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Biomedical subjects

T Wada

Publications and source records attributed to T Wada.

At least 271 records · Page 15Linked to original sources
PubMed1999

A case of metastatic extramammary Paget's disease that responded to combination chemotherapy.

Extramammary Paget's disease is considered to be a malignant tumor originating from the sweat glands. Some cases of extramammary Paget's disease infiltrate the dermis and metastasize to the regional lymph nodes. No standard treatment has been established for advanced cases. Few previous studies of the treatment for metastatic Paget's disease have revealed an effective regimen. The prognosis of metastasized cases is very poor. We encountered a patient in whom extramammary Paget's disease had metastasized to the lymph nodes beyond the regional lymph nodes and systemic chemotherapy was partially effective. Combination chemotherapy consisted of mitomycin C 3.5 mg/m2 and epirubicin 50 mg/m2 on day 1, vincristine 0.6 mg/m2 on days 1 and 7, cisplatin 30 mg/m2 from days 1 to 3, and 5-fluorouracil 350 mg/m2 from days 3 to 7. After two courses of chemotherapy, the metastatic lymph nodes decreased in size by more than 90% compared to that before chemotherapy. We defined the treatment effect of this regimen as a partial response (PR). Microscopic examination of the resected lymph nodes revealed replacement of metastatic lesions by fibrous tissue, suggesting a therapeutic effect. Anorexia, alopecia, and leukopenia (neutropenia) have been reported as toxicities, but all were tolerated. Our results may provide useful indications for the management of this tumor. This particular combination chemotherapy is recommended for extramammary Paget's disease patients with systemic nodal metastases.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Combination chemotherapy with nedaplatin and cyclophosphamide in human ovarian cancer model.

The antitumor efficacy of the combination of nedaplatin (NDP) with cyclophosphamide (CPM) was evaluated using human ovarian cancer models. Since NDP has been found to have greater antitumor activity and lower nephrotoxicity than cisplatin (CDDP), we also compared the antitumor activity of NDP plus CPM with that of CDDP plus CPM. Increasing doses of NDP (16.5, 33 and 66 mg/kg as a total dose) and a fixed amount of CPM (174 or 348 mg/kg as a total dose) were injected three times at intervals of 7 days via the tail vein into mice implanted with RMUG-S, OC9-JCK or KF-28 human ovarian cancer. Simultaneous administration of NDP with CPM resulted in markedly enhanced inhibition of tumor growth for all cancers tested. The growth inhibition and survival effect of the combination therapy of NDP with CPM against KF-28 and OC9-JCK were as potent as those of CDDP plus CPM. Neither increased hematotoxicity nor a significant difference in maximum concentration, half time or area under the curve of platinum or CPM in plasma between the single and combined treatment was found. These results suggest that the combination of NDP with CPM may be clinically effective.

Animals↗
PubMed1999

A U-shaped association between home systolic blood pressure and four-year mortality in community-dwelling older men.

BACKGROUND: Several studies in older people have found a U-shaped or J-shaped association of blood pressure with mortality. The increased mortality associated with the lowest levels of blood pressure in older people have been explained by concurrent illnesses and frailty, but previous studies used blood pressure measured on a single occasion. Such a casual value is different from the long-term average of blood pressure. We investigated the relation between the average level of 5-day consecutive home blood pressure and mortality in older people while adjusting for potential confounding factors including morbidity and frailty at baseline. METHODS: In 1992, 1186 community residents of a rural Japanese town, Kahoku, aged 65 or older, measured their blood pressure in their homes 20 times (four times per day, 5 consecutive days). The mean value of the 20 measurements was used to examine the association between home BP and subsequent 4-year mortality. A proportional hazards model was fitted while adjusting for activities of daily living impairment, medical history, antihypertensive medication, smoking, use of alcohol, and depression. RESULTS: A total of 134 persons died during the four-year follow-up period. There was no significant evidence that frailty is more prevalent in the lowest or highest systolic BP group than in intermediate groups. A U-shaped association between the average level of home systolic blood pressure and mortality was found in men while adjusting for potential confounding factors, including morbidity and frailty. We also showed the U-shaped curve of the association of systolic BP with all cause and noncardiovascular mortality in the whole population and the linear association of systolic BP with cardiovascular mortality. CONCLUSIONS: We showed a U-shaped association between the average level of systolic blood pressure measured at home and mortality in older men while adjusting for potential confounding factors including morbidity and frailty. Not only high home systolic BP, but also low home systolic BP, is an independent risk factor for mortality in older men. The mechanisms underlying the association between BP and mortality differ by levels of systolic BP. Cardiovascular deaths tended to be higher in the highest SBP group, and only noncardiovascular deaths were increased in the lowest SBP group. The latter finding suggests that low SBP may be not only an independent risk of mortality but also an indicator of a subclinical noncardiovascular comorbid condition.

