Biomedical subjects

T Takeda

Publications and source records attributed to T Takeda.

At least 343 records · Page 19Linked to original sources

PubMed1997

Augumentation of splenic antitumor immunity by local immunotherapy in gastric cancer patients.

We previously reported that the antitumor effect of OK-432, a streptococcal preparation, was markedly augmented when this agent was injected into tumors together with fibrinogen. In order to elucidate the effect of this treatment on the spleen, we assessed splenic function in gastric cancer patients receiving preoperative local immunotherapy with OK-432 and fibrinogen. Immunohistochemical studies of the spleen at 7 days after intratumoral injection therapy revealed numerous macrophages phagocytizing OK-432 in the splenic sinuses. Phenotypic analysis of splenocytes by flow cytometry revealed an increase in the CD4/CD8 ratio and in the expression of HLA-DR, CD25, and Leu M3 by splenic T cells of the patients treated with OK-432 plus fibrinogen when compared to patients treated with OK-432 alone or untreated patients. Splenic T cells from patients treated with OK-432 plus fibrinogen showed significantly higher cytotoxicity against Daudi and K562 cells than T cells from control patients (p < 0.05), and culture of these splenic T cells with recombinant IL-2 induced the expansion of lymphokine-activated killer cells. These results demonstrate that local immunotherapy with a mixture of OK-432 and fibrinogen effectively augumented splenic antitumor immunity in gastric cancer patients.

Antineoplastic Agents↗

PubMed1997

Prevalence of GBV-C and hepatitis G virus variants in patients with fulminant hepatic failure in Japan.

BACKGROUND/AIMS: Whether GB virus C and hepatitis G virus participate in fulminant hepatic failure is controversial. We studied the prevalence of the viral RNA in 48 patients. There were possible routes of infection, including blood transfusion, in 22 patients (group 1), and no risk factors in the other 26 (group 2). METHODS: We assayed serum viral RNA with reverse transcription and nested polymerase chain reactions. Serum was obtained at admission, and after transfusion in group 2. RESULTS: Five (10%) serum samples from group 1 at admission had viral RNA of the 5'-untranslated region, and three of these samples had viral RNA of the NS3/helicase region. All five patients had transfusions before sampling. Two (4%) samples from group 2 were positive by both tests only after transfusion. Of two patients, one with non-A-E fulminant hepatic failure survived. Her serum alanine aminotransferase did not increase further after transfusion, but did stay above the reference range during follow-up. The other patient, with infection with hepatitis B virus detected at admission, died. After transfusion, his alanine aminotransferase did not increase further. Partial nucleotide sequences of GB virus C and hepatitis G virus from three fulminant hepatic failure patients and five control patients with chronic hepatitis C were compared with published sequences. A viral variant causing fulminant hepatitis, suggested elsewhere, was not found, nor was all of a characteristic pattern of six mutations found elsewhere. CONCLUSIONS: GB virus C and hepatitis G virus may cause hepatitis, but probably not severe hepatitis such as fulminant hepatic failure.

Base Sequence↗

PubMed1997

Donor-specific cytotoxic lymphocyte activity from bronchoalveolar lavage during acute canine lung allograft rejection.

OBJECTIVE: We investigated the relationship between acute lung rejection and donor-specific cytotoxic activity (DSCA) in recipient's lymphocytes obtained from bronchoalveolar lavage (BAL). METHODS: A total of 26 mongrel dogs underwent left lung allotransplantation. Dogs received either no immunosuppressive treatment (group I), cyclosporine (group II), or cyclosporine and methylprednisolone for evidence of acute rejection (group III). DSCA was measured by a 51Cr release assay, using lymphocytes from BAL samples as effector cells and 51Cr-labeled donor skin fibroblasts as target cells. The pathologic findings of the transplanted lungs were classified according to the working formulation for classification and grading of pulmonary rejection. In addition, the degree of cellular infiltration in the perivascular, peribronchial, interstitial, and intraalveolar areas was determined based on an infiltration score. RESULTS: DSCA in BAL samples was elevated during mild, moderate and severe acute rejection. The accuracy of the diagnosis of mild or moderate rejection was 92.3% at effector:target (E:T) ratios of 100:1 and 50:1. The DSCA in the BAL fluid and the total infiltration score were correlated closely with correlation coefficients of 0.859 and 0.828 at E:T ratios of 100:1 in group I and group II dogs, respectively. Lung aeration improved and DSCA decreased with methylprednisolone therapy in three of four dogs with grade 2 rejection. CONCLUSION: There is a direct relationship between the DSCA in BAL fluid and the degree of tissue damage caused by acute rejection. The DSCA can be detected by a 51Cr release assay which may hold promise for future clinical applications.

