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Biomedical subjects

J C King

Publications and source records attributed to J C King.

At least 19 recordsLinked to original sources

Dynamic alterations in luteinizing hormone-releasing hormone (LHRH) neuronal cell bodies and terminals of adult rats.

1. The decapeptide lueteinizing hormone-releasing hormone (LHRH) is synthesized in neuronal cell bodies diffusely distributed across the basal forebrain and is secreted from neuronal terminals in the median eminence. Once secreted, LHRH enters the portal vessels and is then transported to the anterior pituitary, where it modulates the synthesis and secretion of gonadotropins, which are essential to gonadal function and reproduction. 2. Because of the difficulties encountered in studying these diffusely distributed neurons, we have developed strategies which combine immunocytochemistry and computer-assisted techniques to examine individual LHRH neuronal cell bodies, as well as the entire population of LHRH neurons from the diagonal band of Broca to the mammillary bodies. In addition, we have examined LHRH neuronal terminals in the median eminence using computer-assisted imaging techniques to examine individual terminals by electron microscopy or across all rostral-caudal regions of the median eminence by light microscopy. In our most recent studies using confocal microscopy, we have examined the relationships of LHRH terminals to glial processes. 3. These studies reveal a very dynamic system of LHRH neuronal cell bodies and terminals. The population of neurons in which LHRH can be detected varies as a function of time after gonadectomy, during the estrous cycle, and during the preovulatory surge of LH during the afternoon of proestrus. Dynamic changes are also observed in LHRH terminals in the median eminence as a function of time after gonadectomy and in specific rostral-caudal regions of the median eminence during the preovulatory surge of LH. Finally, confocal microscopy reveals that LHRH terminals are prevented from contacting the basal lamina of the brain by glial end-feet. 4. We are currently examining the hypothesis that these relationships change as a function of endocrine milieu and, therefore, participate in the modulation of LHRH secretion. Ongoing studies focus on defining the sites of action and synergy of multiple sources of regulation of LHRH secretion and their relative importance to ensuring reproductive success.

Animals

The thermic effect of food in normal-weight and overweight pregnant women.

A defective thermic response to food may be an energy-sparing adaptation in both obesity and pregnancy. To evaluate the combined effect of obesity and pregnancy on postprandial thermogenesis, the thermic effect of food was assessed for a 240 min period following a high-carbohydrate meal and a typical mixed meal in nine normal-weight non-pregnant, eight overweight non-pregnant, eight normal-weight pregnant and six overweight pregnant women using indirect calorimetry. A test meal that provided 60% of each subject's measured daily requirement for basal metabolism was used. Pregnant women were studied during weeks 30-35 of gestation. Neither obesity nor pregnancy altered the thermic effect of food, although the response to the mixed meal was greater (P < 0.01) than that to the high-carbohydrate meal in all cases. The mean responses for the high-carbohydrate and mixed meals were 26.9 (SD 6.0) and 30.1 (SD 6.2) % baseline energy expenditure respectively, and 7.4 (SD 1.6) and 8.3 (SD 1.6) % of the meal energy load respectively. Obesity and pregnancy were associated with hyperinsulinaemia (P < 0.005) following both test meals, suggesting that postprandial thermogenesis was not altered by insulin resistance in this group. The incremental glucose response was elevated (P < 0.001) in the pregnant women following both test meals; overweight women tended to have a greater incremental glucose response following the high-carbohydrate meal, but it was not significant (P = 0.065). These results do not provide evidence of an impaired thermic response to food in either overweight or third trimester pregnant women.

Adult

The immunogenicity of Haemophilus influenzae type b conjugate (HbOC) vaccine in human immunodeficiency virus-infected and uninfected infants.

