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Biomedical subjects

H J Gould

Publications and source records attributed to H J Gould.

At least 19 recordsLinked to original sources

Alpha-helical coiled-coil stalks in the low-affinity receptor for IgE (Fc epsilon RII/CD23) and related C-type lectins.

The low-affinity receptor for IgE (Fc epsilon RII/CD23) is a cell surface glycoprotein that plays a role in both cellular immunity and allergic inflammation. Its extracellular IgE-binding domain bears homology to C-type animal lectins, and the protein is, therefore, classified as a member of this superfamily. We predict that this lectin-like domain is separated from the cell membrane by an extensive region of alpha-helical coiled-coil structure, based upon sequence comparisons with tropomyosin, the archetypal alpha-helical coiled-coil structure, and detection of characteristic heptad repeats. Analysis of other receptor protein sequences identified a similar structural motif in other membrane-bound members of the C-type lectin superfamily, including the asialoglycoprotein receptor, the Kupffer cell receptor, and the B-cell differentiation antigen Lyb-2 (CD72). It appears that within the C-type lectin superfamily, there is a subfamily of structurally related membrane-bound receptor proteins that contain alpha-helical coiled-coil stalks of various lengths.

Amino Acid Sequence

Using the derived auditory brain stem response to estimate traveling wave velocity.

An estimate of the traveling wave velocity (TWV) was evaluated in 18 young adults to determine the technique's applicability as a possible tool in evaluating Meniere's disease. This TWV estimation uses a derived auditory brain stem response procedure requiring high-intensity masking. The results indicate that on average, TWVs were similar to those obtained via psychophysical measures or electrocochleography. However, instances of undermasking, due to subjects' intolerance, resulted in a number of subjects exhibiting faster than expected TWVs.

Acoustic Stimulation

Place specific influences on the wave I to V interpeak latency of the auditory brain-stem response.

There is controversy over whether the wave I to V interpeak latency (I-V IPL) of the auditory brain-stem response can be manipulated by cochlear processing. In this study, a forward masking paradigm was used to test the predictions of two contrasting models of I-V IPL generation. The paradigm was designed to determine if the I-V IPL can be affected by masking selected portions of the cochlear response region. The results from ten normal hearing subjects suggest that: (1) waves I and V can be masked semi-independent of each other, and (2) the I-V IPL can be shortened or prolonged by masking the basal or apical portion of the cochlear response region respectively. These findings support the hypothesis that, at least in normal hearing subjects, wave V is biased to reflect more apical cochlear events than wave I. Additionally, they offer tentative support for anecdotal reports of shortened I-V IPLs in the presence of high-frequency hearing loss.

Adult

Quantification technique for the middle latency response.

Few objective analysis techniques have been developed for, or applied to, the auditory evoked middle latency response (MLR). This report demonstrates the applicability of the Fsp statistical technique (Elberling and Don, 1984) to the MLR time domain. Subjects for this study were 10 normal hearing young adults. The stimuli were 60, 40, 20 dB nHL clicks and a NS control. Evoked responses were obtained as a series of 10,000 individual traces for each stimulus presentation and analyzed off line to determine the applicability of the Fsp technique. In addition, the effects of filtering and time window size were examined to determine the optimum collection characteristics for the Fsp analysis method. The results indicate that the Fsp technique is a viable tool for estimating signal-to-noise characteristics of the MLR. When using the Fsp technique with the MLR the high-pass filter should be set to 20 Hz so that a 50-msec time window can be used.

Acoustic Stimulation

Deletional switch recombination occurs in interleukin-4-induced isotype switching to IgE expression by human B cells.

There is controversy as to whether deletional rearrangement occurs between the IgM and IgE switch regions (S mu and S epsilon, respectively) during switching to the IgE isotype. We have addressed the issue by stimulating normal human B cells, sorted for lack of expression of surface IgE, to produce IgE by infection with Epstein-Barr virus (EBV) in the presence of interleukin 4 (IL-4). Genomic DNA was amplified for S mu/S epsilon switch junction fragments by utilizing the nested-primer polymerase chain reaction. Switch junction fragments were amplified from B cells infected with EBV in the presence of IL-4 but not from B cells infected with EBV alone. The DNA sequence of these "switch fragments" revealed direct joining of S mu to S epsilon in each case. The recombination sites within S mu were clustered within 900 base pairs at the 5' end of the switch region, suggesting that there are "hot spots" for recombination within S mu. The S epsilon recombination sites were scattered throughout the S epsilon region. These findings indicate that IL-4-induced isotype switching to IgE production in human B cells is accompanied by DNA rearrangements with joining of S mu to S epsilon.

B-Lymphocytes

Topographic distribution of connections from the primary motor cortex to the corpus striatum in Aotus trivirgatus.

