Biomedical subjects

T Sugimoto

Publications and source records attributed to T Sugimoto.

At least 361 records · Page 20Linked to original sources

PubMed1998

[14C-oxalate autoradiographic studies on distribution of oxalate and calcium oxalate crystal fixation in rat kidney].

To elucidate the intrarenal distribution of oxalate and to reveal the first site of calcium oxalate crystal fixation along the nephron, we carried out 14C-oxalate renal microautoradiography by the thaw mount method 30, 60 and 90 min after intravenous administration of 14C-oxalate, in normal rats and in hyperoxaluric rats fed a vitamin B6-deficient diet for 4 and 9 weeks. In normal rats, radioactivity was observed in the entire kidney area at 30 min after the injection and at 90 min there was radioactivity only in the papilla, where radioactivity appeared in the parenchyma, mamely the epithelial cells of collecting ducts and the surrounding interstitial tissue. In hyperoxaluric rats, microautoradiograms showed the spotted deposits of 14C-oxalate in both renal papilla and medulla. In 600 x magnification of the autoradiograms, most of the deposits were detected in the epithelial cells of collecting ducts and the surrounding interstitial tissue. These deposits were identified by a polarizing microscope and X-ray microanalysis as crystal deposits of calcium oxalate. These results indicated that oxalate remained for an extended period of time in the epithelial cells of collecting ducts and in the surrounding interstitial tissue in renal papilla, and the calcium oxalate crystals fixed to the same tissue was the first step in the development of calcium oxalate stones.

Animals↗

PubMed1998

[Hyperparathyroidism and its management].

Hyperparathyroidism (HPT), resulting from the excess of endogenous parathyroid hormone is cited as one of diseases which cause secondary osteoporosis. HPT consists of primary (1 degree) and secondary (2 degrees) HPT, resulting mainly from chronic renal failure (CRF). HPT is easily distingishable from primary osteoporosis by biochemical measurements. Parathyroidectomy (PTX) is the only option available for the radical cure of 1 degree HPT and more than 10% increase in bone mass occurs after PTX. On the other hand, dietary phosphorus restriction, phosphorus binders, active vitamin D3 metabolites are useful for 2 degrees HPT due to CRF. When these treatments are not effective to inhibit PTH secretion adequately, oral active vitamin D3 pulse therapy, PTX and percutaneous ethanol injection therapy should be considered.

Humans↗

PubMed1998

[Intraoperative local infusion chemotherapy (ILIC) for gastric cancer].

In order to provide a high dose of cis-diammine dichloro platinum (CDDP) into the regional lymph nodes and surrounding organs during operation, "intraoperative local infusion chemotherapy (ILIC)" was devised and has been applied to advanced gastric cancer patients. The aims of this method are 1) to reduce the possibility of metastasis by affecting the cancer cells before flowing out; 2) to administer drugs to the cancer cells which evade surgical resection; 3) to administer drugs to the lymphatic flow; and 4) to reduce the systemic side effects. After the laparotomy, the part of the stomach for gastrectomy was isolated from the blood supply, applying clamps to the proximal and distal parts of the stomach and hemostats to feeding blood vessels. Through a feeding artery to the tumor, 50 mg of CDDP was injected. Twenty-four patients underwent ILIC from June 1986 to December 1993. The 5-year survival rate was significantly better in the ILIC group compared to the control group which was selected by the matched pair method. The newly devised ILIC chemotherapy is a promising way to improve the prognosis of advanced gastric cancer patients. A randomized prospective study should be undertaken.

Animals↗

PubMed1998

[Early and late surgical mortality of acute type A aortic dissections by open distal anastomosis with deep hypothermic retrograde cerebral perfusion].

We have analyzed the operative results and the long-term prognosis of Stanford type A acute aortic dissections. Between 1981 and 1997, 57 patients underwent surgical repairs of acute type A aortic dissection. In the earlier period (1981-1990; n = 21), almost all the operations were performed under aortic cross-clamping with conventional cardiopulmonary bypass, while in the later period (1991-1997; n = 36), radical resections and graft replacements under open distal anastomosis with deep hypothermic retrograde cerebral perfusion (RCP) were performed in 24 patients (66.7%) and with selective cerebral perfusion in 3 (8.3%). The hospital mortality rates were 33.3% in the earlier period and 16.7% in the later period. Two (8.3%) of 24 patients employed RCP failed by preoperative rupture to pulmonary artery and myocardial infarction. Reoperations for enlargement of the remained false lumen were performed in 4 in the earlier period, of whom 2 patients were dead. In the later period, 7 patients were reoperated on, and all patients survived. Over all actuarial survival rates were 57.1% at 5 year and 44.4% at 10 year in the earlier period, while it was 70.7% at 5 year in the later group. We concluded that retrograde cerebral perfusion allows resection of the dissected aorta including primary entry as well as open distal anastomosis, which contributes to the improvement of early and long-term results for acute type A aortic dissection.

