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Biomedical subjects

J Walsh

Publications and source records attributed to J Walsh.

At least 91 records · Page 5Linked to original sources

Changes in testicular steroidogenic acute regulatory (STAR) protein, steroidogenic enzymes and testicular morphology associated with increased testosterone secretion in bulls receiving the luteinizing hormone releasing hormone agonist deslorelin.

Testosterone secretion and the expression and relative contents of steroidogenic acute regulatory (StAR) protein and steroidogenic enzymes cholesterol side-chain cleavage cytochrome P450 (P450SCC), 3beta-hydroxysteroid dehydrogenase/delta(5)-->delta(4)-isomerase (3 beta-HSD), and (17)alpha-hydroxylase cytochrome P450/C17-20 lyase (P450(17)alpha) were determined in testicular tissues of bulls treated with a LHRH agonist. Testis morphology and spermatogenesis were also examined. In Experiment 1, bulls (30-mo-old) received no treatment (control, n = 7) or were implanted for 10 days with the LHRH agonist deslorelin (n = 7). Bulls were castrated on Day 10 and testis tissues prepared for Western and Northern blotting. At castration, bulls implanted with deslorelin had greater plasma testosterone (5-fold) and testis content of testosterone (10-fold) compared with control bulls. Relative content (per micrograms total testis protein or RNA) of StAR protein, 3beta-HSD, P450SCC, and mRNA for P450(17)alpha in bulls treated with deslorelin ranged from 3- to 6-fold that of control bulls. In Experiment 2, bulls (20-mo-old) were left untreated (control, n = 6) or implanted with deslorelin (n = 12) for 120 days. On Day 120, bulls were castrated and right testis tissues prepared for morphology. Testis volume and weight were increased (P < 0.01) in bulls treated with deslorelin compared with control bulls. Stereological analysis revealed that this increase occurred in all compartments (seminiferous epithelium, lumen and interstitium) studied, but was significant (P < 0.01) only for the seminiferous epithelium. Absolute numbers of round spermatids per testis were increased (P < 0.05) in bulls treated with deslorelin compared with control bulls. Increased testosterone secretion in bulls treated with deslorelin was associated with increased testicular StAR protein and steroidogenic enzymes. Bulls treated long-term with deslorelin had a faster rate of testis growth and increased daily sperm production at the end of the experiment.

17-Hydroxysteroid Dehydrogenases↗

Effects of litigation settlements on posttraumatic stress symptoms in motor vehicle accident victims.

In order to investigate the effects of the initiation of litigation and its settlement on victims of motor vehicle accidents (MVAs), we followed up 132 MVA victims from an initial assessment 1 to 4 months post-MVA for 1 year. Of the 67 who had initiated litigation, 18 (27%) settled within the 12 months, while 49 still had litigation pending; 65 never initiated litigation. Those who initiated litigation had more severe injuries and higher initial levels of posttraumatic stress (PTS) symptoms. All three groups improved in major role function and had reduced PTS symptoms over the 1 year follow-up. Those whose suits were still pending, as well as those whose suits had been settled, showed no reduction in measures of anxiety or depression, whereas the nonlitigants did show improvement on these measures.

Accidents, Traffic↗

Mortality following spinal cord injury.

This study analyzed the mortality in 1453 spinal cord injured patients admitted early after injury to a specialised Spinal Injuries Unit within a University teaching hospital over a 40-year period. The cohort comprised 55.3% patients with cervical lesions and 44.7% patients with thoracic/lumbar lesions. Those patients who died within 18 months of the spinal injury (132) were excluded from the final analysis. Standardised Mortality Ratios, survival rates and life expectancy ratios were calculated for specific ranges of current attained age and duration since injury with reference to level and degree of spinal cord injury. The projected mean life expectancy of spinal cord injured people compared to that of the whole population was then estimated to approach 70% of normal for individuals with complete tetraplegia and 84% of normal for complete paraplegia (Frankel grade A). Patients with an incomplete lesion and motor functional capabilities (Frankel grade D) are projected to have a life expectancy of at least 92% of the normal population.