Enzyme-linked immunosorbent assay polyribosyl ribitol phosphate (PRP) antibody responses to Haemophilus influenzae type b conjugate vaccine (HbOC) given at 2, 4 and 6 months of age were retrospectively compared in 23 human immunodeficiency virus (HIV) and 24 non-HIV-infected infants. HIV-infected infants were divided into those who were P1 (asymptomatic) or P2 (symptomatic) by 1 year of age. The P2 group was further divided into P2A (mildly symptomatic) and > P2A (rapidly symptomatic) by 1 year of age. The post-third HbOC dose geometric mean antibody titer to PRP was significantly lower in 12 P2 infants (0.43 microgram/ml) than either the 11 P1 infants (5.03 micrograms/ml, P < 0.05) or the 24 non-HIV infected infants (3.43 micrograms/ml, P < 0.05). Within the P2 group, the geometric mean antibody titer to PRP was significantly higher in 5 P2A infants (1.63 micrograms/ml) compared with 7 infants who were > P2A (0.17 microgram/ml, P < 0.05). After the third HbOC dose, PRP antibody titers were > or = 1.0 micrograms/ml for 4 of 12 P2 compared with 9 of 11 P1 infants (P < 0.05). Within the P2 group, PRP antibody titers were > 1.0 micrograms/ml for 4 of 5 P2A compared to 0 of 7 infants who were > P2A (P < 0.05). HIV-infected infants with PRP antibody titers > or = 1.0 micrograms/ml after the third HbOC dose had significantly higher mean CD4 counts (2842 cells/mm3) at the time of the third HbOC dose than those with lower PRP titers (1655 cells/mm3) (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Bacterial

Reconstructions of populations of luteinizing hormone releasing hormone neurons in young and middle-aged rats reveal progressive increases in subgroups expressing Fos protein on proestrus and age-related deficits.

Fos expression has been used as a marker of activation of neuroendocrine cells including LHRH neurons. In this study, Fos protein was localized within LHRH neurons in young and middle-aged rats to trace the temporal and spatial pattern of LHRH neuronal activation associated with the preovulatory LH surge. Animals were killed during the late morning, afternoon, and evening of proestrus. Dual immunocytochemical protocols localized LHRH and LHRH/Fos neurons, and computer-assisted methods were used to reconstruct forebrain populations of single- and double-labeled LHRH neurons. Although a significant increase in the number of LHRH/Fos neurons was noted by evening in both age groups, a greater increase was observed in young (12% in morning, 28% in afternoon, and 62% by evening) compared with aging females (5% in morning, 10% in afternoon, and 40% by evening). Reconstructions of LHRH and LHRH/Fos neurons revealed time- and age-dependent differences in Fos expression within LHRH neurons. In young females, LHRH/Fos neurons were restricted to central regions of the population of LHRH neurons on the morning of proestrus. By evening, Fos expression was also observed in more peripheral and caudal LHRH neurons. In middle-aged females, Fos expression was restricted to ventral subgroups of LHRH neurons on the afternoon of proestrus. By evening, more LHRH neurons contained Fos protein, however, few were located in the dorsal aspect of the population. These data trace the progressive increase in activation of LHRH neurons during the preovulatory LH surge in young females and reveal deficits in this pattern of activation by middle age.

Aging

Lumbar spondylolysis without spondylolisthesis: recognition of isolated posterior element subluxation on sagittal MR.

PURPOSE: To document the occurrence of isolated dorsal subluxation of posterior elements in cases of lumbar spondylolysis without spondylolisthesis both quantitatively (using spinal canal measurements) and qualitatively (by visual inspection) on sagittal MR images. METHODS: Retrospective analysis identified 63 patients with lumbar spondylolysis (confirmed by CT or conventional radiography) who had undergone MR imaging. From these we identified 12 patients with pars interarticularis defects but no evidence of spondylolisthesis. Measurements of anteroposterior spinal canal diameters were performed in these 12 patients to ascertain whether the sagittal canal diameter at the level of the spondylolysis exceeded the normal range as determined from 100 control subjects. RESULTS: In 9 of 12 patients the spinal canal was abnormally widened at the level of the spondylolysis because of dorsal subluxation of posterior elements. In 5 of these patients, the subluxation was readily visible on midline sagittal MR images. In 4 patients, spinal canal measurements were necessary to document this phenomenon. CONCLUSION: In the majority of patients with spondylolysis but without spondylolisthesis, sagittal MR images can show isolated dorsal subluxation of posterior spinal elements.

Adolescent

Far-field potentials in circular volumes: evidence to support the leading/trailing dipole model.

