Biomedical subjects

Tadashi Matsuda

Publications and source records attributed to Tadashi Matsuda.

82 records · Page 5Linked to original sources

PubMed2002

Mapping of the sites responsible for factor I-cofactor activity for cleavage of C3b and C4b on human C4b-binding protein (C4bp) by deletion mutagenesis.

Human C4b-binding protein (C4bp) facilitates the factor I-mediated proteolytic cleavage of the active forms of complement effectors C3b and C4b into their inactive forms. C4bp comprises a disulfide-linked heptamer of alpha-chains with complement (C) regulatory activity and a beta-chain. Each alpha-chain contains 8 short consensus repeat (SCR) domains. Using SCR-deletion mutants of recombinant multimeric C4bp, we identified the domains responsible for the C3b/C4b-binding and C3b/C4b-inactivating cofactor activity. The C4bp mutant with deletion of SCR2 lost the C4b-binding ability, as judged on C3b/C4b-Sepharose binding assaying and ELISA. In contrast, the essential domains for C3b-binding extended more to the C-terminus, exceeding SCR4. Using fluid phase cofactor assaying and deletion mutants of C4bp, SCR2 and 3 were found to be indispensable for C4b cleavage by factor I, and SCR1 contributed to full expression of the factor I-mediated C4b cleaving activity. On the other hand, SCR1, 2, 3, 4, and 5 participated in the factor I-cofactor activity for C3b cleavage, and SCR2, 3, and 4 were absolutely required for C3b inactivation. Thus, different sets of SCRs participate in C3b and C4b inactivation, and the domain repertoire supporting C3b cofactor activity is broader than that supporting C4b inactivation by C4bp and factor I. Furthermore, the domains participating in C3b/C4b binding are not always identical to those responsible for cofactor activity. The necessity of the wide range of SCRs in C3b inactivation compared to C4b inactivation by C4bp and factor I may reflect the physiological properties of C4bp, which is mainly directed to C4b rather than C3b.

Antibodies, Monoclonal↗

PubMed2002

Mouse model for the equilibration interaction between the host immune system and human T-cell leukemia virus type 1 gene expression.

To study the involvement of immune responses against Tax of human T-cell leukemia virus type 1 (HTLV-1) in the growth of and gene suppression in Tax-expressing tumor cells in vivo, we established a model system involving C57BL/6J mice and a syngeneic lymphoma cell line, EL4. When mice were immunized by DNA-based immunization with Tax expression plasmids, solid tumor formation upon subcutaneous inoculation of EL4 cells expressing green fluorescent protein-fused Tax (Gax) under the control of the HTLV-1 enhancer was strongly inhibited, and in vitro analysis showed that DNA immunization elicited cytotoxic T-lymphocyte (CTL) responses but not production of antibodies to Tax protein. Since EL4/Gax cells inoculated into DNA-immunized mice were not completely eradicated but were maintained as small solid tumors for a long period, there appeared to be a certain equilibrium between CTL activity and the growth of Gax-expressing cells. With such a balance, expression of the Gax gene in EL4/Gax cells was strongly suppressed. These results suggested that gene expression under the control of the HTLV-1 long terminal repeat and Tax is silenced in vivo, resulting in an equilibrium between viral expression and the host immune system. Such a balance would represent a status of persistent infection by HTLV-1 in virus-infected individuals during the latency period.

Animals↗

PubMed2002

Analyses of factors contributing to vulnerability to antenatal periventricular leukomalacia induced by hemorrhagic hypotension in chronically instrumented fetal sheep.

Our purpose was to determine factors contributing to vulnerability to antenatal periventricular leukomalacia (PVL) induced by hemorrhagic hypotension in premature fetal sheep. Systemic hypotension was induced in 10 fetal sheep by acutely withdrawing 35% to 40% of the fetoplacental blood volume at 113 d gestation. Brains were processed for histologic analysis 6 d after the insult. Statistical comparisons of physiologic parameters between fetuses suffering from PVL (n = 5) and those without PVL (n = 5) were performed. Significant correlations were found between induction of PVL and fetal brain weight, changes in fetal mean blood pressure over time, base excess, oxygen content, hematocrit, and plasma arginine vasopressin (AVP) levels in fetal abdominal aortic blood. Brain developmental stage, the magnitude of induced systemic hypotension, and baseline blood oxygen content were important intrinsic factors in the induction of antenatal PVL by hemorrhagic hypotension in premature fetal sheep.

Animals↗

PubMed2002

Cross-talk between bone morphogenic proteins and estrogen receptor signaling.

