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Biomedical subjects

J C Webster

Publications and source records attributed to J C Webster.

At least 19 recordsLinked to original sources

Effect of hearing loss of cochlear origin on the auditory brain stem response.

Auditory brain stem response (ABR) testing is widely used to detect lesions of the auditory neural pathways. The ABR waves depend not only on the integrity of the neural pathways, but also on the condition of the cochlea. To properly interpret the ABR response, it is necessary to understand the effects of cochlear hearing loss on the ABR wave latencies. We studied two populations of subjects with cochlear hearing loss: one with varying degrees of high-frequency hearing loss and the other with varying degrees of flat configuration hearing loss. The degree of cochlear hearing loss was quantified in several different ways and subjected to one linear and three nonlinear regression analyses to test for accuracy in predicting ABR wave latencies and interpeak intervals (waves I, III, V, I-V, I-III, and III-V) for three click intensities. Hearing loss levels from 2 to 6 kHz, in particular 4 kHz, were superior to other audiometric test frequencies as predictors of ABR wave latencies for the group with the high-frequency losses. No particular characterization was found to be superior for the flat hearing loss configurations. From these results, modeled predictions of wave latencies as a function of degree and configuration of hearing loss were made. The modeled predictions are then used to suggest guidelines for interpretations of ABR results where hearing impaired patients are involved.

Adult

Inhibin increases and progesterone decreases receptors for gonadotropin-releasing hormone in ovine pituitary culture.

Treatments (48 h) with highly purified bovine or porcine inhibins (10 ng/ml) induced ovine pituitary cells to increase their binding for des-Gly10-[D-Ala6]LHRH-ethylamide by 3.6- and 5-fold, respectively. Studies with less pure inhibin from porcine follicles showed that increased binding could reach 7-fold within 48 h and was due to higher numbers of receptors for GnRH. The 48-h increase in GnRH receptors was linear with time and was rapidly reversible, since removal of inhibin at 24 h decreased GnRH binding below control levels at 48 h. Inhibin (bovine or porcine) also increased GnRH-stimulated secretion of LH by 2-fold. The ED50 for both inhibin actions noted above was in the range of 0.5-2.0 ng/ml (in terms of highly purified bovine inhibin). Progesterone (P) totally counteracted inhibin induction of GnRH binding and GnRH-stimulated LH secretion at 48 h. In the absence of inhibin, P decreased GnRH binding below control levels by as much as 80% within 48 h, but did not affect GnRH-stimulated LH secretion at 48 h. The ED50 for P action was near 1 nM, which is within the physiological range for P during the luteal phase of the sheep estrous cycle. The data suggest that P may act during the luteal phase to decrease receptors for GnRH. The rapid decrease in P during the 48 h before the preovulatory LH surge should permit GnRH receptors to rise under the influence of inhibin (and estradiol) to boost gonadotroph responsiveness to GnRH so the LH surge may occur to its fullest.

Animals

Estradiol alters the effectiveness of gonadotropin-releasing hormone (GnRH) in ovine pituitary cultures: GnRH receptors versus responsiveness to GnRH.

17 beta-Estradiol (E) rapidly (5-12 h) induced ovine pituitary cultures to increase their binding of des-Gly10-[D-Ala6] GnRH ethylamide by 2.5- to 4.5-fold. The ED50 for E was near 0.1 nM. Scatchard analysis indicated that E increased binding by increasing receptors for GnRH. GnRH-stimulated release of LH increased 2-fold along with the increase in GnRH receptors, but heightened responsiveness to GnRH disappeared after 27 h of E treatment even though GnRH receptors remained elevated. These data are consistent with the concepts that 1) E increased GnRH receptors, which initially enhanced gonadotroph responsiveness to GnRH, and 2) E subsequently nullified the increased response to GnRH by blocking a mechanism of LH secretion not associated with GnRH receptor number. Further support for this hypothesis came from studies with porcine follicular inhibin. Inhibin in ovine pituitary culture concomitantly increased GnRH receptors by 5-fold and GnRH-stimulated LH secretion by 2-fold. Inhibin maintained both effects long term (48 h). When E was added along with inhibin, the increase in GnRH receptor number became greater than with either hormone alone (7-fold increase at 48 h), but the initial increase in GnRH-stimulated LH secretion was fully inhibited by E at 48 h. The increase in GnRH receptors caused by E may be important physiologically to help create the preovulatory LH surge; the delayed inhibitory action of E on GnRH-stimulated LH secretion may limit the LH surge.

Animals

Treatment of behavioral problems with pindolol.