Connections between the primary motor cortex (MI) and the corpus striatum were studied in the owl monkey. Representations of specific body movements were elicited in MI by microstimulation techniques, and the efferent projections from these stimulation sites were labeled with wheat germ agglutinin-horseradish peroxidase conjugate (WGA-HRP). Dense projections were found in the putamen ipsilateral to the injection site and sparser projections occupied comparable areas in the contralateral putamen. Representations of hindpaw regions projected to the dorsomedial portion of the putamen with only slight extensions across cell bridges into the caudate nucleus. Representations of the forepaw and head projected to progressively more ventrolateral zones of the dorsal two-thirds of the putamen. Projections from injections of cortex representing discrete body movements terminated in an irregular or patchy distribution over a relatively large portion of the putamen. Extensive projections from relatively discrete injections in MI are indicative of a large degree of divergence and provide evidence for possible overlap from representations of relatively disparate body parts. The results are consistent with observations reported in other species of primates, but different from those seen in carnivores. This difference is discussed with regard to possible general features of corticostriate organization.

Animals

Prevalence of hearing loss in adults with sickle cell disease.

Hearing status in 75 adult subjects with sickle cell disease was examined. Thirty-one (or 41%) of the subjects failed the hearing screening. When examined by hemoglobin type, it was found that persons with sickle cell C disease had the greatest incidence of hearing loss, although all subject groups exhibited greater prevalence rates than the general population. The results suggest that routine audiologic assessment be incorporated into the regular medical examination for adults with sickle cell disease.

Adolescent

Hearing disorders in sickle cell disease: cochlear and retrocochlear findings.

The auditory system was assessed in 34 adult subjects with sickle cell disease using standard audiometric test techniques. The study results indicate that patients with sickle cell disease are at risk for retro-cochlear as well as cochlear dysfunction of the auditory system. However, there is no consistent audiometric pattern that is pathognomonic of sickle cell disease. The test results indicate that auditory status should be carefully monitored in all adult patients with sickle cell disease.

Acoustic Impedance Tests

Connections between area 3b of the somatosensory cortex and subdivisions of the ventroposterior nuclear complex and the anterior pulvinar nucleus in squirrel monkeys.

The goal of this study was to determine whether somatosensory thalamic nuclei other than the ventroposterior nucleus proper (VP) have connections with area 3b of the postcentral cortex in squirrel monkeys. Small injections of the anatomical tracers wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) or 3H-proline were placed in electrophysiologically identified representations of body parts. The results indicate that, besides the well-established somatotopically organized connections with VP, area 3b has connections with three other nuclei of the somatosensory thalamus: the ventroposterior superior nucleus (VPS ["shell" of VP]), the ventroposterior inferior nucleus (VPI), and the anterior pulvinar nucleus (Pa). Injections confined to area 3b or involving adjacent parts of area 3a or area 1 indicate that connections between VPS, VPI, and Pa and the postcentral cortex are somatotopically organized. In VPS, connections related to the hand were found medially, and connections related to the foot were lateral. In VPI, connections with the cortical representations of the mouth, hand, and foot were successively more lateral. In Pa, connections related to the mouth, hand, and foot were successively more ventral, lateral, and caudal, and the trunk region was caudomedial. The findings suggest that VPI contains a representation of all parts of the body, including the face. The connections of Pa with the primary somatosensory cortex, area 3b, the location of Pa relative to the ventroposterior nucleus, and the high degree of topographic order in the connections of Pa with the postcentral cortex suggest that Pa is an integral part of the somatosensory thalamus in monkeys and is homologous to the medial nucleus of the posterior group (Pom) in other mammals. Overall, the results contribute to the growing evidence that individual somatosensory cortical areas in monkeys receive inputs from multiple thalamic sources, and that a single thalamic nucleus has several cortical targets.

Animals

Hearing loss and cleft palate: the perspective of time.

This study examines the hearing status of individuals with clefts of the palate or lip and palate without other major malformations or syndromes. A total of 1,699 audiometric records were reviewed and classified on the basis of race, gender, cleft type, age, and birth year (pre or post 1969). The results indicate that race, age, and date of birth affect the frequency of hearing loss.

Age Factors

Thalamic and extrathalamic connections of the dysgranular unresponsive zone in the grey squirrel (Sciurus carolinensis).

