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Biomedical subjects

L Berger

Publications and source records attributed to L Berger.

At least 91 records · Page 5Linked to original sources
PubMed1986

Kinetic disposition of morphine in young males after intravenous loading and maintenance infusions.

Loading and maintenance infusions of morphine sulfate were administered to 5 young male patients 23-34-yr-old prior to elective surgery. Apparent steady-state plasma concentrations were achieved 30 minutes after the start of the drug infusion. The volume of distribution at steady-state (2.43 +/- 0.48 L X kg-1), beta elimination rate constant (0.700 +/- 0.162/h) and plasma clearance (1.66 +/- 0.33 L X kg-1 X h-1) were similar to values previously determined in young healthy subjects receiving a single bolus infusion. These data confirm our findings concerning morphine disposition in healthy young subjects and demonstrate the feasibility of achieving predictable plasma concentrations of morphine for future assessment of pharmacodynamic/pharmacokinetic relationships for this drug.

Adult↗
PubMed1985

Akinetic mutism and parkinsonism associated with obstructive hydrocephalus.

We report the case of a patient with idiopathic aqueductal stenosis and hydrocephalus who had several episodes of akinetic mutism, each preceded by shunt malfunction, that resolved with shunt revision. She also developed a parkinson's syndrome resistant to shunt revision but responsive to antiparkinsonian medications. The parkinson's syndrome and the episodes of akinetic mutism may be related to a reduction of dopaminergic input to the striatum and to the cingulate and frontal cortex brought about or worsened by ventricular dilatation.

Adult↗
PubMed1985

Complete nucleotide sequences of three VH genes in Caiman, a phylogenetically ancient reptile: evolutionary diversification in coding segments and variation in the structure and organization of recombination elements.

Complete nucleotide sequences are described for three caiman (Caiman crocodylus crocodylus) immunoglobulin VH genes (C3, E1, and G4) that hybridize with a murine VH probe. The E1 and G4 genes are physically linked (intergenic distance, approximately equal to 6.5 kilobases) in the same transcriptional orientation but are not directly contiguous with the C3 gene. When the coding segments, including both framework and complementarity-determining regions, of these genes and the murine probe sequences are compared by metric analysis, it is apparent that the caiman genes are only slightly more related to each other than to the mammalian sequence, consistent with significant preservation of nucleotide sequence over an extended period of phylogenetic time. Based on the presence of transcriptionally critical 5' sequences and the absence of terminator codons, frameshift mutations, or other recognizable alterations, the genes do not appear to be pseudogenes. The E1 gene, however, is distinguished from other VH genes because (i) the spacer region within the 3' recombination signal sequence is 12 base pairs, typical of VK genes but not of VH genes, which possess 22- to 23-base-pair spacers and (ii) a near-perfect VH recombination signal sequence is present within the intervening sequence that splits the segment encoding the leader. These studies establish VH gene multiplicity in a species that arose prior to mammalian radiation and provide a description of differences in the configuration and location of recombination elements associated with an otherwise potentially functional gene.

Alligators and Crocodiles↗
PubMed1985

Immunoglobulin VH gene structure and diversity in Heterodontus, a phylogenetically primitive shark.

A mouse VH probe has been used to identify and isolate VH homologs in a DNA library of Heterodontus francisci (horned shark). The complete nucleotide sequence of one VH gene, HXIA, has been determined and found to exhibit striking organizational homology and nucleotide identity with mammalian prototype VH genes. Metric analysis of the complete sequence is consistent with the early phylogenetic diversification of framework and complementarity-determining regions (CDR). Both the predicted amino acid sequence and the specific hybridization of the CDR2-specific, synthetic oligodeoxynucleotide probe in spleen mRNA suggest that HXIA is functionally expressed. A probe consisting of the entire coding region of this gene hybridizes with multiple components in Southern blot analysis of Heterodontus genomic DNA and together with the identification of additional unique VH+-lambda clones indicates that considerable complexity is associated with the germline VH gene family in a contemporary species that represents an early stage in the phylogenetic development of the vertebrates.

Amino Acid Sequence↗
PubMed1983

Complete nucleotide sequence of an immunoglobulin VH gene homologue from Caiman, a phylogenetically ancient reptile.

Immunoglobulin variable (V) gene regions typify extensive multigenic families in terms of overall size, chromosomal arrangement and presence of large numbers of apparent pseudogenes. A unique mechanism of somatic reorganization involving recombination of VH, D and JH or VL and JL segments accompanies the differentiation of lymphoid cells and together with somatic mutation and other types of recombination accounts for V-region diversity. Although these processes have been well characterized in higher mammals, little is known concerning their origin and diversification during phylogenetic time. Previously, we described the blot-hybridization characteristics of murine VHIII probes with restriction enzyme-digested genomic DNA isolated from several phylogenetically critical species, including Caiman crocodylus, a modern representative of an ancient reptilian subclass. Here we have used a murine probe, S107V, to select homologous clones from a library of Caiman genomic DNA constructed in a lambda bacteriophage. The complete nucleotide sequence of a Caiman gene homologous to the murine VH gene and its adjacent 5' and 3' region is described. Comparison of the sequence with mammalian prototypes shows evidence of considerable organizational and structural homology extending outside the presumed VH-coding region and including elements believed to be involved in somatic recombination. Inferences about the evolution of this multigenic family can now be extended to the level of phylogenetic class.

Alligators and Crocodiles↗
PubMed1983

Age-related morphine kinetics.

