Biomedical subjects
Publications and source records attributed to A Meyer.
The population of Bury and Rochdale has a much higher rate of Coronary Heart Disease than the national average. This paper develops an approach, based on the Framingham score method, of making patients aware in a lucid manner of their risk of suffering a fatal heart attack by assigning them a position in a queue of people who are similar to them so far as non-modifiable risk factors are concerned.
The p16 protein plays an important role in the transition of cells into the G1 phase of the cell cycle. We have studied the prevalence of p16 protein expression in breast carcinomas in a prospective series of 368 invasive and 52 non-invasive malignancies, as well as in 88 locally recurring tumours and three tumour cell lines. p16 protein expression was evaluated immunohistochemically on paraffin sections using monoclonal and polyclonal anti-p16 antibodies, and by immunoblotting of tumour cell suspensions. Tumour cell lines were also subjected to polymerase chain reaction-single strand polymorphism (PCR-SSCP) analysis and direct DNA sequencing. The results were compared with established prognostic parameters, DNA flow cytometry and p53 protein expression. In 33 (9%) invasive and two (4%) intraductal carcinomas, a cytoplasmic accumulation of the p16 protein was seen. These cases were characterized by poor histological grade of differentiation, loss of of oestrogen receptors and progesterone receptors and frequent overexpression of the p53 protein. In addition, breast carcinomas with aberrant p16 expression demonstrated a high proliferative activity, with median S-phase fractions 74% higher than in the control group and the median Ki67 fractions elevated to 75%. A genetic alteration of the p16 gene was not detectable in three analysed cell lines with cytoplasmic p16 expression applying PCR-SSCP and direct DNA sequencing. These results indicate that cytoplasmic accumulation of the p16 protein identifies a subset of highly malignant breast carcinomas with accelerated tumour proliferation and other unfavourable parameters in breast cancer. The described protein accumulation is apparently not caused by an alteration of the p16 gene.
The phylogenetic relationships of the African lungfish (Protopterus dolloi) and the coelacanth (Latimeria chalumnae) with respect to tetrapods were analyzed using complete mitochondrial genome DNA sequences. A lungfish + coelancanth clade was favored by maximum parsimony (although this result is dependent on which transition:transversion weights are applied), and a lungfish + tetrapod clade was supported by neighbor-joining and maximum-likelihood analyses. These two hypotheses received the strongest statistical and bootstrap support to the exclusion of the third alternative, the coelacanth + tetrapod sister group relationship. All mitochondrial protein coding genes combined favor a lungfish + tetrapod grouping. We can confidently reject the hypothesis that the coelacanth is the closest living relative of tetrapods. When the complete mitochondrial sequence data were combined with nuclear 28S rRNA gene data, a lungfish + coelacanth clade was supported by maximum parsimony and maximum likelihood, but a lungfish + tetrapod clade was favored by neighbor-joining. The seeming conflicting results based on different data sets and phylogenetic methods were typically not statistically strongly supported based on Kishino-Hasegawa and Templeton tests, although they were often supported by strong bootstrap values. Differences in rate of evolution of the different mitochondrial genes (slowly evolving genes such as the cytochrome oxidase and tRNA genes favored a lungfish + coelacanth clade, whereas genes of relatively faster substitution rate, such as several NADH dehydrogenase genes, supported a lungfish + tetrapod grouping), as well as the rapid radiation of the lineages back in the Devonian, rather than base compositional biases among taxa seem to be directly responsible for the remaining uncertainty in accepting one of the two alternate hypotheses.
