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Biomedical subjects

M Smith

Publications and source records attributed to M Smith.

At least 955 records · Page 53Linked to original sources

The insulin-like growth factor-II (IGF-II) receptor of rat brain: regional distribution visualized by autoradiography.

The presence of insulin-like growth factor-II (IGF-II) in brain and cerebral spinal fluid prompted us to investigate the distribution of receptors for this peptide in rat brain slices. Human 125I-IGF-II (10 pM) was incubated for 16 h at 4 degrees C with thaw-mounted slices of rat brain from 11 different brain regions. Incubations in the absence or presence of excess unlabeled human IGF-II or insulin were performed and the labeled tissues were exposed to X-ray film for 4-7 days. Autoradiographs showed dense labeling in the granule layers of the olfactory bulbs, deep layers of the cerebral cortex, pineal gland, anterior pituitary, hippocampus (CA1-CA4, and dentate gyrus), and the granule cell layers of the cerebellum. Unlabeled IGF-II eliminated most of the binding in these brain regions while insulin produced only a minimal reduction in the amount of 125I-IGF-II bound. These results indicate that a neural receptor for IGF-II is uniquely distributed in rat brain tissue supporting the notion that this peptide might play an important role in neuronal functioning.

Animals↗

Serial [18F]N-methylspiroperidol PET studies to measure changes in antipsychotic drug D-2 receptor occupancy in schizophrenic patients.

An indirect approach to the relationship among drug dose, plasma level, and the competition between a labeled neuroleptic drug [18F]N-methylspiroperidol (18F-NMS) for binding sites in striatal tissue in normal and schizophrenic subjects is described. The slope of the line plotting the ratio of activity in the striatum (As) to activity in the cerebellum (Ac) versus time up to 5 hr postinjection of 18F-NMS is taken as a marker of site occupancy. An inverse relation between labeled competitor uptake and drug plasma level has been demonstrated for the classes of antipsychotic drug studied. Striatal uptake studies showed a progressive increase in all subjects following drug withdrawal up to 156 hr postwithdrawal. Uptake and clearance of 18F-NMS in cerebellar tissue was not appreciably affected by antipsychotic medication or drug withdrawal.

Adult↗

Human brain glycogen phosphorylase. Cloning, sequence analysis, chromosomal mapping, tissue expression, and comparison with the human liver and muscle isozymes.

We have cloned the cDNA encoding a new isozyme of glycogen phosphorylase (1,4-D-glucan:orthosphosphate D-glucosyltransferase, EC 2.4.1.1) from a cDNA library prepared from a human brain astrocytoma cell line. Blot-hybridization analysis reveals that this message is preferentially expressed in human brain, but is also found at a low level in human fetal liver and adult liver and muscle tissues. Although previous studies have suggested that the major isozyme of phosphorylase found in all fetal tissues is the brain type, our data show that the predominant mRNA in fetal liver (24-week gestation) is the adult liver form. The protein sequence deduced from the nucleotide sequence of the brain phosphorylase cDNA is 862 amino acids long compared with 846 and 841 amino acids for the liver and muscle isozymes, respectively; the greater length of brain phosphorylase is entirely due to an extension at the far C-terminal portion of the protein. The muscle and brain isozymes share greater identity with regard to nucleotide and deduced amino acid sequences, codon usage, and nucleotide composition than either do with the liver sequence, suggesting a closer evolutionary relationship between them. Spot blot hybridization of the brain phosphorylase cDNA to laser-sorted human chromosome fractions, and Southern blot analysis of hamster/human hybrid cell line DNA reveals that the exact homolog of the newly cloned cDNA maps to chromosome 20, but that a slightly less homologous gene is found on chromosome 10 as well. The liver and muscle genes have previously been localized to chromosomes 14 and 11, respectively. This suggests that the phosphorylase genes evolved by duplication and translocation of a common ancestral gene, leading to divergence of elements controlling gene expression and of structural features of the phosphorylase proteins that confer tissue-specific functional properties.

Amino Acid Sequence↗

Four mating-type genes control sexual differentiation in the fission yeast.

The mating-type region of fission yeast consists of three components, mat1, mat2-P and mat3-M, each separated by 15 kb. Cell-type is determined by the alternate allele present at mat1, either P in an h+ or M in an h- cell. mat2-P and mat3-M serve as donors of information that is transposed to mat1 during a switch of mating type. We have determined the nucleotide sequence of each component of mat. The P and M specific regions are 1104 and 1128 bp, respectively, and bounded by sequences common to each mating-type cassette (H1; 59 bp and H2; 135 bp). A third sequence is present at mat2-P and mat3-M but absent at mat1 (H3; 57 bp), and may be involved in transcriptional repression of these cassettes. mat1-P and mat1-M each encode two genes (Pc; 118 amino acids, Pi; 159 amino acids, Mc; 181 amino acids and Mi; 42 amino acids). Introduction of opal or frame-shift mutations into the open-reading-frame of each gene revealed that Pc and Mc are necessary and sufficient for mating and confer an h+ or h- mating type respectively. All four genes are required for meiotic competence in an h+/h- diploid. The transcription of each mat gene is strongly influenced by nutritional conditions and full induction was observed only in nitrogen-free medium. The predicted product of the Pi gene contains a region of homology with the homeobox sequence, suggesting that this gene encodes a DNA binding protein that directly regulates the expression of other genes.

