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Biomedical subjects

R G Smith

Publications and source records attributed to R G Smith.

At least 217 records · Page 12Linked to original sources

NeuronC: a computational language for investigating functional architecture of neural circuits.

A computational language was developed to simulate neural circuits. A model of a neural circuit with up to 50,000 compartments is constructed from predefined parts of neurons, called "neural elements". A 2-dimensional (2-D) light stimulus and a photoreceptor model allow simulating a visual physiology experiment. Circuit function is computed by integrating difference equations according to standard methods. Large-scale structure in the neural circuit, such as whole neurons, their synaptic connections, and arrays of neurons, are constructed with procedural rules. The language was evaluated with a simulation of the receptive field of a single cone in cat retina, which required a model of cone-horizontal cell network on the order of 1000 neurons. The model was calibrated by adjusting biophysical parameters to match known physiological data. Eliminating specific synaptic connections from the circuit suggested the influence of individual neuron types on the receptive field of a single cone. An advantage of using neural elements in such a model is to simplify the description of a neuron's structure. An advantage of using procedural rules to define connections between neurons is to simplify the network definition.

Computer Simulation↗

Reduction of multiple aberrant behaviors and concurrent development of self-care skills with differential reinforcement.

A modified functional analysis was used to assess the behavioral function of a profoundly retarded man's self-injurious behavior (SIB). Results of that analysis showed that the behavior was most likely to occur in a demand context (self-care instructions) but was maintained by positive reinforcement in the form of attention and physical contact. The results of the functional analysis also prescribed a treatment involving differential reinforcement of alternative behavior (DRA). Further investigation showed that other aberrant behaviors, such as aggression and disruption, were members of the same functional response class as SIB. The differential reinforcement of alternative behavior (DRA) procedure effectively reduced those behaviors while compliance to a self-care acquisition task increased markedly. The results are discussed in terms of the importance of determining behavioral function prior to treatment.

Activities of Daily Living↗

Malate- and pyruvate-dependent Fatty Acid synthesis in leucoplasts from developing castor endosperm.

Leucoplasts were isolated from the endosperm of developing castor (Ricinis communis) endosperm using a discontinuous Percoll gradient. The rate of fatty acid synthesis was highest when malate was the precursor, at 155 nanomoles acetyl-CoA equivalents per milligram protein per hour. Pyruvate and acetate also were precursors of fatty acid synthesis, but the rates were approximately 4.5 and 120 times less, respectively, than when malate was the precursor. When acetate was supplied to leucoplasts, exogenous ATP, NADH, and NADPH were required to obtain maximal rates of fatty acid synthesis. In contrast, the incorporation of malate and pyruvate into fatty acids did not require a supply of exogenous reductant. Further, the incorporation of radiolabel into fatty acids by leucoplasts supplied with radiolabeled malate, pyruvate, or acetate was reduced upon coincubation with cold pyruvate or malate. The data suggest that malate and pyruvate may be good in vivo sources of carbon for fatty acid synthesis and that, in these preparations, leucoplast fatty acid synthesis may be limited by activity at or downstream of the acetyl-CoA carboxylase reaction.

Journal Article↗

Prospective study of necropsy audit of geriatric inpatient deaths.

AIMS: To evaluate the accuracy of clinical diagnosis by specialists in geriatric medicine and to compare this with a previous study involving non-specialists. METHOD: Clinical and necropsy diagnoses from consecutive hospital inpatient deaths from the University Department of Geriatric Medicine were analysed for discrepancies at regular audit meetings. Three main categories of diagnosis were considered and any therapeutic implications discussed. RESULTS: Between 1987 and 1989 necropsies were performed on 100 patients (38 men, 62 women, aged 63 to 99 years) from a total of 207 deaths, a necropsy rate of 50%. There was complete agreement between necropsy and clinical diagnoses in 32% of cases. Disagreement involved the main diagnosis in 28%, contributory conditions in 32%, and cause of death in 34%. In 10% of cases the diagnostic discrepancy was considered therapeutically important. Specialist geriatricians correctly diagnosed the main diagnosis in 72% of cases; non-specialists in the previous study were correct in only 47% of cases. CONCLUSION: Specialist geriatricians diagnose elderly people more accurately than non-specialists. But rates of misdiagnosis are still significant and necropsies continue to be a useful form of audit.

Aged↗

Dose related acute irritant symptom responses to occupational exposure to sodium borate dusts.