Among vertebrates, cichlid fishes are the paradigmatic example of adaptive radiation and ecological specialization. In turn, molecular genetic studies of cichlids have focused primarily on more recently diverged groups. Here, we present an evolutionary hypothesis of the major lineages of cichlid fishes based on DNA sequence data from two nuclear loci. One marker, Tmo-4C4, is a single-copy locus containing a region of amino acid similarity to the muscle protein TITIN. Flanking sequence from a second, microsatellite, locus Tmo-M27, shows similarity to mammalian RAS guanine nucleotide-releasing factor. We compare and combine data from these loci to evaluate phylogenetic performance. In separate and combined analyses, the sequence data support and clarify previous morphological hypotheses of cichlid major-group relationships. Indian and Malagasy cichlids form a basal, paraphyletic group. Neotropical cichlids are the sister clade to an African assemblage composed of the paraphyletic west and Pan-African lineages and a group of east African rift lake taxa. We use a consensus phylogeny of the Cichlidae to trace evolutionary changes in the microsatellite repeat motif at Tmo-M27. Analysis reveals that the repeat region was nearly lost in the ancestor to cichlids and then amplified extensively in African taxa. Results demonstrate that the two new DNA markers could be widely applied in perciform systematics. Furthermore, the comparative approach can unveil mutational dynamics of simple-sequence repeat loci over long periods of fish evolution. Simple-sequence repeat regions are increasingly being found in introns of important regulatory genes. We address issues involving their function and suggest caution in making assumptions of strict neutrality.
The issue of the interplay of optimal dosage and frequency regimens for enzyme replacement therapy in type I Gaucher disease has been a source of controversy during the 7 years since the introduction of the placenta-derived enzymatic preparation in 1991. We present the results of treatment with the human recombinant form of the enzyme in 28 type I Gaucher patients, who have been treated for 6 to 24 months. As long as cost is an important factor in the management of patients with Gaucher disease, low-dose low-frequency imiglucerase promises satisfactory clinical improvement without compromising quality of life.
PURPOSE: We demonstrate the effect of chronic inflammation of the prostate on the ratio of free-to-total prostate specific antigen (PSA) in serum calculated as a percentage of free PSA and, therefore, that percentage of free PSA is an unspecific means to distinguish among prostate cancer, chronic prostatitis and benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Total, free and percentage of free PSA was measured in 66 men with prostate cancer, 119 with BPH and 17 with asymptomatic chronic prostatitis. In all patients the diagnosis was histopathologically confirmed by microscopic examination of prostatic specimens after sextant biopsy, transurethral prostatic resection or prostatectomy. RESULTS: The median values of total, free and percentage of free PSA were 4.11 microg./l., 0.75 microg./l. and 20.4% in patients with BPH, 10.0 microg./l., 0.84 microg./l. and 8.5% in those with prostate cancer, and 7.60 microg./l., 1.23 microg./l. and 10.6% in those with chronic prostatitis. Patients with prostate cancer and chronic prostatitis had a significantly lower percentage of free PSA than those with BPH. Receiver operating characteristics curve analysis showed that percentage of free PSA as a discriminator between prostate cancer and BPH was not suitable for differentiating between prostate cancer and chronic prostatitis. CONCLUSIONS: Chronic prostatitis is not characterized by elevated total PSA concentrations alone but also by a decreased percentage of free PSA, a tendency similar to that in prostate cancer. This unspecific change in percentage of free PSA must be considered to interpret the percentage of free PSA correctly.
