Preferential expression of insulin-like growth factor binding proteins-1, -3, and -5 during early diabetic renal hypertrophy in rats

The renal insulin-like growth factor-I (IGF-I) system has been implicated in the pathogenesis of renal hypertrophy, altered hemodynamics, and extracellular matrix expansion associated with early diabetes. The relative abundance of IGF binding proteins (IGFBPs) in the renal microenvironment may modulate IGF-I actions. However, the precise IGFBPs expressed in the glomerular and tubulointerstitial compartments during diabetic renal growth have not been characterized. In the present study, in situ hybridization studies were performed to examine the expression of IGFBP-1 to -6 messenger RNAs (mRNAs) 3, 7, and 14 days after streptozotocin (STZ) injection in rats. In control, nondiabetic kidneys, all six IGFBP mRNAs were differentially expressed with a predominance of IGFBP-5. The onset of renal hypertrophy in STZ-induced diabetes was associated with a rapid and site-specific induction of IGFBP-1, -3, and -5 mRNAs. In contrast, basal expression of IGFBP-2, -4, and -6 mRNAs was not altered in diabetic rats. IGFBP-5 mRNA expression increased in diabetic glomeruli, cortical, and inner medullary peritubular interstitial cells at days 3, 7, and 14. Although normal glomeruli failed to express IGFBP-3, it was induced concomitantly with IGFBP-5 in diabetic glomeruli and cortical peritubular interstitial cells. IGFBP-1 mRNA levels also increased in cortical tubular cells at each time point tested. Peak induction of IGFBP-3 and -5 was observed at day 3, whereas IGFBP-1 was delayed until day 7. IGFBP-1, -3, and -5 mRNA levels declined by day 14, but remained persistently elevated above control. By immunoperoxidase staining, similar alterations in the pattern of IGFBP-3 and -5 protein expression were observed at each time point. The preferential and site-specific increase in IGFBP-1, -3, and -5 suggest that these IGFBPs may regulate the local autocrine and/or paracrine actions of IGF-I and contribute to the pathogenesis of the early manifestations of diabetic nephropathy.     

Extensive Aberrant Mongolian Spot

A 9-month-old male infant had generalized diffuse blue-gray pigmentation over most of his body, sparing the scalp, face, neck, palms, soles, periumbilical area, genital area, and nipples. Within the lesion, there were several conspicuous macules of considerably darker hue. Histologic examination revealed numerous dermal melanocytes. By 16 months of age, the child's blue-gray pigmentation had decreased substantially.     

Flavonoids ofElscholtzia cristata

Apigenin, apigenin-7-O-glucoside, luteolin-7-O-glucoside and linarin were isolated fromElscholtzia cristata (Labiatae).     

Immobilization and characterization of beta-galactosidase in thermally reversible hydrogel beads

Beta-Galactosidase has been immobilized within thermally reversible hydrogel beads and has been studied in batch and packed bed reactor systems. The enzyme was entrapped in a copolymer hydrogel of N-isopropylacrylamide (NIPAAm) and acrylamide (AAm) as beads were formed in an inverse suspension polymerization. A reversible deswelling and reswelling of the hydrogel matrix was induced by first warming and then cooling through 37-40 degrees C, which is the lower critical solution temperature, LCST, of the backbone copolymer. The optimum temperature for maximum activity of the immobilized enzyme-gel bead system was found to be 30-35 degrees C in a batch mode and 40 degrees C in a packed bed reactor, which were both below the 50 degrees C optimum for the free enzyme. These differences are understandable, since the mass transfer rates of substrate and product within the pores of the gel matrix are controlled mainly by the temperature, so therefore it is the temperature which governs the overall activity of the immobilized enzyme system. It was also found that when the operational temperature in the packed bed reactor was cycled between temperatures below (35 degrees C) and above (45 degrees C) the copolymer gel LCST, the activity of the immobilized enzyme almost fully recovered after each cycle. In fact, the enzyme-gel system exhibited a complete "shut-off" in activity at 50 degrees C which was the temperature where the free enzyme showed its maximum activity. The thermal cycling operation of LCST enzyme-gel beads can be used to enhance overall activity and productivity of a packed bed reactor, when compared to isothermal operation of this reactor. This is due to the thermally induced "pumping" which enhances mass transfer rates of substrate in and product out of the gel beads.     

