Biomedical subjects

S Kobayashi

Publications and source records attributed to S Kobayashi.

At least 181 records · Page 10Linked to original sources

PubMed2001

Activation of Reg gene, a gene for insulin-producing beta -cell regeneration: poly(ADP-ribose) polymerase binds Reg promoter and regulates the transcription by autopoly(ADP-ribosyl)ation.

The regeneration of pancreatic islet beta cells is important for the prevention and cure of diabetes mellitus. We have demonstrated that the administration of poly(ADP-ribose) synthetase/polymerase (PARP) inhibitors such as nicotinamide to 90% depancreatized rats induces islet regeneration. From the regenerating islet-derived cDNA library, we have isolated Reg (regenerating gene) and demonstrated that Reg protein induces beta-cell replication via the Reg receptor and ameliorates experimental diabetes. However, the mechanism by which Reg gene is activated in beta cells has been elusive. In this study, we found that the combined addition of IL-6 and dexamethasone induced the expression of Reg gene in beta cells and that PARP inhibitors enhanced the expression. Reporter gene assays revealed that the -81 approximately -70 region (TGCCCCTCCCAT) of the Reg gene promoter is a cis-element for the expression of Reg gene. Gel mobility shift assays showed that the active transcriptional DNA/protein complex was formed by the stimulation with IL-6 and dexamethasone. Surprisingly, PARP bound to the cis-element and was involved in the active transcriptional DNA/protein complex. The DNA/protein complex formation was inhibited depending on the autopoly(ADP-ribosyl)ation of PARP in the complex. Thus, PARP inhibitors enhance the DNA/protein complex formation for Reg gene transcription and stabilize the complex by inhibiting the autopoly(ADP-ribosyl)ation of PARP.

Animals↗

PubMed2001

IL-2 independent transformation of a unique human T cell line, TY8-3, and its subclones by HTLV-I and -II.

Human T cell leukemia virus type I (HTLV-I) is etiologically associated with adult T cell leukemia (ATL) and chronic neurological disease, tropical spastic paraparesis (TSP). In our study, a unique IL-2 dependent human T cell line, designated TY8-3, was established from a thymoma obtained from a myasthenia gravis patient. The cells were heterogeneous and mainly consisted of those with CD4 , CD8 as well as activation markers and adhesion molecules including IL-2Ralpha,beta,gamma, CD45RO, Tf-R, HLA-DR, LFA-1alpha,beta, LFA-3, ICAM-1 and OX40 but without CD3 surface markers. Furthermore, these cells underwent an efficient and reproducible IL-2 independent transformation upon cocultivation with HTLV-I/II producing cell lines. Interestingly, although the infected cells became IL-2 independent, the growth rate of infected cells was significantly lower than those of parental TY8-3 cells. Clonal HTLV-I proviral DNA and viral particles were detected in the cells. Down-regulation of the lck and fyn genes and activation of the lyn gene was demonstrated in the IL-2 independent HTLV-positive TY8-3 cells. Subclones of TY8-3 cells were again able to be efficiently transformed and became IL-2 independent several months after coculture. Our results thus exhibit that TY8-3 cells and its subclones provide us with a very unique model whereby IL-2 independent transformation events of human T cells by HTLV-I/II in vitro can be studied at a clonal level.

CD4 Antigens↗

PubMed2001

Diphenylpyraline-responsive parkinsonism in cerebrotendinous xanthomatosis: long-term follow up of three patients.

A long-term follow-up study was made of three patients with cerebrotendinous xanthomatosis (CTX) associated with parkinsonism, two of whom were siblings. Besides typical CTX symptoms, all three patients showed severe parkinsonism. This observation has been rarely reported in CTX. The fact that the two siblings showed parkinsonism strongly suggests the genetic propensity to parkinsonism in these CTX patients. Positron emission tomography studies of the two patients revealed presynaptic dysfunction of the nigro-striatal dopaminergic system. Treatment with the reductase inhibitor hydroxymethyl glutaryl coenzyme successfully corrected the serum cholestanol level in the early stage of the disease, which, however, did not arrest the progression of clinical symptoms, particularly their parkinsonism. Clinically, levodopa had a little effect on parkinsonism, whereas an antihistamine drug, diphenylpyraline hydrochloride (DPP) had excellent effects on all three patients throughout the long-term follow up. The mechanism of the action of DPP on parkinsonism is unclear, however, the drug seems to be a therapeutic choice for treating parkinsonism in CTX.

Adult↗

PubMed2001

Prophylactic excision of the gallbladder and bile duct for patients with pancreaticobiliary maljunction.