Animals↗

PubMed1997

Two-dimensional aortographic coronary arteriography with above-K-edge monochromatic synchrotron radiation.

RATIONALE AND OBJECTIVES: The diagnostic potential of two-dimensional aortographic coronary arteriography with synchrotron radiation was examined in dogs. METHODS: The experiment was performed at a wiggler beam line by using a silicon monocrystal, fluorescent plate, and avalanche-type camera. The x-ray energy was adjusted to just above the iodine K-edge to obtain the highest contrast. Quantitative densitometry was used to compare intravenous coronary arteriography with aortographic coronary arteriography. RESULTS: Aortographic coronary arteriography clearly depicted the branches of the coronary arteries such as the left anterior descending coronary artery, circumferential coronary artery, and right coronary artery to sizes of less than 0.2 mm without major overlap of coronary arteries. Intravenous coronary arteriography depicted only the branches of the left anterior descending coronary artery and right coronary artery with poor image quality. The ratio of contrast material dilution was about 2.4 to 3.4 in aortographic procedures, whereas in intravenous procedures it ranged widely from 7.7 to 15.6. CONCLUSION: These preliminary investigations indicate that two-dimensional aortographic coronary arteriography with synchrotron radiation promises to be a minimally invasive and easily repeatable method of clearly imaging the coronary arteries.

Animals↗

PubMed1997

Mass-screening of neuroblastoma using urine from infants by high-performance liquid chromatographic method: results of first (6th month) and second (14th month) screening.

To detect neuroblastoma in early stages, mass-screening of this tumor was carried out by HPLC method using the urine of six-month-old infants. Screening began in April, 1981, and a total of 42 cases were detected by December, 1994. The incidence of detection was about 1:5,000 babies tested. All of these patients have survived without relapses except one, who died of surgical complications. Nevertheless, tumors developed at later stages in 14 cases from the group which resulted negative at the 6-month screening. To determine whether such tumors could be detected by a second check, a 14-month screening was carried out, beginning in April, 1991. By December, 1994, 3 patients with neuroblastoma were found among 41,809 babies tested, and were subsequently treated. While one of these three patients was not screened at 6 months, the other two had shown approximate cut-off values in urinary VMA as well as HVA at their 6-month screening. Therefore, if the tumors had already existed at the 6-month screening, and had grown gradually until the second check at 14 months, at least some of these tumors were of the late-onset variety and could have been detected at an earlier stage.

Chromatography, High Pressure Liquid↗

PubMed1997

p21(Waf1/Cip1) and p53 protein expression in breast cancer.

p21/Cip1/Waf1 (wild-type p53 activated fragment 1/cyclin-dependent kinase [Cdk]-interacting protein 1) is a prominent Cdk inhibitor and has been shown to be a downstream mediator of p53. In this study, we sought to clarify the clinical significance of Waf1 and the relationship between Waf1 and p53 in breast cancer. For this purpose, the expressions of Waf1 and p53 were evaluated immunohistochemically in a series of 104 patients. Waf1 was expressed in 51 (49%) of 104 tumors tested, and p53 in 33 tumors (32%). Inverse expression of these two proteins was seen in 76 cases (73%); 47 were Waf1-positive and p53-negative, and 29 were Waf1-negative and p53-positive. A comparison with clinicopathologic parameters showed that Waf1 expression correlated with negative lymph nodes (P<.01), a low histologic grade (P<.0001), and positive estrogen receptor status (P<.01). Recurrence-free survival was lower for patients with Waf1-negative tumors than for those with Waf1-positive tumors (P<.0001). In multivariate analysis, Waf1 expression and low histologic grade (1 or 2) tumors had an independent prognostic significance for recurrence-free survival. These results suggest that Waf1 is induced mainly by a p53-dependent pathway and could be a reliable indicator of recurrence in breast cancer.

