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D Cohen

Publications and source records attributed to D Cohen.

At least 19 recordsLinked to original sources
PubMed1992

The involvement of a LINE-1 element in a DNA rearrangement upstream of the mdr1a gene in a taxol multidrug-resistant murine cell line.

Two closely related but functionally distinct P-glycoprotein isoforms are encoded by the murine multidrug-resistance genes mdr1a and mdr1b. In a series of independently selected multidrug-resistant (MDR) J774.2 cell lines, mdr gene amplification and/or overexpression and overproduction of either the mdr1a or mdr1b products, or both gene products, correlates with the MDR phenotype. To investigate the possibility that mutations in the promoter regions of the mdr1a or mdr1b genes could influence their differential expression, mdr promoter-specific probes were used to detect and map potential structural alterations. An unusual structural rearrangement was found in the 5'-region of the amplified mdr1a allele in J7.T1, a cell line selected with taxol. To characterize this rearrangement, the regulatory regions of the mdr1a and mdr1b genes were analyzed. Whereas no gross structural alterations were detected by Southern blot hybridization using the mdr1b promoter probe, a novel amplified EcoRI fragment was detected by the mdr1a promoter probe. To determine the precise nature of this mutation, an mdr1a 5'-genomic clone was isolated from J7.T1 cells. Sequence analysis revealed an unusual DNA rearrangement consisting of the mdr1b gene, from its fourth intron toward its 3'-end, upstream of an intact mdr1a promoter on the amplified allele. We propose that this event occurred by an unequal sister chromatid exchange that was mediated by LINE-1 repetitive elements.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Seroprevalence of antibodies to Borrelia burgdorferi in a population of horses in central Texas.

Four hundred sixty-nine serum samples were obtained from horses admitted to the internal medicine service of the Texas Veterinary Medical Center between Jan 1 and Dec 31, 1990. Serum samples were tested by ELISA for antibody to Borrelia burgdorferi. Of these 469 samples, 1 (0.2%) was repeatedly seropositive for the organism by ELISA. Confirmatory testing by protein immunoblot was negative. The observed seroprevalence was 0%; the upper bound of the 95% confidence interval was 0.6%. These findings indicate the evidence of infection with B burgdorferi is presently uncommon in horses in central Texas.

Animals↗
PubMed1992

Primary pancreatic beta-cell secretory defect caused by mutations in glucokinase gene in kindreds of maturity onset diabetes of the young.

Maturity-onset diabetes of the young (MODY), characterised by non-insulin-dependent diabetes mellitus (NIDDM) with an early age of onset, is a genetically heterogeneous disorder. In most MODY kindreds described in France, chronic hyperglycaemia is caused by mutations in the gene encoding pancreatic beta-cell and liver glucokinase (GCK). We here report the beta-cell secretory profiles of nine patients from four GCK-linked MODY kindreds. First-phase insulin secretion assessed by an intravenous glucose test was comparable in patients and seven controls. However, beta-cell secretory response to continuous glucose stimulus during a hyperglycaemic glucose clamp was significantly reduced: mean plasma insulin values of 12 (SD 7) vs 40 (11) mU/l (p = 0.0001) and mean plasma C-peptide values 1.20 (0.30) vs 2.61 (0.37) (p = 0.0001). This secretory profile is different from those for NIDDM with late age of onset or MODY not linked to GCK. Fasting plasma insulin and C-peptide in patients were inappropriately low in relation to concomitant plasma glucose level. Furthermore, during a hyperinsulinaemic euglycaemic clamp, endogenous insulin secretion at euglycaemia (5 mmol/l) was suppressed in patients but not in controls. These results suggest that mutant GCK may lead to chronic hyperglycaemia by raising the threshold of circulating glucose level which induces insulin secretion. These data provide the first demonstration of a primary pancreatic secretory defect associated with a form of NIDDM.

Adolescent↗
PubMed1992

Biochemical and genetic characterization of the multidrug resistance phenotype in murine macrophage-like J774.2 cells.

The development of multidrug resistance (MDR) in malignant tumors is a major obstacle to the treatment of many cancers. MDR sublines have been derived from the J774.2 mouse macrophage-like cell line and utilized to characterize the phenotype at the biochemical and genetic level. Two isoforms of the drug resistance-associated P-glycoprotein are present and distinguishable both electrophoretically and pharmacologically. Genetic analysis has revealed the presence of a three-member gene family; expression of two of these genes, mdr1a and mdr1b, is associated with MDR whereas the expression of the third, mdr2, is not. Studies of these three genes have revealed similarities and differences in the manner in which they are regulated at the transcriptional level, and have suggested that post-transcriptional effects may also be important.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Hydration of DNA bases: analysis of crystallographic data.

We present a systematic analysis of water structure around nucleic acid bases. We have examined 28 crystal structures of oligonucleotides, and have studied the patterns of water around the four bases, guanine, cytosine, adenine, and thymine. The geometries of water positions were calculated up to 4.00 A from base atoms. We have found conformation-dependent differences in both the geometry and extent of hydration of the bases.

