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Biomedical subjects

J L Smith

Publications and source records attributed to J L Smith.

At least 235 records · Page 13Linked to original sources

Absence of strong HLA-DR/DQ-DP linkage disequilibrium in the British and French Canadian Caucasoid populations.

HLA-DR/DQ-DP linkage disequilibrium was investigated in healthy, unrelated British (n = 150) and French Canadian (n = 67) Caucasoid subjects. HLA-DR and DQ typing was performed by Taq I DNA-RFLP analysis, while DPB1 typing was performed by PCR-SSOP. chi 2 and Fisher's exact tests were performed for all 2-locus biallelic comparisons and coefficients of linkage disequilibrium determined. In the British population, only one example of linkage disequilibrium, significant at P = 0.05 (after correction for the number of comparisons made) was seen (DPB1*0101-DRB1*0301[17(1)]). Additional associations, significant at P = 0.05 before correction for the number of comparisons were also seen, including DPB1*0401-DRB1*15, DPB1*1101-DRB1*0701(7(1)), DPB1*1701-DRB1*0701/ 2(7(2)), DPB1*0101-DQA1*0501, DPB1*0401-DQA1*0102, DPB1*0501-DQA1*0102, DPB1*0101-DQB1*0201, DPB1*0401-DQB1*0602/0603 and DPB1*1101-DQB1*0201. With one exception (DPB1*1101-DQB1*0201), none of these associations was seen in the French Canadian group. These results indicate that although more frequent than thought hitherto, HLA class II linkage disequilibrium involving DPB1 alleles is generally weak, and can differ even between different caucasoid populations. This may have implications for HLA and disease studies.

Alleles↗

Adaptive control for backward quadrupedal walking. III. Stumbling corrective reactions and cutaneous reflex sensitivity.

1. Four cats were trained to walk backward (BWD) and forward (FWD) on a motorized treadmill. Mechanical (taps) or electrical (pulses) stimuli were applied to the dorsal or ventral aspect of the hind paw during swing or stance. Hindlimb kinematic data, obtained by digitizing 16-mm high-speed film, were synchronized with computer-analyzed electromyograms (EMG) recorded from anterior biceps femoris (ABF), vastus lateralis (VL), lateral gastrocnemius (LG), tibialis anterior (TA), and semitendinosus (ST). Responses to taps and pulses, as well as the modulation in cutaneous reflex sensitivity to pulses, were described for both walking directions and stimulus locations. 2. After dorsal taps that obstructed FWD swing, the hindlimb initially drew back away from the obstacle with knee flexion and ST activation, ankle extension with TA suppression and LG activation, and hip extension with ABF facilitation. Next, the limb was raised over the obstacle with resumed TA activity and enhanced knee and ankle flexion, and then compensatory knee and ankle extension positioned the limb for the ensuing stance phase. 3. For ventral taps that obstructed BWD swing, the initial response also tended to draw the limb away from the obstacle with hip and ankle flexion and TA facilitation and reduced knee flexion with weak VL facilitation and suppression of ST activity. Next, ST activity resumed as knee and ankle flexion raised the limb over the obstacle, and then compensatory extension completed the swing phase for BWD walking. Thus the initial kinematic and EMG responses to obstacles were opposite for BWD versus FWD swing, and these responses were consistent with active avoidance of the obstacles. Responses during BWD walking were subtle, however, compared with those for FWD. 4. After nonobstructing taps (ventral FWD, dorsal BWD), ST and TA activation and knee and ankle flexion were coincident, demonstrating that the aforementioned differences in responses to obstructing obstacles were not simply location dependent. Regardless of the direction of walking or the location of stimulation, taps applied during stance had little immediate kinematic effect, but the subsequent swing phase was usually exaggerated, as if the response was programmed to avoid any lingering obstacle. 5. Electrical pulses did not elicit the full-blown responses typically evoked by taps. The sequencing in activation of ST and TA characteristic after laps was absent after pulses, and there were rarely dramatic kinematic responses to pulses like those easily elicited by taps. There were, in fact, few differences in responses to electrical stimulation for BWD versus FWD walking.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

Adaptive control for backward quadrupedal walking. IV. Hindlimb kinetics during stance and swing.

