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Biomedical subjects

J Nelson

Publications and source records attributed to J Nelson.

At least 145 records · Page 8Linked to original sources

Investigations using a novel monoclonal antibody to the glycosylphosphatidylinositol-anchored protein that carries Gregory, Holley, and Dombrock blood group antigens.

BACKGROUND: The high-frequency Hy and Gya antigens have been shown to reside on the same protein. Gy(a-) Hy-negative red cells are also Do(a-b-). A mouse monoclonal antibody, 5B10, was produced with specificity related to the human Gregory, Holley, and Dombrock blood group antigens. STUDY DESIGN AND METHODS: The antibody reacted in direct hemagglutination assays, and its specificity was investigated by radioimmunoassay, inhibition assay, and Western blotting. RESULTS: The 5B10 antibody failed to bind to abnormal paroxysmal nocturnal hemoglobinuria red cells and human erythroleukemia cell line K562, but it was weakly reactive with HEL cells. Red cells, but not other circulating hematopoietic cells, express the 5B10 antigen. The 5B10 antibody had a specificity similar but not identical to that of Gya. Gy(a-) Hy-negative red cells reacted extremely weakly with 5B10 antibody, but Gy(a-) Hy-negative red cells treated with a variety of proteases bound 5B10 antibody strongly. This suggests that these cells express a variant form of the protein recognized by 5B10. CONCLUSION: Identification of a monoclonal antibody to this glycosylphosphatidylinositol-linked protein opens a new avenue for investigation of the biochemistry, genetics, and function of the glycosylphosphatidylinositol-linked protein that bears the Gya, Hy, and Do antigens.

Alleles↗

Factor VIII gene inversions in severe hemophilia A patients.

The mutations causing hemophilia A are very heterogeneous with the exception of a large inversion involving intron 22 in the factor VIII (FVIII) gene which appears to be the underlying defect in approximately 45% of all severely affected patients (FVIII < or = 1%). In these patients it is thought that the factor VIII gene is disrupted within intron 22 due to inappropriate recombination of FVIIIA with one of 2 homologous regions upstream of the factor VIII gene resulting in a large (approximately 500 kb) inversion. The inversion can be detected by Southern blot analysis and greatly enhances the accuracy of genetic counselling services available to families with severe hemophilia A. We report here the presence of this mutation in a study of 27 unrelated families with severe hemophilia. The factor VIII inversion was identified in 12 of 27 (44%) severe hemophilia A patients and has been successfully used for direct carrier analysis and prenatal diagnosis.

Blotting, Southern↗

Selective salpingography with an insemination catheter in the treatment of women with cornual fallopian tube obstruction.

The effectiveness of selective tubal cannulation using a simple and inexpensive tubal insemination catheter was evaluated in 23 infertile patients with cornual obstruction demonstrated by hysterosalpingography. Selective fluoroscopic tubal catheterization was accomplished in 95% of the patients with resulting tubal patency in 70% of the procedures (28 recanalizations out of 40 Fallopian tubes). Eight patients (34.8%, eight out of 23) became pregnant, six went on to full-term deliveries and two experienced spontaneous first-trimester abortions. One women conceived twice, and delivered a singleton pregnancy after the first recanalization and a twin gestation after the second salpingography. No complications were reported. The results of this study emphasize the ease, cost effectiveness and safety of this method, encouraging its use in patients with cornual Fallopian tube obstruction either as the sole therapeutic approach or in association with other assisted conception treatment alternatives.

Adult↗

Engineered serine protease inhibitor prevents furin-catalyzed activation of the fusion glycoprotein and production of infectious measles virus.