Acute Disease↗

PubMed1998

[Significance of hepatocyte growth factor measurement in patients with acute myocardial infarction].

The use of hepatocyte growth factor for acute myocardial infarction was investigated. Several other biochemical markers are already used for noninvasive detection of acute myocardial infarction. Hepatocyte growth factor, creatine phosphokinase (CK) and CK isozyme (CK-MB) levels were measured in 10 patients with stable effort angina after diagnostic catheterization, and in 21 patients with acute myocardial infarction twice a day for the first 3 days and once a day for the next 4 days. The time to reach the maximum level and the time to decline to less than half of the maximum level for each patient was also measured. Hepatocyte growth factor levels (ng/ml) were 0.3 +/- 0.1 for patients with angina pectoris, and 10.4 +/- 8.8 within 6 hours and 6.7 +/- 4.5 within 12 hours after the onset for patients with acute myocardial infarction. The time to reach the maximum (hours) and the time to decline to less than half of the maximum level (days) were 9.2 +/- 5.2 and 1.1 +/- 0.3 for hepatocyte growth factor, 19.5 +/- 7.2 and 2.3 +/- 1.1 for CK and 16.3 +/- 7.2 and 1.5 +/- 0.4 for CK-MB, respectively. The correlation coefficients between the maximum level of hepatocyte growth factor and the maximum levels of CK and CK-MB were 0.64 and 0.70, respectively. Hepatocyte growth factor is useful as a prognostic indicator and reflects the clinical course in patients with acute myocardial infarction.

Aged↗

PubMed1998

[A case of acute polyradiculoneuritis with multiple cranial nerve palsy and cerebral lesion--possible evidence of encephalo-myelo-radiculo-neuropathy].

We report a case of acute polyradiculoneuritis with multiple cranial nerve palsy and cerebral lesions. A boy, born on July 26, 1987, developed unusual sensation on the extremities, backache and sleep disturbance on June 23, 1996. On July 2, following a complaint of blindness he developed a convulsion and was admitted to our hospital. Neurological examination revealed intact consciousness, severe external ophthalmoplegia, bifacial palsy and generalized areflexia. On the next day, flaccid tetraplegia and respiratory dysfunction developed and progressed without disturbance of consciousness. After tracheal intubation he was under mechanical ventilation. A lumbar puncture examination showed clear CSF with increased protein 166 mg/dl. no cells and normal myelin basic protein. Serum antibodies against gangliosides (GM1, asialo-GM1, GD1b and GQ1b) were not detected. A posterior tibial nerve conduction velocity was mildly delayed with disappearance of F- wave. On the other hand, very slow background activity was shown by EEG, extensive focal hypoperfusion of cerebral blood flow by SPECT and supratentorial multiple high intensity lesions by T2 weighted MRI of the brain. There were no abnormal signals in the brainstem and cerebellum on MRI. His condition dramatically improved after plasmapheresis. The abnormal findings of SPECT and MRI promptly disappeared within 3 weeks, although abnormal signs on EEG persisted. He was successfully weaned off the respirator and recovered strength of the limbs. He was discharged on August 28, 1996, with supported walk and bifacial palsy, then he completely recovered by 7 months. The condition of case was compatible with 'encephalo-myelo-radiculo-neuropathy', a disease entity that had previously been reported in a few patients in whom with Guillain-Barré or Fisher syndrome and cerebral symptoms co-existed.

Acute Disease↗

PubMed1998

Clear cell sarcoma of kidney with tumor extension into the right atrium.

A 28-year-old man with a Wilms tumor extending into his right atrium was successfully treated using cardiopulmonary bypass. Histologic examination revealed clear cell sarcoma with invasion of the inferior vena cava. This case represents the oldest patient with clear cell sarcoma of the kidney ever published in the English literature.