1. Hindlimb step-cycle kinetics of forward (FWD) and backward (BWD) walking in adult cats were assessed. The hindlimb was modeled as a linked system of rigid bodies and inverse-dynamics techniques were used to calculate hip, knee, and ankle joint kinetics. For swing, net torque at each joint was divided into three components: gravitational, motion dependent, and a generalized muscle torque. For stance, vertical and horizontal components of the ground-reaction force applied at a point on the paw (center of pressure) were added to the torque calculations. Muscle torque profiles were matched to electromyograms (EMGs) recorded from hindlimb muscles. 2. Torque profiles for BWD swing were the approximate time reversal of those for FWD swing. At each joint, the net torque during swing was small because the mean motion-dependent and muscle torque components counteracted each other. At the hip a flexor muscle torque persisted except for a brief extensor muscle torque late in FWD swing and at the onset of BWD swing. At the knee the muscle torque was relatively negligible except for a peak flexor muscle torque late in FWD swing and early in BWD swing. At the ankle there was a midswing transition from a flexor to an extensor muscle torque during FWD swing and the reverse was true for BWD swing. 3. The vertical ground-reaction force was greater for the forelimbs than the hindlimbs during FWD stance; the reverse was true for BWD stance. Thus the hindlimbs bore a greater percentage (66%) of body weight than the forelimbs during BWD stance, and the forelimbs bore a greater percentage (59%) during FWD stance. For most of FWD stance, the hindlimb exerted a small propulsive ground-reaction force, but for BWD stance the hindlimb first exerted a braking force and then a propulsive force, with the transition occurring after midstance (59% of stance). 4. At the hip the ground-reaction force vector was oriented anteriorly and then posteriorly to the estimated joint center with a midstance transition during FWD stance. The muscle torque and joint power patterns showed similar transitions, changing from extensor and power generation to flexor and power absorption, respectively. For most of BWD stance the ground-reaction force vector was oriented anteriorly to the joint center and was counter-balanced by a large extensor muscle torque; nonetheless, power was absorbed because the hip flexed.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

RNA regulatory element BLE1 directs the early steps of bicoid mRNA localization.

Deployment of the bicoid morphogen gradient in early Drosophila embryos requires the prelocalization of bicoid mRNA to the anterior pole of the egg. This anterior localization is mediated by a cis-acting localization signal contained within the 3' untranslated region of the bicoid mRNA. Here we use a series of bicoid transgenes carrying small deletions in the 3' untranslated region to survey for functional elements that constitute the localization signal. We identify and characterize one essential element, BLE1, which specifically directs the early steps of localization. In addition, we find that many deletions within the bicoid mRNA 3' untranslated region impair but do not prevent localization. One such deletion specifically interferes with a later step in localization. Thus the bicoid mRNA localization signal appears to consist of multiple different elements, each responsible for different steps in the localization process.

Animals↗

Multiple RNA regulatory elements mediate distinct steps in localization of oskar mRNA.

Pattern formation in the early development of many organisms relies on localized cytoplasmic proteins, which can be prelocalized as mRNAs. The Drosophila oskar gene, required both for posterior body patterning and germ cell determination, encodes one such mRNA. Localization of oskar mRNA is an elaborate process involving movement of the transcript first into the oocyte from adjacent interconnected nurse cells and then across the length of the oocyte to its posterior pole. We have mapped RNA regulatory elements that direct this localization. Using a hybrid lacZ/oskar mRNA, we identify several elements within the oskar 3' untranslated region that affect different steps in the process: the early movement into the oocyte, accumulation at the anterior margin of the oocyte and finally localization to the posterior pole. This use of multiple cis-acting elements suggests that localization may be orchestrated in a combinatorial fashion, thereby allowing localized mRNAs with ultimately different destinations to employ common mechanisms for shared intermediate steps.

Animals↗

Genotypic heterogeneity of node based peripheral T-cell lymphoma.

