PubMed Health⌕ Search

Biomedical subjects

A Jacob

Publications and source records attributed to A Jacob.

At least 73 records · Page 4Linked to original sources
PubMed1995

Molecular cloning and expression pattern of genes from a 470 Kb region near BRCA1 locus on chromosome 17q21.

We have used direct cDNA selection to isolate expressed sequences from a set of four overlapping YACs, spanning approximately 470 kb of the chromosomal interval 17q21 centromeric to BRCA1 gene. Thirty-eight nonoverlapping unique cDNA fragments were identified in this region. Twenty-two of the selected cDNAs showed complete identity with known genes and expressed sequence tags. Two of these cDNAs shared sequence homology with genes known to encode potential DNA binding motifs and hence could function in transcriptional regulation. The remaining 16 unique cDNA fragments showed no significant similarity to sequences in the databases and could potentially encode novel genes. Northern analysis of the novel cDNAs showed differential expression in various tissues, supporting the transcribed nature of these sequences. Our results place the gene for a G-protein coupled receptor (GPR2) previously mapped to 17q within a 400 kb region on 17q21.

BRCA1 Protein↗
PubMed1994

Retinoic acid-mediated activation of HNF-3 alpha during EC stem cell differentiation.

We present evidence demonstrating that the liver-enriched transcription factor HNF-3 alpha is activated upon retinoic acid-induced differentiation of mouse F9 embryonal carcinoma cells. We have detected increases in the DNA binding activity and mRNA level of HNF-3 alpha. Both are reflections of the actual activation mechanism at the level of transcriptional initiation, which we showed with the help of HNF-3 alpha promoter constructs. Time course studies clearly show that HNF-3 alpha activation is a transient event. Employing Northern blots, HNF-3 alpha mRNA can be detected between 16 and 24 hours post-differentiation, reaches its zenith at approximately 1 day, and then declines to virtually undetectable levels. F9 cells can give rise to three distinct differentiated cell types; visceral endoderm, parietal endoderm, and primitive endoderm. We have clearly shown that HNF-3 alpha stimulation occurs upon primitive endoderm formation. In addition, the transcription factor is also activated during the induction of cell lineages that give rise to parietal and visceral endoderm. HNF-3 alpha stimulation upon visceral endoderm differentiation is accompanied by the activation of HNF-3 target genes such as transthyretin, suggesting that HNF-3 alpha is involved in the developmental activation of this gene. In contrast, HNF-3 alpha target genes in parietal and primitive endoderm have yet to be identified. However, the stimulation of HNF-3 alpha during primitive endoderm formation, which is an extremely early event during murine embryogenesis, points towards a role for the factor in crucial determination processes that occur early during development.

Animals↗
PubMed1994

Delayed activation of HNF-3 beta upon retinoic acid-induced teratocarcinoma cell differentiation.

We have investigated the retinoic acid-mediated activation of the transcriptional regulator HNF-3 beta during differentiation of mouse F9 embryonal carcinoma cells. Using gel shifts, HNF-3 beta DNA binding activity was clearly detected in differentiated cells, while F9 stem cells were devoid of this activity. We also demonstrated that HNF-3 beta mRNA is specific for differentiated cells. Addition of retinoic acid to F9 stem cells results in delayed activation of HNF-3 beta mRNA which can be detected 1-2 days after the initiation of differentiation. HNF-3 beta mRNA concentrations are maximal at approximately 4 days postdifferentiation and stay at elevated levels for at least 4 additional days. Nuclear run-on experiments clearly show that HNF-3 beta is activated at the level of transcriptional initiation, suggesting that the increases of beta-specific DNA binding activity and mRNA concentration are merely a reflection of this activation mechanism. F9 cells can give rise to three distinct differentiated cell types, visceral endoderm, parietal endoderm, and primitive endoderm, and we have observed HNF-3 beta stimulation during the formation of all three tissues. HNF-3 beta stimulation upon visceral endoderm differentiation is accompanied by the activation of HNF-3 target genes such as transthyretin, suggesting that HNF-3 beta is involved in the developmental activation of this gene. In contrast, HNF-3 beta target genes in parietal and primitive endoderm have yet to be identified. However, the stimulation of HNF-3 beta during primitive endoderm formation, which is an extremely early event during murine embryogenesis, points toward a role for the factor in crucial determination processes that occur early during development.

Animals↗
PubMed1994

Randomized controlled trial of oral captopril, of oral isosorbide mononitrate and of intravenous magnesium sulphate started early in acute myocardial infarction: safety and haemodynamic effects. ISIS-4 (Fourth International Study of Infarct Survival) Pilot Study Investigators.