HYPOTHESIS: Pancreaticobiliary maljunction (PBM) is a high-risk factor for biliary tract carcinogenesis because of a continuous reflux of pancreatic juice into the biliary tract. It remains to be disclosed whether we should perform prophylactic excision of gallbladders and bile ducts. DESIGN: A person-year method. SETTING: A university hospital. PATIENTS: We studied 68 patients with PBM treated between August 1, 1974, and December 31, 1999. MAIN OUTCOME MEASURES: Relative risks (observed number-expected number ratios) of gallbladder and bile duct carcinomas according to type of bile duct dilation (ie, cystic dilation, diffuse dilation, and nondilation). RESULTS: Observed number-expected number ratios of gallbladder carcinomas were high: 291.3 in 43 patients with cystic dilation, 167.2 in 16 patients with diffuse dilation, and 419.6 in 7 patients with nondilation. Observed number-expected number ratios of bile duct carcinomas were 194.2 in 43 patients with cystic dilation before surgery and 142.8 in 39 patients with cystic dilation after long postsurgical follow-up. All these values were statistically significant (P<.01). CONCLUSIONS: The gallbladder carries a high risk for carcinogenesis in all types of dilation in patients with PBM. The bile duct carcinomas of PBM were exclusively identified by the type of cystic dilation. Prophylactic cholecystectomy should be recommended for all dilation types, and prophylactic excision of bile ducts including cholecystectomy should be performed in patients with PBM and cystic dilation. Complete excision of extrahepatic dilated bile ducts and careful follow-up for carcinogenesis in residual dilated bile ducts should be recommended for patients with PBM and cystic dilation.

Adult↗

PubMed2001

Anti-lymphoma effect of naproxen and indomethacin in a patient with relapsed diffuse large B-cell lymphoma.

A 77-year-old man with relapsed non-Hodgkin's lymphoma, diffuse large B-cell type, was treated with naproxen, a nonsteroidal anti-inflammatory drug (NSAID), for paraneoplastic fever. A dramatic disappearance of not only the fever but also generalized lymphadenopathy was observed. Naproxen was continued, and he maintained remission for 10 months. When relapse of lymphoma occurred in spite of continuous naproxen administration, indomethacin, another type of NSAID, was tried. Surprisingly, rapid regression of lymphoma occurred again and was maintained for almost 1 year. These results indicate that NSAIDs are effective in some patients with non-Hodgkin's lymphoma.

Aged↗

PubMed2001

Ascitic fluid cytology of adenosarcoma of the ovary: a case report.

Extrauterine adenosarcoma is very rare and originates in the ovary, adnexa, or myometrium. Cytologic study of ascites is very important to determine clinical staging of malignant ovarian tumors and provide adequate therapy for recurrence. The cytomorphologic features of adenosarcoma have been only rarely described. A 77-yr-old woman visited a hospital with a complaint of lower abdominal pain for 1 mo. A tumor originating from the right adnexa in the pelvis, and involving the rectum, was found in surgery. In the ascitic fluid cytology, a few dispersed tumor cells with large cytoplasm and nuclei were oval-shaped, with nuclear invagination. The chromatin was finely granular; one or two nucleoli were conspicuous. To our knowledge, this is the fifteenth reported case of adenosarcoma of the ovary, and there have been no prior reports describing the cytological features of ascitic fluid cells in adenosarcoma of the ovary.

Adenosarcoma↗

PubMed2001

Proportional treatment effects for count response panel data: effects of binary exercise on health care demand.

We define conditional and marginal treatment effects appropriate for count data, and then conduct an empirical analysis for the effects of exercise on health care demand using panel data from the Health Retirement Study. The response variables are office visits to doctors and hospitalization days, and the treatments of interest are light and vigorous exercises. We found that short-run light exercise increases health care demand by 3-5%, whereas long-run light exercise decreases it by 3-6%. We also found that short-run vigorous exercise decreases health care demand by 1-2%, whereas long-run vigorous exercise decreases it by 1-3%. However, many of these numbers are not statistically significantly different from zero. These findings suggest that it will be difficult to reduce health care cost much by encouraging people to do more exercise--at least in the short-run.

Adult↗

PubMed2001

T2-weighted MRI of the female pelvis: comparison of breath-hold fast-recovery fast spin-echo and nonbreath-hold fast spin-echo sequences.

