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Biomedical subjects

T Wada

Publications and source records attributed to T Wada.

At least 181 records · Page 10Linked to original sources

Synthesis and conformation control of peptide ribonucleic acid containing 5'-amino-5'-deoxyribopurinenucleosides.

A novel nucleic acid model, i.e. peptide ribonucleic acid (PRNA), tethering 5'-amino-5'-deoxypyrimidine ribonucleoside as a recognition site for nucleic acids, has been designed and synthesized. We have demonstrated that the recognition behavior of PRNA with complementary oligopurinenucleotides can be controlled externally through the orientational switching of the pyrimidine nucleobase of PRNA induced by added borates. We extend this methodology of controlling the nucleobase orientation and recognition behavior of novel mono and oligomeric PRNAs containing 5'-amino-5'-deoxypyrimidine and/or purinenucleosides. In case of the PRNA oligomer containing pyrimidine-purine mixed sequence, efficient orientational switching of nucleobases induced by added borates was also observed.

Borates↗

Predictors of female condom use among women exchanging street sex in New York City.

BACKGROUND: Alternative female-initiated barrier methods, such as the female condom, are needed among women exchanging street sex to enhance their ability to protect themselves from HIV and STD infection. OBJECTIVE: To describe predictors of female condom use among 96 women exchanging sex for money and drugs on the streets of New York City. STUDY DESIGN: A total of 113 sex workers received a baseline interview, a demonstration on proper female condom use, and 10 female condoms. A total of 101 sex workers received a followed-up evaluation at 2 weeks, of which 96 were included in data analysis. Predictors of condom use were analyzed for (1) any type of use; and (2) use with commercial partners. RESULTS: The strongest predictors of female condom use among this sample of sex workers were (1) living with someone with a drug or alcohol problem; (2) having heard of the female condom; and (3) homelessness. Current physical or sexual abuse by a commercial partner and marriage decreased the probability of female condom use. CONCLUSIONS: Female condom distribution encouraged sex workers who may be most vulnerable or who reported characteristics or behaviors associated with the highest sexually transmitted disease and HIV risk to try female condoms with commercial partners. Implications for intervention development include the need to develop innovative programs provided on the street (e.g., through peers) that can access homeless, drug-using sex workers in the most at-risk environments.

Adult↗

Diffusion over a saddle with a langevin equation

The diffusion problem over a saddle is studied using a multidimensional Langevin equation. An analytical solution is derived for a quadratic potential and the probability to pass over the barrier deduced. A very simple solution is given for the one-dimensional problem and a general scheme is shown for higher dimensions.

Journal Article↗

RPT2. A signal transducer of the phototropic response in Arabidopsis.

The blue light receptor NPH1 (for nonphototropic hypocotyl) has been considered to be the only UV-A/blue light receptor that induces a phototropic response by the hypocotyl and root of Arabidopsis. By analysis of root phototropism (rpt) mutants, we show, however, the involvement of another blue light receptor as well as the existence of two separate signaling pathways working downstream of these receptors in the phototropic response. A newly isolated gene, RPT2, controls one of these pathways. The RPT2 gene is light inducible; encodes a novel protein with putative phosphorylation sites, a nuclear localization signal, a BTB/POZ domain, and a coiled-coil domain; and belongs to a large gene family that includes the recently isolated NPH3 gene. From genetic, physiological, and biochemical evidence, we propose a genetic model of the signaling pathways that induce the phototropic response in Arabidopsis.

Amino Acid Sequence↗

Induction of cytotoxic T lymphocytes from peripheral blood of human histocompatibility antigen (HLA)-A31(+) gastric cancer patients by in vitro stimulation with antigenic peptide of signet ring cell carcinoma.

