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Biomedical subjects

L Allen

Publications and source records attributed to L Allen.

At least 19 recordsLinked to original sources
PubMed1992

Preliminary assessment of a scientific curriculum in a surgical residency program.

A structured, basic science curriculum was instituted for surgical residents of the University of Connecticut (Farmington) Integrated Residency Program during the 1990-1991 academic year in concordance with American Board of Surgery guidelines. The impact of the new program was measured by comparing performance on monthly basic science examinations, the in-training examination, and "mock" oral examinations for the 1990-1991 academic year with that of the preceding academic year. While monthly examination scores improved for the entire group of residents (67.7 vs 64.6), in-training and oral examination scores did not change significantly. Categorical residents generally demonstrated superior performance and greater improvement than did preliminary residents. Data analysis suggested that the new curriculum was an effective educational device and that university-designed monthly examinations were valid testing instruments, but there was an apparent incongruity between the goals of the curriculum and the American Board of Surgery In-Training Examination.

Attitude↗
PubMed1992

Effects of surfactant apolipoproteins on liposome structure: implications for tubular myelin formation.

Tubular myelin is one of several forms of lung surfactant and may play an important role in its surface activity. To determine possible mechanisms of tubular myelin formation, we studied the effects of purified surfactant proteins (SP-A, SP-B, and SP-C) on large unilamellar dipalmitoylphosphatidylcholine-egg phosphatidylglycerol (7/3; wt/wt) liposomes. We studied different types of membrane interaction induced by the apolipoproteins and correlated these with the observed changes in ultrastructure. Aggregation was assessed by measurement of light absorbance, lysis, and fusion by measurement of the fluorescence emitted by water-soluble and lipid-soluble probes, respectively. Mixtures of the apolipoproteins and liposomes were examined in ultrastructural studies by negative staining and by thin sectioning. We found that each protein had a pronounced and distinct effect on liposome structure. SP-A caused aggregation, whereas SP-B and SP-C also caused extensive leakage of liposome contents (lysis) and some degree of lipid mixing (fusion). The disruptive effects of SP-B and to a lesser extent those of SP-C were correlated by negative staining with the appearance of bilayer disks, which tended to aggregate into large sheets. There was a marked synergy between SP-A and SP-B in the process of membrane fusion in the presence of calcium, which correlated with an early (10 min) and extensive rearrangement of the structures seen by electron microscopy followed by a delayed (24 h) appearance of small amounts of tubular myelin.

Animals↗
PubMed1992

Phase I trial of the chimeric anti-GD2 monoclonal antibody ch14.18 in patients with malignant melanoma.

The chimeric monoclonal anti-GD2 antibody ch14.18 is made up of the variable region of the murine anti-GD2 antibody 14.18 (or its IgG2a switch variant 14G2a) and the constant region of human IgG1k. Ch14.18 mediates antibody dependent cytotoxicity and complement dependent lysis in vitro. In a phase I trial, 13 patients with metastatic melanoma received ch14.18 as a single dose of 5-100 mg. Therapy was associated with an infusion-related abdominal/pelvic pain syndrome, which required intravenous morphine for control. The pharmacokinetics of ch14.18 best fit a two-compartment model with a T1/2 alpha of 24 +/- 1 hr and a T1/2 beta of 181 +/- 73 hr. Eight of 13 patients developed a weak-modest antibody response directed at the variable region of ch14.18. Clinical antitumor responses were not observed at the doses employed in this study. However, patients receiving greater than 45 mg of ch14.18 had antibody detectable on tumor cells analyzed by fluorescent activated cell sorter. Further modification of the therapeutic regime employing larger doses and frequent administration of ch14.18 are planned.

Adult↗
PubMed1991

Multiple human D5 dopamine receptor genes: a functional receptor and two pseudogenes.

Three genes closely related to the D1 dopamine receptor were identified in the human genome. One of the genes lacks introns and encodes a functional human dopamine receptor, D5, whose deduced amino acid sequence is 49% identical to that of the human D1 receptor. Compared with the human D1 dopamine receptor, the D5 receptor displayed a higher affinity for dopamine and was able to stimulate a biphasic rather than a monophasic intracellular accumulation of cAMP. Neither of the other two genes was able to direct the synthesis of a receptor. Nucleotide sequence analysis revealed that these two genes are 98% identical to each other and 95% identical to the D5 sequence. Relative to the D5 sequence, both contain insertions and deletions that result in several in-frame termination codons. Premature termination of translation is the most likely explanation for the failure of these genes to produce receptors in COS-7 and 293 cells even though their messages are transcribed. We conclude that the two are pseudogenes. Blot hybridization experiments performed on rat genomic DNA suggest that there is one D5 gene in this species and that the pseudogenes may be the result of a relatively recent evolutionary event.

