Biomedical subjects

P S Li

Publications and source records attributed to P S Li.

At least 19 recordsLinked to original sources

PubMed2004

Correlation of ultrasonographic and orchidometer measurements of testis volume in adults.

OBJECTIVE: To determine the correlation between testicular volume measured with an orchidometer or high-resolution scrotal ultrasonography (US) with colour-flow Doppler analysis. PATIENTS AND METHODS: In all, 159 men (mean age 36.6 years) presenting for infertility evaluation underwent both a physical examination by a one experienced examiner and high-resolution US with colour-flow Doppler analysis. An orchidometer was also used to measure testicular volume after stretching the scrotal skin tightly over the testis and after warming with a heating pad. The US was interpreted by a radiologist who had no knowledge of the orchidometer estimates. The volume was calculated as 0.71 x length x width x height. RESULTS: For the right testes the mean orchidometer and US estimates were 18.4 and 18.3 mL, yielding a correlation coefficient of 0.72 (r (2) = 0.52, P < 0.01). On the left the respective values were 17.1 and 16.9 mL, with a correlation coefficient of 0.69 (r (2) = 0.48, P < 0.01). CONCLUSION: Orchidometer estimates of testicular volume correlate closely and very significantly with US estimates in adults. In the hands of an experienced examiner orchidometer measurements provide an accurate, rapid and inexpensive assessment of testicular volume.

Adult↗

PubMed2002

Is bag urine culture useful in monitoring urinary tract infection in infants?

OBJECTIVES: We studied the false-positive rate of bag urine cultures in diagnosing bacteriuria in infants and examined the factors responsible for contamination. METHODS: One hundred asymptomatic patients with previous urinary tract infections (UTI; age range 5-23 months; sex ratio M : F 73:27) were screened by bag urine cultures and confirmed by suprapubic aspiration or catheterization. Those producing contaminated and clean samples were interviewed with a standard questionnaire. RESULTS: Sixty patients had insignificant growth and 40 had doubtful or mixed growth. After further interview and instructions, the latter group produced a second bag urine sample with negative results in 23 and positive results in 17. Among the latter, UTI was confirmed in five and excluded in 12 cases. The false-positive rate of first urine collection was 36.8%. Comparing patients with contaminated urine to those with negative urine samples, we found the former were associated with waiting for more than one void to complete urine collection, and with uncircumcised boys. Other factors did not reach statistical significance. Proper counselling and repeating a second culture reduced the overall false-positive rate to 12.6%. CONCLUSION: In our population, the contamination rate of one bag urine culture was 36.8%, which is unacceptable and alternative methods need to be sought. Contamination was associated with improper collection procedures and with uncircumcised boys. Proper instructions and doing a second urine culture reduced the overall rate to 12.6%, but at the expense of delaying diagnosis and treatment.

Bacteriuria↗

PubMed2001

Protein phosphatase inhibitor cantharidin inhibits steroidogenesis and steroidogenic acute regulatory protein expression in cultured rat preovulatory follicles.

The effect of cantharidin, a natural toxicant of blister beetles and a strong inhibitor of protein phosphatases types 1 and 2A, on luteinizing hormone (LH)-induced synthesis of steroidogenic acute regulatory (StAR) protein was studied in a serum-free culture of preovulatory follicles. StAR protein is a steroidogenic tissue-specific, hormone-induced, rapidly synthesized protein previously shown to be involved in the acute regulation of steroidogenesis, probably by promoting the transfer of cholesterol to the inner mitochondrial membrane and the cytochrome P450 side-chain cleavage (P450scc) enzyme. Treatment of preovulatory follicles dissected from ovaries of immature rats primed with pregnant mares' serum gonadotropin (10 IU) with LH for 24 h resulted in a dose-dependent increase in the level of StAR protein that reached a maximum at 100 ng LH/ml. This increase was associated with an increase in progesterone production. Treatment of follicles with increasing concentrations (10 - 1000 ng/ml) of cantharidin suppresssed LH (100 ng/ml)-induced StAR protein levels and progesterone production in a dose-dependent manner. The amount of P450scc protein and the conversion of 22R-hydroxycholesterol to progesterone were not affected by cantharidin. This indicates that cantharidin did not interfere with the activity of P450scc. Cantharidin also decreased StAR protein levels and progesterone production induced by the adenylate cyclase activator forskolin (10(-5) M) or a cAMP analog 8-Br-cAMP (0.5 mM). These results demonstrate that cantharidin inhibits the LH-induced StAR protein levels, and, thus, suggest that phosphoprotein phosphatase activity is required for the cAMP-protein kinase A-stimulated steroidogenic activity of the preovulatory follicle.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2001

Expression of human BRE in multiple isoforms.

