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Biomedical subjects

A Cohen

Publications and source records attributed to A Cohen.

At least 19 recordsLinked to original sources
PubMed1992

tDNA(ser) sequences are involved in the excision of Streptomyces griseus plasmid pSG1.

Plasmid pSG1 is maintained in some derivatives of Streptomyces griseus NRRL3851 mainly in the chromosomally integrated form (pSG1int). In others, the integrated plasmid is co-maintained with free pSG1 [Cohen et al., Plasmid 13 (1985) 41-50]. The pSG1 plasmid integration site (attP) and the pSG1int-chromosome boundaries (attL and attR) were cloned and sequenced. The results indicate that pSG1int is flanked at attL by a functional tRNA(ser) gene and at attR by a 60-nt sequence of the 3' end of the same tRNA(ser) gene. A single mismatch distinguishes the 60-nt sequence at attR from its direct repeat at attL. The attP site contains a single copy of the 60-nt repeat, identical to the one at attL. This observation indicates that pSG1, like integrating plasmids of other Actinomycetes, is integrated in a tRNA gene and suggests that the exact excision of pSG1int occurs by a recombinational crossing-over event at the first 43 nt of the 60-nt repeat.

Amino Acid Sequence↗
PubMed1992

Immunization of colorectal cancer patients with modified ovine submaxillary gland mucin and adjuvants induces IgM and IgG antibodies to sialylated Tn.

Tn and sialylated Tn (sTn) are blood group-related epitopes expressed on mucins of colon carcinoma and other epithelial tumors and are, therefore, potential targets for immunological control. We have immunized 20 colorectal cancer patients at high risk for recurrence with a vaccine consisting of partially desialylated ovine submaxillary gland mucin (modified OSM) which contains both Tn and sTn determinants. Six patients were treated with modified OSM alone (group 1), eight patients were treated with modified OSM and the immunological adjuvant DETOX (group 2), and six patients were treated with modified OSM and Bacillus Calmette-Guérin (group 3). Pre- and postvaccination sera were tested by enzyme-linked immunosorbent assay and dot blot immune stains for antibodies reactive with modified OSM. Antibody titers increased in 4 of 8 patients immunized with modified OSM and DETOX, in 5 of 6 patients immunized with modified OSM and B. Calmette-Guérin, and in 0 of 6 patients receiving modified OSM without adjuvant. The specificity of induced IgM and IgG antibodies was confirmed by demonstrating reactivity with OSM, bovine submaxillary mucin, and synthetic glycoconjugates sTn-human serum albumin (HSA) and Tn-HSA in enzyme-linked immunosorbent assay and immune stains. Median IgM pre-postvaccination reciprocal titers were 20/80 for Tn-HSA and 10/320 for sTn-HSA. Low level IgG antibody titers against sTn-HSA were detected after vaccination in 7 patients. Toxicity was limited to inflammatory skin reactions at the site of vaccination resulting from the adjuvants. No inflammatory infiltrates were seen in the skin when the modified OSM vaccine was administered in the absence of an immunological adjuvant. These results demonstrate that sTn and Tn can be recognized by the human immune system and that vaccines containing these structures can be administered safely with immunological adjuvants. Attempts to augment the immunogenicity of these carbohydrate antigens by covalent attachment to immunogenic carrier proteins and the use of more potent immunological adjuvants are now being pursued.

Adjuvants, Immunologic↗
PubMed1992

Decreased platelet imipramine binding in Tourette syndrome children with obsessive-compulsive disorder.

[3H]Imipramine binding to blood platelets was assessed in eight untreated Tourette syndrome (TS) children, nine drug-free TS children with obsessive-compulsive disorder (OCD), and nine age-matched and gender-matched control subjects. The density of [3H]imipramine binding sites in TS + OCD patients was significantly lower compared with TS-OCD patients (28%) as well as when compared with controls (31%). This alteration was not accompanied by differences in the affinity of the binding site to the ligand. The decreased density of the platelet serotonin "transporter" might implicate the involvement of the serotonergic system in the pathophysiology of OCD in TS patients, but not in TS per se.

