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Biomedical subjects

D Frank

Publications and source records attributed to D Frank.

At least 91 records · Page 5Linked to original sources
PubMed1990

Dopamine stimulation of cAMP production in cultured opossum kidney cells.

Dopamine receptors have been identified in many tissues including the kidney. To establish an in vitro system as a model for dopamine action, we studied the effect of dopamine (DA) receptor agonists and antagonists on adenosine 3',5'-cyclic monophosphate (cAMP) formation in opossum kidney (OK) cells. The stimulation of cAMP production in these cells by dopamine was dose dependent, and markedly higher levels were observed in the presence of dopamine plus a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine. Half-maximal stimulation was found with 1.15 +/- 0.22 microM dopamine. A DA1-receptor agonist, SKF 82526J, stimulated cAMP production, whereas a DA2-receptor agonist, Ly 171555, did not. The stimulatory effects of dopamine and SKF 82526J were abolished by a specific DA1-receptor antagonist, Sch 23390 with half-maximal inhibition concentrations of 1.24 +/- 0.18 and 4.0 +/- 0.5 nM, respectively. In contrast, the DA2-receptor antagonist, spiperone, had no inhibitory effect on dopamine- and SKF 82526J-stimulated cAMP production. Beta-Adrenergic antagonists failed to attenuate the stimulatory effects of dopamine and SKF 82526J on cAMP production. In addition, the beta-adrenergic receptor agonist, isoproterenol, did not stimulate cAMP production. These results suggest that the action of dopamine was not mediated through beta-adrenergic receptors. Furthermore, our results clearly demonstrated the existence of DA1-receptors linked to adenylate cyclase in OK cells.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Localization of specific mRNAs in Xenopus embryos by whole-mount in situ hybridization.

We have adapted a non-radioactive technique to detect localized mRNAs in whole-mount Xenopus embryos. Synthetic antisense RNA transcribed in the presence of digoxygenin-UTP is used as a probe and is detected via an anti-digoxygenin antibody. We show that localized mRNAs can be detected from late gastrula to tadpole stages and that high as well as low abundance RNAs can be detected. The method was tested on muscle actin and alpha-globin RNAs, whose localization has previously been characterized. In addition, we used the method to determine the distribution of XA-1 RNA, an anterior ectoderm-specific RNA, which we show is expressed in the periphery of the cement gland as well as in the region of the hatching gland. The sequence of an XA-1 cDNA predicts a protein rich in proline and histidine.

Alpha-Globulins↗
PubMed1990

Termination of pregnancy and induction of premature luteolysis by the antiprogestagen, mifepristone, in dogs.

Five pregnant beagle bitches were treated with 2.5 mg mifepristone/kg body weight, twice a day, for 4.5 days starting at Day 32 of gestation. Results of fetal ultrasonography and assay of serum progesterone concentrations every 2-4 days were compared to those in 5 control bitches. Mifepristone resulted in a premature (P less than 0.01) termination of pregnancy (36 +/- 1 vs 65 +/- 1 days), without side effects. The antiprogestagen also caused progesterone to decline to less than 1 ng/ml by Day 40-45 after the preovulatory LH peak (vs 64-67 days in controls) and reduced (P less than 0.05) mean concentrations on Days 34-50 (2.2 +/- 0.5 vs 6.3 +/- 0.3 ng/ml). The results suggest that antiprogestagen therapy is a safe means to terminate unwanted pregnancy in dogs, and that luteal function in pregnant bitches is dependent on luteotrophic support that is blocked by antiprogestagen treatment, directly or indirectly, due to termination of pregnancy.

Abortion, Induced↗
PubMed1990

Evaluation of drug-induced prostatic involution in dogs by transabdominal B-mode ultrasonography.

