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Biomedical subjects

L Nelson

Publications and source records attributed to L Nelson.

At least 55 records · Page 3Linked to original sources

Angiotensinogen T235 expression is elevated in decidual spiral arteries.

Preeclampsia is associated with a common molecular variant of angiotensinogen (Met235Thr). This variant is in tight linkage disequilibrium with a mutation in the angiotensinogen promoter, G(-6)A, which leads to elevated expression in vitro. Since angiotensin II levels could play a role in atherotic changes of the uterine spiral arteries associated with preeclampsia, we investigated angiotensinogen expression in the first trimester uterus. We localized angiotensinogen transcription in uterine decidua using in situ reverse transcription PCR. We then compared decidual T235 expression levels to M235 levels in heterozygous women using an allele-specific ligation assay and a single nucleotide primer extension assay. In human decidua, angiotensinogen is expressed only in spiral artery smooth muscle cells. Heterozygous women have significantly elevated expression of the T235 allele compared to the M235 allele (P < 0.0001). These observations suggest that elevated expression of the T235 allele in decidual spiral arteries may cause first trimester atherotic changes leading to preeclampsia.

Alleles↗

Leukodystrophy in patients with ovarian dysgenesis.

We describe clinical, biochemical, pathological, and spectroscopic findings in 4 women, aged 15 to 29 years, from three unrelated families who had a unique combination of a central nervous system white matter disease and primary ovarian failure. All had normal initial development but 3 had borderline low IQ and academic difficulties in primary school. Puberty did not develop in 2 patients and was arrested in a third patient. The fourth patient had premature ovarian failure at the age of 13 years. Head magnetic resonance imaging showed diffuse white matter disease, with frontal cortical atrophy in the most clinically advanced patient. All patients had normal karyotype and normal findings on extensive evaluations for known leukodystrophies, for other metabolic diseases, and for causes of ovarian failure. Proton magnetic resonance spectroscopic imaging showed reduction of choline-containing compounds in the affected white matter in all patients and reduction of N-acetylaspartate in the unaffected frontal white matter of 2 patients. All patients had evidence of primary gonadal insufficiency with a normal hypothalamic-hypophyseal axis. Pathological analysis showed streak ovaries in 1 patient and signs of hypomyelination, and gliosis on brain biopsy in another patient. In conclusion, we present a novel group of patients who have in common leukodystrophy, primary ovarian dysfunction, and magnetic resonance spectroscopic abnormalities.

Adolescent↗

Hypothalamic-pituitary-adrenal activation by the bacterial superantigen staphylococcal enterotoxin B: role of macrophages and T cells.

Staphylococcal enterotoxin B (SEB) is a bacterial superantigen which stimulates T cells bearing the V beta 8 motif on the T-cell receptor. This stimulation is MHC class II dependent, and in vivo results in a rapid and pronounced T-cell cytokine response. Based on previous evidence that SEB stimulates corticosterone production in BALB/c mice, which possess a high percentage of V beta 8+ T cells, we explored the effects of SEB on the hypothalamic-pituitary-adrenal (HPA) axis and identified the peripheral immunologic cellular requirements for these effects. Administration of SEB stimulates corticosterone in a dose-dependent manner, with peak production of corticosterone occurring by 2 h after intraperitoneal challenge with 50 micrograms SEB. Challenge with staphylococcal enterotoxin A, which activates V beta 3+ and V beta 11+ T cells (deleted during ontogenesis in BALB/c mice), did not increase ACTH or corticosterone production. Furthermore, SEB challenge increased plasma ACTH, which accounted for the increased plasma corticosterone, and increased the expression of c-fos in the PVN region of the hypothalamus. In vivo elimination of macrophages did not prevent the corticosterone response to SEB, suggesting that pituitary-adrenal activation does not require macrophages. However, when mice were pretreated with the T-cell immunosuppressant cyclosporin A, the significantly increased ACTH and corticosterone production in response to SEB was dramatically attenuated. These results demonstrate that bacterial superantigens can stimulate the HPA axis, and that functional T cells may play an obligatory role in this effect.