Activities of Daily Living↗
PubMed1999

Transcranial Doppler findings during balloon test occlusion of the internal carotid artery.

The authors performed transcranial Doppler ultrasonography (TCD) during internal carotid artery (ICA) balloon test occlusion (BTO) and observed changes in mean flow velocity (Vm) in the middle cerebral artery (MCA), and pulsatility index (PI) while monitoring the stump pressure (Sp) of the internal carotid artery (ICA), and neurologic findings. A group of 17 patients requiring possible temporary or permanent occlusion of the ICA in the course of planned procedures first underwent BTO. A patient who either developed neurologic changes or maintained less than 60% of preocclusion Sp or Vm in the ipsilateral MCA during BTO was considered to have a positive test. Eleven patients had negative results, while in six patients, tests were positive. Mean flow velocity showed a decrease after occlusion in all cases but not to a remarkable extent in some patients. Stump pressure decreased in all negative cases after balloon inflation and than tended to increase progressively during 15 minutes of BTO. Pulsatility index tended to decrease gradually during BTO in all negative patients. However, in positive cases, PI and Sp fell steeply. Only one positive case had a neurologic symptom of severe headache. The decreased PI in the MCA reflected autoregulatory dilation of cerebral vessels to compensate for decreased absolute cerebral blood volume following ICA occlusion. Changes in PI are a good indicator for evaluating blood flow during BTO.

Blood Flow Velocity↗
PubMed1999

Tat-SF1 protein associates with RAP30 and human SPT5 proteins.

The potent transactivator Tat recognizes the transactivation response RNA element (TAR) of human immunodeficiency virus type 1 and stimulates the processivity of elongation of RNA polymerase (Pol) II complexes. The cellular proteins Tat-SF1 and human SPT5 (hSPT5) are required for Tat activation as shown by immunodepletion with specific sera and complementation with recombinant proteins. In nuclear extracts, small fractions of both hSPT5 and Pol II are associated with Tat-SF1 protein. Surprisingly, the RAP30 protein of the heterodimeric transcription TFIIF factor is associated with Tat-SF1, while the RAP74 subunit of TFIIF is not coimmunoprecipitated with Tat-SF1. Overexpression of Tat-SF1 and hSPT5 specifically stimulates the transcriptional activity of Tat in vivo. These results suggest that Tat-SF1 and hSPT5 are indispensable cellular factors supporting Tat-specific transcription activation and that they may interact with RAP30 in controlling elongation.

Chromosomal Proteins, Non-Histone↗
PubMed1999

DISI Deformity and Post-Operative Symptoms of Scaphoid Non-Union.

The correlation between the residual dorsal intercalated segmental instability (DISI) deformity and symptoms of the wrist was investigated in 20 patients with healed scaphoid non-union who had open reduction and bone grafting. In seven patients, inlay corticocancellous bone grafting (modified Russe procedure) was performed. In four of the seven patients, an additional Herbert bone screw was used for internal fixation. The remaining 13 patients were treated with open reduction, anterior bone grafting, and internal fixation with Herbert bone screw. Average duration of follow-up period after operation was 20 months (range, 6 to 57 months). The average extension-flexion arc of the injured wrists was 129 degrees, which was 31 degrees less than that of the uninjured wrists. The average grip strength of the injured wrists was 89% of that of the uninjured wrist. Before the operation, all 20 patients were symptomatic and complained of wrist pains. Post-operatively, three patients experienced mild pains and only one complained of moderate wrist pains. Post-operative radiolunate angle ranged from 0 degrees to 34 degrees (average 10 degrees ). DISI deformity remained uncorrected in eight patients. Post-operative symptoms were compared amongst the eight patients who had DISI deformity and 12 patients who had no deformity. There was no significant difference in range of motion, grip strength, and incidence of pain between these two groups of patients. The presence of DISI deformity after bone grafting for a symptomatic scaphoid non-union was not predictive of post-operative symptoms of the wrist.

