Clinicopathological significant and prognostic influence of cadherin-17 expression in gastric cancer

Cadherin-17 (CDH17), also called liver–intestine cadherin, is a structurally unique member of the cadherin superfamily. Our serial analysis of gene expression demonstrated that CDH17 was one of the most up-regulated genes in advanced gastric carcinomas. CDH17 expression is known to be regulated by Cdx2. In the present study, we examined the expression of CDH17 in primary gastric carcinoma tissues by immunohistochemistry, and analyzed the correlation of CDH17 expression with clinicopathological characteristics and patients prognosis. CDH17 expression was detected in 63/94 (67%) of gastric adenocarcinomas in addition to intestinal metaplasia. The expression of CDH17 tended to be associated with intestinal type carcinoma, and carcinomas with CDH17 expression was significantly more frequent in advanced stage cases (80%) than in early stage (53%). The prognosis of patients with positive CDH17 expression was significantly poorer than that of the negative cases (P=0.0314). However, multivariate analysis revealed that CDH17 was not an independent prognostic factor. Six of seven cases that showed positive expression of Cdx2 simultaneously expressed CDH17 protein. These results suggested that the expression of CDH17 was characteristic of the advanced gastric carcinoma that is associated with poor prognosis.     

Trivalent heat-labile- and heat-stable-enterotoxin probe conjugated with horseradish peroxidase for detection of enterotoxigenic Escherichia coli by hybridization.

A 1,268-bp polynucleotide probe for heat-labile and heat-stable enterotoxins (LTh, STIa, STIb) was conjugated with horseradish peroxidase (HRP). The HRP-conjugated trivalent probe was applied to the detection of enterotoxigenic Escherichia coli (ETEC) by colony and stool hybridizations. The binding of the probe to its targets was assayed by the addition of HRP substrates hydrogen peroxide and luminol in the presence of an enhancer, and the chemiluminescence was recorded by exposure to X-ray film. Slot blot hybridization demonstrated that the HRP-conjugated trivalent probe specifically hybridized with the DNA isolated from ETEC strains. The trivalent probe also specifically identified bacterial colonies of ETEC that produced LTh, STIa, STIb, LTh-STIa, or LTh-STIb. Treatment of targets with sodium dodecyl sulfate and proteinase K remarkably reduced nonspecific hybridization to DNAs of non-ETEC strains. Furthermore, this probe was able to detect stool specimens seeded with 10(2) original ETEC cells per 5 mg of feces. These results suggest that the HRP-conjugated trivalent probe is a candidate for use in the clinical laboratory to detect ETEC.     

Skeletal disorders associated with skin pigmentation: a role of melatonin?

Although frequently encountered, no available consensus about the association between skeletal abnormalities and skin pigmentation. Several syndromes are characterized by the presence of skin pigmentation in association with skeletal disorders like neurofibroamtosis 1, McCune-Albright Syndrome, Jaffe-Campanacci Syndrome and Jaffe-Lichtenstein Syndrome. Even in the absence of these syndromes, skeletal abnormalities were detected in all radiologically examined patients having patterned skin pigmentation. Although skin pigmentation is controlled by several factors, melatonin is the most reliable factor to have relation to development of skeletal abnormalities. Recent research works support that melatonin might play a role in bone development and several hypotheses link melatonin with some bone diseases associated with skin pigmentation. It seems that melatonin deficiency is a probable operating co-factor in a lot of clinical situations characterized by skin pigmentation and skeletal disorders. This would explain some of the un-explained observations related to these syndromes and research works along these lines might lead to the development of efficient treatment for these diseases.     

