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Biomedical subjects

C Chase

Publications and source records attributed to C Chase.

At least 37 records · Page 2Linked to original sources
PubMed1995

Cardiac effects of growth hormone in short normal children: results after four years of treatment.

Growth hormone excess is known to have adverse effects on the heart. The long term cardiac effects of growth hormone given to short normal children as part of a prospective randomised controlled trial of growth hormone treatment (Genotropin 30 IU/m2/week v no treatment) were therefore investigated. Echocardiographic findings are presented for 28 children who have been followed up for a minimum of four years. At the outset, the treated (n = 15) and untreated groups (n = 13) did not differ for any anthropometric or echocardiographic parameter. Their mean (SD) age at onset was 7.8 (0.5) years. After four years of treatment mean height SD score increased from -2.4 to -1.2 compared with no change (-2.5) in the untreated group. Left ventricular posterior wall and septal thickness and left ventricular shortening fraction did not differ between the groups, but a tendency towards increased left ventricular mass was seen in the treatment group (93 v 73 g). No such differential was observed after indexing left ventricular mass for body surface area (79 v 71 g/m2) or lean body mass (3.15 v 3.05 g/kg). It is concluded that prolonged growth hormone treatment does not cause important changes to the heart. A tendency towards increased left ventricular mass simply reflects the increase in lean body mass during treatment.

Anthropometry↗
PubMed1994

Substitution of class II alpha chain polymorphic residues defines location of A alpha k serologic epitopes and alters association between alpha beta and Ii polypeptides.

Structure-function studies of the MHC class II alpha chain have been performed by constructing a panel of A alpha k cDNA genes with one or more d allele substitutions at each polymorphic residue of the alpha 1 domain. The altered genes (A alpha k*) were transfected into a B lymphoma cell line (BKO), which is deficient in A alpha mRNA but retains constitutive wild-type A beta k mRNA expression. Cytofluorometric analysis of cell surface A alpha k* Ak beta molecules was used to map the polymorphic alpha chain residues comprising four serologic epitopes. A alpha k-reactive mAbs 1E9, 2A2, and 3F12 recognize an epitope that includes the polymorphic residue 44 of the A alpha k polypeptide, and the A alpha k-reactive antibody, K24-199, recognizes a conformationally determined epitope influenced by residues from all three polymorphic regions. In addition, we confirmed previous studies demonstrating that la.19 and la.2 mAbs bind to epitopes adjacent to residue 75 in A alpha k. A cell surface negative expression variant also was identified in the panel of mutant cell lines and biochemically characterized. Substitution of six d allele polymorphic residues at positions 11, 14, 28, 69, 70, and 75 in the A alpha k polypeptide (T.EG A alpha k* A beta k*) results in an A alpha k* polypeptide that associates with the A alpha k polypeptide but does not associate with the li polypeptide. This defect in li-A alpha k A beta k interaction is associated with a conformational change in the alpha 1 beta 1 domain that was identified by altered reactivity of the T.EG complex with conformationally dependent anti-alpha and anti-beta mAbs.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Comprehension and expression of affect in language-impaired children.

Eight children with developmental language impairment (LI) and eight age-, sex-, socioeconomic-status-, and I.Q.-matched controls were given tests of comprehension and expression of affective intent in spoken language and through facial expression. The LI children performed significantly more poorly than did controls in both comprehension and spontaneous expression of vocal affect. On tasks involving emotional facial expression, the opposite results were observed: The LI children were more dramatic in their expression of facial affect than were the controls. Children with language impairment appear to have a deficit in affective comprehension and expression that is modality-specific, i.e., limited to vocal affect. The heightened range of affective facial expression that they demonstrate may be a compensatory mechanism to offset their difficulties with vocal affect.

Adolescent↗
PubMed1993

Adsorption losses from urine-based cannabinoid calibrators during routine use.

The major metabolite of cannabis found in urine, 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (delta 9-THC), is the compound most often used to calibrate cannabinoid immunoassays. The hydrophobic delta 9-THC molecule is known to adsorb to solid surfaces. This loss of analyte from calibrator solutions can lead to inaccuracy in the analytical system. Because the calibrators remain stable when not used, analyte loss is most probably caused by handling techniques. In an effort to develop an effective means of overcoming adsorption losses, we quantified cannabinoid loss from calibrators during the testing process. In studying handling of these solutions, we found noticeable, significant losses attributable to both the kind of pipette used for transfer and the contact surface-to-volume ratio of calibrator solution in the analyzer cup. Losses were quantified by immunoassay and by radioactive tracer. We suggest handling techniques that can minimize adsorption of delta 9-THC to surfaces. Using the appropriate pipette and maintaining a minimum surface-to-volume ratio in the analyzer cup effectively reduces analyte loss.

