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Biomedical subjects

R Goldenberg

Publications and source records attributed to R Goldenberg.

At least 19 recordsLinked to original sources
PubMed2000

Antidepressant effects on GABA-stimulated 36Cl(-) influx in rat cerebral cortex are altered after treatment with GABA(A) receptor antisense oligodeoxynucleotides.

Antidepressants act at the GABA(A) receptor to inhibit GABA-stimulated 36Cl(-) influx and GABA reduction of [35S]TBPS binding. This study examined how selective knock-down (via antisense oligodeoxynucleotides, aODNs) of GABA(A) receptor subunits modified antidepressant activity. The specific aODNs used were for the alpha1, beta1, beta2 or gamma2 subunits of the GABA(A) receptor. The aODN microinjections reduced corresponding GABA(A) receptor subunit mRNA levels by 30-40% as assessed by RT-PCR. The inhibitory effect of the antidepressants amitriptyline and mianserin on GABA-stimulated 36Cl(-) influx was decreased after microinjections of alpha1, beta1, or beta2 subunit aODNs but potentiated after microinjections of gamma2 subunit aODNs. This pattern of aODNs effect on amitriptyline and mianserin modulation of GABA-stimulated 36Cl(-) influx was the same for both antidepressants and similar to GABA but different than that of diazepam and bicuculline. We conclude that multiple subunits of the GABA(A) receptor regulate the effect of amitriptyline and mianserin on the GABA(A) receptor chloride ionophore complex. However, the exact identity of the subunit mediating the direct or allosteric modulation of the antidepressant effect on GABA-stimulated 36Cl(-) influx remains unclear.

Amitriptyline↗
PubMed2000

Maternal serum ferritin and fetal growth.

OBJECTIVE: To determine the relationship between maternal serum ferritin and concentrations and specific types of fetal growth restriction (FGR). METHODS: Serum ferritin concentrations were measured at approximately 25 and 36 weeks' gestation in 480 multiparas with singleton fetuses who participated in a study of risk factors for repeated FGR. Asymmetric FGR was defined by low birth weight for gestational age criteria and a ponderal index less than 2.32, and symmetric FGR was defined by the same birth weight for gestational age criteria and a ponderal index of at least 2.32. RESULTS: Among 480 infants, 370 were appropriate for gestational age (AGA), 58 had asymmetric FGR, and 52 had symmetric FGR. Higher ferritin concentrations were associated with black race, maternal age 25 years or older, and smoking. Mothers of asymmetric-FGR infants had higher mean ferritin levels than mothers of AGA infants at 25 weeks' (38.0 versus 20.2 microg/L, P < .01) and 36 weeks' gestation (21.0 versus 13.3 microg/L, P < .01), whereas mothers of symmetric-FGR infants had significantly lower ferritin levels at 36 weeks (8.3 microg/L). For mothers with serum ferritin levels of at least 26 microg/L (highest quartile at 25 weeks), the adjusted odds ratio (OR) for asymmetric-FGR infants was 3.4, 95% confidence interval (CI) 1.6, 7.2. There was a similar association between the highest quartile of serum ferritin at 36 weeks (at least 20 microg/L) and asymmetric FGR (adjusted OR 2.7, 95% CI 1.3, 5.8). Women with serum ferritin levels less than 3 microg/L (lowest quartile at 36 weeks) had an adjusted OR for symmetric-FGR infants of 2.2, 95% CI 1.01, 4.6. CONCLUSION: High maternal serum ferritin levels are associated with asymmetric FGR, whereas low serum ferritin levels are associated with symmetric FGR.

Embryonic and Fetal Development↗
PubMed2000

Effects of treatment with GABA(A) receptor subunit antisense oligodeoxynucleotides on GABA-stimulated 36Cl- influx in the rat cerebral cortex.

