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C Chase

Publications and source records attributed to C Chase.

18 recordsLinked to original sources

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

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

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

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

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

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

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

Testing the significance of risk estimates for the predisposition of heterozygotes to common diseases.

A maximum-likelihood method has been used previously to estimate, from family studies, the relative risk of common disorders for heterozygous carriers of genes for certain autosomal recessive syndromes. In this paper statistical significance of relative risk estimates was evaluated using critical values from computer-generated sampling distributions of the test statistic. In several practical cases a significance test based on the computer-generated distribution was more conservative than a test which assumed normality for the sampling distribution.

Genes, Recessive

Malignant neoplasms in the families of patients with ataxia-telangiectasia.

Ataxia-telangiectasia (A-T) is an autosomal recessive syndrome associated with a greatly increased incidence of malignant neoplasms in homozygous affected individuals. Heterozygotes for the gene for A-T are thought to comprise about 1% of the general population and, therefore, it is important to know whether this gene also predisposes the heterozygous carrier to cancers. Heterozygous carriers of this gene are common among the close relatives of patients with A-T, although individual carriers cannot be identified by any clinical criterion or laboratory test. For this reason, we compared the incidence of death from malignant neoplasms in 2 families of patients with A-T to that expected in a random sample of the general population. There were 59 deaths from malignant neoplasms in relatives dying before age 75, compared to 42.6 expected (p less than 0.02). For A-T heterozygotes younger than age 45, the risk of dying from a malignant neoplasm was estimated to be greater than 5 times the risk for the general population. A-T heterozygotes may comprise more than 5% of all persons dying from a cancer before age 45. The incidence of ovarian, gastric, and biliary system carcinomas and of leukemia and lymphoma was increased in these A-T families. Other neoplasms that may be associated with this gene in heterozygotes include pancreatic, basal cell, colonic, breast, and cervical carcinomas.

Ataxia Telangiectasia

Neurologic features of Williams and Down syndromes.

Eight patients with Williams syndrome and 6 with Down syndrome, matched for age and full-scale IQ, underwent detailed neurologic testing as part of a large multidisciplinary research center study. Williams syndrome patients were small for gestational age and often had histories of failure-to-thrive and feeding problems as infants. Half of the Williams syndrome patients had epilepsy. On neurologic testing, Williams syndrome patients had greater difficulty with gross and fine motor coordination, oromotor skills, and cerebellar function than did those with Down syndrome. The neurologic distinctions between these 2 groups may reflect an underlying, as yet undefined, metabolic defect in Williams syndrome.

Adolescent

Diagnosis and treatment of personality factors in chronic low back pain.

The differentiation between primary versus secondary gains is useful for an understanding of the management of chronic low back pain. Primary gain is defined as the direct reduction of pain and emotional distress. Secondary gain is defined as the reduction of anticipatory pain-fear through the avoidance of the occasions of rearousal of pain. This differentiation helps to clarify the diagnosis as well as the treatment of back pain. A person's fear of pain is considered to be the central psychological factor that interferes with successful treatment of chronic low back pain. Research provides insight into how the person both internally and externally protects against pain-fear. The Hysterical Conversion Scale on the MMPI is interpreted to be a measurement of the current level of pain-fear rather than a statement about the physical versus psychological nature of the pain. The reduction of pain-fear is shown to explain the behavior of hysterical conversion patients. Treatment suggestions are made that focus on reducing the patient's fear of pain. These include: considerations for when to operate; a recommendation to give the patient accurate expectations about the pain he/she will experience during treatment; and a specialized pain counselor in hospitals and clinics in order to help manage the level of pain-fear among low back patients.

Back Pain

Puppets for Prevention: "playing safe is playing smart".

Successful use of puppetry for education of children is well documented in literature. However, in this age of mechanically animated toys and sophisticated children, we have matched realism with an element of high technology for optimal learning experience. This 15-minute video is the basis for a burn prevention and education program entitled "Puppets for Prevention." The video is a creative and lively discussion between two puppets. The dialogue is delivered in a manner that is not threatening. It covers the child's hospitalization, types of burns and how they heal, feelings on scarring and returning to school as well as the conventional preventive measures. The realism in the video comes from the puppets, which have been specially constructed to teach children about burns, skin grafts, donor sites, and rehabilitative garments. High technology comes from the use of the puppets' pretaped accounts incorporated with the actual puppet show creating a completely integrated presentation. Initial response has been overwhelmingly positive. Our survey of one control group one week after viewing the puppet show demonstrated that all found it favorable. Forty percent remembered basic first aid and 65% mentioned significant points of the presentation. We plan to continue ongoing evaluations with the estimated 1,500 children who will view our program this school year.

Burns

An education program for nurses from referring hospitals in a perinatal regionalization system.

Administering high-quality perinatal care at a regional center involves more than providing in-center service. An outreach education program was developed for nurses in referring hospitals. The authors believe that through the carefully phased development of an outreach education program, quality perinatal care on all levels can be realized.

Education, Nursing, Continuing