In 49 patients who had pelvic abnormalities, breath-hold T2-weighted fast-recovery (FR)-fast spin-echo (FSE) (imaging time = 24 sec) and nonbreath-hold FSE MR images (2 min 8 sec) were compared qualitatively (on a four-point scale) and quantitatively (using signal-to-noise ratios (SNRs) and contrast ratios (/SIs of the lesions-SIs of the myometrium/SIs of the myometrium)). Motion artifacts were reduced on breath-hold FR-FSE (3.8:3.2 = breath-hold FSE:nonbreath-hold FSE, P < 0.01) and image quality was comparable (3.8:3.7, NS). In all patients, pathology (leiomyoma [N = 26], adenomyosis [N = 10], endometrial carcinoma [N = 8], and ovarian cystic lesions [N = 21]) was recognized with comparable lesion conspicuity (3.8:3.7, NS) and better delineation of the structures (3.9:3.6, P < 0.05) on the FR-FSE images. There was no significant difference in contrast ratios, although SNRs (e.g., myometrium 18.3:25.8, P < 0.01) were better and the uterine zonal anatomy was recognized better on the nonbreath-hold FSE (3.4:3.7, P < 0.05). These differences did not affect the diagnosis. Breath-hold FR-FSE provides the benefits of motionless imaging and a short examination time, although lower SNRs were noted. J. Magn. Reson. Imaging 2001;13:930-937.

Adolescent↗

PubMed2001

Fat-suppressed T2-weighted MRI of the liver: comparison of respiratory-triggered fast spin-echo, breath-hold single-shot fast spin-echo, and breath-hold fast-recovery fast spin-echo sequences.

The purpose of our study was to compare the value of respiratory-triggered fast spin-echo, breath-hold single-shot fast spin-echo, and breath-hold fast-recovery fast spin-echo sequences in detecting hepatic lesions. Fat-suppressed T2-weighted magnetic resonance (MR) images obtained with the three sequences in 36 patients with 138 lesions and nine patients without lesions were prospectively analyzed. Quantitative and qualitative analyses, including receiver operating characteristic (ROC) analyses, were performed. The mean lesion-to-liver contrast-to-noise ratio (CNR) for hepatic lesions was highest with the respiratory-triggered fast spin-echo sequence. On the basis of receiver-operating characteristic analyses, tumor detection rates were higher with the breath-hold fast-recovery fast spin-echo sequence (Az = 0.94) than with the respiratory-triggered fast spin-echo sequence (AZ = 0.80, P < 0.0001) or the single-shot fast spin-echo sequence (Az = 0.77, P < 0.0001). The image quality with the breath-hold fast-recovery fast spin-echo sequence was acceptable in all patients. The breath-hold fast-recovery fast spin-echo sequence provided the highest tumor detection in a short imaging time, although the mean lesion-to-liver CNRs were inferior to those of the respiratory-triggered fast spin-echo and the breath-hold single-shot fast spin-echo sequences.

Adult↗

PubMed2001

Functional assessment of pancreatic parenchyma after secretin administration using serial T2-weighted echo-planar magnetic resonance imaging.

Signal intensity (SI) changes of pancreatic parenchyma were evaluated after intravenous administration of secretin using T2-weighted single-shot spin-echo echo-planar imaging (EPI) to assess this method as a magnetic resonance (MR) test of pancreatic exocrine function. Nine volunteers were studied with serial single-shot EPI of the pancreas for 15 minutes after the injection of secretin or saline. The normal pattern of pancreatic SI change was demonstrated after intravenous injection of secretin, a single peak at 3-4 minutes in the head, body, and tail, followed by a gradual decrease in SI. Saline injection did not induce a significant SI change. There was no statistical difference in the peak contrast ratios (first mean, 1.21-1.25, vs. second mean, 1.18-1.22) and peak times (first mean, 3.2-3.7 minutes, vs. second mean, 3.1-3.6) in a repeat study. By evaluating the pattern of time-response curves obtained from serial T2-weighted EPI after secretin injection, pancreatic exocrine function may be directly assessed at the level of the head, body, and tail.

Adult↗

PubMed2001

Clinical significance of E-cadherin expression in thyroid neoplasms.

BACKGROUND AND OBJECTIVE: E-cadherin, a calcium-dependent transmembrane glycoprotein, is an adhesion molecule. We studied clinical significance of E-cadherin expression in thyroid neoplasms. METHODS: We immunohistochemically studied E-cadherin expression in 60 normal tissue specimens of thyroid tissues and in 82 follicular adenomas, 53 papillary carcinomas, 4 follicular carcinomas, 2 medullary carcinomas, and 5 anaplastic carcinomas of the thyroid. RESULTS: In papillary carcinoma, E-cadherin expression was preserved significantly less often than in follicular adenoma or normal thyroid tissue (P < 0.01). Preserved E-cadherin expression was seen less often among papillary carcinomas with lymph node metastasis than in those without metastasis (P < 0.05). CONCLUSIONS: This loss of E-cadherin expression may be involved in regional lymph node metastasis and in malignant potential of thyroid neoplasms. J. Surg. Oncol. 2001;76:176-180.