The relative antiandrogen-induced prostate involution activity of the newly synthesized hydroxyflutamide pro-drug was compared with that of flutamide in 25 Beagles. Secondary antiandrogen activity of both drugs on the testes and mammary tissue was investigated. Daily oral administration of both compounds at 2 dosages (ie, 2.5 and 5.0 mg/kg of body weight) during a 7-week period was monitored by transabdominal ultrasonography of the prostate twice a week. Cross-sectional area estimates of the prostate gland calculated from oblique dorsoventral, and transverse sonographic measurements were diminished significantly in some of the treated dogs as early as day 14 of drug administration. All treated dogs had significant differences in reduction by day 47. Involution was related directly to dose (P less than 0.05), but no difference was observed between test compounds. Differences in secondary antiandrogen activity were not remarkable. Flutamide was not found to have any activity advantage in vivo over hydroxyflutamide. It was concluded that ultrasonography can be a highly effective means of monitoring prostate size, and of monitoring drug-induced involution over time.

Animals↗
PubMed1990

Jitteriness in full-term neonates: prevalence and correlates.

The prevalence and correlates of jitteriness were evaluated in a sample of 936 healthy full-term infants. Jitteriness was seen in 44% of this sample: 23% were classified as mildly jittery, 8% as moderately jittery, and 13% as extremely jittery. Jitteriness was seen most commonly in infants who were sleepy or active and least commonly in infants who were quietly wakeful during the neonatal examination. Jittery infants were more likely to be difficult to console when crying (P less than .01) and less visually alert (P less than .001) than were nonjittery infants. Jitteriness was seen more commonly in slightly smaller (P less than .05) and shorter (P less than .001) infants, in those more than 12 hours old (P less than .01), and in those not exposed to general anesthesia (P less than .05). In an expanded sample of 1054 healthy and sick full-term infants, jitteriness was observed more commonly in neonates who had been exposed prenatally to maternal marijuana use (P less than .01), but not to cocaine use (P = .1), and whose mothers had a positive postpartum urine assay for marijuana (P less than .05) or cocaine (P = .06). The magnitude of these drug effects, however, was small. These findings have important implications for the early parent-infant relationship, pediatric practice, and future research.

Child Behavior↗
PubMed1989

Structural analysis of specificity: alpha-lytic protease complexes with analogues of reaction intermediates.

To better understand the structural basis of enzyme specificity, the structures of complexes formed between alpha-lytic protease, an extracellular serine protease of Lysobacter enzymogenes, and five inhibitory peptide boronic acids (R2-boroX, where R2 is methoxysuccinyl-Ala-Ala-Pro- and boroX is the alpha-aminoboronic acid analogue of Ala, Val, Ile, Norleu, or Phe) have been studied at high resolution by X-ray crystallography. The enzyme has primary specificity for Ala in the P1 position of peptide substrates with catalytic efficiency decreasing with increasing side-chain volume. Enzyme affinity for inhibitors with boroVal, boroIle, and boroPhe residues is much higher than expected on the basis of the catalytic efficiencies of homologous substrates. Covalent tetrahedral adducts are formed between the active-site serine and the boronic acid moieties of R2-boroAla, R2-boroVal R2-boroIle, and R2-boroNorleu. Though R2-boroVal is a slowly bound inhibitor and R2-boroAla is rapidly bound [Kettner, C. A., Bone, R., Agard, D. A., & Bachovchin, W. W. (1988) Biochemistry 27, 7682-7688], there appear to be no structural differences that could account for slow binding. The removal from solution of 20% more hydrophobic surface on binding accounts for the improved affinity of alpha-lytic protease for R2-boroVal relative to R2-boroAla. The high affinity of the enzyme for R2-boroIle derives from the selective binding of the L-allo stereoisomer of the boroIle residue, which can avoid bad steric interactions in the binding pocket.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1989

Simulated drought influences reproduction in male prairie voles.

The environmental factors that arrest breeding in prairie voles during the middle of the breeding season are unknown. The role of water availability on reproductive function was examined by limiting water intake to 50% of ad lib water consumption for 10 weeks. At autopsy, testicular, epididymal and seminal vesicle masses were reduced in water restricted males as compared to animals with ad lib access to water. Body mass was also reduced in water restricted males. Plasma testosterone levels and the number of testicular and epididymal sperm were significantly reduced in water restricted voles as compared to animals drinking water ad lib, but plasma levels of luteinizing hormone were unaffected. Taken together, these data suggest that reduced water availability can inhibit male prairie vole breeding.

