Biomedical subjects

M Sano

Publications and source records attributed to M Sano.

At least 847 records · Page 47Linked to original sources

PubMedDate not supplied

Trial of a cysteine proteinase inhibitor, EST, in experimental chloroquine myopathy in rats.

The administration of 50 mg/kg/day of chloroquine to rats for 8 weeks produced the chloroquine myopathy characterized by autophagic vacuole formation and increases in lysosomal enzymes, especially cathepsins B & L. Coadministration of 10 mg/kg/day of a potent cysteine proteinase inhibitor, EST, and chloroquine prevented the induction of the chloroquine myopathy. Rats already suffering from the chloroquine myopathy were treated with 10 mg/kg/day of EST together with chloroquine injections for 5 weeks and also recovered remarkably from the myopathy. Thus, EST may be beneficial for myopathies associated with autophagic vacuoles.

Animals↗

PubMedDate not supplied

Alpha-methyltyptamine blocks facilitation of lordosis by progesterone in spayed, extrogen-primed rats.

Alpha-methyltryptamine, a drug which stimulates serotonergic receptors in the central nervous system, inhibited the induction of sexual receptivity in spayed female rats by estradiol benzoate and progesterone. The drug had no effect on the sexual receptivity induced by estradiol benzoate alone. These data are consistent with the hypothesis that progesterone facilitates lordosis in estrogen-primed rats by inhibiting a serotonergic system in the brain. The data also suggest that estradiol and progesterone act on separate neurochemical systems to induce estrous behavior in rats.

Animals↗

PubMedDate not supplied

Clinical evaluation of posterior embryotoxon in one institution.

To elucidate the pathogenesis of posterior embryotoxon, we estimated its incidence in our clinic and evaluated its associated ocular and systemic anomalies. Slit-lamp and gonioscopic examinations were performed on 440 randomly selected patients at Nagoya City University Hospital over a 10-month period. Posterior embryotoxon was detected in 107, 50 bilateral and 57 unilateral, cases (24.3%). Twelve (11.2%) of the 107 cases had open-angle glaucoma. Accompanying ocular anomalies included six cases of sclerocornea, two each of persistent pupillary membrane and familial exudative vitreoretinopathy, and 1 each of melanocytoma of the optic nervehead, choroidal nevus and subconjunctival dermoid cyst. Associated systemic anomalies included three cases of Alagille syndrome, two of congenital biliary atresia, and one each of congenital facial palsy with microtia, congenital adrenal hyperplasia, empty sella syndrome, Hirschsprung disease and Wilson disease. Many of these ocular and systemic anomalies were caused by the maldevelopment of neural crest cells. Patients with posterior embryotoxon should be examined for the possible presence of open-angle glucoma and for ocular and systemic anomalies related to maldevelopment of neural crest cells.

Adolescent↗

PubMedDate not supplied

Involvement of EAT/mcl-1, a bcl-2 related gene, in the apoptotic mechanisms underlying human placental development and maintenance.

The EAT/mcl-1 gene was isolated during the early differentiation of a retinoic acid-induced human embryonal carcinoma cell line to the trophectoderm lineage. EAT/mcl-1, a bcl-2 related gene, is involved in the genetic pathway of apoptosis; this suggests a role for apoptosis and the involvement of this gene in early placental development. In the current investigation, we analysed expression of EAT/mcl-1 at the mRNA level by Northern blot analysis and in situ hybridization, as well as at the protein level, by immunoblot analysis and immunohistochemistry. Our results identified constant expression of this gene in the placenta throughout pregnancy as well as a shift in its localization from the cytotrophoblast in the first trimester to the syncytiotrophoblast in the third trimester. In addition, there was an inverse correlation between EAT/mcl-1 expression and TaT-mediated deoxyuridine triphosphate nick-end labelling (TUNEL) reactivity in trophoblasts in the first trimester. These results suggest a role for EAT/mcl-1 in both early placental development in regulating trophoblast differentiation as well as a role for this gene in placental maintenance in regulating the process of trophoblast turnover.

Apoptosis↗

PubMedDate not supplied

Bactericidal effect of levofloxacin on strains with equal susceptibility in an in vitro urinary bladder model.

The in vitro bactericidal effects of therapeutic concentrations of levofloxacin (LVFX) on clinical isolates of Pseudomonas aeruginosa and Enterococcus faecalis were assessed. Starting from 10(7) CFU/ml, the bacterial count was determined serially during the exposure to LVFX present at concentrations automatically simulated to its clinically achievable urinary levels at the recommended dosage (100 mg 3 times daily). An isolate of P. aeruginosa for which the MIC of LVFX was 16 microgram/ml was completely eradicated after 10 h of exposure to LVFX. On the other hand, 40 h of exposure to LVFX were required for complete eradication of an isolate of E. faecalis with equal susceptibility, although the bacterial count was rapidly reduced to 10(2) CFU/ml in the early phase of the exposure. It was concluded that LVFX exerts a more potent bactericidal effect on P. aeruginosa than on E. faecalis despite a similar susceptibility of these organisms to LVFX.

