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Biomedical subjects

T Iwama

Publications and source records attributed to T Iwama.

At least 73 records · Page 4Linked to original sources

Cardiac malignant pheochromocytoma with bone metastases.

A patient with malignant cardiac pheochromocytoma with bone metastases is described. The primary tumor was located between the pulmonary trunk and the left atrium, while metastatic lesions were found in the iliac bones. Treatments with antihypertensive agents, alpha-methylparatyrosine, and combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine partially improved the patient's symptoms, catecholamine levels, and the metastatic lesion of the iliac bones. However, the primary tumor in the heart progressively increased in size and the patient died of disseminated intravascular coagulation and other various complications about 4 years after the diagnosis of the disease.

Antineoplastic Combined Chemotherapy Protocols↗

Histochemical study of apoptosis and cell proliferation in hereditary intestinal diseases.

The occurrence of apoptosis and cell proliferation in hereditary intestinal diseases was analyzed for possible diagnostic markers that could discriminate the formation of tumors that would develope into cancer. In all, 15 adenomas in familial adenomatous polyposis, 3 juvenile polyposis, 5 Peutz-Jeghers syndrome, 14 sporadic adenomas, and 46 colorectal carcinomas were investigated. Tissue specimens were examined for apoptotic cells by TdT-mediated dUTP-biotin nick end labeling (TUNEL), and proliferating cells by immunohistochemistry of proliferating cells nuclear antigen (PCNA). In hereditary intestinal diseases, the apoptotic and proliferating indexes were significantly lower than those in colorectal carcinoma, and higher apoptotic and proliferating indexes were observed in poorly differentiated colorectal adenocarcinoma and in subserosal stages of invasion. There were no significant differences in proliferating and apoptotic indexes between adenoma in FAP and sporadic adenoma. No apoptotic and proliferating cells were observed in juvenile polyposis, and only occasional proliferating cells were seen in Peutz-Jeghers syndrome. These findings demonstrated that TUNEL and PCNA staining are useful in correctly reflecting disease progression in hereditary intestinal diseases.

Adenocarcinoma↗

Uncoupling of ligand-binding affinity of the bacterial serine chemoreceptor from methylation- and temperature-modulated signaling states.

The Escherichia coli chemoreceptor Tsr mediates tactic responses to serine, repellents, and changes in temperature. We have previously shown that the serine-sensing ability of Tsr-T156C, which has a unique cysteine in place of threonine at residue 156, is specifically inactivated by thiol-modifying reagents and that L-serine protects the receptor from modification. In this study, we demonstrated the correlation between protective effects of various attractants and their potencies to elicit attractant responses. This indirect binding assay was used to monitor the affinity of the receptor for L-serine under various conditions. It has been demonstrated by in vitro assays that the ligand-binding affinities of Tsr and the related chemoreceptor Tar are unaffected by changes in the methylation state of the receptor. Using the serine protection assay, we re-examined this issue both in vitro and in vivo. The methylation levels of Tsr-T156C did not affect its ligand-binding affinity. We also showed both in vitro and in vivo that the ligand-binding affinity was unaffected by temperature. These results suggest that the structure of the periplasmic domain of the receptor is uncoupled from the signaling states of the cytoplasmic domain. This ligand-binding assay system should be applicable to other receptors.

Amides↗

Magnum Meier wires with Crag Fx wire catheter for total occlusive coronary arteries.

Magnum Meier wire was used with Crag Fx wire catheter instead of Magnum balloon catheter to facilitate wire crossing through total occlusion by improving flexibility of the system without losing wire pushability. Of 372 coronary angioplasty procedures performed between January 1994 and April 1995, there were 12 subacute occlusions with an interval of 3 wk or less and 30 chronic occlusions with an interval of > 3 wk. Regular over-the-wire-type balloon catheters failed to dilate four subacute occlusions and nine chronic total occlusions. Magnum Meier wire with Crag Fx wire catheter was tried for one subacute occlusion and four chronic occlusions that were undilatable with a regular balloon system and successfully dilated the subacute occlusion and three of the chronic occlusions. The lesions successfully dilated by this new approach were either long or tandem lesions in vessels that were excessively tortuous or showed an acute angle at the orifice. Thus the Magnum Meier wire with Crag Fx wire catheter can be a useful tool for dilating totally occluded lesions in tortuous coronary arteries.

Angioplasty, Balloon↗

Improvement of oxygen metabolic reserve after extracranial-intracranial bypass surgery in patients with severe haemodynamic insufficiency.