We have identified the major cellular endoprotease that activates the fusion (F) glycoprotein of measles virus (MV) and have engineered a serine protease inhibitor (serpin) to target the endoprotease and inhibit the production of infectious MV. The F-protein precursor of MV was not cleaved efficiently into the mature F protein in human colon carcinoma cells lacking functional furin, indicating that furin is the major enzyme responsible for activation of the MV F protein. A human serpin alpha 1-antitrypsin variant was engineered to specifically inhibit furin. When expressed from a recombinant vaccinia virus in primate cells infected by MV, the engineered serpin (alpha 1-PDX) specifically inhibited furin-catalyzed cleavage of the F-protein precursor without affecting synthesis of other MV proteins. We generated human glioma cells stably expressing alpha 1-PDX. MV infection in these cells did not result in syncytia. The infected cells produced all the MV proteins, but the F-protein precursor remained largely uncleaved. This did not prevent virus assembly. However, the released virions contained inactive F-protein precursor rather than mature F protein, and infectious-virus titers were reduced by 3 to 4 orders of magnitude. These results show that a mature F protein is not required for the assembly of MV but is crucial for virus infectivity. The engineered serpin may offer a novel molecular antiviral approach against MV.

Animals↗

Value of screening for oro-pharyngeal Chlamydia trachomatis infection.

AIMS: To determine whether oro-pharyngeal colonisation by Chlamydia trachomatis occurs in patients at risk of genital chlamydia infection; to determine whether screening pharyngeal specimens by polymerase chain reaction (PCR) increases detection of C trachomatis compared with isolation and the immune dot blot test; and to correlate the detection of C trachomatis and Neisseria gonorrhoeae in the pharynx with a history of oro-genital contact. METHODS: Thirteen homosexuals and 11 heterosexuals were included in the study. Urogenital and pharyngeal specimens were tested for C trachomatis and N gonorrhoeae using standard clinical diagnostic procedures. Two different PCR methodologies were also used to detect C trachomatis in the pharyngeal specimens. Results were correlated with the mode of sexual practice. RESULTS: Oro-genital sexual contact was practised by 64.9% (72/111) of heterosexuals in addition to penetrative penovaginal intercourse. Additionally, 62.1% (77/124) of all patients did not use any form of barrier protection. Of those who admitted to oro-genital sexual contact, 17.6% of patients with a genital chlamydial infection and 36.4% of those with genital gonorrhoea also had asymptomatic pharyngeal colonisation. C trachomatis was detected in three of 124 (2.4%) pharyngeal specimens by PCR which were reported as negative by chlamydial culture; one was positive by the immune dot blot test. CONCLUSION: The majority of patients practised unprotected oro-genital contact and significant pharyngeal colonisation by C trachomatis and N gonorrhoeae occurred if genital infection was present. Despite the use of PCR in a population at high risk of sexually transmitted disease, the prevalence of chlamydia in the pharynx was very low. This indicates that transmission of C trachomatis to the oro-pharynx does not pose a serious health risk and that screening of patients for oro-pharyngeal C trachomatis is not worthwhile.

Adolescent↗

Epidural administration of methylprednisolone and morphine for pain after a spinal operation. A randomized, prospective, comparative study.

The results of postoperative epidural administration of saline solution (a placebo), morphine, methylprednisolone, and a combination of morphine and methylprednisolone for the reduction of pain after an operation for spinal stenosis or a herniated intervertebral disc were compared in a prospective, randomized blinded study. Epidural administration of morphine and methylprednisolone--either alone or in combination--significantly reduced the need for analgesia after an operation for spinal stenosis (p < 0.05) but not after an operation for a herniated intervertebral disc. Morphine and methylprednisolone did not have an addictive effect on the reduction of pain. Itching was significantly more common in the patients who had received morphine than in those who had received the placebo (p = 0.04). Although urinary retention was more frequent after the use of morphine than after the use of the placebo, the difference was not significant with the size of the sample that was analyzed (p = 0.25).

Adult↗

The influence of environmental factors in incidents of disruptive behavior.