A repeated measurement design was employed in the study of acute symptoms of eye and respiratory tract irritation resulting from occupational exposure to sodium borate dusts. The symptom assessment of the 79 exposed and 27 unexposed subjects comprised interviews before the shift began and then at regular hourly intervals for the next six hours of the shift, four days in a row. Exposures were monitored concurrently with a personal real time aerosol monitor. Two different exposure profiles, a daily average and short term (15 minute) average, were used in the analysis. Exposure-response relations were evaluated by linking incidence rates for each symptom with categories of exposure. Acute incidence rates for nasal, eye, and throat irritation, and coughing and breathlessness were found to be associated with increased exposure levels of both exposure indices. Steeper exposure-response slopes were seen when short term exposure concentrations were used. Results from multivariate logistic regression analysis suggest that current smokers tended to be less sensitive to the exposure to airborne sodium borate dust. There was no indication that anhydrous sodium borate was more potent than the other sodium borates in this work environment.

Adult↗

On the relationship between self-injurious behavior and self-restraint.

Many individuals who exhibit self-injurious behavior (SIB) also exhibit self-restraint. Three hypotheses about the determinants of self-restraint have been suggested: (a) Self-restraint is maintained by escape from or avoidance of aversive aspects of SIB, (b) self-restraint and SIB are members of the same functional class, and (c) self-restraint and SIB are functionally independent. This study examined a method by which the relationship between self-restraint and SIB may be investigated using functional analysis. Data were collected on the self-restraint and SIB exhibited by 5 mentally retarded males, while conditions suspected to maintain SIB were manipulated. Results suggested that self-restraint, like SIB, may be maintained by idiosyncratic contingencies. Implications of an understanding of self-restraint for the analysis and treatment of SIB are discussed, as are some general possibilities for future research.

Adolescent↗

A novel N18TG2 x mesencephalon cell hybrid expresses properties that suggest a dopaminergic cell line of substantia nigra origin.

A dopaminergic neuroblastoma was derived using somatic cell fusion of rat embryonic mesencephalon cells and the murine neuroblastoma-glioma cell line N18TG2. The resulting interspecies hybrid, named MES23.5, has retained a stable phenotype and karyotype for a continuous culture period of 1 year. The hybrid exhibits several properties that suggest that the parent primary neurons originated in the substantia nigra. The cell line contains tyrosine hydroxylase, which is identifiable both by biochemical and immunological methods and synthesizes dopamine, but no other catecholamine. Additionally, the cell line expresses apparent voltage-gated CA2+ channels as measured by high-affinity omega-conotoxin binding. The MES23.5 omega-conotoxin receptors are of similar affinity class to those found in adult rat mesencephalon. No dihydropyridine receptors, as measured by PN200-100 ligand binding, are present. None of these properties are found in the N18TG2 parent. At least three neuronal features, namely, tyrosine hydroxylase, dopamine synthesis, and omega-conotoxin receptor expression, are quantitatively elevated after sustained treatment with cAMP analogs. The cell line expresses a complex range of neural properties found in the dopaminergic neurons of the substantia nigra, and may therefore be useful elucidating further details of their cell biology.

Animals↗

[Complications of orbito-frontobasal fractures].

Complications of fronto-basal trauma can, as a function of their severity, be divided into three classes: life-threatening situations, functional complications and cosmetic defects or facial deformities. They find their origin in the type of trauma, the extent of the lesions of bone and soft tissues, as well as in their timely management and quality of treatment. The etiology of the most common complications and their significance are covered with accent on inadequate primary treatment, insufficient repair of dural lesions, inadequate drainage, unstable osteosynthesis, insufficient treatment of scalp- and frontal defects, and finally the lack of antibiotic prophylaxis. The major complications of frontobasal trauma such as chronic cerebral spinal fluid fistulae and pneumocephalus are reviewed. Attention is also given to the importance of adequate drainage in cases of chronic ethmoidofrontal sinusitis, and on the treatment of osteomyelitis and sinus cysts. The therapeutic possibilities in patients with tissue deficits, i.e. reconstruction of frontal skull defects using autologous hip and rib material, as well as split calvarial bone grafts is discussed.

Adult↗

Aesthetic maxillo-facial surgery: face lifting and S.M.A.S.

The article illustrates the importance of face lifting and S.M.A.S. tightening as an adjunct to the aesthetic aspect of maxillo facial surgery, for instance in combination with extreme mandibular set back or advancement in adults. The theory and basic techniques of the face lifting procedure and the S.M.A.S. tightening technique are described. A clinical example is presented. The indications pre- and postoperative management and complications have been mentioned.

Adult↗

Submental liposuction in maxillo-facial surgery.