The leading/trailing dipole model explains the production of far-field potentials as an asymmetry in the leading and trailing dipole moments of a propagating action potential detected by a referential montage. This investigation documents the production of far-field potentials produced by a pure dipole generator in a circular volume conductor. Multiple equipotential waveforms are recorded in an adjoining circular volume conductor attached to the one in which the dipole generator is located. This finding substantiates the "wick electrode" effect that explains the equipotential and instantaneous distribution of far-field potentials over relatively large distances in volume conductors. The present findings support a number of the leading/trailing dipole model proposals which explain far-field potential generation.

Action Potentials

Far-field potentials in circular volumes: the effect of different volume sizes and intercompartmental openings.

Preliminary investigations of circular volume conductors suggested that far-field potential magnitude declines progressively slower with increasing radial distance from a current source and follows a cosine function with angular displacement of the recording electrode from the electrical generator's axis. Using circular volumes of 6 differing radii, the mathematical relationship between angle, radii, and far-field potential amplitude is determined. Previous theoretical relationships of amplitude versus dipolar spacing, current, and distance from a dipole generator in a bounded volume conducting medium are verified for the near-field. Far-field potentials in circular volumes are found to become constant at radii greater than 75% of the bounded volume's radius. Additionally, an adjoining volume conductor acts simply as a passive fluid-filled electrode (wick electrode) to the circular volume containing the generator until the intercompartmental opening to the circular volume exceeds 20% of its circumference. This finding was clinically supported by recording similar P9 somatosensory-evoked far-field potentials generated caudal to the foramen magnum from various portions of the cranium, whose connections to the torso, foramen magnum, and neck, average 6.2% and 17.8%, respectively. Finally, 3 circular volume conductors were connected in series by channels less than 20% of the volume conductor's circumference. Both adjoining circular volumes were equipotential to the far-field potential present at the boundary of the first circular volume containing the dipole generator. This observation supports the clinical finding of far-field potential transmission through multiple human bodies in conductive contact.

Action Potentials

The effect of different needle recording electrodes on somatosensory-evoked potentials and intertrial waveform variation.

This investigation examined the cortical somatosensory-evoked potentials (SEP) waveforms obtained from four sets of commercially available subdermal needle electrodes in 19 normal subjects. The composite materials of the four electrodes were stainless steel and a platinum/iridium alloy. Tibial nerve SEP peak latencies for P37 and N45 as well as P37/N45 amplitudes were recorded from each electrode pair in a random fashion. Using nonparametric analysis, no significant differences of waveform parameters were found between electrode pairs (P greater than 0.01). Correlation evaluation demonstrated values in excess of 0.92. Additionally, intertrial waveform analysis for each of the electrode pairs was performed. Again, nonparametric evaluation demonstrated no statistically significant waveform differences. Correlation coefficients were also highly correlative. Variable temperature response to prolonged tibial nerve stimulation was recorded that did not significantly effect the latencies or amplitudes of the cortical SEP responses. We conclude that within temperature ranges typically encountered in clinical practice, there is no statistically significant waveform differences recorded with commonly available subdermal needle electrodes. Additionally, although intertrial waveform variation may exist during SEP recordings, these differences do not reach statistically significant levels.

Adult

Deoxyribonucleic acid (DNA) ploidy and proliferative characteristics of metastatic squamous cell carcinoma determined by flow cytometric analysis.

BACKGROUND: The deoxyribonucleic acid (DNA) index and the proliferative index (the fraction of cells in the S phase) can be independent prognostic indicators of the biologic aggressiveness of certain malignant neoplasms. OBJECTIVE: To determine whether the DNA index or proliferative index could predict metastases in cutaneous squamous cell carcinoma. METHODS: Nineteen different metastases from 15 patients with primary cutaneous squamous cell carcinoma (SCC) were reviewed, graded, and had DNA proliferative indexing performed by fluorescent activated cytometry. A control group of 13 patients with primary cutaneous SCC without metastases were studied in a similar manner. RESULTS: No significant difference between the metastatic and the nonmetastatic SCC groups for either DNA index or proliferative index (non-paired t-test) was observed. No correlative association with histologic grading with DNA index or proliferative index was observed for either group. CONCLUSION: We conclude that aneuploidy and S-phase fraction by fluorescent activated cytometry are not significant predictors of potential metastases in cutaneous squamous cell carcinoma.

