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Biomedical subjects

S Brown

Publications and source records attributed to S Brown.

At least 361 records · Page 20Linked to original sources
PubMed1995

Phosphatidylinositol 3,4,5-trisphosphate is a substrate for the 75 kDa inositol polyphosphate 5-phosphatase and a novel 5-phosphatase which forms a complex with the p85/p110 form of phosphoinositide 3-kinase.

Agonist-stimulated production of phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3], is considered the primary output signal of activated phosphoinositide (PI) 3-kinase. The physiological targets of this novel phospholipid and the identity of enzymes involved in its metabolism have not yet been established. We report here the identification of two enzymes which hydrolyze the 5-position phosphate of PtdIns(3,4,5)P3, forming phosphatidylinositol (3,4)-bisphosphate. One of these enzymes is the 75 kDa inositol polyphosphate 5-phosphatase (75 kDa 5-phosphatase), which has previously been demonstrated to metabolize inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2]. We have identified a second PtdIns(3,4,5)P3 5-phosphatase in the cytosolic fraction of platelets, which forms a complex with the p85/p110 form of PI 3-kinase. This enzyme is immunologically and chromatographically distinct from the platelet 43 kDa and 75 kDa 5-phosphatases and is unique in that it removes the 5-position phosphate from PtdIns(3,4,5)P3, but does not metabolize PtdIns(4,5)P2, Ins(1,4,5)P3 or Ins(1,3,4,5)P4. These studies demonstrate the existence of multiple PtdIns(3,4,5)P3 5-phosphatases within the cell.

Amino Acid Sequence↗
PubMed1995

Maternal uniparental disomy of chromosome 2 in a baby with trisomy 2 mosaicism in amniotic fluid culture.

We describe the first case of a baby with maternal uniparental disomy of chromosome 2. Growth failure, hypothyroidism, and hyaline membrane disease were present at birth, and the first year of life was complicated by bronchopulmonary dysplasia. At age 14 months, motor and intellectual development were normal, but growth remained below the 10th centile. The baby was investigated for uniparental disomy because trisomy 2 mosaicism had been detected in a second trimester amniocentesis. This is the first reported case in which amniotic fluid chromosome mosaicism has been associated with uniparental disomy. Implications for prenatal diagnosis are considered.

Amniocentesis↗
PubMed1995

Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contribute to long-term engraftment after autologous transplantation.

We report here on a preliminary human autologous transplantation study of retroviral gene transfer to bone marrow (BM) and peripheral blood (PB)-derived CD34-enriched cells. Eleven patients with multiple myeloma or breast cancer had cyclophosphamide and filgrastim-mobilized PB cells CD34-enriched and transduced with a retroviral marking vector containing the neomycin resistance gene, and CD34-enriched BM cells transduced with a second marking vector also containing a neomycin resistance gene. After high-dose conditioning therapy, both transduced cell populations were reinfused and patients were followed over time for the presence of the marker gene and any adverse effects related to the gene-transfer procedure. All 10 evaluable patients had the marker gene detected at the time of engraftment, and 3 of 9 patients had persistence of the marker gene for greater than 18 months posttransplantation. The marker gene was detected in multiple lineages, including granulocytes, T cells, and B cells. The source of the marking was both the transduced PB graft and the BM graft, with a suggestion of better long-term marking originating from the PB graft. The steady-state levels of marking were low, with only 1:1000 to 1:10,000 cells positive. There was no toxicity noted, and patients did not develop detectable replication-competent helper virus at any time posttransplantation. These results suggest that mobilized PB cells may be preferable to BM for gene therapy applications and that progeny of mobilized peripheral blood cells can contribute long-term to engraftment of multiple lineages.

Antigens, CD↗
PubMed1995

An assessment of the antisense properties of RNase H-competent and steric-blocking oligomers.

