Search PubMed⌕ Search

Biomedical subjects

J L Hall

Publications and source records attributed to J L Hall.

At least 127 records · Page 7Linked to original sources

A procedure for detecting variability of psychophysical thresholds.

In adaptive psychophysical testing, it is desirable to identify experimental runs during which the subject's threshold changes. This is not easy to do, because the testing level changes during the course of the run. The following screening procedure can assist in detecting threshold variability. At the conclusion of the run, determine for each trial the discrepancy between observed and expected response. Next, determine the linear regression of this discrepancy upon trial number. If the subject's response behavior is stable and well described by the psychometric function, then the expected value of slope of the linear regression is equal to zero. If the observed slope differs greatly from zero, then it is unlikely that the subject's response behavior is stable. Results from computer simulations and psychophysical experiments are presented.

Auditory Threshold↗

Identification of two human beta-tubulin isotypes.

The sequence of a human beta-tubulin cDNA clone (D beta-1) is described; our data revealed 95.6% homology compared with the sequence of a human beta-tubulin processed pseudogene derived by reverse transcription of a processed mRNA (Wilde et al., Nature [London] 297:83-84, 1982). However, the amino acid sequence encoded by this cDNA showed less homology with pig and chicken beta-tubulin sequences than the latter did to each other, with major divergence within the 15 carboxy-terminal amino acids. On the other hand, an independently isolated, functionally expressed genomic human beta-tubulin sequence (5 beta) possessed a very high degree of homology with chicken and pig beta-tubulins in this region. Thus, human cells appear to contain two distinct beta-tubulin isotypes. Both the intact beta-tubulin cDNA clone and a subclone containing only the 3' untranslated region detected two mRNA species in HeLa cells; these mRNAs were 1.8 and 2.6 kilobases long and were present in about equal amounts. Two independently subcloned probes constructed from the 3' untranslated region of the 5 beta genomic sequence also detected a 2.6-kilobase beta-tubulin mRNA. However, the 3'-untranslated-region probes from the cDNA clone and the genomic sequence did not cross-hybridize. Thus, at least two human beta-tubulin genes, each specifying a distinct isotype, are expressed in HeLa cells, and the 2.6-kilobase mRNA band is a composite of at least two comigrating beta-tubulin mRNAs.

Amino Acid Sequence↗

Application of interspecies in vitro fertilization in the initial assessment of the infertile couple.

Methods to evaluate male reproductive potential are limited. Conventional semen analysis does not necessarily reflect sperm functionality. In this study we investigated the correlation of the interspecies penetration test with clinical evaluation of 106 infertile couples. In vitro penetration results in 92 of 106 men correlated well with clinical diagnosis. In 28 couples with a male infertility factor, the mean penetration rate was 18%, whereas in 78 infertile couples with no known male factor, the rate was 50%. The mean for all patients tested was 40%. This was well below a mean of 73% for a donor population. The major discrepancy between the interspecies penetration test and clinical findings occurred in a group of nine patients with 0% penetration who had been judged normal by history and semen analysis. In general, the interspecies penetration test correlates well with male clinical evaluation but does the complementary information in certain cases. At present, its greatest utility seems to be in evaluation of unexplained infertility, in unexplained failure of female therapy, or in selection of patients for donor insemination.

Animals↗

Localization and properties of ATPase activity in pea stems and wheat coleoptiles.

Microsomal fractions from wheat coleoptiles and pea stems contain a microsomal ATPase activity that requires divalent cations (Ca2+ is more effective than Mg2+) and shows further stimulation by KCl. The effects of added indoleacetic acid were inconclusive. Cytochemical studies on both species showed most pronounced staining for ATPase in the plasmalemma at pH 7.0. However, at pH 5.5, the coleoptile cells showed heaviest staining for ATPase in the endoplasmic reticulum and dictyosomes. The results are discussed with regard to the postulated role of ATPase activity in relation to proton pumping and plant cell elongation.

Adenosine Triphosphatases↗

Effect of pelvic fluid from endometriosis patients on human sperm penetration of zona-free hamster ova.