BRE, a putative stress-modulating gene, found able to down-regulate TNF-alpha-induced NF-kappaB activation upon overexpression, is now shown in human cells expressed as multiple mRNA isoforms. A total of six isoforms are produced by alternative splicing predominantly at either end of the gene. Predicted from the cDNA sequences of these isoforms, three of them (alpha(a), alpha(b), and alpha(c)) code for BRE of different C-terminus, and the other three (beta(a), beta(b), and beta(c)) may possibly be the nonfunctional counterparts. All human cells examined coexpress all the predominant splice variants, albeit at different ratios. Comparing with normal cells, immortalized human cell lines uniformly express higher levels of BRE. Interestingly, peripheral blood monocytes responded to LPS by down-regulating the expression of all the BRE isoforms, which was however less obvious in the cell line counterpart, THP-1. Isoform alpha(a), which codes for the canonical BRE with a C-terminal peroxisomal targeting sequence, is the most abundant transcript. We propose that the function of BRE and its isoforms is to regulate peroxisomal activities.

Animals↗

PubMed2001

Dexamethasone enhances follicle stimulating hormone-induced P450scc mRNA expression and progesterone production in pig granulosa cells.

The effect of dexamethasone on follicle-stimulating hormone (FSH)-stimulated expression of cholesterol side-chain cleavage (P450scc) enzyme and production of progesterone by ovarian granulosa cells was studied in vitro. Granulosa cells from 3- to 5-mm pig antral follicles were cultured for 48 h in the presence or absence of FSH and/or dexamethasone. Treatment with FSH resulted in a dose-dependent increase in the level of P450scc mRNA that reached a submaximum at 100 ng FSH/ml. This increase was associated with an increase in progesterone production. Treatment of the cells with increasing concentrations (10(-9)-10(-6) M) of dexamethasone for 48 h increased constitutive and potentiated FSH-stimulated P450scc mRNA levels and progesterone production in a dose-dependent manner. Increasing duration (12-48 h) of treatment with dexamethasone (100 nM) led to a time-dependent increase in basal and FSH-stimulated progesteorne production, achieving statistical significance by 48 and 24 h, respectively. Dexamethasone also increased P450scc mRNA level and progesterone production induced by the adenylate cyclase activator forskolin (10 microM) or a cAMP analog 8-Br-cAMP (1 mM). The effects of dexamethasone on FSH-induced progesterone production were blocked by cotreatment of the cells with glucocorticoid receptor antagonist RU-486. These results demonstrate that dexamethasone potentiates FSH actions on steroidoogenesis in the pig ovary. Possible mechanisms for this potentiation include the ability of dexamethasone to stimulate P450scc gene expression.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2001

Self-expandable chitosan stent: design and preparation.

Stents are largely used in surgical procedures to relieve pathological obstructions. The purpose of the present study was to design and prepare a biocompatible stent with a self-expandable mechanism. Thin films were prepared from deacetylated chitosan (4% w/v) dissolved in acetic acid solution (2% v/v). The chitosan films were tested by a calibrated tensiometer to measure the Young's module (E). The films were used to manufacture stents by pulling and winding them around a cylindrical rod in a helical fashion. Thirteen stents (diameter = 0.5 +/- 0.05 mm, length approximately 4 mm) were inserted into the vas deferens of wistar rats. Upon stent insertion, the vasal anastomosis was achieved with a laser-soldering technique. The animals were sacrificied 8 weeks later. The stress test showed that the chitosan film was elastic (maximum strain = 105% +/- 6%, E = 0.7655 +/- 0.0288 Mpa). The stents self-expanded by releasing their elastic energy. All the stents but one remained open inside the vasa despite high incidence of sperm granuloma. A biocompatible and self-expandable stent with a helical design is proposed.

