Evidence for autosomal dominant inheritance?
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Adenomatous Polyposis Coli↗
Biomedical subjects
T Iwama
Publications and source records attributed to T Iwama.
Efficacy of direct revascularization in adult Moyamoya disease: haemodynamic evaluation by positron emission tomography.
To evaluate the efficacy of direct cerebrovascular reconstruction to prevent intracranial bleeding from the point of view of haemodynamic status, we performed positron emission tomography (PET) studies in 5 adult patients with Moyamoya disease before and after superficial temporal artery to middle cerebral artery (STA-MCA) anastomosis. Regional cerebral blood flow (rCBF), regional cerebral metabolic rate of oxygen (rCMRO2) and regional oxygen extraction fraction (rOEF) in the MCA territories and regional cerebral blood volume (rCBV) in the striatum were measured before and after STA-MCA anastomosis. Correlation between the change of these PET parameters and post-operative decreased opacification of Moyamoya vessels were analyzed. Pre-operatively, significant elevation of rCBV were observed in the basal ganglia as well as significant reduction of rCBF and elevation of rOEF with reduction of rCMRO2 in the MCA territories, indicating "misery" perfusion in the cerebral hemisphere and blood pooling in the Moyamoya vessels under increased haemodynamic stress. Post-operative PET study showed improvement of misery perfusion and reduction of rCBV in the basal ganglia. Reduction of rCBV in the basal ganglia generally compatible with decreasing Moyamoya vessels on angiographic findings. Our results suggests that direct bypass surgery could have a potential both for decreasing haemodynamic stress on Moyamoya vessels and to improve misery perfusion in the hemisphere.
Adult↗
Hemodynamic changes around a cerebral arteriovenous malformation before and after embolization measured with PET
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Journal Article↗
Somatic mutation of the APC gene in thyroid carcinoma associated with familial adenomatous polyposis.
We report the existence of both germline and somatic mutations of the APC gene in thyroid carcinomas from familial adenomatous polyposis (FAP) patients. One papillary thyroid carcinoma from a 210-year-old woman, with germline mutation of the APC gene (TCA to TGA at codon 1110), showed a somatic mutation of AAAAC deletion between codons 1060 and 1063. Another somatic mutation of CAG to TAG at codon 886 was also found in one of multiple thyroid carcinomas from a 26-year-old woman with attenuated FAP and germline mutation at codon 175 (C deletion). This is the first evidence that total absence of the normal function of the APC gene is involved in development of thyroid carcinomas in FAP.
Adenomatous Polyposis Coli↗
Screening SMAD1, SMAD2, SMAD3, and SMAD5 for germline mutations in juvenile polyposis syndrome.
BACKGROUND AND AIMS: Juvenile polyps occur in several Mendelian disorders, whether in association with gastrointestinal cancer alone (juvenile polyposis syndrome, JPS) or as part of known syndromes (Cowden, Gorlin, and Bannayan-Zonana) in association with developmental abnormalities, dysmorphic features, or extraintestinal tumours. Recently, some JPS families were shown to harbour germline mutations in the SMAD4 (DPC4) gene, providing further evidence for the importance of the TGFbeta signalling pathway in colorectal cancer. There remains, however, considerable, unexplained genetic heterogeneity in JPS. Other members of the SMAD family are excellent candidates for JPS, especially SMAD2 (which, like SMAD4, is mutated somatically in colorectal cancers), SMAD3 (which causes colorectal cancer when "knocked out" in mice), SMAD5, and SMAD1. METHODS: SMAD1, SMAD2, SMAD3, and SMAD5 were screened for germline mutations in 30 patients with JPS and without SMAD4 mutations. RESULTS: No mutations were found in any of these genes. A G-A C89Y polymorphism with possible effects on protein function was found in SMAD3, but the frequencies of the G and A alleles did not differ between patients with JPS and controls. CONCLUSIONS: It remains to be determined whether or not this polymorphism is involved in a minor predisposition to colorectal or other carcinomas. SMAD4 may be the only member of the SMAD family which causes JPS when mutant in the germline. The other genes underlying JPS remain to be identified.
Adenomatous Polyposis Coli↗
Hemodynamic changes around cerebral arteriovenous malformation before and after embolization measured with PET.
To estimate the changes in regional cerebral blood flow (rCBF) around cerebral arteriovenous malformation (AVM) before and after embolization, 6 patients with AVM were sequentially examined with positron emission tomography (PET). PET depicted the remodeling of rCBF in the ipsilateral hemisphere of AVM after embolization. Decrease of rCBF in the ipsilateral hemisphere was also detected in patients with focal symptoms before embolization, and improvement of clinical symptoms after embolization corresponded to disappearance of rCBF decrease. PET can detect hemodynamic changes after embolization, and has a possibility to estimate the effect of embolization in patients with AVM.