The purpose of this randomized controlled study was to assess the haemodynamic effects, safety and tolerability in acute myocardial infarction (AMI) of one month of oral captopril, one month of oral isosorbide mononitrate and 24 h of intravenous magnesium. It was carried out in four United Kingdom and six Polish hospitals in consecutive phases: oral captopril vs oral mononitrate vs placebo were compared among 400 patients in a 'three-way' study; and then oral captopril vs placebo and oral mononitrate vs placebo were compared among 474 patients in '2 x 2' and '2 x 2 x 2' factorial studies (with 208 patients in the latter study also randomized between intravenous magnesium and open control). The factorial studies differed from the three-way study in that one group of patients was allocated both oral captopril and oral mononitrate, a higher maintenance dose of captopril was used (following the same initial dose), and once daily controlled-release mononitrate was used. In the three-way study, the mean of the lowest systolic blood pressures recorded during the first 4 h after randomization were (mmHg +/- standard error): 104 +/- 2 captopril vs 105 +/- 1 mononitrate vs 112 +/- 2 placebo (P < 0.001 for captopril or for mononitrate vs placebo), and in the factorial studies were 105 +/- 1 captopril vs 110 +/- 1 placebo (P < 0.01) and 106 +/- 1 mononitrate vs 108 +/- 1 placebo (NS). There was an excess of hypotension recorded among patients allocated active treatment (captopril > mononitrate > placebo) and there was a small, but significant, excess of cardiogenic shock with captopril compared with control in the factorial study. However, in these studies, neither captopril nor mononitrate were associated with any overall increase in the incidence of hypotension considered severe enough to lead to treatment being stopped. No other serious complications were observed, and compliance with study tablets at hospital discharge was not significantly different between the active and placebo groups. Patients allocated magnesium in the 2 x 2 x 2 factorial study had a slightly lower mean systolic blood pressure just after the initial 15 min bolus injection (126 +/- 2 magnesium vs 134 +/- 3 control; P < 0.05) but there were no significant differences during the subsequent 24 h maintenance infusion period. Apart from some facial flushing, magnesium did not appear to be associated with any complications.(ABSTRACT TRUNCATED AT 400 WORDS)

Captopril↗
PubMed1994

Chronic granulocytic leukaemia presenting with an extramedullary T lymphoblastic crisis.

A 33-year-old man presented with hepatosplenomegaly and lymphadenopathy. Bone marrow findings were consistent with Philadelphia-positive accelerated-phase chronic granulocytic leukaemia (CGL). Lymph node histology and immunhistochemistry were diagnostic of T lymphoblastic lymphoma. Molecular studies on lymph node DNA identified rearrangement within the major breakpoint cluster region (M-bcr), indicating a common clonal origin of CGL and the T lymphoblastic lymphoma. We report the second case where extramedullary T lymphoblastic crisis was the presenting feature of CGL.

Adult↗
PubMed1993

Inhibition of viral growth by an alpha-oligonucleotide directed to the splice junction of herpes simplex virus type-1 immediate-early pre-mRNA species 22 and 47.

A 13-residue alpha-anomeric oligonucleotide [alpha-5'-d(GGGCGTCCTCCTT)3'], 5'-substituted with a psoralen derivative, Pso-alpha-13 psoralen linked to the 5' end of an alpha-anomeric n-residue oligonucleotide, was targeted to the acceptor splice junction of Herpes simplex virus type-1 immediate-early pre-mRNA species 22 and 47. Inhibition of viral growth was observed upon irradiation of Vero cells infected with Herpes simplex virus type-1 and treatment with Pso-alpha-13. The virus titer was decreased by 80% at an oligonucleotide concentration of 0.5 microM and at a multiplicity of infection of 0.1 plaque-forming units/cell. The 13-residue oligonucleotide did not induce any cytotoxic effect after irradiation and the inhibition of viral growth was clearly sequence specific. A non-specific 5' Pso-alpha-15 did not inhibit Herpes simplex virus type-1 growth. The 5' Pso-alpha-13 targeted to the acceptor splice junction of Herpes simplex virus type 1, contained five mismatches with respect to the corresponding sequence of Herpes simplex virus type 2, and did not exhibit any inhibitory effects on Herpes simplex virus type-2 growth. These results show that alpha-oligonucleotides can exhibit a sequence-specific antiviral effect and suggest that they may inhibit splicing reactions and be useful in targeting specific nucleic acid sequences within the cell nucleus.

