestrogen at physiological doses, and glucocorticoid at pharmacological doses prevent it.

Animals↗

Suppressive effect of estrogen on hepatocellular tumorigenesis induced in mice by 3'-methyl-4-dimethylaminoazobenzene.

Treatment of female C57BL/6 x DS-F1 mice with 3'-methyl-4- dimethylaminoazobenzene (3'-Me-DAB) neonatally resulted in the development of hepatocellular adenomatous nodules. Ovariectomy at 1 month of age greatly hastened the time of appearance of these nodules and significantly increased their incidence. The incidence of adenomatous nodules in females ovariectomized at 1 month of age was about 70% at 12 months of age, and was decreased to 4% by implantation of a pellet containing estradiol-17 beta (E2 pellet) at 1 month of age (at the time of ovariectomy). The incidence of adenomatous nodules at 12 months of age was not decreased significantly when the implanted E2 pellet was removed at 4 or 6 months of age, but was decreased significantly when it was removed at 8 or 10 months of age. Implantation of E2 pellets into ovariectomized females at 4 and 6 months of age decreased the incidence of adenomatous nodules as effectively as their implantation at 1 month of age. The implantation of E2 pellets into ovariectomized females at 8 or 10 months of age resulted in significantly lower incidences of adenomatous nodules at 12 months of age, than that in females ovariectomized at 1 month of age. The present results suggest that the ovarian hormone, estrogen suppresses the development of hepatocellular tumors induced by 3'-Me-DAB, exerting its effect from about 6 months of age.

Adenoma, Liver Cell↗

Creatine kinase-catalyzed reaction rate in the cyanide-poisoned mouse brain.

Brain creatine kinase (CK)-catalyzed phosphorus flux from phosphocreatine (PC) to ATP was measured in vivo in young adult mice made reversibly hypoxic by injection of cyanide. Phosphorus spectra and saturation transfer measurements of CK-catalyzed flux were acquired using a high-field (8.45 T) nuclear magnetic resonance (NMR) spectrometer. After low cyanide doses (1-3 mg/kg of body weight), there were no measurable changes in brain pH or in concentrations of PC, the nucleoside triphosphates (including ATP), and Pi. The CK-catalyzed phosphorus flux increased about 75% after the low cyanide dose. Higher doses (4-6 mg/kg) produced a transient 30-40% decrease in PC concentration, doubling of Pi, and a 0.2 unit decrease in pH. The CK-catalyzed phosphorus flux decreased 50-80% after the higher cyanide doses. This decrease in phosphorus flux was present long after reactant concentrations returned to precyanide values. It is proposed that the increase in brain CK-catalyzed phosphorus flux with the lower cyanide doses is due to an increase in ADP concentration. The large, prolonged decrease in CK-catalyzed reaction rate in the moderately poisoned brain may be due to loss of activity of the mitochondrial CK isoform.

Adenosine Triphosphate↗

Role of the endothelium on extraluminal and intraluminal vasoactive mechanisms in the perfused rabbit basilar artery.

In order to investigate the role of the endothelium in the regulation of cerebrovascular tone, we studied selective intraluminal and extraluminal vasoactive mechanisms of acetylcholine, potassium and serotonin. We also examined the effects of removal of the endothelium on these vasoactive responses. With 0.75 g of tension, isolated rabbit basilar arteries were fixed in a perfusion system with the ability to isolate the intraluminal and extraluminal surfaces, and perfused at 8 ml-1 min-1 under a pressure of 8 mmHg. To remove the endothelium, we applied several concentrations of saponin. The endothelium was completely removed by 0.05 mg-1 ml-1 saponin, confirmed histologically. Extraluminal and intraluminal acetylcholine induced endothelium-dependent relaxations. Intraluminal potassium induced greater contraction than extraluminal potassium in both saponin denuded (p < 0.01) and intact preparations (p < 0.05, n = 8). Intraluminal and extraluminal serotonin induced symmetric contractions, and for both sides the response was enhanced by removal of the endothelium (p < 0.05, n = 6). Our results suggest that inhibitory (relaxant) contribution of the endothelium to contractile responses varies depending on the vasoactive agent. The fact that the effects of some extraluminal agents were enhanced when the endothelium was denuded, may be of some importance in potentiating the mechanism of vasospasm following subarachnoid haemorrhage.

