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This paper makes three points about how the chick corneal epithelium lays down the primary stroma, an orthogonally arranged array of well-spaced, 20-nm-diameter collagen fibrils. (1) Isolated corneal epithelia will, when cultured, lay down de novo stromas whose fibril-diameter distribution, fibril spacing, and proteoglycan profile are similar to those laid down in vivo. They differ from embryonic stromas in two ways: first, much of the chondroitin sulfate is released to the medium and, second, there is a relatively small amount of orthogonal organization. Epithelia seem only to lay down such stromas if they are separated from their original stromas with dispase, which leaves an intact basal lamina, and spread out, basal lamina downward, on a Nuclepore filter (poresize, 0.1 micron). (2) Chondroitin sulfate (CS), the predominant proteoglycan (greater than 85%), seems to play no significant role in collagen fibrillogenesis in vitro. Stromas laid down in its absence were indistinguishable from controls as assayed by fibril diameter, organization, and spacing and the amount of collagen synthesized. For these experiments, epithelia were cultured in the presence of hyaluronidase, which degrades CS, and p-nitrophenyl beta-D-xyloside, which inhibits the formation of links between the core protein and glycosaminoglycan side chains in the PG; the absence of intact CS was confirmed by gel filtration. We suggest that, in vivo, CS may facilitate the interfibrillar movement that takes place as the cornea grows. We have also found that keratinase, which degrades the very small amount of keratan sulfate present in the primary stroma, has no effect on stromal deposition. (3) There are substantial amounts of unidentified matrix components in primary stromas laid down both in vivo and in vitro. This conclusion was drawn from SEM observations on both types of stroma after they had been freeze-dried, a process which does not condense hydrated macromolecules. Even after being treated with hyaluronidase to remove the CS, substantial amounts of interfibrillar matrix were still present. Until these components are identified and their interactions with collagen are understood, the mechanisms responsible for stromal morphogenesis are unlikely to be understood.
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PMID:Does chondroitin sulfate have a role to play in the morphogenesis of the chick primary corneal stroma? 249 96

Steroid sulfatase (STS) activity was studied in the Long-Evans rat testis. The rate of dehydroepiandrosterone sulfate (DHA-S) hydrolysis determined in whole testis homogenates was low compared to that of the corresponding microsomal fractions, which was, in contrast, as high as that expressed in homogenates from purified Leydig cells. Such an increment in STS activity between total homogenates and the corresponding microsomes was not observed for the seminiferous tubules. The STS affinity reported for total testicular microsomes (Km = 3.47 +/- 0.54 microM; mean +/- SEM) was of the same magnitude as that previously reported for Leydig cells, but was about 3 times higher than that measured for whole testis homogenate (Km = 10.11 +/- 0.92 microM). In vivo hCG treatment decreased the STS affinity in total testicular microsomes without affecting this kinetic parameter in whole testis homogenate. These data suggest that the steroid sulfatase expressed in total testicular microsomes (activity and regulation by hCG) could be considered as a good index of Leydig cell STS activity.
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PMID:Steroid sulfatase activity in homogenates, microsomes and purified Leydig cells from adult rat testis. 253 91

The effect of diet on serum estrogen levels was investigated in 17 healthy premenopausal women consuming defined diets prepared in a metabolic unit. During an initial 4-wk control period all women consumed a typical Western diet (40% of total calories from fat, 400 mg cholesterol/d, 12 g dietary fiber/d, and a ratio of polyunsaturated to saturated fatty acids [P:S] of 0.5). After this control period they were switched to a low-fat, high-fiber diet for 8-10 wk, which consisted of 25% of calories from fat, P:S of 1.0, cholesterol of 200 mg cholesterol/d, and 40 g dietary fiber/d. Compared with the control period 16 of 17 women had lower serum estrone sulfate levels on the low-fat, high-fiber diet. There was an average decrease of 36% with mean levels decreasing from 2.11 +/- 0.25 nmol/L (means +/- SEM) on the control diet to 1.29 +/- 0.19 nmol/L on the experimental diet (p less than 0.001). We conclude that a low-fat, high-fiber diet can significantly reduce serum estrone sulfate levels.
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PMID:Low-fat, high-fiber diet and serum estrone sulfate in premenopausal women. 254 3