Adsorption↗
PubMed1991

Functional effects of N-linked oligosaccharides located on the external domain of murine class II molecules.

To evaluate the potential functional role of the alpha- and beta-chain N-linked oligosaccharides we used site-directed mutagenesis to construct class II Ak alpha and Ak beta genes that encode polypeptides with altered N-linked oligosaccharide acceptor sites in the N-terminal domain of both polypeptides. The alpha 1 domain acceptor site at positions 82 to 84 was eliminated by substituting Gln for Asn at position 82. The beta 1 domain acceptor site at positions 19 to 21 was deleted by substituting Gln for Asn at position 19 or Ala for Thr at position 21. The mutant genes (Ak alpha* or Ak beta*) were transfected either individually (mutants T.19, T.21, and T.82) or together (mutant T.82-21) into class II cell surface negative B lymphoma cell lines. Quantitative immunofluorescence with a panel of Ak beta- or Ak alpha- reactive mAb demonstrated that although the oligosaccharide-deleted Ak alpha Ak beta molecules were serologically wild type, the Ad alpha serologic epitope defined by mAb K24-199 was eliminated in both the T.19 and T.21 Ak beta* Ad alpha molecules. Cloned cell lines expressing the T.19 or T.21 Ak beta* Ak alpha molecules exhibited limited functional Ag presentation defects. Cells expressing the T.82 Ak alpha* Ak beta molecules exhibited defects in Ag presentation function to nine of the ten T hybridomas tested. Surprisingly, cells expressing the mutant T.82-21 class II molecule stimulated a response that was equal to the wild-type response from three of the nine T hybrids and a response that was significantly greater than that of wild-type cells from five of nine T hybridomas. These functional and serological analyses also indicate that some of the observed Ag presentation defects may be due to altered secondary structure caused by either deletion of the oligosaccharide or the amino acid substitution used to delete the N-linked oligosaccharide acceptor site.

Amino Acid Sequence↗
PubMed1990

Otitis media in infancy and intellectual ability, school achievement, speech, and language at age 7 years. Greater Boston Otitis Media Study Group.

To determine intellectual and linguistic sequelae of middle ear disease, 207 children were randomly selected from a cohort of 498 followed prospectively from birth until age 7 years. After controlling for confounding variables, estimated time spent with middle ear effusion (MEE) during the first 3 years of life was significantly associated with lower scores on tests of cognitive ability, speech and language, and school performance at age 7 years. The adjusted mean full-scale WISC-R were 113.1 for those with least time with MEE, 107.5 for those with moderate time, and 105.4 for those with most time. Similar significant differences were found for verbal and performance IQ scores. For the Metropolitan Achievement Test, we found that middle ear disease in the first 3 years of life was associated with significantly lower scores in mathematics and reading. Similar differences were found for articulation and use of morphologic markers. After considering time spent with MEE during the first 3 years of life, time spent after age 3 years was not a significant predictor of scores on any of the tests administered.

Child↗
PubMed1988

Regulation of murine MHC class II molecule expression. Identification of A beta residues responsible for allele-specific cell surface expression.

A panel of mutant class II genes have been constructed using site-directed mutagenesis and DNA-mediated gene transfer. Using this technique, Ak beta polypeptides have been altered by substituting one or more Ad beta-specific residues at polymorphic positions in the beta 1 domain. Transfection of M12.C3 B lymphoma cells with most mutant Ak beta* genes results in the expression of Ak beta* Ad alpha molecules on the cell surface. However, the substitution of a single d allele residue at position 78 or 86 in the Ak beta polypeptide results in either the complete absence or very low levels, respectively, of cell surface expression of the Ak beta* Ad alpha molecule, but does not alter Ak beta* Ak alpha expression. The T.86 Ak beta* Ad alpha is expressed primarily in an intracellular compartment while the T.78 Ak beta* molecule does not appear to be produced. The core-glycosylated T.78 Ak beta* polypeptide does, however, form a complex intracellularly with the core-glycosylated Ii polypeptide. Substitution of the combination of d allele residues at Ak beta polymorphic positions 9, 12, 13, 14, and 17 results in the absence of Ak beta* Ak alpha cell surface expression but does not alter the expression of this mutant Ak beta* polypeptide with the Ad alpha polypeptide. These allele-specific expression mutants demonstrate that substitution at certain beta 1 domain positions may result in the alteration of Ia cell surface expression and that the transport of Ia molecules from the Golgi apparatus to the cell surface may be regulated by signals that are determined by the interaction of polymorphic residues in both the alpha and beta polypeptides.