Amino Acid Sequence↗

Molecular organisation of the quinic acid utilization (QUT) gene cluster in Aspergillus nidulans.

The functional integrity of the QUTB gene (encoding quinate dehydrogenase) has been confirmed by transformation of a qutB mutant strain. The DNA sequence of the contiguous genes QUTD (quinate permease), QUTB and QUTG (function unknown) has been determined and analysed, together with that of QUTE (catabolic 3-dehydroquinase). The QUTB sequence shows significant homology with the shikimate dehydrogenase function of the complex AROM locus of Aspergillus nidulans, and with the QA-3 quinate dehydrogenase and QA-1S (repressor) genes of Neurospora crassa. The QUTD gene shows strong homology with the N. crassa QA-Y gene and QUTG with the QA-X gene. QUTD, QUTB, and QUTG, QUTE form two pairs of divergently transcribed genes, and conserved sequence motifs identified in the two common 5' non-coding regions show significant homology with UASGAL and UASQA sequences of the Saccharomyces cerevisiae and N. crassa Gal and QA systems. In addition, conserved 5' sequences homologous to the mammalian CAAT box are noted and a previously unreported conserved 22 nucleotide motif is presented.

Alcohol Oxidoreductases↗

Programmed follicular stimulation reduces cycle cost and stress with no compromise in cycle quality: use of a modified programmed protocol.

To reduce cycle cost and patient/staff stress in an ongoing in vitro fertilization (IVF) program, we have utilized a modified "programmed" (PP) follicle stimulation protocol with limited monitoring. We have compared our PP results with those using a conventional, individualized, and fully monitored protocol (OP) in order to show that PP does not compromise the quality of care. Hormonal presuppression made possible an arbitrary starting day for the cycle. In 80% of the cycles, oocyte retrieval (OR) was performed on the planned day or 1 day later. There was no statistically significant difference between the two regimens in oocyte/embryo numbers, quality or pregnancy rates. The cycle cost was significantly reduced. In addition, patient stress was lessened because of the reasonable predictability of cycle timing. We conclude that PP has significant financial and emotional advantages for the patient over OP but does not appear to diminish the chance for pregnancy in an IVF cycle. PP also allows program staff to manage time more effectively, thereby reducing staff stress.

Clinical Protocols↗

Preliminary studies of clonidine in psychotic patients.

Twelve psychotic patients received a mean dose of 3.3 mg/day of clonidine. In four clonidine was the only treatment and in the remaining eight clonidine was superadded to a neuroleptic regimen after symptomatology was stable. Clonidine caused reduction of scores for both productive psychotic symptoms and anxiety. Negative symptoms were unaffected. These findings are discussed with respect to the small magnitude of the effects, questions as to specificity of the effects and methodologic limitations of this pilot study.

Adult↗

Pseudallescheria boydii brain abscess. Complication of an intravenous catheter.

An adult patient survived a brain abscess with Pseudallescheria boydii. She received intraventricular miconazole, 20 mg every 72 hours (minimal inhibitory concentration = 0.4 microgram/ml), and surgery. The abscess resulted from an infected central venous catheter (Port-A-Cath) and steroid therapy. Miconazole caused a ventriculitis. There are 12 reported cases of P. boydii brain abscesses from 1965 to 1985 with only two survivors.

Adult↗

Sequence of a bovine herpesvirus type-1 glycoprotein gene that is homologous to the herpes simplex gene for the glycoprotein gB.

The 130-kDa bovine herpesvirus-1 (BHV-1) glycoprotein GVP 6 was found to cross-react immunologically with the herpes simplex glycoprotein gB. Antibodies in polyclonal serum against gB immunoprecipitated GVP 6 and its cleavage products from a lysate of BHV-1-infected cells. Conversely, polyclonal serum against GVP 6 precipitated gB from HSV-1-infected cell lysates. Sera against the other glycoproteins did not demonstrate cross-reactivity. A 3.6-kb Kpnl-Hpal fragment of BHV-1 DNA that hybridized to the gene for gB was cloned and the nucleotide sequence of both strands was determined. The longest codon reading frame in the fragment coded for a protein that showed extensive homology with gB1 and related sequences from pseudorabies virus, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus. The strongest homologies were observed in two segments of the ectodomain, the transmembrane domain, and sequences adjacent to the transmembrane domain.

Amino Acid Sequence↗

Left ventricular distensibility and passive elastic stiffness in atrial septal defect.