The antisense activity and gene specificity of two classes of oligonucleotides (ONs) were directly compared in a highly controlled assay. One class of ONs has been proposed to act by targeting the degradation of specific RNAs through an RNase H-mediated mechanism and consists of C-5 propynyl pyrimidine phosphorothioate ONs (propyne-S-ON). The second class of antisense agents has been proposed to function by sterically blocking target RNA formation, transport or translation and includes sugar modified (2'-O-allyl) ONs and peptide nucleic acids (PNAs). Using a CV-1 cell based microinjection assay, we targeted antisense agents representing both classes to various cloned sequences localized within the SV40 large T antigen RNA. We determined the propyne-S-ON was the most potent and gene-specific agent of the two classes which likely reflected its ability to allow RNase H cleavage of its target. The PNA oligomer inhibited T Ag expression via an antisense mechanism, but was less effective than the propyne-S-ON; the lack of potency may have been due in part to the PNAs slow kinetics of RNA association. Interestingly, unlike the 2'-O-allyl ON, the antisense activity of the PNA was not restricted to the 5' untranslated region of the T Ag RNA. Based on these findings we conclude that PNAs could be effective antisense agents with additional chemical modification that will lead to more rapid association with their RNA target.

Allosteric Site↗
PubMed1995

Isolation of a full-length mitotic cyclin cDNA clone CycIIIMs from Medicago sativa: chromosomal mapping and expression.

Cyclins in association with the protein kinase p34cdc2 and related cyclin-dependent protein kinases (cdks) are key regulatory elements in controlling the cell division cycle. Here, we describe the identification and characterization of a full-length cDNA clone of alfalfa mitotic cyclin, termed CycIIIMs. Computer analysis of known plant cyclin gene sequences revealed that this cyclin belongs to the same structural group as the other known partial alfalfa cyclin sequences. Genetic segregation analysis based on DNA-DNA hybridization data showed that the CycIIIMs gene(s) locates in a single chromosomal region on linkage group 5 of the alfalfa genetic map between RFLP markers UO89A and CG13. The assignment of this cyclin to the mitotic cyclin class was based on its cDNA-derived sequence and its differential expression during G2/M cell cycle phase transition of a partially synchronized alfalfa cell culture. Sequence analysis indicated common motifs with both the A- and B-types of mitotic cyclins similarly to the newly described B3-type of animal cyclins.

Amino Acid Sequence↗
PubMed1995

Transperitoneal closure of the internal ring in incarcerated infantile inguinal hernias.

Over a 6-year period, 14 infants with a total of 16 inguinal hernias (IH) underwent transperitoneal closure of the internal ring (TPIR). This was performed through a minilaparotomy, using a purse-string suture placed around the internal ring from within. A difficult inguinal dissection of an edematous and friable spermatic cord was avoided. TPIR was performed for incarceration in 13 of the infants and for recurrence of the hernia within 24 hours of herniotomy in one. There were no intraoperative problems, and during follow-up there was no evidence of testicular atrophy or recurrence of the hernia. This suggests that TPIR is a reliable and safe operation in babies for whom the alternative inguinal approach would be difficult. These situations include hernias that are irreducible and early recurrence in which dissection of the cord would risk damage to the vas deferens or testicular vessels.

Constriction, Pathologic↗
PubMed1995

Expression of alkaline phosphatase by a B-cell hybridoma and its modulation during cell growth and apoptosis.

The 7TD1 B-cell hybridoma was found to spontaneously express alkaline phosphatase (ALP), an enzyme which is produced by splenic B lymphocytes once optimally activated. Determination of ALP levels during cell growth and departure to apoptosis showed fluctuations. Following a temporary increase within the first 24 h, enzyme expression was maintained at high levels during the early proliferation stage, and then declined from 3 to 4 days in mid-exponential phase to basal levels at day 6 when living cells were no longer detectable and the apoptotic process was completed. The protein synthesis inhibitor, cycloheximide (1 microg/ml), decreased ALP production while stimulating a strong apoptosis of 7TD1 cells, within 4 h. Aphidicolin (1 microg/ml) maintained ALP production and provoked a release of ALP activity into the surrounding medium; it also induced apoptosis, but with a 24 h delay. Quantification of apoptosis and ALP expression by flow cytometry, after simultaneous staining of DNA with Hoechst 33342 and ALP with naphthol AS-TR phosphate/Fast Red RC fluorescent reagent, revealed cell cycle modulation of ALP expression, its activity increasing as 7TD1 cells progressed from G1 phase into S and G2/M phases of the cell cycle in control as well as in drug-treated cells. Kinetics of drug-induced apoptosis and higher expression of ALP associated preferentially with active cell growth during the prevention stage of apoptosis suggested a possible link between cellular ALP expression and cell survival.