The effectiveness of extracranial-intracranial arterial bypass (EC-IC bypass) surgery on impaired haemodynamic status was studied in 12 patients with reduced regional cerebral perfusion pressure (rCPP) and elevated regional oxygen extraction fraction (rOEF) in the area distal to the symptomatic arterial lesion. Postoperative positron emission tomography (PET) study demonstrated a statistically significant decrease of rOEF in the operated hemispheres with disappearance of the pre-operative interhemispheric rOEF difference. Regional cerebral blood flow (rCBF) and regional cerebral oxygen metabolism (rCMRO2) were also increased in the operated hemispheres with disappearance of the pre-operative interhemispheric differences. Regional CBF/regional cerebral blood volume (rCBV) ratios of the symptomatic hemispheres were increased after surgery, but were still lower than in the contralateral hemispheres. We conclude that EC-IC bypass surgery improves impaired cerebral oxygen metabolic reserve.

Aged↗

Transforming growth factor beta type II receptor gene mutations in adenomas from hereditary nonpolyposis colorectal cancer.

BACKGROUND & AIMS: Germline mutations of DNA mismatch repair genes are responsible for cancer susceptibility in hereditary nonpolyposis colorectal cancer (HNPCC) kindreds. Transforming growth factor beta type II receptor (TGF-beta RII) has been found to be somatically altered in HNPCC. The aim of this study was to clarify further the role of TGF-beta RII alterations in HNPCC tumorigenesis, particularly in adenomas. METHODS: Fourteen adenoma specimens and 13 cancer specimens from 10 patients with HNPCC were screened for mutations in the short repeated sequences of the TGF-beta RII gene by polymerase chain reaction-single-strand conformation polymorphism. Mismatch repair genes, replication errors, and c-K-ras 2 were also analyzed in HNPCC tumors. RESULTS: Alterations of the TGF-beta RII gene at the short poly(A) repeat were found in 8 (57%) adenoma specimens and 11 (85%) cancer specimens. They were found at an earlier stage of adenomas. Two adenoma specimens showed two-hit inactivation of mismatch repair genes. Replication errors were detectable in 13 (93%) adenoma specimens. Mutations in c-K-ras 2 codon 12 were detected at a 50% frequency in adenoma specimens. CONCLUSIONS: These data indicate a strong association between TGF-beta RII gene alterations and adenoma-carcinoma progression in HNPCC.

Adult↗

Superficial temporal artery to anterior cerebral artery direct anastomosis in patients with moyamoya disease.

Some patients with Moyamoya disease require revascularization not only to the territory of the middle cerebral artery (MCA) but also to that of the anterior cerebral artery (ACA). To revascularize the ACA territory, we performed superficial temporal artery (STA)-ACA direct anastomosis in five patients with Moyamoya disease. After paramedian frontal craniotomy (approximately 5 cm diameter), STA-ACA anastomosis was carried out at the convexity using a cortical branch of the ACA as a recipient. An interposed STA graft was used in four patients: all of the grafts were shorter than 4 cm. Bypass flow was satisfactory in four patients. One patient who underwent simultaneous STA-ACA and STA-MCA anastomoses had poor bypass flow probably due to spontaneous leptomeningeal collateral channels between the ACA and MCA. Our method using a cortical branch of the ACA as a recipient and a branch of the STA for the interposed graft can be performed at the convexity and much easier than in a deep operative field. A short arterial graft does not easily occlude. The diameter of a branch of the STA is small and therefore, a size discrepancy does not present a problem. Our STA-ACA anastomosis method is useful and effective for revascularization of the ACA territory in any patients with Moyamoya disease.

Adolescent↗

Direct surgery for major artery aneurysm associated with moyamoya disease.

Moyamoya disease is often accompanied by intracranial major artery aneurysms in the posterior circulation which acts as collateral channels in place of the stenotic internal carotid arteries. These major artery aneurysms are considered to have high risk of enlargement and rupture due to increased hemodynamic stress. Direct surgical intervention has been recommended for the treatment of these aneurysms, but the direct approach to them is often difficult due to interference by intertwined abnormal vessels. We have performed direct surgery for seven major artery aneurysms in five patients with Moyamoya disease. Of these three aneurysms located in the anterior circulation were successfully clipped via pterional or interhemispheric approach. Of four posterior circulation aneurysms (two at the junction of the basilar artery and the superior cerebellar artery and two at the P1-P2 junction of the posterior cerebral artery), one was approached via pterional route because collateral vessels in the basal cistern was judged not to be rich on angiograms. However, the operative field was interfered by abundant fragile collateral vessels and it was difficult to reach the distal portion of the basilar artery. In contrast, in the other three cases in which the subtemporal approach was employed, there weren't any problems in exposures of the aneurysms. Our experiences indicate that subtemporal approach is superior than the pterional approach to reach the distal portion of the basilar artery in patients with Moyamoya disease.