Adenine↗
PubMed1992

A 530kb YAC contig tightly linked to the Friedreich ataxia locus contains five CpG clusters and a new highly polymorphic microsatellite.

Friedreich ataxia (FA) is a severe autosomal recessive neurodegenerative disease. The defective gene has been previously assigned to chromosome 9q13-q21 by demonstration of tight linkage to the two independent loci D9S15 and D9S5. Linkage data indicate that FRDA is at less than 1 cM from both markers. Previous physical mapping has shown that probes defining D9S15 (MCT112) and D9S5 (26P) are less than 260 kb apart and are surrounded by at least six CpG clusters within 450 kb, which might indicate the presence of "candidate" genes for FA. We isolated and characterized a 530 kb YAC (yeast artificial chromosome) contig that contains five of the CpG clusters. The YACs were used to search for new polymorphic markers needed to map FRDA precisely with respect to the cloned segment. In particular, we found a (CA)n microsatellite polymorphism, GS4, that detects 13 alleles with a PIC value of 0.83 and allows the definition of haplotypes extending over 310 kb when used in combination with polymorphic markers at D9S5 and D9S15.

Base Sequence↗
PubMed1992

Molecular epidemiology of Shigella infections in Israel.

The DNAs of Shigella sonnei or Shigella dysenteriae type 1 strains isolated in outbreaks of shigellosis or in sporadic cases were analysed by restriction fragment length polymorphism (RFLP). Southern blots of the DNAs of 36 S. sonnei isolates digested by 8 restriction enzymes were hybridized with an Escherichia coli rRNA probe. The S. sonnei strains were unexpectedly diverse in their RFLP. Antibiotypes of the same isolates showed clusters of strains corresponding to the various outbreaks. On the other hand, RFLP analysis suggested concomitant multiple sources of infection rather than a common source and thereby introduced a new insight in the epidemiology of shigellosis. RFLP was also used to trace S. dysenteriae type 1 transmission in a recent cluster of clinical cases. Although antibiotic resistance patterns indicated the presence of more than one strain, RFLP analysis showed that the six isolates were identical clones and suggested the loss of an R episome after one person-to-person passage.

Blotting, Southern↗
PubMed1992

Assessing the reliability of clinical scales when the data have both nominal and ordinal features: proposed guidelines for neuropsychological assessments.

The purpose of this article is to present, for the first time, a comprehensive methodology for assessing the reliability of a clinical scale that is frequently utilized in neuropsychological research and in biomedical studies, more generally. The dichotomous-ordinal scale is characterized by a single category of "absence" and two or more ordinalized categories of "presence" of a symptom trait, state, or behavior, and it also has special properties that need to be understood in order for its reliability to be appropriately assessed. Using the Brief Psychiatric Rating Scale (BPRS) as a clinical example, we cover the principles of expressing scale reliability in terms of a dichotomy ("absence" - "presence" of a given BPRS symptom); as a trichotomy ("none"; "mild to moderate" symptomatology; and "severe" symptomatology); and as the full 7-category dichotomous-ordinal scale: "none," "very mild," "mild," "moderate," "moderately severe," "severe," and "extremely severe." Criteria are presented that can be used to evaluate which of these three formats produces the most reliable results. Finally, we address, with a second sample, the important issue of replication, or whether the original reliability findings generalize to other independent populations.

Adult↗
PubMed1992

Functional status and clinical findings in patients with Alzheimer's disease.

We analyzed the association of clinical findings with impaired functional status, i.e., activities of daily living (ADLs), in a sample of 240 patients diagnosed with Alzheimer's disease by NINCDS/ADRDA or DSM-III-R criteria. Logistic regression models were used to determine independent predictors of both the number of ADL impairments and number of ADL impairments characterized as moderate to severe. Two psychiatric problems, behavioral disorders and apathy, as well as a history of hypertension were significantly associated with ADL impairment independent of age, sex, race, and cognitive impairment. Behavioral disorders and apathy were also significantly associated with moderate to severe ADL impairment, but hypertension was not significant at this level.

Activities of Daily Living↗
PubMed1992

Severe family violence and Alzheimer's disease: prevalence and risk factors.

This study describes the prevalence of violence and the putative risk factors for violence in 184 Alzheimer patients and their primary caregivers living in the community. Analysis of the severe violence subscale of the Conflict Tactics Scale indicated that 15.8% of patients had been violent in the year since diagnosis. A total of 5.4% of caregivers reported being violent toward the patient. The overall prevalence of violence was 17.4%. The variables most associated with violence were caregiver depression and living arrangement.

Aged↗
PubMed1992

Mapping of the formin gene and exclusion as a candidate gene for the autosomal recessive form of limb-girdle muscular dystrophy.

Limb-Girdle Muscular Dystrophy (LGMD) is a myopathy with clinical and transmission heterogeneity. The recessive form, LGMD2, has been recently mapped by linkage analysis to 15q. As an attempt to identify the gene involved in this pathology, we tested as candidate gene the LD locus, called LD for limb deformity. This gene has recently been identified and mapped to chromosome 15q13-q14. It is homologous to the murine formin gene which is localized to mouse chromosome 2. Mutations in this murine gene have been shown to cause limb deformity and kidney defect. YAC clones containing the LD gene were isolated and utilised to confirm the cytogenetic localisation. Internal DNA polymorphisms of the LD locus were analyzed in LGMD2 and CEPH families. The LD gene was mapped between the alpha cardiac actin gene and the D15S24 locus. Crossovers between the LGMD2 and the LD loci excluded the LD gene as a candidate for LGMD2.

