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Biomedical subjects

M L Bach

Publications and source records attributed to M L Bach.

At least 19 recordsLinked to original sources

Do morphological anomalies reflect chromosomal aneuploidies?: case report.

In cases of severe teratozoospermia, the current morphological criteria used to assess chromosomal status is insufficient for the selection of spermatozoa for intracytoplasmic sperm injection (ICSI). Case histories are reported of four patients presenting 100% teratozoospermia, and the integrity of their individual chromosomal statuses is determined using a three-colour fluorescence in-situ hybridization (FISH) technique. Patient 1 presented shortened flagella syndrome, patient 2 globozoospermia, patient 3 spermatozoa with irregular acrosomes, and patient 4 macrocephalic spermatozoa with associated multiple flagella. Three-colour FISH analysis using chromosome X, Y and 1-specific probes showed that approximately 95% of the spermatozoa analysed from patients 1, 2 and 3 presented X,1 and Y,1 signals, X,Y ratios and aneuploidy/diploidy rates comparable with those observed in normal controls. In contrast, patient 4 showed a highly elevated Y to X sex ratio and a highly elevated aneuploidy/diploidy rate. Three-colour FISH analysis thus demonstrates an increased incidence of chromosomal abnormalities in association with macrocephalic spermatozoa. Moreover, the analysis shows that in patients affected with either globozoospermia, shortened flagella syndrome or a condition of abnormal acrosomal spermatozoa, no association exists between chromosomal status and phenotype. Since these patients display normal haploid, sex chromosome and aneuploidy status, ICSI can be conceivably offered as a treatment for their infertility.

Abortion, Spontaneous↗

The uracil permease of Schizosaccharomyces pombe: a representative of a family of 10 transmembrane helix transporter proteins of yeasts.

The uracil permease gene of Schizosaccharomyces pombe was cloned and sequenced. The deduced protein sequence shares strong similarities with five open reading frames from Saccharomyces cerevisiae, namely the uracil permease encoded by the FUR4 gene, the allantoin permease encoded by DAL4, a putative uridine permease (YBL042C) and two unknown ORFs YOR071c and YLR237w. A topological model retaining ten transmembrane helices, based on predictions and on experimental data established for the uracil permease of S. cerevisiae by Galan and coworkers (1996), is discussed for the four closest proteins of this family of transporters. The sequence of the uracil permease gene of S. pombe has been deposited in the EMBL data bank under Accession Number X98696.

Amino Acid Sequence↗

Appropriate and necessary healthcare: new language for a new era.

Conceptual and language changes are necessary to accompany the paradigm shift from fee-for-service medicine to managed care. Medical necessity is an inadequate and ambiguous term defined differently by providers, payers, patients, and legislators. The attempt by legislators in Minnesota to develop a universal standard benefits set for healthcare services strikingly underscores the need to define relevant terminology to accompany the transition to managed care. We suggest the term appropriate and necessary healthcare as a state-of-the-art term for the new era of managed care.

Centers for Medicare and Medicaid Services, U.S.↗

Recovery of gene function by gene duplication in Saccharomyces cerevisiae.

A prototroph revertant (Rev9) selected from an ATCase- mutant of the URA2 gene containing three nonsense mutations was shown to contain two ATCase coding sequences. We cloned both ATCase coding areas to show that the duplicated locus (dl9) was the only functional one. Its size corresponded roughly to the second half of the URA2 wild-type gene. Sequence analysis of the 5' end of dl9 indicated that this duplicated sequence was inserted within the intergenic region close to the MRS3 gene and was transcribed from an unknown promoter divergently from the MRS3 gene. The event leading to the revertant strain Rev9 included a rearrangement that increased the size of chromosome X by about 60 kb. In agreement with such a rearrangement, recombination was undetectable in the vicinity of the locus dl9. Genetic mapping confirms that the MRS3 gene is 2 cM distal to the URA2 gene on the right arm of chromosome X.

Aspartate Carbamoyltransferase↗

Ethics and Medicaid: a new look at an old problem.

Recent proposals to reform Medicaid, driven primarily by the need for cost containment, rarely pay explicit attention to values. This paper presents the Medicaid Values Framework, the authors' interpretation of a set of societal ideals embodied in Title XIX of the Social Security Amendments of 1965. The Framework comprises seven interlocking values that are stratified into three interdependent tiers--access, quality, and equity. We use the access and equity tiers to analyze treatment of Aid to Families with Dependent Children (AFDC) and Supplemental Security Income (SSI) recipients under Medicaid. We document striking inequities in eligibility standards and in funding for the two groups--inequities that unexpectedly fail to translate into marked disparities in access to Medicaid. In conclusion, we comment on why the present inequities exist and why they are ethically unacceptable.

Aid to Families with Dependent Children↗

Cloning and expression of the OMP decarboxylase gene URA4 from Schizosaccharomyces pombe.

URA4, the gene coding for orotidine monophosphate decarboxylase (OMPdecase), has been cloned from the fission yeast by homologous complementation and restricted in an Escherichia coli-Schizosaccharomyces pombe (E. coli-S. pombe) replicative plasmid to a 1.76 kb HindIII fragment. This plasmid is maintained at a high copy number in S. pombe and allows OMPdecase expression in Saccharomyces cerevisiae (S. cerevisiae) as well as in E. coli. After characterisation by restriction mapping and Southern hybridisation, the cloned gene was used as a probe to measure URA4 transcription and to examine its regulation. Messenger RNA levels were measured by DNA/RNA filter-hybridisation with pulse labelled RNAs during 6-azauridine (6-AUR) inhibited growth in wild type and 6-AUR sensitive strains. We found that in S. pombe the OMP analogue 6-AUR does not regulate the level of OMPdecase formation as it does in S. cerevisiae but rather modifies the ratio of total polyA+ to polyA- RNAs in the cell. Based on these results and on corresponding enzyme activities this study demonstrates divergent pyrimidine pathway regulation in the two yeasts S. cerevisiae and S. pombe. Finally, we propose the use of the URA4 gene as a convenient selective marker for genetic engineering in S. pombe.