Adolescent↗
PubMed1992

Localizing genes on the map of the genome of Haloferax volcanii, one of the Archaea.

We have assigned genetic markers to locations on the physical map of the genome of the archaeon Haloferax volcanii, using both a physical method (hybridization) and a more specific genetic technique (transformation with cosmids). Hybridizations were against restriction digests of each of 151 cosmids making up a minimally overlapping set and covering 96% of the genome. Results with a cloned insertion sequence and a tRNA probe indicated that transposable elements are concentrated on two of the four plasmids of this species, whereas regions complementary to tRNA are largely chromosomal. For a genetic analysis of genes involved in the biosynthesis of amino acids, purines, and pyrimidines, we used cosmid transformation to assign 139 of 243 ethyl methanesulfonate-induced auxotrophic mutations, generated and characterized for this study, to single cosmids or pairs of cosmids from the minimal set. Mutations affecting the biosynthesis of uracil, adenine, guanine, and 14 amino acids have been mapped in this way. All mutations mapped to the 2920-kilobase-pair chromosome of Hf. volcanii and seemed uniformly distributed around this circular replicon. In some cases, many mutations affecting a single pathway map to the same or overlapping cosmids, as would be expected were genes for the pathway linked. For other biosynthetic pathways, several unlinked genetic loci can be identified.

Archaea↗
PubMed1992

[Treatment of onychomycosis using 40% urea with 1% bifonazole].

The rate of success in treating onychomycosis with 40% urea ointment containing 1% bifonazole, with and without oral griseofulvin, was evaluated. Most patients had onychomycosis of the toes. 11 patients (group A: 5 men and 6 women, average age 48.5) were treated locally under occlusion with the ointment until dissolution of most of the nail, and then with 1% bifonazole cream for a total of 6 months. 11 others (group B: 3 men and 8 women, average age 42.5) received, in addition, griseofulvin 500 mg/day orally during that period. Treatment with the ointment alone did not give higher cure rates than the average of reported cure rates for griseofulvin alone. However, the results of treatment with 40% urea and 1% bifonazole ointment concomitantly with oral griseofulvin seemed superior to those of either of these agents alone, with full cure, partial cure and failure in group A of 22.2, 33.3 and 44.5%, respectively, and in group B, 45.4, 27.3 and 27.3%. This therapeutic experiment should be repeated in larger series of patients.

Administration, Oral↗
PubMed1992

A randomized trial of intrahepatic infusion of fluorodeoxyuridine with dexamethasone versus fluorodeoxyuridine alone in the treatment of metastatic colorectal cancer.

To decrease the toxicity of hepatic arterial fluorodeoxyuridine (FUDR) administered through an Infusaid pump (Shiley Infusaid, Inc., Norwood, MA), 50 patients with liver metastases from colorectal cancer were selected randomly to receive FUDR, 0.3 mg/kg/d, for 14 of 28 days, with or without a total dose of 20 mg of hepatic arterial dexamethasone for 14 of 28 days. Patients were stratified according to the percentage of liver involvement by tumor and the perfusion pattern on macroaggrated albumin perfusion scan (MAA) scan. There was a trend toward decreased frequency of bilirubin levels in the group receiving dexamethasone plus FUDR versus the group receiving FUDR alone (9% and 30%, respectively, had a 200% or greater increase from baseline; P = 0.07). Patients in the group treated with dexamethasone and FUDR received higher doses of FUDR in the second, third, fifth, and sixth months than those receiving FUDR alone; however, this was statistically significant only in the fifth month (percentages of planned dose received: 42% and 19%, respectively; P = 0.05), and there was no overall difference for the total 6-month period. The complete and partial response rates were increased in patients receiving dexamethasone and FUDR versus FUDR alone (8% and 63% versus 4% and 36%, respectively; P = 0.03), and there was a trend toward increased survival with the addition of dexamethasone (median, 23 months and 15 months, respectively; P = 0.06). In conclusion, the use of hepatic arterial dexamethasone is associated with an increased response rate and a trend toward increased survival and decreased bilirubin levels. Therefore, the authors recommend additional investigation of the use of dexamethasone with chemotherapy to treat hepatic metastases.