Carcinoma, Squamous Cell

Subgroups of luteinizing hormone-releasing hormone perikarya defined by computer analyses in the basal forebrain of intact female rats.

The hypothesis that the basal forebrain population of LHRH perikarya is composed of heterogeneous subgroups was examined in this study. We used three-dimensional computerized reconstruction to examine populations of LHRH-immunopositive neurons detected in noncolchicine treated cycling female rats. Perikarya were detected with two antisera capable of detecting LHRH decapeptide within larger mol wt species, i.e. Millar's (RM) 1076 and Arimura's (AA) 419. No immunopositive perikarya were detected with antiserum AA 422, which requires the fully processed decapeptide for binding. A more broadly distributed population of LHRH neurons was detected in females killed on proestrus than in females killed on estrus or the other days of the cycle. These relationships were observed with both antisera, RM 1076 and AA 419. Subgroups of cells were clearly defined when the population of LHRH neurons detected on proestrus was simultaneously displayed with the population detected on estrus. Strikingly similar subgroups were revealed by simultaneous displays of populations of LHRH neurons detected by the antisera RM 1076 and AA 419 in proestrous females. This study revealed a three-dimensional onion skin-like laminar organization of LHRH subgroups expanding from the ventricle outward laterally and from the diagonal band of Broca to the hypothalamus caudally. We propose that these subgroups vary in their metabolic activity of biosynthesis, processing, transport, or release of LHRH in relation to the proestrous preovulatory release of LH.

Animals

Integrating experienced and novice nurses into graduate home health education.

Preparing master's-level professionals in home health nursing presents challenges because nurses come to graduate programs with varying degrees of home health experience. The purpose of this study was to examine how nurses with varying experience in home health nursing are integrated into graduate clinical practicum courses. Representations of 10 home health graduate programs were surveyed regarding how they adapt their clinical practicums to meet the special needs of their novice and experienced nurses. Respondents revealed that individualization was used to meet the individual needs of students. Individualization allows for creativity in developing learning experiences that are both challenging and satisfying for the student. However, lack of consistency in the advanced practice skills of graduates, and lack of time efficiency for faculty and agency personnel can also occur. Faculty members need to share creative ways of teaching students, to identify unique opportunities for clinical experiences, and to collaborate on research.

Clinical Competence

Far-field potentials in muscle: a quantitative investigation.

Far-field potentials have been produced from muscle tissue and shown to arise from both the proximal and distal musculotendinous junctions after the activation of a small group of muscle fibers. This investigation demonstrated that the polarity of muscle far-field potentials is consistent with the predictions of the leading/trailing dipole model. Far-field potential polarity was dependent upon the active electrode's orientation with respect to the positive or negative aspect of the trailing dipole after extinction of the leading dipole at the musculotendinous junction. This study also quantitatively measured the duration and magnitude of the two far-field potentials generated in the human biceps muscle by both proximal and distal muscle stimulation. The muscle far-field potential resulting from distal muscle stimulation closest to the musculotendinous junction was consistently shorter in mean duration (5.2msec +/- 2.1) but larger in mean amplitude (22.3 microV +/- 12.9) compared with the second far-field potential mean duration (10.4msec +/- 3.9) and amplitude (10.0 microV +/- 3.7). The mean areas under the curve for these far-field potentials, however, were comparable at 48.0msec microV and 48.7msec microV. Proximal muscle stimulation resulted in similar findings for the first far-field potential's mean duration, amplitude, and area (6.0msec; 19.7 microV; 50.6msec microV, respectively) in relation to those of the second far-field potential (12.5msec; 9.1 microV 49.1msec microV). The differences in amplitude and duration of the two far-field potentials, with similar areas, are consistent with, and can be adequately explained by, temporal dispersion effects of the muscle fiber action potentials' propagation over distance.

Action Potentials

Far-field potentials in muscle.

