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Dietary soy protein effects on disease and IGF-I in male and female Han:SPRD-cy rats.BackgroundDietary soy protein compared with casein retards disease progression in a gender-specific manner in the pcy mouse. In this model of polycystic kidney disease (PKD), kidney insulin-like growth factor-I (IGF-I) levels are elevated. The present study examined the gender-specific effects of soy protein feeding on disease and IGF-I in Han:SPRD-cy rats.MethodsNormal (+/+) and affected (cy/+) weanling male and female Han:SPRD-cy rats were given either casein- or soy protein-based diets for six weeks. Renal size, water content, cyst size and IGF-I, serum creatinine, urea and IGF-I, and creatinine clearance were determined.ResultsSoy protein-fed cy/+ animals had lower kidney weight, water content and cyst size, lower serum urea and creatinine, and higher creatinine clearance. In cy/+ females, dietary soy protein resulted in normalized serum creatinine and creatinine clearance. Kidney IGF-I levels (ng/kidney) were 32 to 76% higher in cy/+ compared with +/+ groups (P < 0.001). Soy protein feeding resulted in lower kidney IGF-I in cy/+ males (1123 vs. 1496 ng/kidney, P < 0.001) and cy/+ females (816 vs. 943 ng/kidney, P < 0.05). In males, soy protein feeding resulted in lower serum IGF-I concentrations in +/+ (1439 vs. 1708 ng/mL, P < 0.05) and in cy/+ (1483 vs. 2073 ng/mL, P < 0.001) animals.ConclusionsDietary soy protein compared with casein delays the progression of disease in male and female Han:SPRD-cy rats. Overall, IGF-I was lower in +/+ animals, in females, and in animals consuming the soy protein diet, supporting a role for IGF-I in the pathogenesis of disease in the Han:SPRD-cy rat and an ameliorating role for dietary soy protein.

BACKGROUND The macrofollicular variant of papillary thyroid carcinoma that is the subject of this study has only recently been characterized. Information about its morphologic spectrum and biologic behavior is limited. METHODS The authors reviewed 29 examples, including 17 previously reported cases. The clinical and pathologic features of five patients who had the macrofollicular variant of papillary thyroid carcinoma with a minor insular component were analyzed in detail. The insular component in thyroid carcinomas has been associated with aggressive clinical behavior. RESULTS The ages of the 5 patients ranged from 31 to 70 years; the mean age was 40 years. Three patients presented with a palpable thyroid nodule and two with a large thyroid mass of long duration. The latter two tumors, which metastasized, were the largest (8 and 11 cm) and showed extrathyroidal and blood vessel invasion. All five tumors were composed predominantly of macrofollicles (>50%) and had a minor insular component that comprised less than 5% of the tumor mass. In most tumors, the macrofollicles were lined by cells with large, clear, grooved nuclei, and all five contained areas of conventional follicular variant of papillary thyroid carcinoma. In the two that metastasized, however, the lining of many macrofollicles consisted of cuboidal cells with small, hyperchromatic, follicular-type nuclei. Only the macrofollicular component was identified in the metastatic deposits in these two patients. All five patients were alive at last follow-up, two with metastases; but follow-up for this study is limited. CONCLUSIONS A minor insular component is an additional feature of the macrofollicular variant of papillary thyroid carcinoma that may aid in diagnosis and does not appear to have an adverse effect on the excellent prognosis of patients with these tumors. Cancer 1997; 80:1110-6. © 1997 American Cancer Society.

Reperfusion after ischemia induces cytokines, chemoattractant chemokines, adhesion molecules, and nitric oxide (NO). The resultant neutrophil adherence and NO potentiates renal injury. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a potent anti-inflammatory agent that inhibits neutrophil migration and production of neutrophil chemokines and NO. Since neutrophils and NO promote renal ischemic injury, we sought to determine if alpha-MSH inhibits renal injury in a model of bilateral renal ischemia. alpha-MSH significantly reduced ischemia-induced renal damage, measured by changes in renal histology and plasma blood urea nitrogen and creatinine in mice. alpha-MSH significantly decreased tubule necrosis, neutrophil plugging, and capillary congestion. Delay of alpha-MSH treatment for 6 h after ischemia also significantly inhibited renal damage. alpha-MSH also significantly inhibited ischemic damage in rats. To begin to determine the mechanism of action of alpha-MSH, we measured its effects on mediators of neutrophil trafficking and induction of the inducible isoform of NO synthase-II. alpha-MSH inhibited ischemia-induced increases in mRNA for the murine neutrophil chemokine KC/IL-8. alpha-MSH also inhibited induction of mRNA for the adhesion molecule ICAM-1, which is known to be critical in renal ischemic injury. alpha-MSH inhibited nitration of kidney proteins and induction of NO synthase-II. We conclude: (a) alpha-MSH protects against renal ischemia/reperfusion injury; and (b) it may act, in part, by inhibiting the maladaptive activation of genes that cause neutrophil activation and adhesion, and induction of NO synthase.

