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Biomedical subjects

L Chamberlain

Publications and source records attributed to L Chamberlain.

7 recordsLinked to original sources

AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1.

A novel human G protein-coupled receptor named AXOR12, exhibiting 81% homology to the rat orphan receptor GPR54, was cloned from a human brain cDNA library. Heterologous expression of AXOR12 in mammalian cells permitted the identification of three surrogate agonist peptides, all with a common C-terminal amidated motif. High potency agonism, indicative of a cognate ligand, was evident from peptides derived from the gene KiSS-1, the expression of which prevents metastasis in melanoma cells. Quantitative reverse transcriptase-polymerase chain reaction was used to study the expression of AXOR12 and KiSS-1 in a variety of tissues. The highest levels of expression of AXOR12 mRNA were observed in brain, pituitary gland, and placenta. The highest levels of KiSS-1 gene expression were observed in placenta and brain. A polyclonal antibody raised to the C terminus of AXOR12 was generated and used to show localization of the receptor to neurons in the cerebellum, cerebral cortex, and brainstem. The biological significance of these expression patterns and the nature of the putative cognate ligand for AXOR12 are discussed.

Amino Acid Sequence↗

Cardiac markers in the diagnosis of acute coronary syndromes.

Evolution of the role of cardiac markers has ranged from the diagnosis of acute myocardial infarction in patients with nondiagnostic electrocardiograms to prognostic risk stratification and to guide therapy. The technology to provide rapid, real time measurements by immunoassay has provided the laboratory and clinician with a range of test options. The principal changes have been the use of rapid serial marker measurements of well-recognized cardiac markers, and the development of immunoassays for the cardiac structural proteins. Measurement of cardiac troponins has generated a new diagnostic paradigm in patients with suspected acute coronary syndromes. There is now a new gold standard biochemical test for myocardial infarction. A range of interventions can be guided by troponin measurement. The use of troponin measurements is central to management of patients with suspected acute coronary syndromes. Future developments in this field will focus on the role of existing and novel markers of inflammation and ischemia.

Acute Disease↗

Physicians' screening practices for female partner abuse during prenatal visits.

OBJECTIVE: Our purpose was to examine physicians' screening practices for female partner abuse during prenatal visits and to identify barriers to screening. METHODS: A self-administered questionnaire was developed to collect data on physicians' screening practices and their beliefs about screening for female partner abuse. The survey was mailed to all primary care physicians practicing in Alaska. The response rate was 80% (305/383). These analyses were limited to physicians who indicated that they provided prenatal care (n = 157). RESULTS: More than one-half of respondents providing prenatal care estimated that 10% or more of their female patients had experienced abuse. Less than one-half of respondents had recent training on partner abuse. Only 17% of respondents routinely screened at the first prenatal visit and 5% at follow-up visits. Respondents were more likely to screen at the first prenatal visit compared to follow-up visits. Multivariate analyses failed to support any associations between physicians' characteristics and screening practices. Physicians' perception that abuse was prevalent among their patients and physicians' belief that they have a responsibility to deal with abuse were the only variables that were independently associated with screening at prenatal visits. Other barriers frequently cited in the literature were not predictive of screening. CONCLUSION: Most Alaskan physicians do not routinely screen for abuse during prenatal visits. Medical education should increase physicians' index of suspicion for abuse, emphasize physicians' responsibility to address partner abuse, and reinforce the importance of routine screening throughout the pregnancy. More research is needed to identify barriers to screening and strategies for integrating routine screening into prenatal care.

Alaska↗

Colocalization of somatostatin receptor sst5 and insulin in rat pancreatic beta-cells.

Somatostatin, also known as somatotropin release-inhibiting factor (SRIF), is secreted by pancreatic delta-cells and inhibits the secretion of both insulin and glucagon. SRIF initiates its actions by binding to a family of six G protein-coupled receptors (sst1, -2A, -2B, -3, -4, and -5) encoded by five genes. Messenger RNA for both sst2 and sst5 have been reported in the rat pancreas, and the sst2A receptor protein has been localized to rat pancreatic alpha and pancreatic polypeptide-secreting cells in the islets as well as to pancreatic acinar cells. In this study we have used double immunostaining to show that the sst5 protein is expressed exclusively in the beta-cells of rat pancreatic islets and localizes with insulin-secreting alpha-cells. The sst5 receptor is not colocalized with sst2A. Thus, in the rat SRIF inhibits pancreatic insulin and glucagon secretion via different sst receptor subtypes.

Alternative Splicing↗

Mucosal delivery of murine interleukin-2 (IL-2) and IL-6 by recombinant strains of Lactococcus lactis coexpressing antigen and cytokine.

