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Biomedical subjects

M Sano

Publications and source records attributed to M Sano.

At least 217 records · Page 12Linked to original sources
PubMed1997

Multicenter evaluation of new instruments for Alzheimer's disease clinical trials: summary of results. The Alzheimer's Disease Cooperative Study.

The Instrument Development Project of the Alzheimer's Disease Cooperative Study (ADCS) evaluated new assessments in five domains: (a) cognitive function; (b) clinical global change; (c) activities of daily living; (d) behavioral symptoms, and (e) cognition in severely impaired patients. These new instruments demonstrate excellent discrimination between normal controls and patient groups and show adequate validity and reliability. Stability of measurement and sensitivity to longitudinal change were also demonstrated in each of these areas. Examination of several domain-specific questions also contributed new information on the measurement of cognitive function with different subtasks across AD severity levels, the stability of clinical ratings of global change, and the applicability of behavioral assessment across severity levels. The success of this project enhances the state of the art in the measurement of efficacy in AD clinical trials and also provides a basis for future research on improving AD outcome measures.

Activities of Daily Living↗
PubMed1997

Molecular and genetic analysis of two patients with Bernard-Soulier syndrome--identification of new mutations in glycoprotein Ib alpha gene.

We investigated two unrelated patients with Bernard-Soulier syndrome (BSS) by performing molecular and genetic analysis. A flow cytometric and immunoblotting analysis showed GP Ib alpha to be absent from the platelet membrane of both patients. Other glycoproteins that formed GP Ib/IX/V complex were present on the platelets, but in decreased amounts. Therefore, GP Ib alpha gene from both cases was sequenced after PCR amplification and subcloning. We identified a homozygous mutation of a dinucleotide deletion within the TGTG repeat at cDNA number 972 to 975 in GP Ib alpha gene from Case 1. In Case 2, compound heterozygosity was demonstrated in GP Ib alpha gene; an insertion of a single base (T) at cDNA number 1,418 in one allele, and a deletion of a single base (A) within the 7-adenine repeat at cDNA number 1,438 to 1,444 in another allele. The three new mutations in both patients appeared to cause a frameshift, which created a new termination codon shortly thereafter, and thus lead to a GP Ib alpha deficiency on the platelet membrane. Truncated mutant proteins could be detected in the plasma and platelets of Case 2, but not of Case 1. According to these findings, it is thus supposed that the properties and conformation of additional COOH-terminal peptides, which were supposedly synthesized as results of the mutations, may have an important role on the processing of mutant GP Ib alpha in megakaryocytes and platelets.

Adult↗
PubMed1997

[Two cases of remitting seronegative symmetrical synovitis with pitting edema].

We report 2 elderly patients who present with a relatively acute onset of a severe symmetrical synovitis affecting the flexor digitorum tendon sheaths and wrist joints with pitting edema of the dorsum of both hands. These patients were seronegative for rheumatoid factor and responded to treatment with low dose predonisone (10 mg daily) without relapse. These presenting features were closely linked with the RS3PE syndrome originally described by McCarty.

Aged↗
PubMed1997

[Investigation of doxorubicin cardiotoxicity by echocardiogram and the appropriate method of using doxorubicin].

For a sample of 136 adults on whom Doxorubicin (DXR) had been used, we looked for the ejection fraction (EF) by echocardiography and examined its relationship with the amount of DXR. Our results showed that as the amount of DXR increased the EF decreased significantly, particularly with aging. The use of previous mediastinal radiation and 5-FU, etc. on breast cancer patients had no effect on the EF. From our examination of patients developing congestive heart failure, we repeatedly performed echocardiography and found that DXR can be safely used until the EF decreases to 55 percent. In this way, we can find many patients with whom it is possible to use DXR in larger amounts than 550 mg/m2. In general, large quantities of DXR can be used on young people, but for elderly people, large quantities of DXR should be used with caution.

Adult↗
PubMed1997

[Retinoic acid-induced cell growth inhibition and differentiation in testicular carcinoma cells in culture].

Testicular germ tumor cells could be differentiated spontaneously or by some chemotherapeutic compounds. However, the mechanism by which the cells are differentiating from the stem cell remains unclear. The KU-MT cells, which were newly established from lung metastasis of testicular carcinoma, have been continuously producing alpha fetoprotein (AFP). Retinoic acids are well-known to induce cellular differentiation in culture and have already been applied for a clinical usage against leukemia. In the present study, all-trans-retionic acid (ATRA) elevated the level of AFP and inhibited the growth of KU-MT cells in vitro. ATRA also arrested the cell cycle in G1 and reduced the percentage of the S phase cell in terms of wild type p53, leading to apoptosis in part. Retinoids, especially retinoic acid receptor (RAR)-alpha specific agonists induced laminin production, a marker of endodermal differentiation; whereas arotinoid, a retinoid not bound to RAR-alpha, did not affect laminin expression. In summary, retinoic acids could mediate cell growth and differentiation of testicular tumor through RAR-alpha.

