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J Goldfarb

Publications and source records attributed to J Goldfarb.

At least 19 recordsLinked to original sources
PubMed1998

Seminal fluid factor increases the resistance of the tight junctional complex of cultured human cervical epithelium CaSki cells.

OBJECTIVE: To determine the effects of human seminal fluid on cervical paracellular resistance. DESIGN: Experimental study. SETTING: Healthy volunteers in an academic research environment; cultures of human CaSki cells on filters, with phenotypic characteristics of the endocervix. PATIENT(S): Healthy men donating sperm to a sperm bank. INTERVENTION(S): Seminal fluid was obtained as the discarded fluid from ejaculates. MAIN OUTCOME MEASURE(S): Changes in transepithelial electrical resistance across CaSki cells on filters were determined in an Ussing chamber from successive measurements of the short-circuit current and the transepithelial potential difference. Changes in the dilution potential (and hence in the ratio of Cl- to Na+ mobilities) were determined after lowering the NaCl concentration in the luminal solution. RESULT(S): Seminal fluid increased transepithelial electrical resistance acutely (t1/2, 2 minutes), reversibly, and in a dose-related manner (ED50, 1%). The effect of seminal fluid was abolished when the extracellular calcium level was lowered, and the increase in transepithelial electrical resistance correlated with a decrease in the ratio Cl- to Na+ mobilities, indicating an increase in the resistance of the tight junctional complex. The increase in transepithelial electrical resistance in response to seminal fluid was nonadditive to that of sn-1,2-dioctanoyl diglyceride (a stable diacylglyceride and activator of protein kinase C), and it was abolished by prolonged preincubation with the phorbol ester phorbol 12-myristate 13-acetate (to downregulate protein kinase C) or with staurosporin (to inhibit protein kinase C), suggesting that seminal fluid acts through a protein kinase C-dependent mechanism. Slower (t1/2, 3.3 minutes) increases in transepithelial electrical resistance occurred when seminal fluid was added only to the luminal or the subluminal solution. Treatment with pertussis toxin, adenosine triphosphatase, or trypsin had no effect on the changes in transepithelial electrical resistance. Seminal fluid increased cytosolic calcium, but changes in cytosolic calcium are not important for the increases in transepithelial electrical resistance, suggesting that the effect of seminal fluid is not receptor-mediated. Preliminary studies indicate that the factor(s) in seminal fluid that increases transepithelial electrical resistance is a labile, low molecular weight (< 10 kd) lipid. CONCLUSION(S): Seminal fluid may regulate cervical mucus production in vivo by modulating endocervical permeability.

Calcium↗
PubMed1998

HIV vertical transmission rate determinations are subject to differing definitions and therefore different rates. The Pediatric Pulmonary and Cardiovascular Complications of Vertically Transmitted HIV Infection Study Group.

The HIV infection status of a cohort of 600 prospectively followed children born to HIV infected mothers was determined using HIV peripheral blood culture tests at 0, 3, and 6 months of age, HIV serology at > or = 15 months, and CDC AIDS criteria. We estimated transmission rates using five methods which differed in how HIV indeterminates are handled. These methods were applied at two points in time to illustrate effects of length of follow-up of the cohort on results. In January 1997, 30 months after the last birth, transmission rate estimates ranged from 15.5% (known positives/known positives x known negatives) to 18.1% (known positives x those with one positive culture x deaths/entire cohort minus those lacking negative cultures at age > or = 5 months). Estimates ranged from 14.8% to 20.7% using the subcohort of 284 children followed > or = 12 months as of May 1993. These results indicate that methods for assigning HIV infection status and for handling HIV indeterminates should be carefully defined when estimating transmission rates.

Adult↗
PubMed1998

The meiotic competence of in-vitro matured human oocytes is influenced by donor age: evidence that folliculogenesis is compromised in the reproductively aged ovary.