Peritoneal fluid (PF) samples from fertile women, infertile women without signs of endometriosis, and infertile women with endometriosis were examined for effects on motility of normal spermatozoa and for effects on their fertilizing capacity as measured by the interspecies penetration test (ISPT). All unheated peritoneal fluid samples caused rapid destructive changes in the female hamster gametes, presumably due to the presence of unidentified serum components, and caused clumping of spermatozoa but no change in sperm motility. Heat-treated fluid samples were therefore used in subsequent experiments to assess their effect on the ISPT. The mean penetration rate for fertile women was 58%; for infertile women without endometriosis, 55%; and 54% for infertile women with endometriosis. The differences between the penetration rates in these patient groups were not significant. No adverse thus found on the fertilizing capacity of fertile spermatozoa.

Animals↗

Relationship between semen quality and human sperm penetration of zona-free hamster ova.

Spermatozoa from 22 presumably fertile donors and from the male partners of 43 infertile couples were evaluated for their ability to fertilize zona pellucida-free hamster ova. All "fertile" donors gave positive results ion the interspecies in vitro fertilization test; 26% of the male partners (patients) gave negative results. Correlations of in vitro fertilization rates and standard semen analysis results indicate that, except for extremely low semen values, sperm fertilizing capacity in vitro could not be predicted accurately from ejaculate sperm number, motility, or morphology. Sperm motility evaluation agreed better with in vitro fertilization test results than did either sperm number or morphology; however, 9 of 31 patients (29%) with normal sperm motility in the ejaculate were judged subfertile in vitro. Also, although higher in vitro fertilization rates were related to greater numbers of normal parameters in a semen sample, 8 of 25 male patients (32%) appraised as "normal" according to the usual semen analysis yielded below-normal in vitro fertilization results. These results support the idea that deficient sperm fertilizing capacity often is a characteristic of poor-quality semen. However, deficiencies in fertilizing capacity also were observed in patient semen samples with excellent properties. Therefore, the interspecies in vitro fertilization test might be useful as an additional tool in clinical investigations of the fertility of the male partners of childless couples, particularly in cases in which infertility continues for no readily apparent reason.

Animals↗

Hybrid adaptive procedure for estimation of psychometric functions.

Adaptive psychophysical procedures that have been described in the literature generally fall into one of two categories. (1) Simple procedures, such as UDTR and PEST, can be implemented without an on-line computer. The decision to change testing level is based on the outcome of the few most recent trials, and the final estimate of threshold is given by the final testing level or the average of a few testing levels. (2) "Maximum likelihood" methods require an on-line computer. A parametric form of the psychometric function is assumed, and after each trial a maximum-likelihood estimate of the parameters of the psychometric function is made on the basis of all preceding trials. This estimate is used to set the next testing level and to estimate threshold. We describe here a hybrid procedure, in which testing levels are determined by PEST and the final estimate of threshold is made by fitting an assumed psychometric function to all preceding trials. The PEST rules were tuned to yield results that were accurate and insensitive to errors in initial estimates of the psychometric function. These parameters differ from those that yield optimum results with classical PEST. Results of computer simulations and of experiments with human subjects are presented.

Humans↗

Primary sex determination: genetics and biochemistry.