Animals↗
PubMed1993

Coxiella burnetii infection among subjects infected with HIV type 1 in the Central African Republic.

Sixty-six sera from HIV-1-seropositive adult African subjects and 49 sera from HIV-seronegative age and sex matched healthy African controls living in Bangui, Central African Republic, were screened for Coxiella burnetii antibody by an indirect immunofluorescent antibody test. 16.7% of HIV-infected patients and 16.3% of the HIV-negative controls had positive IgG titres, with no significant difference between the two groups. Two of the seven HIV-infected patients seropositive for Coxiella burnetii for whom clinical data was available had a medical history compatible with symptomatic Q fever. These findings indicate that there is a high degree of exposure to Coxiella burnetii infection in Bangui. In individuals co-infected with HIV and Coxiella burnetii, cellular immunosuppression could favour symptomatic Q fever. Physicians should be aware of the possibility of symptomatic Coxiella burnetii infection among HIV-infected people, particularly in endemic regions for both infections such as in sub-saharan Africa.

AIDS-Related Opportunistic Infections↗
PubMed1993

Identification of the flagellar antigens of Vibrio cholerae El Tor and their role in protection.

Antiserum to the surface antigens of the wild-type flagellate strain KB207 of Vibrio cholerae El Tor was absorbed with isogenic aflagellate mutant CD12. Antibodies remaining in the absorbed serum exhibited specificity to KB207 but not to CD12 and inhibited motility of KB207. Proteins from cell-free lysates of KB207 and CD12 were analysed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. CD12 differed from KB207 in the absence of two proteins of 40 and 38 kDa. These proteins were detected in KB207 when electrophoretically separated proteins were immunoblotted with unabsorbed and absorbed sera. These two proteins were isolated by immunoaffinity chromatography using purified antibodies from absorbed serum. Although antigenic, the 40 and 38 kDa proteins did not induce protection against cholera in the rabbit ileal loop model.

Animals↗
PubMed1993

Identification of a 33 kDa antigen associated with an adhesive and colonizing strain of Vibrio cholerae El Tor and its role in protection.

Proteins from the cell-free lysates of the wild-type strain KB207 of Vibrio cholerae El Tor and the isogenic non-adhesive mutant CD11 were analysed by native and denaturing polyacrylamide gel electrophoresis. A protein of 33 kDa present in KB207 was absent from CD11. Antiserum to the surface antigens of KB207 was absorbed with CD11. Antibodies remaining in the serum after absorption reacted to KB207 but not to CD11 as judged by slide agglutination, double gel diffusion and dot blot ELISA. Antibodies in the absorbed serum inhibited adherence of KB207 to rabbit intestinal mucosa and colonization in an infant mice model. The 33 kDa protein was isolated from KB207 by immunoaffinity chromatography. Antibodies present in the absorbed serum were used as ligand. The 33 kDa antigen was immunogenic and conferred protection in the rabbit ileal loop model. Combined administration of 33 kDa protein and B-subunit of cholera toxin offered full protection.

Animals↗
PubMed1993

Retention of bioprosthetic valve annulus in mitral prosthetic replacement.

Mitral valve prosthetic replacement carries high mortality rates by modern standards, and mitral bioprostheses are particularly prone to degeneration. Bioprosthetic replacement may be technically difficult when there is calcification of the tissue ingrowth, strut incorporation, or valve-to-annulus size mismatch at the primary operation. A "valve-in-valve" technique is described where the mechanical prosthesis is implanted in the bioprosthetic annulus in order to avoid such difficulties. The results in the first eight patients are presented, showing post-operative Doppler-derived transvalvar mean gradients between 3.9 mmHg and 7.5 mmHg, and estimated valve areas between 1.9 cm2 and 3.5 cm2. All patients are alive at between 20 and 30 months (mean 23.6 months) after operation, they are without serious post-operative morbidity and are in functional class I or II (NYHA classification).

Aged↗
PubMed1993

Incidence of complications following 5-fluorouracil with trabeculectomies.

To investigate the incidence of complications reportedly caused by the use of 5-fluorouracil (5-FU) in glaucoma filtering surgery, we performed trabeculectomy with 5-FU on 57 eyes of 56 patients with advanced glaucoma. The mean preoperative intraocular pressure was 34.8 mm Hg. The most frequent complication encountered was superficial punctate keratopathy (26%), followed by shallowing of the anterior chamber (12%), choroidal detachment (9%), and flap retraction (7%). We, however, did not encounter any cases of confluent corneal epithelial defect, subepithelial scarring, or striate melanokeratosis which are usually described with the use of 5-FU. With a mean follow-up of 7.1 months, an intraocular pressure less than 16 mm Hg without hypotensive therapy were achieved in 73.7% of cases, and less than 21 mm Hg without hypotensive therapy in 86%. Considering the low incidence of complications and the high success rate, we recommend the use of 5-FU in routine glaucoma filtering surgery.

