Contrast-enhanced, wide-band harmonic gray scale imaging of hepatocellular carcinoma: correlation with helical computed tomographic findings.

We evaluated the usefulness of contrast-enhanced, wide-band harmonic gray scale imaging for the diagnosis of hepatocellular carcinoma and compared it with helical computed tomography. Forty-eight patients with 61 hepatocellular carcinoma lesions were scanned by contrast-enhanced, wide-band harmonic gray scale imaging after an intravenous bolus injection of the contrast agent Levovist. Fifty-seven of the 61 hepatocellular carcinoma lesions showed hypervascular enhancement, and intratumoral vessels could be observed in 40 of the 57 lesions. Helical computed tomography revealed a high-attenuation area in 54 of the 61 lesions, whereas the other lesions showed an equivocal-attenuation area. Contrast-enhanced, wide-band harmonic gray scale imaging is a useful method for diagnosing the vascularity of hepatocellular carcinoma.     

Comparison of the effect on intragastric pH of a single dose of omeprazole or rabeprazole: Which is suitable for on‐demand therapy?

BACKGROUND AND AIMS: An ideal medication for heartburn should have the rapid onset of action needed for on-demand treatment. However, assessment of the onset of action of proton pump inhibitors has been largely subjective. We compared the inhibitory effect on gastric acid secretion of a single oral dose of omeprazole with that of rabeprazole. METHODS: Fourteen Helicobacter pylori-negative men participated in this randomized, double-masked, two-way cross-over study. Intragastric pH was monitored continuously for 6 h after a single, randomly assigned 20 mg oral dose of either omeprazole or rabeprazole. After a 7-day washout period, the other drug was administered. Each patient's S-mephenytoin 4'-hydroxylase (CYP2C19) genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Intragastric pH and pH holding time did not differ between treatments when the data were analyzed for the whole group without stratifying for CYP2C19 status. In CYP2C19 homozygous and heterozygous extensive metabolizers (10 subjects), rabeprazole maintained the intragastric at pH > 3 and> 4 for longer than omeprazole during both the 5 and 6 h study periods, and the average pH during the 6 h study period was higher with rabeprazole than with omeprazole. In these extensive metabolizers, rabeprazole maintained the pH > 2,> 3,> 3.5 and> 4 for longer during the 6 h study period than did omeprazole. CONCLUSIONS: In H. pylori-negative men who are CYP2C19 homozygous or heterozygous extensive metabolizers, the intragastric pH after a single dose of 20 mg rabeprazole is higher during first 5-6 h than that after a single dose of 20 mg omeprazole.     

Solitary lymph node metastasis of gastric cancer as a basis for sentinel lymph node biopsy

BACKGROUND/AIMS: In order to examine the biology of sentinel lymph node of stomach cancer, we investigated solitary lymph node metastases that were hypothesized to represent sentinel lymph node. METHODOLOGY: In the 4,620 primary gastric cancers between 1964 and 1997, 1271 cases with a localized tumor were selected and the localization of the solitary metastases in relation to the primary tumors were studied. RESULTS: Of the 130 tumors with a single basin metastasis, only 71% of the tumors in the upper third, 75% of the middle and 80% of the lower involved the node basins in the close vicinity. In the anterior wall and the greater curvature the rates of adjacent metastasis were more than 90%, while in the posterior wall and the lesser curvature they were 76% and 43%, respectively. Metastases of the remaining cases were found at more distant basins. CONCLUSIONS: In stomach cancer sensitivity of sentinel lymph node biopsy would be very low by the exploration of the adjacent basin especially for the lesions in the lesser curvature and posterior wall.     

The generation of monoclonal antibodies against human peroxisome proliferator-activated receptors (PPARs)

Monoclonal antibodies (Mabs) are valuable reagents for the purification, characterization and immunolocalization of proteins.In this study, we raised Mabs against human peroxisome proliferator-activated receptors (PPARs) using baculovirus particles displaying surface glycoprotein gp64-fusion proteins as the immunizing agent.In this system, to display fusion proteins on the viral surface, the amino terminal sequences of human PPARd and PPARg2 are inserted in-frame between the signal sequence and the mature domain of the gp64 nucleotide sequence.Mabs were raised by immunization with whole virus without a purification of the target antigens.The Mabs generated by this novel method were shown to recognize not only the gp64-PPARs fusion protein, but also mature, expressed proteins by a wide variety of techniques, including immunohistochemistry, immunoblotting, and electrophoretic mobility shift assays (EMSAs).Transfection of the transfer vector containing a nucleotide sequence encoding less than 30 amino acids along with linearized baculovirus DNA allows for the production of a high affinity antibody against the corresponding mature form.This method is of potential utility in that it allows the production of valuable antibodies without the requirement of a protein purification step.     