Antineoplastic Agents↗
PubMed1996

Inhibition of the nerve growth factor-induced outgrowth of neurites by trichostatin A requires protein synthesis de novo in PC12D cells.

Trichostatin A (TSA) inhibits the activity of histone deacetylase and blocks both oncogenic ras-induced and nerve growth factor-induced (NGF-induced) outgrowth of neurites from PC12 cells. Cells of the PC12D subline extend neurites very rapidly in response to NGF, basic fibroblast growth factor (bFGF), dibutyryl cAMP (dbcAMP) and to staurosporine, even in the presence of an inhibitor of RNA synthesis, as do primed PC12 cells or cultured sympathetic neurons. TSA at 100 nM selectively blocked the NGF- and bFGF-induced outgrowth of neurites from PC12D cells, but not the outgrowth induced by dbcAMP or staurosporine. The NGF-induced changes in morphology with the relocalization of F-actin, were not inhibited by TSA. However, the subsequent formation of growth cones and the outgrowth of neurites was blocked. The activation of mitogen-activated protein (MAP) kinases in NGF-stimulated cells was also unaffected by TSA. When TSA was added to cells that were extending neurites in response to NGF, the number of neurite-bearing cells decreased after a lag period. In the presence of inhibitors of RNA or protein synthesis namely, actinomycin D, cordycepin, and cycloheximide, TSA no longer blocked the NGF- and bFGF-dependent outgrowth of neurites from PC12D cells. Regardless of the effect of TSA, the rapid outgrowth of neurites from PC12D cells was unaffected by the presence of cycloheximide, which inhibited protein synthesis by 97%, as determined by monitoring the incorporation of [35S]methionine/cysteine. This study provides proof that the NGF-induced elongation of neurites does not require protein synthesis de novo. These observations suggest that TSA might not inhibit the early signal-transduction pathway of NGF, but might block the late pathway, which is related to the formation of growth cones and/or neurites. Cellular conditions that no longer allow the NGF- and bFGF-mediated elongation of neurites might be produced by TSA via synthesis of some specific protein(s) due to changes in RNA(s) synthesis de novo.

Animals↗
PubMed1996

Re-examination of the local control by nerve growth factor of the outgrowth of neurites in PC12D cells.

We have examined the local control by nerve growth factor (NGF) of the outgrowth of neurites from clonal cells, PC12D, a subline whose phenotype resembles that of the parent PC12 cell line in the NGF-primed state. We show here that (i) the outgrowth of neurites, and their survival can be induced by NGF in enucleated PC12D cells (ii) individual neurites of a single 'giant cell', produced by cell fusion of PC12D cells, can respond independently to the NGF in the local environment, (iii) dissected neurites from giant cells survive for longer in medium that contains NGF than in medium that does not, (iv) in PC12D cells, the rapid formation of ruffles in response to NGF, which appears to be based on increased cell-substratum adhesion, leads to the subsequent formation of neurites, and (v) upon addition of NGF, the movement of short processes displaces polylysine-coated beads in the vicinity of neurites. These observations suggest that the NGF-dependent maintenance or extension of neurites might be controlled within the neurites themselves and might not require the direct involvement of the cell body, even in PC12 cells. It seems possible that any NGF-induced changes that promote an increase in cell-substratum adhesion might be responsible for the initiation and elongation of neurites. It also seems possible that the growth of neurites towards a source of NGF might be based on repeated rounds of extension and retraction of filopodia and neurites in a manner that depends on the concentration of NGF.

Animals↗
PubMed1996

Lack of tumor promoting effects of KCB-1, a recombinant human basic fibroblast growth factor, on two-stage skin carcinogenesis in female CD-1 (ICR) mice.

Skin tumor promoting and co-promoting potentials of KCB-1, a recombinant human basic fibroblast growth factor, were investigated in a two-stage skin carcinogenesis model using female ICR mice. Animals were allocated to either normal (non-injured) or injured skin groups, and given a single topical application of dimethylbenz[alpha]anthracene (DMBA) at 100 micrograms/mouse to fur-clipped back skin. One week after the DMBA initiation step, mice were injected with KCB-1 (0.4, 4.0 and 40 micrograms/mouse, s.c.) and/or 12-O-tetradecanoylphorbol-13-acetate (TPA) at 4.0 micrograms/mouse twice a week until the termination at week 20. The treatment with KCB-1 was not associated with any increases of papillomas and hyperplasias in either the normal or the wounded skin cases. High incidences and multiplicities of skin papillomas and hyperplasias developed in TPA-treated groups. The positive control TPA promotion was not influenced by the KCB-1 treatment in the present initiation/promotion protocol. Thus, KCB-1 exerted no tumor promoting effects on mouse skin two-stage carcinogenesis, and also no amplification activity for the established skin tumor promoter TPA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

An attempt to generate an antitumor effect in the regional lymph nodes against endometrial cancer cells by inducing antitumor cytokines.

