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Biomedical subjects

Y Kitano

Publications and source records attributed to Y Kitano.

At least 109 records · Page 6Linked to original sources

Protective effects of kampo medicines and baicalin against intestinal toxicity of a new anticancer camptothecin derivative, irinotecan hydrochloride (CPT-11), in rats.

In clinical use, irinotecan hydrochloride (CPT-11; 7-ethyl-10-[4-(piperidino)-1-piperidino]carbonyloxycamptothecin), a novel antitumor agent, causes a relatively high incidence of severe forms of diarrhea. We investigated whether baicalin, an inhibitor of beta-glucuronidase, which deconjugates the glucuronide of the active metabolite of CPT-11, SN-38 (7-ethyl-10-hydorxycamptothecin), and Japanese herbal medicines (Kampo medicines) which contain baicalin can ameliorate CPT-11-induced intestinal toxicity in rats. CPT-11 (60 mg/kg i.v. once daily for 4 consecutive days) induced intestinal toxicity characterized by diarrhea, loss of body weight, anorexia and disruption of intestinal epithelium. Treatment with baicalin (25 mg/kg p.o. twice daily) or Kampo medicines (TJ-14 and TJ-114; 1 g/kg p.o. twice daily) from the day before to 4 or 10 days after the start of CPT-11 administration resulted in significantly decreased weight loss, improved anorexia and delayed onset of diarrheal symptoms. Histological examination revealed that Kampo medicine-treated animals had less damage to the intestinal epithelium and that damage was repaired more rapidly than in control rats. These results suggest that the prophylactic use of Kampo medicines (TJ-14 and TJ-114) may be of value against CPT-11-induced intestinal toxicity.

Animals↗

Cell cycle regulators in the keratinocyte (cyclin-cdk).

It has recently become clear that cyclin-dependent kinase (cdk) complex regulates the cell cycle by phosphorylating Rb protein, a tumor suppressor protein. It is likely that this complex is a target of various growth factors and anti-growth factors (UV, TGF-beta etc.) in keratinocyte (KC). It has also been suggested that abnormalities in the cell cycle regulating mechanism such as increased activity of cyclin-cdk due to mutation of p53, a tumor suppressor gene, and overexpression of cyclin D may be concerned with carcinogenesis of KC. Thus, recent studies indicate that the cyclin-cdk complex is a common target of proliferation and carcinogenesis in KC.

Animals↗

Enhancement of adhesive property of epithelial cell line Mm2T by culture in the presence of methylated vitamin B12.

A thymic epithelial cell line Mm2T was cultured in a medium containing a high concentration (100 micrograms/ml) of methylated vitamin B12 (CH3-B12). After 19 days, cells were found to have a flat phenotype, to have lost the floating cells which were observed in the control cells at the confluent stage, and to have acquired a resistance to trypsin. However, treatment of the CH3-B12-treated cells with EDTA resulted in a dissociation of cell-to-cell contact and reaggregation was achieved by addition of Ca2+, indicating the involvement of Ca2+ ion in cell-to-cell contact. Electron microscopic analyses revealed that the CH3-B12-treated cells were nearly square in their vertical section, which was in contrast to the dome-shaped feature of the control cells, and their cell-to-cell contact area was significantly widespread, as compared to those of the control, indicating that Mm2T cells acquires an adhesive property by treatment with CH3-B12. Biochemical analyses of both cells indicated that the concentration of glucosylceramide in the CH3-B12-treated cells was higher than that of the control. Free glucose characteristically inhibited the reattachment of cells dissociated with EDTA, suggesting the involvement of glucose in the cell-to-cell adhesion of CH3-B12-treated cells. In addition, WGA-binding glycoconjugates were intensely observed in the boundary region of CH3-B12-treated cells by immunohistochemical staining, but not in that of the control cells. It is suggested that CH3-B12 may affect the morphological alteration of Mm2T by enhancing cell adhesion through elevated expression of the C-type lectin.

Animals↗

[Study on the mechanisms of diarrhea induced by a new anticancer camptothecin derivative, irinotecan hydrochloride (CPT-11), in rats].

We investigated the mechanisms of CPT-11-induced diarrhea. 1) CPT-11 (80 mg/kg, i.v.) induced watery diarrhea within 1 hr after dosing in saline-loaded (10 ml/kg, p.o.) rats. This was partially inhibited by subcutaneous injection of atropine (1 mg/kg) or ondansetron (1 mg/kg) and almost completely inhibited by a combination of atropine and ondansetron or by clonidine (0.3 mg/kg) or morphine (10 mg/kg) alone. 2) CPT-11 at the same dose reduced intestinal fluid absorption, which was blocked by the anti-diarrheal agents mentioned above. Intraluminal injection of CPT-11 (20 mg/2 ml) inhibited fluid absorption and induced fluid secretion. 3) CPT-11, 60 mg/kg, by single intravenous injection induced fewer enzymological and histological changes in the small intestine than 5-FU at 270 mg/kg, while 4 consecutive dosings of CPT-11 induced delayed diarrhea (days 5-7) associated with disruption of intestinal integrity. Co-administration with anti-diarrheal agents, except for ondansetron, protected against watery diarrhea appearing within 1 hr after CPT-11 on days 3 and 4, but worsened delayed diarrhea. These results suggest that single injection of higher doses of CPT-11 causes watery diarrhea at an acute phase at least partly by reducing fluid absorption or increasing secretion, and that while conventional anti-diarrheal agents protect against watery diarrhea, their co-administration in repeated CPT-11 administration has no ameliorative effect on CPT-11-induced delayed diarrhea.