Anti-Infective Agents, Urinary↗

PubMedDate not supplied

Bactericidal activity of gatifloxacin (AM-1155) against Pseudomonas aeruginosa and Enterococcus faecalis in an in vitro bladder model simulating human urinary concentrations after oral administration.

The bactericidal activity of gatifloxacin, a new 6-fluoro-8-methoxy quinolone, was determined in a dynamic in vitro model mimicking complicated lower urinary tract infection. Strains of Pseudomonas aeruginosa and Enterococcus faecalis with different susceptibility were exposed to changing gatifloxacin concentrations, simulating human urinary concentrations afer oral treatment with 200 mg twice daily for 3 consecutive days. Bacterial numbers of P. aeruginosa (minimal inhibitory concentrations, MIC: < or =32 microg/ml) and of E. faecalis (MIC: 16 microg/ml) were reduced to undetectable levels during exposure. For the strains with lower susceptibility, gatifloxacin showed bactericidal activity, but eradication was not complete. Thus, in a complicated urinary tract infection model, breakpoint MICs of gatifloxacin for uropathogenic organisms were presumed to range from 16 to 32 microg/ml. At least 86% of recent clinical isolates of P. aeruginosa and E. faecalis were inhibited at its breakpoint MIC. These results suggest that gatifloxacin may be useful in the treatment of urinary tract infections.

Administration, Oral↗

PubMedDate not supplied

Changes in susceptibility of Pseudomonas aeruginosa to gatifloxacin and carbapenem in an in vitro urinary bladder model.

To study the changes of bacterial susceptibility during exposure to antimicrobials, the respective minimal inhibitory concentrations (MICs) of 50 colonies from each of various bacterial test strains were determined in an experimental system using an in vitro urinary bladder model. The MICs of gatifloxacin and meropenem for Pseudomonas aeruginosa strains were not homogeneous before exposure to the drugs. The MICs of the strains examined reflected only that of their dominant population. When starting from 10(7)CFU/ml, the bacterial count was determined serially during exposure to gatifloxacin or meropenem in therapeutic urinary concentrations. The MIC of the less susceptible population of each strain was changed serially to a higher one. The more susceptible strains were eradicated before the change of the MIC. The bacteria originally consisted of strains having heterogeneous susceptibility to drugs, in which major strains had susceptibility expressed by the MIC and minor ones had a higher or lower MIC. This heterogeneity may be responsible for the change of susceptibility in strains after exposure to the drugs.

Anti-Infective Agents↗

PubMedDate not supplied

Fluctuation of lipid peroxides and related enzyme activities at time of stroke in stroke-prone spontaneously hypertensive rats.

The levels of lipid peroxides, determined as thiobarbituric acid reactive substances (TBARS), and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), were examined in the blood from stroke-prone spontaneously hypertensive rats (SHRSP), with and without cerebral lesions, and normotensive Wistar Kyoto (WK) rats. The levels of TBARS in the blood from healthy SHRSP were not significantly different from those of WK rats, while the values of SHRSP (male) with stroke were more than twice as high as those of healthy SHRSP. The activities of SOD and GSH-Px in stroke SHRSP were also statistically different from those of healthy SHRSP.

Animals↗

PubMedDate not supplied

Effects of adenosine diphosphate administration on the vestibulo-oculomotor reflex of rabbits.

Adenosine diphosphate (ADP) injection into a unilateral vertebral artery in rabbits decreased per-rotational nystagmus; the nystagmus beating toward the injected side was predominantly suppressed. This influence became obvious when the animal's blood pressure was low. Field potentials were recorded in the vestibular nuclei upon electric stimulation of the vestibular labyrinth. ADP administration into the vertebral artery also suppressed the amplitude of vestibular evoked potentials (VEPs). Effects of ADP upon the vestibulo-ocular reflex and VEP were considered to be due to regional ischemia induced by the microemboli, which consisted of platelet aggregation.

Adenosine Diphosphate↗

PubMedDate not supplied

The discrepancy between chemotaxis and leukotriene B4 production in a patient with chronic neutrophilic leukemia.

Chronic neutrophilic leukemia (CNL) is a rare type of leukemia. We diagnosed a 81-year-old woman as CNL because she showed that sustained leukocytosis dominated by mature neutrophils, hepatosplenomegaly, high neutrophilic alkaline phosphatase (NAP) score, absence of the Ph1 chromosome and no evidence of leukemoid reaction. During the clinical course, she did not manifest hemorrhagic tendency or infection. We also examined neutrophilic function including chemotaxis, chemiluminescence, nitroblue tetrazolium (NBT) dye reduction, which all indicated normal neutrophil function. Using a reversed phase-high pressure liquid chromatography (HPLC), we detected the production of leukotriene B4 (LTB4) in neutrophils. We found that the LTB4 production was decreased in neutrophils whereas they showed normal chemotaxis. This discrepancy has never, to our knowledge, been reported before in case of CNL.