Adult↗

PubMed1998

[Disseminated carcinomatosis of the bone marrow occurring 11 years after subtotal gastrectomy for gastric cancer].

A 44-year-old man was admitted to our hospital because of purpura, increased serum alkaline phosphatase, and thrombocytopenia. He had undergone subtotal gastrectomy for gastric cancer 11 years earlier. A biopsy specimen of the bone marrow revealed metastatic mucin-forming, moderately differentiated adenocarcinoma. Because the primary tumor was not detected in any other organ, the gastric cancer the patient was treated for 11 years earlier was suspected as the primary tumor. Microangiopathic hemolytic anemia and disseminated intravascular coagulation developed during the clinical course, and the patient deteriorated despite treatment with anticoagulants. Finally, he died of pulmonary carcinomatous lymphangitis. Autopsy revealed a small number of adenocarcinomatous cells in the lymphoduct of the remaining stomach in spite of its mucosa being intact. We concluded that the bone marrow was infiltrated by cancer cells which originated in the stomach 11 years before. It is unclear why adenocarcinoma cells remained dormant for as long as 11 years in the gastric lymphoduct and bone marrow.

Adenocarcinoma↗

PubMed1998

[A case of renal pelvic cancer with high serum level of CA 19-9].

A case of left renal pelvic cancer with a high level of serum CA19-9 is reported. Radiological examination showed a left renal pelvic cancer with lymph node metastasis, but did not reveal any tumors producing CA19-9 in any other organs. Chemotherapy was performed in addition to left total nephroureterectomy. The serum level of CA19-9 decreased to the normal range within three weeks after the operation. Immunohistochemical examination demonstrated that CA19-9 might have been produced from the tumor cells themselves in this case.

Biomarkers, Tumor↗

PubMed1998

[A case report of infective endocarditis with total rupture of the posterior papillary muscle after aortic valve replacement].

We reported a case with severe mitral regurgitation caused by total rupture of the posterior papillary muscle two days after aortic valve replacement. A 62-year-old man was transferred to our hospital with high fever and dyspnea with severe aortic regurgitation caused by infective endocarditis. The left heart failure occurred suddenly two days after the initial operation. Echocardiogram revealed massive mitral regurgitation and rupture of the posterior papillary muscle. He underwent emergent mitral valve replacement. Histological examination of the papillary muscle showed typical ischemic necrosis without inflammation. The postoperative course was uneventful. We suggested the papillary muscle rupture in this case may be due to coronary artery emboli occurred in association with infective endocarditis.

Aortic Valve↗

PubMed1997

Immunohistochemical Detection of P-glycoprotein in Breast Cancer and Its Significance as a Prognostic Factor.

Overexpression of P-glycoprotein (Pgp) in tumors is one of the major mechanisms which mediates the multidrug resistance (MDR) phenotype. To evaluate the prognostic significance of Pgp in breast cancer, Pgp expression was examined in paraffin-embedded tissue sections of 94 breast cancer specimens by immunohistochemistry. Tissue specimens were obtained by mastectomy without preoperative chemotherapy. UIC2 monoclonal antibody which recognizes an extracellular epitope of human Pgp was employed. Of the 94 breast cancer specimens, 35(37.2%)were positive for Pgp expression. Pgp expression had no correlation with menopausal or hormone receptor status, axillary Iymph node involvement or tumor size. However, a significant correlation was observed between Pgp expression and disease relapse (p=0.0322). Pgp-positive patients showed a significantly shorter disease-free survival period than Pgp-negative patients by the Kaplan-Meier method (p=0.0433). These results suggest that immunohistochemical detection of Pgp in breast cancer tissue may have prognostic value after radical operation.

Journal Article↗

PubMed1997

The calcium/calmodulin-dependent protein phosphatase calcineurin is the major Elk-1 phosphatase.