Animals↗

PubMed2001

Evaluation of Th1/Th2 ratio and cytokine production profile during acute exacerbation and convalescence in asthmatic children.

BACKGROUND: Th2-type cytokines, such as IL-4 and IL-5, are generally believed to play an important role in the pathogenesis of allergic asthma. In contrast, Th1-type cytokine, especially interferon (IFN)-gamma, is thought to have a downregulatory effect on Th2 immune response cells. Thus, the imbalance of Th1 and Th2 cells may be a key factor in relation to disease severity. OBJECTIVE: The aim of this study is to examine the changes in the Th1/Th2 ratios and cytokine production profiles of asthmatic children at acute attacks and convalescent stages. METHODS: Twelve asthmatic patients were included in this study. The percentages of IFN-gamma- or IL-4-producing cells were determined with a flow-cytometric method of intracellular protein detection. Fresh whole blood obtained from normal controls and patients at two stages was stimulated with brefeldin A, phorbol myristate acetate, and ionomycin for 4 hours. Cells were fixed and stained intracellularly with fluorescein isothiocyanate- or phycoerythrin-conjugated antibody specific to each cytokine in combination with anti-CD4. ELISA assays were applied to measure cytokine concentrations of supernatant from peripheral blood mononuclear cells (PBMC) activated with phorbol myristate acetate and ionomycin for 24 hours. RESULTS: Among CD4+ cells, the percentage of IL-4+ cells decreased significantly from 8.18 +/- 4.77% at acute attacks to 4.18 +/- 1.26% (P < .020) at convalescence. The percentage of IFN-gamma+ cells also decreased from 13.49 +/- 4.21% to 9.03 +/- 5.42% (P < .052). The Th1/Th2 ratios of patients at the two stages were similar, and both were lower than the normal controls. Significantly higher IL-5 and lower IFN-gamma production were detected from activated PBMC of asthmatic patients than normal controls. CONCLUSIONS: The decrease of IFN-gamma+ and IL-4+ cells detected at the single-cell level may explain the potential mechanism of convalescence from acute asthma attacks. High Th1/Th2 ratio and low IL-5 production from the PBMC of normal controls support the idea of a biased Th2 immune response in asthmatic patients.

Acute Disease↗

PubMed2000

Effect of dexamethasone on the expression of p34(cdc2) and cyclin B1 in pig oocytes in vitro.

The meiotic division in oocytes is arrested in the G2 phase of the cell cycle. Resumption of meiosis, also known as oocyte maturation, entails a G2 to M transition. At the G2-M boundary, maturation promoting factor (MPF) activation is usually induced via several ways, including tyrosine dephosphorylation of p34(cdc2) and synthesis of cyclin B according to cell type and species. Previous studies in our laboratory demonstrated that glucocorticoids directly inhibit the meiotic maturation of pig oocytes in vitro. The aim of this study was therefore to investigate the influence of glucocorticoids on the expression of p34(cdc2) and cyclin B1 in resumption of meiosis of pig oocytes. We detected the relative levels and association of p34(cdc2) and cyclin B1. Isolated cumulus-enclosed oocytes were cultured in Waymouth MB752/1 medium supplemented with sodium pyruvate (50 microgram/ml), LH (0.5 microgram/ml), FSH (0.5 microgram/ml), and estradiol-17beta (1 microgram/ml) in the presence or absence of dexamethasone (DEX) for 24 hr; they then were cultured without hormonal supplements in the presence or absence of DEX for an additional 24 hr. We found that cyclin B1, as well as p34(cdc2), was already present in fully grown G2-arrested pig oocytes when removed from the follicle. In these oocytes, cyclin B1 and p34(cdc2) were already associated in complex. Treatment with DEX at concentrations of 1 microgram/ml or above decreased the level of cyclin B1, but had no effect on the level of p34(cdc2). The exposure of oocytes to DEX also decreased the amount of complexed p34(cdc2)-cyclin B1. These findings suggest that the inhibitory action of DEX on meiotic maturation could be due, at least in part, to the reduced amount of p34(cdc2)-cyclin B1 complex.

Animals↗

PubMed2000

Strand bias in Ig somatic hypermutation is determined by signal sequence within the variable region.