Aged↗

PubMedDate not supplied

Increased capillary permeability of the stria vascularis to HRP, induced by experimental acute hypotension in rats.

Acute hypotension was produced in rats by using two experimental techniques: intravenous infusion of a ganglion-blocking agent (Arfonad), and venesection of a femoral vein. Horseradish peroxidase (HRP) was injected intravenously after each procedure, and subsequently observed in the inner ear by light and electron microscopy. In both experimental models, a large amount of tracer spread into the intercellular spaces, but it was halted by tight junctions bordering the stria vascularis. The endothelium exhibited a high distribution density of labelled vesicles, which suggested increased vesicular transport. There was no extravasation of HRP from capillaries in the spiral ligament in spite of the presence of some labelled pinocytotic vesicles. The present study was concerned with the discovery of enhanced capillary permeability of the stria vascularis under acute hypotension, as in the case of acute hypertension (Sakagami et al., 1984).

Animals↗

PubMedDate not supplied

Ultrastructural study of the effect of acute hypertension on the stria vascularis and spiral ligament.

The effect of acute hypertension, induced in rats by intravenous injection of methoxamine chloride (Mexan), on the stria vascularis and spiral ligament was studied electronmicroscopically with the tracer method of horseradish peroxidase (HRP). Considerable extravasation of HRP occurred in the stria vascularis, due to the increased vesicular transport. The leaked HRP spread into intercellular spaces, but was prevented from spreading towards the endolymph by zonulae occludentes between marginal cells and towards the perilymph by zonulae occludentes between basal cells. The reaction product was occasionally found between basal cells. No leakage of HRP from capillaries was observed in the spiral ligament, although some labelled micropinocytotic vesicles were present in the endothelium. It is suggested that, under acute hypertensive conditions, areas of zonulae occludentes bordering the stria vascularis play an important role as a barrier to HRP, whereas capillaries in the spiral ligament themselves act as a barrier to it.

Animals↗

PubMedDate not supplied

Morphological study of blood-labyrinth barrier in the vestibular organs under normal and experimental acute hypertensive and acute hypotensive conditions.

In order to examine a blood-labyrinth barrier in the vestibular region, capillary permeability of the vestibular organs, i.e. the sacculus, the utriculus and the ampullae of semicircular canals, were studied light and electron microscopically by the horseradish peroxidase (HRP) tracer method. Intravenously infused HRP was not observed outside capillaries because of the tightness of endothelial tight junctions and the paucity of pinocytotic vesicles. Furthermore, the effect of drug-induced acute hypertension and acute hypotension on the capillaries of the vestibular organs was studied morphologically using the tracer technique. In each experiment, there was no extravasation of HRP from capillaries, thus agreeing with the results of the experiment made under normal conditions. These findings mean that capillaries of the vestibular region are of ordinary brain capillary type and contribute to the blood-labyrinth barrier to macromolecules such as HRP both under normal conditions and following abrupt changes in blood pressure.

Animals↗

PubMedDate not supplied

Basic plan and assessment of an information system designed to aid patient transfer.

One of the important assignments in the planning of community medical care is to find an effective way of implementing the sharing of facilities together with their coordination. In particular, the establishment of a smooth and effective system co-ordinating facilities and functions of medical organizations, comprising clinics and hospitals of various levels, and the installation of an information system, designed to provide positive assistance in information control as well as in its operation, should be undertaken urgently. In this paper, we discuss the patient-transfer system, which is one of the facility-co-ordination-system for medical organizations, from the point of view of total community medical care. Specifically we describe the purpose, features and total structure of the patient-transfer system, and discuss the basic plan for an information system designed to aid patient transfer, from information control together with an advance assessment from the system-engineering point of view. This research has been promoted by the Aichi Medical Association committee for medical care system. The proposed system is planned to be operational in the near future.

Information Systems↗

PubMedDate not supplied

The cognitive syndrome of vascular dementia: implications for clinical trials.

