Elevated blood pressure and risk of end-stage renal disease in subjects without baseline kidney disease

BACKGROUND: Many cases of end-stage renal disease (ESRD) are ascribed to hypertension. However, because renal disease itself can raise blood pressure, some investigators argue that ESRD seen in patients with hypertension is due to underlying primary renal disease. Previous cohort studies of the relationship between blood pressure and ESRD did not uniformly screen out baseline kidney disease. METHODS: We conducted a historical cohort study among members of Kaiser Permanente of Northern California, a large integrated health care delivery system. The ESRD cases were ascertained by matching with the US Renal Data System registry. RESULTS: A total of 316 675 adult Kaiser members participated in the Multiphasic Health Checkups from 1964 to 1985. All subjects had estimated glomerular filtration rates of 60 mL /min per 1.73 m(2) or higher and negative dipstick urinalysis results for proteinuria or hematuria. During 8 210 431 person-years of follow-up, 1149 cases of ESRD occurred. Compared with subjects with a blood pressure less than 120/80 mm Hg, the adjusted relative risks for developing ESRD were 1.62 (95% confidence interval [CI], 1.27-2.07) for blood pressures of 120 to 129/80 to 84 mm Hg, 1.98 (95% CI, 1.55-2.52) for blood pressures of 130 to 139/85 to 89 mm Hg, 2.59 (95% CI, 2.07-3.25) for blood pressures of 140 to 159/90 to 99 mm Hg, 3.86 (95% CI, 3.00-4.96) for blood pressures of 160 to 179/100 to 109 mm Hg, 3.88 (95% CI, 2.82-5.34) for blood pressures of 180 to 209/110 to 119 mm Hg, and 4.25 (95% CI, 2.63-6.86) for blood pressures of 210/120 mm Hg or higher. Similar associations between blood pressure level and ESRD risk were seen in all subgroup analyses. CONCLUSIONS: Even relatively modest elevation in blood pressure is an independent risk factor for ESRD. The observed relationship does not appear to be due to confounding by clinically evident baseline kidney disease.     

A modified cell culture method for autologous chondrocyte transplantation

Autologous chondrocyte transplantation (ACT) is a promising method to treat chondral and osteochondral defects. This study introduced a modified method for cell culture in ACT. Porcine chondrocytes were cultured for 3 weeks under low hydrostatic pressure at 250 Pa. The results showed that the dry weight of the cartilage-like membrane in the loading group was 3.0 times more than the control group (no loading) (p < 0.01), and cell numbers were significantly increased by 3.1 times (p < 0.01) after a 3-week culture. Compared with the fresh tissue sample, the mRNA expression of collagen II was not statistically different and the mRNA of aggrecan was only slightly decreased by 19%. These data suggest that the hydrostatic pressure at this level significantly increased the cell numbers and biosynthesis of cultured chondrocytes.     

Green tea polyphenol-induced epidermal keratinocyte differentiation is associated with coordinated expression of p57/KIP2 and caspase 14

Epigallocatechin-3-gallate (EGCG), the most abundant polyphenol in green tea, exerts chemopreventive effects by selectively inducing apoptosis in tumor cells. In contrast, EGCG accelerates terminal differentiation in normal human epidermal keratinocytes (NHEK) mediated partially by up-regulation of p57/KIP2, a cyclin-dependent kinase inhibitor that confers growth arrest and differentiation. However, it is unclear if EGCG modulates caspase 14, a unique regulator of epithelial cell terminal differentiation associated with cornification. Here, we examined the effect of EGCG on caspase 14 expression in NHEK and correlated the protein and mRNA expression of p57/KIP2 with those of caspase 14 in either normal keratinocytes or p57/KIP2-expressing tumor cells (OSC2, an oral squamous cell carcinoma cell line). Additionally, paraffin-embedded normal and untreated psoriatic (aberrant keratinization) skin sections from humans were assessed for caspase 14 by immunohistochemistry. In NHEK, EGCG induced the expression of caspase 14 mRNA and protein levels within a 24-h period. The expression of p57/KIP2 in OSC2 cells was adequate to induce caspase 14 in the absence of EGCG; this induction of caspase 14 was down-regulated by transforming growth factor-beta1. In human psoriatic skin samples, caspase 14 staining in the upper epidermis was reduced, especially in nuclear areas. These results suggest that, in addition to p57/KIP2, EGCG-induced terminal differentiation of epidermal keratinocytes involves up-regulation of caspase 14. Further understanding of how EGCG modulates cellular differentiation may be useful in developing green tea preparations for selected clinical applications.     