Amino Acid Sequence↗
PubMed1991

Pharmacokinetics and immune response of 131I-chimeric mouse/human B72.3 (human gamma 4) monoclonal antibody in humans.

Chimeric B72.3, composed of the V-regions of murine B72.3 and the constant regions of human immunoglobulin G4 heavy and kappa light chain, was administered as a 131I-labeled conjugate to 12 patients with metastatic colon cancer. Seven of these patients had an antibody response after initial infusion, and the immune response was primarily directed to the murine V-region, although a small proportion of the antibody response was directed to topographical epitopes requiring the presence of both murine V-region and human CH-1 and kappa constant regions (neo-epitopes). The pharmacokinetics included a plasma disappearance curve best fit by a two-compartmental model with an alpha t 1/2 of 18 +/- 7 h and a beta t 1/2 of 224 +/- 66 h. A second infusion of the same dose of 131I-chimeric B72.3 was administered to four of these patients 8 wk after the first infusion. Two patients who had a high antibody response to initial infusion had an anamnestic antibody response, and the infused ch-B72.3 rapidly disappeared from the circulation with associated immune complexes and free 131I in the plasma. One patient with no initial antibody response had no antibody response and identical pharmacokinetics on second infusion. One patient with a modest transient antibody response to initial infusion had no antibody response on second infusion and a modest shortening of plasma circulation. Thus, the human immunoglobulin G4 isotype chimeric B72.3 monoclonal antibody has a plasma half-life 6 to 8 times as long as murine B72.3 and retains considerable immunogenicity in some patients which can adversely affect repetitive infusions.

Animals↗
PubMed1991

Intrachromosomal location of the telomeric repeat (TTAGGG)n.

Eukaryotic telomeres are specialized DNA-protein structures that are thought to ensure chromosomal stability and complete replication of the chromosome ends. All telomeres which have been studied consist of a tandem array of G-rich repeats which seem to be sufficient for telomere function. Originally, the human telomeric repeat (TTAGGG)n was assumed to be exclusively located at the very end of all human chromosomes. More recent evidence, however, suggests an extension into proterminal regions. Very little is known about the interstitial distribution of telomeric repeats. Here we present evidence for the presence of (TTAGGG)n repeats in internal loci on the long and short arms of different human chromosomes. In addition, we studied the genomic organization of these repeats in more detail and discuss possible functions of interstitial telomeric repeats in the human genome.

Base Sequence↗
PubMed1991

Mineral homeostasis in obesity: effects of euglycemic hyperinsulinemia.

We explored the effects of insulin on mineral homeostasis in five lean and six moderately obese nondiabetic premenopausal women. Serum and urine minerals were measured before and during the steady-state phase of a euglycemic insulin clamp. Each subject participated in two insulin clamp studies on separate days at insulin infusion rates of 10 and 40 mU/m2/min. Euglycemic hyperinsulinemia was associated with (1) a significant increase in urinary calcium excretion when expressed per minute with no change in total serum calcium; (2) a decrease in urine and serum phosphate; (3) a decrease in serum potassium with no change in urine potassium; and (4) no measurable effects on urine or serum sodium. At any given insulin level, the obese individuals excreted significantly more calcium, phosphate, and potassium per minute than lean controls. While insulin administration had no effect on serum parathyroid hormone (PTH) or vitamin D levels, baseline serum 1,25(OH)2D concentration was significantly higher and serum ultrafilterable calcium was significantly lower in obese subjects than in lean controls.

Adult↗
PubMed1991

Localization of the fibrillin (FBN) gene to chromosome 15, band q21.1.

Fibrillin (FBN), a large extracellular matrix glycoprotein, is an important component of structures called microfibrils. Because fibrillin microfibrils appear to be abnormal in patients with the Marfan syndrome, fibrillin is a candidate for the gene defect in the Marfan syndrome. Derived clones from fibrillin cDNA were used as probes in isotopic and nonisotopic in situ hybridization studies to map the chromosomal location of the fibrillin gene. Fluorescent signals were found on chromosome 15 band q21.1; an excess of silver grains was noted over a similar region of chromosome 15 following in situ hybridization with a tritium-labeled probe. These results are consistent with linkage studies that localize the Marfan gene to chromosome 15.

Amino Acid Sequence↗
PubMed1991

A low-copy repeat located in subtelomeric regions of 14 different human chromosomal termini.

Two cosmid clones, cG1A3 and cG1A6, containing large blocks of a telomeric repeat sequence, (TTAGGG)n, were isolated independently. Restriction mapping and fingerprinting studies suggested that cosmid cG1A6 is entirely contained within cG1A3. Competitive in situ hybridization localized cG1A3 to 14 different human telomeres and one internal site at 2q14----q21, indicating the presence of a subtelomeric low-copy repeat within this cosmid.

