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Biomedical subjects

A C Davis

Publications and source records attributed to A C Davis.

At least 55 records · Page 3Linked to original sources

Molecular characterization of the C3HfB/HeN H-2Kkm2 mutation. Implications for the molecular basis of alloreactivity.

The C3HfB/HeN (C3Hf) mouse strain expresses an H-2Kk molecule, previously denoted H-2Kkv1, that is structurally and functionally distinct from H-2Kk of the parental C3H strain. By molecular genetic analysis, we demonstrate that the C3Hf H-2K gene carries a homozygous coding region mutation relative to the C3H allele, revealing that C3Hf meets the requirements for assignment of a mutant haplotype, H-2km2. C3Hf H-2Kkm2 bears a single clustered substitution of four nucleotides within 14 contiguous nucleotides in exon 3. Since this sequence also is present intact at the homologous position in H-2Dk of both C3H and C3Hf, the origin of the H-2Kkm2 mutation is consistent with a nonreciprocal sequence transfer from the H-2Dk donor gene, analogous to the mechanism proposed for generation of the H-2Kb mutations. The H-2Kkm2 mutation encodes three clustered amino acid substitutions, at positions 95, 98, and 99, that map to one of the large beta strands at the bottom of the peptide antigen binding cleft of the H-2Kkm2 molecule. The nature and location of these amino acid substitutions are unique relative to any other known H-2 mutant or HLA variant, and underscore the importance of the beta-pleated sheet in influencing CTL recognition. These results indicate that H-2Kkm2 alloantigenicity may derive largely from altered presentation of self cellular peptides.

Amino Acid Sequence↗

On the structure of polymeric IgM.

The cysteine at position 575 of the immunoglobulin mu heavy chain is thought to provide the only disulfide bonds joining the monomer subunits of mouse polymeric IgM. The importance of this cysteine in the assembly of polymeric IgM was investigated by using site-directed mutagenesis to produce mu chains with serine at position 575. Thirty percent of the secreted mutant IgM was covalently assembled polymer implying that cysteines other than Cys575 can form inter-subunit disulfide bonds. The polymeric IgM lacked J chain, mediated complement-dependent cytolysis and appeared to have a higher molecular weight than conventional IgM pentamers, as judged by sucrose gradient sedimentation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis mobility. Electron microscopy revealed that the mutant IgM molecule contained six subunits. Wild-type IgM, while synthesized predominantly as a pentameric molecule, was assembled in at least two other forms, which were distinguished by their electrophoretic mobility. The apparently higher molecular weight forms of wild-type IgM include hexameric molecules which, like the hexameric mutant IgM, contained much less J chain that the pentameric form and were 20-fold more efficient at activating complement-dependent cytolysis.

Animals↗

Spectro-temporal analysis in normal-hearing and cochlear-impaired listeners.

Detection thresholds for a 1.0-kHz pure tone were determined in unmodulated noise and in noise modulated by a 15-Hz square wave. Comodulation masking release (CMR) was calculated as the difference in threshold between the modulated and unmodulated conditions. The noise bandwidth varied between 100 and 1000 Hz. Frequency selectivity was also examined using an abbreviated notched-noise masking method. The subjects in the main experiment consisted of 12 normal-hearing and 12 hearing-impaired subjects with hearing loss of cochlear origin. The most discriminating conditions were repeated on 16 additional hearing-impaired subjects. The CMR of the hearing-impaired group was reduced for the 1000-Hz noise bandwidth. The reduced CMR at this bandwidth correlated significantly with reduced frequency selectivity, consistent with the hypothesis that the across-frequency difference cue used in CMR is diminished by poor frequency selectivity. The results indicated that good frequency selectivity is a prerequisite, but not a guarantee, of large CMR.

Adult↗

Reaction time as an indicator of access to frequency-resolved information.

Response times, measured as a simple reaction time (RT), to tones in a notch-noise background vary systematically with the notch width. As notch width increases so RT decreases. The slope of decrease of RT with notch width is a function of the sensation level (SL) at which the tone is presented above threshold in broad-band noise, particularly of narrow notch widths. The function is interpreted as reflecting both frequency resolution and the increase in partial loudness of the tone as notch width increases.

Adult↗

A region of the immunoglobulin-mu heavy chain necessary for forming pentameric IgM.