Carboxy-Lyases↗

Clinical evaluation of a new test of hemostasis: the Filter Bleeding Time.

The clinical value of a new in vitro test of hemostasis, which we have called Filter Bleeding Time (FBT), was determined in 59 patients referred because of a suspected bleeding disorder. FBT is based on the progressive slowing of the drop rate of citrated blood through a filter of woven Dacron under constant pressure as platelet aggregates occlude the filter. The value for FBT is defined as the time when the blood drop interval has reached 1 minute. The Mayo modification of the Ivy bleeding time (IBT) was performed in all patients; platelet response to ADP, collagen, epinephrine and arachidonate was performed in 24 patients. In 30 normal volunteers FBT measured 1-3 hr after venipuncture was 2.8 +/- 1.5 (means +/- 1SD) min. The FBT was prolonged in 3 of 3 patients with Glanzmann's thrombasthenia, 2 with disseminated intravascular coagulation, 1 with chronic lymphocytic leukemia, 1 with myelofibrosis, and 1 who had taken aspirin. In 6 patients FBT was prolonged while IBT was normal: 4 after taking aspirin, 2 with polycythemia vera. All 6 had reduced platelet aggregation (PA) to ADP (5 microM), collagen (2 mg/ml), epinephrine (5 microM) and/or arachidonate (1.7 mM). In 3 patients FBT was normal while IBT was abnormal: 1 with disseminated intravascular coagulation, 2 undiagnosed; 1 of these 3 had abnormal PA. Of 6 patients with von Willebrand's disease, FBT was prolonged in 5 and borderline in 1; IBT was prolonged in 3, normal in 1, and not done in 2 infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonic Acids↗

Ty1-promoted expression of aspartate transcarbamylase in the yeast Saccharomyces cerevisiae.

An entire copy of a Ty1 yeast transposon has been found inserted between two regions comprising the single transcriptional and translational URA2 units in yeast that code respectively for carbamylphosphate synthetase (CPSase) and aspartate transcarbamylase (ATCase). The mutant Rev 16 was obtained from an ATCase- strain blocked by multiple nonsense mutations in the proximal CPSase region and submitted to selective pressure for recovery of the enzyme activity coded by the distal part of the gene. The inserted Ty1 has one XhoI site in both delta elements, delimiting a 5.6 kb piece of DNA that shows a classical Ty1 restriction pattern. The orientation of this sequence in URA2 is the same as in the previously described examples in which Ty1 has positive effects on the expression of adjacent genes. In this case the Ty1 is situated more than 1 kb from the URA2 region in which ATCase structural mutants have been mapped. Nevertheless, transcription of the entire sequence distal to the Ty1 is restored and has become subject to mating-type control, leading to a weak enzyme activity. Our observations are in agreement with generally accepted ideas regarding the way in which Ty1 elements affect gene expression, and additionally, represent the first example of a Ty1 -promoted reinitiation occurring in the middle of a single transcription unit.

Aspartate Carbamoyltransferase↗

Evidence for transcriptional regulation of orotidine-5'-phosphate decarboxylase in yeast by hybridization of mRNA to the yeast structural gene cloned in Escherichia coli.

From a large population of strains of Escherichia coli carrying shear fragments of yeast (Saccharomyces cerevisiae) DNA attached by in vitro recombination to the plasmid vector pMB9, two hybrid plasmids were selected that relieve the pyrimidine requirement of nonreverting pyrF mutants of E. coli. An 1100-base-pair DNA fragment common to the two complementing plasmids was recloned into another plasmid vector, pBR322; these new hybrids retained the ability to specify orotidine-5'-phosphate decarboxylase (orotidine-5'-phosphate carboxy-lyase, EC 4.1.1.23) synthesis in E. coli. Evidence is presented that this common fragment is yeast DNA and thus apparently carried the structural information for yeast orotidine-5'-phosphate decarboxylase, the product of yeast gene ura3. A hybrid plasmid containing the 1100-base-pair fragment was used to measure levels of putative ura3 mRNA from yeast cultures labeled with [3H]adenine, ura3 mRNA was unstable with an apparent half-life of 10.5 min. Under different circumstances previously shown to alter the level of orotidine-5'-phosphate decarboxylase in yeast, a coordinate variation in proportion of labeled RNA complementary to the hybrid plasmid was found. These data support the hypothesis that regulation of the ura3 gene in yeast is at the level of transcription.

Carboxy-Lyases↗

Past, present, and future aspects of histocompatibility.

We have stressed problems attendant on studies of the MHC, ignoring non-HLA factors and their role in allograft immunity. Many other topics could have been chosen for discussion is any such overview; our selection reflects our own interests. We felt assured, however, that excellent coverage by our many colleagues of the diverse and varied aspects of histocompatibility not approached in this summary has allowed us this freedom.

Cells, Cultured↗

Pool-priming: A means of generating T lymphocytes cytotoxin to tumour or virus-infected cells.

It is proposed that cells cytotoxic for autologous or syngeneic tumour cells can be produced in vitro by sensitisation of lymphocytes to a pool of normal cells from 20 unrelated individuals. Restriction on molecules that can serve as cytotoxic determinants (C.D.), may explain why a random pool of cells from 20 people could present essentially all of the determinants (C.D.) may explain why a random pool of occur because of extensive cross-reactivity of antigens on tumour cells with normal alloantigens present in the stimulating pool.

Antigens, Neoplasm↗