PTCL represents a diverse group of histological entities that defy classification schemes based on normal T cell differentiation, differ in their clinical presentation and behave unpredictably. Genetic analyses of this phenotypically heterogeneous group have clearly shown that histologically defined PTCL may be subdivided on the basis of clonal gene rearrangements. The absence of clonal gene rearrangements in a significant proportion of PTCL cases has increased the complexity of classification. The data presented in this review suggest that a molecular classification would allow true reflection of PTCL aetiology, but carefully coordinated studies are required to evaluate the clinical usefulness of such a classification scheme.

Clone Cells↗

Ocular pulsation in neurofibromatosis. A clinical/neuroradiologic correlation.

A 61-year-old woman presented with early cataract formation in an eye which had been pulsating synchronously with her heart beat all of her life. This report presents the first, to our knowledge, three dimensional reconstruction CT images of this form of neurofibromatosis 1. It also documents by MRI and MRA the association of an asymptomatic carotid-ophthalmic junction aneurysm ipsilateral to the sphenoid dysplasia.

Blood Flow Velocity↗

Incidence, management and significance of surgical complications after pancreatic transplantation.

Despite recent advances, pancreatic transplantation is still in evolution and is associated with considerable surgical morbidity. We reviewed the surgical complications of 127 consecutive whole pancreatic transplants performed at the University of Iowa between March 1984 and January 1992, to evaluate the impact of these complications on graft and patient outcome. Of these transplantations, 89 were simultaneous pancreatic and renal transplants, 32 pancreas after kidney and six pancreas alone. Of all complications requiring hospital admission, 29 percent were surgical in nature. Graft thrombosis (19 percent), deep wound infection (18 percent), duodenal leak (7 percent) and iliac artery disruption (3 percent) were all associated with significant graft (n = 28) and patient (n = 6) loss. In contrast, recurrent urinary tract infections (20 percent), recurrent pancreatitis (17 percent), superficial wound infections (13 percent) and recurrent hematuria (12 percent) did not affect patient or graft outcome. Surgical complications after technically successful transplants were associated with a 4.9 percent mortality rate and a 4.9 percent graft loss. The overall one year actuarial patient and pancreas graft survival rate was 86 and 75 percent, respectively. Despite ongoing refinements in surgical technique, pancreatic transplantation is still associated with considerable surgical morbidity. However, the outcome is favorable if these complications are managed aggressively.

Abscess↗

Overexpression of oskar directs ectopic activation of nanos and presumptive pole cell formation in Drosophila embryos.

In Drosophila, a small group of maternal effect genes, including oskar, defines a shared pathway leading to the provision of two determinants at the posterior pole of the embryo. One determinant is the posterior body patterning morphogen nanos, and the other directs germ cell formation. Overexpression of oskar causes the shared pathway to be hyperactivated, with excess nanos activity present throughout the embryo and a superabundance of posterior pole cells. In addition, presumptive pole cells appear at a novel anterior position. Strikingly, formation of these ectopic pole cells is enhanced in nanos mutants. This observation may reflect competition between nanos and the germ cell determinant for a shared and limiting precursor.

Animals↗

T-cell receptor variable (V) gene usage by lymphoid populations in T-cell lymphoma.

A panel of monoclonal antibodies specific for TcR V gene families was used to study TcR V region expression in 28 cases of malignant and reactive T-cell expansions including four cases of mixed cellularity Hodgkin's disease (HD) and five reactive cases. TcR V beta 5 gene products were represented in three cases of lymphoblastic malignancy (V beta 5.1, V beta 5.2) and two cases of peripheral T-cell lymphoma (PTCL) (V beta 5.1). In the PTCL cases, the expanded family was found in the absence of clonal TcR gene rearrangements and in one of these cases with Ig JH and Ck clonal gene rearrangements consistent with the presence of a phenotypically and histologically undetectable clonal B-cell population. In a third PTCL case not investigated for genotype, the TCR V alpha 12 family was overrepresented. Expanded TcR V alpha 2 and V beta 5.1 families were identified in HD and V beta 8 and V beta 5.2/V beta 5.3 families in a reactive lymph node and CD3 and CD8-positive blood lymphocytosis respectively. Further study of PTCL and related entities are needed to establish whether expanded TcR families are common in those cases that fail to exhibit clonal TcR gene rearrangement.

