Mucinous gastric carcinoma: is it more malignant?
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Publications and source records attributed to K Yasuda.
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AIMS/HYPOTHESIS: Neurogenin 3 (ngn3) is a transcription factor expressed in the endocrine precursor cells of the pancreas. It has recently been reported that ngn3-deficient mice show absence of pancreatic endocrine cells and die of postnatal diabetes. The purpose of this investigation was to screen for polymorphisms of the ngn3 gene and to test whether these polymorphisms are associated with Type II (non-insulin-dependent) diabetes mellitus in the Japanese subjects. METHODS: We screened ngn3 gene and upstream region by direct sequencing and estimated the prevalence of polymorphisms in 197 patients with Type II (non-insulin-dependent) diabetes mellitus and 216 control subjects. RESULTS: We identified four novel polymorphisms, Ser199Phe (596C/T), -43insCA, -983C/T and -1822G/A. In an association study the allelic frequencies of the major allele of these four polymorphisms were 0.721, 0.914, 0.912 and 0.530 in diabetic patients, respectively, and 0.694, 0.905, 0.917 and 0.537 in control subjects, respectively. CONCLUSION/INTERPRETATION: Mutations and polymorphisms of ngn3 gene are not significantly associated with Type II (non-insulin-dependent) diabetes mellitus in the Japanese subjects.
A method is described for continuous observation of isolated single cells that enables genetically identical cells to be compared; it uses an on-chip microculture system and optical tweezers. Photolithography is used to construct microchambers with 5-microm-high walls made of thick photoresist (SU-8) on the surface of a glass slide. These microchambers are connected by a channel through which cells are transported, by means of optical tweezers, from a cultivation microchamber to an analysis microchamber, or from the analysis microchamber to a waste microchamber. The microchambers are covered with a semi-permeable membrane to separate them from nutrient medium circulating through a "cover chamber" above. Differential analysis of isolated direct descendants of single cells showed that this system could be used to compare genetically identical cells under contamination-free conditions. It should thus help in the clarification of heterogeneous phenomena, for example unequal cell division and cell differentiation.
The purpose of the present study was to examine the effects of cilostazol on endothelial cell denudation and proliferation in vein grafts used as arterial substitutes. Unilateral aortoiliac bypass was performed using the lateral jugular vein in 20 mongrel dogs. The animals were divided into two groups according to whether or not cilostazol was given. The grafts were removed at intervals of 1 day and 50 days, and the luminal surface was assessed for endothelial cell coverage (%). The denudation of endothelial cells was less extensive in the cilostazol group than in the control group on postoperative day 1. There was significantly more proliferation of endothelial cells in the control group over the course of time than in the cilostazol group. In conclusion, cilostazol significantly prevented early endothelial cell denudation, although it did not appear to stimulate successive endothelial cell proliferation. Therefore, cilostazol may help preserve an intact intima, which would potentially result in the inhibition of intimal hyperplasia.
We report herein a case of leiomyosarcoma of Meckel's diverticulum which presented as a rare manifestation of perforation. A previously healthy 63-year-old man was referred to the Tetsujinkai Eniwa hospital following the sudden development of acute abdominal pain. Abdominal computed tomography revealed a solid mass in the pelvic cavity, and an emergency operation was performed under a provisional diagnosis of peritonitis associated with a pelvic tumor. A perforated tumoral mass was found in Meckel's diverticulum. Segmental resection of the ileum, including the tumor-bearing diverticulum, was performed along with regional lymph node dissection. Histologic examination revealed the lesion to be leiomyosarcoma.
Gastric cancer associated with human immunodeficiency virus (HIV) infection is rare, and mostly results in a poor outcome. We report a patient with HIV infection and early gastric cancer successfully treated by gastrectomy. A 49-year-old man with a 6-year history of HIV infection underwent gastric fiberscopy, and a IIc-type depressed lesion was detected in the gastric antrum. With a diagnosis of early gastric cancer, we abided strictly by standard precautions for patients with HIV infection and carried out Billroth I gastrectomy. Histologic examination revealed that the lesion (which measured 0.9 x 0.4 cm in size), was well differentiated tubular adenocarcinoma confined to the mucosa. A review of the literature disclosed that this is the first reported case of early gastric cancer associated with HIV infection.