The human oocyte appears to be particularly prone to meiotic errors, and the incidence of these errors is strongly influenced by maternal age. We have initiated studies of human oocytes from unstimulated ovaries and have observed age-related effects on the meiotic process in oocytes from unselected antral follicles. Specifically, in oocytes obtained from donors over the age of 35 years, the majority of oocytes that extruded a first polar body in culture and arrested at second meiotic metaphase had aberrations in spindle formation and chromosome alignment. Similarly, observations of a limited number of oocytes at first meiotic metaphase suggest disturbances at this stage of meiosis as well. Finally, preliminary results of non-disjunction studies suggest that the frequency of errors in chromosome segregation at the first meiotic division is influenced by donor age in in-vitro matured oocytes as it is in oocytes undergoing meiotic maturation in vivo. These data provide direct evidence that the meiotic competence of oocytes from unstimulated ovaries declines with donor age. Similarly, studies of in-vitro fertilization (IVF) pregnancies in older women indicate that the developmental competence of the human oocyte declines with age. Since both meiotic and developmental competence are acquired during the late stages of oocyte growth, we postulate that an age-related decline in the process of folliculogenesis results in reduced oocyte quality and that the well characterized age-related increase in meiotic non-disjunction is one symptom of compromised oocyte growth.

Adolescent↗
PubMed1998

Co-cultured human embryos may be subjected to widely different microenvironments: pattern of growth factor/cytokine release by Vero cells during the co-culture interval.

This study was designed to identify and quantify concentrations of growth factors/cytokines released by Vero cells during the co-culture interval. The factors screened for in this preliminary investigation, namely platelet-derived growth factor (PDGF), transforming growth factor beta (TGFbeta), interleukin-6 (IL-6), leukaemia inhibitory factor (LIF) and epidermal growth factor (EGF) have each been identified to impact on early embryo development or are secreted by embryos themselves, suggesting an autocrine regulatory role. Vero cell culture supernatants were collected at 2, 3, 4, 5 and 6 days after seeding. Samples were assessed by enzyme-linked immunoassay for growth factor/cytokine secretion at each designated time interval. Conditioned medium from all days contained IL-6, PDGF and LIF. The concentration of IL-6 increased from 294 pg/well on day 2 to almost 1600 pg/well on day 6. PDGF also accumulated rapidly in co-culture wells, rising from 19-40 pg/well early in the culture period to around 500 pg/ well by day 6. In the second half of this study, medium supernatants from patients enrolled in our co-culture programme were analysed. Retrospective evaluation of medium supernatants collected at the time of transfer from co-cultures from 11 randomly selected patients showed considerable patient-to-patient variation in concentrations of secreted growth factors and cytokines. These findings indicate that during the co-culture interval embryos are exposed to a dynamic environment, with increasing concentrations of growth factors and cytokines. The positive effects of co-culture on embryo quality and in-vitro blastulation need to be balanced against the variation that this technique can potentially introduce into the embryo culture system.

Animals↗
PubMed1998

Infectious diseases presentations of Munchausen syndrome by proxy: case report and review of the literature.

Munchausen syndrome by proxy is a form of abuse, usually of a child by a parent, in which a factitious illness is reported or produced in the child, resulting in unnecessary medical evaluations and treatments. A dramatic case of a 17-month-old infant with recurrent polymicrobial bacteremia prompted a review of cases diagnosed by the Pediatric Infectious Diseases consultation service at our referral children's hospital and a review of the infectious diseases presentations in the medical literature. The infectious diseases presentations of the syndrome as well as criteria for the diagnosis are reviewed and discussed.

Child↗
PubMed1998

Randomized, single-blinded comparative study of the efficacy of amoxicillin (40 mg/kg/day) versus standard-dose penicillin V in the treatment of group A streptococcal pharyngitis in children.

A 10-day course of amoxicillin at a dosage of 40 mg per kilogram per day was compared with conventional (lower dosage) penicillin V therapy in the treatment of culture-proven Group A streptococcal pharyngitis in children 3 to 18 years of age in a prospective, randomized, and single-blinded study. Children had to have signs and symptoms compatible with the diagnosis of streptococcal pharyngitis and to have a throat swab positive for Group A streptococci. A second throat culture was obtained 10 to 14 days after the completion of therapy. Serotyping was performed to help differentiate carrier states from reinfections. Of 161 children enrolled, 113 were evaluable; 55 received penicillin and 58 received amoxicillin. At the completion of therapy 70.9% (39/55) of patients in the penicillin group vs 87.9% (51/58) of patients in the amoxicillin group were asymptomatic (clinical cure, P = 0.025). At the completion of therapy, 54.5% (30/55) of patients in the penicillin group vs 79.3% (46/58) of patients in the amoxicillin group had negative throat cultures (bacteriologic cure, P = 0.005). The carrier rate (children who were well but who were still carrying the same serotype of Group A streptococcus) also differed between the groups: 13 (23.6%) in the penicillin group compared with six (10.3%) in the amoxicillin group. Amoxicillin at 40 mg/kg/day was significantly more effective than lower dosages of penicillin V for clinical and bacteriologic cure in the treatment of Group A streptococcal pharyngitis in children. The current perception that penicillin is declining in effectiveness may be due to inadequate dosing.

