Prognostic impact of histological categorisation of epithelial-mesenchymal transition in colorectal cancer.

BACKGROUND: The crosstalk between cancer cells and stroma is involved in the acquired capability for metastasis through the induction of epithelial-mesenchymal transition (EMT). We aimed to clarify the prognostic value of the histological category of EMT in colorectal cancer (CRC). METHODS: Tumour EMT was graded into one of three histological categories on the basis of integrated assessment of poorly differentiated clusters and pro-EMT desmoplasia at the leading edge of the primary tumour (Histology(EMT)). Stage II and III CRC patients (cohort 1, N=500) and stage IV patients (cohort 2, N=196) were retrospectively analysed. RESULTS: In cohort 1, patients were stratified into three groups with widely different disease-free survival rates (95%, 83% and 39%) on the basis of Histology(EMT) (P<0.0001). In cohort 2, Histology(EMT) significantly stratified overall survival of patients irrespective of metasectomy. Multivariate analyses indicated that Histology(EMT) had a strong prognostic impact independent of staging factors. Statistically, Histology(EMT) had a better prognostic stratification power than T and N stages; however, in cohort 2, the power of M substage was superior. CONCLUSIONS: A histological model to categorise EMT by integrated assessment of dedifferentiation and desmoplastic environment is a potent prognostic index independent of staging factors.

Longevity-associated mitochondrial DNA 5178 A/C polymorphism and blood pressure in the Japanese population.

It has been reported that the mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism, also called NADH dehydrogenase subunit 2-237 methionine/leucine (ND2-237 Met/Leu) polymorphism, may be associated with longevity in Japanese individuals, and that the mt5178A genotype may have an antiatherogenic influence. To determine whether mt5178 A/C polymorphism influences blood pressure, we genotyped 412 healthy Japanese individuals and performed a cross-sectional study investigating the relationship between genotype and blood pressure. In women with mt5178A, the mean diastolic blood pressure was higher than in those with mt5178C by 3.2 mmHg (P=0.040). In men, no statistically significant difference in systolic or diastolic blood pressure was observed between mt5178 A/C genotypes. However, a significant correlation between mt5178 A/C genotypes and the effects of habitual drinking on blood pressure was found. After adjustment for several factors, in men carrying mt5178C, both systolic and diastolic blood pressure were significantly higher in daily drinkers than in occasional (P=0.002 and 0.002, respectively) as well as nondrinkers (P<0.001 and 0.001, respectively), whereas in men carrying mt5178A, no significant differences in blood pressure were detected, irrespective of alcohol consumption. These results suggest that mt5178 A/C (=ND2-237 Met/Leu) polymorphism may influence both diastolic blood pressure in Japanese women and the blood-pressure-increasing effect of drinking in Japanese men.

[Clinical evaluation of granisetron hydrochloride for nausea and vomiting induced by oral anticancer drugs].

We investigated the antiemetic effect, safety and usefulness of granisetron hydrochloride tablets on nausea and vomiting induced by oral anticancer drugs used in chemotherapy for gastric cancer and colorectal cancer. In the present trial, oral administration of granisetron hydrochloride was performed during 5 days after nausea or vomiting. 1) Clinically, the effective rate of granisetron hydrochloride (the percentage of cases in which the drug was assessed as "Remarkably effective" or "Effective") was more than 75% on each day of administration. There were no adverse events or abnormal laboratory tests. 2) In terms of usefulness, granisetron hydrochloride was rated "Extremely useful" or "Useful" in 17 out of 23 cases (78.2%). The above results have shown that granisetron hydrochloride tablets, administrated orally once daily at a dose of 2 mg, have an excellent antiemetic effect, and that this is a safe and useful drug.

Angiographic classification of cerebral embolism. Relation with the response to local intra-arterial thrombolysis.

Since 1994, we have treated 62 cases with hyperacute cerebral embolism with local intraarterial thrombolysis (LIT), but not all cases showed recanalization. We tried to classify these cases by angiographic results. Angiographically they could be classified into four types; tapering type, fading type, stump type, and edge type. The tapering and fading type had a significantly higher tendency to recanalize than the stump and edge type. We think these classifications indicate the dissolubility of the cerebral emboli; the former two types dissoluble, the latter two types indissoluble. The tapering and fading type are the good indicators for LIT, but the stump and edge type may not be.