1. Disruptive behavior is an annoying and potentially dangerous problem in most nursing homes. Disruptive behaviors can be both physical and verbal. 2. Changes associated with termination of disruptive behaviors included the reduction of external environmental stimuli, reduction of perceived threats to the patient's personal freedom and fulfillment of basic physical needs, fulfillment of needs for interpersonal support, a simple request to the disruptive person that the behavior be discontinued, provision for increased freedom by releasing the person from a gerichair or wheelchair with rollbar, separation of residents involved in disputes, and resolution of disputes over belongings. 3. In order to initiate changes that will reduce the frequency of such behavior or mitigate its harmful effects, nurses must have a better understanding of how environmental factors influence the evolution of disruptive episodes and plan appropriate and specific nursing interventions.

Aged↗

Preovulatory sonographic uterine receptivity index (SURI): usefulness as an indicator of pregnancy in women undergoing assisted reproductive treatments.

To evaluate the uterine component as a determinant variable in the probability of establishing a pregnancy after assisted reproductive treatments, we introduced a mathematical formula derived from standard endovaginal uterine monitored color Doppler imaging parameters. We analyzed 102 cycles of ovarian stimulation with leuprolide acetate and exogenous gonadotropins resulting in 52 clinical pregnancies by stepwise logistic regression analysis. Sonographic endometrial pattern, thickness, diastolic blood flow, and resistive index variables were transformed into categorical variables and forced to yield a regression equation. Sonographic uterine receptivity index was calculated as a summation of four times endometrial pattern, five times resistive index, and two times diastolic blood flow. This index yielded values for each patient in a range of 0 to 15. Scores > or = 13 were associated with a successful outcome in 79.4% of the patients, whereas scores between 8 and 12 were accompanied by 45.8% pregnancy rates (P = 0.01), and scores < or = 7 had successful treatment outcome in only 7.7% (P = 0.0001). The scores obtained by this mathematical equation provide the ability to make reliable predictions about the outcome of assisted reproductive treatments in women undergoing ovulation induction with leuprolide acetate and human menopausal gonadotropins.

Adult↗

Massive overdose of sustained-release verapamil: a case report and review of literature.

Verapamil 99 is a commonly prescribed medicine for treatment of hypertension, angina, and migraine headache. Toxicity with sustained-release verapamil may be prolonged, and manifest with hypotension, bradycardia, metabolic acidosis, and hyperglycemia. Currently, because of the lack of a specific antidote management of verapamil, toxicity is mainly supportive. Treatment with inotropic support, glucagon, calcium, and cardiac pacing may be effective in some cases. A review of 20 cases and a case report of sustained-release verapamil overdose are described. The authors describe a patient who ingested 24 g of slow-release verapamil. This is the largest overdose of sustained-release verapamil reported in English literature. The patient was managed aggressively with gastric lavage, inotropic support, and continuous infusion of calcium and glucagon. The patient's survival may have been due to the continuous intravenous calcium gluconate and glucagon infusion. Both of these treatment modalities should be considered in patients with moderate to severe calcium channel blocker overdose.

Calcium Gluconate↗

Secondary structure of the 33 kDa, extrinsic protein of Photosystem II: a far-UV circular dichroism study.

The 33 kDa extrinsic protein of Photosystem II is an important component of the oxygen-evolving apparatus which functions to stabilize the manganese cluster at physiological chloride concentrations and to lower the calcium requirement for oxygen evolution. Chou-Fasman analysis of the amino-acid sequence of this protein suggests that this component contains a high proportion of alpha-helical structure and only relatively small amounts of beta-sheet structure. A computational study using more sophisticated techniques (Beauregard, M. (1992) Environ. Exp. Bot. 32, 411-429) concluded that the protein contained little periodically ordered secondary structure. In this study, we have directly measured the relative proportions of secondary structure present in the 33 kDa protein using far-ultraviolet circular dichroism spectroscopy. Our results indicate that, in solution, this protein contains a large proportion of beta-sheet structure (38%) and relatively small amounts of alpha-helical structure (9%). A structural model of the 33 kDa protein based on a constrained Chou-Fasman analysis (Teeter, M.M. and Whitlow, M (1988) Proteins 4, 262-273) is presented.

Amino Acid Sequence↗

Polydactyly in a carrier of the gene for the Meckel syndrome.

