Phenotypic analysis--making the most of your mouse.
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Animals↗
Biomedical subjects
J E Martin
Publications and source records attributed to J E Martin.
Prospective evaluation of three smoking interventions in 205 recovering alcoholics: one-year results of Project SCRAP-Tobacco.
A total of 205 (113 male, 92 female) nonhospitalized recovering alcoholics with > 3 months of continuous abstinence from alcohol and drugs and relatively heavy tobacco dependence (Fagerstrom Tolerance Questionnaire score = 7.7; mean number of cigarettes per day, 26.8; mean number of years smoked, 24.4) were randomized to standard treatment (ST) American Lung Association quit program plus nicotine anonymous meetings (n = 70), behavioral counseling plus physical exercise (BEX; n = 72), or behavioral counseling plus nicotine gum (BNIC; n = 63). A 3 x 4 repeated measures design was used to evaluate the effectiveness of the interventions on smoking outcome at baseline, posttreatment, and 6- and 12-month follow-ups. Self-reported smoking status was verified with biochemical and informant report. Verified self-report indicated that significantly more smokers in BEX quit by posttreatment (60%) than in either BNIC (52%) or ST (31%), chi 2 (2, N = 205) = 17.85, p < .01, but not at the 6-month (29%, 27%, and 21%, respectively) or 12-month (27%, 27%, and 26%, respectively) follow-up. Only 4% (7 of 188) relapsed to alcohol or drugs. Alcohol relapse did not differ by treatment group or smoking status. Length of alcohol abstinence was not associated with smoking cessation outcome.
Adult↗
Morphological and morphometric characterisation of Onuf's nucleus in the spinal cord in man.
In the absence of a systematic morphometric study of Onuf's nucleus in man, this investigation defines the limits of variation of segmental position and the range of length and volume of Onuf's nucleus in 6 normal humans displaying no neurological disease (2 males, 4 females). Serial section reconstruction methods in conjunction with the disector method provided information on the numbers, sizes and shapes of the constituent motor neurons of Onuf's nucleus. In contrast to previous descriptions, the cranial origin of Onuf's nucleus occurred in rostral S1 in 50% of subjects, and midcaudal S1 in the remaining subjects. Onuf's nucleus varied in length between 4 and 7 mm, and was 0.2-0.37 mm3 in volume. Differences in length or volume between males or females, or between the left and right side of the cord were not statistically significant. Neurons in Onuf's nucleus varied in diameter between 10 microns and 60 microns (mean 26 microns) and their mean number was 625 +/- 137. A higher density of neurons occurred at the cranial and caudal ends of the nucleus relative to the middle. While 37% of neurons were approximately spherical (shape index approximately 1), 44% were ellipsoid and 19% fusiform (shape indices varying between 0.26 and 0.8). These findings are compared with previous studies of Onuf's nucleus in man and animals. The results form a basis for further studies on Onuf's nucleus in normality and neurodegenerative diseases.
Aged↗
Behavior of Na131I and meta(131I) iodobenzylguanidine (MIBG) in municipal sewerage.
Behavior of 131I activity in primary sludge at the Ann Arbor, Michigan, Municipal Waste Water Treatment Plant was studied in relation to known radioiodine therapy events at the University of Michigan Hospital complex. The principal compounds administered are Na131I, which has widespread use, and meta (131I) iodobenzylguanidine (MIBG), which is a compound unique to the University of Michigan, although labeled antibodies and other forms are also used in therapy and research. The objectives of the study were to determine the environmental fate of such discharges and to determine radiation exposures to workers and the public when sludges are incinerated. Approximately 17% of the MIBG activity administered in a therapy was found in the primary sludge, whereas only 1.1% of the Na131I was in sludge. When land applied, the short half life of 131I in the sludge presents few radiological health concerns; however, incineration, which is done in winter months, is assumed to release organically bound 131I to the atmosphere. Radiation doses due to incineration of sludge containing measured concentrations were calculated for a maximally exposed worker to be 1.7 microSv (0.17 mrem) of which 0.48 microSv (0.048 mrem) was due to a 2-d upset condition. For a more typically exposed worker, and a member of the public, the committed effective dose equivalents were 1.2 microSv (0.12 mrem) and 0.06 microSv (0.006 mrem), respectively, for a 22-wk incineration period with release of all radioiodine in the sludge. Transport time to the treatment plant for radioiodine was found to be much longer than that of normal sewage, possibly due to organic material in sewer lines that absorb iodine. The residence time of radioiodine in the sewer also appears to be longer than expected; whether other radioactive materials are held up the same way is not known but chemical form is surely a factor.