The connections of the cortical dysgranular "unresponsive zone" (UZ) (Sur et al.: J. Comp. Neurol. 179:425-450, '78) in the grey squirrel were studied with horseradish peroxidase and autoradiographic techniques. The results of these experiments show that the major subcortical connections of the unresponsive zone are in large part reciprocal. Connections are distributed within the thalamus in a poorly defined region including restricted portions of several nuclei that lie along the rostral, dorsal, and caudal borders of the ventral posterior nucleus. Additional thalamic connections of the UZ terminate in the reticular nucleus and are reciprocally related to the paralaminar and central median nuclei. Extrathalamic terminations were observed in the zona incerta, the intermediate and deep layers of the superior colliculus, the red nucleus, and several subdivisions of the pontine nuclei. The similarity between the pattern of subcortical connections of the UZ in the grey squirrel and patterns reported for the parietal septal region in rats (Chapin and Lin: J. Comp. Neurol. 229:199-213, '84) and for area 3a in primates (Friedman and Jones: J. Neurophysiol. 45:59-85, '81), suggests that the UZ in the grey squirrel may represent a counterpart of at least part of area 3a as described in primates. The results are further discussed with respect to a possible role of the thalamus in control or modulation of interhemispheric circuits and of the UZ in the modulation of nociceptive and kinesthetic pathways through the thalamus. Finally, the term parietal dysgranular cortex (PDC) is proposed as an alternative to denote the region currently called the unresponsive zone.

Animals

Audiologic findings in Pierre Robin sequence.

The hearing status of 20 individuals with Pierre Robin Sequence (micrognathia, cleft palate, and glossoptosis leading to respiratory distress and feeding difficulty) was examined and compared to a sample exhibiting only isolated cleft palate. The results indicate that there is no difference in the prevalence or degree of hearing loss in these two groups.

Adolescent

Recombinant human IgE.

The gene for a human epsilon chain Fc fragment has been cloned and expressed at a high level in Escherichia coli, and its biological activity in binding to the high-affinity receptors on mast cells and basophils and mediating histamine release has been examined in a variety of assays, including the inhibition of passive cutaneous anaphylaxis in human skin, which was induced by ragweed immunoglobulin IgE antibody and antigen. The positive results obtained in these assays encouraged us to try to analyse the binding site on IgE by site-directed mutagenesis. We describe deletion mutants here that narrow down the binding site on IgE for the mast cell receptor to a stretch of 76 amino acids (residues 301-376 on the ND epsilon chain) spanning the CH2 and CH3 domains. This peptide displays activity in the human skin test indistinguishable from that of a myeloma IgE.

Basophils

Craniofacial growth data for cleft lip patients infancy to 6 years of age: potential applications.

The present work was undertaken to provide craniofacial roentgenocephalometric growth data on a group of patients with cleft lip ranging in age from infancy to 6 years. Included are variables related to the neurocranium and orbit. Mensurational data were derived from cephalograms of 72 patients (44 male and 28 female subjects) with cleft lip only (n = 38) or cleft lip with varying degrees of alveolar cleft (n = 34). The data in this mixed longitudinal sample are reported for ten age groups. On the basis of comparison with reported noncleft roentgenocephalometric values, it is suggested that the data may serve as a reference for early craniofacial growth. Measurements from four persons with different types of craniofacial anomalies are also presented to illustrate the application of the reported data in the assessment of craniofacial growth.

Alveolar Process

Inhibition of mast cell sensitization in vitro by a human immunoglobulin epsilon-chain fragment synthesized in Escherichia coli.

An immunoglobulin epsilon-chain fragment was synthesized in E. coli by cloning and expression of the gene coding for the second, third and fourth constant domains of the human IgE heavy chain. The bacterial CH2-4 polypeptide product was assembled by oxidation into a covalently linked dimeric epsilon-chain molecule presumably analogous to the Fc region of native IgE. This bacterial Fc epsilon preparation, within the concentration range 0.01-10 micrograms/ml, inhibited sensitization of human lung mast cells, determined as histamine released upon challenge with specific antigen. Monomer CH2-4 epsilon-chain polypeptide, prepared by reduction and alkylation of the active bacterial Fc epsilon fragment, was inactive as an inhibitor of sensitization. The molar potency of the active bacterial Fc epsilon product was approximately one fourth of that of native IgE. Since the bacterial Fc epsilon is nonglycosylated, carbohydrate does not make an essential contribution to the Fc receptor binding activity of IgE. These results show that a functionally active immunoglobulin molecule can be synthesized by gene cloning and expression in E. coli.

Antibodies, Bacterial

Pathway-dependent reconstitution of chromatin structure from separated constituents.

Chicken reticulocyte chromatin can be reassembled from its separated constituents, viz. DNA, H1 plus H5, core histones, and non-histone proteins, to yield a product resembling the native starting material by a series of structural criteria. In particular, it possesses nucleosomes separated by spacer regions; the particles contain DNA with a unit length of approximately 200 base pairs. The recovery of the correctly reassembled product depends critically on the annealing conditions: the components are initially mixed in 2 M NaCl and 5 M urea, and it seems to be important to remove urea at a relatively high salt concentration. The results suggest that the characteristic chromatin structure is formed only when core histones bind to DNA in their native conformation and are followed by the addition of H1 and H5 to the spacer regions.

Animals