Phase-dependent filtering of sensory information in the oscillatory olfactory center of a terrestrial mollusk

With electrophysiological techniques, we found phase-dependent modification of the efficacy of signal transmission in the procerebrum (PC), the oscillatory olfactory center, of the terrestrial mollusk Limax marginatus and elucidated its neuronal mechanism. Previous studies have indicated that about 10(5) PC neurons can be classified into only two types: bursting (B) neurons and nonbursting (NB) neurons, and both types of neurons have ongoing and phase-locked periodic oscillation of their membrane potentials. On olfactory nerve stimulation, excitatory postsynaptic potentials (EPSPs) were evoked with a constant latency in NB neurons, while EPSPs with a variable latency were evoked in B neurons. These findings suggest a monosynaptic connection from the olfactory nerve to NB neurons, but a polysynaptic connection between the olfactory nerve and B neurons. This polysynaptic transmission is most likely mediated by NB neurons because the olfactory nerve makes synaptic connection only with NB neurons in the PC. The latency of the evoked EPSPs in B neurons depended on the phase of the PC oscillatory activity, presumably because of the oscillation of the intervening NB neurons. These results suggest that the efficacy of olfactory nerve-B neuron polysynaptic transmission is regulated by the activity level of the phasically oscillating NB neurons. Thus, the intrinsic oscillation in the PC can serve as a filter for olfactory information conveyed from the olfactory nerve as a train of neuronal spikes. This filtering system may also produce a phase-dependent modification by the olfactory input of the PC oscillation frequency.     

Effects of nerve growth factor and glucocorticoid on cultured human pheochromocytoma cells

Primary cell cultures of two human pheochromocytomas (PC) that were associated with high serum levels of adrenaline and noradrenaline were developed to study the effects of nerve growth factor (NGF) and dexamethasone on the morphology and function of PC cells in vitro. By phase-contrast microscopy, cultured cells were small and hyperchromatic on the first day of culture; neurite-like processes that extended to other cells developed several days later and were maintained for more than 3 months. NGF (100ng/ml), dexamethasone (10^–5M), or NGF + dexamethasone were added to the culture media 2 weeks after the cultured cells had stabilized. Catecholamine concentrations in the medium were maintained at higher levels after addition of NGF, dexamethasone, or NGF + dexamethasone as compared to control cells. In the presence of NGF, extension of neurite-like processes was clearly accelerated, while high levels of dexamethasone inhibited growth of processes. These in vitro studies showed that the addition of NGF or the removal of dexamethasone induces differentiation of adrenal neurons present in pheochromocytomas, suggesting that adrenocortical steroid hormones influence the morphological control of adrenal medullary cells.     

Positive regulator for the expression of Mba protein of the virulence plasmid, pKDSC50, of Salmonella choleraesuis.

A positive regulator was identified within a 2.3 kb fragment of the 6.4 kb mouse bacteremia region (mba region) of the virulence pKDSC50 plasmid of Salmonella choleraesuis. Sodium dodecyl sulphate polyacrylamide gel electrophoresis showed that Escherichia coli K-12 carrying the recombinant plasmids of the 2.3 kb fragment produced Mba1 protein with a molecular mass of 32 kDa. The recombinant plasmids carrying a 4.1 kb fragment, the other part of 6.4 kb region, produced Mba2 (32 kDa), Mba3 (70 kDa) and Mba4 (29 kDa) proteins. All three proteins were expressed by using the lacZ promoter under isopropyl thiogalactoside induction. In contrast to this, Mba3 protein was overexpressed independently of the lacZ promoter when the 2.3 kb fragment coexisted either in cis or trans. These results suggest that Mba1 is a trans-acting positive regulator for the expression of the Mba3 protein of mba region of pKDSC50.     

Control of feeding rhythm in the terrestrial slug Incilaria bilineata.

A modulatory neuron of feeding rhythm was newly identified in the buccal ganglia of the isolated central nervous system (CNS) of the terrestrial slug Incilaria bilineata. This neuron was termed the "feeding rhythm modulator" (FRM). Its morphological and electrical properties were compared with those of the MGC (metacerebral giant cell, a cerebral modulatory neuron of feeding rhythm). There was no direct connection between FRM and MGC. In order to investigate the control mechanism of the buccal central pattern generator, feeding rhythm was observed by varying the activities of MGC and FRM simultaneously. At a lower level of activity of MGC, feeding rhythm was not only sensitive to the activity of MGC but also to that of FRM. As the level of activity of MGC increased, feeding rhythm was exclusively controlled by the activity of MGC, and became unaffected by the activity of FRM. This indicates that cerebral neurons such as MGC primarily control feeding rhythm and modulate the contribution of FRM in a hierarchical manner.     