Base Sequence↗
PubMed1990

A human D1 dopamine receptor gene is located on chromosome 5 at q35.1 and identifies an EcoRI RFLP.

Dopaminergic neurons have been shown to affect voluntary movement, hormone secretion, and emotional tone. Mediating these activities are two receptor subtypes, D1 and D2, which are biochemically and pharmacologically distinct. The D1 subtype, the most abundant form of dopamine receptor in the central nervous system, stimulates adenylate cyclase, modulates D2 receptor activity, regulates neuron growth and differentiation, and mediates several behavioral responses. Recently we reported the cloning of a human D1 dopamine receptor gene (DRD1). High-stringency hybridization of the DRD1 clone to human genomic blots suggests that DRD1 is single copy. When used to probe a Southern blot made with DNAs from a rodent-human somatic cell hybrid panel, DRD1 hybridized to a 6.5-kb EcoRI restriction fragment which was assigned to chromosome 5. Fluorescent in situ hybridization of this gene to human metaphase chromosomes refined the location of DRD1 to 5q35.1. A search for RFLPs associated with DRD1 identified a two-allele EcoRI RFLP, allowing confirmation of DRD1's localization by linkage analysis in Centre d'Etude du Polymorphisme Humain families.

Alleles↗
PubMed1979

Self-concept and identified problem differences between pre- and postmenarcheal adolescents.

Examined differences in the number and types of problems as well as in self-reported self-concept between 232 middle and low SES pre- and postmenarcheal adolescents. The study also examined differences in these variables across four developmental levels of menarcheal status: Initial, Intermediate, Middle, and Established. These data were analyzed by a multiple ANOVA technique, and significant differences were found between pre- and postmenarcheal girls and between the two social class groups. Postmenarcheal adolescents had more problems, but were also higher on self-concept variables. Low SES females experienced the menarche earlier than middle class SES females, had different problems, and described themselves differently on the self-concept measures. These data were interpreted as supporting the view that menarche onset is a positive event for most young females.

Adolescent↗
PubMed1977

Comparison of the curative antimalarial activities and toxicities of primaquine and its d and l isomers.

This investigation was undertaken to determine whether either d-primaquine or l-primaquine has sufficient advantage over primaquine to warrant evaluation for curative activity in human volunteers infected with Plasmodium vivax. It was found: (i) that the capacities of the isomers and the racemate to cure infections with Plasmodium cynomolgi in rhesus monkeys were essentially identical; (ii) that the subacute toxicities of the isomers and racemate for this monkey were qualitatively the same, but that l-primaquine was three to five times as toxic as d-primaquine and at least twice as toxic as primaquine; and (iii) that the acute single-dose toxicities of the isomers for mice were not only qualitatively different, but that the d isomer was at least four times as toxic as l-primaquine. Since previous appraisals of curative activity and tolerability of 8-aminoquinolines in rhesus monkeys have correlated well with appraisals in human volunteers, attention was focused on results acquired with these test subjects. The relevant evaluations showed that d-primaquine had a therapeutic index at least twice that of primaquine. If this advantage carries over to man, problems that now complicate routine use of primaquine might be obviated. Therefore, a critical comparison of d-primaquine and primaquine in human volunteers seems indicated.

Animals↗
PubMed1976

Malignant lymphoma of the small intestine in multiple family members: association with an immunologic deficiency.

Four cases of malignant lymphoma all in male members of a family are described. In three of the affected individuals the primary tumor arose in the small intestine and in the other the site of origin was the retroperitoneum. Immunologic studies were carried out on the two surviving patients and on all other living members of their families. Low levels of immunoglobulins were found in one of the affected boys. During a recurrence of the tumor, the other boy showed temporary partial impairment of cellular immunity as measured by failure to react to delayed hypersensitivity skin tests, although lymphocyte transformation studies were normal. Nine months after treatment was completed his response to skin tests was normal. No immunologic defect was detected in the studies of the non-involved family members. The histologic appearance of the tumors was similar in the tissue sections which were available for review from three of the four patients; the tumor was classified as a malignant lymphoma, diffuse, mixed cell type (lymphocytic and histiocytic).

Agammaglobulinemia↗
PubMed1976

Surgical correction of superior sulcus deformity occurring after enucleation.

A prefabricated, sculptured, subperiosteal orbital floor implant was used in six cases of cosmetically unacceptable deep superior eyelid sulcus that occurred after enucleation. The implant provided anterior and superior displacement of orbital contents. Surgical placement was similar to the approach for implant placement in orbital floor fracture and provided satisfactory cosmetic and functional results.

Eye, Artificial↗