Adult↗

Impact of pediatric traumatic brain injury on components of verbal memory.

This 3-month longitudinal study examined spared and impaired components of verbal learning and memory after pediatric traumatic brain injury (TBI), using the California Verbal Learning Test for Children. School-aged participants with severe or mild-to-moderate TBI were compared to traumatically injured control subjects without head trauma. Participants were initially evaluated approximately 1 month post injury, and again 3 months later. At Times 1 and 2, participants with severe TBI displayed deficits in immediate recall, delayed recall, and recognition accuracy, consistent with a mild encoding deficit. In both evaluations, participants with mild-to-moderate TBI performed similarly to controls. On average, mild verbal encoding deficits appear to be associated with severe, but not mild-to-moderate, pediatric TBI in the first several months post injury.

Brain Damage, Chronic↗

Co-localization of dystrophin and beta-dystroglycan demonstrated in en face view by double immunogold labeling of freeze-fractured skeletal muscle.

An absence of dystrophin causes Duchenne muscular dystrophy, but the precise mechanism underlying necrosis of the muscle cells is still unclear. Dystrophin and beta-dystroglycan are components of a complex of at least nine proteins, the dystrophin-glycoprotein complex (DGC), that links the membrane cytoskeleton to extracellular elements in skeletal and cardiac muscle. Biochemical studies indicate that dystrophin is bound to other components of the DGC via beta-dystroglycan, which suggests that the distribution of these two proteins should be almost identical. In this study, therefore, we examined the spatial relationship between dystrophin and beta-dystroglycan with a range of different imaging techniques to investigate the extent of the predicted co-localization. We used (a) double immunogold fracture-label, a freeze-fracture cytochemical technique that allows high-resolution face-on views of labeled membrane components in thin sections and in platinum-carbon replicas, (b) double immunogold labeling of cryosections and (c) confocal microscopy. Both dystrophin and beta-dystroglycan were found over the entire fiber surface and, when labeled singly, the nearest neighbor spacing of labeling sites for the two proteins was indistinguishable. With double labeling, very close co-localization could be demonstrated. The results support the conclusion that dystrophin and beta-dystroglycan directly interact at the muscle plasma membrane. (J Histochem Cytochem 46:945-953, 1998)

Animals↗

Shaker-1 mutations reveal roles for myosin VIIA in both development and function of cochlear hair cells.

The mouse shaker-1 locus, Myo7a, encodes myosin VIIA and mutations in the orthologous gene in humans cause Usher syndrome type 1B or non-syndromic deafness. Myo7a is expressed very early in sensory hair cell development in the inner ear. We describe the effects of three mutations on cochlear hair cell development and function. In the Myo7a816SB and Myo7a6J mutants, stereocilia grow and form rows of graded heights as normal, but the bundles become progressively more disorganised. Most of these mutants show no gross electrophysiological responses, but some did show evidence of hair cell depolarisation despite the disorganisation of their bundles. In contrast, the original shaker-1 mutants, Myo7ash1, had normal early development of stereocilia bundles, but still showed abnormal cochlear responses. These findings suggest that myosin VIIA is required for normal stereocilia bundle organisation and has a role in the function of cochlear hair cells.

Animals↗

The clinical case management of clients with major depression.

In the field of mental health, clinical case management represents a set of interventions that feature ongoing support to persons with chronic mental disorders. In this paper a specific case management approach to working with persons having major depression is outlined. The causes of depression may be primarily biological, but psychological and social conditions also have impact on the course of the disorder. The clinical case management approach includes a variety of interventions which attend to both counseling and environmental work and accommodate the changing severity of the client's depression over time. The interventions described include ego support, crisis intervention, interpersonal therapy, and cognitive-behavioral techniques. Case examples are included as illustrations.

