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Biomedical subjects

T Toyama

Publications and source records attributed to T Toyama.

At least 37 records · Page 2Linked to original sources
PubMed2001

Metachronous primary hyperparathyroidism due to a parathyroid adenoma and a subsequent carcinoma: report of a case.

An extremely rare case of metachronous primary hyperparathyroidism (PHP) due to a parathyroid adenoma and subsequent carcinoma with local lymphatic spread is presented herein. A 55-year-old woman was operated on for a parathyroid adenoma in the right inferior gland. Thirteen years after the first operation, she was again hospitalized for hypercalcemia and the presence of a hard mass in the right anterior neck region. Exploratory surgery and a histological examination of the resected tumor provided evidence of a parathyroid neoplasm in the right superior gland but the malignancy was equivocal. Postoperatively, her serum parathyroid hormone (PTH) level remained at 1.5-fold the upper limit of the normal range, and hypercalcemia again gradually developed. The results of higher positive rates by Ki-67 immunohistochemical staining and an aneuploid pattern by a flow cytometric analysis of the second neoplasm were consistent with a histological diagnosis of carcinoma, and she therefore underwent further surgery. A radical neck dissection revealed two lymph node metastases which were both successfully removed. The postoperative serum PTH and calcium levels then returned to within the normal ranges. These findings indicate the usefulness of Ki-67 immunohistochemical staining and a flow cytometric analysis for differentiating malignant lesions from benign parathyroid lesions, and the importance of surgically treating cases limited to local regions without distant metastasis.

Adenoma↗
PubMed2001

Telomerase activity levels for evaluating the surgical margin in breast-conserving surgery.

To evaluate the efficiency of measuring telomerase activity levels in clinical diagnosis, we performed a semiquantitative analysis of telomerase activity in breast tumors and compared the results with the histological findings. Breast tissue adjacent to areas of cancer were also serially resected and checked for telomerase activity. The amount of telomerase activity in the breast cancers ranged widely, from 0.36 to 1180 units/microg, with 31 of the 34 (91.2%) showing a value above 1.0unit/microg. None of the normal breast tissues including mastopathy, and only 4 (23.5%) of 17 benign breast masses had values above 1.0unit/microg. Telomerase activity was detectable in serial sections of adjacent tissues as far as 10mm from the macroscopic tumor margin with histologically detectable cancer cells. Furthermore, telomerase activity was detectable in the scrape specimens obtained from the stump of the surgical margins for breast-conserving surgery, and this activity was in accordance with the histological findings. These findings show that conducting a semiquantitative assay of telomerase activity is useful for evaluating the surgical margin in breast-conserving surgery.

Biomarkers, Tumor↗
PubMed2001

Successful management of breast cancer with liver metastases with medroxyprogesterone acetate treatment.

A 38-year-old woman with cancer in the left breast underwent standard radical mastectomy. The estrogen receptor and progesterone receptor status of the primary tumor was unknown. Ten years after the surgery, a metastatic liver tumor was detected, and chemoendocrine therapy, consisting of cyclophosphamide, epirubicin, 5-fluorouracil (CEF) and medroxyprogesterone acetate (MPA) was initiated. The metastatic liver tumor showed a partial response after 11 cycles of such chemoendocrine therapy. Subsequently, MPA alone was given daily as maintenance therapy, and the disease has remained stable for 6 years. For women with metastatic breast cancer, complete remission is uncommon, and stable disease is a reasonable goal of successful therapy. In this respect, chemoendocrine therapy with CEF and MPA, followed by MPA alone as maintenance therapy, was successful in the patient reported here. Importantly, the patient's quality of life has remained favorable for several years after the partial response was achieved.

Adult↗
PubMed2001

Clinical significance of elevated serum interferon- inducible protein-10 levels in hepatitis C virus carriers with persistently normal serum transaminase levels.