Responsiveness of gonadotropes to GnRH depends, in part, on the number of plasma membrane GnRH receptors. Since the steady state level of these plasma membrane receptors is a function of the rates of both receptor generation (synthesis, unmasking, and recycling) and loss (internalization, degradation, and inactivation) we have sought to quantify the rate of synthesis of GnRH receptors in pituitary cell cultures. Further, since the protein kinase-C activator phorbol 12-myristate 13-acetate (PMA) has been shown to unmask a class of GnRH receptors that appear to be uncoupled from phosphoinositide turnover, we have measured the rate of synthesis of this second receptor population. The present studies use the density shift technique; incorporation of densely labeled amino acids confers a higher density to newly synthesized proteins and allows their separation by physical means. Cultures of pituitary cells were prepared from female weanling rats. After cells had attached to the culture dishes, medium was replaced at 12-h intervals with medium containing either densely labeled or normal amino acids. After the incubation, GnRH receptors were covalently linked to a photoaffinity receptor agonist [( 125I]Tyr5-[azido-benzoyl-D-Lys6-GnRH]), then solubilized with 1+ sodium dodecyl sulfate. In some cultures PMA (50 nM) was included during the photoaffinity agonist-binding step. Newly synthesized (dense) receptors were separated from previously synthesized receptors by velocity sedimentation (0-20% sucrose in 1% sodium dodecyl sulfate-10 mM Tris-HCl, pH 7.0; centrifuged at 156,000 x g for 24 h). Gradients were fractionated, and the radioactivity contained in each fraction was quantified. Newly synthesized GnRH receptors exhibited a higher density, as evidenced by further migration into the gradient, than did normal GnRH receptors. There was a delay of approximately 6 h between exposure to dense amino acids and the appearance of densely labeled GnRH receptors at the plasma membrane. Equilibrium for incorporation of dense amino acids into GnRH receptors was 48 h of exposure to dense amino acids. The time required for synthesis of half the entire population of GnRH receptors was 28 +/- 2 h (mean +/- SEM; n = 4). Scatchard analysis and the pattern of GnRH-stimulated LH release from densely labeled cells indicated that they bound the photoaffinity label (Kd = 0.4 nM; approximately 1 fmol receptor/microgram DNA) and secreted gonadotropin normally. Additionally, treatment with PMA caused a significant increase (181 +/- 24%) in photoaffinity agonist binding, consistent with previous observations.
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PMID:Synthesis of gonadotropin-releasing hormone receptors by gonadotrope cell cultures: both preexisting receptors and those unmasked by protein kinase-C activators show a similar synthetic rate. 254 92

To characterize the molecular properties conveyed by the isoforms of the alpha subunit of Na,K-ATPase, the two major transepithelial transporting organs in the brine shrimp (Artemia salina), the salt glands and intestines, were isolated in pure form. The alpha isoforms were quantified by ATP-sensitive fluorescein isothiocyanate (FITC) labeling. The salt gland enzyme exhibits only the alpha 1 isoform, whereas the intestinal enzyme exhibits both the alpha 1 and the alpha 2 isoforms. After 32 hours of development, Na,K-ATPase activity [in mumol Pi/mg protein/hr (1 mu)] in whole homogenates was 32 +/- 6 in the salt glands and 12 +/- 3 in the intestinal preparations (mean +/- SEM). The apparent half-maximal activation constants (K1/2) of the salt gland enzyme as compared to the intestinal enzyme were 3.7 +/- 0.6 mM vs. 23.5 +/- 4 mM (P less than 0.01) for Na+, 16.6 +/- 2.2 mM vs. 8.29 +/- 1.5 mM for K+ (P less than 0.01), and 0.87 +/- 0.8 mM vs. 0.79 +/- 1.1 mM for ATP (NS). The apparent Ki's for ouabain inhibition were 1.1 x 10(-4) M vs. 2 x 10(-5) M, respectively. Treatment of whole homogenates with deoxycholic acid (DOC) produced a maximal Na,K-ATPase activation of 46% in the salt gland as compared to 23% in the intestinal enzyme. Similar differences were found with sodium dodecyl sulfate (SDS). The two distinct forms of Na,K-ATPase isolated from the brine shrimp differed markedly in three kinetic parameters as well as in detergent sensitivity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Isoforms of Na,K-ATPase in Artemia salina: II. Tissue distribution and kinetic characterization. 255 Jun 50