Animals↗

[General pharmacological study of iodixanol, a new non-ionic isotonic contrast medium].

The general pharmacological study of iodixanol, a non-ionic isotonic contrast medium, was conducted. 1) Iodixanol administered intravenously over a dose range of 320 to 3,200 mgI/kg had little or no effect on the general behavior, spontaneous locomotor activity, hexobarbital sleeping time, pain response, electroshock- or pentylenetetrazol-induced convulsion (mouse), EEG or body temperature (rabbit), gastrointestinal propulsion (mouse) or skeletal muscle contraction (rabbit). Iodixanol had no specific interaction with acetylcholine, histamine, serotonin, nicotin, BaCl2 (ileum), methacholine (trachea), isoprenaline (atrium) or oxytocin (pregnant uterus), nor had any effect on spontaneous contractility (atrium and uterus), or transmural electrostimulation-induced contractility (vas deferens) at concentrations of < or = 3.2 x 10(-3) gI/ml in vitro. Iodixanol had no effect on the cardiovascular system of dog, except that it increased femoral blood flow and respiratory rate at doses of > or = 1,000 mgI/kg. Iodixanol at 3,200 mgI/kg i.v. reduced urine output with a decrease in Na+ and Cl- excretion, whereas at 320 mgI/kg i.v., it slightly increased urine output (rat). 2) Injections of iodixanol into the cerebroventricular (0.96, 9.6 mgI/mouse and 3.2, 32 mgI/rat), left ventricular (1,920, 6,400 mgI/dog) or coronary artery (640, 1,920 mgI/dog) had no conspicuous effect on the central nervous system or the cardiovascular system, respectively. There was no marked difference among iodixanol, iohexol and iopamidol in this respect. Vascular pain during injection into the femoral artery (300-320 mgI/guinea pig) appeared to be less intense with iodixanol, compared with the other contrast media iohexol and iopamidol. These results suggest that intravenous injection of iodixanol is relatively free from pharmacological activity, and effects of iodixanol on the central nervous system (intracerebroventricular injection) and cardiovascular system (intra-left ventricular and -coronary injections) are comparable to those of iohexol and iopamidol. Furthermore, intra-femoral injection of iodixanol has less of a tendency to produce vascular pain than those of iohexol and iopamidol.

Animals↗

Kimura's disease with high serum levels of eosinophil cationic protein and major basic protein.

This study reports a case of Kimura's disease. The patient was a 58-year-old man and satisfied the clinico-pathological findings of Kimura's disease. Serum eosinophil cationic protein (ECP) and major basic protein (MBP) levels in this patient were also measured. In the active stage of the disease, the patient's serum ECP and MBP levels were higher than those of healthy controls and declined in the remission stage. This finding suggests that ECP and MBP may be important agents in the development of Kimura's disease.

Angiolymphoid Hyperplasia with Eosinophilia↗

Fibroblasts of neurofibromatosis type 1 showed no abnormality in p21ras-mediated response to serum in culture.

In order to disclose the possible disturbance in regulation of p21ras function in neurofibromatosis type 1, we investigated the recovery from the quiescent to cycling states of the cell cycle in the skin fibroblasts of the patients. When cells cultured in serum-dependent medium are deprived of the serum, these go into the quiescent state (G0). On being returned to the serum-containing medium, the cells re-enter S phase. The skin fibroblasts from neurofibromatosis type 1 patients, and normal subjects were brought into the quiescent state by serum-starvation, and after the re-addition of the serum, the recovery to cycling states were analysed by flow cytometry. There was no apparent difference between these fibroblasts in the progression from G0 to S phase.

Alkaloids↗

A congenital abnormality of calves, suggestive of a new type of arthropod-borne virus infection.