The aim of this study was to assess the immunological profile in hepatitis C virus carriers with persistently normal serum transaminase levels. Forty-two serum HCV RNA positive patients with persistently normal serum transaminase levels (22 natural 'asymptomatic HCV carriers' and 20 biochemical responders to IFN therapy) and 23 complete responders to IFN therapy were enrolled. The HCV genotypes and serum HCV RNA levels were determined before IFN therapy in treatment responders, and at entry in the others. The serum levels of IFN-inducible protein-10 (IP-10) (a protein mainly induced by IFN-gamma), interleukin (IL)-10, and IL-4 were measured in all patients while the serum transaminase levels were normal. The serum transaminase levels and platelet counts were then monitored for the next 4 years and the changes in liver fibrosis were assessed. The serum levels of IP-10 in infected and biochemically normal patients were significantly higher than the levels in complete responders to therapy, whereas the serum levels of IL-10 and IL-4 did not vary significantly among the different groups. During the 4-year follow-up period, 10/20 (50%) biochemical responders and 12/22 (55%) asymptomatic carriers had an elevation of the serum transaminase levels. A significant (P=0.0370) increase in platelet count after 4 years and improvement in liver fibrosis were noted in treatment responders but not in infected patients. The weak but significant residual immune response as reflected by the increased serum IP-10 level may underlie the outcome of HCV carriers with persistently normal serum transaminase levels.

Alanine Transaminase↗
PubMed2001

Time course profile and cell-type-specific production of monokine induced by interferon-gamma in Concanavalin A-induced hepatic injury in mice: comparative study with interferon-inducible protein-10.

BACKGROUND: We have previously shown that interferon-inducible protein-10 (IP-10), a chemokine for activated lymphocytes, was specifically induced in the liver of Concanavalin A (Con A)-treated mice. The aim of this study was to investigate the time course profile and cell-type-specific hepatic production of monokine induced by interferon-gamma (MIG), a chemokine which shares its receptor and most of its activity with IP-10, in Con A-treated mice and to compare them with those of IP-10. METHODS: Hepatic mRNA expression of MIG and IP-10 was studied by means of Northern blot analysis and in situ hybridization in Con A-treated mice. The levels of MIG and IP-10 in the serum and culture supernatants of murine hepatoma-, hepatic sinusoidal endothelial cell-, hepatic stellate cell- and macrophage-derived cell lines were determined by means of specific enzyme-linked immunosorbent assays. RESULTS: The serum level of MIG slowly reached a maximum at 12 h after Con A injection and remained elevated for a long time, whereas that of IP-10 reached a maximum at 3 h and declined quickly, a finding supported by Northern blot analysis. Using in situ hybridization, the mRNA of MIG as well as IP-10 was found to be expressed in hepatocytes and hepatic non-parenchymal cells. Similar to IP-10, MIG was produced by hepatoma-, hepatic sinusoidal endothelial cell-, hepatic stellate cell- and macrophage-derived cell lines in vitro. CONCLUSIONS: Although both MIG and IP-10 were produced by hepatocytes and hepatic non-parenchymal cells in Con A-treated mice, the time course profile of MIG was distinguishable from that of IP-10. The fact that hepatic MIG and IP-10 were produced sequentially in this hepatitis model may suggest that a non-redundant role is played by these two chemokines in the process of hepatic necro-inflammation.

Animals↗
PubMed2001

Electrocardiographic ST-segment elevation and changes in the regional work of the left ventricle during coronary angioplasty.

This study evaluated the reduction in regional work of the left ventricle caused by acute myocardial ischemia during coronary angioplasty, and correlated it with ST-segment elevation. Regional work of the left ventricular myocardium, which is derived from a stress-strain loop, is a useful index of the function of a diseased heart. However, the effects of transient ischemia on the regional work of the myocardium have not been fully elucidated. The subjects consisted of 25 patients who had proximal left anterior descending artery stenosis with normal wall motion and without collateral circulation. The patients were classified as showing ST-segment elevation > or = 0.2 mV (group A, 10 patients), or ST-segment elevation < 0.2mV (group B, 15 patients) during coronary angioplasty. Group A showed a greater reduction in the regional work of the interventricular septum than group B. Regional work recovered to the baseline level 30 s after balloon deflation in group B, but took 40 s in group A. A greater ST elevation during balloon inflation was associated with a greater, prolonged reduction of work performance in the ischemic region and a greater concomitant increase in the opposite nonischemic region.