The transcription factor Elk-1 is a component of ternary complex factor and regulates gene expression in response to a wide variety of extracellular stimuli. Phosphorylation of the C-terminal domain of Elk-1, especially at serine 383, is important for its transactivation activity. Recently mitogen-activated protein kinases, such as extracellular signal-regulated kinase, stress-activated protein kinase, and p38 mitogen-activated protein kinase have been demonstrated to be Elk-1 kinases. However, negative regulators of Elk-1, such as protein phosphatases, still remain to be identified. Here we report that COS cell lysates were able to dephosphorylate an extracellular signal-regulated kinase-phosphorylated glutathione S-transferase-Elkc fusion protein, including serine 383. The phosphatase activity was inhibited by cyclosporin A (a calcineurin inhibitor) but not by okadaic acid (a PP1 and PP2A inhibitor). Purified calcineurin also could efficiently dephosphorylate glutathione S-transferase-Elkc in vitro. Pretreatment of COS cells with cyclosporin A significantly enhanced epidermal growth factor-induced serine 383 Elk-1 phosphorylation whereas ionomycin inhibited the Elk-1 phosphorylation. These data provide both in vitro and in vivo evidence that calcineurin is the major Elk-1 phosphatase and plays a critical role in Elk-1 regulation. The identification of calcineurin as the major Elk-1 phosphatase may provide a mechanism for Elk-1 regulation by Ca2+ signals as well as a possible biochemical basis for the neurotoxicity and nephrotoxicity of the immunosuppressant drug cyclosporin A.

Animals↗

PubMed1997

Odor exposure reveals non-uniform expression profiles of c-Jun protein in rat olfactory bulb neurons.

In the main olfactory bulb, neurons are arranged strategically in distinct layers among which translaminar synaptic transmission can be made from the superficial, sensory to the deep, output layers that account for the processing of olfactory information. To search for stimulus-transcription coupling thought to be operated differentially in several cell types, c-Jun expression was examined immunohistochemically in rat olfactory bulb following 30-min odor stimulation with acetic acid and 1-butanol. c-Jun was rapidly induced in neuronal cell nuclei belonging to periglomerular, tufted, mitral and granule cells. The disappearance of c-Jun, however, differed between each cell type. In the glomerular layer, the glomeruli composed of c-Jun-expressing periglomerular cells were seen. Different odors led to labeling of different sets of glomeruli. The labeled periglomerular cells disappeared within 2 h. In all the deeper layers, however, a rather homogeneous label was noted for the tufted, mitral and granule cells present throughout the olfactory bulb, regardless of the difference in odor. In tufted and mitral cells, the c-Jun expression persisted for 4 days after odor stimulation. In the granule cell layer, numerous granule cells increased c-Jun immunoreactivity which lasted for 1 day following odor application. In control rats which were given clean air, the basal amount of c-Jun expression was seen confined to scattered granule cells. The results suggest that c-Jun is expressed in a variety of odorant-stimulated bulb neurons with a time course being dependent on cell type.

1-Butanol↗

PubMed1997

Regulation of eIF-4E BP1 phosphorylation by mTOR.

The proteins eIF-4E BP1 and p70 S6 kinase each undergo an insulin/mitogen-stimulated phosphorylation in situ that is partially inhibited by rapamycin. Previous work has established that the protein known as mTOR/RAFT-1/FRAP is the target through which the rapamycin.FKBP12 complex acts to dephosphorylate/deactivate the p70 S6 kinase; thus, some mTOR mutants that have lost the ability to bind to the rapamycin.FKBP12 complex in vitro can protect the p70 S6 kinase against rapamycin-induced dephosphorylation/deactivation in situ. We show herein that such mTOR mutants also protect eIF-4E BP1 against rapamycin-induced dephosphorylation, and for both p70 S6 kinase and eIF-4E BP1, such protection requires that the rapamycin-resistant mTOR variant retains an active catalytic domain. In contrast, mutants of p70 S6 kinase rendered intrinsically resistant to inhibition by rapamycin in situ are not able to protect coexpressed eIF-4E BP1 from rapamycin-induced dephosphorylation. We conclude that mTOR is an upstream regulator of eIF-4E BP1 as well as the p70 S6 kinase; moreover, these two mTOR targets are regulated in a parallel rather than sequential manner.

Animals↗

PubMed1997

Beraprost sodium, an analogue of prostacyclin, induces the expression of mitogen-activated protein kinase phosphatase and inhibits the proliferation of cultured mesangial cells.

Beraprost sodium, an analogue of prostacyclin, increases intracellular cyclic adenosine monophosphate (cAMP) in cultured glomerular mesangial cells. We examined the effect of beraprost on mesangial cell proliferation. Beraprost was able to inhibit fetal bovine serum-stimulated proliferation of mesangial cells in concentrations enough to increase cellular cAMP. By northern blot analysis, beraprost induced the expression of MKP-1, a mitogen-activated protein kinase phosphatase, in a dose- and time-dependent manner, similarly to dibutyryl cAMP and adrenomedullin. These results indicate that beraprost inhibits the proliferation of mesangial cells and one of the mechanisms might be cAMP-dependent induction of MKP-1.

