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Biomedical subjects

M Gorman

Publications and source records attributed to M Gorman.

At least 55 records · Page 3Linked to original sources
PubMed1994

How flies make one equal two: dosage compensation in Drosophila.

Dosage compensation is the process by which the expression of X-linked genes is equalized in males and females. In Drosophila, dosage compensation occurs by coordinately upregulating the transcription rates of all the genes on the single X chromosome in males. This hypertranscription requires the functioning of four autosomal male-specific lethal (msl) genes and is under the control of the Sxl gene. Recent genetic and molecular studies have suggested that the msl proteins may associate with one another in a sex-specific heteromeric complex on the male X chromosome, where they may function to alter its chromatin structure.

Animals↗
PubMed1994

Thermosensitive mutants of Aspergillus awamori glucoamylase by random mutagenesis: inactivation kinetics and structural interpretation.

Seven thermosensitive glucoamylase mutants generated by random mutagenesis and expressed in Saccharomyces cerevisiae were sequenced and their inactivation kinetics were determined. Wild-type glucoamylase expressed in S. cerevisiae was more glycosylated and more stable than the native Aspergillus niger enzyme. All mutants had lower free energies of inactivation than wild-type glucoamylase. In the Ala39-->Val, Ala302-->Val and Leu410-->Phe mutants, small hydrophobic residues were replaced by larger ones, showing that increases in size and hydrophobicity of residues included in hydrophobic clusters were destabilizing. The Gly396-->Ser and Gly407-->Asp mutants had very flexible residues replaced by more rigid ones, and this probably induced changes in the backbone conformation that destabilized the protein. The Pro128-->Ser mutation changed a rigid residue in an alpha-helix to a more flexible one, and destabilized the protein by increasing the entropy of the unfolded state. The Ala residue in the Ala442-->Thr mutation is in the highly O-glycosylated region surrounded by hydrophilic residues, where it may be a hydrophobic anchor linking the O-glycosylated arm to the catalytic core. It was replaced by a residue that potentially is O-glycosylated. In five of the seven mutations, residues that were part of hydrophobic microdomains were changed, confirming the importance of the latter in protein stability and structure.

Amino Acid Sequence↗
PubMed1994

First example of Rh:-32,-46 red cell phenotype.

The red cells of a white male blood donor typed as Rh:-1, -2, -3,w4,w5,6,-17,w19,-31,-32,-34, and -46. Although the donor has no history of transfusion, his serum contains an alloantibody that is weakly reactive with most red blood cells (RBCs) tested. Only Rhnull and D-- RBCs are nonreactive. Reactivity is enhanced with ficin- or papain-treated RBCs and is unaffected by AET or DTT treatment of the RBCs. Previously described Rh:-46 RBCs have been of deletion types D--, D, and Rhnull, or Rh:32. In three multitransfused patients, the Rh46 antigen was temporarily suppressed and the phenotype eventually reverted to normal. This is the first report of RBCs of the Rh:-32,-46 phenotype that are not of a rare Rh deletion or Rhnull type. In addition, the Rh:w5,w19,-31,-34 phenotype is rarely found in whites.

Journal Article↗
PubMed1993

Regulation of the sex-specific binding of the maleless dosage compensation protein to the male X chromosome in Drosophila.

In Drosophila, the single male X chromosome is transcribed at twice the rate of a single female X chromosome. This hypertranscription requires the functions of at least four autosomal male-specific lethal genes (msls) and is under the control of the Sex-lethal (Sxl) gene. One of the msls, the maleless (mle) gene, encodes a protein that is associated with the male X chromosome. To investigate how dosage compensation is regulated, we have determined whether Sxl and the other msls are required for mle X chromosome binding. We have found that in females, Sxl functions to prevent mle from binding to the two X chromosomes. Additionally, we have found that mle X chromosome binding requires wild-type msl1, msl2, and msl3 functions. These data support a model whereby the activity of the mle protein is regulated through its association with one or more of the other msl proteins.

Animals↗
PubMed1991

Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells.

In this report we describe the biochemical characterization of neutrophil and monocyte p8 and p14. Together the two proteins comprise approximately 45% of cytosolic protein in neutrophils and approximately 40-fold less in monocytes. They fractionated together in several chromatographic procedures and were found to exist as a noncovalently associated complex with a stoichiometry of 1:1, named p8,14. Cross-linking experiments showed p8,14 to form heterodimers under conditions simulating the cytosol. An apparent molecular mass of 35,000 daltons was obtained for the p8,14 complex in molecular sizing experiments which suggests the presence of modifications or distinctive structural features. Two major forms of p14 can be identified by two-dimensional gel electrophoresis, both of which form heterodimers with p8. The lower molecular weight variant of p14 lacks Cys-3 (Met-Thr-Cys-Lys-Met...) suggesting that differing translational start sites account for these two forms of p14. A protocol has been devised for the rapid purification of milligram quantities of p8 and p14 from neutrophil cytosol using fast-protein liquid chromatography.

Blotting, Western↗
PubMed1991

Exposure to phenothiazine drugs and risk of cataract.