A study was conducted on a group of chronically hospitalized, brain-damaged male patients to assess the effectiveness of treatment with pindolol on behavioral problems. The study was conducted in two parts. The first was a double-blind, placebo-controlled analysis of the effect of pindolol on assaultive behavior, both verbal and physical. The second part was open and sought to determine whether pindolol would diminish such behaviors as resistance to care, sexual preoccupation, or provocation of others, which were sufficient to preclude placement at a lower level of care. These target behaviors and nursing interventions were monitored and clinical global assessments of improvement in behavior and of suitability for lower levels of care were developed. Eight of 13 patients were considered improved. Those with significant premorbid personality disorders showed little benefit. Pindolol appears to ameliorate some management problems and, by inference, improve the quality of life in many patients with behavioral pathology due to organic brain disease.

Aged

Changes in glycoprotein carbohydrate content in the aging human brain.

There is no significant change in the concentration, per gram of fresh tissue, of the total carbohydrate associated with brain glycoproteins as the human brain ages from 25 to 85 years. Nevertheless, notable shifts in the concentration of varied types of oligosaccharides do occur. The concentration and percentage of total glycopeptide-carbohydrate recovered from the whole brain represented by the N-glycosidically linked complex sialooligosaccharides of the tri- and tetraantennary type show a marked decline with age. On the other hand, the N-linked mannose high oligosaccharides of the ovalbumin type, the N-linked biantennary sialoglycopeptides of the transferrin type, and the O-linked oligosaccharides show an increase as the brain ages. Other age related changes that were noted include an increase in the number of sulfate ester groups associated with the N-linked sialoglycopeptides and a decrease in the number of phosphorylated high mannose oligosaccharides as the brain ages.

Adult

Interlist equivalencies for a numeral and a vowel/consonant multiple-choice monosyllabic test for severely/profoundly deaf young adults.

Conventional multiple-choice speech tests measuring discrimination of initial/final consonants, and the CID "Everyday" Sentences test are too difficult for many young adults whose hearing is severely/profoundly limited. Using the 6-choice closed-set paradigm, a new 12-item Numerals test was developed as well as a modification of the Pickett et al (Gallaudet) modified rhyme test of vowel and consonantal discrimination. This test, here called the Webster-Pickett (W/P) test, essentially expands the original 2 alternative lists to 6, with some further minor changes. Both these tests were administered to 35 students at the National Technical Institute for the Deaf (NTID). In combination, the new tests provided usable scores for the NTID population. Most of those who yielded scores of zero on the W-22, on the CID sentences tests and on the W/P test nevertheless scored above zero on Numerals, while those who scored 100% on Numerals scored between 0 and 100% on the W/P test. All 6 recorded lists of the Numerals test were equivalent. Slight corrections to those raw scores between 10 and 90% on the 6 lists of the W/P were proposed to yield interlist equivalence.

Deafness

Isolation of synaptic junction-enriched fraction from the forebrain of day-old chickens. Preparation and characterization of chick forebrain subcellular fractions.

Synaptosomal plasma membrane (SPM) and other subcellular fractions were isolated from the forebrain of 1-day-old chickens by a procedure based on that of Davis and Bloom (16) and Cotman and Taylor (13). The procedure involves the centrifugation through a discontinuous sucrose gradient of a crude synaptosomal-mitochondrial fraction which has been lysed and weighed with iodonitrotetrazolium. SPM isolated by this method contains only small amounts of lysosomal or mitochondrial membranes and is practically devoid of contaminating microsomal membranes, as estimated by enzyme marker assays. The purity of chick-brain SPM prepared by this method is compared to the purity of chick-brain fractions obtained by two other laboratories, using different methods (4, 59). The SPM were extracted with Triton X-100 and all fractions solubilized in sodium dodecyl sulfate (sds). The delipidated proteins of all fractions were subjected to SDS-polyacrylamide electrophoresis on slab gels and stained for protein. A distinct difference was observed between the patterns given by the Triton-soluble and -insoluble fractions. Electron microscopy of the synaptic junction fraction showed numerous junctional complexes.

Animals

Ear disease in relation to age in the cleft palate child and adolescent.

Ninety-eight cleft palate subjects were studied to ascertain the eventual adolescent and adult hearing. There were 72 complete clefts of lip and palate and 26 clefts of the palate alone. The incidence or side of ear disease did not appear to be influenced by this type of cleft. Other systemic anomalies were present in 11 cases with congenital middle ear abnormalities in 3 and sensory neural hearing loss in 8 subjects. Progressive improvement in incidence of hearing loss from 94% at 4 years to 42% at 20 years was noted with the strict definition of hearing loss as 10 dB conductive loss at any one frequency. 10% of ears were left with permanent structural changes in the middle ear. In only 2 patients was there a bilateral hearing loss of 20 dB or more through the speech range.

Adolescent