Adenocarcinoma, Follicular↗

PubMed2001

Entamoeba invadens: enhancement of excystation and metacystic development by cytochalasin D.

Effects of three actin-modifying drugs, cytochalasin D, latrunculin A, and jasplakinolide, on the excystation and metacystic development in vitro of Entamoeba invadens were examined by transfer of the cysts to growth medium with the drugs. Cytochalasin D unexpectedly increased the number of metacystic amoebae of E. invadens strain IP-1 during incubation. Metacystic development, which was determined by the number of nuclei of metacystic amoebae, was faster in the culture with cytochalasin D than in the culture without the drug. These results suggest that cytochalasin D enhances the excystation and metacystic development. In contrast, latrunculin A and jasplakinolide inhibited these process. No excystation occurred in encystation medium even in the presence of cytochalasin D, suggesting that growth medium is essential for excystation. Excystation was further enhanced when the cysts were incubated with cytochalasin D before culture in growth medium with the drug. The enhancing effect of cytochalasin D on the excystation and metacystic development was abrogated by jasplakinolide. Thus, the results indicate that cytochalasin D, unlike latrunculin A and jasplakinolide, caused enhancement of the excystation and metacystic development of this parasite.

Animals↗

PubMed2001

Entamoeba dispar: molecular characterization of the galactose/N-acetyl-d-galactosamine lectin.

Amebiasis contributes to approximately 50 million cases of life-threatening dysentery worldwide. Comparison of the lectins from Entamoeba histolytica (pathogenic) and Entamoeba dispar (nonpathogenic) was undertaken to elucidate the differential roles of this molecule in invasion versus colonization. Surface lectin was less abundant on axenic E. dispar than on axenic E. histolytica, commensurate with differences in lectin (heavy and light subunits) RNA when assessed by semiquantitative RT-PCR. The 1G7 epitope, which falls within the immunodominant and immunoprotective cysteine-rich region (480-900), was absent on axenic E. dispar. Indirect immunofluorescence, transient transection of COS7, and immunoprecipitation demonstrated that the 1G7 epitope was conserved in the nonpathogenic lectin homologue but not exposed on live E. dispar trophozoites. Hgl2 (E. histolytica) and Dhgl2 (E. dispar) lectin homologues demonstrated comparable high-affinity binding to multivalent GalNAc(19) BSA. These data provide evidence for relative gene and conformational regulation of the E.dispar lectin.

Animals↗

PubMed2001

Autologous bone marrow implantation induced angiogenesis and improved deteriorated exercise capacity in a rat ischemic hindlimb model.

BACKGROUND: Bone marrow possesses endothelial progenitor cells that secrete several growth factors and can contribute to the formation of new capillaries. In the present study, we investigated the extent of angiogenesis induced by implantation of autologous bone marrow cells (BMCs) in a rat ischemic hindlimb model and studied whether the increased collateral vessels can improve deteriorated physical function. MATERIALS AND METHODS: Ischemic hindlimb was created by ligation of the femoral artery and its branches in Dark Agouti (DA) rats. BMCs (1 x 10(7)) were injected percutaneously at six points into the gastrocnemius muscle. To assess angiogenesis, histologic evaluation and microangiography were performed at 2 weeks postligation. Severity of the ischemic insult was evaluated by measuring blood flow in the adductor and gastrocnemius muscles using nonradioactive colored microspheres and by determining the femoral arteriovenous oxygen difference (AVDO(2)) at 2 weeks postligation. Running time on a motor-driven treadmill was used to represent exercise capacity. RESULTS: The histologic evaluation and microangiogram showed that the implanted BMCs induce angiogenesis. Blood flow to the adductor muscle on the treated side in the bone marrow cell implantation (BMI) group was significantly restored to 77.3 +/- 19.3% of that of the normally perfused limb in comparison to that in control groups (P < 0.05). AVDO(2) in the BMI group significantly decreased when compared with AVDO(2) in control groups. Rats in the BMI group ran approximately 1.5 times longer than rats in control groups at 2 and 4 weeks postligation (P < 0.01). CONCLUSIONS: Implantation of autologous BMCs induced angiogenesis and improved deteriorated exercise capacity in our rat ischemic hindlimb model.

Angiography↗

PubMed2001

In vitro biosynthesis of polyesters.