Using serum cholesterol to identify high risk and stimulate behavior change: will it work?

If the measurement of serum cholesterol is to be used to identify a sub-population at high risk of subsequent disease and to stimulate behavior change in this group to lower serum cholesterol, the test must be able to both discriminate and motivate the group. The ability of the test to motivate has been documented in a randomized trial. This paper therefore tests, in a cohort of United States men ages 40-59 at entry, the ability of serum cholesterol to discriminate between individuals who would and would not die from coronary heart disease. While risk of death increased with increasing serum cholesterol, the values for men who developed coronary heart disease overlapped the values of the men who did not develop the disease. Overall test accuracy declined from 92% correctly classified when 5% of the population was defined as "at high risk" to 55% when 50% of the population was defined as "at high risk". On a receiver operating curve, defining 5% of the men as "high risk" yielded a false positive rate of 5% and a true positive rate of 8%. Increasing the proportion of men defined as "at high risk" to 50% increased the true positive rate to 75% but also increased the false positive rate to over 50%. Monte Carlo simulation demonstrated that lowering mean serum cholesterol 0.78 mmol/l in the entire population would lower deaths from coronary heart disease by 28%. The same effect could be achieved by lowering the serum cholesterol of all people in the top 20% of the distribution to 4.66 mmol/l.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differences among hospitals in Medicare patient mortality.

Using hospital discharge abstract data for fiscal year 1984 for all acute care hospitals treating Medicare patients (age greater than or equal to 65), we measured four mortality rates: inpatient deaths, deaths within 30 days after discharge, and deaths within two fixed periods following admission (30 days, and the 95th percentile length of stay for each condition). The metric of interest was the probability that a hospital would have as many deaths as it did (taking age, race, and sex into account). Differences among hospitals in inpatient death rates were large and significant (p less than .05) for 22 of 48 specific conditions studied and for all conditions together; among these 22 "high-variation" conditions, medical conditions accounted for far more deaths than did surgical conditions. We compared pairs of conditions in terms of hospital rankings by probability of observed numbers of inpatient deaths; we found relatively low correlations (Spearman correlation coefficients of 0.3 or lower) for most comparisons except between a few surgical conditions. When we compared different pairs of the four death measures on their rankings of hospitals by probabilities of the observed numbers of deaths, the correlations were moderate to high (Spearman correlation coefficients of 0.54 to 0.99). Hospitals with low probabilities of the number of observed deaths were not distributed randomly geographically; a small number of states had significantly more than their share of these hospitals (p less than .01). Information from hospital discharge abstract data is insufficient to determine the extent to which differences in severity of illness or quality of care account for this marked variability, so data on hospital death rates cannot now be used to draw inferences about quality of care. The magnitude of variability in death rates and the geographic clustering of facilities with low probabilities, however, both argue for further study of hospital death rates. These data may prove most useful as a screening mechanism to identify patterns of potentially poor quality of care. Careful choice of the mortality measure used is needed, however, to maximize the probability of identifying those hospitals, and only those hospitals, warranting more in-depth review.     