Antigenic peptides have been used as a cancer vaccine in melanoma patients and have led to a drastic regression of metastatic tumors. However, few antigens have been identified in non-melanoma tumors. We recently purified a new natural antigenic peptide, designated F4. 2, by biochemical elution from a human gastric signet cell carcinoma cell line and showed that it is recognized by an autologous human histocompatibility antigen (HLA)-A31-restricted cytotoxic T lymphocyte (CTL) clone. Here we describe in vitro induction of F4. 2-specific CTLs from peripheral blood T lymphocytes of HLA-A31( +) gastric cancer patients. The T cells of seven HLA-A31( +) patients with gastric cancers were stimulated in vitro by F4.2-pulsed autologous dendritic cells which had been induced from peripheral blood of each patient by incubation in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF) and IL-4. We tested the cytotoxicity of the T cells against F4.2-loaded C1R-A*31012 by a 6-h (51)Cr release assay after 3 stimulations with F4.2-pulsed dendritic cells. F4.2-specific cytotoxicity was detectable in the stimulated T cells from two of the seven HLA-A31( +) patients. Further, both F4.2-specific CTLs also lysed the gastric cancer cell line, HST-2, from which F4.2 was derived. These results suggest that F4.2 peptide may be useful as an HLA-A31-restricted peptide vaccine in certain patients with gastric cancer.

Adjuvants, Immunologic↗

ADAMTS-1: a metalloproteinase-disintegrin essential for normal growth, fertility, and organ morphology and function.

A disintegrin and metalloproteinase (ADAM) represents a protein family possessing both metalloproteinase and disintegrin domains. ADAMTS-1, an ADAM family member cloned from cachexigenic colon adenocarcinoma, is unusual in that it contains thrombospondin type I motifs and anchors to the extracellular matrix. To elucidate the biological role of ADAMTS-1, we developed ADAMTS-1-null mice by gene targeting. Targeted disruption of the mouse ADAMTS-1 gene resulted in growth retardation with adipose tissue malformation. Impaired female fertilization accompanied by histological changes in the uterus and ovaries also resulted. Furthermore, ADAMTS-1(-/-) mice demonstrated enlarged renal calices with fibrotic changes from the ureteropelvic junction through the ureter, and abnormal adrenal medullary architecture without capillary formation. ADAMTS-1 thus appears necessary for normal growth, fertility, and organ morphology and function. Moreover, the resemblance of the renal phenotype to human ureteropelvic junction obstruction may provide a clue to the pathogenesis of this common congenital disease.

ADAM Proteins↗

Effect of 7-nitroindazole upon cochlear dysfunction induced by transient local anoxia.

The purpose of the present study was to further elucidate how nitric oxide (NO) is involved in cochlear anoxia-reperfusion injury. Transient local anoxia of the cochlea was induced in albino guinea pigs for 15, 30, or 60 minutes by transiently compressing the labyrinthine artery through a skull base approach. 7-Nitroindazole (7NI), a relatively selective neuronal nitric oxide synthase (nNOS) inhibitor. was intraperitoneally administered to the guinea pigs 30 minutes before the onset of local anoxia. The compound action potential (CAP) thresholds were measured before the administration of 7NI and 4 hours after the onset of reperfusion. A statistically significant reduction in the postanoxic CAP threshold shift from the preadministration value was observed in the 7NI-administered animals as compared with the control animals after 15- and 30-minute periods of anoxia. These results confirm the involvement of NO and nNOS in the cochlear injury induced by transient local anoxia.

Action Potentials↗

Inhibitory effects of tetrahydroisoquinoline derivatives on Ca2+ and Na+ channels in crude nerve endings.

Semi-synthetic tetrahydroisoquinoline derivatives prepared from natural alkaloids, possess Ca2+ antagonistic properties. These derivatives significantly blocked KCl-stimulated Ca2+ uptake (In chick and rat crude nerve endings) which can be partially inhibited by the selective N-type Ca2+ channel blocker omega-conotoxin GVIA or the selective P-type Ca2+ channel blocker omega-agatoxin IVA. Moreover, PX42 (10 microM; for the tetrahydroisoquinoline compounds in this study) could inhibit the activity of calmodulin-dependent phosphodiesterase and block veratridine-induced (or tetrodotoxin-sensitive) Na+ uptake. The possible mechanism(s) of non-selective inhibition of ion channels of PX42 is discussed.