Acetylcholine↗

Characterisation of the local inflammatory response in appendicitis.

In this study we have characterised the local inflammatory response in acute suppurative appendicitis (S), focal appendicitis (F), and normal appendices (C). Enumeration of lymphocyte subpopulations, cells expressing IL-2 receptor, natural killer (NK) cells, monocytes and plasma cell isotypes and subclasses infiltrating the lamina propria was carried out on all specimens using immunoperoxidase staining procedures. Total T cells were significantly increased in both acute suppurative appendicitis and focal appendicitis compared with controls (p < 0.001). Cells infiltrating the lamina propria expressed IL-2 receptor in all appendiceal specimens but were significantly increased in both acute and focal appendicitis (p < 0.01). IgG and IgA plasma cell isotypes were significantly increased in all S and F appendiceal specimens (p < 0.001). Monocyte and NK cell numbers, however, were only increased in acute suppurative appendiceal specimens. The increased lymphocyte and plasma cell isotypes seen in focal appendicitis occurred throughout the entire organ even through the inflammatory focus was confined to only three to seven serial sections. These results clearly show a differential pattern of cellular infiltration in focal appendicitis from that seen in acute suppurative appendicitis. The selective lymphocyte and plasma cell nature of the cellular infiltrate in the lamina propria of focal appendicitis may reflect the presence of a specific immune response to an as yet unidentified luminal antigen as a possible cause of appendicitis.

Acute-Phase Reaction↗

Echocardiographic evaluation of vagolytic effects of atropine sulfate during pediatric halothane anesthesia.

The aims of this study were to define the antagonistic effects of atropine sulfate to halothane-induced cardiovascular depression in children, and to clarify whether or not a larger dose of atropine is more effective in attenuating the cardiovascular depression. Thirty-four children aged 1-12 years who had undergone minor surgery, free from cardiac or pulmonary disease, were assigned at random to two groups. M-mode echocardiographic evaluation of left ventricular function in each patient was performed at three points (before induction, point A; after induction, point B; and following administration of atropine, point C). Results were compared between points A and B, B and C and C and A, and between the two study groups with different doses of atropine (0.01 mg/kg vs 0.02 mg/kg). Heart rate (HR), mean blood pressure (MBP) and left ventricular shortening fraction (LVSF) decreased, and left ventricular end-diastolic dimension (LVEDD) were increased significantly by halothane induction. Although HR and MBP recovered following atropine, LVSF and LVEDD remained unchanged. There were no differences found between the values after vagolysis in both study groups, except for HR and mean velocity of circumferential fiber shortening (mVcf). Heart rate increased above that of pre-induction, even following the smaller dose of atropine. The myocardial depression cannot be necessarily attenuated by vagolysis regardless of the dosage of atropine. The smaller dose (i.e. 0.01 mg/kg) seems to be sufficient only to antagonize the bradycardia and hypotension during halothane anesthesia in children.

Adolescent↗

Further evaluation of a new penetration enhancer, HPE-101.

The penetration enhancer, 1-[2-(decylthio)ethyl]azacyclopentan-2-one (HPE-101), significantly enhanced the excretion of topically applied [14C]indomethacin when dissolved in dipropylene glycol, triethylene glycol, diethylene glycol, 1,3-butylene glycol, trimethylene glycol, glycerin, water, silicone or triethanolamine, but not when dissolved in ethanol, isopropyl alcohol, oleyl alcohol, olive oil, peppermint oil, isopropyl myristate or hexylene glycol. HPE-101 significantly enhanced the excrection of [14C]indomethacin, [14C]nicotinic acid, [14C]5-fluorouracil, [3H]oestradiol and [3H]triamcinolone acetonide, but not that of [3H]testosterone. HPE-101 also significantly enhanced the excretion of [14C]indomethacin applied to intact skin of rabbit, guinea-pig and rat, and to tape-stripped skin of guinea-pig, but did not enhance the excretion of [14C]indomethacin applied to tape-stripped skin of rat or rabbit.