Adult↗
Comparison of positron emission tomography study results of cerebral hemodynamics in patients with bleeding- and ischemic-type moyamoya disease.
The purpose of this study was to elucidate the difference in cerebral hemodynamics and metabolic status between patients with bleeding- and ischemic-type moyamoya disease. Regional cerebral blood flow (rCBF), regional cerebral metabolic rate of oxygen (rCMRO2), regional oxygen extraction fraction (rOEF), and regional cerebral blood volume (rCBV) in the cortex of the middle cerebral artery (MCA) territories and rCBV in the striatum were measured using positron emission tomography (PET) in 17 patients with moyamoya disease. Patients were divided into three subgroups according to type of disease manifestation and age: adult bleeding type (five cases), adult ischemic type (10 cases), and childhood ischemic type (two cases). When compared with adult controls, statistically significant reductions in rCBF and rCMRO2, elevation in rOEF in the MCA territories, and elevation of rCBV in the striatum were observed in PET studies for all three subgroups. Between the adult bleeding type and ischemic type, rCBF, rCMRO2, and rOEF in the MCA territories were not different, but rCBV in the striatum was higher in patients with ischemic-type moyamoya disease than in those with the bleeding type. In adult patients with bleeding and ischemic types, rOEF and rCBV in the MCA territories and rCBV in the striatum were significantly lower than in patients with childhood ischemic-type moyamoya disease. In adult patients with bleeding-type moyamoya disease, cerebral hemodynamics were impaired and similar to those in adult ischemic type.
Journal Article↗
Structural basis for chemical inhibition of human blood coagulation factor Xa.
Factor Xa, the converting enzyme of prothrombin to thrombin, has emerged as an alternative (to thrombin) target for drug discovery for thromboembolic diseases. An inhibitor has been synthesized and the crystal structure of the complex between Des[1-44] factor Xa and the inhibitor has been determined by crystallographic methods in two different crystal forms to 2.3- and 2.4-A resolution. The racemic mixture of inhibitor FX-2212, (2RS)-(3'-amidino-3-biphenylyl)-5-(4-pyridylamino)pentanoic acid, inhibits factor Xa activity by 50% at 272 nM in vitro. The S-isomer of FX-2212 (FX-2212a) was found to bind to the active site of factor Xa in both crystal forms. The biphenylamidine of FX-2212a occupies the S1-pocket, and the pyridine ring makes hydrophobic interactions with the factor Xa aryl-binding site. Several water molecules meditate inhibitor binding to residues in the active site. In contrast to the earlier crystal structures of factor Xa, such as those of apo-Des[1-45] factor Xa and Des[1-44] factor Xa in complex with a naphthyl inhibitor DX-9065a, two epidermal growth factor-like domains of factor Xa are well ordered in both our crystal forms as well as the region between the two domains, which recently was found to be the binding site of the effector cell protease receptor-1. This structure provides a basis for designing next generation inhibitors of factor Xa.
Binding Sites↗
Chondromyxoid fibroma of the ethmoid sinus.
Only a small proportion of cases of this rare neoplasm occur in the skull. We present an unusually extensive tumour in a young man.
Adult↗
Use of 123I-IMP brain SPET to predict outcome following STA-MCA bypass surgery: cerebral blood flow but not vasoreactivity is a predictive parameter.
Superficial temporal artery - middle cerebral artery (STA-MCA) bypass surgery might improve the cerebral blood flow (CBF) but fail to reduce the risk of post-surgical events such as ischaemic stroke. In this study, we studied retrospectively whether the risk of post-surgical events corresponded to the change in resting CBF and/or the change in vasoreactivity observed before and after STA-MCA surgery using N-isopropyl-I-123-p-iodoamphetamine (123I-IMP) brain single-photon emission tomography (SPET). 123I-IMP brain SPET images obtained at rest and following acetazolamide challenge both before and after STA-MCA surgery were studied in 30 patients. Resting CBF was estimated semiquantitatively using the resting count ratios of the middle cerebral artery (MCA) area to the cerebellum. Acetazolamide c hallenge was assumed to result in an average increase in flow of 40% in the cerebellum. The vasoreactive response was then estimated as the ratio of the change in counts (acetazolamide - rest) to the resting cerebellar counts multiplied by 1.4. We classified 14 patients (50.5 +/- 19.3 years) into group I, who h a change in their resting CBF from before to after surgery of >10%, and 16 patients (54.0 +/- 18.8 years) into group II, who had a change in their resting CBF from before to after surgery of ¿leq10%. Oxygen-15 positron emission tomography (PET) studies were performed in five patients from group I and five patients from group II. One post-surgical event occurred in group I while there were eight post-surgical events in group II (P<0.05). Resting CBF improved by 20.4% +/- 7.5% in group I and by 0.9% +/- 6.9% in group II patients after surgery (P<0.001). No significant difference in the improvement in vasoreactivity was observed between group I patients (32.6% +/- 17.7%) and group II patients (24.6% +/- 15.6%) following surgery. Patients in the group I PET subset showed normalization of oxygen extraction fraction (OEF) from 0.59 +/- 0.09 before surgery to 0.46 +/- 0.06 after surgery (P<0.05), while patients in the group II PET subset showed no statistical difference in OEF before surgery (0.58 +/- 0.14) and after surgery (0.54 +/- 0.05). We conclude that the outcome of STA-MCA bypass surgery can be predicted by the improvement in resting CBF but not by the improvement in vasoreactivity.