Adaptation, Psychological↗

Transscleral diode laser retinopexy in retinal detachment surgery: results of a multicenter trial.

PURPOSE: To evaluate the safety and efficacy of transscleral diode laser for retinopexy in rhegmatogenous retinal detachment surgery in a multicenter trial. METHODS: Seventy-two patients with primary rhegmatogenous retinal detachments were enrolled. No patient with chronic detachment, a retinal break greater than 90 degrees, history of uveitis or infectious retinopathy, or proliferative vitreoretinopathy was enrolled. RESULTS: Information from follow-up of 6 months or longer was available on 65 eyes. Retinas were attached at 6 months with a single operation in 58 (89%) of these eyes. Complications included apparent pinpoint breaks in Bruch's membrane in 15 eyes, scleral-thermal effect in 14 eyes, and limited hemorrhage, which was intraretinal in 10 eyes and extended into the vitreous in 3 eyes. In one case, hemorrhage was judged perhaps to have contributed to initial surgical failure. The other complications had no known adverse effects. Complications were significantly associated with the physician's experience in using transscleral laser retinopexy. CONCLUSIONS: In this multicenter study, transscleral diode laser retinopexy served as a safe and effective means of creating chorioretinal adhesion during retinal reattachment surgery. Minor complications were minimized by increasing experience with the technique.

Adolescent↗

Localization of neuropeptide Y Y1 receptors in cerebral blood vessels.

The localization of neuropeptide Y (NPY) Y1 receptor (R) -like immunoreactivity (LI) has been studied in cerebral arteries and arterioles of the rat by immunohistochemistry using fluorescence, confocal, and electron microscopy. High levels of Y1-R-LI were observed in smooth muscle cells (SMCs) in the small arterioles of the pial arterial network, especially on the basal surface of the brain, and low levels in the major basal cerebral arteries. The levels of Y1-R-LI varied strongly between adjacent SMCs. Y1-R-LI was associated with small endocytosis vesicles, mainly on the outer surface of the SMCs, but also on their endothelial side and often laterally at the interface between two SMCs. NPY-immunoreactive (Ir) nerve fibers could not be detected in association with the Y1-R-rich small arterioles but only around arteries with low Y1-R levels. A dense network of central NPY-Ir nerve fibers in the superficial layers of the brain was lying close to the strongly Y1-R-Ir small arterioles. The results indicate that NPY has a profound effect on small arterioles of the brain acting on Y1-Rs, both on the peripheral and luminal side of the SMCs. However, the source of the endogenous ligand, NPY, remains unclear. NPY released from central neurons may play a role, in addition to blood-borne NPY.

Animals↗

Effects of shaker-1 mutations on myosin-VIIa protein and mRNA expression.

Numerous mammalian diseases have been found to be due to mutations in components of the actin cytoskeleton. Recently, mutations in the gene for an unconventional myosin, myosin-VIIa, were found to be the basis for the deafness and vestibular dysfunction observed in shaker-1 (sh1) mice and for a human deafness-blindness syndrome, Usher syndrome type 1B. Seven alleles of sh1 mice were analyzed to assess the affects of different myosin-VIIa mutations on both gene expression and tissue function. Myosin-VIIa is expressed in the inner ear and the retina, as well as the kidney, lung, and testis. Northern blot analysis indicated that myosin-VIIa mRNA expression, size, and stability were unaffected in the seven sh1 alleles. Immunoblot analysis showed that all seven alleles expressed some full-length myosin-VIIa protein. The range of expression, however, ran from sh1 [original], which expressed wild-type levels of protein, to two strains, sh1(4494SB) and sh1(4626SB), which expressed less than 1% of the normal level of myosin-VIIa protein. For the three alleles of sh1 that have been characterized and that have mutations in the motor domain, sh1 [original], sh1(816SB) and sh1(6J), the level of protein expression observed in these sh1 alleles correlated well with the predicted effects of the mutations on motor function. No change in retinal or testicular structure was observed at the light microscopic level during the life span of the seven sh1 alleles. Myosin-VIIa protein, when detectable, was observed to locate properly in the sh1 mice. On the basis of these results, we propose that the mutations in myosin-VIIa in the sh1 alleles leads to both motor dysfunction and to a protein destabilization phenotype.