GABA(A) receptor function was studied in cerebral cortical vesicles prepared from rats after intracerebroventricular microinjections of antisense oligodeoxynucleotides (aODNs) for alpha1, gamma2, beta1, beta2 subunits. GABA(A) receptor alpha1 subunit aODNs decreased alpha1 subunit mRNA by 59+/-10%. Specific [3H]GABA binding was decreased by alpha1 or beta2 subunit aODNs (to 63+/-3% and 64+/-9%, respectively) but not changed by gamma2 subunit aODNs (94+/-5%). Specific [3H]flunitrazepam binding was increased by alpha1 or beta2 subunit aODNs (122+/-8% and 126+/-11%, respectively) and decreased by gamma2 subunit aODNs (50+/-13%). The "knockdown" of specific subunits of the GABA(A )receptor significantly influenced GABA-stimulated 36Cl- influx. Injection of alpha1 subunit aODNs decreased basal 36Cl- influx and the GABA Emax; enhanced GABA modulation by diazepam; and decreased antagonism of GABA activity by bicuculline. Injection of gamma2 subunit aODNs increased the GABA Emax; reversed the modulatory efficacy of diazepam from enhancement to inhibition of GABA-stimulation; and reduced the antagonist effect of bicuculline. Injection of beta2 subunit aODNs reduced the effect of diazepam whereas treatment with beta1 subunit aODNs had no effect on the drugs studied. Conclusions from our studies are: (1) alpha1 subunits promote, beta2 subunits maintain, and gamma2 subunits suppress GABA stimulation of 36Cl- influx; (2) alpha1 subunits suppress, whereas beta2, and gamma2 subunits promote allosteric modulation by benzodiazepines; (3) diazepam can act as an agonist or inverse agonist depending on the relative composition of the receptor subunits: and (4) the mixed competitive/non-competitive effects of bicuculline result from activity at alpha1 and gamma2 subunits and the lack of activity at beta1 and beta2 subunits.

Animals↗
PubMed1999

The GABA(A) receptor complex as a target for fluoxetine action.

The clinically important antidepressant fluoxetine is established as a selective serotonin reuptake inhibitor. This study demonstrates that fluoxetine also interacts with the GABA(A) receptor complex. At concentrations above 10 microM fluoxetine inhibited the binding of both [3H]GABA (IC50 = 2 mM) and [3H]flunitrazepam (IC50 = 132 microM) to the GABA(A) receptor complex in brain cortical membranes. Low fluoxetine concentrations (1 nM) enhanced GABA-stimulated Cl- uptake by a rat cerebral cortical vesicular preparation. At higher concentrations (100 microM and 1 mM), however, fluoxetine inhibited GABA-stimulated Cl- uptake, an effect related to a reduction in Emax. These observations might assist in an explanation of the basis of the antidepressant action of fluoxetine.

Animals↗
PubMed1999

Racial differences in birthweight for gestational age and infant mortality in extremely-low-risk US populations.

Using national data, we develop and contrast the birth-weight percentiles for gestational age by infants of extremely-low-risk (ELR) White and African-American women and examine racial differences in the proportion of small-for-gestational-age (SGA) births. We then scrutinise racial variations in infant mortality rates of the infants of ELR women. We further compare the infant mortality rates of infants at or below the 10th percentile of birthweight for gestational age of each race group to determine whether infants with similar restricted fetal growth have comparable risks of subsequent mortality. Single live births, 34-42 weeks' gestation, to White and African-American US-resident mothers were selected from the 1990-91 US Linked Live Birth--Infant Death File (n = 4,360,829). Extremely-low-risk mothers were defined as: married, aged 20-34 years, 13+ years of education, multiparae, with average parity for age, adequate prenatal care, vaginal delivery, and no reports of medical risk factors, tobacco use or alcohol use during pregnancy. Marked racial variation in birthweight percentiles by gestational age was evident. Compared with ELR White mothers, the risk of an SGA infant was 2.64 times greater for ELR African-American mothers and the risk of infant mortality was 1.61 times greater. For the ELR group, the infant mortality rates of African-American and White infants at or below the 10th percentile of birthweight for gestational age of their respective maternal race group were essentially identical after controlling for gestational age. In conclusion, race differences in fetal growth patterns remained after controlling for risk status. Efforts to remove racial disparities in infant mortality will need to develop aetiological pathways that can explain why African-Americans have relatively higher rates of preterm birth and higher infant mortality rates among term and non-SGA infants.