To assess optimal hemodynamics in relation to stimulation site during right ventricular pacing, 17 consecutive patients who underwent cardiac catheterization were studied. In all patients, right ventricular apex and right ventricular outflow tract stimulation was performed at 85, 100, and 120 beats/min. Cardiac index at both pacing sites was compared using the left ventricular outflow tract continuous wave Doppler technique. Comparison of the two stimulation sites demonstrated that right ventricular outflow tract pacing resulted in a higher cardiac index at 85 beats/min (2.42 +/- 1.2 vs 2.04 +/- 1.0 L/min per m2, P < 0.002) at 100 beats/min (2.78 +/- 1.4 vs 2.35 +/- 1.1 L/min per m2, P < 0.001) and 120 beats/min (3.00 +/- 1.5 vs 2.61 +/- 0.9 L/min per m2, P < 0.001). From a total of 51 paired observations, 45 showed an increase in cardiac index during outflow tract pacing as compared to apex pacing. Right ventricular outflow tract pacing at 120 beats/min resulted in a lower cardiac index than right ventricular apex pacing in patients with significant coronary artery disease and/or impaired left ventricular function (ejection fraction < or = 50%), whereas right ventricular outflow tract pacing produced higher cardiac indices in the absence of these abnormalities. Right ventricular outflow tract pacing resulted in higher cardiac indices as compared to apex pacing in all other subgroups at all other pacing sites tested. It is concluded that stimulation of the right ventricular outflow tract offers a significant hemodynamic benefit during single chamber pacing as compared to conventional apex pacing, particularly in the absence of significant coronary artery disease and/or left ventricular dysfunction.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Pseudo-tumoral presentation of a superficial conjunctival foreign body. A 4-year-old girl was seen in consultation for an apparent conjunctival tumor of the inner canthus of the right eye. With a soft traction, the tumor was detached of the conjunctiva, as it represented in fact a foreign body. Histopathology helped to diagnose that the foreign body was made of textile fiber. Superficial conjunctival foreign bodies may sometimes appear difficult to identify primarily especially in children.
The ratio of free prostate-specific antigen (f-PSA) to total PSA (t-PSA) in serum, calculated as percent free PSA (f-PSA%), is lower in patients with prostate carcinoma (PCa) than in patients with benign prostate hyperplasia (BPH). This parameter facilitates discrimination between the 2 groups of patients, but there is an overlapping of data. A better understanding of factors influencing this ratio is of practical importance. Therefore, f-PSA% was measured in controls and patients suffering from BPH, PCa and chronic prostatic inflammation with t-PSA concentrations up to 20 microg/l using the IMMULITE assays. The relationships of f-PSA% to clinical situation, age, prostate volume, kind of treatment, and stage and grade of tumor were calculated. Compared with controls or BPH patients, mean f-PSA% values were reduced in PCa patients and in patients with chronic prostatic inflammation. The prostate volume was the most important factor to influence f-PSA%. The difference of f-PSA% between PCa and BPH patients with prostate volumes smaller than 40 cm3 was lost if the prostate volumes exceeded 40 cm3. No relationship of f-PSA% to pTNM stage or grade of tumor was observed. In contrast to t-PSA concentrations, the f-PSA% values were not age-dependent and were not influenced by any kind of treatment in BPH and PCa patients either, which simplifies the use of f-PSA% compared with t-PSA. Thus, for using f-PSA% in clinical practice and for interpreting the data correctly, the advantages shown have to be considered along with the potential limitations of f-PSA%.
Dendritic cells are potent antigen-presenting cells involved in the initiation of immune responses. The trafficking of these cells to tissues and lymph nodes is mediated by members of the chemokine family. Recently, a novel CC chemokine known as MIP-3alpha or liver and activation-regulated chemokine has been identified from the EMBL/GenBank/DDBJ expressed sequence tag database. In the present study, we have shown that the messenger RNA for MIP-3alpha is expressed predominantly in inflamed and mucosal tissues. MIP-3alpha produced either synthetically or by human embryonic kidney 293 cells is chemotactic for CD34(+)-derived dendritic cells and T cells, but is inactive on monocytes and neutrophils. MIP-3alpha was unable to displace the binding of specific CC or CXC chemokines to stable cell lines expressing their respective high affinity receptors, namely CCR1-5 and CXCR1 and CXCR2, suggesting that MIP-3alpha acts through a novel CC chemokine receptor. Therefore, we used degenerate oligonucleotide-based reverse transcriptase PCR to identify candidate MIP-3alpha receptors in lung dendritic cells. Our results show that the orphan receptor known as GCY-4, CKRL-3, or STRL-22 is a specific receptor for MIP-3alpha, and that its activation leads to pertussis toxin-sensitive and phospholipase C-dependent intracellular Ca2+ mobilization when it is expressed in HEK 293 cells.