Animals↗

The medial approach for operative release of post-traumatic contracture of the elbow.

We treated post-traumatic contracture of the elbow in 13 consecutive patients (14 elbows) by operative release. Through a single medial approach, the posterior oblique bundle of the medial collateral ligament was resected, followed by posterior and anterior capsulectomies. An additional lateral release through a separate incision was required in only four elbows. The results were assessed at a mean interval of 57 months after operation. Before surgery active extension lacked 43 degrees which improved to 17 degrees after operation. Active flexion before operation was 89 degrees, which improved to 127 degrees. The mean arc of movement increased from 46 degrees to 110 degrees. All 14 elbows showed scarring of the posterior oblique bundle of the medial collateral ligament. Neither the interval from injury to operative release nor the age of the patient affected the results. A medial approach is useful to reveal and excise the pathological changes in the medial collateral ligament. It is a safe and effective route through which to correct post-traumatic contracture of the elbow.

Adolescent↗

Resection arthrodesis of the knee with a vascularised fibular graft. Medium- to long-term results.

We present the results in 12 patients of arthrodesis of the knee using a vascularised fibular graft after resection of a malignant bone tumour. At a mean follow-up of 95 months (60 to 178) all patients were free from disease although 11 had had at least one complication, with stress fracture of the graft in five patients, nonunion in two and deep infection requiring above-knee amputation in one. Despite the high rate of complications, satisfactory results can be obtained using this technique. Careful preoperative counselling is required.

Adolescent↗

Reconstruction and limb salvage using a free vascularised fibular graft for periacetabular malignant bone tumours.

We treated four patients with periacetabular malignant tumours by pelvic reconstruction with a free vascularised fibular graft after resection of the tumour. The mean follow-up period was 32 months (9 to 39). The diagnosis was chondrosarcoma in three patients and osteosarcoma in one. In two patients total resection of the hemipelvis was required and in the other two less, but still massive, resection was undertaken. All were treated with an immediate free vascularised fibular graft which included arthrodesis of the hip and reconstruction of the pelvic ring. One patient died. The other three have remained free from recurrence. Solid union of the graft was achieved between four and 14 months after surgery. Shortening of the involved limbs was less than 2 cm. The patients had no pain and were independent walkers without external support. Emotional acceptance was satisfactory. Our results suggest that reconstruction with the use of a free vascularised graft is an alternative to other types of reconstructive procedure after resection of periacetabular tumours.

Acetabulum↗

Nasalance score variation in normal adult Japanese speakers of Mid-West Japanese dialect.

OBJECTIVE: The aims of this study were to examine nasalance score variation for normal adult Japanese speakers of Mid-West dialect and the gender difference in average mean nasalance score. DESIGN: Nasalance scores were obtained using a nasometer model 6200. The sample stimulus "Kitsutsuki passage," constructed of four sentences containing no Japanese nasal sounds, was used three times by each subject. PARTICIPANTS: One hundred normal adult speakers (50 women and 50 men) of Japanese served as subjects. The subjects ranged in age from 19 to 35 years of age (24.0 +/- 3.2). MAIN OUTCOME MEASURE: A mean nasalance score as well as an overall average nasalance value across speakers was calculated for each subject. The average mean nasalance scores between men and women were compared. RESULTS: The average mean nasalance score for the normal Japanese speakers was 9.1% (+/- 3.9). There was no statistically significant sex difference (p < .01). Average mean scores of 9.8% (+/- 3.5) and 8.3% (+/- 4.0) were obtained for the female and male speakers, respectively. CONCLUSIONS: The results provide important information concerning criteria to evaluate hypernasal speech due to velopharyngeal inadequacy of Japanese speakers with cleft palate using the nasometer.