Ig genes undergo hypermutation with a nucleotide preference of A over T for mutation on the coding strand. As only with concomitant strand bias can such nucleotide bias be observed, Ig gene hypermutation is generally accepted as a strand-specific process, for which the mechanistic basis remains unknown. It has previously been shown that different non-Ig sequences replacing the LVJ region of an Ig transgene to various extents are targeted for hypermutation with similar mutation frequencies. However, the nucleotide bias characteristic of Ig hypermutation was not found in two of the three such sequences studied. To test whether it is the DNA sequences of the non-Ig substrates that determine the pattern of nucleotide bias in hypermutation or whether the LVJ sequence may contain element(s) that confer strand bias, we have added back all the replaced LVJ sequences to one of the transgenes, L(kappa)-Vgpt*, that expresses no strand bias in hypermutation and studied the outcome. The results show that the gpt sequence in the presence of the complete LVJ sequence hypermutates differently from the same sequence in L(kappa)-Vgpt* where 84% of the LVJ was replaced. The main difference is the resumption of strand bias characteristic of Ig hypermutation. Thus, whether or not a substrate sequence manifests strand bias in hypermutation is not inherently determined by the substrate DNA sequence. This indicates the presence of special element(s) within the LVJ that confer strand bias.

Animals↗

PubMed1999

Effect of methylene blue, indigo carmine, and Renografin on human sperm motility.

OBJECTIVES: To evaluate the effect of commonly used intraoperative vasography and tissue staining agents, indigo carmine, methylene blue, and Renografin, on sperm motility. METHODS: Semen from 20 healthy men was obtained after 2 to 4 days of abstinence. Sperm motility was initially evaluated in each specimen. Standard solutions of indigo carmine, methylene blue, and Renografin-60 were diluted 2x and 4x with lactated Ringer's solution. Equal aliquots of sperm were mixed with undiluted and diluted drugs, and sperm motility was assessed. RESULTS: Initial mean sperm motility was 70.3%+/-3.0%. Undiluted methylene blue and Renografin severely depressed sperm motility to 1.1%+/-0.5% and 2.3%+/-0.7%, respectively (P <0.05). Diluted methylene blue depressed motility to 4.9%+/-1.8% and 11.2%+/-3.0% (P < 0.05). Diluted Renografin depressed motility to 25.1%+/-4.1% and 55.3%+/-3.3% (P < 0.05). Although undiluted and 2x-diluted indigo carmine moderately decreased sperm motility (48.9%+/-3.2% and 61.7%+/-3.0%, P < 0.05), 4x-diluted indigo carmine had minimal effect on sperm motility (67.3%+/-2.8%, P > 0.05). Lactated Ringer's solution had no effect on sperm motility. CONCLUSIONS: We found a severe, immediate reduction in sperm motility after exposure to undiluted standard solutions of methylene blue and Renografin. Dilution of Renografin significantly decreased its negative impact on the sperm motility, whereas the adverse effect of methylene blue remained fairly constant even with increasing dilution. Sperm motility should be assessed prior to application of these agents. Sperm should be aspirated for immediate use and/or cryopreservation prior to the use of these agents. Indigo carmine may be safely used as a tissue stain or vasography agent with a minimal effect on sperm motility in dilutions of 4x and higher.

Adult↗

PubMed1999

Comparison of absorbable and nonabsorbable sutures for microsurgical vasovasostomy in rats.