Dementia is common among patients with cerebrovascular disease, particularly in a setting of one or more clinically evident strokes. Prior cohort and case studies have suggested that the cognitive syndrome of vascular dementia is characterized by predominant executive dysfunction, in contrast to the deficits in memory and language function that are typical of patients with Alzheimer disease. The course of cognitive decline may also differ between those dementia subtypes, with many, but not all, patients with vascular dementia exhibiting a stepwise course of decline caused by recurrent stroke and most patients with Alzheimer disease exhibiting a gradually progressive course of decline. The findings of prior studies of the cognitive syndrome of vascular dementia must be interpreted with caution, however, because of (1) possible inaccuracies in the determination of the dementia subtype and the loss of precision that might result from pooling heterogeneous subgroups of patients with vascular dementia, (2) difficulties inherent in identifying a pattern of strengths and weaknesses in patients who are required to have memory impairment and other deficits to meet operationalized criteria for dementia, and (3) the use of limited test batteries whose psychometric properties are incompletely understood. Specific questions that should be addressed by future studies are discussed.

Clinical Trials as Topic↗

PubMedDate not supplied

Anticancer effect of 4-[3,5-bis(trimethylsilyl)benzamido] benzoic acid (TAC-101) against A549 non-small cell lung cancer cell line is related to its anti-invasive activity.

We examined the effects of TAC-101 on the invasion and metastasis of human non-small cell lung cancer (NSCLC) cell lines. TAC-101 showed an ability to inhibit in vitro invasiveness of NSCLC at a non-cytotoxic concentration range of 3-10 microM; such concentration levels were easily achievable following oral administration of therapeutically effective doses. The inhibition of cell invasion at 10 microM of TAC-101 accounted for 58-69% when compared with control cells. Oral administration of TAC-101 (4 mg/kg/day) to mice bearing lung implanted A549 lung cancer resulted in significant life-prolonging effect (T/C: 143%). More pronounced life-prolonging effect was observed in the experimental liver metastasis model of A549, where T/C of 215% was observed following administration at 4 mg/kg/day of TAC-101. However, TAC-101 did not show the direct anti-tumor effect against the established A549 tumor xenografts after subcutaneous implantation. These findings suggest that TAC-101 interferes with cell-to-cell interaction processes leading, for instance, to the inhibition of the invasion of NSCLC cells. Taking into account the pharmacological properties of TAC-101, it is expected that TAC-101 may be a suitable candidate drug for the treatment of lung cancer patients, especially those with a predictable metastasizing potential.

Animals↗

PubMedDate not supplied

The induction of apoptosis and inhibition of AP-1 activity by TAC-101 (4-[3,5-bis(trimethylsilyl) benzamido] benzoic acid) may result in life prolonging effect in animals bearing metastasizing cancer.

BACKGROUND: The incidence of cancers of the digestive tract has been high among all of the cancers in Japan and the western hemisphere. The poor prognosis of patients, especially those with liver metastases, has become a great challenge for the development of a new drug to cope with this problem. MATERIALS AND METHODS: Mice implanted by intrasplenic injection of TMK-1, human gastric carcinoma cells, were used to examine the life-prolonging effect of TAC-101. To elucidate a mechanism of action of TAC-101, the drug-induced apoptosis was assessed by DNA ladder formation whilst the prevention of transcription factor AP-1 binding to its DNA recognition sequence was assessed by gel shift assay. RESULTS: TAC-101 showed the life prolonging effect in a model of experimental liver metastasis of TMK-1. The antitumor effect, expressed as T/C (%), was 201, 141 and 112%, for TAC-101 (2 mg/kg), ATRA (8 mg/kg) and 5-FU (19 mg/kg), respectively. The in vitro experiments revealed that the anticancer activity of TAC-101 is related to its ability to induce apoptosis within a short period of time in TMK-1 cells and human leukemic cells, HL-60. TAC-101-induced apoptosis was suppressed by the inhibitors of proteases, specifically by Z-Val-Ala-DL-Asp-fluoromethylketone, indicating the involvement of caspase activation. TAC-101 also inhibited, in a concentration-dependent manner, the binding of AP-1 to its DNA binding sites present in the promoter region of the genes involved in the control of cell migration, invasion, and angiogenesis. CONCLUSION: TAC-101 may suppress liver metastasis by the induction of an apoptotic mechanism(s) in cancer cells and possibly by controlling transcriptional activity of AP-1.

Animals↗

PubMedDate not supplied

Realistic expectations for treatment success in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive degenerative disease that warrants active management to delay or slow progression of its symptoms. The symptoms of AD encompass behavior and daily function as well as cognition, so clinicians should take a global view in the assessment of treatment success. Because there is currently no cure for AD, one cannot expect an initial cognitive improvement observed in the first few months of therapy to be sustained indefinitely. However, one should expect that the patient who is treated early and persistently with medication for AD will show less evidence of behavioral, functional, and cognitive deterioration over a period of time than one would expect in the absence of pharmacotherapy. Thus, treatment success includes not only short-term improvement of symptoms but also less decline over the long term. Determination of treatment success therefore also requires awareness of the typical progression of untreated AD. In this article we review the natural history of AD and evidence for the effectiveness of the treatments indicated for AD: donepezil, galantamine, rivastigmine, and memantine.

Aged↗