Bone morphogenic proteins (BMPs) play central roles in differentiation, development, and physiological tissue remodeling. Estrogens have key roles in a variety of biological events, such as the development and maintenance of numerous target tissues. Previous studies demonstrated that estrogens suppress BMP functions by repressing BMP gene expression. Here we present a novel mechanism for the inhibitory effect of estrogens on BMP function. BMP-2-induced activation of Sma and Mad (mothers against decapentaplegic)-related protein (Smad) activity and BMP-2-mediated gene expression were suppressed by 17beta-E2 in breast cancer cells and mesangial cells. E2-mediated inhibition of Smad activation was reversed by tamoxifen, an ER antagonist. We provide evidence that the inhibitory action of ER on Smad activity was due to direct physical interactions between Smads and ER, which represents a novel mechanism for the cross-talk between BMP and ER signaling pathways.

Blotting, Northern↗

PubMed2002

[Cholinergic crisis following administration of distigmine bromide: a case report].

The long-acting anticholinesterase, distigmine bromide (Ubretid), is widely used for the treatment of underactive neurogenic bladder. Therefore, we emphasize its hazardable side-effect of cholinergic crisis. A 78-year-old man with duodenal ulcer complained of nocturia, and was administered distigmine bromide 10 mg daily under the diagnosis of mild benign prostatic hypertrophy with underactive neurogenic bladder. It seemed that administration slightly improved his symptom but he developed bradycardia, dyspnea and drowsiness suddenly on the 4th day. Blood examination revealed extremely low cholinesterase in his serum, suggesting distigmine bromide intoxication. He was treated intensively with several intravenous injections of atropine, high-concentration oxygen and transfusion of fresh frozen plasma. Nevertheless, his condition did not recover, resulting in death of "cholinergic crisis" on the 6th day.

Aged↗

PubMed2002

[A clinical analysis of patients with early-stage prostate cancer managed without initial treatment].

To search for a more suitable qualification indicating watchful waiting, we performed a retrospective study against early-stage prostate cancer patients managed without initial treatment. Thirty-three patients who had not been treated for more than 6 months after diagnosed as T1c or T2 prostate cancer were studied. The median values of total observation period, age at diagnosis, and initial PSA were 27.0 months, 69.0 years old, and 7.0 ng/ml, respectively. Among 28 patients who had had measurement of serum PSA at least three times, seven patients showed a significant PSA elevation when transition of PSA level was analyzed using linear regression analysis. The other patients had been stable or PSA level declined. Between these two groups, there was no significant difference regarding age, initial PSA, PSA density, Gleason score, number of cancer-positive core, and cancer-occupying rate in biopsy specimen. The median PSA doubling time in patients showing PSA elevation was 36.3 months. There were no patients showing PSA elevation among those with a cancer-occupying rate of less than 5%. Clinical disease progression was obviously observed in two cases although one did not show PSA elevation. During the observation period, treatment was eventually started in seven patients. The 5-year rate of no treatment was 53.8%. Although a significant independent factor predicting the future treatment was not identified, univariate analysis revealed that the initial PSA value in patients undergoing treatment was significantly higher than that of those without treatment (p = 0.032). We concluded that early-stage prostate cancer has clinical variability, and regular clinical evaluations as digital rectal examination should be performed when the patient was managed with watchful waiting.

Aged↗

PubMed2002

[The experience of laparoscopic radical nephrectomy for renal tumors].

We evaluate the safety and feasibility of laparoscopic radical nephrectomy for renal tumors. Between September 1993 and October 2001, 18 patients with renal tumors underwent laparoscopic radical nephrectomy. The mean patient age was 57.1 years ranging from 36 to 78. Clinical stage was T1N0 in all patients. The mean tumor diameter was 4.0 cm ranging from 1.8 to 7.0. Laparoscopic radical nephrectomy was performed by using the transperitoneal anterior approach on 11 patients and retroperitoneal approach on 7 patients. The specimen was removed through an extended stab wound after blunt segmentation of renal parenchyma in a specimen bag (LapSac). The mean operative time was 405 (270-550) and 453 (325-635) min for the transperitoneal approach and retroperitoneal approach respectively, and the mean blood loss was 281 (52-700) and 223 (10-850) ml, respectively. There was an intraoperative complication of minor splenic injury in 2 patients receiving the transperitoneal approach, which was conservatively managed. Histopathology revealed renal cell carcinoma in 17 patients and renal oncocytoma in one patient. There was no recurrence with a mean follow-up of 28.9 months. Compared with 13 patients who underwent open radical nephrectomy during the same period, laparoscopic nephrectomy has a longer operative time (424 versus 214 min, p < 0.001), equal blood loss (259 versus 210 ml, p = 0.59), quicker resumption of ambulation (1.8 versus 2.5 days, p = 0.016) and food intake (1.4 versus 2.2 days, p = 0.003), shorter postoperative hospital stay (10.9 versus 18 days, p = 0.0016), and a tendency of less frequent analgesic requirements (1.9 versus 4.7 times, p = 0.09). Laparoscopic radical nephrectomy is a safe and useful surgery for renal tumors providing minimal invasiveness.