Adult↗
PubMed1992

Analysis of premature ventricular counts in long term ECG following myocardial infarction.

Frequent and recurrent ventricular premature beats (VPB's) are considered to be associated with a higher risk of sudden cardiac death, particularly for survivors of myocardial infarction (MI). The distribution of VPB's has a large probability mass at zero, and a very heavy right hand tail. In this research, we fitted a model to VPB for patients for which VPB was present. The model was fitted on the basis of a relatively large data set on MI survivors in Israel. The model was fitted by a method which is based on the generalized linear model. This method, which was introduced by Zeger and Liang, is designed for longitudinal data and uses the quasi-likelihood concept. No specific assumptions are required on the shape of the distribution of the dependent variable. The results indicate that the model fits the data quite well but underestimates the very extreme high values. This research demonstrates the applicability of generalized linear models for longitudinal non-Gaussian data. Such data often arise in medical studies. The study also points out the distributional properties of VPB counts. In particular, it shows their associations with simple clinical and epidemiological variables, and with certain time periods during the day.

Cardiac Complexes, Premature↗
PubMed1992

Interleukin 6 induces myeloid differentiation of a human biphenotypic leukemic cell line.

The human leukemic cell line B1, is characterized by a specific 4;11 chromosomal translocation, immature myeloid/pre-B biphenotypic features, expression of multiple cytokine receptors and IL-1-dependent autocrine growth regulation [Cohen et al. (1991) Blood 78, 94]. Exposure of B1 cells to low concentrations of IL-6 abolished the leukemic cells ability to form colonies in semi-solid medium and slowed down their proliferation rate in suspension. Associated with these changes in growth characteristics, the B1 cells differentiated along the myeloid lineage as judged by the induction of the myeloid-specific surface antigens CD33, CD13 and CD11b, as well as histochemical and morphological changes characteristic of myeloid cells. The induction of differentiation was specific to IL-6 since none of the other cytokines which inhibited B1 cell growth (IL-7, gamma IFN and TNF alpha) were able to induce myeloid or lymphoid differentiation in these cells. The IL-6-induced differentiation was completed over a two week period and was essentially irreversible. Together with the phenotypic changes, IL-6 induced the expression of the protein tyrosine phosphatase (CD45) which may be associated with altered growth observed in IL-6-treated cells. Induction of terminal differentiation of leukemic cells by recombinant bioregulators has therapeutic implications and merits further study.

Bone Marrow↗
PubMed1992

The human T cell receptor gamma genes are transcribed from TATA-less promoters containing a conserved heptamer sequence.

We have used the anchored polymerase chain reaction (A-PCR) to clone and compare the 5' upstream regions of the human T cell receptor gamma (TRG) genes. Whereas little homology was found among subgroups I, II, III and IV, sequence alignment of TRG subgroup I members revealed a high degree of homology in the 5' sequences. A conserved heptamer sequence (CTGCAGG), which was found upstream from the translation initiation site of all TRG genes in our analysis. Determination of the transcription initiation site located the conserved heptamer 65 base pairs upstream from the cap sites of V5. No TATA box or other cis-acting promoter sequences could be identified in any of the human TRG upstream sequences.

Base Sequence↗
PubMed1992

Experimental model of lead nephropathy. II. Effect of removal from lead exposure and chelation treatment with dimercaptosuccinic acid (DMSA).