Base Sequence↗
PubMed1992

Tumor necrosis factor in alcohol enhanced endotoxin liver injury.

Endotoxin administration causes liver injury. Patients with alcoholic liver disease frequently have portal vein and systemic endotoxemia, and some investigators have suggested that endotoxin plays an etiologic role in alcoholic liver injury. Many of the metabolic effects of endotoxin are mediated by the cytokine tumor necrosis factor (TNF). It was the purpose of this study to determine whether TNF plays a role in ethanol-enhanced endotoxin liver injury. Rats were fed either a diet in which 36% of the calories were from ethanol or an isocaloric control diet. After 6 weeks, groups of 10 rats were intravenously injected with either saline, 1 mg/kg endotoxin, or 30 micrograms/kg of a prostaglandin E1 (PGE1) analogue + 1 mg/kg endotoxin 24 hr prior to sacrifice. Ethanol/endotoxin-treated rats had significantly higher liver enzyme levels (ALT: 1064 +/- 355 IU/liter, AST: 2024 +/- 515 IU/liter) compared with isocaloric/endotoxin controls (ALT: 237 +/- 54 IU/liter, AST: 602 +/- 80 IU/liter). Ethanol/endotoxin rats also had significantly higher peak serum TNF concentrations (992 +/- 200 units/ml) compared with isocaloric/endotoxin controls (344 +/- 96 units/ml). Pretreatment of ethanol/endotoxin rats with PGE1 caused significant attenuation of liver injury (ALT: 267 +/- 64 IU/liter, AST: 612 +/- 77 IU/liter) and a diminished serum TNF response. In contrast to chronic ethanol administration, acute gavage with 2 mg/kg ethanol (30% w/v) followed by intravenous injection of 2 mg/kg endotoxin produced significantly lower peak serum TNF concentrations (401 +/- 76 units/ml) than gavage with distilled water (1152 +/- 208 units/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1992

A cluster of cases of Escherichia coli O157 infection in a day-care center in a communal settlement (Kibbutz) in Israel.

This is the first report in Israel of a cluster of cases of diarrhea associated with the isolation of Escherichia coli O157 in stool samples. E. coli O157:NM (nonmotile), producing verotoxins 1 and 2 was isolated from the stool samples of three infants less than 1 year of age with diarrhea and from a fourth asymptomatic infant staying in the same day-care class in a communal settlement (kibbutz). The clinical presentation included nonbloody diarrhea without other symptoms. Surveillance efforts should be enacted in order to define the relative importance of E. coli O157 infections in Israel.

Child Day Care Centers↗
PubMed1992

Antibodies to shiga holotoxin and to two synthetic peptides of the B subunit in sera of patients with Shigella dysenteriae 1 dysentery.

Acute- and convalescent-phase sera from 18 Thai patients and convalescent-phase sera from two Israeli patients and one Bangladeshi patient with Shigella dysenteriae 1 (Shiga) dysentery were tested by enzyme-linked immunosorbent assay to detect antibodies that bind S. dysenteriae lipopolysaccharide (LPS), Shiga holotoxin, or two synthetic peptides representing epitopes from the B subunit of Shiga toxin. Paired sera from 24 Maryland adults with Shigella flexneri 2a or Shigella sonnei diarrhea served as negative controls. Of the 16 paired Thai serum samples tested for immunoglobulin G LPS antibody, 10 had greater than or equal to 4-fold rises (the two subjects with the highest convalescent-phase titers exhibited toxin-neutralizing activity); acute-phase specimens from four of the remaining six individuals already had elevated Shiga LPS titers in their acute specimens ranging from 1:800 to 1:12,800. Similarly, convalescent-phase sera from the two Israeli patients and the Bangladeshi patient revealed LPS titers of 1:800 to 1:3,200. In contrast, none of the Maryland volunteers with S. flexneri or S. sonnei diarrhea manifested rises in Shiga anti-LPS (P less than 0.00001 versus 10 of 16 Thai patients). Only 4 of the 18 Thai patients had significant rise in antibody to purified Shiga toxin, while one of the two Israeli patients and the one Bangladeshi patient had elevated convalescent-phase titers. None of the sera that reacted with Shiga holotoxin had antibody that bound to the peptides. This report, which describes a search for serum antibodies that bind Shiga toxin in patients with Shiga dysentery, demonstrates such antibodies in only a minority of patients with bacteriologically confirmed disease. During Shiga dysentery, Shiga toxin may be elaborated in such small quantities in vivo that it fails to elicit an immune response in most patients even though it may exert biological effects. In this behavior Shiga toxin resembles tetanus toxin, another potent exotoxin that fails to elicit antitoxic responses in people who recover from clinical tetanus.

Adolescent↗