OBJECTIVES: At least 12% of initially patent vasovasostomies (VVs) shut down. Currently, only nonabsorbable sutures are used for VV. A synthetic, slowly absorbing, monofilament polyglactin suture has been developed that retains tensile strength for up to 6 months. We performed a prospective controlled randomized study comparing absorbable and nonabsorbable sutures for rat VVs. METHODS: Bilateral microsurgical VV was performed in three groups of 36 Wistar male rats, with 10-0 nylon, 10-0 polypropylene, and 10-0 polyglactin sutures. Twelve control rats underwent sham operations. Three rats in each group were killed at 2, 6, 12, and 24 weeks. The abdominal end of the vas deferens was transected and the intraluminal fluid examined microscopically for presence of sperm. The segment of the vas deferens containing the anastomosis was excised. Fluid from the testicular end was examined for sperm to confirm spermatogenesis. Patency was confirmed by an antegrade indigo carmine vasogram of the anastomotic segment. Segments were randomly sent for histologic or tensile strength evaluation. RESULTS: The mean tensile strength of the anastomoses performed with nylon was slightly higher than in polypropylene and polyglactin sutures, although the difference was not statistically significant. Polyglactin consistently maintained tensile strength throughout 6 months without significant fluctuations. The mean patency rate in the polyglactin group was 96%, in nylon 81%, and in polypropylene 61%. Although polyglactin had a consistently higher patency rate compared with nonabsorbable sutures, the difference was not statistically significant (P = 0.11) but indicated a strong trend. The occurrence of microscopic sperm granuloma, muscle layer injuries, intimal fibrosis, and adventitial fibrosis of the vas deferens was not significantly different between suture types. CONCLUSIONS: The three suture materials appear equivalent with respect to overall tensile strength of anastomosis; with histologic evaluation, the trend was toward better patency with polyglactin. Polyglactin 10-0 microsurgical suture is a viable alternative to nonabsorbable sutures in microsurgical VVs, although further studies are indicated to assess long-term results.

Animals↗

PubMed1999

Effects of glucocorticoids on maturation of pig oocytes and their subsequent fertilizing capacity in vitro.

The aim of this study was to assess the possible role of glucocorticoids in the maturation of pig oocytes and their subsequent fertilizing capacity in vitro. Pig cumulus-enclosed oocytes collected from prepubertal gilts were cultured in Waymouth MB752/1 medium supplemented with sodium pyruvate (50 microg/ml), LH (0.5 microg/ml), FSH (0.5 microg/ml), and estradiol-17beta (1 microg/ml) in the presence or absence of cortisol or dexamethasone (DEX) for 24 h; they then were cultured without hormonal supplements in the presence or absence of cortisol or DEX for an additional 16-24 h. Treatment of cumulus-enclosed or denuded oocytes with increasing concentrations of cortisol or DEX for 48 h resulted in a dose-response inhibition of germinal vesicle breakdown (GVB). Increasing duration (12-48 h) of treatment with DEX (10 microg/ml) led to a time-dependent inhibition of GVB, which achieved statistical significance by 12 h. The addition of DEX (10 microg/ml) to maturation medium immediately after culture or at 12 h, 24 h, or 36 h after culture also decreased the percentage of oocytes with GVB. When oocytes were exposed to DEX for 48 h, the maturation rate was reduced. The degree of this reduction was dependent on DEX, and a concentration of DEX higher than 0.1 microg/ml was needed. The inhibitory effect of DEX on the maturation of oocytes was prevented by the glucocorticoid receptor antagonist RU-486. Exposure of oocytes to DEX for 40 h did not prevent sperm penetration, affect the incidence of polyspermy, or decrease the ability of oocytes to form a male pronucleus. The intracellular concentration of glutathione (GSH) in cumulus-enclosed oocytes was 4.4 mM per oocyte. Exposure of oocytes to DEX (0.01-10 microg/ml) had no effect on GSH concentration. These results demonstrate that glucocorticoids directly inhibit the meiotic but not cytoplasmic maturation of pig oocytes in vitro. This inhibitory effect is not mediated through a decrease in the level of intracellular GSH.

Animals↗

PubMed1998

Effects of cyclophosphamide on maturation and subsequent fertilizing capacity of pig oocytes in vitro.