Adult↗

PubMed1997

Transient liver accumulation of Tc-99m phytate in hepatocellular carcinoma after percutaneous ethanol injection.

PURPOSE: We report that colloid liver scanning gave early evidence of the return to normal of Kupffer cell functions after ethanol injections into the liver. PATIENT AND METHODS: A 71-year-old man with hepatocellular carcinoma received percutaneous ethanol injections twice of 15 mL of ethanol, 1 week apart. RESULTS: Abdominal CT after the second injection showed an irregularly shaped low-density area in the left side of the tumor, extending outside the tumor. Liver imaging with To-99m phytate 10 days later showed increased activity at the corresponding site. Thirty days after the second injection, liver imaging did not show high activity. CONCLUSIONS: Ethanol that leaked into the normal part of the liver probably temporarily activated Kupffer cell function.

Aged↗

PubMed1997

Case report: interferon induced coma in Sheehan's syndrome.

A 54-year-old woman who was being treated with 10 million units (mu) of natural interferon (IFN)-alpha per day for chronic active hepatitis C at a local clinic, developed coma on the fourth day of treatment. On admission to Yamagata University Hospital, she was still in a state of semicoma with severe hyponatraemia (122 mEq/L) and hypochloraemia (89 mEq/L). After the administration of electrolytes, her condition improved remarkably. Endocrinological loading tests showed a hypofunction of the anterior pituitary gland. In consideration of these results, and her past experiences of haemorrhage during childbirth and subsequent amenorrhoea, we diagnosed her illness as a coma as a result of Sheehan's syndrome which had become overt during IFN therapy. She recovered completely after treatment with hydrocortisone and l-thyroxine.

Adrenocorticotropic Hormone↗

PubMed1997

Low-grade adenosquamous carcinoma of the breast: a case report with cytologic findings and review of the literature.

The cytological and histopathological features of a case of low-grade adenosquamous carcinoma of the breast in a 47-year-old Japanese female was studied. The fine needle aspiration biopsy specimen of this case revealed proliferating ductal cells and atypical squamous cells in the same cell clusters. The resected left breast mass had a relatively well-circumscribed hard mass measuring 1.6 cm at its greatest dimension. Histologic examination demonstrated the co-existence of atypical squamous and ductal components in the same lesion, with transition between these two components. Desmoplastic stromal reaction was observed. The majority of ductal components had a two-layered composition, and sclerosing adenosis-like lesions were also observed at the periphery of the tumor. Based on these cytologic and histological findings, this tumor was diagnosed as low-grade adenosquamous carcinoma of the breast. This is the first report of the cytological findings of low-grade adenosquamous carcinoma of the breast, and it is important for pathologists to consider the possibility of low-grade adenosquamous carcinoma when the cytological findings described above are present in an aspiration cytology specimen of the breast.

Biopsy, Needle↗

PubMed1997

Analysis of phosphorylation of pRB and its regulatory proteins in breast cancer.

AIM: In order to study the role of retinoblastoma protein (pRB) in breast cancer, the phosphorylation of pRB and the expression of its related proteins-such as cyclin E, cyclin dependent kinase 2 (Cdk2), and p21/Cdk interacting protein 1 (Cip1)-were examined in 30 breast cancers in which pRB overexpression was confirmed immunohistochemically. METHODS: The phosphorylation of pRB for 30 tumours was investigated with western blotting. The expression of pRB, Cdk2/Cdc2, cyclin E, and p21/Cip1 was identified by immunohistochemistry and western blotting. RESULTS: The expression of pRB was confirmed in 52 of 70 tumours (74%) by immunostaining. Western blotting for pRB showed that 25 of 30 representative cancers (83%) were underphosphorylated, while only five tumours showed the hyperphosphorylated form of pRB. However, cyclin E and Cdk2-which promote phosphorylation of pRB-were expressed in all tumours. On the other hand p21/Cip1, a Cdk2 inhibitor, was expressed in 18 of 25 tumours with underphosphorylated pRB, while four of the five tumours with hyperphosphorylated pRB showed no expression of p21/Cip1. Examination of the relation between pRB phosphorylation and clinicopathological variables showed that the underphosphorylated group was characterised by low risk of lymph node metastasis (p < 0.01). CONCLUSIONS: The phosphorylation of pRB appears to be regulated mainly by p21/Cip1 through the suppression of cyclin E and Cdk2 in breast cancer. The underphosphorylated form of pRB may be useful as a prognostic factor.