Adult↗

Effect of placement of a speech appliance on levator veli palatini muscle activity during speech.

OBJECTIVE: The purposes of this electromyographic study were to examine whether levator veli palatini muscle activity during speech can be changed with placement of a speech appliance and to clarify whether or not the change is related to the type of speech appliance used. DESIGN: Electromyography (EMG) was performed during production of speech samples in two conditions: with placement and with removal of a speech appliance. Speech samples were the vowel /omega/ and consonant-vowel (omega) syllables, including nasal, plosive, fricative, and affricate consonants. SETTING: Division for Oral-Facial Disorders, Faculty of Dentistry, Osaka University Dental Hospital, Japan. PARTICIPANTS: Subjects were six patients with repaired cleft palate and velopharyngeal inadequacy (VPI); three routinely wore a palatal lift prosthesis to correct borderline VPI, and the other three wore a speech appliance hybrid that consisted of a pharyngeal bulb and a palatal lift. INTERVENTIONS: Each patient was asked to produce each speech sample in both conditions of placement and removal of their respective appliances. MAIN OUTCOME MEASURES: Smoothed EMG signals of the levator veli palatini muscle were recorded with and without the appliance during five repetitions of each speech sample. The average value of peak smoothed levator EMG was compared between placement and removal conditions for all subjects and between the two subject groups in each experimental condition. RESULTS: With a speech appliance in place, the range of levator activity was distributed in a portion lower than that in the removed condition for subjects in both appliance groups. In addition, the intervals were smaller in the placement condition than in the removed condition. CONCLUSION: A speech appliance may prevent hypernasality, nasal emission of air, or both associated with VPI because of mechanical obturation of the velopharynx and an alteration in velopharyngeal function.

Adolescent↗

[The comparison of blood pressure of community-dwelling elderly subjects in Okinawa and Shikoku].

In Japan hypertension is frequent, but the prevalence of hypertension in Okinawa has been known to be lower than in other areas in Japan. Now it has been almost 30 years since Okinawa reverted to Japan. So we investigated to know whether the prevalence of hypertension was still lower today or not. We compared the differences of prevalence of hypertension and blood pressure (BP) levels between the two community-dwelling elderly subjects aged 75 years or more: 305 in Ie in Okinawa (M:F = 107:198, mean age: 81 years old), and 99 in Omogo in Ehime, Shikoku (M:F = 45:54, mean age: 81 years old). We visited the homes of the elderly and measured their BP twice in a sitting position and asked them whether they were taking medicine for hypertension or not. According to the 1999 revised guidelines on the treatment of hypertension in the elderly by the Japanese Society of Geriatrics, we defined hypertension as systolic BP (SBP) > or = 160 mmHg or diastolic BP (DBP) > or = 90 mmHg or taking medicine for hypertension, and normotension as SBP < 160 mmHg and DBP < 90 mmHg and not taking medicine for hypertension. Hypertension rates were 52% in Ie, and 59% in Omogo, indicating no significant difference. However, in Ie only 54% of the elderly with hypertension were taking medicine for hypertension, as opposed to 74% in Omogo. These results suggest the possibility that in Okinawa hypertension is thought to be less important than in other districts in Japan.

Aged↗

[Changes in liver function induced by flutamide in patients with prostate cancer (studies in patients treated with total androgen blockage)].