Adrenal Glands↗

Different excitation-contraction coupling mechanisms exist in squid, cuttlefish and octopod mantle muscle

Excitation-contraction (EC) coupling was studied in central zone mantle muscle fibres of a squid (Alloteuthis subulata), a cuttlefish (Sepia officinalis) and an octopod (Eledone cirrhosa). Thin slices of muscle were used for twitch experiments and enzymatic isolation of single fibres for whole-cell patch-clamp studies. The current required for a supramaximal twitch response during direct stimulation of muscle slices was lower for squid than for cuttlefish. In squid, but not in cuttlefish, the current-response relationship was independent of slice thickness (range 0.1-0.5 mm). Twitches of squid and cuttlefish slices were reversibly abolished by removal of extracellular Ca2+. In squid, but not in cuttlefish, the current-response relationship was Na+-dependent, and in the absence of Na+ higher current strengths were required to generate a supramaximal response. In whole-cell voltage-clamp experiments on isolated muscle fibres from squid, cuttlefish and Eledone cirrhosa, a sustained inward current was recorded upon depolarisation. This current was blocked by 5 mmol l-1 Co2+ and suppressed by 10 micromol l-1 nifedipine. In squid, an additional inward fast-activating transient current was seen which was blocked by 2 micromol l-1 tetrodotoxin and depolarised holding potentials. The fast current represents a voltage-activated Na+ channel, and the slow currents represent L-type Ca2+ channels. We conclude that squid possess a specialised rapid EC coupling mechanism in central zone fibres that is absent in cuttlefish and Eledone cirrhosa.

Journal Article↗

The use of epidural steroid injection and manipulation on patients with chronic low back pain.

OBJECTIVES: To document the efficacy of combined epidural steroid injection (ESI) and manipulation to the lumbar spine in patients suffering from chronic low back pain (LBP). SUMMARY OF BACKGROUND DATA: The use of ESI in conjunction with lumbar manipulation has seldom been reported in the literature but has offered promising results when studied. STUDY DESIGN: Retrospective repeated-measures analysis of patients with chronic LBP who received ESIs combined with spinal manipulation. METHODS: A retrospective analysis using a repeated-measures format was performed on 17 cases of patients who had received ESI and manipulation to the lumbar spine. All patients were medically stable for chronic mechanical LBP and had experienced a suboptimal response to conventional care. The principle investigator was blinded from data outcomes when determining patient eligibility for the study. A subjective patient improvement scale was used to monitor degree of success. RESULTS: Ten of the 17 patients were eligible for the study. Patients were eliminated for lack of consistency of data collection, having received an additional procedure after conventional care, involvement of the cervical spine; one patient experienced an unrelated medical problem. After 1 yr of conventional care, the patients reported a 25.5% improvement. (Conventional care included ESI and manipulation done at separate times.) After on ESI with subsequent manipulation, these same patients reported a 50.5% improvement. Mean improvement was 25.00% (SD = 19.51, SEM 6.19, t = 4.04 and p = .0015). CONCLUSION: The use of ESI performed with manipulation seems to offer promise for a carefully selected group of patients. ESI combined with manipulation should be considered in patients who do not respond to conventional forms of care.

Adult↗

Isolation and characterization of an avian slow myosin heavy chain gene expressed during embryonic skeletal muscle fiber formation.

We have isolated and begun characterization of the quail slow myosin heavy chain (MyHC) 3 gene, the first reported avian slow MyHC gene. Expression of slow MyHC 3 in skeletal muscle is restricted to the embryonic period of development, when the fiber pattern of future fast and slow muscle is established. In embryonic hindlimb development, slow MyHC 3 gene expression coincides with slow muscle fiber formation as distinguished by slow MyHC-specific antibody staining. In addition to expression in embryonic appendicular muscle, slow MyHC 3 is expressed continuously in the atria. Transfection of slow MyHC 3 promoter-reporter constructs into embryonic myoblasts that form slow MyHC-expressing fibers identified two regions regulating expression of this gene in skeletal muscle. The proximal promoter, containing potential muscle-specific regulatory motifs, permits expression of a reporter gene in embryonic slow muscle fibers, while a distal element, located greater than 2600 base pairs upstream, further enhances expression 3-fold. The slow muscle fiber-restricted expression of slow MyHC 3 during embryonic development, and expression of slow MyHC 3 promoter-reporter constructs in embryonic muscle fibers in vitro, makes this gene a useful marker to study the mechanism establishing the slow fiber lineage in the embryo.