The effect of insulin on skeletal growth was examined by (1) systemic injection, (2) local administration into the tibia growth plate and (3) in vitro by use of chondrocytes in culture. (1) Male rats, body weight 60-75 g, were hypophysectomised. One week after the operation, the animals were divided into three groups. Group A received intraperitoneally saline, group B insulin (5-30 U.kg-1.day-1) and group C human growth hormone (250 micrograms/kg/day) for the following 10 days. In addition, on day 10 the rats were injected with 10 mu-Ci 35-S-sulfate intraperitoneally. Twenty-four h later in the non-fasting state plasma glucose, insulin, somatomedin activity (porcine assay), body weight, nose-rump length, width of the tibia growth plate, and the 35-S-sulfate incorporation into rib cartilage were determined. Compared to saline, growth hormone and insulin treatment significantly enhanced body weights, nose-rump lengths, the widths of the proximal tibia growth plates and the incorporation of sulfate into rib cartilage. For the three skeletal growth parameters, growth hormone was more effective than insulin, while body weights did not differ after insulin or growth hormone treatment. Somatomedin activity (U/ml) was low in group A (0.39 +/- 0.04, n = 9, Mean +/- SEM) and group B (0.34 +/- 0.08, n = 8) and high in the growth hormone treated group C (0.90 +/- 0.09, n = 7; p less than 0.002). (2) To test the possibility that insulin might directly augment skeletal growth, insulin (80 mU) was injected into the proximal tibia growth plate of one leg and saline into the cartilage zone of the other leg.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin stimulates skeletal growth in vivo and in vitro--comparison with growth hormone in rats. 266 11

The effects of Ketoconazole (600 mg/day) were evaluated in 10 patients with Cushing's syndrome during a mean period of 4.5 weeks (range 1-12). The urinary free cortisol excretion (UFC) decreased by 21 +/- 15% (mean +/- SEM) (p less than 0.01) on day 1; 54 +/- 8% (p less than 0.0001) on day 2; 60 +/- 15% (p less than 0.0001) on day 3 and 87 +/- 3% (p less than 0.0001) on day 8 compared to baseline. Salivary cortisol at 0800 h decreased similarly. On day 3, 7 patients showed normal UFC values and on day 8, only 1 patient, with the ectopic ACTH syndrome, had persistent hypercortisolism. The cortisol decrease was associated with an increase in desoxycorticosterone values (p less than 0.01) and a decrease in dehydroepiandrosterone sulfate (p less than 0.001), delta 4 androstenedione (p less than 0.05) and testosterone (p less than 0.05). No significant variations were observed in ACTH, 11 desoxycortisol, aldosterone, plasma renin activity, corticosteroid-binding globulin and sex hormone-binding globulin. Side effects were few: mild clinical adrenal insufficiency (n = 5), oedema (n = 3) and reversible hepatic toxicity (n = 1). We conclude that Ketoconazole is an effective inhibitor of cortisol and androgens synthesis. It is well tolerated, rapidly effective and its efficacy persists unchanged for at least one month in all forms of Cushing's syndromes. For these reasons Ketoconazole may be a valuable drug for preoperative treatment of Cushing's syndrome.
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PMID:[Short term effects of ketoconazole in Cushing's syndrome]. 269 87