Adult↗
PubMed1998

Perinatal mortality and its relationship to the reporting of low-birthweight infants.

OBJECTIVES: This study examined changes in the reporting of very low-birthweight infants in Alabama from 1974 to 1994 and the impact on perinatal mortality rates. METHODS: Linked live birth, neonatal death, and stillbirth records of infants born weighing less than 1500 g were compared. RESULTS: The changes in mortality over time ranged from a drop from 100% to 92% in the under-500-g group to a drop from 39% to 4% in the 1000-to 1499-g group. The percentage of total births weighing less than 500 g increased by 155%; the percentage of 1000- to 1499-g births increased by only 7%. As a result, the percentage of neonatal mortality attributable to live births below 500 g increased from 3% to 32%. CONCLUSIONS: Increased reporting of births below 500 g has masked improvements in neonatal mortality.

Alabama↗
PubMed1994

Clinical experience with the Hewlett-Packard M-1350A fetal monitor: correlation of Doppler-detected fetal body movements with fetal heart rate parameters and perinatal outcome.

OBJECTIVE: Our purpose was to correlate measures of Doppler-detected fetal movements with standard fetal heart rate parameters and perinatal outcomes. STUDY DESIGN: This prospective, multiinstitutional trial used the Hewlett-Packard M1350A monitor to record simultaneous fetal heart rate baseline, variability, accelerations, decelerations, and number of fetal movements, and duration and percent of total time. These data were compared at 10- and 30-minute intervals during nonstress tests and were correlated with fetal heart rate baseline parameters and maternally perceived fetal movements and with outcomes of infants delivered within 7 days of the last test. RESULTS: At six centers 1704 actocardiograms from 884 third-trimester patients were analyzed. Doppler-detected fetal movement counts, durations, and percent of total time correlated weakly with all baseline fetal heart rate parameters (all values < 0.20). All fetal movement parameters increased significantly in successive 10-minute blocks and in periods of increased or normal fetal heart rate variability compared with those with fetal heart rate variability. The sensitivity, specificity, and predictive values of the percent of total movement time were comparable to those of standard nonstress test parameters. The risk of poor perinatal outcomes after nonreactive nonstress tests was lower in cases with fetal movements than in those without. CONCLUSIONS: Doppler actocardiography may help to discriminate fetal states during antepartum testing. It may prevent inappropriate diagnosis of fetal compromise when the nonstress test is nonreactive or nonreassuring.

Female↗
PubMed1993

The effect of low-dose aspirin on fetal urine output and amniotic fluid volume.

OBJECTIVE: Patients given prostaglandin synthetase inhibitors in doses sufficient to inhibit labor are at risk for developing oligohydramnios (possibly related to a reduction in fetal urine output). We sought to ascertain whether the fetuses of women who received 60 mg of aspirin daily had a lower urine output than those whose mothers were given a placebo. STUDY DESIGN: Nulliparous women with singleton gestations in a double-blind preeclampsia prevention trial were randomly selected at 24 weeks' gestation to receive either 60 mg of aspirin daily or a placebo. Urine output was assessed in 59 fetuses (aspirin 32, placebo 27) by serial ultrasonographic measurement of their bladder volume (volume = 4/3 pi r3). Biochemical evidence of aspirin compliance was defined as an 80% reduction in maternal serum thromboxane B2 levels when comparing values obtained at randomization with those at 34 to 36 weeks' gestation. RESULTS: Visual assessment of amniotic fluid volume was similar in both groups. Four-quadrant amniotic fluid indexes also were similar (13.5 cm in aspirin group vs 12.2 cm in placebo group, p = 0.15). Mean fetal urine outputs were similar in the aspirin (57.7 ml/hr) and placebo (55.1 ml/hr) groups (p = 0.71). Moreover, the 23 women with a fourfold thromboxane B2 reduction had a higher mean fetal urine output (63.5 vs 51.8 ml/hr, p = 0.08) than did the remaining 35 patients. This study has a 96% chance (1-beta) of detecting a 50% (30 ml) reduction in fetal urine output. CONCLUSIONS: Daily maternal ingestion of 60 mg of aspirin did not decrease fetal urine output or amniotic fluid volume.