Clinical reports have indicated an increased risk of ocular opacities in users of phenothiazine drugs, and some recent epidemiologic studies have found an association between cataract and a history of tranquilizer use. To examine the effects of major tranquilizers (phenothiazines and haloperidol) on the risk of cataract extraction, while controlling for suspected risk factors such as diabetes and steroid use, a matched cohort study was performed using information from a large health maintenance organization in Seattle, Wash. The use of either antipsychotic or other phenothiazine drugs increased the risk of cataract extraction by roughly 3.5 times in individuals who were both current users and were exposed some time in the 2 to 5 years prior to their extraction. Risk was also increased in individuals with prior use of antidiabetic agents, systemic steroids, and benzodiazepines. Contrary to some prior reports, there was no elevated risk associated with use of antihypertensives, and there was no protective effect for aspirin, acetaminophen, or ibuprofen.

Aged↗
PubMed1989

State policies and the financing of acquired immunodeficiency syndrome care.

State policies, with respect to the operation of Medicaid programs and the regulation of private health insurance, affect who gets what care, how much is spent, and who ultimately pays. A RAND Corporation study was used to assess States and the District of Columbia in terms of the effects of their Medicaid and health insurance regulations on people with acquired immunodeficiency syndrome and other human immunodeficiency virus-related illnesses. State characteristics are used to explain the individual State policy rankings.

Acquired Immunodeficiency Syndrome↗
PubMed1989

A case report: unusual Gerbich antibody in a patient with sickle cell anemia.

A patient whose red blood cells (RBCs) typed as Ge:2,3 produced an alloantibody to a high-frequency antigen in the Gerbich system. This antibody was shown to be nonreactive with Ge:-2,-3 KBCs using adsorption-elution studies. A monocyte monolayer assay (MMA) suggested that transfusion of Ge:2,3 KBCs to this patient would have reduced in vivo survival.

Journal Article↗
PubMed1988

The sex-determining gene tra-2 of Drosophila encodes a putative RNA binding protein.

The gene transformer-2 (tra-2) of Drosophila is necessary not only for female sexual differentiation but also for normal spermatogenesis in males. We have cloned and characterized the tra-2 gene. Its putative protein has a domain that is homologous to RNA binding proteins. This suggests that the tra-2 protein might achieve the female-specific splicing of the transcript of dsx, a sex-determining gene whose mode of expression depends on tra-2. The protein coding region of the tra-2 transcript is identical in males and females. In both sexes, a low level of transcript is present in the soma and a high level in the germ line. This indicates that tra-2 is regulated in a way different from other sex-determining genes.

Animals↗
PubMed1986

Preoperative prediction of hyphemas.

In a prospective study, 139 patients undergoing cataract extraction were evaluated preoperatively with a panel of coagulation studies: prothrombin time, partial thromboplastin time, platelet count, and total bleeding time. Patients were monitored postoperatively for the presence of a hyphema which was then correlated with the test results. There was an overall incidence of 10.8% hyphemas in the population, and a statistically significant correlation was revealed with abnormal test results only if all the tests were considered together.

Bleeding Time↗
PubMed1985

The isolation of nuclear envelopes. Effects of thiol-group oxidation and of calcium ions.

The effects of (a) oxidative cross-linking of protein thiol groups and (b) the presence or absence of Ca2+ ions on rat liver nuclear-envelope isolation were studied. Two envelope-isolation procedures were compared: a well characterized low-ionic-strength method and a recently developed high-ionic-strength method. The latter method seems preferable to the former in respect of lower intranuclear contamination of the envelopes, suppression of endogenous serine proteinase, and maintenance of high specific activities of envelope-associated enzymes. In both procedures, however, the presence of Ca2+ gave rise to a rapid, apparently irreversible, contamination of the envelopes by intranuclear material. This effect was half-maximal at 20 microM-Ca2+. In addition, the envelopes became contaminated with intranuclear material by a Ca2+-independent mechanism, apparently resulting from N-ethylmaleimide-sensitive intermolecular disulphide-bond formation. This oxidative process seemed to have two major kinetic components (half-life, t1/2, approx. 2 min and 10 min). In view of these findings, it is recommended that (i) for most purposes, nuclear envelopes be isolated by the newly developed high-ionic-strength procedure, (ii) irrespective of the method used, Ca2+-chelators be included in all the buffers, (iii) thiol-group oxidation be prevented or reversed during the procedure.

Animals↗
PubMed1985

Calvarial grafts for midface rehabilitation.

Access, pain, prolonged hospitalization, or inadequacy of consistency and quantity of a graft are drawbacks to traditional donor sites of autologous bone for reconstruction of severe midface trauma with bone loss. The sectioning of human skulls resulted in selection of the parietal bone as a technically feasible donor site for obtaining adequate autologous bone for the rehabilitation of generous defects in the floor of the orbit or the anterior maxillary wall. The examination of various animal skulls resulted in the selection of the large canine as an adequate experimental model to evaluate the technique. The parietal bone served as a harvest site, without morbidity, for autologous bone used to fill in the defects in the orbit and anterior malar wall in the live canine model. Subsequently, human autografts of outer cranial table parietal bone provided adequate material to repair severe floor of orbit and maxillary defects with minimal patient discomfort and donor site morbidity.

Adult↗