Amino Acid Sequence↗

Evaluation of a HIV/AIDS education program for adolescents.

The adolescent population has recently been recognized as one of the groups at risk for human immunodeficiency virus (HIV) infection. Statistics are beginning to document the extent of this trend. This study is aimed at determining adolescent sexual behaviors and the efficacy of a medical student-run acquired immune deficiency syndrome (AIDS) education program. Medical students taught 2,169 high school students in the St. Louis area with a pre- and post- intervention questionnaire administered to record levels of HIV/AIDS knowledge and sexual practices. Data revealed that 56.4% of the respondents were sexually active with 70.4% having multiple partners and 61.0% admitting to unprotected sex. These students demonstrated a significant increase in their knowledge about HIV infection after the educational program. The results show that, adolescents are sexually active and more importantly, they are practicing behaviors that put them at risk for HIV/AIDS, a risk which they recognize. Finally, the educational intervention did increase students' knowledge of HIV/AIDS. This may not translate into a change in behaviors, but it is a first step.

Adolescent↗

Rates of flow of technetium 99m--labeled human serum albumin from peripheral injection sites to sentinel lymph nodes.

BACKGROUND: The new technique of sentinel lymphadenectomy for cutaneous melanoma provided us with a unique opportunity to quantitate the rates of lymphatic flow in afferent lymphatics. METHODS: Seventeen melanoma patients underwent preoperative lymphoscintigraphy with technetium 99m-human serum albumin (HSA). The time and distance between the injection site and the sentinel lymph node (LN) were recorded. By comparison, lymphatic flow rates between footpad, popliteal LN, femoral LN, and systemic blood were measured in 60 female mice (C57BL/6) after footpad injection of 99mTc-HSA. RESULTS: The rate of lymphatic flow to 14 axillary, four inguinal, one popliteal, and one parotid sentinel LNs averaged 10.4 +/- 7.3 cm/min. In contrast, the lymphatic flow rate between the footpad and the popliteal LN in mice (analogous to the sentinel LN in human beings) averaged 1.33 +/- 0.52 cm/min. There was a marked delay in the passage of radionuclide through the popliteal LN with consequent slowing of the rate of flow between the popliteal and femoral LNs to 0.22 cm/min. CONCLUSION: Lymphatic flow to the sentinel LN occurs rapidly from both human skin and murine footpads. This information might be helpful in planning the timing of the incision after vital blue dye injection for identifying the sentinel LN.

Animals↗

Intraventricular bleeding after the use of thrombolytics in a cocaine user.

Cocaine-induced myocardial infarct is a medical emergency with increasing prevalence. The efficacy of thrombolytics in patients with cocaine-induced infarcts has not been well studied. This report describes the case of a patient who presented with presumed cocaine-induced myocardial infarct. The patient was treated with intravenous thrombolysis and developed an intraventricular bleed with herniation and death. Physicians should be aware of this grave consequence in a generally young population.

Cerebral Hemorrhage↗

Efficacy of vitamin B6 and magnesium in the treatment of autism: a methodology review and summary of outcomes.

Pauling's orthomolecular hypothesis appeared in 1968, stating that some forms of mental illness and disease are related to biochemical errors in the body. Vitamin therapy is believed to be a means of compensating for such errors. There have been few empirical studies on vitamin therapy in individuals with autism. This article presents a critical analysis of the 12 published studies located through an extensive computerized search. Studies were systematically evaluated to provide an objective assessment of empirical evidence supporting the efficacy of vitamin treatment. The majority of studies report a favorable response to vitamin treatment. However, interpretation of these positive findings needs to be tempered because of methodological shortcomings inherent in many of the studies. For example, a number of studies employed imprecise outcome measures, were based on small samples and possible repeat use of the same subjects in more than one study, did not adjust for regression effects in measuring improvement, and omitted collecting long-term follow-up data. Recommendations are offered to assist researchers in designing future investigations.