The polycation protamine sulfate was compared to polybrene, the usual agent employed, for its ability to increase the efficiency of retroviral infection. The murine retroviral vector SAX, which contains the neoR gene and the human adenosine deaminase (ADA) cDNA, was used as a marker of cell infection. SAX viral supernate was titered on NIH 3T3 cells in varying concentrations of polycation. The highest infection efficiency for protamine was seen at 5 micrograms/ml and was 7-fold greater than infections performed in the absence of polycation. Infection efficiency using protamine averaged 92% +/- 11 (SEM) of the highest efficiency obtained with polybrene. Total ADA activity attained when human-ADA deficient T cells were exposed to SAX supernate in the presence of protamine was 83% of that attained with polybrene. The infection rate of mouse bone marrow early progenitor cells (CFU-S) was similar with each polycation. In summary, for supernate infections, concentrations of 5-10 micrograms/ml of protamine provided essentially the same infection efficiency as polybrene with low toxicity on a range of cell types. Since protamine is approved for human use by the U.S. Food and Drug Administration it provides an effective alternative to polybrene when developing human gene therapy protocols.
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PMID:Protamine sulfate as an effective alternative to polybrene in retroviral-mediated gene-transfer: implications for human gene therapy. 278

The mechanism of irritant dermatitis and the immunologic consequences of such reactions are unclear. We evaluated the number and function of epidermal antigen-presenting cells contained in epidermal cell suspensions obtained from normal and irritant patch test reaction sites. Application of sodium lauryl sulfate or croton oil to human skin in vivo resulted in a progressive depletion in the number of epidermal OKT6+HLA-DR+ (T6+DR+) Langerhans cells (LC) from 3.1 +/- 0.2% of total epidermal cells (EC) to 1.2 +/- 0.1% after 8 d (mean values +/- SEM, N = 9). Between 1-4 d irritant patch test sites demonstrated an influx of non-Langerhans cell T6-DR+ cells. These cells were not DR+ keratinocytes but appeared to be of bone marrow derivation because they expressed the marker, HLe1. Among bone marrow derived cells, the T6-DR+EC appeared to be of monocyte, macrophage lineage, because they expressed the determinant recognized by the OKM5 (M5) antibody. Despite the induction of M5+DR+EC the total number of DR+EC showed progressively decreasing percentages over an 8-d period. Partial recovery to 73 +/- 12% of control value was observed at 2 weeks, with full recovery by 4 weeks after challenge. Concomitantly with the depletion of DR+EC, the capacity of EC to present alloantigens to T cells decreased. This reduction in antigen-presenting cell activity was strongly correlated to the reduction in total DR+ EC (r = 0.94, p less than 0.05). Thus, the capacity of irritants such as croton oil to abrogate the function of epidermal antigen-presenting cells may be related to the tumor promoting potential of these agents.
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PMID:Decreased number and function of antigen-presenting cells in the skin following application of irritant agents: relevance for skin cancer? 278 39

Plasma copper and ceruloplasmin concentrations at ages 0, 2, 4, 6, 9, and 12 mo were longitudinally evaluated in our Finnish nutritional survey of 200 infants. The infants, who were weaned by age 3.5 mo, were randomly assigned to receive either a liquid cow-milk-based formula containing 1.3 mumol Cu/L (n = 16) or the same formula supplemented with 7.8 mumol Cu/L as Cu sulfate (n = 16). They were compared with exclusively breast-fed infants. Plasma Cu and ceruloplasmin concentrations increased steadily and similarly in all three groups from 4.6 +/- 0.2 mumol/L (means +/- SEM) and 0.9 +/- 0.1 mumol/L, respectively, in umbilical samples to 19.7 +/- 0.3 mumol/L and 3.2 +/- 0.1 mumol/L, respectively, at age 12 mo. Our results indicate that concentrations of plasma Cu and ceruloplasmin in healthy full-term infants are resistant to dietary supplementation.
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PMID:Copper supplementation: failure to increase plasma copper and ceruloplasmin concentrations in healthy infants. 280 90


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