Journal Article↗
PubMed1999

Oxidative stress causes enhanced endothelial cell injury in human heme oxygenase-1 deficiency.

The first known human case of heme oxygenase-1 (HO-1) deficiency is presented in this report. The patient is a six-year-old boy with severe growth retardation. He has been suffering from persistent hemolytic anemia characterized by marked erythrocyte fragmentation and intravascular hemolysis, with paradoxical increase of serum haptoglobin and low bilirubin. An abnormal coagulation/fibrinolysis system, associated with elevated thrombomodulin and von Willebrand factor, indicated the presence of severe, persistent endothelial damage. Electron microscopy of renal glomeruli revealed detachment of endothelium, with subendothelial deposition of an unidentified material. Iron deposition was noted in renal and hepatic tissue. Immunohistochemistry of hepatic tissue and immunoblotting of a cadmium-stimulated Epstein-Barr virus-transformed lymphoblastoid cell line (LCL) revealed complete absence of HO-1 production. An LCL derived from the patient was extremely sensitive to hemin-induced cell injury. Sequence analysis of the patient's HO-1 gene revealed complete loss of exon-2 of the maternal allele and a two-nucleotide deletion within exon3 of the paternal allele. Growth retardation, anemia, iron deposition, and vulnerability to stressful injury are all characteristics observed in recently described HO-1 targeted mice. This study presents not only the first human case of HO-1 deficiency but may also provide clues to the key roles played by this important enzyme in vivo.

Animals↗
PubMed1999

Age-dependent increase of IgE-binding and FcepsilonRI expression on circulating basophils in children.

Peripheral blood basophils are sparse in the circulation, but they express high-affinity receptors for IgE (FCepsilonRI) and bind IgE efficiently. The present study was performed to elucidate the role of IgE bound on the basophil surface in the development of allergic responses during infancy and early childhood. IgE-binding and FcepsilonRI expression on basophils were evaluated by two-color flow cytometry. Basophil-bound IgE increased rapidly and reached adult levels during infancy in atopic patients, while it gradually increased with advancing age in parallel with serum IgE in normal controls. IgE-binding and FcepsilonRI expression in atopic children were higher than in normal controls among various age groups. They correlated with serum IgE levels but reached a plateau when serum IgE exceeded 300 ng/mL. A low, but significant level of FcepsilonRI expression was observed on cord blood basophils, although IgE-binding was usually undetectable. Incubation of cord blood with IgE rapidly saturated the preexisting IgE receptors and basophil-bound IgE levels increased. When neonatal basophils were cultured for 48 h with IgE, FcepsilonRI expression was upregulated dose-dependently and IgE-binding increased further. The up-regulation of FcepsilonRI was completely inhibited by cycloheximide, indicating that it was dependent on de novo protein synthesis. These results suggest that IgE-binding on basophils serves as a sensitive indicator of allergic sensitization, and that IgE functions as a positive regulator of FcepsilonRI expression in vivo.

Adolescent↗
PubMed1999

Role of the Src homology 2 (SH2) domain and C-terminus tyrosine phosphorylation sites of SH2-containing inositol phosphatase (SHIP) in the regulation of insulin-induced mitogenesis.