Acetazolamide↗
A simple method to avoid contamination while performing an immediate mucocutaneous suture of the intestinal stoma.
We herein report a simple method using intestinal clamps to prevent intraoperative contamination during an immediate mucocutaneous suture of the intestinal stoma. Using this technique, a protruded intestinal stoma can be constructed reliably without soiling. The technique can be used both for constructing an end as well as a loop intestinal stoma.
Bacterial Infections↗
Bromodeoxyuridine uptake by early liver metastases in rats: a comparison of the hepatic artery and portal vein infusion routes.
Liver metastases generated by the intraportal inoculation of ascites hepatoma cells in Donryu rats were labeled with bromodeoxyuridine (BrdU) through the hepatic artery, or through the portal vein with or without ligation of the hepatic artery, 3, 6, or 9 days after tumor inoculation. The distribution of BrdU-labeled cells was evaluated in 174 metastases, 110-1640 microm in diameter, by immunohistochemical methods. When a dual blood supply from the portal vein and hepatic artery existed, the BrdU-labeled cells were diffusely found in the metastases regardless of their size and the route of BrdU infusion. When blood supply to metastases larger than 610 microm in diameter was from a single source, namely the portal vein, the BrdU-labeled cells were located within 90-290 microm from the margin of the metastases. These results indicate first, that drug uptake by the inner part of the early metastatic liver tumors is achieved through the hepatic artery, and second, that drug uptake by early liver metastases through the portal vein is limited to within the extent of portal diffusion regardless of the size of the metastases. Thus, we conclude that prophylactic treatment against liver metastases would be more effective when given via the hepatic artery route rather than via the portal vein route.
Animals↗
Long-term angiographic prognosis of lesions dilated by coronary angioplasty.
BACKGROUND: To examine the long-term outcome of coronary angioplasty, lesions that remained patent after 3 to 12 months were monitored angiographically at 3-year intervals. There were 252 lesions successfully dilated (from 83% +/- 13% preprocedural stenosis to 19% +/- 14% residual stenosis) between 1983 and 1986 that remained patent on follow-up angiography (23% +/- 15% stenosis) and were monitored further at our outpatient department. METHODS AND RESULTS: Repeat angiography was done for 186 lesions at 2 to 4 years and showed that 179 were patent (0% to 50% stenosis), one had mild stenosis (55% to 70% stenosis), and six had severe stenosis (75% to 100% stenosis). Angiography was repeated for 138 lesions at 5 to 7 years, showing that 127 were patent, four had mild stenosis, and seven had severe stenosis. Finally, angiography was performed for 78 lesions at 8 to 10 years, showing that 63 were patent, four had mild stenosis, and 11 had severe stenosis. CONCLUSIONS: Although numerous lesions were lost to follow-up, most appeared to remain patent for 4 years, after which a significant number developed restenosis.
Angioplasty, Balloon, Coronary↗
Proapoptotic gene BAX is frequently mutated in hereditary nonpolyposis colorectal cancers but not in adenomas.