Autistic Disorder↗

Insight in schizophrenia and mania.

We administered a series of 12 brief vignettes depicting examples of positive, negative, and manic psychopathology in everyday language to 21 patients with schizophrenia and 20 patients with mania. We asked patients to rate, first, how similar they were to the individual depicted in each vignette, and, second, the degree to which the experiences or behaviors depicted in each vignette reflected mental illness. Psychiatrists also rated how similar each patient was to each vignette. At admission, patients with schizophrenia rated themselves as significantly less similar to the positive symptom vignettes than the psychiatrists rated them. Patients with mania did not differ from the psychiatrist in rating their similarity to the vignettes, but they strongly denied that the vignettes reflected mental illness.

Adult↗

A radiation hybrid map of 40 loci for the distal long arm of human chromosome 8.

We generated a panel of 97 radiation hybrids from the cell line GM10156B, which contains only human chromosome 8 in a Chinese hamster ovary cell line background. Statistical analysis of the cosegregation of markers in the 97 radiation hybrids was used to construct a physical map delineating the order and intermarker distance of 40 8q24 loci. Twenty-one loci were ordered with maximum likelihood ratios greater than 1000:1. A high level of consistency was seen between our RH map and the published genetic map, suggesting that our panel will be a valuable resource for the rapid mapping of markers derived from human chromosome 8.

Adenine Phosphoribosyltransferase↗

Human leukocyte antigen DQ alpha sharing is not increased in couples with recurrent miscarriage.

PROBLEM: The results regarding human leukocyte antigen (HLA) DQ alpha allele sharing in recurrent miscarriage couples are conflicting. The purpose of this study was to determine the frequency of HLA DQ alpha allele sharing in our unexplained recurrent spontaneous abortion (RSA) patients using modern DNA analytical techniques. METHODS: DNA was extracted from whole blood samples of 1) 51 couples with at least three miscarriages, and 2) 43 fertile couples (with at least seven children and no known history of recurrent miscarriage). The polymerase chain reaction (PCR) was used to amplify the second exon of the HLA DQ alpha locus on chromosome 6. Genotypes were identified by allele specific hybridization with 12 sequence-specific oligonucleotide probes. RESULTS: 47% of recurrent miscarriage couples and 35% of fertile couples shared no alleles. 47% of recurrent miscarriage couples compared to 58% of fertile couples shared one allele, and 6% of recurrent miscarriage couples and 7% of fertile couples shared two alleles. CONCLUSIONS: Reproductive partners with unexplained recurrent pregnancy loss have no increased frequency of HLA DQ alpha allele sharing. It is unlikely that HLA DQ alpha genotyping will be helpful in the management of patients with RSA.

Abortion, Habitual↗

Behind the curve: a critical assessment of how little is known about arrangements between managed care plans and physicians.

Extraordinary growth in managed care arrangements over the past decade has been both widely praised and criticized. Proponents and critics agree that the nature of medical practice is being profoundly altered by this growth, even if they cannot articulate the direction and consequences of this change. We explore the roots of this uncertainty by examining the available evidence on critical features of the arrangements managed care plans currently have with affiliated physicians. Our approach is to review and synthesize the literature in several key substantive areas from a broad range of sources. We found that existing knowledge is dated, derived form a limited subset of plans, inattentive to important structural differences between plans, and responsive to a very narrow set of issues poorly reflecting the range of medical practice and change introduced by managed care. We highlight key questions of interest and the knowledge gaps critical to address so that policy and management decisions can both reflect and be informed on these issues that define the arrangements managed care plans make with physicians and ultimately influence medical practice.

Capitation Fee↗