Adult↗
PubMed1993

A video image analyzing system for open-field behavior in the rat focusing on behavioral asymmetries.

A video image analyzing system is presented which measures turning behavior, thigmotactic scanning and locomotion in rats. The system works by analyzing digitized video images obtained by a black/white video camera. Turning behavior is expressed in different diameter classes and as partial or full turns. Thigmotactic scanning is expressed as distance or time locomoted with the left or right side of the body along one of the walls of the testing environment. Locomotion is measured as distance travelled and is expressed in meters. Examples for the application of these behavioral measures are given which include: the measurement of spontaneous or drug-dependent behavioral asymmetries after brain lesion (the unilateral 6-hydroxydopamine model), a unilateral peripheral manipulation (hemivibrissotomy), and the measurement of open-field behavior (spontaneous or drug-induced) in intact animals. Among others, these examples show that the analysis of thigmotactic scanning may provide an alternative behavioral measure, which may be especially useful in the study of functional asymmetries.

Animals↗
PubMed1985

Generalized inhibition of cell-free translation by the amino-terminal propeptide of chick type I procollagen.

Fragments of the amino-terminal propeptide of procollagen have been shown to inhibit the synthesis of procollagen in cultured cells and in a reticulocyte lysate cell-free system (for review see Timpl, R. and Glanville, R.W. (1981) Clin. Orth. Rel. Res. 158, 224-242). In this report, we show that the full-length amino-terminal propeptide of chick pro alpha1(I) chains inhibits the translation of chick tendon mRNA and rat brain mRNA in a reticulocyte lysate cell-free system. The synthesis of procollagen and non-collagenous proteins was equally affected. Inhibition was dose-dependent up to 10 microM. A similar pattern of inhibition was observed for the collagenase-resistant fragment, col 1(I).

Animals↗
PubMed1985

Coated vesicles purified from chick tendon fibroblasts contain newly synthesized type I procollagen.

Coated vesicles were purified from embryonic chick tendon fibroblasts pulsed with [3H]proline. They were morphologically and biochemically similar to coated vesicles purified from other sources. Furthermore, they contained newly synthesized Type I procollagen which was protected from bacterial collagenase digestion unless detergent was present. The procollagen remained associated with coated vesicles during immune precipitation and agarose gel electrophoresis. Data from pulse-chase experiments demonstrated that the specific activity of the coated vesicle preparations was approx. 5-fold higher at the 10 min chase point than at either the 0 or 40 min chase points. These data are consistent with the hypothesis that coated vesicles are intermediates in the intracellular transport of newly synthesized Type I procollagen in chick tendon fibroblasts.

Animals↗
PubMed1981

Subcellular structures involved in internalization and degradation of epidermal growth factor.