Far-field potentials have been predicted by computer simulations as well as demonstrated in both animals and humans with respect to the peripheral and central nervous systems. Computer simulations have also predicted far-field potentials originating at the termination of muscle tissue. This investigation demonstrates the occurrence of 2 far-field potentials in the human biceps muscle resulting from action potential termination at the musculotendonous junctions. A monophasic potential is produced at both the muscle's origin and insertion, and the polarity is entirely dependent upon the recording montage. Sequential stimulation of the biceps muscle at 2.5-cm increments resulted in the 2 far-field potentials and their respective latencies changing proportional to the distance between the stimulus site and the 2 musculotendonous junctions. Various stimulation and recording montages are used to investigate the properties of these far-field potentials. The leading/trailing dipole model is utilized to explain the production and polarity of far-field potentials generated by muscle tissue.

Action Potentials

Safety and immunogenicity of live attenuated cold-adapted influenza B/Ann Arbor/1/86 reassortant virus vaccine in infants and children.

A cold-adapted (ca) influenza B reassortant vaccine consisting of two genes encoding the hemagglutinin and neuraminidase from wild-type influenza B/Ann Arbor/1/86 virus and the six internal RNA segments from influenza B/Ann Arbor/1/66 ca virus was evaluated in 18 seropositive and 57 seronegative infants and children. The ca reassortant was infectious in seronegative vaccinees, with an estimated 50% human infectious dose of 10(2.5) TCID50. Nasal wash specimens from vaccinees retained the temperature-sensitive phenotype, indicating that the virus was phenotypically stable after replication in fully susceptible children. The vaccine was highly immunogenic in the seronegative vaccinees; 54% of the seropositive vaccinees also developed an increase in serum antibody. The ca vaccine was well tolerated, with only a mild increase in upper respiratory tract symptoms seen in the seronegative vaccinees. These studies indicate that the B/Ann Arbor/1/86 ca reassortant is safe, immunogenic, and phenotypically stable in infants and children.

Antibodies, Viral

Safety and immunogenicity of human rotavirus vaccine strain M37 in adults, children, and infants.

Rotavirus vaccine strain M37 (serotype 1), recovered from the stool of an asymptomatic newborn infant and serially passaged in cell culture, was given orally to adults, children, and infants. Serologic responses were detected by neutralization assay or EIA in 59% of 17 adults (10(5)-pfu dose), 55%-60% of 21 infants and children (10(4)-pfu dose), and 70% of 10 infants (10(5)-pfu dose), vaccine virus was shed by 24%, 20%-36%, and 70%, respectively. In adults, neutralizing antibody rises to strain M37 and the related serotype 1 strain Wa occurred with equal frequency (41% vs. 47%). In pediatric subjects, the former were more frequent (36%-40%) than the latter (10%-18%). This was also true of 8 infants who received two doses of vaccine. Mild gastrointestinal illnesses occurred with equal frequency in pediatric subjects who received vaccine or placebo. Thus, strain M37 was well tolerated and immunogenic in young infants, but elicited primarily vaccine-strain-specific rather than serotype-specific neutralizing antibody responses.

Adult

Computer-assisted mapping of immunoreactive mammalian gonadotropin-releasing hormone in adult human basal forebrain and amygdala.

Immunocytochemistry performed on 80-microns unembedded tissue sections was used to study the localization of GnRH-containing neurons and fibers in the basal forebrain and amygdala of six adult (four male, two female) human brains. Sections from one of the female brains were subjected to computer-assisted microscopic mapping to generate a three-dimensional analysis of immunoreactive structures. In all six brains examined, cell bodies were concentrated in the preoptic area and basal hypothalamus, but were also evident in the septal region, anterior olfactory area, and cortical and medial amygdaloid nuclei. GnRH-containing fibers were observed within the hypothalamus (predominantly infundibular region and preoptic area), septum, stria terminalis, ventral pallidum, dorsomedial thalamus, olfactory stria, and anterior olfactory area. Many fibers could also be seen coursing along the base of the brain between the hypothalamus and cortical and medial amygdaloid nuclei. The localization of GnRH-containing cells and fibers in several of these areas represents new observations in the human brain and suggests a role for the amygdaloid complex in the regulation of gonadotropin secretion. The comprehensive view provided by these data may be useful in the clinical application of novel transplantation strategies.

Adult