Animals↗
PubMed1989

Pedigree analysis of aryl hydrocarbon hydroxylase inducibility in acute leukemia of childhood.

We determined lymphocyte aryl hydrocarbon hydroxylase (AHH) inducibility for members of 13 families with one or more children with acute lymphoblastic leukemia (ALL) and 12 control families. Pedigree analysis suggested that aromatic hydrocarbon responsiveness (i.e. inducibility) is a codominant trait. Heterozygotes were found to be moderately responsive with IR values intermediate between homozygous minimally responsive and homozygous highly responsive individuals. Homozygous recessive and heterozygous genotypes accounted for 54% and 36% of ALL children respectively. The risk of ALL among minimally aromatic hydrocarbon responsive children was twice that of highly responsive children.

Aryl Hydrocarbon Hydroxylases↗
PubMed1989

Photoperiod and temperature affect reproductive and nonreproductive functions in male prairie voles (Microtus ochrogaster).

Adult male prairie voles (Microtus ochrogaster) were housed for 10 wk and exposed to long (16L:8D) or short (8L:16D) photoperiods at 21 degrees or 5 degrees C. Maintenance in short day lengths reduced testicular, epididymal, and seminal vesicle mass and also significantly depressed spermatogenic activity. Cold ambient temperature further suppressed gonadal size in voles exposed to short days. Several pelage characteristics were affected by photoperiod, but not by temperature. Increased fur density, fur depth, and length of guard hair and underhair were observed in voles exposed to short days. Intrascapular brown fat and gonadal fat pad mass as well as body mass were significantly less in voles housed in cold temperatures than in voles exposed to warm ambient temperatures; photoperiod did not affect these parameters. Approximately 30% of the male voles exposed to short days maintained their reproductive systems, yet they clearly processed photoperiodic information; all short-day males, regardless of reproductive condition, had comparable winter pelage development. Our results suggest that in prairie voles, photoperiod may be a predictive cue for reproductive function in nature; however, it appears that pelage development is a more obligatory response to photoperiod than is reproduction.

Animals↗
PubMed1989

Noncognitive criteria for assessing students in North American medical schools.

In 1986 the authors mailed a one-page questionnaire to 135 North American medical schools requesting information about written expectations for students that contain noncognitive criteria. Eighty-eight questionnaires (65.2%) were returned, and 48 schools (54.5%) indicated they possessed written noncognitive criteria. Those schools having noncognitive criteria were asked to submit the criteria for review and were questioned about their reasons for establishing such criteria. Those schools not having noncognitive criteria were asked whether they perceived a need for such criteria and had plans for developing them. The study showed an increasing trend to create criteria that assist in administrative actions when problems arise. In the 31 sets of noncognitive criteria submitted for the study, the rank order of specific expectations was, from most to least frequently mentioned: honesty, professional behavior, dedication to learning, appearance, respect for law, respect for others, confidentiality, aid to others, substance abuse, and financial responsibility. The authors make recommendations for schools wishing to create noncognitive criteria and explain why they feel such criteria should receive the recognition and importance given to cognitive criteria.

Attitude↗
PubMed1989

Analysis of prepro-alpha-lytic protease expression in Escherichia coli reveals that the pro region is required for activity.

The alpha-lytic protease of Lysobacter enzymogenes was successfully expressed in Escherichia coli by fusing the promoter and signal sequence of the E. coli phoA gene to the proenzyme portion of the alpha-lytic protease gene. Following induction, active enzyme was found both within cells and in the extracellular medium, where it slowly accumulated to high levels. Use of a similar gene fusion to express the protease domain alone produced inactive enzyme, indicating that the large amino-terminal pro region is necessary for activity. The implications for protein folding are discussed. Furthermore, inactivation of the protease by mutation of the catalytic serine residue resulted in the production of a higher-molecular-weight form of the alpha-lytic protease, suggesting that the enzyme is self-processing in E. coli.

Cloning, Molecular↗
PubMed1988

Risk of sudden infant death syndrome among infants with in utero exposure to cocaine.