3-Iodobenzylguanidine↗
Internal anal sphincter myopathy causing proctalgia fugax and constipation: further clinical and radiological characterization in a patient.
We report a case of a distinctive familial internal anal sphincter myopathy with unique histological and radiological features. A 67-year-old woman presented with a 20-year history of proctalgia fugax and outlet obstruction; other family members were similarly affected. Computed tomograpy and magnetic resonance imaging demonstrated a grossly hypertrophied internal anal sphincter. Strip myectomy of the sphincter was carried out with improvement in evacuation but little relief of proctalgia. Further relief of symptoms was obtained using oral and transdermal nitrates and a calcium antagonist. Histological examination of the excised muscle revealed hypertrophy and an abnormal arrangement of fibres in whorls; many fibres contained vacuoles with inclusion bodies positive for periodic acid-Schiff. This description of a specific anal sphincter myopathy illustrates the potential importance of histopathological studies of smooth muscle in functional disorders of the gut.
Aged↗
Calcium, magnesium, and phosphorus: emergency department testing yield.
OBJECTIVES: To investigate how often the ED ordering of stat serum calcium (Ca+2), magnesium (Mg+2), and phosphorus (PO4(-3)) levels affected clinical treatment; to define the diagnoses of patients for whom Ca+2, Mg+2, and PO4(-3) measurements did affect clinical therapy; and to suggest guidelines for more appropriate ordering of these laboratory tests. METHODS: A retrospective chart review was performed in an academic teaching hospital. All adult ED patients who had Ca+2, Mg+2, or PO4(-3) laboratory testing during the 9-month study period were included and evaluated for potential clinical impact of an abnormal Ca+2, Mg+2, or PO4(-3) laboratory test. RESULTS: 1.477 patients had Ca+2, Mg+2, or PO4(-3) measured while in the ED during the study period. Of these, 260 patients (17.6%) had a total of 312 abnormal Ca+2, Mg+2, or PO4(-3) values as defined by results exceeding +/- 15% of normal reference values. Of these, only 5 patients (0.3%) received treatment for abnormal values in the ED, while 75 patients (5.1%) were treated once admitted to the hospital. In this study, the only diagnostic groups to whom significant treatment was administered were diabetic patients (Ca+2 and PO4(-3); alcoholic patients (Mg+2); and renal failure patients (Ca+2, Mg+2, and PO4(-3). CONCLUSION: These results suggest that stat Ca+2, Mg+2, and PO4(-3) levels seldom affect clinical treatment in the ED. The frequency of ordering these tests may be reduced by obtaining Ca+2, Mg+2, or PO4(-3) measurements only for patients known to be at risk for such abnormalities, based on their existing or suspected diagnoses. The authors suggest obtaining these tests, when indicated, on a "non-stat" basis, with the subsequent laboratory results becoming available in-hospital, where treatment is more likely to occur.
Adult↗
The mouse lysosomal membrane protein 1 gene as a candidate for the motorneuron degeneration (mnd) locus.