Adolescent↗
PubMed1998

Parvovirus: a review.

Infections caused by human parvovirus B19 result in a variety of clinical manifestations, the severity of which depends on the immune and hematologic status of the host. Arthropathy is known to occur in children and adults with acute parvovirus B19 infection. In adults, the arthropathy is common and is usually brief and self-limited, although a chronic arthropathy due to HPV B19 infections can occur rarely. It is important to differentiate between such chronic infection and RA, because of the similar clinical manifestations and different modes of treatment. An association between HPV B19 and other rheumatologic diseases such as vasculitis needs further research before confirmation is possible.

Arthritis↗
PubMed1998

Serotonergic modulation of acetylcholine release from cortex of freely moving rats.

The modulation of acetylcholine (ACh) release by 5-HT3 receptor activation was studied using in vivo microdialysis. Spontaneous and K+-stimulated ACh release were measured in frontoparietal cortex and hippocampus of freely moving rats. Two consecutive exposures to high K+ produced ACh release of similar magnitude. In the cortex, serotonin (5-HT) failed to alter spontaneous ACh release, but caused a concentration-dependent decrease of K+-evoked ACh release. Phenylbiguanide (PBG) and m-chlorophenylbiguanide, two selective 5-HT3 agonists, mimicked the 5-HT responses, but 8-hydroxy-2-(di-n-propylamino)tetralin, a selective 5-HT1A agonist, was without effect. However, PBG failed to modify K+-evoked ACh release from the hippocampus. Systemic and local administration of a highly selective 5-HT3 antagonist, tropisetron ((3-alpha-tropanyl)1H-indole-carboxylic acid ester) blocked the effect of both 5-HT and PBG. The inhibition of ACh release by PBG was sensitive to tetrodotoxin. These observations provide direct evidence that, in rat cortex, 5-HT modulates in-vivo release of ACh through activation of 5-HT3 receptors.

Acetylcholine↗
PubMed1998

Effector pathway-dependent relative efficacy at serotonin type 2A and 2C receptors: evidence for agonist-directed trafficking of receptor stimulus.

There are many examples of a single receptor coupling directly to more than one cellular signal transduction pathway. Although traditional receptor theory allows for activation of multiple cellular effectors by agonists, it predicts that the relative degree of activation of each effector pathway by an agonist (relative efficacy) must be the same. In the current experiments, we demonstrate that agonists at the human serotonin2A (5-HT2A) and 5-HT2C receptors activate differentially two signal transduction pathways independently coupled to the receptors [phospholipase C (PLC)-mediated inositol phosphate (IP) accumulation and phospholipase A2 (PLA2)-mediated arachidonic acid (AA) release]. The relative efficacies of agonists differed depending on which signal transduction pathway was measured. Moreover, relative to 5-HT, some 5-HT2C agonists (e.g., 3-trifluoromethylphenyl-piperazine) preferentially activated the PLC-IP pathway, whereas others (e.g., lysergic acid diethylamide) favored the PLA2-AA pathway. In contrast, when two dependent responses were measured (IP accumulation and calcium mobilization), agonist relative efficacies were not different. These data strongly support the hypothesis termed "agonist-directed trafficking of receptor stimulus" recently proposed by Kenakin [Trends Pharmacol Sci 16:232-238 (1995)]. Concentration-response curves to 5-HT2C agonists were fit well by a three-state model of receptor activation, suggesting that two active receptor states may be sufficient to explain pathway-dependent agonist efficacy. Rational drug design that optimizes preferential effector activity within a group of receptor-selective drugs holds the promise of increased selectivity in clinically useful agents.

Animals↗
PubMed1997

Effects of subinguinal varicocele ligation on sperm concentration, motility and Kruger morphology.

