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Biomedical subjects

A Cohen

Publications and source records attributed to A Cohen.

At least 613 records · Page 34Linked to original sources

Cyclosporine as primary therapy for A-matched living related donor kidney graft recipients.

Between 1981-87, 48 HLA identical sibling graft recipients were allocated to one of three treatment groups: Group I-15 patients Aza and Pred; Group II-12 CyA alone; Group III-21 CyA and steroids. Only one patient died from a fatal hereditary disease. Graft survival was 100% at one year in all groups and at three years was 86% for Aza, 94% for CyA alone and 100% for CyA and steroids. Rejection episodes occurred in 50% of Aza patients versus 18% in the CyA groups. However 55% of CyA patients require anti-hypertensives versus 20% of Aza recipients, and 12% of CyA patients were switched because of drug toxicity. In a previous study of 36 Aza treated A-matched patients, five of eight losses occurred after the first 5 years--most related to long term effects of immunosuppression. We may have to wait for longer follow-up before drawing conclusions regarding the use of CyA in identically matched living related recipients.

ABO Blood-Group System↗

ABO-incompatible living related donor kidney transplantation: report of two cases.

The courses of two recipients of ABO-incompatible HLA-identical living related donor kidney transplants are described, the first an A into O and the second a B into A. Both patients were prepared by a month of preoperative azathioprine and a week of plasmapheresis to reduce isohemagglutinin titers in one to 1:2 and in the other to 0 at the time of transplant. Both had early mild steroid-reversible rejections, and the first patient has had an uneventful subsequent course 20 months postgrafting on low-dose cyclosporine and prednisone. The second patient developed a further immunologic event at 1 month that may have been isohemagglutinin mediated or may have been rejection but subsided with OKT3 therapy and plasmapheresis. She lost her graft at 5 months despite normal function during attempts to repair a ureteric fibrosis. Neither patient had donor-specific transfusion or splenectomy. This approach is feasible and should be considered for those patients having related but ABO-incompatible donors.

ABO Blood-Group System↗

Living related donor kidney grafts in the cyclosporine era.

The results of 120 LRD kidney grafts, 49 HLA identical and 71 haploidentical, performed between 1981 and 1987 during the CyA era have been analyzed. The reduction in the incidence of rejection in diploidenticals with CyA vs AZA did not increase short- or long-term graft survival but was accompanied by worse kidney function and a greater need for antihypertensives. CyA did improve the results in haploidentical recipients over our historical experience, although prior sensitization was still a major hazard in this group.

Adolescent↗

Effects of ocular functioning and time upon reading proficiency.

We hypothesize that children with fusional and/or accommodative abnormalities will tend to tire more readily when reading than will children with normal vision and that, consequently, they will show a greater decrement in reading proficiency over time on a task requiring reading. Forty-five subjects who passed the New York State Optometric Association Vision Screening Battery and 32 who failed were given a "maze" reading test developed for the study. The abnormal vision group made significantly more errors than did the normal vision group on the reading test. The abnormal vision group also made progressively more errors than did the normal vision group at the end of each segment of the reading test. The differences, however, were not statistically significant. While the correlations between speed and accuracy reversed over time, the abnormal vision group began and ended at the most extreme levels, having undergone a significantly more radical shift in this regard.

Accommodation, Ocular↗

[Fluoroprophylaxis of dental caries. Current status in the provinces of Genoa and Savona].

A total of 60 pediatricians from the districts of Genova and Savona, randomly selected, responded to a survey designed to determine several aspects of their attitude toward the prevention of dental caries and particularly the use of fluoride supplement (table II). The survey demonstrated (table III) that 80% of the physicians prescribe fluoride without knowing the fluoride content in the water supply of their region. Therefore, the dosage schedule used by 56% of the physicians is higher than the optimal, 27.5% is lower and only 16.5% use the optimal dosage as recommended by the American Academy of Pediatric, Committee on Nutrition.

Adolescent↗

Urban unfinished business.

Water and sanitation services and hygiene education are crucial in preventing communicable and other diseases which daily take an enormous toll both in morbidity and mortality around the world. Diarrheal diseases are the most prevalent, affecting hundreds of millions of infants, children, and others. There is a current major demographic trend of migration to and explosive growth of low-income peri-urban settlements in and around large cities in developing nations. These settlements lack adequate and affordable water supplies and often have no sanitary facilities whatsoever. They are perfectly suited for the flourishing of water- and sanitation-related communicable and other diseases, which add considerably to the misery of abject poverty. However, working with members of these communities to provide water and sanitation services can both prevent such diseases and improve economic conditions. International assistance must be facilitative rather than interventionist. Developed nations should greatly increase their financial contribution for the facilities necessary for better water and sanitation. Initially, it is important to create an international urban information center to act as a clearinghouse of information. It would also be helpful to begin a four-decade urban sanitation planning effort along with an "Urban Watch" to promote significant developments in peri-urban settlements.