Animals↗

PubMed1997

Coexpression of calretinin and parvalbumin in Ruffini-like endings in the rat incisor periodontal ligament.

The coexpression of calretinin- (CR) and parvalbumin-immunoreactivities (irs) was examined in oro-facial tissues of the rat. Nerve fibers coexpressing these calcium-binding proteins (CaBPs) were observed in the lingual periodontal ligament of incisors but not other tissues. In the part of periodontal ligament adjacent to the alveolar bone, such nerve fibers left nerve bundles and formed bush-like endings, i.e., they ramified repeatedly and terminated with one to four twigs. An immunoelectron microscopic method indicated that these endings were identical to Ruffini-like endings, 4% of trigeminal neurons retrogradely labeled from the inferior alveolar nerve coexpressed CR- and parvalbumin-irs. The present observations suggest that the coexpression of these CaBPs may be a specific marker for low-threshold mechanoreceptors in the trigeminal ganglion.

Animals↗

PubMed1997

Cloning of mouse diastrophic dysplasia sulfate transporter gene induced during osteoblast differentiation by bone morphogenetic protein-2.

Although intensive studies have been directed at understanding osteoblastic differentiation, the molecular mechanisms are still unclear. In this study, we describe a cDNA that encodes a sulfate transporter that was cloned as a gene induced in osteoblast precursor cells in association with osteoblastic differentiation. Based on the fact that bone morphogenetic protein-2 (BMP-2) induces osteoblastic phenotypes in immature mouse fibroblastic C3H10T1/2 cells, we performed a subtraction hybridization between BMP-2-treated and untreated cells, and have isolated one clone (designated as st-ob for sulfate transporter in osteoblast) induced by BMP-2 that is constantly expressed in osteoblastic cells. The deduced amino acid sequence and proposed structure of st-ob are mostly identical to those of the human diastrophic dysplasia sulfate transporter gene product (DTDST). St-ob mRNA was abundantly expressed in the thymus, testis, calvaria and osteoblastic MC3T3-E1 cells, whereas its expression was faint in C3H10T1/2 cells. Expression of st-ob in C3H10T1/2 cells was increased by transforming growth factor-beta1 (TGF-beta1), retinoic acid and dexamethasone as well as BMP-2. Furthermore, BMP-2 increased sulfate incorporation in C3H10T1/2 cells about twice as high as the baseline level. Osteoblasts actively take up sulfate to synthesize proteoglycans, which are one of the major components of the extracellular matrix of bone and cartilage. The present study demonstrates that st-ob induced during osteoblastic differentiation is an important phenotype of osteoblasts for characterizing their function.

Animals↗

PubMed1997

Cloning and characterization of the 5'-flanking region of the mouse diastrophic dysplasia sulfate transporter gene.

Dyastrophic dysplasia sulfate transporter (DTDST) plays an important role in proteoglycan synthesis in the extracellular matrix of bone and cartilage. Recently, we found that the mouse DTDST gene was induced in pluripotent C3H10T1/2 cells during differentiation by bone morphogenetic protein-2 (BMP-2). To clarify the transcriptional regulation of the DTDST gene, we have cloned the 5'-flanking region of the mouse DTDST gene by the PCR based gene walking method. Sequence analysis revealed the presence of the TATA box followed by GC rich sequences containing two Sp-1 binding sites and a CBFA1 binding site. Transient transfection assays demonstrated that the basal transcriptional activity in osteoblastic MC3T3-E1 cells was mainly present between -309 and -275 bp upstream of the transcription start site (Segment -309/-275) which contained the consensus sequence for the xenobiotic-responsible element (XRE). Nuclear proteins from MC3T3-E1 cells and C3H10T1/2 cells could bind to this short segment in vitro. BMP-2 increased the promoter activity as well as the nuclear protein binding to the sequence in C3H10T1/2 cells. The present data suggest that the DTDST gene expression in osteoblasts and differentiating precursor cells to osteoblast/chondrocyte lineage would be mainly regulated by undetermined XRE binding transcription factors.

Animals↗