Adult↗

PubMed1997

The Watanabe heritable hyperlipidemic rabbit is a suitable experimental model to study differences in tissue response between intimal and medical injury after balloon angioplasty.

The study evaluates whether the Watanabe heritable hyperlipidemic (WHHL) rabbit is an adequate model to study mechanisms that underlie differences in tissue response after postangioplasty injury. Postangioplasty studies of human coronary arteries have revealed that healing and restenotic processes differ depending on whether the laceration is limited to the atherosclerotic plaque or whether injury extends into the media. Forty-five homozygous WHHL rabbits underwent percutaneous transluminal angioplasty of the left subclavian artery. The inflated arterial segment was studied histologically at 3, 7, 14, 28, and 56 days, using conventional and immunohistochemical techniques to identify macrophages, smooth muscle cell (SMC) phenotypes, and cell proliferation. Electron microscopy was done to study reendothelialization. There were marked differences in response between those segments with medial injury and those with injury limited to the atherosclerotic plaque tissues. The latter category shows a distinct retardation in redifferentiation of SMCs, confirming previous observations in human coronary arteries. In these segments, moreover, cell proliferation occurred mainly in macrophages and spindle cells. Medial injury showed a more florid fibrocellular response, as in human coronary arteries, with cell proliferation initially confined to areas with dedifferentiated SMCs in the preexistent media and, once neointimal tissue was formed, among spindle cells also. The similarities with the repair processes encountered in postangioplasty human coronary arteries suggest that the WHHL rabbit is an adequate model to study differences in the response related to different types of angioplasty injury.

Angioplasty, Balloon↗

PubMed1997

Thyroid hormone receptor beta 1 expression in developing mouse limbs and face.

Thyroid hormone, acting through thyroid hormone receptors (TRs), plays an important role in amphibian metamorphosis and vertebrate development. To identify where and when TR beta 1 promoter is activated during fetal life, we carried out an in vivo functional study of a 1.3 kilobase (kb) TR beta 1 gene promoter using transgenic mice that express the beta-galactosidase gene under control of the TR beta 1 promoter. Transactivation of the gene was determined by blue staining of tissues after incubation with X-gal. High expression of transgene was detected in the limbs and face of the 12.5-day-old fetus (12.5 F) and 14.5 F, reminiscent of the changes occurring during amphibian metamorphosis, and this disappeared at 17.5 F. The expression was confined to the tip of finger bones, between fingers in the limb buds, and was detected in the root of whisker follicles, nose, and around the eyes. Signal was detected in the oral cavity, nasal cavity, lung, and urogenital sinus of 14.5 F, and disappeared at 17.5 F. Signal was detected in the midbrain and auditory vesicles of 9.5 F but was reduced between 12.5F and 17.5F, and there was no expression in the cerebral cortex layer of 0 days old neonates (PO). Expression was detected in the cortex after P5. There was signal in the cerebral cortex, cerebellum, kidney, and liver of adult mice. TR beta 1 messenger RNA was detected by RT-PCR in the developing limbs and face. Transgene expression in the interdigital tissues, which regress during development, suggests that TR beta 1 is expressed in mammals in areas undergoing apoptosis as well as in areas undergoing differentiation.

Aging↗

PubMed1997

Alternative signaling mechanism of leukemia inhibitory factor responsiveness in a differentiating embryonal carcinoma cell.