Adult↗

PubMed2002

Detection of circulating prostate tumor cells: alternative spliced variant of PSM induced false-positive result.

RT-nested PCR has been introduced as a highly specific and sensitive assay method to detect the prostate-specific membrane antigen (PSM) mRNA in peripheral blood. However, appreciable percentages of false-positive cases have been reported. Additionally, primer sets reported previously could not discriminate between PSM and PSM', an alternatively spliced variant, mRNA. These isoforms can be produced from a single gene. Switches in alternative splicing patterns are often controlled with strict cell-type or developmental-stage specificity. Therefore, it is most important to discriminate between PSM mRNA and PSM' mRNA. Using our highly specific primer sets, PSM mRNA was detected in 3 of 24 peripheral blood samples of normal male volunteers (12.5%) and was not detected in peripheral blood of 11 normal female volunteers. PSM' mRNA was detected in 5 of 24 peripheral blood samples of normal male volunteers (20.8%) and in 4 of 11 of normal female volunteers (36.4%). PSM' mRNA induced false-positive results, it is important for genetic diagnosis of prostate cancer to discriminate between PSM and PSM' using our primer sets with high specificity. The advances in the uniquely designed primer sets may allow researchers to detect a real PSM mRNA without PSM' mRNA.

Adult↗

PubMedDate not supplied

Genetic detection for hematogenous micrometastasis in patients with various types of malignant tumors using Uroplakin II derived primers in polymerase chain reaction.

The presence of circulatory metastasis is one of the most significant factors for poor-prognosis in patients with several types of cancer. To establish a sensitive reverse transcription PCR assay to detect micrometastasis in blood containing several cancer types, we first investigated Uroplakin II (UP II), a novel molecular marker for human transitional cell carcinoma of the bladder, in 25 types of normal organs. In our study, UP II mRNA was detected in 10 types of organs, including bladder, kidney, lung and pancreas, but was not detected in normal lymph nodes or leukocytes. The data indicated evidence of UP II expression in various types of normal tissues by RT-nested PCR analysis. UP II mRNA was detected in 2 of 11 (18.2%) peripheral blood samples from lung cancer patients with no metastasis, and in 5 of 12 (41.7%) peripheral blood samples of lung cancer patients with metastasis. UP II was also detected in 6 of 16 (37.5%) peripheral blood samples of patients with pancreatic cancer. The data are particularly important in that the molecular detection of micrometastasis in the blood by means of UP II mRNA identification is feasible for UP II-positive neoplasms, including lung and pancreatic cancers.

Adult↗

PubMedDate not supplied

The effect of eicosapentaenoic acid on prostate-specific antigen.

The "Study of EPA Effects on Prostate Cancer" (SEEPC) Group has been conducting a clinical trial with patients who underwent radical prostatectomy. The main purpose of the SEEPC is to evaluate whether eicosapentaenoic acid (EPA) prevents prostate cancer (PC) recurrence. As the surrogate marker of recurrence, the prostate-specific antigen (PSA) level was measured. However, if EPA affects the PSA values independently of PC, PSA may not be a good marker of recurrence in the event of EPA treatment. Thus, in the present study, whether EPA affected the PSA values was investigated using non-PC volunteers. Twenty men, of at least 50 years of age, were recruited, mostly from hospital staff The volunteers were randomly allocated either to the EPA group or the control. The subjects in the EPA group were administered EPA-ethyl ester a dose of 2400 mg/day for 12 weeks, whereas the controls were administered none. Fasting blood samples were obtained before the start of EPA administration and 4 and 12 weeks later. The EPA concentrations in erythrocytes increased in all the subjects in the EPA group (174+/-96%) with no significant changes in the control group (8.5+/-14.0%). There were no significant differences between the two groups in the serum PSA levels, allowing the conclusion that the PSA is an appropriate surrogate marker of recurrence in prostate cancer.

Aged↗