Adult↗

Predictability of extracranial/intracranial bypass function: a retrospective study of patients with occlusive cerebrovascular disease.

OBJECTIVE: When the efficacy of extracranial/intracranial bypass surgery is discussed, can we include the patients with extensive collateral circulation through the bypass and those with poor collateral circulation in the same group? The bypass function should be determined not by the patency of the bypass but by the extent of collateral circulation through the bypass. We retrospectively analyzed our patients to determine whether the extent of bypass flow can be predicted from the results of preoperative studies. METHODS: In 51 hemispheres of 44 consecutive patients who underwent extracranial/intracranial bypass surgery, correlation between the extent of bypass flow and the preoperative results of angiographic and stimulated cerebral blood flow studies were investigated. RESULTS: The bypass function is highly predictable with the aid of preoperative studies. In 11 hemispheres that showed both retrograde spontaneous circulation via leptomeningeal anastomoses and decreased reactivity to acetazolamide of cerebral blood flow in an area distal to the arterial lesion, collateral circulation through the bypass developed well and reactivity to acetazolamide improved. In all of 13 hemispheres that showed normal reactivity to acetazolamide, the bypass was patent but the collateral circulation did not develop well. In only 4 of 24 hemispheres with spontaneous antegrade circulation distal to the lesion was there satisfactory collateral circulation through the bypass. CONCLUSION: Our results indicate that improvement of the hemodynamic status by bypass surgery should be expected only in patients with both spontaneously developed leptomeningeal anastomoses and decreased reactivity to acetazolamide.

Acetazolamide↗

Hypertrophic cardiomyopathy complicated with acute myocardial infarction due to coronary embolism.

We report a case of acute myocardial infarction due to coronary embolism in a patient with echocardiographically documented hypertrophic cardiomyopathy. Emergency coronary arteriography revealed embolic occlusion of the proximal left circumflex coronary artery and the first diagonal branch. Intracoronary thrombolysis with urokinase and subsequent balloon angioplasty was successful. Transesophageal echocardiography revealed thrombus in the left atrial appendage. Coronary arteriography performed on the 46th hospital day revealed a patent left circumflex coronary artery and diagonal branch. The patient was discharged uneventfully.

Aged↗

Cross-relaxation times of normal and biochemically induced osteoarthritic rabbit knee cartilages.

We measured the spin-lattice relaxation times (T1) of water protons and intermolecular cross-relaxation times (T(IS)) from irradiated protein protons (f2-irradiation at 1.95 or -4.00 ppm) of rabbit normal and monoiodoacetate-induced degenerated knee articular cartilages to observed water protons. The mean values of T1 (T1) for control and degenerated rabbit knee cartilages were 1.87+/-0.15 (mean+/-SD, n=29) and 1.82+/-0.13 s (n=34), respectively. The mean values of water content (W(H2O)) for control and degenerated rabbit knee cartilages were 82.9+/-2.09 (n=26) and 83.1+/-2.57% (n=28), respectively. These values were not statistically different from each other. However, the mean values of T(IS) (T(IS)) for normal knee articular cartilage were significantly different from those for degenerated cartilage: (normal), T(IS) (f2=1.95 ppm)=2.46+/-0.62 s (n=28), T(IS) (f2=-4.00 ppm)=4.25+/-1.26 s (n=26); (degenerated), T(IS) (f2=1.95 ppm)=1.99+/-0.76s (n=34), T(IS) (f2=-4.00 ppm)=3.33+/-0.76 s (n=31). Obtained results may be attributed to the reported switchover from type II to type I collagen syntheses in osteoarthritic cartilage, resulting in broad collagen fibers. This specificity of cross-relaxation effect may prove useful in the noninvasive and pathophysiological evaluation of cartilage tissues in vivo.

Animals↗

Hemodynamic and metabolic disturbances in patients with intracranial dural arteriovenous fistulas: positron emission tomography evaluation before and after treatment.