Abnormalities, Multiple↗

Use of a GnRH agonist to prevent the endogenous LH surge and injection of exogenous LH to induce ovulation in heifers superstimulated with FSH: a new model for superovulation.

A new protocol for superovulating cattle which allows for control of the timing of ovulation after superstimulation with FSH was developed. The preovulatory LH surge was blocked with the GnRH agonist deslorelin, and ovulation was induced by injection of LH. In Experiment 1, heifers (3-yr-old) were assigned to a control group (Group 1A, n = 4) or a group with deslorelin implants (Group 1B, n = 5). On Day -7, heifers in Group 1A received a progestagen CIDR-B((R))device, while heifers in Group 1B received a CIDR-B((R))device + deslorelin implants. Both groups were superstimulated with twice daily injections of FSH (Folltropin((R))-V): Day 0, 40 mg (80 mg total dose on Day 0); Day 1, 30 mg; Day 2, 20 mg; Day 3, 10 mg. On Day 2, heifers were given PGF (a.m.) and CIDR-B((R)) devices were removed (p.m.). Three heifers in Group 1A had a LH surge and ovulated, whereas neither of these events occurred in Group 1B (with deslorelin implants) heifers. In Experiment 2, heifers (3-yr-old) were assigned to 1 of 4 equal groups (n = 6). On Day -7, heifers in Group 2A received a norgestomet implant, while heifers in Groups 2B, 2C and 2D received norgestomet + deslorelin implants. Heifers were superstimulated with FSH starting on Day 0 as in Experiment 1. On Day 2, heifers were given PGF (a.m.) and norgestomet implants were removed (p.m.). Heifers in Groups 2B to 2D were given 25 mg LH (Lutropin((R))): Group 2B, Day 4 (a.m.); Group 2C, Day 4 (p.m.); Group 2D, Day 5 (a.m.). Heifers in Group 2A were inseminated at estrus and 12 and 24 h later, while heifers in Groups 2B to 2D were inseminated at the time of respective LH injection and 12 and 24 h later. Injection of LH induced ovulation in heifers in Groups 2B to 2D. Heifers in Group 2C had similar total ova and embryos (15.2 +/- 1.4) as heifers in Group 2A (11.0 +/- 2.8) but greater (P < 0.05) numbers than heifers in Group 2B (7.0 +/- 2.3) and Group 2D (6.3 +/- 2.0). The number of transferable embryos was similar for heifers in Group 2A (5.8 +/- 1.8) and Group 2C (7.3 +/- 2.1) but lower (P < 0.05) for heifers in Group 2B (1.2 +/- 0.8) and Group 2D (1.3 +/- 1.0). The new GnRH agonist-LH protocol does not require observation of estrus, and induces ovulation in superstimulated heifers that would not have an endogenous LH surge.

Journal Article↗

Comparison of induced versus expectorated sputum for diagnosis of pulmonary tuberculosis by acid-fast smear.

OBJECTIVE: To evaluate the sensitivity of induced versus expectorated sputum for the diagnosis of pulmonary tuberculosis by acid-fast smear. METHODS: We performed a retrospective review of data on patients with cultures from respiratory secretions that were positive for Mycobacterium tuberculosis. We analyzed data on the 114 patients with positive cultures during a 4-year period in an urban tertiary care academic medical center. RESULTS: Sputum samples had been obtained for 103 of the 114 patients with cultures positive for tuberculosis. Forty-four of the 114 patients were HIV seropositive. Overall 33 of 79 patients (42%) had positive acid-fast smears of expectorated sputum, and 6 of 24 (25%) had positive smears of induced sputum (p = 0.21). When data were analyzed for subgroups by HIV serostatus, there was no significant difference in the results. Estimated cost of sputum induction for 1 year was approximately $45,000. CONCLUSIONS: We found sputum induction to be costly, and induced sputum offered no advantage over routine expectorated sputum for the diagnosis of pulmonary tuberculosis.