Diminished left ventricular distensibility has been postulated as a cause of left ventricular failure in atrial septal defect. To evaluate this hypothesis the indexes of left ventricular compliance and stiffness were estimated in 15 patients with atrial septal defect and the results compared with those in 10 normal subjects. Age, peak left ventricular systolic pressure, end-diastolic pressure, ejection fraction and cardiac index did not differ significantly between groups. Left ventricular end-diastolic volume for the atrial septal defect group was significantly less than that for the control group (mean +/- SD, 61 +/- 9 ml/m2 versus 73 +/- 13, p less than 0.05) in keeping with previous studies. The slope of the log pressure-volume relation was significantly greater in the group with atrial septal defect than in the normal group (0.056 +/- 0.010 versus 0.044 +/- 0.008, p less than 0.01), consistent with increased chamber stiffness. For a group of six patients with atrial septal defect and elevated left ventricular end-diastolic pressure, normalized compliance was significantly less than that in the control group (0.017 +/- 0.001 versus 0.036 +/- 0.007, p less than 0.02). The slope k of the elastic stiffness-stress relation for the total group with atrial septal defect was significantly greater than that of the normal group (21.0 +/- 2.3 versus 18.1 +/- 2.3, p less than 0.01). An index of muscle fiber stretch (dV/VdP x end-diastolic stress x 100) was significantly less in the atrial septal defect group than in the control group (74 +/- 24 versus 106 +/- 22, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Regional assignment of the gene for human liver/bone/kidney alkaline phosphatase to chromosome 1p36.1-p34.

We have used three different methods to map the human liver/bone/kidney alkaline phosphatase (ALPL) locus: (1) Southern blot analysis of DNA derived from a panel of human-rodent somatic cell hybrids; (2) in situ hybridization to human chromosomes; and (3) genetic linkage analysis. Our results indicate that the ALPL locus maps to human chromosome bands 1p36.1-p34 and is genetically linked to the Rh (maximum lod score of 15.66 at a recombination value of 0.10) and fucosidase A (maximum lod score of 8.24 at a recombination value of 0.02) loci. These results, combined with restriction fragment length polymorphisms identified by ALPL DNA probes, provide a useful marker for gene mapping studies involving the short arm of chromosome 1. In addition, our results help to elucidate further the structure and evolution of the human alkaline phosphatase multigene enzyme family.

Alkaline Phosphatase↗

Physician assessments of practice patterns in emergency department radiograph interpretation.

Emergency and radiology department directors at 517 acute-care US teaching hospitals were sent identical questionnaires surveying practice patterns of ED plain film radiograph interpretation. Fifty-seven percent of ED directors and 51% of radiology department (RD) directors responded. Both groups reported that the most common practice pattern (60%) was alternating responsibility for immediate interpretation between emergency physicians and radiologists during a 168-hour week. Remaining hospitals were nearly equally divided between systems in which radiologists always provided immediate interpretation and those in which the emergency physicians always provided the initial interpretation. In all systems in which emergency physicians provided some immediate radiograph interpretation, radiologists provided subsequent review. Institutions varied as to the level of training of the physician in both the ED and RD who provided immediate radiograph interpretation; at least 30% of the institutions responding were reported to have either emergency physicians or radiologists of resident level providing immediate interpretation at least part of the 24-hour day. Interpretation discrepancy rates between emergency physicians and radiologists were estimated to be 4% to 6%. The large amount of variation among hospitals in ED radiograph interpretation systems suggests that these systems were not designed with quality of care concerns as their primary criterion. As a consequence, objective patient outcome and process measures need to be developed and measured to ensure that a particular internal system for ED radiograph interpretation is providing an acceptably high standard of patient care.

Emergency Service, Hospital↗

Blast injuries from glass bottles containing dry ice.

We present three cases (two incidents) of severe blast injury from the explosion of covered glass bottles containing dry ice. The first patient sustained lacerations of the face, left eye, right wrist and forearm, and abdomen with protrusion of the small bowel. The second sustained a deep laceration to her anterior neck. The third sustained multiple lacerations to her lower extremities and one to the labia majora. All three patients were taken to the operating room for surgical exploration and repair and were discharged without complications.

Blast Injuries↗

Effect of renal impairment on the pharmacokinetics of cibenzoline.

Sixteen subjects completed an open-label study designed to assess the effect of renal impairment on the disposition of cibenzoline. The study included 10 patients with mild or moderate renal impairment creatinine clearance less than 60 ml/min/70 kg) and six healthy subjects in the same age range, each of whom received a single 130 mg oral dose of cibenzoline. The pharmacokinetic parameters observed in the healthy volunteers were similar to those reported previously. Maximum plasma concentration, time of maximum concentration, and apparent volume of distribution after single doses in patients with renal impairment were in the same range as those observed in healthy volunteers. The elimination half-life increased with decreasing renal function from a mean value of approximately 8 hours in healthy volunteers to more than 20 hours in patients with moderate renal impairment. Renal clearance and the fraction of the dose excreted unchanged in the urine decreased with decreasing creatinine clearance. The results of this study suggest that the dosage of cibenzoline should be reduced or the dosage interval increased in patients with reduced renal function to avoid excessive drug accumulation.

Administration, Oral↗