BACKGROUND & AIMS: The p53 and BAX genes have been linked to apoptosis. p53 was not frequently found to be mutated in colorectal carcinomas with a microsatellite mutator phenotype, but frame-shift mutations in a tract of eight guanines within BAX were frequently found in these carcinomas. To understand the roles of these genes in hereditary nonpolyposis colorectal cancer (HNPCC) tumorigenesis, we examined whether BAX mutations occur in adenoma and carcinoma specimens from patients with HNPCC and also determined the frequencies of p53 mutations. METHODS: Thirteen colorectal adenomas and 24 adenocarcinomas from patients with HNPCC showing a microsatellite instability phenotype were screened by polymerase chain reaction followed by denaturing polyacrylamide gel electrophoresis and direct sequencing. RESULTS: Two of the 13 adenomas (15.4%) and 13 of the 24 adenocarcinomas (54.2%) showed mutation patterns and were confirmed to have frame-shift mutations at the BAX repeat site by direct sequencing. For p53, only 1 of the 24 adenocarcinomas (4.2%) showed a missense mutation. CONCLUSIONS: In HNPCC colorectal carcinomas, BAX was significantly (P = 0.024) more mutated than in adenomas. p53 was not frequently found to be mutated in these carcinomas. These data suggest that mutations in BAX, rather than mutations in p53, may contribute to the adenoma-carcinoma transition in HNPCC tumorigenesis.
Adenoma↗
Mutations in DPC4 (SMAD4) cause juvenile polyposis syndrome, but only account for a minority of cases.
Juvenile polyps are present in a number of Mendelian disorders, sometimes in association only with gastrointestinal cancer [juvenile polyposis syndrome (JPS)] and sometimes as part of known syndromes (Cowden, Gorlin and Banayan-Zonana) in association with developmental abnormalities, dysmorphic features or extra-intestinal tumours. Recently, a gene for JPS was mapped to 18q21.1 and the candidate gene DPC4 (SMAD4) was shown to carry frameshift mutations in some JPS families. We have analysed eight JPS families for linkage to DPC4. Overall, there was no evidence for linkage to DPC4; linkage could be excluded in two of the eight pedigrees and was unlikely in two others. We then tested these eight families and a further 13 familial and sporadic JPS cases for germline mutations in DPC4. Just one germline DPC4 mutation was found (in a familial JPS patient from a pedigree unsuitable for linkage analysis). Like all three previously reported germline mutations, this variant occurred towards the C-terminus of the DPC4 protein. However, our patient's mutation is a missense change (R361C); somatic missense mutations in DPC4 have been reported previously in tumours. We therefore confirm DPC4 as a cause of JPS, but show that there is considerable remaining, uncharacterized genetic heterogeneity in this disease.
DNA-Binding Proteins↗
Direct revascularization to the anterior cerebral artery territory in patients with moyamoya disease: report of five cases.
OBJECTIVE: In some patients with moyamoya disease, the development of spontaneous leptomeningeal collateral channels between the anterior cerebral artery (ACA) and other major arteries is poor. These patients require revascularization not only to the territory of the middle cerebral artery (MCA) but also to that of the ACA. For reliable revascularization to the ACA territory, we performed superficial temporal artery (STA)-ACA direct anastomosis in 5 of 58 patients with moyamoya disease who underwent cerebral revascularization at our institute during the last 8 years. METHODS: Because two patients presented with ischemic symptoms corresponding to the ACA territory after the ipsilateral STA-MCA anastomosis, we subsequently performed STA-ACA anastomosis. In three patients in whom hypoperfusion in the ACA territory was suspected based on preoperative angiograms and/or stimulated cerebral blood flow studies, we performed STA-ACA and STA-MCA anastomoses during a single operative procedure. After paramedian frontal craniotomy (diameter, approximately 5 cm), STA-ACA anastomosis was performed 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. RESULTS: Bypass flow was satisfactory in four patients. One patient who underwent simultaneous STA-ACA and STA-MCA anastomoses had poor bypass flow, probably caused by spontaneous leptomeningeal collateral channels between the ACA and MCA. No patient had an ischemic attack after surgery. CONCLUSION: 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 more easily than in a deep operative field. Our experience with STA-ACA anastomosis indicates that this procedure is effective for revascularization of the ACA territory in patients with moyamoya disease.
Adolescent↗
Familial case of choledochocele.
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Choledochal Cyst↗
Peutz-Jeghers disease: most, but not all, families are compatible with linkage to 19p13.3.
A locus for Peutz-Jeghers syndrome (PJS) was recently mapped to chromosome 19p13.3. Each of 12 families studied was compatible with linkage to the marker D19S886. We have analysed 20 further families and found that the majority of these are consistent with a PJS gene on 19p13.3. Three families were, however, unlinked to 19p13.3 and none of the available PJS polyps from these families showed allele loss at D19S886. There were no obvious clinicopathological or ethnic differences between the 19p13.3 linked and unlinked families. There appears, therefore, to be a major PJS locus on chromosome 19p13.3 and the possibility exists of a minor locus (or loci) elsewhere.
Chromosomes, Human, Pair 19↗