This study examines the effects of cyclophosphamide, a widely used anti-cancer agent, on the maturation of pig oocytes and on their subsequent fertilizing capacity in vitro. Pig cumulus-oocyte complexes collected from prepubertal gilts were cultured in Waymouth MB 752/1 medium supplemented with sodium pyruvate (50 micrograms/ml), luteinizing hormone (0.5 microgram/ml), follicle-stimulating hormone (0.5 microgram/ml), and 17 beta-estradiol (1 microgram/ml) in the presence or absence of cyclophosphamide for 24 hr; they then were cultured without hormonal supplements in the presence or absence of cyclophosphamide for an additional 16-24 hr. The breakdown of germinal vesicle (GVBD) and changes in glutathione (GSH) content before in vitro fertilization were assessed. Oocytes containing one polar body and a metaphase plate were regarded as matured. Cytoplasmic maturation as determined by male pronuclear formation following fertilization in vitro was also examined. Treatment of oocytes with increasing concentrations (1-1000 micrograms/ml) of cyclophosphamide for 48 hr resulted in a dose-response inhibition of the rate of maturation, but had no effect on GVBD. Increasing duration (12-48 hr) of treatment with cyclophosphamide (100 micrograms/ml) led to a time-dependent inhibition of nuclear maturation, achieving statistical significance by 24 hr. The addition of cyclophosphamide (100 micrograms/ml) to maturation medium immediately after culture, 12 hr or 24 hr after culture also decreased the percentage of oocytes matured during a 48-h culture period. Exposure of oocytes to cyclophosphamide (100 micrograms/ml) for 40 hr did not prevent sperm penetration, not affect the incidence of polyspermy, or decrease the ability of oocytes to form a male pronucleus at 8 hr after insemination. The concentration of GSH, an important factor for male pronuclear formation, in pig oocytes was determined by an enzymatic cycling assay. The concentration found was 8.15 +/- 1.19 mM per oocyte. Exposure of oocytes to cyclophosphamide (100 micrograms/ml) had no effect on GSH concentration. These results demonstrate that cyclophosphamide directly inhibits the meiotic but not cytoplasmic maturation of pig oocytes in vitro. This inhibitory effect, apparently, is not mediated through a decrease in the level of intracellular glutathione.

Animals↗

PubMed1998

Microsurgical vasovasostomy: the microdot technique of precision suture placement.

PURPOSE: A technique of vasovasostomy that facilitates precision suture placement is presented. MATERIALS AND METHODS: The technique involves mapping of the planned suture exit points with "microdots" placed on the cut ends of the vas deferens with a microtip marking pen. Microdots are placed at 12, 3, 6 and 9 o'clock positions. Four additional dots are placed between each of the previous 4 dots. Exactly 8 mucosal sutures (double armed 10-zero monofilament sutures) are used for each anastomosis. The anastomosis is completed with 8 muscularis sutures (9-zero monofilament) and 6 to 8 sutures (6-zero monofilament) approximating the vasal sheath. RESULTS: In a series of 194 consecutive vasovasostomy procedures using this technique a patency rate of 99.5% was achieved. Pregnancy rates of 54% (crude) and 64% (excluding female factor infertility) were observed for the first 100 subjects of this cohort. CONCLUSIONS: The microdot technique ensures precision suture placement and facilitates the anastomosis of lumens of discrepant diameters by exact mapping of each planned suture. The microdot method separates the planning from the placement. Patency rates using the microdot technique approach 100%.

Anastomosis, Surgical↗

PubMed1997

Increases in mRNA levels of glucose transporters types 1 and 3 in Ehrlich ascites tumor cells during tumor development.

A common feature of many tumors is an increase in glucose catabolism during tumor growth. We studied the mechanism of this phenomenon by using Ehrlich ascites tumor bearing mice as the animal model. We found that Ehrlich ascites tumor cells possess only glucose transporter 1 (GLUT1) and GLUT3 but not GLUT2, GLUT4, or GLUT5. The mRNA levels of GLUT1 and GLUT3 increased progressively in the tumour during development; however, there were no changes observable in mRNA levels of glucose transporters of all types in brain, liver, and heart of the host mice. These findings suggest that Ehrlich ascites tumor augments its glucose transport mechanism relative to other tissues in response to its unique growth needs.

Animals↗

PubMed1996

Properties of human prolactin (PRL) and H27A-PRL, a mutant that does not bind Zn++.

The ability of protein hormones to self-associate is likely to play an important role in concentrating hormones into secretory granules; therefore, the aggregation properties of human PRL and H27A mutant were investigated. Human PRL bound (65)Zn++; the Scatchard analysis was convex up, and limited by the solubility of PRL, but at least 0.7 mole Zn++ bound per mole of PRL. Binding of (65)Zn++ to H27A-PRL was greatly reduced. The biological activity in an Nb2 cell assay and the circular dichroism spectrum of wild type and H27A-PRL were similar, indicating the H27A mutant folded correctly, and the binding of Zn++ to the high affinity site is not essential for biological activity. Dynamic light scattering measurements indicated 10 and 20 mu M Zn++ caused some aggregation of both wild type and H27A-PRL. Sedimentation equilibrium analysis indicated that PRL is primarily a monomer in the absence of Zn++ and that there is increasing self-association in the presence of 5 and 10 mu M Zn++. The mutant H27A exhibited a greater tendency to aggregate without changing detectably the mode of association. Although human PRL binds Zn++ as human GH does, it differs in that the ability to bind Zn++ and to self-associate were decoupled in PRL. Human PRL must have two types of interactions with Zn++; one is binding to a site involving histidine 27, and the other is weaker interactions that induce self-association of PRL.