In vitro synthesis of polyesters using isolated enzymes as catalyst via non-biosynthetic pathways is reviewed. In most cases, lipase was used as catalyst and various monomer combinations, typically oxyacids or their esters, dicarboxylic acids or their derivatives/glycols, and lactones, afforded the polyesters. The enzymatic polymerization often proceeded under mild reaction conditions in comparison with chemical processes. By utilizing characteristic properties of lipases, regio- and enantioselective polymerizations proceeded to give functional polymers, most of which are difficult to synthesize by conventional methodologies.

Chemical Engineering↗

PubMed2001

Immunohistochemical analysis on biological markers in ductal carcinoma in situ of the breast.

BACKGROUND: The increasing use of mammographic screening has led to an increased detection of ductal carcinoma in situ (DCIS) of the breast. The detailed biological characteristics of DCIS and a new classification of DCIS based on these characteristics are needed. METHODS: Immunohistochemical studies were performed to assess the expression of c-erbB-2 (ErbB-2), estrogen receptor (ER), p53 and proliferative activity (Ki-67) in 65 patients with pure DCIS and 60 with invasive ductal carcinoma (IDC). We classified pure DCIS tumors using three classifications, the architectural, Nottingham, and Van Nuys classifications. RESULTS: ErbB-2, ER and p53 staining was positive in 34%, 66% and 21% of patients with DCIS, respectively, and 58%, 42% and 33% in patients with IDC, respectively. Ki-67 stained positively in 1.5% of patients with DCIS and 11.2% of patients with IDC. The comedo type showed a high rate of positive ErbB-2 and p53 staining. The cribriform and papillary types showed a high rate of positive ER staining. Under the Van Nuys classification, ErbB-2, p53 and Ki-67 expression were highest in the group with high nuclear grade and lowest in the group with non-high nuclear grade without necrosis. CONCLUSION: Although the biological markers of IDC tended to suggest aggressive behavior more so than those of DCIS, these differences were based on the histological sub-type, comedo or non-comedo. The Van Nuys classification best defined the subgroups of DCIS with a distinct expression pattern of biological markers, and the best candidates for breast-conserving surgery.

Adult↗

PubMed2001

Localization of gelatinolytic activity can be detected in breast cancer tissues by film in situ zymography.

BACKGROUND: Extracellular matrix-degrading proteinases secreted by malignant tumor cells have been thought to play an essential role in the processes of invasion and metastasis. However, existence and localization of gelatinase activity in breast cancer tissues have not been clarified. METHODS: We developed a novel film for highly reproducible detection and the localization of gelatinolytic activity. This film has a gelatin layer with a constant thickness 7 microm, and adequate crosslinking to control the speed of degradation by proteases. Cryosections of several breast cancer tissues were put on this gelatin film and incubated for 16 hrs at 37 degrees C. After staining with ponceau 3R dye, the digested area was evaluated under light microscopy. RESULTS: Digestion of gelatin was detected in more than 90%of breast cancer specimens, although it varied in degree and area for each case. In most cases, the gelatinolytic activity was located within cancer nests, and was not detected in stromal cells surrounding cancer cells. The gelatinolytic activity was inhibited by 1,10-phenanthroline, an inhibitor of matrix metalloproteinases (MMPs). CONCLUSIONS: In this study, the localization of net MMP activity was confirmed in breast cancer nest using film in situ zymography. Detailed analysis on the relationship between the strength or distribution of MMP activity and malignancy are anticipated in the future.

Azo Compounds↗

PubMed2001

Staging of palpable T1-2 invasive breast cancer with helical CT.

BACKGROUND: The purpose of this study was to evaluate the accuracy of contrast-enhanced high resolution helical computed tomography (CT) for assessing locoregional staging of palpable T1-2 invasive breast cancer. METHODS: Helical CT studies of 156 lesions from 156 patients with invasive breast cancer before breast-conserving surgery were examined. A lesion was defined as positive if focal enhancement was detected by CT within 100 seconds after contrast material administration. After resection, tumors were histopathologically mapped and comparison made with the extent of contrast enhancement. RESULTS: Helical CT enabled detection of all 156 index tumors. CT enabled detection of 28 of 43 multifocal lesions (65%) and five of five multicentric lesions (100%). In 24 of 33 lesions (73%), CT revealed additional cancers not seen on mammography. The extent of tumor significantly correlated with CT measurements (r=0.76, p<0.0001). CONCLUSION: Helical CT of the breast is an accurate preoperative imaging modality for assessing the locoregional staging of T1-2 invasive breast cancer.

Adult↗