Epidermal Growth Factor (EGF), a small polypeptide which acts as a mitogen for many cell types, has previously been shown to bind to a specific plasma membrane receptor on 3T3 cells. If 125I-EGF is bound to 3T3 cells for one hour at 4 degrees C, it remains predominantly associated with the plasma membrane-containing fractions obtained by subjecting cell supernatants to equilibrium sedimentation on sucrose gradients. When binding is followed by a 10-minute incubation at 37 degrees C, over 50% of the 125I-EGF is associated with two internal membrane-containing peaks having higher densities than the plasma membrane. After one hour at 37 degrees C, over 80% of the 125I-EGF is degraded and removed from the cells. The most rapidly labeled internal peak corresponds in density to brain-coated vesicles (CVs). Antiserum prepared against coated vesicles from brain precipitates the 125I-EGF in this peak. In addition, CVs containing 125I-EGF can be co-purified from 3T3 cells exposed to 125I-EGF, using brain as a carrier. Several lines of evidence suggest that the other 125I-EGF-labeled intracellular peak is 125I-EGF in lysosomes. These results provide kinetic and biochemical evidence for a unidirectional pathway for EGF catabolism by 3T3 cells. EGF first binds to the plasma membrane bound receptors, is then moved to the cytoplasm in CVs, and finally appears in lysosomes, where it is degraded and released from the cells. Ten-millimolar NH4Cl blocks lysosomal hydrolysis of EGF almost completely. Subsequently, EGF internalization is inhibited. This finding suggests that the pathway for EGF internalization and degradation is tightly coupled.

Animals↗
PubMed1979

Cefaclor in the treatment of susceptible infections in infants and children.

Cefaclor is a new oral cephalosporin with in vitro activity against a wide variety of organisms including S. aureus, S. pneumoniae, S. pyogenes and H. influenzae (including ampicillin-resistant strains). Seventy-nine patients ranging in age from 2 months to 14 years with soft tissue infections (17 cases), otitis media (17), and streptococcal pharyngitis (45) were studied. They received cefaclor orally at a dose of 40 mg/kg per day in three or four divided doses for a minimum of five days. Results were generally good with favourable clinical and bacteriological responses obtained in 90% of cases. Most patients became afebrile within 48 hours after starting cefaclor. Two patients with H. influenzae cellulitis and bacteraemia defervesced within 24 hours and their blood cultures became negative promptly. Hepatic, renal and haematopoietic studies showed no adverse reactions except for an occasional increase in the eosinophil count with no clinical counterpart of hypersensitivity. Pharmacokinetic studies revealed that following a 10 mg/kg oral dose, peak serum levels of 8 micrograms/ml were observed at one hour, followed by a rather rapid tapering off so that at the end of four hours, virtually no cefaclor was detectable in serum.

Adolescent↗
PubMed1978

Clinical and laboratory evaluation of cefamandole in infants and children.

Fifty-three infants and children, aged three months to 15 years, were treated with an average daily dose of 100 mg of cefamandole/kg intravenously. Of these patients, 47 had soft tissue cellulitis and six had pneumonia. Primary pathogens, including Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, and Haemophilus influenzae, were isolated from 43 of the 53 patients. Bacteremia was documented in six of the 53 patients. A satisfactory clinical and bacteriologic response to cefamandole was achieved in all cases except on (98%). The only treatment failure occurred in an infant with both periorbital cellulitis and bacteremia due to H. influenzae who developed meningitis while receiving cefamandole; no extravasation of the drug across the blood-brain barrier could be detected in spite of inflamed meninges. In general, the only aberrant effects of cefamandole were the appearance of eosinophilia in 28% of patients and a positive indirect Cooms' test without hemolysis in one patient. Cefamandole showed excellent in vitro activity against 87 ampicillin-resistant strains of H. influenzae. Because it has greater activity than any of the other cephalosporins against this important pediatric pathogen, cefamandole may have particular pertinence in the treatment of infections in infants and young children.

Adolescent↗
PubMed1978

Gingivitis and cellulitis in diffuse pneumococcal infection.

Gingivitis occurring with a cystic lesions in young patients with facial cellulitis is highly suggestive of a pneumococcal etiology. Two cases of pneumococcal cellulitis and gingivitis with bacteremia are reported, and the pertinent literature is reviewed.

Cellulitis↗