Relationship of a leukemia-associated antigen to the presence of lymphoblasts in the peripheral blood in children with acute lymphocytic leukemia

Peripheral blood samples from 57 children with newly diagnosed E- rosette-negative, surface-immunoglobulin negative acute lymphocytic leukemia (ALL) were studied for the presence of a leukemia-associated antigen (ALLA). Ficoll-Hypaque separated cells were tested using a rabbit antiserum to human null lymphoblasts and an indirect immunofluorescent assay. The percentage of ALLA-positive cells were compared to the percentage of lymphoblasts determined by differential counts of a Wright-Giemsa-stained smear of a concurrently obtained peripheral blood sample. The mean ratio of percentage of lymphoblasts to percentage of ALLA-positive cells was 0.90. However, in 13 patients, the ratio of percent of ALLA-positive cells to percent of lymphoblasts was equal to or greater than 2:1. In the blood of 6 additional children (5 newly diagnosed, 1 relapsed patient) in whom no morphologically identifiable lymphoblasts were detected. ALLA-positive cells were present (7%-49%). These results indicate that testing for ALLA-positive cells in a sensitive technique for detection of leukemic cells in children with ALLA-positive ALL.     

Aromatic alkylamine N-acetyltransferase in regional tissues of developing rat brain

The specific activities of N-acetyltransferase (EC 2.3.1.5) were examined in several regions of rat brain of both sexes at various times after birth. The enzyme activity increased with development in whole brain, hippocampus, midbrain, cerebellum and the remainder of brain, peaking around 36 days of age. Lineweaver-Burk plots indicated linear kinetics for N-acetyltransferase in dialyzed supernatant and ammonium sulfate precipitates from the newborn rat brain, whereas enzyme preparation further purified by Bio Gel yielded biphasic kinetics. These data remain consistent with the possibility that there are two forms of N-acetyltransferase in rat brain even from birth.     

Immunologic reactivity in patients with nasopharyngeal carcinoma

Immunologic reactivity was measured in 344 patients with nasopharyngeal carcinoma (NPC), before treatment, and in 398 age-matched control subjects. The data recorded suggest that depressed cell-mediated immunity in patients with NPC is a consequence rather than a cause of the disease. In order to reduce tumor burden in patients with NPC, radiation therapy with chemotherapy or immunopotentiation or both is recommended.     

Studies using releasing factors in Klinefelter's Syndrome: The responses of LH and FSH to luteinizing hormone-releasing hormone and of prolactin and TSH to thyrotropin-releasing hormone before and after testosterone

(1) During an investigation of their pituitary function, the TSH prolactin (PRL) and gonadotropin, (LH, FSH) response to TRH was measured in four patients with documented euthyroid Klinefelter's syndrome. (2) In all four patients, the serum testosterone was low, the gonadotropins were elevated and thyroid antibodies undetectable. (3) The identical study was repeated after each patient had received intramuscular testosterone cypionate 200 mg bi-weekly for three doses. This raised the serum testosterone at least four-fold. (4) Basal TSH was normal in all four patients but its response to TRH was blunted (mean peak TSH 9.6 μU/ml), compared with normal controls (mean peak TSH 18 μU/ml). Following testosterone this response to TRH was further suppressed to a mean peak of 3.4 μU/ml TSH. (5) Basal PRL levels were also normal and the mean peak response to TRH, 28 ng/ml. When repeated after testosterone, TRH produced a mean peak PRL of 58 ng/ml. (6) LH and FSH, both elevated basally, did not change with TRH administration, but both were stimulated by LHRH 100 μg i.v., LH briskly, FSH more variably. (7) FSH was suppressed sharply but LH only partially with testosterone therapy. (8) Our studies indicate that the TSH response to TRH in Klinefelter's syndrome is blunted and further suppressed with short term testosterone replacement. The PRL response to TRH under these same circumstances, however, is enhanced. Previous reports of abnormal LH feedback control are confirmed. (9) Klinefelter's syndrome is associated with subtle abnormalities in hypothalamic pituitary regulation not expected in typical primary hypogonadism.