Phytohemagglutinin-stimulated regional lymph node cells obtained from gynecological cancer patients exerted a significant antiproliferative activity against an endometrial cancer cell line, RL95-2 on a human tumor clonogenic assay, and released a high amount of tumor necrosis factor alpha (TNF alpha), and interferons. The activity was thought to be partly due to released TNF alpha, because RL95-2 was highly sensitive to recombinant TNF alpha. However, anti-TNF alpha failed to inhibit the activity, which indicated the probability of some as yet unclarified participation of cytokines. Therefore, the regional lymph nodes might be used as sites of endogenous cytokine therapy in endometrial cancer patients.

Antibodies↗
PubMed1996

Modeling the influence of extrapyramidal signs on the progression of Alzheimer disease.

OBJECTIVE: To determine how the advent of extrapyramidal signs influences the progression of Alzheimer disease as measured by standard clinical measures. DESIGN: We applied growth curve models to prospective data to characterize patients' cognitive and functional changes over time. To detect changes in disease course related to extrapyramidal signs, their onset was treated as a time-dependent covariate. SETTING: Three research medical centers. PARTICIPANTS: Patients (n = 217) with probable Alzheimer disease. INTERVENTION: Patients were followed up semiannually for 5 years. MAIN OUTCOME MEASURES: Scores on the modified Mini-Mental State Examination and measures of basic and instrumental activities of daily living from the Blessed Dementia Rating Scale. RESULTS: For basic and instrumental activities of daily living, disease course was more rapid once extrapyramidal signs developed. Decline in the modified Mini-Mental State Examination score was greater at the time the signs developed, but not at subsequent visits. CONCLUSIONS: The point at which extrapyramidal signs emerge is associated with measurable acceleration in the progression of Alzheimer disease. This may in part explain why extrapyramidal signs are associated with a poorer prognosis. The differential influence of extrapyramidal signs on cognitive and functional measures suggests that the pathological changes underlying these disease features may vary.

Aged↗
PubMed1996

Depressed mood and the incidence of Alzheimer's disease in the elderly living in the community.

BACKGROUND: It remains unclear whether depression increases the risk for dementia in the elderly. We evaluated the relationship between depressed mood at baseline and the incidence of dementia, particularly Alzheimer's disease, in the elderly living in the community. METHODS: A total of 1070 elderly individuals, aged 60 years or older, were identified as part of a registry for dementia in the Washington Heights community of North Manhattan, NY. In a prospective, longitudinal design with follow-up for 1 to 5 years, annual physician evaluation and neuropsychological testing were used to assess levels of cognitive impairment and to diagnose dementia. Depressive symptoms were evaluated with the 17-item Hamilton Rating Scale for Depression. Based on clinical considerations and a validity study, a positive score for the depressed mood item was used in statistical analyses. To confirm the results, the total Hamilton Rating Scale for Depression score was also evaluated as the "depression" variable. RESULTS: Of the 1070 subjects, 218 met criteria for dementia at baseline evaluation. In the 852 subjects without dementia, depressed mood was more common in individuals with greater cognitive impairment. In a follow-up study of 478 of these subjects without dementia (mean +/- SD, 2.54 +/- 1.12 years of follow-up), the effect of baseline depressed mood on the end-point diagnosis of dementia (93% had possible or probable Alzheimer's disease) was evaluated in a Cox proportional hazards model. Depressed mood at baseline was associated with an increased risk of incident dementia (relative risk, 2.94; 95% confidence interval, 1.76 to 4.91; P < .001). This effect remained after adjustment for age, gender, education, language of assessment, Blessed Memory Information and Concentration test scores, and Blessed Functional Activity Scale scores (relative risk, 2.05; 95% confidence interval, 1.16 to 3.62; P < .02). Similar results were obtained when the total Hamilton Rating Scale for Depression score was used as the depression variable, with the use of the same covariates (relative risk, 1.07 per point interval; 95% confidence interval, 1.02 to 1.11; P < .01). CONCLUSIONS: Depressed mood moderately increased the risk of developing dementia, primarily Alzheimer's disease. Whether depressed mood is a very early manifestation of Alzheimer's disease, or increases susceptibility through another mechanism, remains to be determined.

Age Factors↗
PubMed1996

Cough threshold for capsaicin increases by azelastine in patients with cough-variant asthma.

To assess the effects of azelastine in patients with cough-variant asthma, we measured the cough threshold for capsaicin (the concentration required to elicit more than five coughs) in 16 patients with cough-variant asthma before and after 4 weeks of treatment with azelastine (2 mg; b.i.d.) or placebo. After treatment, coughing decreased in all patients and the cough threshold for capsaicin increased significantly, from 0.67 +/- 0.30 microM to 4.76 +/- 1.55 microM (P < 0.01) in the azelastine group. However, the cough threshold for capsaicin did not increase significantly, from 0.86 +/- 0.33 microM to 1.11 +/- 0.35 microM (P > 0.10) in the placebo group. These results suggest that azelastine inhibits coughing in patients with cough-variant asthma.

Adult↗