Administration, Cutaneous↗

Augmentation of murine tumor necrosis factor production by amphotericin B in vitro and in vivo.

Murine peritoneal macrophages were preincubated with amphotericin B (AMPH) and were then stimulated with bacterial lipopolysaccharide or streptococcal preparation (OK432). These macrophages produced a large amount of tumor necrosis factor. When administered to mice, the priming activity of amphotericin B for tumor necrosis factor production in vivo was also observed.

Amphotericin B↗

Functional maturation of creatine kinase in rat brain.

The physiological role of the phosphocreatine (PCr)/creatine kinase (CK) system has been studied in rat brain by comparing maturational changes in in vivo CK-catalyzed reaction rate and activities of CK isoenzymes. The CK-catalyzed reaction rates, measured by 31P-nuclear magnetic resonance spectroscopy, increased 4-fold between 12 and 17 days of age. The mitochondrial CK (Mi-CK) isoenzyme, as a percentage of total CK, increased to the same extent over this relatively narrow age period. Cytosolic CK (B-CK) was active earlier and, with the total CK activity, increased steadily over a longer time course. An immunohistochemical study of cerebellum showed Mi-CK predominantly in gray matter, while the cytosolic CK was present in rather large concentrations in both gray and white matter. In the molecular layer, B-CK was most prominent in the Bergmann glial cells, while Mi-CK was more prominent in Purkinje neurons. During development a redistribution of Mi-CK from the Purkinje cell bodies to their processes was observed. These results point to regional differences in CK content and in isoenzyme-specific localizations. The increase in CK activity is temporally coincident with the maturational appearance of closely coupled decreases in brain PCr and ATP during hypoxia. These maturational changes suggest that the activity of the PCr/CK system, particularly the Mi-CK isoenzyme, is central in regulation of brain ATP.

Animals↗

[Effects of disinfectants on erythrocytes and isolated hepatocytes from rats and surface tension].

The effects of formaldehyde (F), m-cresol (C), guaiacol (G), ethanol (E) and their mixture (FC, FCE, FG, FGE) on erythrocytes and isolated hepatocytes from rats and surface tension in water were examined. Hypotonic hemolysis of erythrocytes was inhibited by m-cresol, while guaiacol, formaldehyde and ethanol accelerated the hemolysis. Lower concentrations of the mixture inhibited hypotonic hemolysis, but higher concentrations accelerated hemolysis. Formaldehyde caused a decrease of transaminase (GOT, GPT) in the medium and hepatocytes. GOT and GPT in the medium were increased by m-cresol, but those in the hepatocyte were decreased by this agent. FC and FCE at 10 mM increased GOT in the medium, but FG and FGE decreased GOT. All mixtures decreased GOT and GPT in hepatocytes and GPT in the medium. All mixtures and formaldehyde inhibited GOT and GPT activity. Formaldehyde and m-cresol decreased hepatocyte viability. In the all mixtures-added hepatocytes, the viability was markedly lowered. Formaldehyde, m-cresol, guaiacol and ethanol caused a depression of surface tension, but the depressive effects of FG and FGE were weaker than that of guaiacol. These results suggest that the observed effects of the drug mixtures on erythrocytes and hepatocytes were the additive effects of the component drugs.

Alanine Transaminase↗

IGF-II producing hepatic fibrosarcoma associated with hypoglycemia.

A 67-year-old male was admitted with the complaint of weakness at hunger early in the morning, when blood glucose was less than 40 mg/dl. The abdominal ultrasonogram and computerized tomogram demonstrated a huge tumor in the right liver lobe. Hypoglycemia disappeared after transcatheter arterial embolization. Then hepatic lobectomy was performed. The tumor was histologically shown to be a fibrosarcoma. Insulin-like growth factor-II was intensely stained in the Golgi area of the tumor cells, suggesting its role in the mechanism of hypoglycemia.