Liposuction is a relatively recent surgical technique used in body contouring plastic surgery to correct fatty dysharmonies. It is of particular interest to the maxillo-facial surgeon to treat submental fat excess. This relatively easy technique is described, using a few clinical examples. Indications in maxillo-facial surgery are the correction of "double chin" deformity and increased submental fullness after orthognathic surgical procedures as mandibular setback, as well as an adjunct to rhytidectomy.

Adolescent↗

The delivery of interim discharge summaries to general practitioners by the elderly.

Two hundred and four patients discharged from an acute geriatric unit were given an interim discharge summary for delivery to their General Practitioner (GP). All but three summaries were received by the practices. Information regarding mode and timing of receipt was available in 191 patients. The summaries were received in a median of 1.0 day in both those living alone and those living with family; 75% of summaries had been received within two days of discharge and 93% within four days. General practitioners collected the summaries from patients' homes in a high proportion of both groups. Interim discharge summaries should be given to elderly patients for delivery to their GPs: this is both reliable and rapid, and clearly more cost-effective than any other form of delivery.

Aged↗

Long-term bridge to transplantation with the Symbion acute ventricular assist device system.

A 48-year-old man was supported for 164 days with Symbion biventricular assist devices. During that time, his cytotoxic antibody screen fell from 97% positivity to less than 10%, enabling cardiac transplantation. Complications during the implantation included a 3-minute episode of amaurosis fugax, one positive blood culture, and anemia, which responded to decreased frequency of blood drawing. He is now alive 7 months after transplantation.

Coronary Artery Bypass↗

Avian cells expressing the murine Mx1 protein are resistant to influenza virus infection.

The cDNA encoding the murine Mx1 protein, a mediator of resistance to influenza virus, was inserted into a replication-competent avian retroviral vector in either the sense (referred to as Mx+) or the antisense (referred to as Mx-) orientation relative to the viral structural genes. Both vectors produced virus retaining the Mx insert (Mx recombinant viruses referred to as Mx+ and Mx-) following transfection into chicken embryo fibroblasts (CEF). Mx protein of the appropriate size and nuclear localization was expressed only in CEF cells infected with the Mx+ virus. Mx expression was observed in all Mx(+)-infected cells and was stable during long-term culture. Cells infected with the Mx+ virus were resistant to infection by human influenza A/WSN/33 (H1N1) and avian influenza viruses A/Turkey/Wisconsin/68 (H5N9) and A/Turkey/Massachusetts/65 (H6N2), but were susceptible to infection by the enveloped RNA viruses Sindbis and vesicular stomatitis virus (VSV). Normal CEF and cells infected with the Mx virus were susceptible to influenza A, Sindbis, and VSV. The synthesis of influenza proteins, especially the larger polymerase and hemagglutinin proteins, was reduced in Mx+ retrovirus-infected cells superinfected by influenza A.

Animals↗

Evidence for altered receptor-binding activity of serum follicle-stimulating hormone in male infertility.

It is generally assumed that the immunological activity of the follicle-stimulating hormone (FSH) molecule, as reported in the radioimmunoassay (RIA), is identical to the molecule's biological activity. To test the validity of this assumption, the receptor-binding and immunological activities of FSH in the serum of 35 infertile males and 11 fertile males were determined by radioreceptor assay (RRA) and by the standard RIA. The results were analyzed in terms of the ratio of binding (RRA) to immunological (RIA) activity x 100%, referred to as the B/I%, for each patient based on data from the RRA and RIA, respectively. The B/I% for fertile men ranged from 44% to 113% (mean of 80%). In the group of 11 infertile men with normal FSH levels by RIA (50 to 300 ng/mL), there was no significant difference in B/I% (range of 27% to 99%, mean of 59%) from the fertile controls. However, a statistically significant decrease in B/I% (range of 7% to 35%, mean of 18%) was noted in the 24 hypergonadotropic infertile men with RIA levels of serum FSH greater than 300 ng/mL. These significant discrepancies between receptor-binding and immunological activities of serum FSH raise the question of whether RIAs alone are valid parameters for the endocrine evaluation of infertile men with elevated serum FSH levels.

Adult↗

Rearrangements of the tal-1 locus as clonal markers for T cell acute lymphoblastic leukemia.

