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Biomedical subjects

J A Bell

Publications and source records attributed to J A Bell.

At least 127 records · Page 7Linked to original sources
PubMed1988

Replacements of Pro86 in phage T4 lysozyme extend an alpha-helix but do not alter protein stability.

To investigate the relation between protein stability and the predicted stabilities of individual secondary structural elements, residue Pro86 in an alpha-helix in phage T4 lysozyme was replaced by ten different amino acids. The x-ray crystal structures of seven of the mutant lysozymes were determined at high resolution. In each case, replacement of the proline resulted in the formation of an extended alpha-helix. This involves a large conformational change in residues 81 to 83 and smaller shifts that extend 20 angstroms across the protein surface. Unexpectedly, all ten amino acid substitutions marginally reduce protein thermostability. This insensitivity of stability to the amino acid at position 86 is not simply explained by statistical and thermodynamic criteria for helical propensity. The observed conformational changes illustrate a general mechanism by which proteins can tolerate mutations.

Enzyme Stability↗
PubMed1988

Partial agonists of the morphine type: facilitative effects on electrophysiologically recorded C-fiber reflexes in the cat.

The purpose of the present study was to examine the effects of the partial agonists of the morphine type, buprenorphine, profadol and propiram on the spinally-mediated C-fiber reflex. Buprenorphine, profadol and propiram facilitated the C-fiber reflex. In the presence of naltrexone, the effects of buprenorphine were changed to depression of the C-fiber reflex. Profadol and propiram continued to facilitate the C-fiber reflex in the presence of naltrexone. The present results suggest that buprenorphine facilitated the C-fiber reflex by blocking endogenous opioid peptide inhibition of the C-fiber reflex whereas profadol and propiram facilitated it by a non-opioid mechanism.

Analgesics↗
PubMed1987

Prenatal cytogenetic diagnosis--a current audit. A review of 2000 cases of prenatal cytogenetic diagnoses after amniocentesis, and comparisons with early experience.

An audit of 2000 cases of prenatal cytogenetic diagnoses is presented. This comprises two consecutive series of 1000 cases (1974-1980 and 1980-1983). Chromosomal studies were performed after mid-trimester amniocentesis. For both series detailed results of the reasons for referral and the outcome of laboratory studies and pregnancy follow-up (in 95% of cases) are presented. In current practice 75% of prenatal cytogenetic diagnoses were for advanced maternal age. Ten per cent of tests were undertaken because of a family history of Down's syndrome. The detection rate of chromosomal abnormality in prenatal cytogenetic diagnoses was 2.06%. Two per cent of amniotic cell cultures failed to grow, necessitating a repeat amniocentesis. The rate of culture failure due to undefinable causes was 0.55%. Fetal loss after amniocentesis for prenatal cytogenetic diagnosis at 16 weeks' gestation has halved since 1980, with a current miscarriage rate of 0.6% within four weeks of the procedure. One maternal death (as a result of amniotic fluid embolism) and one case of amnionitis occurred in the first series of 1000 consecutive cases (up to 1980), but no such complication has occurred since. Secular trends in the indications for referral, laboratory complications, clinical outcome and diagnostic patterns are presented.

Abortion, Induced↗
PubMed1987

Prenatal cytogenetic diagnosis. Amniotic cell culture versus chorionic villus sampling.

Chorionic villus sampling is under evaluation throughout the world. Amniocentesis with amniotic cell culture is reliable for the diagnosis of certain types of genetic disease in the second trimester, and has been the subject of extensive clinical and laboratory audit. Chorionic villus sampling has the advantage of the early diagnosis (for example, at 10 weeks) of chromosomal abnormalities, a shorter delay with results after the diagnostic procedure, and is, for some couples, a more socially and morally acceptable method of antenatal diagnosis. In current experience, the disadvantages of chorionic villus sampling include an increased fetal loss and an increased diagnostic error rate. Another factor is the early diagnosis of fetuses with chromosomal abnormalities--a proportion of whom would have miscarried spontaneously before being detected at an amniocentesis at 16 weeks. This has implications for an increased rate of therapeutic terminations of pregnancy. Chorionic villus sampling and amniotic cell culture are discussed and comparisons are drawn that concern the clinical advantages and diagnostic issues which are inherent in each method of prenatal diagnosis.