Insulin-induced cell cycle progression is impaired in chinese hamster ovary cells overexpressing insulin receptor substrate-3

To analyze the roles of insulin receptor substrate (IRS) proteins in insulin-stimulated cell cycle progression, we examined the functions of rat IRS-1 and IRS-3 in Chinese hamster ovary cells overexpressing the human insulin receptor. In this type of cell overexpressing IRS-1 or IRS-3, we showed that: 1) overexpression of IRS-3, but not IRS-1, suppressed the G1/S transition induced by insulin; 2) IRS-3 was more preferentially localized to the nucleus than IRS-1; 3) phosphorylation of glycogen synthase kinase 3 and MAPK/ERK was unaffected by IRS-3 overexpression, whereas that of protein kinase B was enhanced by either IRS; 4) overexpressed IRS-3 suppressed cyclin D1 expression in response to insulin; 5) among the signaling molecules regulating cyclin D1 expression, activation of the small G protein Ral was unchanged, whereas insulin-induced gene expression of c-myc, a critical component for growth control and cell cycle progression, was suppressed by overexpressed IRS-3; and 6) insulin-induced expression of p21, a cyclin-dependent kinase inhibitor, was decreased by overexpressed IRS-3. These findings imply that: 1) IRS-3 may play a unique role in mitogenesis by inhibiting insulin-stimulated cell cycle progression via a decrease in cyclin D1 and p21 expressions as well as suppression of c-myc mRNA induction in a manner independent of the activation of MAPK, protein kinase B, glycogen synthase kinase 3 and Ral; and 2) the interaction of IRS-3 with nuclear proteins may be involved in this process.     

A case of malignant hemangioendothelioma of the stomach

A case of malignant hemangioendothelioma of the stomach is reported. The patient was a 21-year-old female who developed bloody stool. Pathological studies on the stomach revealed a gastric submucosal tumor. This tumor was growing on the outside of the stomach wall and formed a large abdominal mass. Evidence of metastases was detected in the liver, omentum and parietovisceral peritoneum. Biopsies were taken of the gastric mucosa and the metastatic lesions of the liver and omentum, and histological studies on these specimens led to the diagnosis of malignant hemangioendothelioma. A laparoscopic examination yielded very interesting findings: the presence of small red tumors on the omentum and the parietovisceral peritoneum. The usefulness of laparoscopic examination in the diagnosis of malignant hemangioendothelioma of the stomach is stressed.     

19-Hydroxyandrostenedione: evidence for a new class of sodium-retaining and hypertensinogenic steroids

The biological activities of 19-hydroxyandrostenedione (19-OH-A-dione), which we reported as an amplifier of the action of aldosterone on the basis of the results obtained in bioassays using adrenalectomized rats, were evaluated in rats with the adrenals. The administration of 19-OH-A-dione to the rats caused sodium retention, high blood pressure, suppressed PRA and low plasma aldosterone, corticosterone, and deoxycorticosterone concentrations. The sodium-retaining and hypertensinogenic effects of 19-OH-A-dione were more potent than those of deoxycorticosterone acetate. Spironolactone inhibited the action of 19-OH-A-dione. The results indicate that 19-OH-A-dione, although it is devoid of mineralocorticoid activity, works as a potent sodium-retaining agent and causes a hypertensive state simulating mineralocorticoid excess in the presence of the adrenal cortex.     

Pancreatic exocrine dysfunction associated with mitochondrial tRNA(Leu)(UUR) mutation.

We report on pancreatic exocrine dysfunction in families that have the mitochondrial tRNA(Leu)(UUR) gene mutation. These families exhibited maternally inherited diabetes mellitus (DM) and an A to G substitution at nt 3243 of the mitochondrial tRNA(Leu)(UUR) gene (A3243G mutation). Pancreatic necropsy samples from one proband showed accumulation of degenerated mitochondria in pancreatic acinar cells. Pancreatic exocrine dysfunction was recognised by a functional pancreatic study. This study indicates that exocrine pancreatic dysfunction may be associated with the A3243G mutation.