Amino Acid Sequence↗
PubMed1986

Evaluation of the efficacy of piracetam in treating information processing, reading and writing disorders in dyslexic children.

Piracetam, a new class of drug (nootropil) thought to enhance specific cognitive skills, was given in a 3300 mg daily dose to half of a group of fifty-five dyslexic boys aged 8-13 years, in a 12-week, double-blind, placebo-controlled study. The other half of the subjects received placebo. All subjects met the following criteria: normal intelligence, normal educational opportunities, no severe emotional problems, no neurological handicaps, good physical health, not taking other psychotropic medication, and scoring at least one and one half years below their mental age equivalent on the Gilmore Oral Reading Test. Non-verbal (auditory and visual) and verbal perceptual, and memory skills were examined, and reading, spelling, language and writing abilities were measured using standardized instruments. Compared to the placebo control group, individuals treated with Piracetam did not show statistically significant improvements above their baseline scores on measures of perception, memory, language, reading accuracy or comprehension, or writing accuracy. However, reading speed and numbers of words written in a timed period were significantly enhanced in subjects treated with Piracetam as compared to placebo. Effective reading and writing ability, taking both rate and accuracy into consideration, were also significantly improved in the Piracetam as compared to the placebo treatment group. The medication was well-tolerated and medical examinations showed no significant adverse reactions. These results encourage further study of Piracetam to determine more precisely the mechanism of action by which specific cognitive skills are affected.

Adolescent↗
PubMed1985

A point-addressable transfer system for automated sampling, feeding, and expansion of hybridoma cultures.

A Dynatech Autoprep liquid sampling system has been modified to perform fully automated aseptic sampling, feeding, and expansion of hybridoma cultures in standard 96- and 24-well culture plates. The system is controlled by an Apple IIe computer, and uses a single teflon probe to transfer culture medium from randomly located wells to EIA plates and deliver fresh medium to the sampled wells. An 'expansion mode' allows suspension of cells for transfer to another plate. The sampling probe may be washed with sterile medium, buffer, or water between each transfer. Any combination of up to 6 assay plates, sterile growth plates, and expansion plates may be operated on at one time, and each transaction is recorded on a floppy disk file. Experiments with various hybridoma cultures indicated that transfers were reproducible, sterility was maintained, and the washing procedure reduced cross-contamination of cultures with other cells or antibodies to negligible levels. The APPLE BASIC computer programs which perform the functions and record the transactions are described in the paper and the Appendix, and are available upon request.

Animals↗
PubMed1980

Reassessment of cancer predisposition of Fanconi anemia heterozygotes.

The hypothesis that heterozygotes for the Fanconi anemia (FA) gene are predisposed to cancer was investigated by comparing the observed and expected numbers of cancer cases and deaths in 25 extended families of FA probands. This study demonstrated no overall excess of cancers of cancer deaths for any age or sex category of blood relatives and no unusual number of cancers among the obligate heterozygotes. Deaths from leukemia among blood relatives were fewer than expected. For bladder, stomach, and breast cancer there were more deaths and cases among blood relatives than expected, although the differences were not statistically significant. An excess of deaths at an early age from lung and stomach cancer was noted among the FA blood relatives. Among spouse controls there were fewer deaths than expected from bladder, stomach, and breast cancer; thus the expected numbers may be inappropriately high for this sample. Therefore, the question of predisposition to bladder, stomach, and breast cancer among FA heterozygotes remains unresolved.

Adolescent↗
PubMed1979

Cancer in families with xeroderma pigmentosum.

In 31 families of xeroderma pigmentosum (XP) patients, significantly more blood relatives than spouse controls had had nonmelanoma skin cancer. These family data support the hypothesis that heterozygosity for XP genes may predispose persons to skin cancer, particularly in association with substantial exposure to sunlight.

Adult↗