Search PubMed⌕ Search

Biomedical subjects

M Rose

Publications and source records attributed to M Rose.

At least 235 records · Page 13Linked to original sources

Structure and function of the yeast URA3 gene. Differentially regulated expression of hybrid beta-galactosidase from overlapping coding sequences in yeast.

Expression of the URA3 gene of Saccharomyces cerevisiae was studied by analysis of URA3-lacZ gene fusions constructed in vitro. Synthesis of hybrid beta-galactosidase by fusions in frame with the coding sequence for orotidine-5'-phosphate decarboxylase (OMPdecarboxylase) was found to be normally regulated even when only 11 nucleotides of URA3 coding sequence remained, indicating that all transcription initiation and regulatory sites are present at the beginning of the URA3 gene. An upstream initiator codon that begins a short overlapping coding sequence in another reading frame was also found to be active in producing hybrid beta-galactosidase. However this beta-galactosidase synthesis showed little or no regulation. Nuclease protection experiments revealed numerous species of URA3 mRNA. The regulation of these is consistent with the idea that the URA3 protein and the overlapping peptide are translated from differentially regulated mRNAs of different lengths.

Base Sequence↗

A comparison of antithrombin III procedures.

Antithrombin III (AT III) is the most potent physiologic inactivator of thrombin and other serine proteases in the blood clotting mechanism. Hereditary deficiency of this protein is associated with recurrent deep-vein thrombosis that begins in late adolescence. Untreated, this disease may lead to early death from recurrent and massive pulmonary emboli. Attempts to identify groups of patients who are the most likely to develop thromboembolic disease because of an acquired deficiency of AT III have been frustrated by the lack of standardization of the assays and the inability to compare results of the different AT III assays. The functional assays and immunoelectrophoretic determinations do not measure the same component. In order to compare the ability of current AT III procedures to determine levels of AT III in various disease states, we used immunoelectrophoretic, chromogenic, and clottable assays to measure the AT III of patients with congenital AT III deficiency and of patients with possible acquired AT III deficiency.

Antithrombin III↗

Adult T-cell lymphoma-leukaemia in Blacks from the West Indies.

Six Black patients (five born in the West Indies and one in Guyana), aged 21-55 years, had adult T-cell lymphoma-leukaemia diagnosed in the U.K. This disorder is rare in Europe and the U.S.A., but is more common in Japan. Five patients had severe hypercalcaemia which correlated with disease activity, although osteolytic lesions were found in only one. Other clinical features were lymphadenopathy and a high white blood-cell count (range 27-67 X 10(9)/l) with a predominance of pleomorphic lymphoid cells with pronounced nuclear irregularities prominent at ultrastructural level. The cells in all cases formed rosettes with sheep red blood-cells and lacked terminal transferase. Analysis with OKT monoclonal antibodies in four cases confirmed a mature T-cell phenotype defined as helper/inducer (T4+, T6-, T8-) in three. Combination chemotherapy resulted in short-lived remissions; four patients died and two have survived 3-6 months. The disease in these patients is indistinguishable on clinical and pathological grounds from adult T-cell leukaemia/lymphoma in Japan. Geographical clustering among certain racial groups suggests common aetiological factors in the pathogenesis of this disease. The finding of high titre antibody against the structural core protein (p24) of a new human C-type leukaemia virus (human T-cell leukaemia/lymphoma virus) in all tested cases from this series and data from all but one case from Japan suggest that one such factor may be viral.

Adult↗

Factors influencing hepatic glutathione concentrations: a study in surgical patients.

1. Hepatic total glutathione (reduced plus oxidized) and oxidized glutathione levels were measured in operative wedge liver biopsy specimens obtained from 70 patients. 2. The effects on hepatic reduced glutathione (GSH) level of four potential risk factors (abnormal liver histology, abnormal preoperative tests fo liver function, drug ingestion and protein malnutrition) were examined. 3. Each of the four risk factors was associated with a significant reduction in hepatic GSH. Multivariate analysis indicated that only three of these risk factors (abnormal liver histology, drug ingestion and protein malnutrition) had independent effects in reducing hepatic GSH. 4. Twenty-five of the 70 patients studied did not have any of the four risk factors. The mean hepatic GSH level in these patients was 3.92 mumol/g of liver wet weight (SD 0.62), giving a 95% reference range of 2.71-5.14 mumol/g of liver net weight.

Adolescent↗

Leukaemia of platelet precursors: diverse features in four cases.