Acute Disease↗
PubMed2001

Short-term physical training improves ventilatory response to exercise after coronary arterial bypass surgery.

The issue of whether exercise training improves exercise hyperpnea in patients after coronary arterial bypass graft (CABG) surgery has not been fully explored. Effects of short-term physical training on ventilatory response and cardiac output during exercise in patients following coronary arterial bypass grafting surgery is studied. Thirty-four patients underwent exercise training for 2 weeks after the second postoperative week (Ex group); 23 stayed sedentary (Sed group). Ventilatory and cardiac output response during the cardiopulmonary exercise test was measured before and after the training period. The minute ventilation-carbon dioxide output (VE-VCO2) slope decreased from 38.9+/-8.1 to 35.1+/-6.7 (p<0.05) in the Ex group, but failed to decrease in the Sed group (39.7+/-11.1 to 41.5+/-11.4). Cardiac output during exercise at 20W and at peak exercise, and peak oxygen pulse (VO2/HR) increased significantly only in the Ex group after training. There was a correlation between improvement of the VE-VCO2 slope and peak cardiac output during the training interval (r=-0.47) in the Ex group. Short-term physical training after CABG improves ventilatory response to exercise and increases cardiac output during exercise. Improvement of cardiac output is correlated with a decreased value of the VE-VCO2 slope.

Aged↗
PubMed2001

Stress thallium-201 myocardial scintigraphy in patients with complete occlusion of the left main coronary artery.

Complete occlusion (CO) of the left main coronary artery (LMCA) is a rare but often fatal condition. The diagnosis is frequently missed because the signs and symptoms are often obscure and diverse. We describe three patients with CO-LMCA who showed unusual myocardial scintigraphic findings. The patients had extensive right-to-left collateral channels and decreased uptake and washout rates at the basal anterior and anterolateral portions of the heart wall during stress thallium-201 scintigraphy. The basal anterior to anterolateral portion of the heart wall is the most distant from the collateral artery and should be the most ischemic area shown during exercise, resulting in this scintigraphic pattern. This scintigraphic finding may be useful for the noninvasive diagnosis of CO-LMCA.

Aged↗
PubMed2001

[Outcome of patients with significant coronary stenosis but without ischemic evidence on exercise myocardial perfusion scintigraphy].

OBJECTIVES: The rates of cardiac events and coronary revascularization were evaluated in patients with significant coronary stenosis of more than 75% by the American Heart Association (AHA) classification but no ischemic evidence by exercise myocardial perfusion scintigraphy. METHODS: Subjects were 171 patients (113 males, 58 females, mean age 66 +/- 9 years) undergoing coronary angiography and without scintigraphic evidence of myocardial ischemia. They were divided into two groups according to the severity of coronary artery stenosis based on AHA classification. Group A was composed of 139 patients with more than 75% stenosis (101 patients with 75% stenosis and 38 patients with more than 90% stenosis), and Group B was composed of 32 patients with 50% stenosis. Cardiac events including angina pectoris (n = 63), myocardial infarction (n = 1), heart failure (n = 2) and cardiac death (n = 0), coronary revascularization and predictive factors were evaluated during follow-up of 34 +/- 21 months. Furthermore, the interval between coronary revascularization and exercise myocardial perfusion scintigraphy was estimated. RESULTS: The rates of cardiac events (45%) and coronary revascularization (29%) in Group A were significantly higher than the rate of cardiac events (9%, p < 0.05) and coronary revascularization (6%, p < 0.05) in Group B. Only percentage stenosis and the number of diseased vessels affected the rates of cardiac event and coronary revascularization. CONCLUSIONS: Patients with significant coronary stenosis, but without ischemic evidence by exercise myocardial perfusion scintigraphy, have a relatively high rate of cardiac event and coronary revascularization, especially in patients with severe stenosis or multivessel disease. However, coronary revascularization should not be performed in all patients with significant coronary stenosis.