Developing Countries↗

Promoter analysis of myosin alkali light chain genes expressed in mouse striated muscle.

There are three principal myosin alkali light chain (MLC) genes expressed in mouse striated muscle. The skeletal muscle gene MLC1F/MLC3F, the ventricular muscle/slow skeletal muscle gene MLC1V(MLC1S), and the atrial muscle/foetal striated muscle gene MLC1A(MLC1emb). MLC1V and MLC1A are expressed in both cardiac and skeletal muscle, and we show here that these genes use a single site of initiation of transcription, and therefore the same proximal promoter region, in both muscle types, and in myogenic cell lines in culture. We have previously shown that for the MLC1F/MLC3F gene, 1200bp of upstream sequence from the MLC1F promoter is sufficient to allow tissue specific and developmentally regulated expression. We have therefore isolated, characterised, and sequenced over 1200bp upstream of each of the three MLC genes in order to look for elements which may be involved in their regulation. Detailed comparison of their promoter sequences, as well as those of the cardiac and skeletal muscle alpha-actin genes, reveals a number of common elements. Among these is an "MLC-sequence" (CCTTTTATAG) common to all MLC genes, including those of chick and rat, and a "cardiac sequence" common to the mouse MLC1A, MLC1V and alpha-cardiac actin genes expressed in the heart.

Amino Acid Sequence↗

Use of a bioluminescence gene reporter for the investigation of red-dependent and gam-dependent plasmid recombination in Escherichia coli K12.

A plasmid recombination assay, which utilized mutated Vibrio fischeri luciferase genes, cloned in Escherichia coli plasmids was developed. Expression of the recombination product, a functional luxA gene, was assayed by measuring light intensity. This system was used to investigate the effect of E. coli gene functions on lambda Red- and Gam-dependent plasmid recombination. The genetic and physiological requirements for Red- and Gam-dependent plasmid recombination are similar to the conditions which allow synthesis of plasmid linear multimers. Both recombination and linear multimer synthesis are mediated by Red activity in recBrecC and in sbcB mutants and by Gam activity in sbcB and sbcA mutants, but neither recombination nor linear multimer synthesis is mediated by Red or Gam functions in RecBCD+ExoI+ cells. When mediated by Red in sbcB mutants, both recombination and linear multimer synthesis are RecA-independent, and when mediated by Gam, in the same genetic background, both are RecA-dependent. A role for replication in Red- and Gam-mediated plasmid recombination is suggested by the dependence of the recombination activity on DnaB. A model which hypothesizes mutual dependence of linear plasmid multimer synthesis and plasmid recombination by the RecE, RecF and Red pathways is presented. We propose that ends that are produced during this type of replication are recombinogenic in all three pathways and that new rounds of replication are primed by a recombination-dependent invasion of duplex DNA by 3' single strand ends.

Cloning, Molecular↗

Structure and sequence of the myosin alkali light chain gene expressed in adult cardiac atria and fetal striated muscle.

Mammalian cardiac muscle contains two myosin alkali light chains which are the major isoforms present in either atrial (MLC1A) or ventricular (MLC1V) muscle, and which are different from the fast skeletal muscle isoforms (MLC1F and MLC3F). The atrial isoform is also expressed in fetal skeletal and fetal ventricular muscle, where this isoform is also described as the fetal isoform MLC1emb. We have previously isolated a cDNA clone encoding part of the mouse MLC1A/MLC1emb isoform and have used this clone to demonstrate the identity of MLC1A and MLC1emb in the mouse. To date no information on the amino acid sequence of this mammalian atrial/fetal isoform has been available. Here we present the complete structure and sequence of the mouse MLC1A/MLC1emb gene, together with the predicted amino acid sequence of this isoform. Comparison of the MLC1A/MLC1emb gene and polypeptide with those of MLC1F and MLC1V suggests that MLC1A/MLC1emb and MLC1V were generated from a common ancestral gene. The NH2-terminal region of MLC1A/MLC1emb, thought to be involved in the actomyosin interaction, shows conservation with MLC1V but not with MLC1F suggesting a shared functional domain in these cardiac isoforms. Comparison with the chicken embryonic MLC (L23) suggests that although MLC1A/MLC1emb and L23 show very different patterns of expression, both during development and in the adult, they probably represent the homologous gene in these two species.

Amino Acid Sequence↗

Sotalol for refractory sustained ventricular tachycardia and nonfatal cardiac arrest.