Pathological Aspects of Radiofrequency Catheter Ablation of the Canine Atrioventricular Node and Bundle of His

Radiofrequency catheter ablation of the atrioventricular (AV) node or bundle of His was performed in 12 adult mongrel dogs. The aim was to create chronic incomplete AV block (first- and second-degree AV block) and to examine the histopathology of the ablated lesions. However, the late electrophysiological results (2 4 weeks follow up) were various: normal in 2 dogs, mild PR prolongation (< 50%) in 2 dogs, first-degree AV block (PR prolongation a 50%) in 2 dogs, second degree AV block in 2 dogs, complete AV block in 4 dogs. The maximally ablated area (%) of the atrioventricular conduction system in serial histologic sections from dogs with these conditions was 69%, 75%, 89.5%, 95% and 99.5%, respectively. The number of intact conduction cells at the maximally ablated site varied from 6 to 30 in the four cases of incomplete AV block. The mean ablated volume (%) of either the AV node or penetrating His bundle correlated roughly with the degree of AV block. The ablated lesions were well demarcated and almost replaced by dense fibrous tissue at 4 weeks. Interruption (3 dogs) or thinning (1 dog) of the endocardial elastic lamellae was detected, in association with endocardial thickening (mean 913 μm). Endocardial thrombi were found in 3 dogs (2 fresh, 1 organized). We conclude that radiofrequency catheter ablation does not cause severe complicated lesions. Several possible conditions for creating chronic incomplete AV block are discussed. Acta Pathol Jpn 41: 487–498, 1991.     

Development of renal potassium excretion capacity in the neonatal rat

We investigated the capacity of newborn rats to excrete an acute potassium load to understand the development of a renal potassium excretion system. Three groups of the rats (7-14 d) were used to collect urine periodically over 6 h after oral infusion of potassium: control (no potassium loading) and low- and high-potassium-loaded rats. In the low-potassium-loaded group, infused with about 0.6 microEq of potassium chloride/g body wt., the rate of renal potassium excretion increased from 0.08 plus minus 0.02 (7 d) to 0.13 plus minus 0.02 (10 d) and 0.21 plus minus 0.03 (14 d) microEq/h/g body wt. The high-potassium-loaded rats (1.5-2.8 microEq/g body wt. potassium load) excreted potassium at a higher rate of 0.18 +/- 0.05 (7 d), 0.30 +/- 0.02 (10 d), and 0.45 +/- 0.10 (14 d) microEq/h/g body wt. They excreted 77% (7 d), 76% (10 d), and 95% (14 d) of the potassium load. These values were much larger than the rate of 0.026 microEq/h/g body wt. of the control rats and of 0.08 microEq/h/g body wt., a mean potassium excretion rate during development from 7 to 14 d calculated from the data in the previous study (Kanno T et al.: J. Pediatr. Gastr. Nutr. 24: 242-252, 1997). In the same period, serum potassium concentration in the newborn rats decreased significantly (p < 0.01) from 7.2 +/- 0.1 (7 d) to 6.7 +/- 0.1 mEq/l (14 d). All these results suggest that a renal potassium excretion system in the rat develops at least in the second week of life, and its capacity is high enough to excrete the daily potassium intake.     

Tissue distribution of the Pk antigen as determined by a monoclonal antibody

Using an anti-Pk monoclonal antibody (mAb) designated CPK-1, the expression of the Pk antigen was assessed on normal human tissue from non-Pk individuals. Although the Pk antigen was detected on fibroblasts and blood vessels as previously reported, it was also found on smooth muscle cells of the digestive tract and the urogenital system. Pk was also found on glandular cells of the stomach, oesophagus and prostate. Additionally, CPK-1 reacted weakly with oesophagus squamous cells, and a small number of glomeruli and tubules in the kidney. The mechanism of expression of the Pk determinant in non-Pk individuals is discussed.