Purification of a factor from CSF in patient after SAH which induces the cytosolic free calcium elevation in vascular smooth muscle cells.

Cerebrospinal fluid from patients with aneurysmal subarachnoid hemorrhage induces the elevation of cytosolic free calcium [Ca2+]i in cultured vascular smooth muscle cells. We have purified a [Ca2+]i elevating factor from cerebrospinal fluid of a patient with subarachnoid hemorrhage due to aneurysm rupture. The calcium-elevating protein factor was purified to homogeneity by ammonium sulfate precipitation and a combination of Mono Q, Superose 12, and Mono S columns using liquid chromatography. Fifteen microgram of the purified protein was obtained from 340 mg of cerebrospinal fluid proteins and the molecular mass of the protein was estimated to be 81 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis. It was also shown that the purified protein was cross-reactive with anti-human transferrin antibody. These results suggested that transferrin may be involved with the cerebral vasospasm after subarachnoid hemorrhage.

Angiographic A-V Shunt during Interventional Thrombolysis for Acute Cerebral Embolism. A New Predictive Sign for Hemorrhagic Complication.

SUMMARY: In order to predict the post-therapeutic hemorrhagic complication of interventional thrombolysis, we retrospectively examined angiographic findings and other factors in 44 patients with acute cerebral embolism. All patients were super selectively catheterized within 5 hours of onset and received a fixed regimen of urokinase or t-PA, unless recanalization was achieved or deterioration was apparent before total infusion. Immediate post-therapeutic CT scan revealed hematoma within the basal ganglia in 10 patients (group 1) and no hemorrhage in the remaining 34 (group 2). A series of angiograms during the therapy showed A-V shunt from lenticulostriate arteries to thalamostriate vein in 7 of 10 cases in group 1; no case in group 2 was accompanied by such abnormal shunt. Prognosis after the therapy was worse in group 1 than in group 2. No other factors, such as therapeutic timing after the disease onset or total doses of urokinase or t-PA infused, differed between the two groups. These findings indicate that angiographic A-V shunt during therapy is a predictive sign of a high incidence of hemorrhagic complication. We recommend performing several angiographic controls during therapy and when A-V shunt is detected, the therapy should be discontinued to prevent hemorrhage which leads to a poor prognosis.

[MRSA enteritis following severe gastroenteritis of salmonellosis].

A 62-year-old female patient was given cancer chemotherapy for lymph nodes metastases in the left breast cancer. She was admitted to the hospital because of severe watery diarrhea, in hypovolemic shock, and was diagnosed as suffering from not-typhoidal Salmonella by stool culture. After systemic administration of antibiotic agents, she became well in a few days, but on the 16th hospital day, she had severe watery diarrhea, hypovolemic shock and then cardiac arrest. She was resuscitated immediately. The stool culture revealed methicillin-resistant Staphylococcus aureus (MRSA), type II coagulase, producing TSST-1 and type BC staphylococcal enterotoxin. It was thought that in this case, MRSA enteritis was caused by damage of the intestinal mucosal barrier of the defense mechanism against infection due to salmonellosis and administration of multiple antibiotic agents.

Cytosolic free calcium elevation in vascular smooth muscle cells induced by cerebrospinal fluid from patients with subarachnoid hemorrhage--biochemical nature of the calcium-mobilizing factor.

The present study was undertaken to characterize the biochemical nature of the factor in cerebrospinal fluid (CSF) from patients with subarachnoid hemorrhage (SAH) that induces a transient elevation of cytosolic free calcium in cultured vascular smooth muscle cells. Cell-free CSF collected from patients on days 7-10 after SAH was treated in three different ways: heating, ultrafiltration, and salting out with ammonium sulfate. The effects of the resultant solutions on the level of cytosolic free calcium in cultured vascular smooth muscle cells were then examined. Heated CSF and ultrafiltrated solution containing substances with molecular weights of less than 10,000 caused no significant elevation of cytosolic free calcium. Proteins precipitated by 50-75% saturated ammonium sulfate caused an increase in the level of cytosolic free calcium and also produced a rapid accumulation of inositol 1,4,5-trisphosphate in vascular smooth muscle cells. The results indicate that the factor responsible for the increase in cytosolic free calcium in cultured vascular smooth muscle cells is a protein with a molecular weight of more than 10,000, and the factor stimulates receptor-mediated phosphoinositide breakdown.