The motorneuron degeneration (mnd) mutation causes one of the few late-onset progressive neurodegenerations in mice; therefore, the mnd mouse is a valuable paradigm for studying neurodegenerative biology. The mnd mutation may also model human neuronal ceroid lipofuscinosis (NCL) or Batten disease. mnd maps to the centromeric region of mouse chromosome 8, which likely corresponds to portions of human chromosomes 13,8, or 19; we note that the chromosome 13 portion maps close to a region thought to contain the human Type V NCL locus. We have identified candidate genes for the mnd locus from human chromosomes 13,8, and 19, and we are mapping these genes in the mouse to determine their proximity to the mutated locus and to refine the comparative human-mouse map in this area. A candidate gene from human chromosome 13 is LAMP1, which encodes lysosomal membrane protein 1. We found that LAMP1 in the mouse lies within the region of the mnd mutation. Therefore, we sequenced LAMP1 cDNAs from homozygous mnd mice and unrelated wildtype C57BL/6 mice. We find no differences between the two cDNA species in the regions examined, and expression analysis shows a similar LAMP1 protein distribution in wildtype and mutant mice, suggesting that an abnormal accumulation of material within normal lysosome structures is unlikely to be the pathogenetic mechanism in the mnd mouse.
Animals↗
The gene encoding tripeptidyl peptidase II maps to chromosome 1 in the mouse.
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Aminopeptidases↗
Measuring tobacco withdrawal: a review of self-report questionnaires.
Little information exists on the various measures used to assess tobacco withdrawal. This article reviews the literature on the assessment of tobacco withdrawal, specifically comparing three commonly used self-report questionnaires of tobacco withdrawal. Several topics are discussed including (a) the frequency and duration of withdrawal assessment, (b) the determination of reliability and validity of self-report measures, (c) a comparison of the existing self-report instruments in terms of psychometric properties and other criteria, and (d) the physiological and behavioral assessment of tobacco withdrawal. Six recommendations for further research are offered.
Arousal↗
More on "right-sizing residencies".
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Health Workforce↗
beta hCG as a prognostic marker in adenocarcinoma of the prostate.
AIMS: To assess the importance of immunohistological detection of beta-human chorionic gonadotrophin (beta hCG) in localised prostatic adenocarcinoma with regard to prognosis and clinical applications. METHODS: Eighty consecutive cases of clinically localised adenocarcinoma of the prostate were studied retrospectively. Immunohistological analysis on formalin fixed, paraffin wax embedded prostate tissue from transurethral resections was related to clinical outcome and survival. Prognosis was also related to tumour grade. RESULTS: beta hCG was detected in 12 cases. Nine of these patients were found to have metastases (75%) at follow up and 11 (92%) were dead within 18 months. There was no correlation with grade and prognosis in this group. Of the 68 beta hCG negative cases, 21 had developed metastases (31%) and 25 (37%) had died within 18 months. In the beta hCG negative group there was an association between histological grade and survival. CONCLUSION: The demonstration of beta hCG in prostatic adenocarcinoma identifies a group of patients with poor prognosis, irrespective of histological grade. This additional information will be extremely valuable in the subsequent clinical management of such patients.
Adenocarcinoma↗
Mapping TNNC1, the gene that encodes cardiac troponin I in the human and the mouse.
We have mapped the TNNC1 gene, whose protein product is the cardiac TnI protein. TnI is one of the proteins that makes up the troponin complex, which mediates the response of muscle to calcium ions. The human TNNC1 locus had been assigned to a large region of chromosome 19, and we have refined the mapping position to the distal end of the chromosome by amplification of DNAs from a chromosome 19 mapping panel. We have also mapped the mouse Tnnc1 locus, by following the segregation of an intron sequence through DNAs from the European Interspecific Backcross. Tnnc1 maps close to the centromere on mouse chromosome 7.
Animals↗
Human glial cell line-derived neurotrophic factor (GDNF) maps to chromosome 5.