Leukemia inhibitory factor (LIF) is a cytokine that plays an important role during mouse embryogenesis. We showed that adenovirus E1A represses the interleukin-6 signal transduction pathway that uses the same JAK tyrosine kinase and STAT (signal transducer and activator of transcription) transcription factor as LIF. Here, we report that the LIF-JAK-STAT signal transduction pathway is blocked in cellular E1A-expressing undifferentiated F9 cells, and that the block is overcome by retinoic acid-induced differentiation. LIF failed to stimulate the expression of the acute phase response element (APRE)-driven luciferase gene in undifferentiated F9 cells, whereas the luciferase activity was remarkably increased by LIF treatment in differentiated F9 (dF9) cells. We analyzed the mechanism of the APRE regulation and found that the LIF-induced APRE-binding activity was regulated in a differentiation-dependent manner. The protein levels and the tyrosine phosphorylation of JAK1, JAK2, and STAT3 in F9 cells were not different from those in dF9 cells. The exogenous expression of activated c-Ha-ras partially recovered the LIF responsiveness of the APRE-luciferase gene in F9 cells, but the dominant negative ras N-17 did not repress the LIF-induced activation of APRE-luciferase in dF9 cells. These results suggested that an unknown coactivation process that is partially compensated by Ras is required for STAT3-APRE binding in F9 cells.

Acute-Phase Proteins↗

PubMed1997

Possible involvement of somatolactin in the regulation of plasma bicarbonate for the compensation of acidosis in rainbow trout

Somatolactin is a putative pituitary hormone of the growth hormone/prolactin family in fish. Its function is still unknown. The effects of environmental hypercapnia and hypoxia, acid (HCl) infusion and exhaustive exercise on plasma somatolactin levels were examined in the chronically cannulated rainbow trout to study the possible physiological roles of somatolactin. Respiratory acidosis induced by hypercapnia (2% CO2) did not affect plasma somatolactin level. In contrast, metabolic acidosis induced by acid infusion and exercise increased plasma somatolactin level. Blood pH was depressed to a similar extent by both types of acidosis, whereas plasma [HCO3-] was elevated by respiratory acidosis but reduced by metabolic acidosis. A moderate hypoxia (water PO2 9.3kPa) affected neither acidbase status nor plasma somatolactin level. A more severe hypoxia (water PO2 6.1kPa) resulted in metabolic acidosis accompanied by an apparent rise in plasma somatolactin level, although the difference in somatolactin level from the control value was not statistically significant. Somatolactin immunoneutralization retarded recovery of plasma [HCO3-] following acid infusion. These results indicate that somatolactin is involved in the retention of HCO3- during metabolic acidosis but not in the active accumulation of HCO3- for acidbase compensation of respiratory acidosis in rainbow trout Oncorhynchus mykiss.

Journal Article↗

PubMed1997

Dynamic intravenous coronary arteriography using synchrotron radiation and its application to the measurement of coronary blood flow.

We have developed dynamic intravenous coronary arteriography (IVCAG) using a monochromatic (33.3 keV), 2-dimensional X-ray beam (70 x 70 mm) generated from synchrotron radiation. To investigate its use to visualize the coronary arteries and to estimate coronary blood flow, we performed IVCAG in 10 dogs and 1 goat. The animals were irradiated with the synchrotron beam after intravenous injection of a contrast agent, and images were obtained using a TV camera and videorecorder. In the dogs, blood flow in the left anterior descending coronary artery (LAD) was also estimated from the images by applying a transit-time analysis. We obtained dynamic IVCAG images in the dogs and goat and could visualize even a deliberately created coronary stenosis about 1 mm in length. In addition, coronary blood flow could be estimated with an acceptable degree of accuracy. LAD flow calculated from IVCAG was 14.7 +/- 5.1 ml/min, whereas measured LAD flow was 16.6 +/- 4.8 ml/min. There was a close correlation between the estimated and measured LAD flows (r = 0.90, p < 0.01). Thus, dynamic IVCAG is minimally invasive, permits the simultaneous evaluation of coronary anatomy and blood flow, and may be feasible for clinical application.

Animals↗

PubMed1997

Participation of JAK, STAT and unknown proteins in human placental lactogen-induced signaling: a unique signaling pathway different from prolactin and growth hormone.