BACKGROUND: Studies of lymph node micrometastases in patients with colorectal cancer have ignored the prognostic significance of the number and level of lymph node micrometastases. The aim of this study was to clarify the prognostic significance of the status of lymph node micrometastases in histologically node-negative colorectal cancer. METHODS: We used immunohistochemistry with anti-cytokeratin antibody CAM5.2 to examine 1013 lymph nodes in 42 patients (12 recurrent and 30 nonrecurrent) with histologically determined Dukes' B colorectal cancer. Five serial 6-microm sections were used for immunohistochemical staining. The frequency, tumor cell pattern, and number and level of lymph node micrometastases were compared between the recurrent and nonrecurrent groups. RESULTS: Micrometastasis was confirmed in 16% (59/373) of lymph nodes in the recurrent group and 12% (77/640) of lymph nodes in the nonrecurrent group, and the frequency of lymph node micrometastases was 92% (11/12) in the recurrent group and 70% (21/30) in the nonrecurrent group. The tumor cell pattern in the metastatic lymph nodes was similar in the recurrent and nonrecurrent groups. Micrometastasis in four or more lymph nodes occurred more frequently in the recurrent group than in the nonrecurrent group (58% vs. 20%, P < .05), and micrometastasis to N2 or higher nodes occurred more frequently in the recurrent group than in the nonrecurrent group (92% vs. 47%, P < .01). CONCLUSIONS: The number and level of positive micrometastatic lymph nodes was significantly correlated with postoperative recurrence of histologically determined Dukes' B colorectal cancer. This parameter is a useful prognostic indicator in histologically node-negative colorectal cancer and is helpful in planning adjuvant chemotherapy.
Conventional surgery for para-anastomotic aortic aneurysms is technically challenging, and is associated with high morbidity and mortality. This report describes the case of a patient with severe pulmonary diseases in whom false para-anastomotic aortic aneurysms were successfully repaired using an endovascular stent graft technique.
BACKGROUND: Little is known about alterations of cytokine levels in cerebrospinal fluid (CSF) during thoracoabdominal aortic surgery. We measured perioperative CSF cytokine levels to determine their clinical significances. METHODS: Perioperative serum and CSF levels of cytokine were measured in 15 adult patients undergoing repair of the descending thoracic aorta (n = 4) or thoracoabdominal aorta (n = 11). All patients underwent prosthetic replacement and perioperative CSF drainage. Serum and CSF levels of tumor necrosis factor-alpha, Interleukin- (IL-) 1beta, IL-6, IL-8, IL-10, and IL-12 were measured before operation and at 0, 6, 12, 18, 24, 48, and 72 hours postoperatively using enzyme-linked immunosorbent assays. RESULTS: There were no hospital deaths, but 1 patient suffered paraplegia. Cerebrospinal fluid IL-8 levels peaked at immediately after operation (751.7 +/- 42.1 pg/mL versus preoperative levels, 54.9 +/- 24.6 pg/mL; p < 0.001), and the higher levels persisted for 72 hours. In contrast, serum IL-8 levels did not change and remained lower than CSF levels. The patient with paraplegia had the highest CSF IL-8 levels throughout the study period. Serum and CSF levels of tumor necrosis factor-alpha, IL-1beta, IL-6, and IL-12 did not significantly change. Serum and CSF levels of IL-10 were significantly elevated after operation compared with preoperative levels. In contrast to IL-8, serum IL-10 levels surpassed CSF levels. CONCLUSIONS: Cerebrospinal fluid IL-8 levels are significantly elevated in thoracoabdominal aortic operation, and may be the most sensitive to the inflammatory response in the ischemic spinal cord injury. Persistent elevation of CSF IL-8 levels may be predictive of further development of neurologic deficits, and a reduction of proinflammatory cytokine levels may be a beneficial effect of CSF drainage, but this requires further investigation.
Mobile atheroma in the proximal aorta is a risk factor for brain complication after cardiovascular operation. We report a new technique of replacing the ascending and transverse aorta by establishing selective hypothermic antegrade cerebral perfusion. After cooling, cerebral vessels are clamped and systemic perfusion is started. This technique was applied in 5 patients. All patients woke up normally and recovered without neurologic complication.