Neurotrophic factors are essential neurone survival promoting molecules that are often secreted and that bind to neuronal cell surface receptors. Glial cell line-derived neurotrophic factor, GDNF, is a potent neurotrophic factor that promotes the survival of dopaminergic neurones in cultures including embryonic neuronal cultures. We have mapped the gene encoding GDNF by two independent methods: using a cell hybrid panel and by fluorescent in situ hybridisation. We find GDNF lies on the short arm of human chromosome 5, at 5p13.1-p13.3 ability to promote dopamine uptake in midbrain cultures. The protein was partially sequenced and a rat GDNF cDNA was isolated by screening a B49 cDNA library with an oligonucleotide probe designed from the amino-terminus of the rat protein. Human GDNF sequences were isolated by screening a human genomic library with a portion of the rat GDNF cDNA (Lin et al. 1993). We wished to localise the GDNF gene in the human genome and determine its proximity to possible sites of mutation, particularly phenotypes affecting neuronal function.
Animals↗
A simple approach to intracytoplasmic sperm injection.
OBJECTIVE: To describe a simple injection apparatus and method for performing intracytoplasmic sperm injection in a clinical IVF program. DESIGN: A prospective clinical trial of intracytoplasmic sperm injection. SETTING: A private office-based fertility program. PATIENTS: Five couples undergoing IVF-ET with intracytoplasmic sperm injection as a treatment for male factor infertility. INTERVENTIONS: Intracytoplasmic sperm injection was performed at room temperature (23.5 to 24.5 degrees C) in a simple zwitterion-buffered medium. MAIN OUTCOME MEASURES: Fertilization rates, cleavage rates, clinical pregnancy rates, implantation rates. RESULTS: Intracytoplasmic sperm injection was performed on 44 fresh oocytes from five patients. Twenty-three oocytes fertilized (52.3%) and 22 zygotes cleaved (95.7%). Three of five patients became pregnant (60%), resulting in the live birth of one normal male infant, one continuing singleton pregnancy, and one continuing twin gestation (46XX, 46XY). The implantation rate was 23.5%. CONCLUSION: Intracytoplasmic sperm injection can be performed successfully in a simple medium at room temperature using commercially available microtools.
Cytoplasm↗
Ultrastructural abnormalities with inclusions in Onuf's nucleus in motor neuron disease (amyotrophic lateral sclerosis).
This study describes an ultrastructural examination focused on motor neurons in Onuf's nucleus in the spinal cord of four control patients without neurological disease (45-70 years) and six motor neuron disease (MND) patients (38-79 years; duration 8 months-19 years) who showed no somato-vesical dysfunction. Prompted by recent studies suggesting some sphincteric motor neurons may succumb to MND, this study sought to determine whether the wider population of neurons in Onuf's nucleus display ultrastructural cytopathology which is normally undetectable in histological preparations. Spinal cords were removed 3-20 h after death, and 1 mm slices of cord rapidly fixed in modified Karnovsky medium were processed for both light- and electronmicroscopy. 'Control motor neurons' had intact neuronal and nuclear membranes. Nissl bodies chiefly comprised ordered structures of alternate lamellae of rough endoplasmic reticulum and arrays of polyribosomes. The Golgi complexes consisted of multilamellated curvilinear stacks of ER. No intraneuronal filamentous or Bunina body inclusions were observed, but occasional axonal spheroids were seen in the neuropil. In MND, histological evidence of sparing in Onuf's nucleus was associated with abnormal ultrastructure of the motor neurons. Some sphincteric neurons were atrophic, whereas in the others, Nissl bodies were reduced in number, showed loss of structural organization or comprised polyribosomal aggregates. Golgi complexes had disrupted lamellated organization or consisted solely of distended ER. Intraneuronal filamentous Lewy-body or skein-like inclusions and Bunina bodies were identified in Onuf's nucleus of three subjects (duration of MND 8 months-2 years). The results of the present study indicate that Onuf's nucleus is vulnerable in MND, and preservation of sphincter function with qualitative histological evidence of 'sparing' does not necessarily imply a corresponding lack of ultrastructural cytopathology in this nucleus.