Much of the Meckel syndrome literature has been concerned with the criteria for diagnosis but little has been said concerning heterozygote expression. We describe 3 affected brothers whose father and his paternal first cousin had postaxial polydactyly of both feet. A review of the literature was undertaken with regard to possible manifesting heterozygotes. We conclude that it is important to examine the relatives of patients with the Meckel syndrome for mild abnormalities, as these may be evidence of a manifesting heterozygote. Such information may be useful for genetic counselling.

Abnormalities, Multiple↗

Identification of marker chromosomes in thirteen patients using FISH probing.

Fourteen marker chromosomes were studied by FISH (fluorescence in-situ hybridization) in cytogenetic preparations from 13 patients. The derived markers were identified as one isodicentric bisatellited mar(22), one fragment sized r(X), one fragment sized r(Y), one i(18p), small autosomal ring markers in three different patients derived from chromosomes 2, 8, and 8, a marker comprised of 9p and part of 9qh, and 3 bisatellited apparently monocentric markers; one of each from chromosomes 13 or 21, 14 or 22, and 15. Two fragment sized small ring markers in one patient and a small ring marker in another were negative with all twenty-two different probes used. In addition, the small ring marker Y chromosome that was found in a boy with karyotype 46,X,-Y,+mar was negative with both pDXZ1 and pDYZ3. This anomaly of negative results with the battery of centromeric alphoid probes can be explained if one breakpoint for some small ring markers is very near to or within the centromere. Only some of the pericentromeric repetitive sequences in the normal chromosome would be represented in the chromosome specific alphoid probes, and presumably those corresponding to the currently available probes are truncated during the formation of the unidentified markers. In three of the small ring markers the FISH signal on the marker was much stronger than on the normal homologues in various proportions of cells, and this may indicate that some of the fragment sized small rings were multicentric. The literature was reviewed for Distamycin A/DAPI negative small ring markers that were present as extra chromosomes. There were only single published cases of most small rings but there were three r(8) cases, two r(1) cases, two r(12) cases, and two r(20) cases, uncomplicated by the presence of other chromosome abnormalities. Most cases with similar small rings were quite dissimilar phenotypically and syndrome identification was not possible, but in pooled data, 18/23 (about 80%) were developmentally and/or phenotypically abnormal. Some patients (5/23, about 20%) with small rings were dysmorphic without intellectual handicap. Of 28 such patients with small ring markers (Distamycin/Dapi negative) in pooled data there are 6 (about 20%) with multiple markers mostly derived from different chromosomes. This is a very high figure and would suggest that the ring formation events, although involving different chromosomes, must be related and must be an indicator of the mechanism of origin of this group of markers.

Adolescent↗

The morphological development of the inferior colliculus in a marsupial, the Northern quoll (Dasyurus hallucatus).

As a part of a project concerning the development of hearing, some features of the morphological development of the inferior colliculus were studied in a marsupial, the Northern quoll or native cat (Dasyurus hallucatus). Marsupials are of particular interest in developmental studies because much embryonic development occurs outside the uterus, in the pouch. Nissl-stained material was prepared from pouch-young at various ages between 11 and 81 days, and for a number of adults. Four pouch-young were injected with tritiated thymidine and killed later during pouch life. The inferior colliculus is first recognizable in pouch-young aged 23 days, when it is bordered by a cell-sparse ring of tissue. By this time, the labelling patterns following injections of tritiated thymidine made on days 7-9 suggest that migration of cells to the inferior colliculus from the ventricular germinal zone has been largely completed. At 81 days, close to the time when the young move out of the pouch, the adult cytoarchitecture--a central nucleus flanked by dorsal and lateral cortical regions--is clear. Cell areas expand monotonically as a function of age. The period of days 45-50 is associated with a large expansion of cell volume and a concomitant decrease in packing density. It is likely that functional connections are forming during this period, which may herald the onset of hearing in the quoll. Total cell numbers increase to a peak at day 36, fall to a minimum at day 50, and rise again to the adult value. The second increase is likely to be a phase of glial proliferation, in part associated with the onset of myelination. This increase correlates with departure of the young from the pouch.