Nationwide survey on familial cases of West syndrome (WS) in first- and second-degree relatives was conducted by mailing a questionnaire to 64 major university hospitals, children's hospitals, and epilepsy centers in Japan, and by review of the Japanese cases in the literatures. Thirty-four familial cases, 20 males and 14 females, were obtained in 15 families including one with five affected members in two generations and another with three affected male siblings including a half brother by a different father (X-linked WS). A mother and the child or children were involved in three families. Nine families had 21 cryptogenic cases and six families had 13 symptomatic cases, and the etiologies were same among the affected members in each family. Familial cases of WS have characteristic clinical features and genetic mechanisms. Age of onset, seizure types, electroencephalographic abnormalities, early seizure outcome, effective treatment, long-term seizure prognosis, and long-term developmental prognosis were concordant among the affected members in each family. Long-term seizure and developmental prognoses were far better than those in WS in general, with seizure-free rate of 82% and normal mental development rate of 44%. Poor prognosis was limited to specific symptomatic cases. Adrenocorticotropic hormone (ACTH) was a treatment of choice, and even in relapse of WS after ACTH therapy, the patients well responded to antiepileptic drugs. Specific inheritance pattern was difficult to imagine in the majority of the present cases, except for one family with X-linked WS and another family with five patients of maternal inheritance. These results are helpful for the treatment choice and prognostication of clinical course for familial cases of WS.
We studied glucocorticoid-induced insulin resistance and possible role of protein kinase C (PKC). Pretreatment with dexamethasone, prednisolone and corticosterone for 60 min decreased insulin-induced [3H] 2-deoxyglucose (DOG) uptake in isolated rat adipocytes. Preincubation with Go6976, LY379196 or myristoylated PKC pseudosubstrate, conventional PKC inhibitor, but not cycloheximide or RU38486, recovered dexamethasone-induced insulin resistance. Dexamethasone activated immunoprecipitates with anti-PKC alpha, beta, and zeta antibodies. PKC zeta activity in adipocytes increased to 163%, and 264% from basal level (100%) with dexamethasone and insulin treatment, respectively. Dexamethasone provoked redistribution of both PKC beta and zeta from the cytosol to the membrane. These results indicate that dexamethasone activates both conventional and atypical PKC. However, conventional PKC is more important in glucocorticoid-induced insulin resistance.
Lens development provides a good model system for studying cellular and molecular mechanisms underlying embryonic induction and morphogenesis. Members of the large Maf family of transcription factors, L-Maf and c-Maf, have been shown to play key roles in chick and mouse lens development. Here we report identification of two Xenopus maf genes, XmafB and XL-maf, which exhibit unique temporal and spatial expression patterns during lens formation. XmafB can first be detected in the presumptive lens-forming ectoderm, when the primary eye vesicle makes contact with the head ectoderm. XL-maf expression appears a little later, just before thickening of the lens placode, and both XmafB and XL-maf can be detected in the lens placode. During lens vesicle formation, the expression domains of XmafB and XL-maf segregated from each other, resulting in restricted expression in lens epithelial and fiber cells, respectively. When the optic cup anlagen was removed, only XmafB expression is detected. Both Mafs can induce the lens fiber cell-specific markers, betaA4- and gamma-crystallins. In animal cap assays, XmafB can induce Pax6, Xlens1 and Sox3 expression, but XL-maf fails to induce Pax6 and Xlens1 expression. These results suggest that these maf genes are involved in the regulation of cell-type specific gene expression and play roles in inductive events during Xenopus lens development.
A new lead generation of non-peptidic ET(A) antagonists from two peptidic ET(A)-selective ones, BQ-123 and FR139317, was performed. Using computer assisted molecular modeling, a putative pharmacophore was constructed from the superposition of the reported three-dimensional structure of the cyclic peptide BQ-123 and a presumable beta-turn active conformation of the linear peptide FR139317 formed by an intramolecular hydrogen bond. According to this model, a new series of indan derivatives were designed and synthesized. Among these, 5-isobutyrylamino-6-(1-naphthylmethyloxy)-3-(2-thienyl)-1-indancarboxylic acid (1b) showed a moderate ET(A) antagonistic activity (IC50 = 28 microM).