On the basis of widespread phylogenetic conservatism, it has been proposed that serologically-defined H-Y antigen is the inducer of primary sex differentiation in mammals, causing the initially indifferent gonad to become a testis rather than an ovary. The proposal has withstood extensive testing in a variety of biological circumstances: XX males have testes and are H-Y+ and fertile XY females lack testicular tissue and are H-Y-; soluble H-Y antigen induces testicular organogenesis in XX indifferent gonads of the fetal calf in culture; H-Y antibody blocks tubular reaggregation of dispersed XY testicular cells, causing them to organize follicular clusters. There is a gonadal receptor for H-Y antigen: fetal ovarian cells that have been exposed to soluble H-Y (released for example by testicular Sertoli cells) take up the molecule and acquire the H-Y+ phenotype; they absorb H-Y antibody in serological tests. Specific uptake of soluble H-Y does not occur in the extra-gonadal tissues. It may be inferred that H-Y antigen is disseminated during embryogenesis and bound by specific receptors in cells of the primordial gonad, and that reaction of H-Y and its receptor signals a program of testicular differentiation, regardless of karyotype. The several anomalies of primary sexual differentiation manifest in such conditions as the XX male, the XX true hermaphrodite, and the XY female can thus reasonably be viewed as specific errors of synthesis, dissemination, and binding of H-Y antigen. H-Y is secreted by 'Daudi' cells, cultured from a human XY Burkitt lymphoma. The Daudi-secreted moiety is a single hydrophobic protein of 18,000 molecular weight. Early attempts to characterize H-Y secreted by testicular Sertoli cells have yielded two molecules, one of 16,500 MW (corresponding to the Daudi-secreted 18,000 MW protein), and one of 31,000 MW. It remains to be ascertained whether both are in fact H-Y antigens, and if so, whether one is a polymer of the other, or whether each represents the product of genes with discrete testis-determining functions.

Animals↗

Serum-borne H-Y antigen in the fetal bovine freemartin.

In mammals, ovarian cells that have been exposed to soluble H-Y antigen acquire the H-Y+ cellular phenotype. They absorb H-Y antibody in serological tests. To determine whether masculinization of the bovine freemartin, the synchorial female twin of a bull, could be due to attachment of circulating bull-twin-derived H-Y in the freemartin gonad, we exposed normal fetal ovarian cells to serum from fetal bulls, fetal cows and fetal freemartins. Ovarian target cells became H-Y+ after exposure to serum from fetal bulls or fetal freemartins, but not after exposure to serum from fetal cows. In a new competitive binding radioassay, uptake of Daudi-secreted tritiated H-Y was inhibited in fetal ovarian target cells first exposed to mouse testis supernatant, a demonstrated source of soluble H-Y. It was also inhibited in ovarian target cells exposed to serum from fetal bulls or fetal freemartins; uptake was unaffected by exposure to serum from fetal cows. Since Daudi-secreted H-Y is known to induce precocious testicular organogenesis in XX indifferent gonads in culture, we infer that initial transformation of the freemartin gonad is due to H-Y antigen that is secreted in the fetal bull, transmitted in the common chorionic vasculature and bound by gonadal receptors of the fetal cow.

Animals↗

Cochlear models: evidence in support of mechanical nonlinearity and a second filter (a review).

We have studied properties of a nonlinear one-dimensional model for motion of the basilar membrane. The model is able to reproduce a variety of physiological and psychophysical effects, and in some instances predictions of the model have been subssequently confirmed. We regard the agreement between model and nature as evidence that the major features of the model are qualitatively correct. Areas of agreement include generation and propagation of two-toine distortion products, two-tone suppression, and Zwicker's psychophysical masking period patterns. In order to reproduce all of the above effects, the model must contain the following major features: (1) A mechanical nonlinearity. This nonlinearity is asymmetric, with membrane damping increasing during the same phase of membrane motion that elicits response activity in primary auditory fibers. (2) An additional stage of sharpening, a 'second filter', between the physical variable controlling mechanical nonlinearity and the physical variable controlling neural excitation.

Basilar Membrane↗

Cochlear models: two-tone suppression and the second filter.

With advances in our understanding of the auditory periphery, models of cochlear mechanics have evolved from descriptions of existing data to the point that they can suggest meaningful observations that should be made and predict expected outcomes. As an example, we discuss relationships among mechanical nonlinearities in the inner ear, two-tone suppression, and the auditory "second filter." Electrophysiological two-tone suppression data indicate that excitatory tuning curves (stimulus intensity required to elicit a specified amount of activity in a primary fiber as a function of frequency) are more sharply tuned than suppressive tuning curves (stimulus intensity required to suppress the response to a continuous tone at the fiber's characteristic frequency by a specified amount as a function of frequency). Model simulations which attempt to account for the above difference suggest that there must be a stage of sharpening between the physical variable governing two-tone suppression (tentatively identified as velocity of the basilar membrane) and the physical variable governing neural excitation. An experiment that would unequivocally demonstrate the simultaneous existence of two representations of the stimulus with significantly different tuning properties in the cochlea is described. The future evolution of cochlear modeling, incorporating nonlinear two-dimensional models, is discussed.