To determine whether the risk of sudden infant death syndrome (SIDS) among infants exposed to cocaine in utero may be elevated, we assessed the risk for SIDS in a large, well-described, prospective cohort of infants whose mothers had or had not used cocaine during pregnancy. Of 996 women consecutively enrolled while registering for prenatal care, 175 used cocaine during pregnancy. Only one infant of the mothers who used cocaine died of SIDS, a risk of 5.6 in 1000, compared with four infants among the 821 nonexposed infants, a risk of 4.9 in 1000. The relative risk for SIDS among infants whose mothers used cocaine during pregnancy compared with those whose mothers did not use cocaine was 1.17 (95% confidence interval 0.13, 10.43), suggesting that there is no increased risk of SIDS among infants exposed in utero to cocaine.

Adult↗
PubMed1988

Effect of in vitro DNA methylation on beta-globin gene expression.

When the human beta-globin gene was methylated at every cytosine residue and was inserted into mouse fibroblasts by DNA-mediated gene transfer, the transcription of the gene was strongly inhibited. This methylation also prevented expression and induction of the gene in mouse erythroleukemia cells. By using partially methylated hybrid molecules, it was shown that methylation-sensitive negative regulatory elements are located in both the 5' and 3' ends of the beta-globin gene but not in the 90-base-pair region usually associated with promoter activity. To further investigate the role of DNA methylation in the regulation of the beta-globin gene, 50-base-pair poly(dG-dC) tracts were introduced into various sites in a mouse-human hybrid gene, and these inserts were methylated by means of the Hha I methylase. Heavy methylation of these artificially added sites had no effect on either transcription initiation or elongation, suggesting that DNA modification operates through fixed endogenous sites in the gene domain.

Animals↗
PubMed1987

Modified scrub technique for sampling infant skin microflora.

Two techniques for quantitatively recovering normal-flora microorganisms from the skin of infants were compared. A technique using a swab to dislodge microorganisms from the skin compared favorably to a technique using a rubber policeman. The swab was easier to use and is suitable for use on infant skin.

Bacteria↗
PubMed1987

The effects of teaching medical students psychotherapy skills in the outpatient department.

A psychiatric clerkship which emphasizes a clinical exposure to the conduct of outpatient psychodynamic psychotherapy is described and evaluated. Compared to more traditional inpatient based clerkships, an outpatient psychotherapy-oriented clerkship attracts significantly greater numbers of students. In addition, medical students taking such a rotation rate its educational value on its completion significantly more positively compared to other clerkship sites. Finally, students taking the psychotherapy oriented clerkship opt for psychiatry as a specialty significantly more frequently than students taking the more traditional clerkships. The impact of such a learning experience on interpersonal skills with non-psychiatric, medical patients is also discussed.

Attitude of Health Personnel↗
PubMed1987

Suppression of luteal function in dogs by luteinizing hormone antiserum and by bromocriptine.

Beagle bitches were treated with equine anti-LH serum (ALHS) or the dopamine agonist bromocriptine at selected times during the 2-month luteal phase of the ovarian cycle or pregnancy. After a single injection of ALHS (10 ml, i.m.) at Day 42 of pregnancy (N = 2) or the ovarian cycle (N = 3), progesterone was reduced (P less than 0.05) to 7-24% of preinjection values within 1-2 days, and by 4-8 days returned to levels not different from those in control bitches treated with normal horse serum. Injections of bromocriptine (0.1 mg/kg, i.m.) daily for 6 days caused abrupt declines in progesterone which lasted 6-8 days in bitches treated at Day 8 or 22 of pregnancy (N = 5). In bitches treated at Day 42 of pregnancy (N = 3) or in non-pregnant cycles (N = 4) the bromocriptine treatment caused declines (P less than 0.05) in progesterone which were permanent, extensive (less than 2 ng/ml), and therefore abortive. The declines in progesterone in response to immunoneutralization of LH and to prolactin-lowering doses of a dopamine agonist demonstrate that normal luteal function in dogs requires both LH and prolactin.

Animals↗