Antibodies, Monoclonal↗

Lack of correlation between IgG T-lymphocyte flow cytometric crossmatches with primary renal allograft outcome.

The flow cytometric crossmatch (FCXM) has been reported to be more sensitive and capable of detecting very low levels of antibodies than the normally used complement dependent cytotoxicity test. We studied both the two colour IgG T cell FCXM and CDC-XM in 146 renal allograft recipients, 111 primary and 35 regrafts, of which 26% (29/111) of 1st and 20% (7/35) of regrafts had a positive FCXM. There was no overall correlation between the FCXM results and early graft outcome in primary renal allografts. The FCXM did not appear to have any advantage over the CDC-XM in predicting graft outcome in unsensitized first grafts. In the small number of regrafts studied, a positive FCXM was associated with a higher degree of graft failure. FCXM can exhibit false negative results if sera are used solely neat although these prozone phenomena do not influence subsequent graft outcome.

Adult↗

Urinary trypsin levels observed in pancreas transplant patients with duodenocystostomies promote in vitro fibrinolysis and in vivo bacterial adherence to urothelial surfaces.

This study evaluated the role of activated urinary trypsin in mediating the increased incidence of infectious and hemorrhagic lower urinary tract complications in pancreas transplant patients with pancreatico-duodenocystostomies (PDC). The effect of trypsin concentrations corresponding to those observed in the urine of PDC patients were studied using an in vitro assay of clot lysis and an in vivo assay of bacterial-urinary tract adherence. Results were compared with those of parallel assays performed using urine from a pancreas transplant patient with a duodenocystostomy and control human urine. All trypsin concentrations studied demonstrated fibrinolytic activity. Fibrinolysis increased as a direct function of both trypsin concentration and duration of substrate exposure (P < 0.0001). Fibrin lysis resulting from the urine of the transplant patient was 4.6 times greater than that predicted based upon assays of total trypsin content in the sample. Fibrinolytic activity in control urine specimens was 0.16% of that observed in transplant urine specimens. Exposure of the rat urinary bladder to 200 micrograms/ml trypsin concentrations, or transplant urine, resulted in a significant increase in bacterial adherence over that seen in control urine from treated animals (P < 0.05). These findings demonstrate a significant effect of urinary trypsin on physiologic processes involved in hemostasis and the prevention of urinary tract infection. Active urinary trypsin may play an etiologic role in hemorrhagic and infectious lower urinary tract complications observed in patients with a PDC.

Animals↗

Single cervical exostosis. Report of a case and review of the literature.

The authors present a rare case of solitary cervical osteochondroma. Because of its rarity and its predilection for the atlantoaxial area, the diagnosis may be overlooked in evaluating patients having cervical myelopathy. Surgical decompression usually improves the patient's neurologic status.

Adult↗

Compound (primordial) adnexal carcinoma arising in a systematized compound epithelial nevus.

A distinctive systematized epithelial nevus and associated multifocal carcinomas of the microcystic and sclerosing sweat duct type affected the lower extremities of a 9-year-old girl. The carcinomas were well differentiated and were both adenosyringomatous and microcystic. They qualify as microcystic and compound. In both the epithelial nevi and the carcinoma, primordial potentials are recapitulated.

Biopsy↗

Prevalence of glioblastoma multiforme in subjects with prior therapeutic radiation.

This retrospective study profiled subjects with glioblastoma multiforme (GBM) who had previously received therapeutic radiation. A chart review was conducted of 100 adult patients diagnosed with GBM and referred to a major medical center in the southwestern United States. Seventeen patients received previous radiation therapy with an average dose of 48.5 Grey (Gy) and an average latency period of 15 years between initial therapy and GBM diagnosis. Of these 17, four white females fit all four attribution criteria for radiation-induced GBM. Two had been treated with radiation for prolactinomas, one for pinealoma and one for squamous cell cancer of the ethmoid sinus. The addition of these four case studies to the previously published descriptions of 80 cases of gliomas, 36 of which were GBM, subsequent to radiation therapy provides additional support for considering therapeutic radiation as a risk factor for GBM development.

Academic Medical Centers↗