In patients with intracranial dural arteriovenous fistulas (AVFs), clinical symptoms and angiographic findings vary. The relevance of disturbed venous drainage to clinical symptoms and prognosis has been recognized. However, the roles of cerebral hemodynamics and metabolism, which are impaired by shunt flow or disturbed venous drainage, have not been fully evaluated. The authors studied the cerebral hemodynamic and metabolic status in 10 patients with intracranial dural AVFs using positron emission tomography (PET) scanning. Ten patients with dural AVFs underwent a PET study before treatment. The regional cerebral blood flow (rCBF), regional oxygen extraction fraction (rOEF), regional cerebral metabolic rate of oxygen (rCMRO2), and regional cerebral blood volume (rCBV) were measured using the 15O-labeled gas inhalation steady-state method The PET parameters that were obtained were analyzed and compared with the patients' neurological and angiographic findings. In six of the 10 patients, a PET study was also performed after treatment. Before treatments, all four patients with cerebral symptoms showed a severe reduction in rCBF and a mild elevation in the rOEF. The areas showing reduced rCBF corresponded with areas in which retrograde venous drainage into the cortical veins and delayed parenchymal circulation were seen on angiograms. In another two patients with occlusion of the affected sinus and/or retrograde drainage into the cortical veins, mild abnormalities were demonstrated in rCBF mapping. In the remaining four patients, all PET parameters except rCBV were within normal limits and venous flow was not impaired on the angiograms. In four patients who underwent surgical excision or transvenous embolization of the affected sinus, the cerebral hemodynamics and metabolism were improved, as were the clinical symptoms. In two patients who underwent transarterial embolization of the feeding vessels only or craniotomy, no hemodynamic improvement was achieved. Our results indicate that hemodynamic insufficiency detected by the PET study corresponded well with cerebral symptoms and angiographic findings of retrograde venous drainage into the cortical veins and delayed parenchymal circulation, but not with sinus occlusion or arterial blood supply. Eradication or prevention of retrograde venous drainage from the affected sinus into the cortical veins should be a treatment goal in patients with dural AVFs.

Aged↗

Resection of a large, high-flow arteriovenous malformation during hypotension and hypothermia induced by a percutaneous cardiopulmonary support system. Case report.

The key to successful surgical resection of cerebral arteriovenous malformations (AVMs) is control of bleeding and cerebral swelling. Induced hypotension is one of the most valuable means of achieving this control. The authors introduced induced hypotension with mild hypothermia by using a percutaneous cardiopulmonary support system (PCPS) to resect a large, high-flow AVM. The efficacy and technical points of this method are discussed. The PCPS, whose entire intraluminal surface was coated with heparin, was established through a transfemoral route. During resection of the AVM, a mean arterial blood pressure of 60 mm Hg and a mean body temperature of 30 degrees C were easily maintained by regulating the flow rate of the PCPS and by blood cooling. The activated coagulation time was maintained at approximately 250 seconds with a minimum systemic administration of heparin. The authors report the case of a 30-year-old woman who presented with intraventricular hemorrhage and was diagnosed as having a large, high-flow AVM located in the left sylvian fissure. The AVM was fed by the left middle, posterior, and anterior cerebral arteries and drained by the many cortical ascending veins and the basal vein. The patient underwent surgery after hypotension and hypothermia had been induced via the PCPS method. Induced hypotension decreased the tension of the nidus and made its dissection easier. The AVM was totally resected and no hemostatic difficulties were encountered. On the basis of the authors' experience, they suggest that hypotension and hypothermia induced by using the PCPS is a powerful tool for the successful resection of large, high-flow AVMs.

Adult↗

Preventive effect of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil on colonic carcinogenesis induced by 1,2-dimethylhydrazine in rats.

Thymidylate synthetase (TS) and thymidine kinase (TK) are key enzymes in de novo and salvage pathways for pyrimidine nucleotide synthesis, respectively. A high incidence of colorectal adenocarcinomas with varied grades of cell differentiation can be induced by 1,2-dimethylhydrazine (DMH) in rats. The marked increases of TS and TK activities were found in the poorly and well-differentiated adenocarcinomas of the colon, respectively. Oral administration of 1-(2-tetrahydrofuryl)-5-fluorouracil in combination with uracil (UFT) markedly reduced the number and accumulated area of colonic carcinomas, and TS activity in the poorly differentiated adenocarcinomas. A potential balance between the de novo and the salvage pathways for pyrimidine nucleotide synthesis was suggested to be related with the histopathological grades of cell differentiation. Suppression of colonic TS activity by UFT administration reduced the colonic carcinogenesis and the potency of the poorly differentiated adenocarcinomas of the colon.