Grafting with split-thickness autograft skin remains the most effective method for treating burn wounds. When insufficient donor sites are present, decreasing the time required for healing of available donor sites permits more frequent reharvests to continue the grafting process. Cultured human keratinocytes speed wound healing by providing cover and by producing growth factors and extracellular matrix proteins. In this study we compare the rates of healing induced by allografts of cultured keratinocytes applied to split-thickness donor sites with healing by a standard treatment. Sheets of cultured human keratinocytes derived from neonatal foreskins are applied to a portion of a split-thickness donor site while the remainder is covered with a temporary skin substitute. The wound is inspected at 5, 7, 9, 11, 14, 17, 20, and 23 days. Biopsies are obtained at 7 days for light and electron microscopy. In 10 patients the average time to healing for sites covered with keratinocytes was 6.6 +/- 1.96 days compared with 12.6 +/- 4.32 days for control sites (p < 0.002). By day 7 most keratinocyte-covered sites showed reepithelization with the formation of a basement membrane and hemidesmosomes at the dermal-epidermal junction. Control areas were unhealed without epithelial coverage. The reepithelized donor sites from three patients treated with cultured keratinocytes were reharvested. In each case these grafts took, and they were equivalent to skin used from donor sites harvested for the first time. Keratinocyte allografts speed healing of split-thickness donor sites, thereby increasing the availability of autograft skin for burn wound coverage.

Localization of the ROMK potassium channel to the apical membrane of distal nephron in rat kidney. Background The apical potassium (K + ) channels mediate K + recycling in thick ascending limb (TAL) and K + secretion in cortical collecting duct (CCD). Recently, the cDNAs for a family of renal K + channels, ROMK1, -2 and -3, were identified. Based on the biophysical properties and mRNA distribution, it is believed that these ROMK cDNAs encode the apical K + channels of TAL and CCD. However, the information for cellular and subcellular localization of the ROMK proteins in these tubules is still not available. Methods Paraffin or frozen kidney sections from adult Sprague-Dawley rats were stained by polyclonal antibodies against the N- and C-terminal domain of ROMK. Immunoreactive staining was visualized by color development from horseradish peroxidase reaction. Membrane homogenates from kidney were analyzed by Western blot analysis. Results The polyclonal antibodies against cytoplasmic epitope of ROMK recognized a ∼42 kD protein in the membrane homogenates from kidney, but not from liver. Staining by immunocytochemistry revealed that ROMK channels were localized to the apical membranes of the distal nephron in cortex and outer medulla, including thick ascending limb and collecting tubule. ROMK staining was absent in glomerulus, proximal tubule and inner medulla. Double staining of the tissue section with both ROMK-specific and H + -ATPase-specific antibodies revealed labeling of ROMK in the principal cells of the collecting tubules. Conclusions These results further strengthen the idea that ROMK channels play important roles in the recycling of K + in TAL and the secretion of K + in CCD.

The effects of dietary soy protein compared to casein were examined in male and female CD1-pcy/pcy (pcy) mice with polycystic kidney disease. Animals 10 wk of age were fed purified diets containing either soy protein isolate or casein given at a level of 17.4 or 6% protein. After 13 wk on the diets, body weights and serum concentrations of albumin and protein indicated that protein nutrition was adequate on all diets. Overall, animals fed soy protein versus casein had 28% lower (P = 0.0037) relative kidney weights (g/100 g body wt), 37% lower (P = 0.0089) cyst scores (% cyst area x relative kidney weight), and 25% less (P = 0.0144) kidney water (g). Dietary protein reduction resulted in 30% lower (P = 0.0010) relative kidney weights, 25% lower (P = 0.0327) cyst scores, and 35% less (P = 0.0001) kidney water. Analysis of interactions between main effects revealed that the effects of soy protein on kidney size were significant only in females, and that effects of soy protein on cyst score were significant only in animals on the low protein diets. In addition, differences in kidney weights and cyst score due to protein reduction were significant in animals fed soy protein, but not in those fed casein as the protein source. These results show that both dietary protein source and level significantly affect polycystic kidney disease in pcy animals, with the effects of dietary soy protein being most pronounced in female animals fed the low protein diets and the effects of protein reduction being most pronounced in animals fed soy protein-based diets.