To examine the role of SHIP in insulin-induced mitogenic signaling, we used a truncated SHIP lacking the SH2 domain (deltaSH2-SHIP) and a Y917/1020F-SHIP (2F-SHIP) in which two tyrosines contributing to Shc binding were mutated to phenylalanine. Wild-type (WT)-, deltaSH2-, and 2F-SHIP were transiently transfected into Rat1 fibroblasts overexpressing insulin receptors (HIRc). Insulin-stimulated tyrosine phosphorylation of WT-SHIP and deltaSH2-SHIP, whereas tyrosine phosphorylation of 2F-SHIP was not detectable, indicating that 917/1020-Tyr are key phosphorylation sites on SHIP. Although SHIP can bind via its 917/1020-Tyr residues and SH2 domain to Shc PTB domain and 317-Tyr residue, respectively, insulin-induced SHIP association with Shc was more greatly decreased in 2F-SHIP cells than that in deltaSH2-SHIP cells. Insulin stimulation of Shc association with Grb2, which is important for p21ras-MAP kinase activation, was decreased by overexpression of WT- and 2F-SHIP. Importantly, insulin-induced Shc x Grb2 association was not detectably reduced in deltaSH2-SHIP cells. In accordance with the extent of Shc association with Grb2, insulin-induced MAP kinase activation was relatively decreased in both WT-SHIP and 2F-SHIP cells, but not in deltaSH2-SHIP cells. To examine the functional role of SHIP in insulin's biological action, insulin-induced mitogenesis was compared among these transfected cells. Insulin stimulation of thymidine incorporation and bromodeoxyuridine incorporation was decreased in WT-SHIP cells compared with that of control HIRc cells. Expression of 2F-SHIP also significantly reduced insulin-induced mitogenesis, whereas it was only slightly affected by overexpression of deltaSH2-SHIP. Furthermore, the reduction of insulin-induced mitogenesis in WT-SHIP cells was partly compensated by coexpression of Shc. These results indicate that SHIP plays a negative regulatory role in insulin-induced mitogenesis and that the SH2 domain of SHIP is important for its negative regulatory function.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Synergistic role of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase cascade in the regulation of insulin receptor trafficking.

To examine the molecular mechanism of insulin receptor trafficking, we investigated the intracellular signaling molecules that regulate this process in Rat1 fibroblasts overexpressing insulin receptors. Cellular localization of insulin receptors was assessed by confocal laser microscopy with indirect immunofluorescence staining. Insulin receptors were visualized diffusely in the basal state. Insulin treatment induced the change of insulin receptor localization to perinuclear compartment. This insulin-induced insulin receptor trafficking was not affected by treatment of the cells with PI3-kinase inhibitor (wortmannin), whereas treatment with MEK [mitogen-activated protein (MAP) kinase-Erk kinase] inhibitor (PD98059) partly inhibited the process in a dose-dependent manner. Interestingly, treatment with both wortmannin and PD98059 almost completely inhibited insulin receptor trafficking. The functional importance of PI3-kinase and MAP kinase in the trafficking process was directly assessed by using single cell microinjection analysis. Microinjection of p85-SH2 and/or catalytically inactive MAP kinase ([K71A]Erk1) GST fusion protein gave the same results as treatment with wortmannin and PD98059. Furthermore, to determine the crucial step for the requirement of PI3-kinase and MAP kinase pathways, the effect of wortmannin and PD98059 on insulin receptor endocytosis was studied. Insulin internalization from the plasma membrane and subsequent insulin degradation were not affected by treatment with wortmannin and PD98059. In contrast, insulin receptor down-regulation from the cell surface and insulin receptor degradation, after prolonged incubation with insulin, were markedly impaired by the treatment. These results suggest that PI3-kinase and MAP kinase pathways synergistically regulate insulin receptor trafficking at a step subsequent to the receptor internalization.

Androstadienes↗
PubMed1999

The inhibitory effect of the toxic fraction from sea urchin (Toxopneustes pileolus) venom on 45Ca2+ uptake in crude synaptosome fraction from chick brain.