Animals↗

PubMed1995

The combined effects of dietary fat and estrogen on survival, 7,12-dimethylbenz(a)anthracene-induced breast cancer and prolactin metabolism in rats.

The relationships between dietary fat concentration (10 or 40% of energy), fat source (corn oil or beef tallow) and estrogen (control, ovariectomy or ovariectomy with estrogen replacement) to 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast carcinogenesis and survival in rats were studied in a 2 x 2 x 3 factorial experiment. Female Sprague-Dawley rats given DMBA (2.5 mg/100 g body wt, intragastric) at 55 d of age were randomly allocated to three groups 48 h later: sham ovariectomy (control), ovariectomy (OVX) or ovariectomy with a subcutaneous estrogen implant (OVX+E). Each group was subdivided into dietary groups fed 10 and 40% of energy as corn oil or beef tallow for 70 wk. OVX+E rats exhibited serum estrogen concentrations in excess of physiologic values. Survival at 70 wk for the 3 hormonal groups was control 51%, OVX 67% and OVX+E 13%. Mortality in controls was doubled by feeding a high fat diet; no diet effect was detected in OVX or OVX+E rats. Palpable tumors developed in 74, 14 and 60% of control, OVX and OVX+E rats, respectively. High fat diets approximately doubled the hazard of developing a palpable tumor. Adenocarcinoma prevalence was 58, 12 and 63% in control, OVX and OVX+E rats, respectively. The odds of having any tumor, an adenocarcinoma or an adenoma were multiplied by 3.6, 2.8 and 2.3, respectively, for rats fed high vs. low fat. Additional studies showed that diet had no effect on serum prolactin or estrogen concentrations or metabolism and clearance of intravenously administered radiolabeled prolactin. We demonstrated that high dietary fat concentration enhances breast carcinogenesis independently of cyclic ovarian function, although the presence of estrogen may be a prerequisite for significant dietary modulation. The effect of fat on breast cancer is not mediated by major changes in systemic prolactin metabolism.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1994

Modulation by cortisol of luteinizing hormone secretion from cultured porcine anterior pituitary cells: effects on secretion induced by phospholipase C, phorbol ester and cAMP.

Cultures of enzymatically dispersed porcine anterior pituitary cells were used to examine the effects of cortisol on luteinizing hormone secretion induced by a variety of compounds which activate different intracellular signal transduction mechanisms. Cells were pre-incubated with or without cortisol (200 micrograms/ml) for 3 days, washed and then incubated for 4 h with or without cortisol in the presence or absence of these compounds. Luteinizing hormone in the media was assayed by radioimmunoassay. Cortisol treatment had no effect on basal luteinizing hormone release, but reduced gonadotropin-releasing hormone (8.5 x 10(-8) mol/l) stimulated luteinizing hormone secretion. Phospholipase C, 8-bromo-cyclic adenosine 3',5'-monophosphate, and 12-O-tetradecanoyl-phorbol-13-acetate (an activator of protein kinase C) all stimulated luteinizing hormone secretion in a dose-dependent manner in cortisol-untreated cells. Pretreatment with cortisol inhibited luteinizing hormone secretion induced by phospholipase C and 8-bromo-cyclic adenosine 3',5'-monophosphate, but did not affect the secretion of luteinizing hormone in response to 12-O-tetradecanoyl-phorbol-13 acetate. Cortisol inhibited GnRH-induced inositol phosphate production. Our results suggest that the inhibitory action of cortisol on stimulus-coupled luteinizing hormone secretion may be exerted at two different intracellular sites: (1) by inhibition of phospholipase C activity and (2) at a point distal to cyclic adenosine 3',5'-monophosphate generation.

Animals↗