Adult↗
Characterization of simian immunodeficiency virus (SIV) infected AA-2 cells by SEM and immunoelectron microscopy.
The ultrastructural features of AA-2 cells infected with either of two strains of simian immunodeficiency virus (SIVMne-E11S or SIVSMM-PBj) were examined by scanning electron microscopy (SEM). Transformed CD4+ human B lymphocytes (AA-2) were inoculated with SIV and observed at 2, 4, and 7 days post-inoculation (dPI). Infected AA-2 cells were distinguished by the progressive loss of microvilli, and variable numbers of free or protruding spherical particles measuring 90-120nm in diameter along the cell surface. Syncytial cell formation (complexes of fused cells) and necrotic cells were evident at each time point with the most numerous observations at 7 dPI. While the distribution and severity of the viral induced changes increased with time and affected virtually all cells by 7 dPI, the alterations were detected sooner and were more pronounced in SIVSMM-PBj infected cells. This finding is consistent with the in vivo data from primate studies using the same strains of SIV. Syncytial cells exhibited slight to moderate indentations which appeared to coincide with the boundaries of individual cells forming the complex. The plasma membrane of syncytial cells was relatively smooth and lacked microvilli. Spherical particles and buds protruding from the plasma membrane were predominate features of syncytial cell surfaces. By the employment of antisera generated against whole SIVMne-E11S, both transmission and scanning immunoelectron microscopy confirmed the identity of the spherical structures as free and budding SIV virions.
Antibodies, Viral↗
Kawasaki syndrome in the ED.
In a retrospective case review of inpatient and emergency department (ED) records during a 55-month period, 155 hospitalizations for Kawasaki syndrome (KS) were identified, of which 44 were seen in the ED. In 16 cases, KS was already suspected by their private physicians and confirmed in the ED by a KS specialist. In the remaining 28, patients presented initially to the ED. In 18 of these 28 (64%), KS was identified or suspected in the ED. In the other 10, the diagnosis was delayed. In four instances, patients were hospitalized for other reasons. In all cases in which the diagnosis of KS was not made in the ED, viral infections or sepsis were suspected. One child presented to the ED in respiratory arrest and severe bradycardia.
Cardiovascular Diseases↗
High continuing pregnancy rates after in vitro fertilization-embryo transfer using medium supplemented with a plasma protein fraction containing alpha- and beta-globulins.
OBJECTIVE: To evaluate both the laboratory and clinical outcomes after IVF-ET using culture media supplemented with a plasma protein fraction (PPF, Plasmatein; Alpha Therapeutics, Los Angeles, CA) containing albumin and significant amounts of alpha- and beta-globulins. DESIGN: One-year clinical trial of a PPF with high globulin content as a medium supplement during IVF, embryo growth, and ET. SETTING: Fertility Center of San Antonio, a private, office-based center for assisted reproduction. PATIENTS: Ninety-eight couples, with women ranging in age from 26 to 46 years, undergoing 103 ovum retrievals for IVF-ET as treatment for infertility because of tubal factor, endometriosis, anovulation, uterine or cervical factor, male factor, and unexplained causes. MAIN OUTCOME MEASURES: Fertilization rate, zygote cleavage rate, clinical pregnancy rate (PR), continuing PRs, and implantation rates. RESULTS: Supplementation with PPF in insemination, growth and transfer medium resulted in a clinical PR of 41.5% per transfer with continuing PRs of 35.2% per retrieval, 37.2% per patient, and 38.7% per transfer. CONCLUSIONS: A PPF containing significant amounts of alpha- and beta-globulins can serve as an effective protein supplement to IVF medium, with outcomes manifested as high continuing PRs. These data indicate a potential role for glycoprotein components of serum in supporting healthy embryo growth in vitro, although the mechanism may relate more to the general physicochemical properties of this fraction than to the actions of a specific component.
Adult↗