The signal transduction mechanism involved in human placental lactogen (hPL) was studied. We have identified that hPL rapidly stimulated the tyrosine phosphorylation of at least 7 proteins including Janus Kinases (JAK1 and JAK2) and a signal transducer and activator of transcription protein (Stat3). This is the first evidence that the JAK-STAT pathway is involved in the hPL signaling. Moreover, two unknown proteins which were different from STAT proteins (Stat1, 3 and 5) in sizes were predominantly tyrosine-phosphorylated. Because human growth hormone (hGH) activates Stat1, 3, 5 and human prolactin (hPRL) activates Stat5, these results show that hPL uses a unique signal transduction pathway which is different from hGH and hPRL.

Acute-Phase Proteins↗

PubMed1997

Evaluation of fulminant hepatic failure by scintigraphy with technetium-99m-GSA.

UNLABELLED: We evaluated the usefulness of hepatic receptor imaging with 99mTc-diethylenetriaminepentaacetic acid galactosyl human serum albumin (GSA) to establish the diagnosis and prognosis of fulminant hepatic failure (FHF). METHODS: Of the 20 patients, 8 had acute hepatitis and 12 had FHF. Computer acquisition of gamma-camera data started just before the injection of 185 MBq 99mTc-GSA and stopped 20 min later. Time-activity curves for the heart and liver were generated from regions of interest (ROIs) for the whole liver and precordium. A receptor index was calculated by division of the radioactivity of the liver ROI by that of the liver plus heart ROIs 15 min after the injection. An index of blood clearance was calculated by division of the radioactivity of the heart ROI at 15 min by that of the heart ROI 5 min after the injection. RESULTS: The receptor index was less than 0.83 in all patients with FHF, but it was more than 0.83 in all patients with acute hepatitis. The index of blood clearance was more than 0.72 in all patients with FHF but less than 0.72 in all patients with acute hepatitis. All six survivors of FHF had receptor indices of 0.58 or more, but in five of the six patients who later died, the receptor index was 0.58 or less. The index of blood clearance was 0.85 or less in all survivors but 0.85 or more in the same five patients who later died. CONCLUSION: Hepatic receptor imaging with 99mTc-GSA facilitated the evaluation of hepatic function reserve and was useful in establishing the diagnosis and prognosis of FHF.

Acute Disease↗

PubMed1997

Changes in results of Gallium-67-citrate scanning after interferon therapy for chronic hepatitis C.

UNLABELLED: Gallium-67 scanning is useful for early diagnosis and grading of interstitial lung disease. In a study of the side effects of interferon (IFN) on the lungs of patients with chronic hepatitis C, we performed 67Ga scanning before and after IFN therapy. METHODS: The 66 subjects who underwent at least one scanning, before IFN therapy, were 8 patients with chronic persistent hepatitis (CPH), 21 with chronic aggressive hepatitis 2A (CAH-2A), 25 with chronic aggressive hepatitis 2B (CAH-2B) and 12 with cirrhosis. All had underlying hepatitis C viral infection. Of those patients, 20 were examined again within 1 mo after IFN therapy. Patients received an intravenous injection of 340 MBq 67Ga-citrate and were imaged 72 hr later. ROIs were established for anterior views of the lungs (Lu), liver (Li) and soft tissue of the upper arm as background (B). The counts per unit size of each region of interest were used in calculation of the ratios Lu/B and Li/B. RESULTS: The medians of Lu/B were 2.46 in CPH, 2.56 in CAH-2A, 2.50 in CAH-2B and 2.47 in cirrhosis. These differences were not statistically significant. The medians of Li/B were 6.42 in CPH, 6.14 in CAH-2A, 5.11 in CAH-2B and 4.03 in cirrhosis. The differences between the median Li/B of cirrhotic patients and the medians for patients with CPH, CAH-2A and CAH-2B were significant. After therapy, Lu/B was higher than before in 16 of the 20 patients and lower in the four other patients; the overall rise was significant (Wilcoxon rank-sum test). Li/B was higher than before in 11 of the 20 patients and lower in the nine other patients. CONCLUSION: IFN caused uptake of the radionuclide to increase in most patients. This method showed changes in the accumulation of 67Ga-citrate that could have been missed if the results had been inspected by eye. IFN can cause interstitial lung disease, but unlike other drugs with this side effect, the onset seems to be gradual enough to be detected quantitatively by 67Ga scanning.

Adult↗