The effects of toxic peaks (P-I, P-II and P-III eluted from Sephadex G-200 column) from the sea urchin Toxopneustes pileolus on time-dependent 45Ca2+ uptake in chick P2 fraction (crude synaptosome fraction) were studied under physiological ionic conditions. Time-dependent 45Ca2+ uptake was inhibited by P-II and P-III, but not by P-I. P-II had the greatest inhibitory effect. The inhibitory effect of P-II was not due to the inhibition of 45Ca2+ binding on P2 fraction, because P-II did not affect 45Ca2+ binding in osmotic-shocked P2 fraction. P-II did not affect KCl-stimulated 45Ca2+ uptake in P2 fraction, (Ca(2+)-Mg2+)-ATPase activity in the synaptic plasma membrane (SPM) fraction, or (Na(+)-K+)-ATPase and Mg(2+)-ATPase activities in osmotically-shocked P2 fraction. In contrast, the Na+/Ca2+ exchanger blocker 2',4'-dichlorobenzamil (DCB; 100 microM), with a poor specificity, inhibited not only time-dependent 45Ca2+ uptake but also KCl-stimulated 45Ca2+ uptake, (Ca(2+)-Mg2+)-ATPase, Mg(2+)-ATPase and (Na(+)-K+)-ATPase. Involvement of Na(+)-Ca2+ exchanger in the time-dependent 45Ca2+ uptake was ruled out, since it was not inhibited by replacement of Na+ with Li+ in reaction medium. These results suggested that the inhibition by P-II on time-dependent 45Ca2+ uptake appeared to be more specific than the commercially available Na+/Ca2+ exchanger blocker DCB, although the mechanism is not clear yet.

Animals↗
PubMed1999

Inhibition of the angiotensin II Type 1 receptor by TCV-116: quantitation by in vitro autoradiography.

Inhibition of angiotensin (Ang) II type 1 (AT1) receptors in various target tissues of adult Sprague-Dawley rats was studied after single oral administration of TCV-116. The effects of TCV-116 on Ang II-receptor binding were assessed by quantitative in vitro autoradiography using 125I-[Sar1,Ile8]Ang II as a ligand. Four hours after the administration of TCV-116 (1 mg/kg), Ang II-receptor binding was markedly inhibited in the kidney (20% of control), adrenal cortex (27%), thoracic aorta (57%), heart (55%) and testis (76%) where AT1 receptors predominate. In the brain, orally administered TCV-116 produced a significant inhibition of binding both to the circumventricular organs (38%), which are devoid of the blood-brain barrier (BBB), and to the discrete regions within the BBB such as the paraventricular hypothalamic nucleus (48%), nucleus of the solitary tract (60%). Twenty-four hours after the administration, Ang II-receptor binding had partly recovered to approximately 50-85% of control levels. In contrast, throughout the experimental period, Ang II-receptor binding was little affected in sites where Ang II type 2 (AT2) receptors predominate such as the adrenal medulla and the nucleus of the inferior olive. These data indicate that orally administered TCV-116 specifically binds to AT1 receptors both in peripheral tissues and the central nervous system.

Administration, Oral↗
PubMed1999

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

Greater access to alternative female-initiated barrier methods, such as the female condom, is needed among women exchanging street sex. This study describes knowledge of and experience with the female condom among 101 women exchanging sex for money and drugs on the streets of New York City, and examines the acceptability of female condom use as an alternative barrier method for HIV/STD prevention among this population. Female condom use among this sample of sex workers was found to be related to having a regular sexual partner, living with someone who is a drug or alcohol abuser, not being homeless, using alcohol or intravenous heroin, having heard of the device, and having discussed the device with other women or with a regular sexual partner. Despite decreased acceptability post-use, most sex workers indicated an intention for future female condom use.

Adult↗
PubMed1999

Reconstruction and limb salvage after resection for malignant bone tumour of the proximal humerus. A sling procedure using a free vascularised fibular graft.