Alkaline Phosphatase↗
PubMed1995

Women's experiences of rheumatoid arthritis.

This paper is based on findings drawn from research undertaken within a qualitative framework of analysis. The purpose of the research was to explore women's experiences of rheumatoid arthritis. Three areas of concern to the women are identified and discussed in the light of relevant literature. They are as follows: seeking help, searching for meaning and uncertainty about symptoms. A major theoretical concern of both authors is to demonstrate the importance of placing patients' personal accounts of their experiences and understandings at the centre of nursing interest and practice. It is argued that there is a need to develop research studies of how patients experience disease, in order to develop a basis for good practice.

Arthritis, Rheumatoid↗
PubMed1995

Treatment of ectoparasitic infections: review of the English-language literature, 1982-1992.

We reviewed the English-language literature of 1982-1992 for papers concerning scabies, pediculosis, and their treatments; this information was supplemented with opinions of workers in the field of ectoparasitic disease. Six treatment trials for scabies, one study of the treatment of pediculosis pubis, and additional studies on the treatment of pediculosis capitis were included. Both lindane 1% and permethrin 5% are effective treatments for scabies, although resistance to lindane does exist. Lindane 1%, permethrin 1%, and pyrethrins with piperonyl butoxide are all effective treatments for pediculosis. Severe reactions to lindane therapy may occur when increased skin absorption of lindane occurs. Permethrin 5% or lindane 1% is recommended for the treatment of scabies. Lindane should be used with precautions to avoid excess skin penetration and should not be used to treat infants, young children, or pregnant or lactating women. Permethrin 1%, lindane 1%, or pyrethrins with piperonyl butoxide is recommended for the treatment of pediculosis pubis. Pregnant and lactating women should be treated with either permethrin or with pyrethrins containing piperonyl butoxide.

Adult↗
PubMed1995

Psychiatric morbidity associated with acquired immune deficiency syndrome-related grief resolution.

This study examined acquired immune deficiency syndrome (AIDS)-related grief resolution and psychiatric morbidity in 286 human immunodeficiency virus (HIV)-positive and HIV-negative gay men examined between 1989 and 1993 in San Diego, CA. Psychiatric morbidity, mood ratings, and bereavement assessments were obtained using the Structured Clinical Interview for DSM-III-R, Hamilton Rating Scales for Depression and Anxiety, and Texas Revised Inventory of Grief. Sixty percent of the men (N = 171) reported a loss within the previous 12 months. Eighteen percent of the bereaved met criteria for unresolved grief. No differences were evident in lifetime psychiatric disorders, yet men with unresolved grief demonstrated an elevated prevalence of current major depression and panic disorder when compared with resolved grievers. Clinician sensitivity to the grief process and its relationship to psychiatric complications is an important component of comprehensive psychiatric and medical care of men at high risk for HIV during this era of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1995

The feminization of the medical profession in Israel.

Two factors have caused major changes in the gender composition of the Israeli medical profession in recent years: (i) a wave of immigration from the former USSR, which increased the doctor population by approximately 70% and which included a majority of women physicians, and (ii) the entry of more Israeli women into medical school. This report presents the current gender status of the Israeli medical profession, regarding students and physicians, and the choice of medical specialty and academic seniority, and compares gender differences in Israel with those in other countries. Traditional patterns of specialization persist in Israel, with women still concentrated in primary care (family medicine, paediatrics and psychiatry). In addition, women still face obstacles in entering the more prestigious (mainly surgical) specialties. Whilst the number of women in academic medicine has increased over the last decade, women are still concentrated in the lowest echelons of academic medicine. However, the steady trend towards the feminization of medicine will inevitably lead to an increase of women in all areas of the medical profession. Because cross-cultural studies have repeatedly revealed that women doctors have a more humanistic and personalized approach to patient care, a higher ratio of women in the profession should have a qualitative effect in this direction, despite the bureaucratic and fiscal constraints incumbent upon practising doctors. As more women become role models for medical students, their approach will influence the education of the doctors of the future.

Career Choice↗