Aging↗

Cloning and sequence of REV7, a gene whose function is required for DNA damage-induced mutagenesis in Saccharomyces cerevisiae.

The function of the REV7 gene is required for DNA damage-induced mutagenesis in budding yeast, Saccharomyces cerevisiae, and is therefore thought to promote replication past sites of mutagen damage in the DNA template. We have cloned this gene by complementation of the rev7-2 mutant defect, and determined its sequence. REV7 encodes a predicted protein of M(r) 28,759 which is unlikely any other protein in the NCBI non-redundant protein sequence data base, and which is inessential for viability.

Amino Acid Sequence↗

Regulation of the glutamate dehydrogenase activity in rat islets of Langerhans and its consequence on insulin release.

Kinetic properties of glutamate dehydrogenase (GDH) and the effects on its activity of several putative modulators were examined in mitochondrial extracts of rat pancreatic islets. In the presence of 40 mmol/L NH4Cl and 0.1 mmol/L NADH, stepwise elevation of the 2-oxoglutarate concentration from 0.005 to 0.05 mmol/L increased glutamate formation, whereas further increases led to a progressive decrease of the reaction velocity. Adenosine diphosphate (ADP) at 0.1 mmol/L partially and at 1 mmol/L completely reversed the inhibitory effect of 2-oxoglutarate. The sensitivity to activation by either ADP or leucine was dependent on 2-oxoglutarate concentrations. At higher concentrations of the latter, greater amounts of the activators were needed to attain maximal effect. In the absence of allosteric activators, sulfate or phosphate at 20 mmol/L partially released the inhibitory effect of 2-oxoglutarate levels and increased the maximal velocity (Vmax) for the reaction. In the presence of 0.1 mmol/L ADP, both anions prevented the inhibition by higher concentrations of 2-oxoglutarate, whereas with 1 mmol/L ADP their only effect was a slight increase in the Vmax. Mg2+ and naturally occurring polyamines decreased glutamate formation in a dose-dependent manner; with 0.1 mmol/L ADP, inhibition was seen at all 2-oxoglutarate concentrations studied, whereas with 1 mmol/L ADP, it was noticeable at substrate concentrations higher than 0.5 mmol/L. This inhibitory effect on GDH activity was partially attenuated by sulfate. Addition of either 2 mmol/L spermidine or extra magnesium (final 2.5 or 5 mmol/L) to the perifusion buffer markedly attenuated the insulin release elicited by alpha-ketoisocaproate. It is suggested that naturally occurring polyamines, magnesium, and phosphate act as physiological modulators of GDH activity in pancreatic beta cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗

Sonographic uterine predictors of pregnancy in women undergoing ovulation induction for assisted reproductive treatments.

OBJECTIVE: To determine preovulatory uterine sonographic predictors of pregnancy in women undergoing ovulation induction for assisted reproductive treatments. DESIGN: Prospective evaluation of uterine sonographic and vascular flow profiles in women stimulated with leuprolide acetate and hMG. SETTING: Private fertility center and tertiary-care academic center. PATIENTS: Ninety-six women underwent 102 cycles of ovulation induction for IVF (46), GIFT (20), and zygote intrafallopian transfer (36). MAIN OUTCOME MEASURES: Endometrial texture, thickness, resistance index at the first branch of uterine artery, diastolic blood flow, and pregnancy outcome (no conception, spontaneous abortion, and delivery). RESULTS: Triple-lined pattern was predominant in women who delivered liveborn infants (P < 0.005). Endometrial pattern and diastolic blood flow were the only predictive markers of term pregnancy (P < 0.001 and P < 0.05, respectively). CONCLUSION: Preovulatory triple-lined sonographic endometrial texture and the presence of end diastole blood velocities at the first branch of uterine artery are the most important uterine predictors of conception.

Adult↗