All four possible stereoisomers of dNTP with regard to deoxyribofuranose C-1' and C-4' carbon atoms were studied as substrates for several template-dependent DNA polymerases and template-independent terminal deoxynucleotidyl transferase. It was shown that DNA polymerases alpha, beta, and epsilon from human placenta and reverse transcriptases of human immunodeficiency virus and avian myeloblastosis virus incorporate into the DNA chain only natural beta-D-dNTPs, whereas calf thymus terminal deoxynucleotidyl transferase incorporates two nucleotide residues of alpha-D-dNTP and extends the resulting oligonucleotide in the presence of beta-D-dNTPs. The latter enzyme also extended alpha-anomeric D-oligodeoxynucleotide primers in the presence of beta-D-dNTPs. None of the studied enzymes utilized L-dNTPs. These data indicate that template-dependent DNA polymerases are highly stereospecific with regard to dNTPs, whereas template-independent terminal deoxynucleotidyl transferase shows less stereodifferentiation. It is likely that the active center of the latter enzyme forms no specific contacts with the nucleic bases of both nucleotide substrate and oligonucleotide primer.
The phylogenetic position of tetrapods relative to the other two living sarcopterygian lineages (lungfishes and the coelacanth) has been subject to debate for many decades, yet remains unresolved. There are three possible alternatives for the phylogenetic relationships among these three living lineages of sarcopterygians, i.e., lungfish as living sister group of tetrapods, the coelacanth as closest living relative of tetrapods, and lungfish and coelacanth equally closely related to tetrapods. To resolve this important evolutionary question several molecular data sets have been collected in recent years, the largest being the almost complete 28S rRNA gene sequences (about 3500 bp) and the complete mitochondrial genomes of the coelacanth and a lungfish (about 16,500 bp each). Phylogenetic analyses of several molecular data sets had not provided unequivocal support for any of the three hypotheses. However, a lungfish + tetrapod or a lungfish + coelacanth clade were predominantly favored over a coelacanth + tetrapod grouping when the entire mitochondrial genomes alone or in combination with the nuclear 28S rRNA gene data were analyzed with maximum parsimony, neighbor-joining, and maximum likelihood phylogenetic methods. Also, current paleontological and morphological data seem to concur with these molecular results. Therefore the currently available molecular data seems to rule out a coelacanth + tetrapod relationship, the traditional textbook hypothesis. These tentative molecular phylogenetic results point to the inherent difficulty in resolving relationships among lineages which apparently originated in rapid succession during the Devonian.
Explore the source record for details and available documents.
Following inactivated virus vaccination trials, the surface glycoprotein gp120 of the feline immunodeficiency virus (FIV) was considered as one of the determinants for protection. However, several vaccination trials using recombinant Env protein or some peptides failed to induce protection. To understand the role of the gp120 protein in vivo, we vaccinated cats with naked DNA coding for FIV structural proteins gp120 and p10. We analyzed the ability of these vaccinations to induce immune protection and to influence the onset of infection. Injection in cat muscles of expression vectors coding for the FIV gp120 protein induced a humoral response. Cats immunized twice with the gp120 gene showed different patterns after challenge. Two cats were, like the control cats, infected from the second week after infection onwards. The two others maintained a low proviral load with no modification of their antibody pattern. The immune response induced by gp120 DNA injection could control the level of viral replication. This protective-like immune response was not correlated to the humoral response. All the cats immunized with the gp120 gene followed by the p10 gene were infected, like the control cats, from the second week but they developed a complete humoral response against viral proteins after challenge. Furthermore, they showed a sudden but transient drop of the proviral load at 4 weeks after infection. Under these conditions, one injection of the p10 gene after one injection of the gp120 gene was not sufficient to stimulate protection. On the contrary, after a period, it seems to facilitate virus replication.