Immunochemical characterization of cytochrome P-450 isozymes responsible for benzene oxidation in the rat liver

The contribution of cytochrome P-450 isozymes to benzene metabolismin liver microsomes from fed, fasted, pyrazole-, pbenobarbital(PB)- and ethanol-treated rats and in respective isocaloriccontrols was investigated using monoclonal antibodies (mAbs).Clone 1-7-1 mAb did not inhibit benzene metabolism, whereasclone 2-66-3 inhibited only in PB-induced microsomes at a highconcentration of benzene (6.26 mM), and clone 1-91-3 mAb inhibitedbenzene metabolism in all cases. The degree of inhibition wasas follows: fed isocaloric control PB < fasted < pyrazole ethanol. The pattern of inhibition was similar with clone 1-91-3for low (0.23 mM) and high concentrations of benzene, exceptin PB-induced mkrosomes. Western blot analysis showed that clone1-7-1 mAb did not bind any liver mkrosomal protein in the regionof cytochrome P-450s, whereas with clone 2-66-3 a clear-cutband was seen only in liver microsomes from PB-treated rats,with clone 1-98-1, a band was detected in mkrosomes from alltreated groups, in the following order: PB = isocaloric control< fed < fasted < pyrazole < ethanol. These resultsindicate that (i) cytochromes P-450b,e and P-450J contributeto benzene metabolism in rat liver; (ii) the former has a lowaffinity to benzene and is induced by PB; and (iii) P-450J hasa high affinity to benzene and is induced by 1-day fasting,pyrazole and ethanol, but decreased by PB treatment.     

Overexpression of S100A4 is closely related to the aggressiveness of gastric cancer

Elevated levels of the calcium-binding protein S100A4 cause metastasis of benign rat mammary tumor cells. To investigate whether S100A4 plays an important role in the invasion and metastasis of gastric cancers, we examined the gene mutations in the coding regions and expression patterns of the S100A4 in gastric adenocarcinoma in Korea. Moderate to strong expression of S100A4 was found in 53 (68.8%) of the 77 gastric adenocarcinomas, whilst normal gastric epithelium either failed to stain or showed weak staining. Interestingly, S100A4 expression was more frequently observed in gastric cancer patients with advanced gastric cancer (p=0.039), positive lymph node metastasis (p=0.001), and peritoneal dissemination (p=0.022). No gene mutations were found in the analyzed genomic area in 77 gastric adenocarcinomas and 15 gastric cancer cell lines. We found one single nucleotide polymorphism without an amino acid change, A99G, in two cases. These data suggest that the overexpression of S100A4 may be closely related to the aggressiveness of gastric cancer in Korea.     

Comparative analysis of NK/T-cell lymphoma and peripheral T-cell lymphoma in Korea: Clinicopathological correlations and analysis of EBV strain type and 30-bp deletion variant LMP1

Natural killer/T-cell lymphoma (NKTL) and peripheral T-cell lymphomas (PTCL) are prevalent in the Asian population and exhibit a high association with the Epstein-Barr virus (EBV). Moreover, differentiation of these two groups is often difficult and problematic. We investigated 35 cases of NKTL (22 nasal cases and 13 extranasal cases) and 30 cases of PTCL in terms of their clinical features, immunohistology, EBV positivity, EBV strain-type polymorphism and latent membrane protein 1 (LMP1) deletion variant distribution. Eighteen cases (82%) of nasal NKTL and seven (54%) of extranasal NKTL showed EBV positivity by EBV in situ hybridization. Fifteen cases (50%) of PTCL revealed EBV positivity. EBV strain type A was predominant in NKTL (18:5), and EBV strain types A and B were distributed evenly in PTCL (6:6). EBV-positive patients had significantly shorter survival than EBV-negative patients (P < 0.05), and EBV positivity correlated with advanced clinical stage (P < 0.05). Patients harboring type A EBV showed slightly poorer prognoses than those having type B, though it was not obviously statistically different (P = 0.07). The LMP1 deletion variant was prevalent in both NKTL (three wild-type LMP1, 15 deletion variants) and PTCL (three wild-type LMP1, eight deletion variants, two coexistent forms) patients, but did not have prognostic impact. Our results indicate that EBV acts as a negative prognostic factor in NKTL and PTCL, and that the intrinsic properties of a specific viral strain might influence the clinical behavior of these diseases.