OBJECTIVES: The incidence of flutamide-induced liver toxicity was studied in 30 consecutive patients with prostate cancer who were treated with total androgen blockage (TAB) therapy (luteinizing hormone releasing hormone [LHRH] analogue and flutamide) in our hospital during the last 3 years and in 20 consecutive patients with prostate cancer who were treated by partial androgen blockage (PAB) therapy (LHRH analogue alone). METHODS: Liver function test, including measurement of serum levels of aspartate aminotransferase (AST) alanine aminotransferase (ALT), total cholesterol, total bilirubin, gamma-glutamyl transpeptidase (gamma-GTP), and cholinesterase were performed at regular interval. RESULTS: The incidence of liver toxicity in patients receiving TAB (10 cases of 25 patients) was significantly higher than in patients receiving PAB (2 of 18 patients). Two patients in whom severe liver toxicity developed after receiving TAB were hospitalized. However, after flutamide was discontinued all patients with liver damage recovered with normalization of AST and ALT levels. Levels of total cholesterol and gamma-GTP did not differ significantly in either patient group. In two patients receiving TAB total bilirubin levels showed slight, transient elevations after maximum elevations of AST and ALT. In 80% of patients receiving TAB serum levels of cholinesterase were significantly higher than those in patients receiving PAB. CONCLUSION: These data suggest that the risk of flutamide-induced liver toxicity is significant in patients receiving TAB. However, this damage can be normalized after flutamide has been discontinued. Serum levels of cholinesterase also increase significantly in patients receiving TAB. This previously unreported phenomenon suggests an unknown effect of flutamide on liver function in patients with prostate cancer.

Aged↗

Vascular endothelial growth factor expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis.

To investigate the clinical significance of vascular endothelial growth factor (VEGF) in osteosarcoma, we immunohistochemically stained biopsy specimens of 27 primary osteosarcomas using an antibody against VEGF and evaluated the correlation between the expression of VEGF and local density of CD34-positive microvessels, clinicopathological variables, and survival of patients. VEGF staining was positive in 17 tumors (63.0%) in which the density of CD34-positive microvessels was significantly higher than that in VEGF-negative 10 tumors (P < 0.05). In terms of clinicopathological variables, there was no correlation between the expression of VEGF and histological subtype, stage, or response to neoadjuvant chemotherapy, or, strikingly, to the development of pulmonary metastasis (89% of VEGF-positive tumors versus 10% of VEGF-negative tumors; P < 0.0003). Moreover, patients with a VEGF-positive tumor were poorer in both disease-free survival (P < 0.001) and overall survival (P < 0.03) compared to those with a VEGF-negative tumor. These findings strongly suggest that VEGF expression in untreated osteosarcoma is predictive of pulmonary metastasis and poor prognosis in patients who underwent aggressive therapy and also provide the basis for a therapeutic strategy targeting angiogeneic property of osteosarcoma.

Adolescent↗

Bladder cancer: allelic deletions at and around the retinoblastoma tumor suppressor gene in relation to stage and grade.

Inhibition of the retinoblastoma tumor suppressor gene (RB) is probably important in the pathogenesis of urinary bladder cancer. Little information is available concerning allelic loss on 13q11 to 13q32 and its relation to grade and stage. In a population-based study, freshly frozen tissue was collected from all new cases of urinary bladder cancer in the Stockholm region during 1995-1996. Here we report the occurrence of loss of heterozygosity (LOH) at seven sites in 13q11 to 13q32 as analyzed in 236 cases by a fluorescent multiplex PCR-based on tumor DNA and peripheral blood. For each site, about 30% of the cases were not informative because of homozygosity. Replication errors were detected in 4% (17 cases). LOH was found in 21 (at 13q11-12.1) to 32% (at 13q14.3 in RB) of the informative cases. A correlation was found between the prevalence of LOH at all observed loci and stage and grade, respectively, and it was statistically significant for 13q14.3. LOH at RB was found in Ta as well as grade 1 tumors. Also, a statistically significant correlation was found between the number of loci with LOH at 13q and tumor stage and grade, respectively. Typically an altered RB function is related to the expected clinical course of urinary bladder cancer, but allelic loss including the gene also occurs in low grade and low stage tumors. An altered RB function probably is not necessary for a malignant transformation of urothelial cells. The causal direction of the relation between the quantity of the deleted DNA and tumor aggressiveness is not clear.

Alleles↗