Acoustic Stimulation↗

Frequency selectivity of the cochlea for formant peaks at high signal levels.

The frequency selectivity for formant peaks in a synthetic continuous vowel was measured on a nonlinear model for motion of the basilar membrane. In spite of the fact that the model becomes more broadly tuned at high levels, the formant peaks in the model response become more sharply defined. This effect is caused by nonlinear suppression of the response to frequencies between adjacent formant peaks.

Auditory Perception↗

H-Y binding in the gonad: inhibition by a supernatant of the fetal ovary.

H-Y antigen, the product of mammalian testis-determining genes, is released in the free state by testicular cells. Molecules of free H-Y antigen are bound in vitro by dispersed cells of the adult ovary. The binding reaction is inhibited by specific H-Y antibody. It is also inhibited by a diffusible factor of the newly differentiated fetal ovary. These observations favor the view that testicular organogenesis depend upon dissemination and binding of H-Y molecules by cells of the undifferentiated gonad (XY or XX, both having H-Y receptors), and raise the question of whether ovarian organogenesis may be promoted by a "female" molecule corresponding to H-Y of the male.

Animals↗

Model study of Zwicker's "masking period patterns".

Zwicker has demonstrated that the threshold for a high-frequency test-tone burst in the presence of a continuous low-frequency masking tone is a complicated function of the frequency and intensity of the masker and the phase of the masker at which the test tone is presented. "Masking period patterns" measured for these stimuli show nonlinear effects in that a high masker levels the threshold of test-tone bursts reaches local maxima at two different phases of the masker. We have investigated the implications of these psychophysical data on a computational model for motion of the basilar membrane. The model consists of a nonlinear mechanical system followed by an additional stage of frequency selectivity ("second filter"). The output of the model is applied as input to a threshold-level detector. With this model it is possible to reproduce the effects Zwicker observed. Masking period patterns are interpreted as a manifestation of two-tone suppression. On the basis of our computer simulation of Zwicker's psychophysical data, we make the following specific predictions concerning the nature of mechanical to neural transduction at the auditory periphery: (1) Membrane motion in one direction produces a nonlinear increase in the loss term, while membrane motion in the other direction does not. (2) The direction of membrane motion that produces increased loss is also the direction of motion that produces neural excitation. (3) There is a stage of sharpening, a "second filter," between membrane motion and the neural excitatory signal.

Auditory Threshold↗

In vitro fertilizing ability of testicular, epididymal, and ejaculated rabbit spermatozoa.

The fertilizing ability of testicular, epididymal, and ejaculated rabbit spermatozoa was evaluated in vitro following in vitro capacitation by high ionic strength treatment. Fewer than 11% of inseminated ova were apparently fertilized (i.e., in pronuclear, two-, and four-cell stages as determined by light microscopy) when testicular sperm treated with caffeine, caput epididymal, or corpus epididymal sperm samples were tested. A greater fertilizing ability, reflected by the percentage of ova fertilized and more normal progression of embryonic development, was exhibited by cauda epididymal sperm. Of 93 ova, 68 (73.1%) were fertilized by cauda sperm, whereas ejaculated sperm from the same 10 bucks fertilized 34 (36.6%) of 93 ova (P is less than 0.005). Ultrastructural examination of selected ova apparently fertilized by sperm from levels of the male reproductive tract proximal to the cauda epididymidis revealed abnormal activation. Authentic fertilization occurred when ova were inseminated with cauda epididymal and ejaculated sperm. An unusual and infrequent form of activation involving failure of cortical granule breakdown in ova penetrated by cauda epididymal and ejaculated sperm was seen. A comparison of fertilizing ability of sperm from first, second, and third ejaculates revealed a significant decrease with the third ejaculate (P is less than 0.01).

Animals↗