Combined Modality Therapy↗
PubMed1993

[The integration process of refugees, a major explanatory factor during intervention].

In light of scientific literature produced over the last ten years, it appears that health and social work professionals should, when dealing with people belonging to minority cultures, go beyond the purely interpersonal approach to problems. Rather, they should lend an ear to the different notions of life and society, and adjust their intervention patterns to the integration conditions of immigrants. The special situation of refugees requires a special approach based on the knowledge of their pre-migrant conditions, as well as on the establishment of closer ties between welcoming institutions and these migrant families.

Empathy↗
PubMed1992

Medical clinic referral letters. Do they say what they mean? Do they mean what they say?

Consecutive general practitioner referrals to three general medical clinics were examined prospectively to assess whether the reason for referral was being correctly interpreted by consultants. The resultant data revealed that although this was not always the case, such misunderstandings did not appear to affect subsequent management. Explicit reasons for referral in the referral letter however could improve both the quality and value of out-patient consultations.

Communication↗
PubMed1992

[Estimated biological markers of progression in human immunodeficiency virus infection].

The biological markers for determining as early as possible the progression in the infection by the human immunodeficiency virus (HIV) are very important for the health care of patients, and to adapt their anti-retroviral treatment. Among those, four independent biological markers for predicting a pejorative evolution in the following 36 months are used in medical practice: two specific for HIV, p24 antigenemia and serum titre of antibodies to the p24 core antigen, and two non-HIV specific surrogate markers, the beta 2-microglobulinemia and the absolute number of CD4 T cell in blood. P24 antigenemia corresponds to an active retroviral in vivo replication. The cut off for detection is about 10 pg/ml. It is difficult to detect in black people, and in the asymptomatic or pauci-symptomatic stages of the disease. The apparition or the increase of the serum p24 antigen levels suggest the occurrence of opportunistic infections. P24 antigenemia decreases or disappears during the treatment by zidovudine. The diminution or the disappearance of serum antibodies directed to the p24 core protein are secondary to the deficiency of the humoral immunity, and to an increase of the viral replication, which occur at the late stage of the disease. The diminution or the disappearance of serum antibodies to p24 precede the occurrence of AIDS by several months. The increase of the serum beta 2-microglobulin level is associated with the severity of the disease. In the San Francisco prospective cohort, the progression to AIDS in 36 months was 69% when beta 2-microglobulinemia was more than 5 mg/l, 33% when it was between 3.1 to 5 mg/l, and 12% when it was less than 3 mg/l. The beta 2-microglobulin intra-thecal synthesis level could serve as a marker for the specific HIV encephalitis. The CD4 lymphocyte count constitutes an independent provisional marker for progression to AIDS, probably the most important, but mainly of statistical value. A lymphocyte count of 200 CD4/mm3 is considered as the threshold of full blown AIDS. Beside these classic biological markers, numerous other parameters have been evaluated, without knowing their practical interest. Although the predictive markers for AIDS have a real statistical significance, their interpretation could be difficult or hazardous when applied to a sole individual. In a relatively short delay, the actual biological markers will probably be completed or changed, in the routine medical practice, by the use of direct virological markers evaluating the viral load (plasmatic or cellular viremia).

Antiviral Agents↗
PubMed1991

A chemiluminescent immunoassay for urinary thromboxane B2.

Because of the vasoactive properties of thromboxane A2 and other related prostaglandins, much research has been conducted on drugs which alter their levels. Urinary levels of thromboxane B2 and 2,3-dinor thromboxane B2 (major urinary metabolite of thromboxane B2) are used as an indication of thromboxane production in-vivo. In order to accurately measure urinary TXB2 levels of subjects on investigative drugs which lower TXA2 and subsequently TXB2, a simple and sensitive analytical tool becomes necessary. We have thus developed a non-radioisotopic (chemiluminescent) assay for urinary TXB2. Sensitivity has been demonstrated to 5 pg/ml. The method correlates well with gas chromatography/mass spectrometry (the accepted reference method) even without column chromatographic purification prior to the conduct of the chemiluminescent assay (r = 0.96). In addition, we have demonstrated feasibility for a chemiluminescent assay to measure urinary 2,3-dinor TXB2.

Acridines↗