Aged↗

[Renal plasmacytoma].

Extramedullary plasmacytoma arising in the kidney is uncommon. So far only 11 cases have been reported. Recently, we noted the 12th case, the third case seen at the Kyoto University Hospital. The literature is reviewed. A 43-year-old man was hospitalized because of paraplegia due to spinal cord compression by the solitary plasmacytoma arising in the cervical spine, producing an IgG-lambda paraprotein. The tumor excision was followed by radiotherapy and standard chemotherapy. Two years later, new lesions on the thoracic spine, the left clavicle, and the occipital bone successively developed with Bence Jones proteinuria (lambda), but without IgG-lambda paraproteinemia. Ga-67 scanning was performed to detect extramedullary tumors. The marked accumulation of the radionuclide revealed intraabdominal tumors. A CT scan of the abdomen revealed a large soft-tissue mass (73 x 50 mm) emanating from the right kidney and several enlarged lymph nodes. Ultrasound of the right kidney revealed a solid mass with hydronephrotic change. RI-renogram showed delayed excretion from the right kidney. Clusters of myeloma cells were repeatedly observed in the urinary sediment. Thus, a diagnosis of plasmacytoma of the kidney was made. Treatment with radiotherapy alone was sufficient.

Adult↗

[A surgical case of solitary cerebral cysticercosis].

A surgical case of solitary cerebral cysticercosis is presented with a review of the literature. A 41 year-old female was admitted to our institute with generalized convulsion. Physical and neurological findings on admission were unremarkable. CT scan revealed a ring-like enhanced mass with perifocal edema in the right rectal gyrus. On MRI, the cyst wall showed iso-signal intensity on T1 weighted image (T1WI) and was markedly enhanced by gadolinium. The cyst fluid showed low signal intensity on T1WI and high signal intensity on T2-weighted image (T2WI). Obvious perifocal edema was seen on T2WI. Laboratory findings were all normal. The mass was totally removed surgically via the right subfrontal route. It was an extraaxial mass and had no attachment to the dura. Histological examination revealed the presence of the scolex, hooklets, and suckers, characteristic of cysticercus. The patient was administered praziquantel at 1200 mg/day for 3 days after surgery. In this case, Taenia solium could not be found in spite of various examinations and sexual transmission was also denied after interview. One possibility was transmission via fresh vegetables grown with excretal compost contaminated with the eggs of T. solium, as the patient often ate spicy pickles called Kimuchi imported from Korea. Physicians should be aware of the possibility of transmission via contaminated fresh vegetables in patients who have never even been to an endemic area, or who have never eaten raw pork.

Adult↗

Distribution of pheophorbide A in normal tissues and in an experimental pancreatic cancer in rats.

The in vivo administration and distribution of a potent new photosensitizer, pheophorbide A (PH-A), was investigated in rats. The spectral characteristics were determined. This hydrophobic compound was solubilized by an ethanol/phosphate-buffered saline (PBS) mixture (v/v) and sonicated immediately before i.v. administration. Tissue distribution and the affinity of PH-A for an acinar pancreatic tumor were determined in Lewis rats for up to 48 h after a single i.v. administration of 3 mg kg-1 body wt. Methanol-extracted PH-A was quantitatively determined by fluorescence spectrophotometry at 665.6 nm. The PH-A uptake pattern showed that the reticulo-endothelial system is the major target of PH-A, followed by the gut and then the lung and pancreas. PH-A concentrations in skin were very low. The presence of an enterohepatic cycle was suggested by the PH-A biliary output, intestinal uptake and blood concentrations. Tumor PH-A retention was longer than pancreatic retention. The ratio of tumoral to peri-tumoral pancreas PH-A was 6.7:1, 24 h after i.v. administration. With its similar tissue pattern, better absorption spectrum and lower skin toxicity, PH-A could be a more potent photosensitizer than hematoporphyrin derivatives.

Animals↗