PURPOSE: We examined the effects of varicocelectomy on semen parameters in 30 subfertile men, with emphasis on potential changes in sperm count, motility and morphology as measured by Kruger's strict morphologic criteria. MATERIALS AND METHODS: A total of 30 patients underwent subinguinal varicocelectomy (25 bilateral and 5 unilateral). Preoperative and postoperative sperm density, motility and morphology were analyzed. Preoperative follicle-stimulating hormone, luteinizing hormone and testosterone levels were measured and compared to those of fertile volunteers enrolled in our sperm donation program. Pregnancy rates after varicocelectomy were also examined: The Wilcoxon signed rank test was used to measure levels of statistical significance in all analyses. RESULTS: We found that sperm density and motility improved significantly (p < 0.05) without concomitant changes in strict morphology (p > 0.05) only in men with clinical bilateral varicoceles. No differences were observed in values among testosterone, follicle-stimulating hormone and luteinizing hormone levels of the fertile control group and preoperative varicocele patients. Of 30 patients 12 (40%) had successful, full-term pregnancies, including 6 via natural cycle intercourse, 5 (43%) by in vitro fertilization embryo transfer and 1 by intracytoplasmic sperm injection. CONCLUSIONS: Although sperm morphology as measured by strict morphologic criteria does not improve after varicocelectomy, there were highly significant changes in motility and concentration. Hormonal differences are not likely to have a role in or be reflective of pathophysiology of varicocele induced male infertility. The recent observation that sperm motility may be an independent or additive predictive factor for fertilization and pregnancy supports the need for continued varicocele repair independent of the lack of varicocelectomy effect on Kruger morphology.

Female↗
PubMed1997

Use of Synthetic Serum Substitute and alpha-minimum essential medium for the extended culture of human embryos to the blastocyst stage.

This study was designed to provide further information on mouse and human embryo development in alpha-modified minimum essential medium (alphaMEM). First, we compared the development and implantation potential of murine in-vitro fertilized (IVF) embryos cultured in alphaMEM, in the presence and absence of co-culture cells. No significant difference was observed in blastocyst rate between alphaMEM alone (76.2%) and alphaMEM plus co-culture (79.9%). The percentage of hatched blastocysts was, however, higher with co-culture (47.5 versus 40%, P < 0.01). Transfer of blastocysts to pseudopregnant foster mothers resulted in similar live birth rates (14.9% alphaMEM alone versus 19.8% alphaMEM/co-culture). alphaMEM was also introduced into our clinical IVF programme for culture of human embryos beyond day 3. Spare human embryos were cultured under oil in microdrops of alphaMEM supplemented with 10% synthetic serum substitute. Blastocysts were evaluated for maturity and the presence and organization of the inner cell mass. A total of 206 embryos from 53 IVF patients underwent extended culture. The overall blastocyst rate was 45.1%. An inner cell mass was observed in 76 blastocysts (81.7%). With regard to developmental maturity, approximately 73% of blastocysts that had been frozen were expanding (cavity > 50% embryo volume) or fully expanded. These data suggest that alphaMEM in conjunction with a commercial protein preparation such as Synthetic Serum Substitute may be a good basal medium for culture of human embryos to the blastocyst stage.

Animals↗
PubMed1997

Extracellular ATP regulates transcervical permeability by modulating two distinct paracellular pathways.

Extracellular ATP stimulates a biphasic change in transepithelial electrical resistance (RTE) across cultures of human cervical epithelial cells: an acute decrease (phase I), followed by a delayed increase in resistance (phase II). The objective of this study was to determine the contributions of changes in the lateral intercellular space resistance (RLIS) and the tight junctional resistance (RTJ) to the changes in RTE. Phase I and phase II effects were uncoupled by treatment with 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA)-acetoxymethyl ester, which blocks the ATP-induced increases in cytosolic Ca2+ and abolishes phase I. BAPTA-loaded cells differed from control cells in that 1) phase I began when ATP was added, in contrast to a delay of 1.5-3.5 min in phase II, 2) phase I decreases in RLIS followed a simple exponential pattern, in contrast to the complex kinetics of phase II, and 3) the magnitude of phase II varied between 20 and 100% for increases of RTJ in day 2-6 cultures; the phase I decrease of 50% in RLIS was unrelated to different experimental conditions. These results indicate that phase I and phase II are induced simultaneously and independently by ATP, and they contribute to the total changes in RTE. We conclude that ATP regulation of RLIS and RTJ may be important mechanisms of modulating cervical mucus production in vivo.

Adenosine Triphosphate↗