About 1000 calves with a congenital disease were born in Kagoshima prefecture, Japan, between October 1990 and October 1991, the peaks of the epidemic being in March and July 1991. Of 85 abnormal calves examined pathologically and serologically, 70 appeared to have been suffering from a viral disease. Of these 70 animals, 17 had lesions bearing some resemblance to those of the diseases produced by Akabane, Chuzan, Aino, bluetongue and bovine viral diarrhoea-mucosal disease viruses-diseases known to occur in Kagoshima-but serum samples contained no antibodies to these viruses or to infectious bovine rhinotracheitis virus. This suggested the occurrence of a new type of viral infection in southern Japan. Six of the 17 calves were born dead and the others manifested clinical signs such as weakness, difficulty in sucking, inability to stand, vertigo, opisthotonus, staggering and weak eyesight or blindness. They were of small size and showed domed head, scoliosis, arthrogryposis, maxillary retraction, sunken eye, cataracts, and irregularities and defects of the teeth. At necropsy, almost all cases showed hydranencephaly, and many had cerebral defects and cerebellar hypoplasia or agenesis. Both cerebral and cerebellar lesions were seen in six cases, two of which showed a hypoplastic defect of the brain stem. Histopathological examination of the affected organs revealed gliosis, loss of cerebral parenchyma resulting from dilation of the ventricles, perivascular cuffing with round cells such as lymphocytes and plasma cells, proliferation of blood vessels, thick-walled blood vessels in the brain stem, dilation of mesencephalic aqueducts, cerebellar cortical dysplasia, decreased nerve cells in the ventral horn of the spinal cord, and myodysplasia of skeletal muscle.

Abnormalities, Multiple↗

An immunohistochemical study of peripheral neuroblastoma, ganglioneuroblastoma, anaplastic ganglioglioma, schwannoma and neurofibroma in cattle.

Immunohistochemical analysis of five paraffin wax-embedded neoplasms was performed to elucidate the characteristics of bovine nervous-tissue tumours. In case 1 (peripheral neuroblastoma), the neoplastic tissue was characterized by the formation of true and Homer-Wright rosettes and the existence of neuron-specific enolase. The neoplastic cells were possibly more immature than those of common neuroblastomas, because similar features are observed in human malignant neuroepitheliomas. The neoplastic cells in case 2 (ganglioneuroblastoma) ranged from large cells with abundant neurofilaments to immature small cells, rarely with neurofilaments or glial fibrillary acidic protein (GFAP). Such expression suggests the presence of pluripotential cells. The neoplastic tissue in case 3 (anaplastic ganglioglioma) was strikingly polymorphous, and had five elements; neuronal, astrocytic, oligodendrocytic, spindle cell and small oval cell. The neoplastic neurocytes and astrocytes were, respectively, characterized by neurofilament and GFAP positivity. The neoplastic oligodendrocytes made a honeycomb appearance, and the neoplastic spindle cells and small oval cells were considered to be less differentiated. The tumours of cases 2 and 3, which contained poorly differentiated cells and revealed both neuronal and glial differentiation, may be specific to calves. In case 4 (schwannoma), almost all the neoplastic cells were positive for S100 protein, while S100-negative fibroblasts were present in many areas of case 5 (neurofibroma). These two tumours were readily distinguished histologically and immunohistochemically.

Animals↗

Physiological expression of the 2',5'-oligoadenylate synthetase gene in mouse intestine.

2',5'-Oligoadenylate synthetase (2-5A synthetase) is an enzyme induced by interferon (IFN) that is considered to play an important role in IFN action. The normal mouse, not treated exogenously with any IFN or IFN inducers, has been shown to have an enhanced level of 2-5A synthetase activity, which is distributed among several lymphoid tissues. In the present report, we investigated the expression of the 42-kD 2-5A synthetase mRNA in the organs of normal mice using RNA blot hybridization and reverse transcriptase polymerase chain reaction (RT-PCR). Among the organs tested, intestinal tissues had the highest levels of this mRNA. Furthermore, the 42-kD 2-5A synthetase mRNA was expressed in intestines from germ-free mice and fetuses. Immunoblotting analysis using a monoclonal antibody against the 42-kD 2-5A synthetase revealed that the 42-kD enzyme as well as a cross-reactive protein of 30 kD were produced in the organs of the normal mouse.

2',5'-Oligoadenylate Synthetase↗

[Flora in the anterior nares of patients in the neurologic ward: the influence of nasogastric intubation and mechanical ventilation].

MRSA has been isolated frequently from patients in the neurologic ward of Minami-Okayama Hospital. We examined the flora in the anterior nares of 37 patients in the neurologic ward and 36 patients in the medical ward. Existence of dysphagia and nasogastric intubation is considered to make a marked difference between nasal flora of neurologic patients and that of medical patients. Patients with nasogastric intubation had higher incidences of colonization with S. aureus, and gram-negative rods. All patients colonized with MRSA had received nasal tube-feeding. Nasogastric intubation is considered to be a significant risk factor for MRSA colonization. The study in patients with nasogastric intubation demonstrated that patients with mechanical ventilation had a significantly higher incidence of colonization with gram-negative rods, such as P. aeruginosa, and a lower incidence of colonization with S. aureus. A incidence of MRSA colonization in patients with mechanical ventilation was significantly low. Mechanical ventilation is not necessarily considered to be a risk factor for MRSA colonization.

Bacterial Infections↗