Four patients are described with malignant cells of definite or probable megakaryocytic lineage in the bone marrow and blood. Megakaryocytic features were defined by morphological and cytochemical studies using light and electron microscopy, and in two cases by reaction with a monoclonal anti-platelet antibody, AN51. All patients had increased bone-marrow reticulin, which developed in less than 15 months in two cases. One of these fitted the clinical pattern of acute myelosclerosis of Lewis and Szur (now widely referred to as acute megakaryoblastic leukaemia). Three cases had unique clinical features which are described in detail. There may be several variants of megakaryocytic leukaemia, including chronic forms. One variant is associated with Down's syndrome (trisomy 21).

Adult↗

Regulation of HIS4-lacZ fusions in Saccharomyces cerevisiae.

The beginning of the Saccharomyces cerevisiae HIS4 gene has been fused to the structural gene for Escherichia coli beta-galactosidase. This construction, which contains HIS4 DNA from -732 to +30 relative to the translation initiation codon, has been integrated into the yeast genome at two chromosomal locations, HIS4 and URA3. At both locations, this 762-base-pair stretch of DNA is sufficient for initiating expression of beta-galactosidase activity in S. cerevisiae and confers upon this activity the regulatory response normally found for HIS4.

Base Sequence↗

[HLA antibodies in retroplacental blood samples. I. Preliminary results of a screening study].

Retroplacental blood samples (between 3 ml and 290 ml) which had been obtained from 327 recently delivered women were tested for the presence of HLA-A, B, C, DR antibodies. The approaches taken by the examiners were the NIH microlymphocytotoxicity test according to Terasaki and the two-colour fluorescence test according to van Rood. The examiners established 66 sera with cytotoxic reactions, and 18 of these serum samples (5.5 per cent) contained good to very good antibodies of the HLA-A, B, C, and DR series (correlation coefficients being between 0.55 and 1.00). Advantages offered by this search test over conventional pregnancy screening are discussed in some detail.

Antibodies↗

Yeast genes fused to beta-galactosidase in Escherichia coli can be expressed normally in yeast.

A plasmid was constructed that allows the selection in vivo of gene fusions between the Escherichia coli beta-galactosidase gene and the yeast (Saccharomyces cerevisiae) URA3 gene. A large yeast DNA fragment containing the URA3 gene was placed upstream of an amino-terminally deleted version of the lacZ gene. The plasmid vehicle contains sequences that allow selection and maintenance of the plasmid in both yeast and E. coli. Selection for Lac+ in E. coli yielded numerous deletions that fused the lacZ gene to the URA3 gene and flanking yeast sequences, to the bacterial tetracycline-resistance gene from the parent plasmid pBR322, and to the yeast 2-micrometer plasmid DNA. Some of these fusion plasmids produced beta-galactosidase activity when introduced into yeast. One of the fusions to the URA3 gene itself has been shown to place the expression of beta-galactosidase activity under uracil regulation in yeasts.

Escherichia coli↗

The role of visual and haptic cues in children's discrimination learning.

Three experiments using kindergarten boys and girls (Ns = 126, 84, and 72, respectively) tested the hypothesis that adding haptic to visual information facilitates discrimination of three-dimensional objects on more difficult (three-choice) problems, but not on easier (two-choice) problems. Kindergartners were given a two-or three-choice discrimination problem under one of four conditions of cue availability: visual cues, haptic cues, and visual plus haptic cues with stimuli touched or not touched before choosing. Addition of haptic cues did not improve performance either on two-choice problems (two or three experiments), as predicted, or on three-choice problems (all three experiments), contrary to predictions.

Child, Preschool↗

A test of evolutionary theories of senescence.

Senescence is the post-maturation decline in survivorship and fecundity that accompanies advancing age. Two main evolutionary theories have been proposed to account for senescence. (1) The mutation-accumulation theory. Deleterious mutations exerting their effects only late in life would tend to accumulate, because of their minimal effects on fitness. More precisely, exclusively late-acting deleterious mutations will attain higher equilibrium frequencies under mutation--selection balance than will mutations that act early, resulting in lower mean values for fitness components late in life (ref. 3, p. 218). Medawar emphasized the possibility that this effect would be enhanced by selection of modifiers that postpone the age of onset of genetic diseases. (2) The pleiotropy theory. Williams suggested that many of the genes with beneficial effects on early fitness components have pleiotropic deleterious effects on late fitness components, but are nevertheless favoured by natural selection. (These theories are based on the decline with age in the effect of age-specific fitness-component changes on total fitness (ref. 3, pp. 206--214 and refs 4, 5). Either or both of these theories could apply in any particular population.) Selection experiments in Drosophila and Tribolium support the pleiotropy theory, although one such experiment gave results that only bordered on significance, but the mutation--accumulation theory has never been tested. The present results provide evidence for the pleiotropy theory, but do not support the mutation--accumulation theory.

Aging↗