Coloring Agents↗

Increased testosterone secretion in bulls treated with a luteinizing hormone releasing hormone (LHRH) agonist requires endogenous LH but not LHRH.

The requirement for endogenous LHRH and LH action in the maintenance of elevated plasma concentrations of testosterone in bulls receiving the LHRH agonist deslorelin was examined. In Experiment 1, bulls were either (i) left untreated (control); (ii) implanted with deslorelin; (iii) actively immunized against LHRH; or (iv) implanted with deslorelin and immunized against LHRH. Experiment 2 was of similar design to Experiment 1, except that bulls were immunized against LH in place of LHRH. In Experiment 1, plasma LH declined in bulls immunized against LHRH, but not in the bulls immunized against LHRH and implanted with deslorelin. Also in Experiment 1, plasma testosterone declined in bulls immunized against LHRH but was elevated in bulls treated with deslorelin and bulls treated with deslorelin and immunized against LHRH. In Experiment 2, bulls immunized against LH and treated with deslorelin had plasma concentrations of testosterone similar to controls, whereas bulls treated only with deslorelin had elevated plasma testosterone. It was concluded from these experiments that endogenous LHRH action was not required for increased steroidogenic activity in bulls treated with a LHRH agonist. However, circulating LH was necessary for increased plasma testosterone in bulls implanted with deslorelin. LH is therefore involved in mediating the response of bulls to treatment with deslorelin, either by acting directly at the testes or through a permissive role that allows a direct action of deslorelin at the testes.

Animals↗

Differential responses in anterior pituitary luteinizing hormone (LH) content and LH beta- and alpha-subunit mRNA, and plasma concentrations of LH and testosterone, in bulls treated with the LH-releasing hormone agonist deslorelin.

Anterior pituitary gland contents of LH and LH beta- and alpha-subunit mRNAs, and circulating concentrations of LH and testosterone, were determined in bulls treated with the LH-releasing hormone (LHRH) agonist deslorelin. Brahman (Bos indicus) bulls (14-month-old) were allocated to two groups and received the following: Control (n = 5), no treatment; Deslorelin (n = 4), four deslorelin implants (approximately 200 micrograms total deslorelin/day) for 36 d. Plasma concentrations of LH were higher in bulls treated with deslorelin on Day 1, had returned to typical levels by Day 8, and did not differ for control bulls and bulls treated with deslorelin from Day 8 to Day 29. Pituitary content of LH on Day 36 was reduced (P < 0.001) in bulls treated with deslorelin (33 +/- 4 ng/mg) compared with control bulls (553 +/- 142 ng/mg). Relative pituitary content of LH beta-subunit mRNA was also reduced on Day 36 in bulls treated with deslorelin (Control, 0.65 +/- 0.10; Deslorelin, 0.22 +/- 0.04; P = 0.003). However, alpha-subunit mRNA relative content did not differ (Control, 0.73 +/- 0.15; Deslorelin, 1.06 +/- 0.12; P > 0.05). Plasma concentrations of testosterone were increased over the period of the experiment in the bulls treated with deslorelin compared with control bulls. This is the first demonstration of reduced pituitary content of LH beta-subunit mRNA and LH, and unaltered content of alpha-subunit mRNA, in bulls treated with LHRH agonist. This was associated with apparently typical plasma concentrations of LH and elevated plasma testosterone. The anterior pituitary in bulls treated with LHRH agonist, therefore, undergoes classical desensitization and downregulation, but plasma LH and testosterone are not suppressed.

Animals↗