Aged↗
PubMed2001

[Strategy for post coronary artery bypass grafting in patients with bypass graft stenosis: comparison of percutaneous transluminal coronary angioplasty for the native coronary artery, internal mammary artery and saphenous vein graft].

OBJECTIVES: The strategy for post coronary artery bypass grafting (CABG) was investigated in patients with graft stenosis. METHODS: The study included 123 post-CABG patients with graft stenosis. The patients were divided into three groups according to target vessels; saphenous vein graft (SVG; n = 72), internal mammary artery (IMA; n = 21) and native coronary artery (n = 30). Furthermore, SVG lesions were divided into proximal anastomosis (n = 23), body (n = 40) and distal anastomosis (n = 9). The procedural success rate and late patency rate were compared between the three groups. Furthermore, the relationships between pre percutaneous transluminal coronary angioplasty (PTCA) percentage diameter stenosis, procedural success rate and late patency rate were evaluated. RESULTS: Procedural success rate was similar in the three groups, but late patency rate was higher in the IMA group. Procedural success rate and late patency rate were significantly lower in proximal anastomoses compared to other sites of SVG stenoses, IMA group and native coronary artery group (p < 0.05). Totally occluded native coronary artery lesions had a high procedural success rate compared with occluded IMA and SVG lesions, but the late patency rate was not higher. Procedural success rate showed no significant difference for 75-99% stenotic lesions, but the late patency rate was significantly higher in the IMA group (p < 0.05). Patients in the stenting group had a greater late patency rate compared with the balloon angioplasty group. There was no significant difference in late patency rate between the IMA group and SVG group. CONCLUSIONS: Late patency rate of the IMA is higher than that of the native coronary artery. SVG with proximal anastomosis and severe stenosis shows a significantly lower late patency rate than the native coronary artery. Therefore, PTCA should be considered for the native coronary artery in the absence of chronic total occlusion.

Aged↗
PubMed2001

[Primary splenic CD8-positive diffuse large B-cell lymphoma].

A 71-year-old woman was admitted for further examination of an increased serum LDH level. Abdominal ultrasonography and CT scan showed a large tumor in her spleen. Because malignant lymphoma was suspected, the spleen was removed for diagnosis and treatment planning. The histopathological and immunohistochemical features of the tumor indicated diffuse large B-cell lymphoma (DLBL). The flow-cytometric immunophenotype of the lymphoma cells was CD2-, CD3-, CD4-, CD5-, CD8+, CD10+, CD19+, CD20+, CD23-, kappa+, lambda-, CD25+, and CD56-. From these findings, the patient was diagnosed as having CD8+ DLBL. To our knowledge, this is the first reported case of primary splenic CD8-positive DLBL.

Aged↗
PubMed2000

Loss of heterozygosity and microsatellite instability in ductal carcinoma in situ of the breast.