The kinetic disposition of morphine was compared in 13 young and 7 older healthy subjects after a single intravenous dose of 10 mg/70 kg morphine. The apparent volume of distribution at steady state in elderly subjects was only half of that in young subjects. This difference was derived from reductions in both central and peripheral kinetic compartment volumes in the older subjects. The beta elimination phase for morphine was more rapid, but its plasma clearance was reduced in older subjects. Calculation of the peripheral compartment morphine concentration for these subjects indicated that drug concentration in this kinetic space was higher in older subjects for 1.5 hr after dosing.

Adult↗
PubMed1982

Multiple components in restriction enzyme digests of mammalian (insectivore), avian and reptilian genomic DNA hybridize with murine immunoglobulin VH probes.

High molecular weight genomic DNAs isolated from an insectivore, Tupaia, and a representative reptilian, Caiman, and avian, Gallus, were digested with restriction endonucleases transferred to nitrocellulose and hybridized with nick-translated probes of murine VH genes. The derivations of the probes designated S107V (1) and mu 107V (2,3) have been described previously. Under conditions of reduced stringency, multiple hybridizing components were observed with Tupaia and Caiman; only mu mu 107V exhibited significant hybridization with the separated fragments of Gallus DNA. The nick-translated S107V probe was digested with Fnu4H1 and subinserts corresponding to the 5' and 3' regions both detected multiple hybridizing components in Tupaia and Caiman DNA. A 5' probe lacking the leader sequence identified the same components as the intact 5' probe, suggesting that VH coding regions distant as the reptilians may possess multiple genetic components which exhibit significant homology with murine immunoglobulin in VH regions.

Alligators and Crocodiles↗
PubMed1982

Impaired renal function gout: its association with hypertensive vascular disease and intrinsic renal disease.

Inulin clearance was measured in 624 patients with gout, and para-aminohippuric acid (PAH) clearance in 359; Group I consisted of 397 patients with uncomplicated gout; Group II, 191 patients with hypertension and/or ischemic heart disease; and Group III, 36 patients with chronic renal disease. Mean inulin clearance was normal in Group I, slightly depressed in Group II and more markedly decreased in Group III. There was some reduction in PAH clearance in all groups, but not in the very young patients with no complications. A disproportionate reduction in PAH clearance was noted in Groups II and III, particularly in the older patients with longer duration of gout. Uncomplicated gout, except in rare cases of fulminating gout, does not lead to decreased renal hemodynamics. An increased incidence of tophi correlates with decreased renal function, but incidence of renal calculi does not. Renal insufficiency when seen in patients with gout usually correlates with coexistence of hypertension, ischemic heart disease, or primary preexistent renal insufficiency.

Adolescent↗
PubMed1982

Task monotony and performance efficacy of mentally retarded young adults.

Mildly mentally retarded young adults were exposed to one of three training arrangements for vigilance performance, a monitoring task that some professionals consider uniquely appropriate for such persons because they are assumed to be less susceptible to boredom. Evidence indicated that accuracy generally declines over time. Training approaches used in this study allowed component analysis of procedures used in a previous study in which accuracy did not decline. Replication of the divergent study's procedures and alternate arrangements produced the characteristic vigilance decrement that was unrelated to on-task errors but varied with certain off-task behavior. Accuracy levels mirrored the degree of tangible reinforcement but, like nonretarded observers, retarded monitors found the task boring or otherwise unrewarding.

Adult↗
PubMed1981

Effects of diuretics on urate and calcium excretion.

Forty-nine patients with gout, many with hypertension and/or renal calculi, were given hydrochlorothiazide, furosemide, or ticrynafen. Diuresis and increased clearances of sodium (Na), potassium (K), chloride (Cl), and calcium (Ca) occurred after a single dose of hydrochlorothiazide, 100 mg, or furosemide, 40 mg, orally. There was very slight change in urate and phosphorus clearances. With prolonged use of hydrochloride or furosemide, diuresis and increased electrolyte excretion disappeared. Urate and Ca excretion fell with hydrochlorothiazide. With long-term use of furosemide, urate excretion was suppressed, but Ca excretion was sustained. Ticrynafen produced diuresis and increased clearances of Na, K, and Cl. Calcium excretion was increased after a single dose and minimally decreased after long-term use. Most striking was the severe and rather sustained uricosuria. Though ticrynafen is an effective uricosuric, natriuretic, and antihypertensive agent, its hepatotoxicity and nephrotoxicity mitigate against its clinical use.

Adult↗
PubMed1981

A dopamine receptor model and its application in the design of a new class of rigid pyrrolo[2,3-g]isoquinoline antipsychotics.

A hypothetical model of the interaction of antipsychotic drugs with the dopamine receptor is described. This three-dimensional molecular model has been developed on the basis of plausible intermolecular interactions between pharmacophoric groups of diverse types of antipsychotic drugs and postulated amino acid side chain substituents of the receptor protein. Three essential binding sites (one possibly required for antagonism) and one lipophilic auxiliary binding site are identified. The geometry is defined via the three-dimensional structures of drugs exhibiting receptor activity, including (R)-apomorphine, (+)-dexclamol, and molindone (whose crystal structure has been determined). A new conformationally rigid pyrrolo[2,3-g]isoquinoline derivative has been designed to conform to the receptor model. The compound (+/-)-1 (2,6-dimethyl-3-ethyl-4,4a,5,6,7,8,8a,9-octahydro-4a,8a-trans-1H-pyrrolo[2,3-g] isoquinolin-4-one; Ro 22-1319) exhibits potent antipsychotic-like activity. The activity is stereospecific, residing in the (-) enantiomer, predicted and confirmed by X-ray crystal structure analysis of (-)-1.HCl to have the 4aR,8aR absolute configuration.

Animals↗