Abortion, Induced↗
PubMed1987

Western blot analysis of staphylococcal antibodies present in human sera during health and disease.

IgG antibodies directed against Staphylococcus aureus were examined by Western blotting in sera from 15 healthy individuals isolated for a year in Antarctica. Sera reacted with many staphylococcal antigens in whole-cell extracts and individuals showed unique and unchanging blot profiles. The IgG and IgM profiles of patients with deep-seated staphylococcal infections were also examined by Western blotting. Anti-staphylococcal IgM antibodies that reacted with an antigen of apparent molecular mass 31 X 10(3) were present in all patients with staphylococcal disease, and were absent from, or detected in much smaller amounts in, control sera.

Antibodies, Bacterial↗
PubMed1987

Clinical research in the elderly: ethical and methodological considerations.

Clinically oriented research in the elderly is of growing interest because of increasing numbers of older persons, the relative lack of research data with this population, and recent Food and Drug Administration mandates to study drugs in the elderly. Studies of young, healthy persons cannot necessarily be extrapolated to the elderly due to changes associated with aging and the increased number of concomitant disease states and medications. Subject recruitment may be more time consuming in finding subjects with the appropriate inclusion criteria and lack of exclusion criteria who are willing to participate. Additional concern must be placed on protecting the subject's rights while allowing autonomous decision making. Likewise, protocols may need to be flexible enough to include persons with concomitant disease and medications.

Aged↗
PubMed1987

Diagnostic trends in childhood chromosome abnormalities and their implications--a total population eight-year survey from Queensland, Australia.

The data from an ongoing total population survey of all diagnosed chromosome anomalies in Queensland, Australia have been presented for an 8-year period (1976-83). A total of 760 patients was diagnosed, principally autosomal trisomies (431) and sex chromosome abnormalities (126). Nearly half of total childhood diagnoses (up to 14 years) were made in the first week. Virtually all expected cases of autosomal trisomies were detected in the first month. The largest component of the pool of unrecognized childhood disorders in this study was the sex chromosome group. This failure of detection has implications in terms of potentially beneficial hormone treatment and predisposition to neoplasia.

Adolescent↗
PubMed1987

Faculty input in book selection: a comparison of alternative methods.

In an era of tight funding, academic medical center libraries need to determine their users' needs in order to provide cost-effective resource collections. Although faculty input is valuable, it is impractical to impose such ongoing responsibility on faculty members. This study tested an alternative method by comparing faculty preferences in discipline-specific subjects with faculty choices on corresponding discipline-specific, new-book approval slips from a vendor. Collection development librarian selections, based on formal selection criteria, were evaluated against both measures of faculty preferences. It was found that faculty members' subject ratings did not accurately predict their book choices. Implications of this and the other findings are discussed.

Book Selection↗
PubMed1986

Fat and cancer.

Experimental studies and epidemiologic data both indicate that high-fat diets increase the risk of cancer at sites such as breast, colon, and pancreas. Dietary polyunsaturated vegetable oils promote tumorigenesis in animals whereas saturated fats and polyunsaturated fish oils either have little effect or are inhibitory. A blend of fats typical of the American diet enhanced mammary tumorigenesis effectively when fed as 40% of calories. After 9 to 10 weeks on this diet, reducing the fat to 10% of calories inhibited subsequent tumor development. Although dietary fat appears to act as a promoter, the exact mechanisms are still unknown. Cancer mortality in humans correlates better with total dietary fat than with degree of unsaturation, perhaps because most diets contain more than the amount of polyunsaturated fatty acids required for maximum effect on tumorigenesis in animals. A reduction in total dietary fat is recommended to reduce the current high cancer mortality.

Animals↗
PubMed1986

Electrophysiological evidence for a presynaptic mechanism of morphine withdrawal in the neonatal rat spinal cord.