1,2-Dimethylhydrazine↗

Mechanism of intracranial rebleeding in moyamoya disease.

Intracranial hemorrhage is the major catastrophic event in the natural course of Moyamoya disease, and outcome of the patients with rebleeding is very poor. However, the mechanism underlying intracranial rebleeding is not well elucidated. We retrospectively analyzed 15 patients who bled two times or more among 46 bled patients with Moyamoya disease. The results indicated that there were two different types in the manner of rebleeding. One group consisted of seven cases, which bled two times or more at the same site than the original bleeding site. In four of these seven cases, a ruptured aneurysm was identified at the distal part of collateral vessel or on the major vessel. In the other three cases, no source of bleeding was identified. In all of these cases, rebleeding occurred within 2 months after the initial insult except for one case. Another group consisted of eight cases, which bled repeatedly but at different sites from the initial bleeding site. In any of these cases, neither aneurysms nor other vascular abnormalities were identified. In all of these cases, rebleeding occurred more than 2 months after the initial bleeding. The present result indicated that intracranial bleeding might occur as a result of rupture of a tiny aneurysm at the periphery of collateral vessels. These aneurysms may be blown out after initial bleeding. When they persist after the event, they may rupture again in a fairly short interval. In other cases, bleeding occur at different sites from the initial site. They are considered to be a result of ruptured weak Moyamoya vessels which are forced to act as collateral pathways and are under unusually increased hemodynamic stress.

Adolescent↗

Mutations of the transforming growth factor-beta type II receptor gene are strongly related to sporadic proximal colon carcinomas with microsatellite instability.

BACKGROUND: Mutations of the transforming growth factor-beta type II receptor gene (TGF-beta RII) have been found in several replication error-positive sporadic colorectal carcinomas and hereditary nonpolyposis colorectal carcinoma cell lines. The aim of this study was to clarify the role of TGF-beta RII in sporadic colorectal carcinogenesis. METHODS: The authors screened for mutations at simple repeated sequences in the TGF-beta RII gene by polymerase chain reaction-single strand conformation polymorphism. They also examined genomic instability, using five microsatellite DNA markers in 69 sporadic colorectal carcinomas. When the carcinomas exhibited the TGF-beta RII mutations, the authors screened further for mutations in two DNA mismatch repair genes, hMSH2 and hMLH1. RESULTS: Seven of the 69 cancers (10%) showed one or two A deletions in TGF-beta RII and resultant frameshift mutations in nucleotide positions 709-718 containing a (A) 10 repeated sequence; but none of these appeared in the corresponding normal DNA, indicating a somatic mutation. All of the seven cancers were located in the proximal colon; there were none in the distal colon (P < 0.01). On the other hand, 22 of the 69 carcinomas (32%) showed the replication error-positive phenotype. The frequency of replication errors in proximal colon carcinomas was higher than that in distal colon carcinomas (P < 0.05). All 7 cancers with TGF-beta RII mutations showed replication errors. One of them revealed a nonsense mutation at codon 413, and 1 revealed a loss of heterozygosity in hMSH2. CONCLUSIONS: These data indicate that mutations of TGF-beta RII are strongly related to proximal colon carcinomas with microsatellite instability and that the mechanism of carcinogenesis in some proximal colon carcinomas is similar to that in hereditary nonpolyposis colorectal carcinoma.

Aged↗

p300 gene alterations in colorectal and gastric carcinomas.

Colorectal tumors frequently have loss of heterozygosity on chromosome 22q, suggesting that inactivation of tumor suppressor gene(s) on 22q participates in the tumor development. Neurofibromatosis 2 (NF2) gene and E1A binding protein p300 gene, recently identified on 22q, are thought to be candidates for tumor suppressor genes. In this study, mutation of the NF2 gene in 59 colorectal carcinomas, and mutation of the p300 gene in 27 colorectal and two gastric carcinomas, were analysed using PCR-SSCP, RT-PCR-SSCP and direct sequencing methods. Missense mutations of p300 gene were detected in a colorectal carcinoma, and in a gastric carcinoma, though no mutation of NF2 gene was detected. Both p300 mutations were somatic and coupled to deletion of the second allele of the gene, which suggests inactivation of the p300 gene, in these carcinomas. The mutations are located within the Cys/His-rich regions, which are assumed to play important roles in the function of p300. These are the first cases in which p300 gene has been found to be altered in both alleles, suggesting that inactivation of the p300 gene may be involved in the development of carcinomas, and that this gene may be the target of loss of 22q in carcinomas of the digestive tract.

Base Sequence↗