Male Sprague-Dawley rats were exposed to high-dose (0.5%) lead acetate for periods ranging from 1 to 9 months; then lead exposure was discontinued, and animals were sacrificed after 12 months. Controls were pair-fed. Two additional groups of low-dose (0.01%) and high-dose (0.5%) rats were exposed to lead for 6 months, then lead was discontinued and the rats were treated with three 5-day courses of 0.5% DMSA (dimercaptosuccinic acid) over the next 6 months. Controls were rats exposed to lead for 6 months, then removed from exposure for 6 months without receiving DMSA. Low-dose lead-treated rats showed no significant pathological changes with or without DMSA treatment, but exhibited a significant increase in GFR after DMSA. High-dose lead-treated animals showed no functional or pathological changes when lead exposure was discontinued after 1 month. However, when duration of exposure was 6 or 9 months, GFR was decreased and serum creatinine and urea nitrogen were increased as compared to controls. Tubulointerstitial disease was severe. Administration of DMSA resulted in an improvement in GFR and a decrease in albuminuria, together with a reduction in size and number of nuclear inclusion bodies in proximal tubules. However, tubulointerstitial scarring was only minimally reduced. It may be concluded that, except for brief initial exposure, discontinuation of high-dose lead exposure fails to reverse lead-induced renal damage. Treatment with the chelator, DMSA, improves renal function but has less effect on pathological alterations. As GFR improved after DMSA treatment in both low-dose and high-dose lead-treated rats, irrespective of the degree of pathological alterations, it may be concluded that the DMSA effect is most likely mediated by hemodynamic changes.

Acetylglucosaminidase↗
PubMed1992

Asymmetry in visual search for targets defined by differences in movement speed.

Perception of motion speed was investigated with the visual search paradigm, using human Ss. When searching for a fast target among slow distractors, reaction time was minimally affected as the number of distractors was increased. In contrast, reaction time to detect a slow target among fast distractors was slow and linearly related to the number of distractors. The effect cannot be attributed to differences in temporal frequency, discriminability, or one type of representation that might result from spatiotemporal filtering. An alternative hypothesis that can account for the asymmetry is that speed detectors operate as high-pass filters in the velocity domain. This hypothesis is in agreement with results obtained in psychophysical studies on motion adaptation as well as data from single-cell recordings in nonhuman species.

Acceleration↗
PubMed1992

Epoetin enhances erythropoiesis in normal men undergoing repeated phlebotomies.

Epoetin may enhance autologous blood donation, but efficacy and dose response have not been established. This multicenter, double-blind trial compared intravenous placebo (n = 23) with epoetin beta, 250 U/kg (n = 23), 500 U/kg (n = 19), and 1000 U/kg (n = 22), administered three times weekly for 26 days. Normal men (age, 28 +/- 7 years; mean +/- SD) received phlebotomies up to three times weekly as long as the hemoglobin remained greater than or equal to 12 gm/dl. Subjects treated with epoetin donated 32% more units of blood (p less than 0.05) compared with placebo. A dose response was not observed. Platelet counts increased with epoetin compared with placebo, but platelet function and bleeding time did not change. Prothrombin times increased and partial thromboplastin times decreased with both epoetin and placebo. The supernatant of packed red blood cells collected after multiple phlebotomies and stored 42 days had slightly lower glucose concentrations and pH after therapy with epoetin. Blood pressure did not change with epoetin or placebo. These findings support the efficacy and safety of epoetin for enhancing the erythropoietic response of normal subjects during intensive phlebotomy.

Adolescent↗
PubMed1992

Clinical decision making for discharge planning in a changing psychiatric environment.

This article reviews the clinical decision-making process involved in planning for continuity of care following discharge from inpatient psychiatric services. The decision-making frame of reference requires the identification of the players in the process, parameters of their roles, performance expectations, and boundaries of rights and obligations; clear definition of objectives; collection of data and analysis of its relevancy; and study of possible alternatives, with evaluations of their consequences. The authors present an approach to clinical decision making that includes an analysis of modalities and practice skills and a critical review of practice in a psychiatric setting that emphasizes the role of the family; the importance of continuity of care; and the need to engage the patient, family, and care systems within briefer time frames.

Adult↗