To investigate the alterations of genetic instabilities in carcinogenesis of the breast, we analyzed the allelotypic profile of 65 ductal carcinomas in situ (DCIS), compared with that of 207 invasive ductal carcinomas (IDC) of the breast. These studies were performed by means of examining microsatellite-length polymorphisms at seven loci (AluVpa, ESR, D11S988, D13S267, D16S398, D17S1159, and D17S855) from microdissected paraffin sections. Allelic loss or imbalance, considered a loss of heterozygosity (LOH), tended to be more frequently seen in IDC than in DCIS. In particular, the frequency of LOH at the 17p locus was significantly higher in IDC than in DCIS (42 vs. 23%, P=0.022). LOH in DCIS was most frequently seen at D16S398 (26%). LOH frequency at D16S398 in low- and intermediate-grade DCIS was higher than that in high-grade DCIS, while LOH frequencies at D11S988 and D17S1159 in low- and intermediate-grade DCIS was lower than those in high-grade DCIS. LOH frequency at D11S988 in non-comedo type DCIS was lower than that in comedo type DCIS. Furthermore, the frequency of microsatellite instability (MSI) at only one locus in DCIS (28%) was statistically higher than that in IDC (6%) (P<0.001), while there was no difference between the frequency of MSI at multiple loci in DCIS (6%) and that in IDC (3%). Together, these observations indicate that chromosomal losses of 16q may occur in low- and intermediate-grade DCIS and those of 11p and 17p may occur high-grade DCIS, and that MSI occurring at only one locus is not yet clear and MSI at multiple loci is uncommon in not only IDC but also DCIS of the breast.

Adult↗
PubMed2000

Expression of estrogen receptor alpha exon 5 and 7 deletion variant in human breast cancers.

BACKGROUND: An exon deletion variant of estrogen receptor (ER) mRNA has been reported, as one of the possible mechanisms of loss of ER function. METHODS: We examined the expression of exons 3, 5, and 7 in ER alpha mRNA and the frequency of exon deletion variant expression in 64 cases of human breast cancers and in 8 non-cancerous breast tissues using reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Approximately the same amount of wild-type (wt) mRNA was detected in all the non-cancerous breast tissues. In cancers, expression of wild-type exon 3 (w3), exon 5 (w5), and exon 7 (w7) was detected in 93.5%, 93.5%, and 91.3% of ER alpha protein (pER) positive cases, respectively, and 27.8%, 38.9%, and 44.4% in negative cases, respectively (p < 0.0001, p = 0.0035, and p = 0.0002). Although the variants for exon 5 (d5) and 7 (d7) were detected in both non-cancerous and cancerous tissues respectively, the variant for exon 3 was not detected at all. Comparatively, the ratio of d5/w5 was significantly higher in pER positive and progesterone receptor protein (pPgR) negative cases. CONCLUSIONS: We suspect that the exon 5 deletion does not work as a dominant positive.

Breast↗
PubMed2000

Comparison of five different antibodies in the immunohistochemical assay of estrogen receptor alpha in human breast cancer.

BACKGROUND: Estrogen receptor alpha (ER) expression is the best prognostic and predictive factor of hormone dependency of human breast cancers. Unlike enzyme immunoassay (EIA), which has been widely used to evaluate ER status in breast cancer, immunohistochemical assay (IHC) can detect ER in a small amounts of tissue with detailed localization. Although there is a sufficient number of ER antibodies against various regions of the protein, the reliability of IHC staining is only well understood for a few. IHC and EIA for the evaluation of the ER status of human breast cancer, therefore, should be compared using the same breast cancer tissues. METHODS: Five different ER antibodies (1D-5, C-314, G-20, C-311 and HC-20) that identify different amino acid sequences were used. The evaluation of ER status by IHC using these antibodies was compared with EIA concomitantly in 97 primary human breast cancer tissues RESULTS: The positivity rate for EIA was 68%. That of IHC for antibodies 1D-5, C-314, G-20, C-311 and HC-20 was 50.5%, 47.4%, 46.4%, 44.3% and 57.7%, respectively. The concordance between EIA was 76.3% for 1D-5 and 77.3% for HC-20, which is statistically highly significant (p<0.0001); Other antibodies were not. CONCLUSIONS: HC-20 is most suitable in the evaluation of the ER status of human breast cancers using the IHC method. Although antibody 1D-5 is also available, C-314, G20 and C-311 are unreliable in such an evaluation.

Antibodies↗
PubMed2000

Readministration of tamoxifen after adjuvant therapy for recurrent breast cancer.