Normal and aberrant immune receptor gene assembly each produce site-specific DNA rearrangements in leukemic lymphoblasts. In either case, these rearrangements provide useful clonal markers for the leukemias in question. In the t(1;14)(p34;q11) translocation associated with T cell acute lymphoblastic leukemia (T-ALL), the breakpoints on chromosome 1 interrupt the tal-1 gene. A site-specific deletion interrupts the same gene in an additional 26% of T-ALL. Thus, nearly one-third of these leukemias contain clustered rearrangements of the tal-1 locus. To test whether these rearrangements can serve as markers for residual disease, we monitored four patients with T-ALL; three of the leukemias contained a deleted (tald) and one a translocated (talt) tal-1 allele. These alleles were recognized by a sensitive amplification/hybridization assay. tald alleles were found in the blood of one patient during the 4th mo of treatment but not thereafter. Using a quantitative assay to measure the fraction of tald alleles in DNA extracts, we estimated that this month 4 sample contained 150 tald copies per 10(6) genome copies. The patient with t(1;14)(p34;q11) (talt) leukemia developed a positive assay during the 20th mo of treatment. By standard criteria, all four patients remain in complete remission 11-20 mo into treatment. We conclude that tal-1 rearrangements provide useful clonal markers for approximately 30% of T-ALLs.

Alleles↗

Evidence for a role of protein kinase-C in His-D-Trp-Ala-Trp-D-Phe-Lys-NH2-induced growth hormone release from rat primary pituitary cells.

We have recently reported that His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) synergizes with GH-releasing factor (GRF) to increase GH release and cAMP accumulation in rat pituitary cells in vitro. This study was undertaken to further investigate the mechanism of action of GHRP-6 on GH release, particularly the involvement of protein kinase-C. Forskolin (10(-5) M), A23187 (10(-6) M), and phorbol 12-myristate 13-acetate (PMA; 10(-7) M) all stimulated GH release. However, only PMA can mimic the synergistic effects of GHRP-6 on GRF-stimulated GH release and intracellular cAMP accumulation. 4 alpha-Phorbol 12,13-didecanoate, an inactive phorbol ester, was unable to stimulate GH release or potentiate the effect of GRF. Extracellularly added phospholipase-C not only stimulated GH release in a dose-dependent manner, but also potentiated GRF-induced GH release. Phloretin, a protein kinase-C inhibitor, in a concentration range of 10-250 microM had very little or no effect on basal and GRF-stimulated GH release, but markedly inhibited the stimulatory effects induced by either PMA or GHRP-6. Incubation of rat pituitary cells with 10(-6) M PMA for 24 h completely down-regulated protein kinase-C, since such PMA-pretreated cells did not release GH in response to a second dose of PMA. The protein kinase-C-depleted cells had an attenuated GHRP-6 response, but they responded normally to GRF. Moreover, the synergistic effects of GHRP-6 and GRF on GH release and cAMP accumulation were also greatly inhibited by protein kinase-C down-regulation. These data suggest that the effects of GHRP-6 on GH release, either alone or together with GRF, are at least partially mediated via the activation of protein kinase-C.

Amino Acid Sequence↗

Desensitization studies using perifused rat pituitary cells show that growth hormone-releasing hormone and His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 stimulate growth hormone release through distinct receptor sites.

The hexapeptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6) and GH-releasing factor (GHRH) produced a rapid release of GH upon perifusion of dispersed rat pituitary cells. In contrast to the native hormone GHRH, GHRP-6 elicited a response of short duration. When perifusion of each secretagogue was continued until the cells no longer released GH, a challenge by the alternative secretagogue immediately resulted in a secondary release of GH. These results are consistent with each secretagogue causing desensitization of discrete receptor-linked second messenger pathways. Cells which were perifused for 1 min with GHRP-6 required continued perifusion with culture medium alone for 60 min before they completely regained responsiveness to a subsequent challenge with GHRP-6. Somatostatin (SRIF) was able to inhibit the action of either secretagogue completely. However, when both GHRH and GHRP-6 were perifused together, SRIF attenuated but did not block GH secretion. These perifusion data add support to conclusions derived from static cell culture studies, that GHRH and GHRP-6 act through different receptor sites and that through discrete signalling pathways their individual effects on GH release are amplified.

Animals↗

Current perspectives on the use of circulatory assist devices.

An overview of currently available circulatory assist devices (CADs) is presented with discussion of each system's optimal use and limitations. Successful application of CAD technology for bridge to transplant or pending recovery of the natural heart requires understanding issues involving team readiness, patient selection, device limitations, patient management, and complications. Currently, many of these devices are in clinical trials with the Food and Drug Administration (FDA). The FDA and the National Institutes of Health play major roles in the ongoing development of this technology. In the near future the learning curve continues as totally implantable systems are used. The ultimate goal is to maintain patients with heart failure on implantable devices with a good quality of life at a reasonable cost.

Assisted Circulation↗