In order to define the molecular requirements for IgM pentamer formation, we have isolated several mutant hybridomas which produce predominantly monomeric IgM. For one such mutant, 102, we synthesized a cDNA clone of its mu-mRNA, and found an in-frame 39-bp deletion, which thus encodes a mu-chain lacking amino acids 550-562, a region spanning the fourth constant domain and the tail of the mu-chain. To prove that this deletion is sufficient to block pentamer formation, we used site-directed mutagenesis to construct a mu-gene lacking these 39 bp, and have shown that the expression of this altered mu-gene results in the production of monomeric IgM.

Amino Acid Sequence↗

Sociacusis.

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Hearing Loss, Noise-Induced↗

A post-anaesthetic scoring system.

A post-anaesthetic scoring system is described. The scoring system scores five parameters that may be quickly assessed by the recovery room staff at five-minute intervals. The system was usefully employed for a month's trial and has now been adopted on a full-time basis at this hospital.

Anesthesia, General↗

One year's experience in a new dental day-stay unit.

The records of six hundred and fifty-five patients treated in the Dental Day-Stay Unit over a twelve-month period were reviewed. 2.1% of 95 patients assessed as suitable for day-stay surgery, and 2.2% of 542 patients not assessed prior to anaesthesia were admitted postoperatively. As an index of outcome, 2.56% of 547 day cases were admitted postoperatively, 0.73% being attributable to anaesthesia. Forty-seven day patients were treated in the dental chair, and 108 were treated as inpatients. Over 37% had at least one concurrent medical problem, while 10.4% were mentally handicapped. Guidelines for day-care selection require that the procedure be straightforward, the patient medically fit, be discharged escorted, and live within a reasonable distance of the hospital. From our study, four specific patient groups are identified. These are: the young and healthy, the mentally handicapped, the medically compromised, and those with airway problems.

Adolescent↗

Blood culture cross contamination associated with a radiometric analyzer.

During a 9-day period in August 1980 in a New Jersey hospital, three pairs of consecutively numbered blood cultures from different patients were identified as positive for the same organism (two pairs of Klebsiella pneumoniae and one pair of group A Streptococcus), for each pair, both cultures were positive in the same atmosphere, both organisms had the same sensitivities, and the second of each pair grew at least 2 days after the first and was the only positive blood culture obtained from the patient. When the hospital laboratory discontinued use of its radiometric culture analyzer for 15 days, no more consecutive pairs of positive cultures occurred. Subsequent use of the machine for 9 days with a new power unit but the original circuit boards resulted in one more similar consecutive pair (Staphylococcus epidermidis). After replacement of the entire power unit, there were no further such pairs. Examination of the machine by the manufacturer revealed a defective circuit board which resulted in inadequate needle sterilization. Laboratories which utilize radiometric analyzers should be aware of the potential for cross contamination. Recognition of such events requires alert microbiologists and infection control practitioners and a record system in the bacteriology laboratory designed to identify such clusters.

Bacteria↗

Some implications of audiological measures in the population for binaural aiding strategies.

The health-economic and statistical problems involved in concluding in favour of provision of binaural aids for subsets of the hearing-impaired are outlined. A positive mean binaural advantage is a first step only; an adequate way of handling individual differences must be the second step. Data comparing two population studies show an appreciable binaural advantage for speech in noise; age differentially affects the binaural advantage in males only, which may explain contradictions in the literature. Evidence is obtained that binaural sentence understanding in noise does depend materially upon symmetry of hearing, despite a generally minimal role for the worse ear a statistical predictor. Detailed results suggest that 15 dB asymmetry at threshold should be used as a contraindication to binaural fitting. At lesser degrees of asymmetry (around 10 dB), asymmetry alone is not an adequate basis for generalised differential prognosis for binaural aids because of various supra-threshold considerations. Hence binaural integration should be directly assessed both in field trials of binaural aiding, and in clinical practice.

Adult↗

Polychlorinated biphenyls in clams and oysters from New Bedford Harbor, Massachusetts, March 1978.

Polychlorinated biphenyl (PCB) concentrations in clams (Mercenaria mercenaria) and oysters (Crassostrea virginica) from 17 stations of the western and New Bedford Harbor areas of Buzzards Bay, Massachusetts, clearly show that the New Bedford Harbor area is severely polluted. Up to 5 ppm PCBs (dry weight) were found in shellfish tissue. The most likely sources of the PCBs are chronic releases from two electrical component manufacturers in New Bedford. Close proximity of the shellfish to the source of input is indicated by a high relative abundance of the di-, tri-, and tetrachlorobiphenyls. The data suggest that the New Bedford Harbor area should be considered, along with the Hudson River and Chesapeake Bay, one of the major sources of PCB inputs to the northeastern United States coastal area.

Animals↗