Effects of a concanavalin A-binding biliary glycoprotein on nucleation time of gallbladder bile.

A study was performed to determine quantitative differences in the total protein concentration of gallbladder bile from gallstone patients and to isolate nucleation-promoting factors from the bile. Total protein concentrations in cholesterol gallstone bile (3.6 +/- 0.6 mg/ml, mean +/- SD, n = 10), calcium bilirubinate gallstone bile (4.2 +/- 1.1 mg/ml, n = 10), black pigment gallstone bile (1.9 +/- 0.6 mg/ml, n = 4) and control gallbladder bile (2.3 +/- 0.5 mg/ml, n = 9) were not significantly different. Also no statistically significant differences in cholesterol saturation index were found among these groups. Gallbladder bile from cholesterol gallstone patients showed significantly faster nucleation than that of controls, calcium bilirubinate gallstone, or black pigment gallstone patients. We partially purified biliary glycoproteins proteins from cholesterol gallstone bile or calcium bilirubinate gallstone bile by chromatography on concanavalin A Sepharose. Nucleation time was measured following the addition of these proteins to control bile in vitro. The glycoproteins obtained from cholesterol gallstone bile had significant nucleation-promoting activity, but nucleation time was not changed following the addition of biliary glycoproteins from calcium bilirubinate gallstone patients. These results suggest that qualitative differences in individual proteins of gallbladder bile are responsible for nucleation-promoting activity in vitro.

[Fibromuscular dysplasia of the cervical arteries associated with a distal vertebral trunk aneurysm. Case report].

A 64-year-old, hypertensive female suddenly experienced severe headache. On admission, the patient had almost clear consciousness but was slightly restless and complained of severe headache and nausea. Neurological examination revealed only neck stiffness. A computed tomographic scan revealed subarachnoid hemorrhage. Angiographically, bilateral internal carotid and vertebral arteries had the "string of beads sign" at their cervical portion, and the left internal carotid artery also had the same sign at its cavernous portion. The left vertebral artery had low-origin posterior inferior cerebellar artery and a berry-shaped aneurysm at its distal trunk. A diagnosis of cervical and intracranial fibromuscular dysplasia (FMD) with a ruptured berry-shaped aneurysm of the distal vertebral trunk was made. The berry-shaped aneurysm was successfully treated with proximal clipping. Angiographically, right renal and axillary arteries also had the "string of beads sign," and the patient's hypertension seemed to be renovascular in etiology. The co-existence of intracranial FMD and cerebral aneurysm of unusual location suggests a possible relationship between the FMD and the development of cerebral aneurysm.

[Effects of noradrenaline and isoproterenol on the insulin secretion from the rat pancreas perfused isolatedly in situ].

Effects of noradrenaline and isoproterenol on insulin secretion in rat pancreas have been studied by means of the in situ perfusion method described previously. Noradrenaline: The insulin secretion from the rat pancreas perfused with the high glucose buffer decreases after the administration of 1 microgram/0.1 ml of noradrenaline into the perfusion fluid. These noradrenaline-induced hyposecretions can be reversed by pretreatment with phentolamine (10 micrograms/ml), while they are potentiated after propranolol (10 micrograms/ml) pretreatment. Isoproterenol: The insulin secretion from the rat pancreas perfused with the same buffer increases after the administration of 1 microgram/0.1 ml of isoproterenol into the perfusion fluid. These isoproterenol-induced hypersecretions are found to be potentiated after pretreatment with phentolamine or propranolol, and atropine (100 micrograms/ml) pretreatment does not produce any changes in the isoproterenol-induced hypersecretion. These results suggest that the beta-receptors on the B-cells stimulate the insulin secretion and the beta-receptors on the D-cells decrease them. This communication gives a short discussion of whether alpha-receptors may be on D-cells or not.