Dorsal and ventral root depolarizing responses to capsaicin (1 microM) and substance P (SP; 1 microM) were measured from the isolated, hemisected spinal cord of the neonatal rat. Capsaicin depolarized the dorsal and ventral roots. The mechanism of ventral root depolarization was presynaptic; since dorsal root depolarization preceded the ventral, and the ventral depolarization was eliminated when synaptic transmission was blocked in the absence of calcium. SP depolarized the ventral root without affecting the dorsal root. The SP-induced depolarization of the ventral root was reduced but not abolished by blocking synaptic transmission with low calcium, suggesting that SP acted postsynaptically on motoneurons and excitatory interneurons to depolarize the ventral root. Morphine (10 microM) abolished the capsaicin-induced ventral root depolarization, but only slightly suppressed the SP response (30%). The capsaicin-induced depolarization of the ventral root was enhanced greatly (238%) when morphine, which had been in the superfusion for 1 h, was removed and naloxone (1 microM) was added to the superfusion solution, whereas the SP response was not augmented during withdrawal from acute morphine. Furthermore, a putative SP antagonist ([D-Arg1, D-Pro2, D-Tryp7,9, Leu11]-SP) prevented the augmented capsaicin ventral root response during precipitated withdrawal. These data provide electrophysiological evidence for a presynaptic mechanism of acute morphine withdrawal in the neonatal rat spinal cord.

Animals↗
PubMed1985

Prenatal cytogenetic diagnosis: medical and social implications. Indications, acceptance by doctors and patients, impact and cost: a 10-year review.

Prenatal cytogenetic diagnosis has been in widespread use for a decade, and access to it has been determined by medical attitudes towards what constitutes "high risk", and by pragmatic questions about the logistics of delivering a new diagnostic test to as many couples as costs will allow. The most common indication - advanced maternal age - has led to different access criteria in various parts of Australia. Factors such as socioeconomic status, education, and religion affect the acceptance of prenatal cytogenetic diagnosis from the point of view both of patients and of the doctors who care for them. Cost-benefit analyses conducted elsewhere indicate that, in purely monetary terms, it is probable that prenatal cytogenetic diagnosis is cost-effective if offered to all couples in which the woman is over the age of 32 years. An assessment of the impact of prenatal cytogenetic diagnosis on the birth incidence of major chromosomal abnormalities, particularly Down's syndrome, indicates that the maximum reduction which might be achieved in current practice is 30%.

Abortion, Induced↗
PubMed1985

Crystallization and preliminary x-ray characterization of bovine growth hormone. Purification of bovine prolactin and growth hormone.

A new purification scheme for both prolactin and growth hormone from bovine pituitaries has been developed which avoids the use of potentially damaging solution conditions. Both hormones were greater than 95% pure as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and had specific activities similar to or greater than standard samples of the same hormone as judged by several bioassays. Small single crystals of bovine growth hormone were obtained by vapor diffusion techniques. Examination of these crystals by x-ray diffraction, using the Cornell High Energy Synchrotron Source, showed that they were well ordered, and exhibited diffraction to 2.8-A resolution on still photographs. Precession and oscillation photographs showed that they belonged to the orthorhombic space group P2(1)2(1)2(1) (or P2(1)2(1)2) with unit cell dimensions a = 219 A, b = 51.9 A, c = 68.9 A. The density of the crystals was 1.19 +/- 0.02 g/ml from which the presence of eight 45,000-dalton dimers/unit cell was deduced. The protein content of the crystals was shown by isoelectric focusing to be identical to that of purified growth hormone in solution. These crystals appear suitable for use in the x-ray structure determination of bovine growth hormone to at least 3.2-A resolution.

Animals↗
PubMed1985

Cue significance and response regulation in 3- to 6-year-old children's learning of multiple choice discrimination tasks.