OBJECTIVES: In repair of acute type A aortic dissection, the type of proximal repair of the ascending aorta has been of great interest; however, very few reports are available regarding this issue in chronic aortic dissection. The surgical strategies for proximal repair in chronic dissection may not the same as those for acute dissection. We reviewed our 10-year experience of both acute and chronic type A aortic dissections in order to elucidate the validity of valve preservation and the long-term results of aortic regurgitation (AR). METHODS: From 1990 to 1999, 93 patients (55 acute and 38 chronic dissections) underwent operation for type A aortic dissection. Five Marfan patients were included in each group. The degree of AR was evaluated by echocardiography before and after (at hospital discharge and late follow-up) operation. RESULTS: In acute type A aortic dissection (n=55), 16 patients had AR grade II or greater (29%), of whom seven had AR grade III (13%). In 29 patients, dissection was found below the sinotubular junction (STJ) and 14 patients had AR grade II or greater (48%). The aortic valve was replaced in four patients (7%), of whom three had Marfan's syndrome. Only one non-Marfan patient required aortic valve replacement because of valve stenosis. In those whose aortic valve was preserved (n=51), three patients still had AR grade II at hospital discharge, while at late follow-up, AR had deteriorated to grade III in two of them, although no reoperation has been required so far. In chronic type A aortic dissection (n=38), 14 patients had AR grade II or greater (37%), of whom 11 had AR grade III or greater (29% vs. 13% in acute dissection; P=0.051). In 15 patients, dissection was found below the STJ and 12 patients had AR grade II or greater (80% vs. 48% in acute dissection; P=0.043). The aortic valve was replaced in eight patients (21% vs. 7% in acute dissection; P=0.051), including three Marfan patients. Of those whose aortic valve was preserved (n=30), two patients required reoperation for severe AR. The freedom from postoperative AR grade III or greater was 89% at 5 years for operative survivors with acute dissection and 92% for those with chronic dissection, respectively. CONCLUSIONS: This retrospective study suggests that preservation of the aortic valve in acute type A aortic dissection is feasible in non-Marfan patients regardless of the degree of AR. In chronic dissection, aortic root replacement needs to be considered when the degree of AR is greater than moderate because of a dilated STJ and/or annulus. In both acute and chronic dissections, satisfactory mid- to long-term results with a low incidence of reoperation were obtained in those whose aortic valve was preserved.
To elucidate the process of TCR-mediated signaling pathways in lipid rafts, we constructed a chimeric molecule that localizes activated SHP-1 to rafts. Raft targeting of activated SHP-1 in Jurkat-derived transfectants completely inhibited the expression of CD69 and transcriptional factors after TCR cross-linking. Whereas the inducible tyrosine phosphorylation of TCR zeta and ZAP-70 and the kinase activity of Lck were intact, phosphorylated LAT was rapidly dephosphorylated by raft targeting of activated SHP-1, leading to defects in LAT activation and subsequent downstream signaling events. Intriguingly, recruitment of endogenous SHP-1 to rafts and its association with LAT were dramatically increased after TCR engagement, suggesting that SHP-1 is involved in raft-mediated T cell activation.
We examined the effect of dehydroepiandrosterone (DHEA) on glucose uptake and phospholipase D (PLD) activation in rat adipocytes. DHEA (1 microM) provoked a twofold increase in [3H]2-deoxyglucose (DG) uptake for 30 min. Incorporation of [3H]glycerol into diacylglycerol was increased 150% above basal level for 20 min after stimulation with 1 microM DHEA. DHEA increased PLD activity, measured by the incorporation into [3H]phosphatidylethanol in [3H]palmitate labelled rat adipocytes, or by [3H]choline release in [methyl-(3)H]choline labeled rat adipocytes. Our results suggest that DHEA stimulates glucose uptake with activation of PLD in rat adipocytes.
OBJECTIVES: We conducted this latency study to clarify the neurophysiological mechanism underlying the synchronous appearance of independent occipital and frontopolar spike discharges in childhood epilepsies. METHODS: The subjects were 13 children with localization-related epilepsies (LRE) who showed apparently synchronous occipital and frontopolar EEG spike discharges. There was idiopathic LRE in 7 children, symptomatic LRE in 4, and cryptogenic LRE and a history of cryptogenic West syndrome in one patient each. Patient ages at the time of the study ranged from 4 years 3 months to 14 years 0 month with a mean of 9 years 4 months. The EEGs were digitized at 1024 samples/s. The latency was measured between the peak of the occipital and frontopolar spike discharges. The conduction velocity was calculated by dividing the distance between the occipital and frontopolar electrodes by the latencies. RESULTS: We studied 19 EEGs including 6 serial EEGs recorded longitudinally in 5 patients. The number of occipito-frontal spike discharges available for the study ranged from 12 to 70 with an average of 36+/-17 in each EEG record. Occipital spikes always preceded the frontopolar spikes by 11.1-31.6 ms (average 19.3+/-5.4 ms). The estimated conduction velocity ranged from 6.7 to 19.2 m/s with a mean of 12.2+/-3.7 m/s. CONCLUSIONS: The synchronizing spike phenomenon we showed in this study was in the posterior to anterior direction (intrahemispheric synchrony) in contrast to that of secondary bilateral interhemispheric synchrony through the corpus callosum. It is suggested that the long occipito-frontal association fibers play a role in synchronizing both spike discharges. This secondary occipito-frontopolar synchrony should be one of the developmental EEG phenomena related to the maturation of brain, and contribute to the multiplication or diffusion of the pre-existing localized spike discharges often seen in pediatric LRE regardless of etiology.