BACKGROUND: Previous series concerning tamoxifen (TAM) rechallenge did not obtain satisfactory results. Using stricter criteria, we now assess the usefulness of readministration of TAM as an initial therapy for patients with recurrent breast cancer. METHOD: The eligibility criteria were postmenopausal, estrogen receptor (ER) positive or unknown, at least 12 months of adjuvant TAM, a 6-month or longer drug-free period and no previous therapy after recurrence. A total of 10 patients were enrolled. TAM was administered in daily doses of 20 or 30 mg. RESULTS: The mean age of the patients at the time of recurrence was 64.8 years. The receptor status was positive in 8 patients and unknown in 2. The median disease-free interval (DFI) after mastectomy was 71.7 months. A complete response was observed in one patient, a partial response in 6, stable disease in 2, and progression in one. The response rate was thus 70%, with an additional two patients showing no progression over 6 months. Although only one patient with a DFI of less than 48 months showed a positive response, all patients with a DFI longer than 48 months showed a clinical response. The duration of response was less than 12 months in 3 patients and longer in 4. CONCLUSION: The post-adjuvant readministration of tamoxifen is a useful first choice therapy for postmenopausal recurrent breast cancer patients with positive ER and longer DFI.

Aged↗
PubMed2000

Does repeated balloon inflation during coronary angioplasty induce ischemic tolerance? Analysis based on regional work.

It has been reported that repeated brief balloon inflation during coronary angioplasty (PTCA) alleviates myocardial dysfunction. However, it has also been reported that PTCA does not induce ischemic tolerance. Six patients with stable angina pectoris were recruited for this study. They were scheduled for PTCA to a significant stenosis of the proximal left anterior descending artery (LAD). All patients had single-vessel coronary artery disease without angiographic evidence of collateral circulation and with normal wall motion. After the stenosis of LAD was dilated by a 30-s inflation, 60 s of balloon inflation was performed five times at 60-s intervals. Left ventricular regional work was determined in the first and fifth inflations, and the data were compared. Regional work of the interventricular septum decreased immediately after the balloon inflation (the first inflation: 5.3 +/- 1.0 --> 0.6 +/- 0.2 mJ/cm3; fifth inflation; 5.3 +/- 1.0 --> 0.6 +/- 0.3 mJ/cm3) and no statistically significant differences were found between the first and fifth inflations. After balloon deflation, the time required for the recovery of regional work was 30s in the fifth inflation, compared with 40 s in the first inflation (at 30 s after deflation, first inflation: 3.6 +/- 1.3 mJ/cm3; fifth inflation: 5.2 +/- 1.2 mJ/cm3). Although repeated balloon inflation did not change the amount of reduction in regional work, it improved the postischemic recovery of regional work. These results suggest ischemic tolerance.

Aged↗
PubMed2000

A novel strategy for cancer therapy by mutated mammalian degenerin gene transfer.

Mammalian degenerin (MDEG) is a member of the amiloride-sensitive sodium ion channel family, and its site-directed active mutant (MDEG-G430F) induces massive Na+ influx into cells, leading to cell ballooning and cell bursting. We attempted a novel therapeutic approach for gastric cancers by transferring MDEG-G430F into cancer cells using tumor-specific promoters. In carcinoembryonic antigen (CEA)-producing gastric cancer cells, the level of cell death observed when MDEG-G430F was used with a CEA promoter was similar to that observed when using a potent nonspecific promoter such as the cytomegalovirus promoter. In an in vivo study, fusogenic liposome complexes containing MDEG-G430F driven by the CEA promoter were injected intraperitoneally into CEA-producing gastric cancer cells in a mouse peritoneal dissemination model. Although all 15 of the control mice were dead by 50 days postinoculation, 13 of the 15 mice treated with MDEG-G430F survived. These results indicate that transferring MDEG-G430F into cancer tissues using tumor-specific promoters can achieve striking and selective cancer cell death irrespective of the transcriptional efficiency of the promoters used in vivo, and suggest that this approach is a promising new strategy for cancer gene therapy.

Acid Sensing Ion Channels↗