We assessed the intermediate functional results of eight patients after wide resection of the proximal humerus for malignant bone tumour. We used a free vascularised fibular graft as a functional spacer and a sling procedure to preserve passive scapulohumeral movement. Scapulohumeral arthrodesis was not carried out. Five patients had osteosarcoma, two achondrosarcoma and one a malignant fibrous histiocytoma of the bone. The mean duration of follow-up was 70 months (median, 76) for the seven patients who were still alive at the time of the latest follow-up. One patient died from the disease 12 months after surgery. There were no local recurrences. The functional results were described and graded quantitatively according to the rating system of the Musculoskeletal Tumour Society. Our results were satisfactory with regard to pain, emotional acceptance and manual dexterity. Function and lifting ability were unsatisfactory in two patients. One patient had delayed union between host and graft, but this united after six months without further surgery. Radiographs of the shoulder showed absorption or collapse of the head of the fibula in four of the eight patients and a fracture in another. No functional problems related to absorption or fracture of the head of the fibula were noted. There was no infection or subluxation of the head. We conclude that this is a reasonably effective technique of limb salvage after resection of the proximal humerus.

Adolescent↗
PubMed1999

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

OBJECTIVE: We have observed clinically that some speakers wearing a speech appliance for correction of velopharyngeal incompetence can blow with variable intensity without nasal air escape. This clinical finding suggests that tightness of velopharyngeal closure may be regulated in accordance with oral air pressure during blowing. The purposes of this electromyographic study were (1) to examine whether levator vell palatini muscle activity can be changed in relation to oral air pressure during blowing when the speech appliance is removed, (2) to clarify whether or not the change is related to the severity of velopharyngeal incompetence, and (3) to examine whether placement of a speech appliance can alter levator muscle activity into the equivalent of that of normal speakers during blowing. DESIGN: Eight patients with repaired cleft palate, who routinely wear a palatal lift prosthesis (PLP) or a hybrid speech appliance of a pharyngeal bulb and palatal lift (bulb-PLP), served as subjects. Subjects were classified into one of two groups according to their speech appliance (PLP group and bulb-PLP group). Electromyography of the levator veli palatini muscle was recorded with a speech appliance in place and then with the speech appliance removed as the subject blew through a tube at three different effort levels. RESULTS: In the removed condition, the change in levator activity in relation to oral air pressure was variable across subjects in the bulb-PLP group, whereas levator activity changed in relation to oral air pressure change for all subjects in the PLP group. However, levator activity changed in relation to oral air pressure with either speech appliance in place for all subjects irrespective of their speech appliance types. CONCLUSION: The severity of velopharyngeal incompetence might be related in part to change in levator activity in association with oral air pressure. The effect of a speech appliance to correct velopharyngeal incompetence might consist not only of mechanical obturation of the velopharynx but also of alteration of velopharyngeal function to become similar to normal speakers. Moreover, it is likely that the velopharyngeal system could be well regulated so as to exhibit a consistent outcome of velopharyngeal function.

Adolescent↗
PubMed1999

Effect of renal denervation on the compensatory renal growth following nephrectomy in the cat.

The purpose of this study was to clarify the effect of denervation on the mass of the remaining kidney with or without unilateral nephrectomy using adult cats. The animals were divided into 4 groups: (1) control group, the weights of the right and left kidneys were measured intact in 5 cats; (2) nephrectomy group (Nx, n = 5 cats), the right kidney was removed and the left kidney was weighed 3-5 d after nephrectomy; (3) nephrectomy and denervation group (Nx+Dx, n = 7 cats), the left kidney was weighed on the 7th day after surgery in which the left kidney was denervated and the right kidney was removed; and (4) denervation group (Dx+Dx, n = 5 cats), both kidneys were weighed on the 7th day after denervation of the kidneys. In the control group, the left and right kidney weights per body weight (LKW and RKW) were the same (LKW, 0.74 +/- 0.06%; RKW, 0. 74 +/- 0.07%). In the Nx group, LKW increased to 0.90 +/- 0.03% 3-5 d after nephrectomy, although RKW of the removed kidney was 0.66 +/- 0.01%. In the Nx+Dx group, LKW increased to 0.97 +/- 0.15%, which was similar to that of the Nx group. In the Dx+Dx group, LKW (0.56 +/- 0.05%) and RKW (0.54 +/- 0.05%) were significantly less than those in the control group. We conclude that the renal nerves may contribute to maintaining the renal mass and that the neural effect on compensatory growth following nephrectomy may be covered by other growth factors.

Adaptation, Physiological↗