The learning of multiple choice discrimination tasks of 3-, 4-, 5-, and 6-year-old children was compared using the components of learning of cue significance and response regulation. No significant differences between age groups were found in the occurrence of cue significance learning, although the younger children's cue significance responses were less accurately related to task solution. On the two easier tasks, the component of response regulation improved significantly over the age range of 3-5 years. On the two more difficult tasks 6-year-olds' response regulation was significantly better than that of 4- and 5-year-olds. In a second experiment involving two different training procedures, 5-year-olds performed better than 4-year-olds. Only for 5-year-olds was performance with the procedure emphasizing response regulation superior to performance with the procedure emphasizing cue significance. These results are discussed in terms of an association between development of response regulation and maturation of hippocampal-prefrontal cortex systems.

Child↗
PubMed1985

Electrophysiologically recorded C-fiber reflexes in intact and acute decerebrate-spinal cats: absence of naloxone facilitation in intact cats.

A C-fiber reflex was obtained from stimulating and recording electrodes attached respectively to the superficial peroneal and posterior biceps semitendinosus nerves in intact cats. Naloxone in a dose dependent manner increased vocalizations produced by nerve stimulation, but it did not facilitate the C-fiber reflex in the intact cat. However, naloxone facilitated C-fiber reflexes in decerebrate-spinal cats under identical stimulating and recording conditions as used in the intact cat. It was concluded that naloxone causes increased nociception to cutaneous nerve stimulation in intact cats but for naloxone to facilitate the C-fiber reflex, removal of supraspinal control is necessary. Many C-fiber afferents transmit nociception to the CNS (Bessou and Perl, 1969). Electrical stimulation of the superficial peroneal nerve that activates C fibers produces a segmental reflex in the unanesthetized decerebrate-spinal cat (Koll, Hasse, Schutz and Muhlberg, 1963). This C-fiber reflex is manifested by a long latency discharge recorded from an ipsilateral L7 or S1 ventral root. The C-fiber reflex is considered nociceptive because only intense stimulation evokes it and morphine depresses it in doses lower than those that depress other spinal reflexes (Koll et al., 1963). Low doses of the opiate antagonists naloxone and naltrexone consistently facilitate the C-fiber reflex (Bell and Martin, 1977). These results support the hypothesis that released endogenous opioids inhibit the C-fiber reflex. However, the facilitative effects of the opiate antagonists could be confined to the decerebrate-spinal preparation where invasive experimental procedures (decerebration, dissection, etc.) may release endogenous opioids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Immunoelectron microscopic localization of glomerular IgA deposits using a protein A-colloidal gold probe.

Currently there is increasing interest in the localization and accurate determination of the composition of protein deposits involved in the pathogenesis of human glomerulonephritis using immunoelectron microscopy. Previous studies have largely relied on capricious immunoperoxidase techniques applying both the preembedding and postembedding methods to renal tissue. Both methods identify a single antigen, but preservation of ultrastructure is suboptimal, and there is the potential problem of imprecise localization of antigen due to diffusion of the peroxidase reaction product. A less demanding method of ultrastructural antigen identification for renal tissue has been employed with success in clearly localizing glomerular deposits of IgA. The technique involves fixation of tissue in periodate-lysine-paraformaldehyde, embedding in L. R. White resin, and labeling by an indirect immunologic reaction using protein A-gold as an electron-dense marker. This technique provides an accurate marker for the localization of glomerular antigen while retaining optimal tissue morphology, and we predict that this method will have wide application in human and experimental renal disease.

Glomerulonephritis↗
PubMed1984

Retinal microangiopathy. Correlation of OCTOPUS perimetry with fluorescein angiography.

The capillary perfusion of 14 eyes with nonproliferative diabetic retinopathy and 14 eyes with retinal branch vein occlusion was assessed by wide-angle fluorescein angiography. Regional perfusion was directly correlated with visual sensitivity determined by OCTOPUS-automated static perimetry. Visual function was found to correlate linearly with capillary perfusion in both diseases. Occasional foci of decreased visual sensitivity that corresponded to a region of good capillary perfusion were found in the central fields of diabetics. Although capillary dropout appears to be the major cause of decreased visual sensitivity in microangiopathy, local metabolic factors may also play a role. Further studies are required to determine whether foci of decreased function are predictive of future capillary dropout or neovascularization.

Adult↗