The efficacy and safety of sotalol were assessed by electrophysiologic testing and ambulatory recordings in 16 patients with recurrent sustained ventricular tachycardia (VT) or nonfatal cardiac arrest who were refractory to an average of 4.8 conventional antiarrhythmic agents. Twenty-four-hour ambulatory recordings were performed before and after sotalol therapy. Fourteen patients underwent baseline electrophysiologic study and sustained VT was inducible in 12. Oral sotalol (320 to 960 mg/day) completely suppressed inducible sustained VT in 7 patients (58%), with modification in 3 (25%). Ventricular premature complexes were suppressed from baseline (mean +/- standard deviation) 431 +/- 616 to 60 +/- 110/hr (p less than 0.03). After a mean follow-up of 19 +/- 7 months, 12 of 14 patients receiving sotalol treatment had successful suppression of ventricular premature complexes (60 +/- 85/hr) and remained clinically free of sustained VT, except 2 who needed additional antiarrhythmic drugs to suppress the recurrent sustained VT. One patient died suddenly after 25 months of sotalol treatment. No severe side effects were noted during sotalol therapy. This study demonstrates that sotalol is a well-tolerated, effective antiarrhythmic agent in patients at high-risk for sudden death. It appears to be beneficial in patients who did not benefit from multiple drug treatment.

Adult↗

Coordinate transcriptional regulation of alpha and delta chains of the T-cell antigen receptors by phorbol esters and cyclic adenosine 5'-monophosphate in human thymocytes.

The regulation of T-cell antigen receptor (TcR) gene expression by phorbol ester and cAMP was studied in human thymocytes. Incubation of human thymocytes in the presence of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate increased the levels of the mRNAs of TcR-alpha and -delta while the levels of TcR-beta and -gamma mRNA were not affected. cAMP, on the other hand, caused a decrease in TcR-alpha and -delta mRNA levels but also did not affect TcR-beta and -gamma mRNA levels. The induction of TcR-alpha and -delta mRNA by 12-O-tetradecanoylphorbol-13-acetate occurred at the transcriptional level only whereas cAMP treatment decreased both TcR-alpha gene transcription and the stability of its mRNA. The similarity in the transcriptional control of TcR-alpha and -delta genes combined with their close chromosomal location raises the possibility that they share common DNA regulatory elements.

Child↗

New chemotherapeutic drug sensitivity assay for colon carcinomas in monolayer culture.

Ten previously untreated colon carcinomas were tested for chemotherapeutic drug sensitivity in primary monolayer culture. Colon carcinomas were partly digested to groups of epithelial cells which plated with a mean efficiency of 42 +/- 9% (SE) on a collagen I-bovine serum albumin substrate in serum-free medium, producing patches of tightly adherent epithelial cells. The cultured cells were judged epithelial by the presence of cytokeratins, an epithelial cell surface epitope, junctional complexes, and brush borders. Each carcinoma was plated in 40 to 60 Petri dishes (35 mm), yielding a mean of 28 +/- 8 (SE) colonies per dish (6832 +/- 1952 cells). Drugs tested in duplicate plates were mitomycin C, cisplatin, streptozotocin, and 5-fluorouracil at 0.1, 1, 10, and 100 micrograms/ml, and at 0.1, 1, and 2x the peak tolerated drug concentration in serum. Twenty-four h after plating, any nonadherent cells were removed, and the adherent tumor cells were continuously exposed to the drugs for 3 days. Each drug induced colony lysis in a dose-dependent manner in responsive tumors. Drug-resistant, cycling cells were identified by [3H]thymidine incorporation in colonies which were not lysed by drug treatment. Each of the ten carcinomas exhibited inherent resistance to one or more chemotherapy drugs within the concentration ranges clinically achievable.

Antineoplastic Agents↗

Extracellular nucleotide catabolism in human B and T lymphocytes. The source of adenosine production.

Extracellular nucleotide degradation was studied in intact human B and T lymphocyte subpopulations and in lymphoblastoid cell lines. Cells of B lymphocyte lineage showed high nucleotide degrading activity, whereas T lymphocytes were unable to degrade extracellular nucleotides. The external surface of B cells contained active sites of ecto-triphosphonucleotidase (ecto-ATPase), ecto-diphosphonucleotidase (ecto-ADPase), and ecto-monophosphonucleotidase (ecto-AMPase). The expression of all three ectoenzyme activities seemed closely associated with B cell development. ATPase and ADPase activities increase continuously during B cell maturation, ecto-AMPase activity, on the other hand, reaches maximal activity in late pre-B cells. These results combined with our previous studies of intracellular ATP catabolism (Barankiewicz, J., and Cohen, A. (1984) J. Biol. Chem. 259, 15178-15181) provide evidence that extracellular ATP catabolism may represent exclusive source for adenosine in lymphocytes. It is suggested that adenosine may serve as a means of communication between B and T cells in lymphoid organs, B lymphocytes being the sole producers of adenosine and T lymphocytes being the recipients of this signal.

Adenosine↗