Lactococcus lactis is a nonpathogenic and noncolonizing bacterium which is being developed as a vaccine delivery vehicle for immunization by mucosal routes. To determine whether lactococci can also deliver cytokines to the immune system, we have constructed novel constitutive expression strains of L. lactis which accumulate a test antigen, tetanus toxin fragment C (TTFC), within the cytoplasmic compartment and also secrete either murine interleukin-2 (IL-2) or IL-6. When mice were immunized intranasally with various different expression strains of L. lactis, the anti-TTFC antibody titers increased more rapidly and were substantially higher in mice immunized with the bacterial strains which secreted IL-2 or IL-6 in addition to their production of TTFC. This adjuvant effect was lost when the recombinant strains of L. lactis were killed by pretreatment with mitomycin C and could therefore be attributed to the secretion of IL-2 or IL-6 by the recombinant lactococci. These results provide the first example of the use of a cytokine-secreting, noninvasive experimental bacterial vaccine vector to enhance immune responses to a coexpressed heterologous antigen and point the way to experiments which will test the possible therapeutic efficacy of this mode of cytokine delivery.

Administration, Intranasal↗

Wernicke encephalopathy and beriberi during total parenteral nutrition attributable to multivitamin infusion shortage.

OBJECTIVE: Wernicke encephalopathy (WE) is an acute neurologic disorder characterized by a triad of ophthalmoplegia, ataxia, and mental confusion. WE is attributable to thiamine (vitamin B1) deficiency. Beriberi is the systemic counterpart of thiamine deficiency and often manifests in cardiovascular collapse. WE is usually associated with alcoholism and malnutrition. It has also been seen in people with gastrointestinal diseases with malabsorption. Patients who have received total parenteral nutrition (TPN) without proper replacement of thiamine have also developed WE. Since November 1996, there has been a shortage of multivitamin infusion (MVI). Many patients who were on chronic TPN with MVI ceased to receive the MVI and were converted to an oral form of the multivitamin. As a result, there have been several reports of children and adults on TPN who have developed WE as a result of thiamine deficiency. With this case report, we bring to attention the association of the MVI shortage and WE. Early diagnosis of WE is important, because if it is treated with thiamine in the acute stages, the neurologic and cardiovascular abnormalities can be reversed. CASE REPORT: We report a 20-year-old female patient with Crohn's disease who developed WE as a result of thiamine deficiency. She had Crohn's disease since age 9 years and was on chronic TPN. Two months before admission, MVI was discontinued in the TPN because of the shortage of its supply. An oral multivitamin tablet was substituted instead. She was admitted to the hospital for persistent vomiting. In the hospital, she continued to receive TPN without MVI, but continued taking an oral multivitamin preparation. Two weeks after admission, she developed signs of WE including diplopia, ophthalmoplegia, nystagmus, and memory disturbance. She also developed hypotension that was thought to be caused by beriberi. She was treated with 50 mg of intravenous thiamine. Within hours of the intravenous thiamine, her hypotension resolved. The day after the infusion, she no longer complained of diplopia, and her ophthalmoplegia had improved dramatically. Magnetic resonance imaging showed several areas of abnormally high signal on T2-weighted images in the brainstem, thalamus, and mamillary bodies. The topographic distribution of these changes was typical of WE. After 2 months, her mental status and neurologic status had recovered completely. CONCLUSION: WE and thiamine deficiency should be considered in all patients with malabsorption, malnutrition, and malignancies. WE from thiamine deficiency can occur as a result of cessation of MVI in the TPN infusion. Even if an oral multivitamin preparation is given instead of MVI, patients with malabsorption may not absorb thiamine adequately. Prompt diagnosis of WE is important because it is potentially fatal and readily treatable with thiamine supplementation. Early recognition of WE may be more difficult in children, because the classic triad of symptoms may not develop fully. Magnetic resonance imaging may be useful in these cases to confirm the diagnosis of WE. Because the shortage of MVI is expected to be a long-term, there are likely to be more cases of WE in the pediatric population of TPN-dependent children. Because there is no shortage of intravenous thiamine, it should be administered with TPN even if MVI is not available.

Administration, Oral↗

Communication skill and behaviour disorder.

The aim was to identify changes in communication skills and behaviour disorder of 15 clients with learning difficulties 6 mo. and 1 yr. after they moved from large- to small-scale accommodations. Clients were allocated into a group of 6 with profound multiple learning difficulties, a preverbal group of 5, and a verbal group of 4. Communication skills were measured using the Preverbal Communication Schedule, and behavioural disorder was measured using the Aberrant Behaviour Checklist. Analysis showed that from the baseline to one year follow-up, there was a significant increase from baseline in social withdrawal by the clients with multiple difficulties but that there were improvements in communication skills of both preverbal and verbal clients. No control group was involved.

Adult↗