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Biomedical subjects

D Cohen

Publications and source records attributed to D Cohen.

At least 415 records · Page 23Linked to original sources
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↗
PubMed1992

Presence of specific immunoglobulin A-secreting cells in peripheral blood after natural infection with Shigella sonnei.

The appearance of antigen-specific immunoglobulin A (IgA) antibody-secreting cells (ASCs) following natural infection with Shigella sonnei during a common-source outbreak caused by this organism was evaluated in a modified enzyme-linked immunosorbent assay (ELISPOT). A mean IgA ASC value of 2,131.6/10(6) cells against homologous S. sonnei lipopolysaccharide (LPS) was detected in blood samples obtained from patients with bacteriologically proven S. sonnei shigellosis 5 and 10 days after the onset of disease. In the same blood samples, the level of ASC measured against heterologous antigen (Shigella flexneri serotype 2a LPS) was significantly lower than that of the homologous antigen (mean value, 33.12/10(6) cells). Furthermore, the mean number of activated B cells that secreted anti-S. sonnei LPS antibodies was significantly higher among patients with S. sonnei shigellosis than it was among patients with non-Shigella diarrhea (2.5/10(6) cells; standard error, 1.0) and healthy subjects (5.1/10(6) cells; standard error, 2.3) (P less than 0.05). The anti-LPS IgA ASC activity was easily detected within 5 days of the onset of disease, a point at which the levels of anti-S. sonnei LPS IgG and even IgA antibodies were hardly detectable in serum.

Adolescent↗
PubMed1992

Exclusion of cardiac myosin heavy chain and actin gene involvement in hypertrophic cardiomyopathy of several French families.

Familial hypertrophic cardiomyopathy (FHC) is characterized by idiopathic myocardial hypertrophy, which often and predominantly involves the interventricular septum. The disease is transmitted as an autosomal dominant trait, and its major risk is sudden death. It was recently demonstrated that this disease is genetically heterogeneous and that in 13 of 18 unrelated families the morbid locus, termed FHC-1, maps to chromosome 14q11-12 in and/or very near the cardiac beta-myosin heavy chain gene. We have performed linkage analysis with five chromosomal markers detecting polymorphisms in either the cardiac beta-myosin heavy chain gene or the cardiac actin gene (located on chromosome 15q) on eight families from different regions of France. We show that 1) it is possible to analyze medium-sized families by using highly informative microsatellite markers located in these genes and 2) the disease is not linked to the two contractile protein genes in any of these families. Moreover, 10-20% of chromosome 14 and 20-40% of chromosome 15 in the vicinity of the respective markers were excluded as possible locations for the morbid locus. These results provide new insights into the identification of the genes responsible for FHC.

Actins↗
PubMed1992

An empirical evaluation of the Global Deterioration Scale for staging Alzheimer's disease.

OBJECTIVE: Although the Global Deterioration Scale has been widely used since its publication in 1982, its stages are based on implicit assumptions about the linearity, temporality, and interdependence of cognitive, functional, and behavioral impairment in Alzheimer's disease. The authors evaluated the validity of these assumptions and tested the hypothesis that psychopathology and functional impairment would occur in earlier stages than the Global Deterioration Scale predicts. METHOD: The analyses were based on data on 324 patients with Alzheimer's disease who were selected from a registry of such patients. Data analyses included 1) descriptive statistics on the frequency of psychiatric symptoms and difficulties with activities of daily living and 2) logistic regression, with symptoms and functional impairment as independent variables, to test for significant changes in patients' status between stages of the Global Deterioration Scale. RESULTS: More than 50% of the patients at stage 2 displayed psychopathology, and 32% had two or more symptoms. The significant increase in psychiatric symptoms occurred between stages 3 and 4, not between stages 5 and 6 as predicted by the Global Deterioration Scale. Impairment in functional status was observed at all stages, and significant increases occurred between stages 3 and 4 as well as between stages 5 and 6. CONCLUSIONS: Psychiatric symptoms and functional impairment occur earlier than predicted by the Global Deterioration Scale, and the rate of change is also different from that specified in the scale. Separate scales to describe cognitive, clinical, and functional status may be the best way to describe the illness until better multidimensional instruments are developed.

Activities of Daily Living↗
PubMed1992

Are there clinical differences between familial and nonfamilial Alzheimer's disease?

OBJECTIVE: The purpose of the study was to determine whether there are differences in clinical characteristics in two groups of patients with Alzheimer's disease, those reported to have a family history of dementia and those without a family history of dementia. METHOD: Using a data set from an Alzheimer's disease patient registry, funded as part of a National Institute on Aging cooperative agreement, the authors made comparisons of sociodemographic and clinical variables in a group of 462 patients with Alzheimer's disease, 172 reported to have at least one first-degree relative with dementia and 290 classified with no family history. RESULTS: Patients with a presumptive family history differed from those without a family history in two ways: the course of dementia was described as having a fast rather than a slow progression from onset of symptoms to diagnosis, and caregivers reported a higher prevalence of family history of psychiatric disorders. There were no significant differences in age at onset, duration, female gender, aphasia and apraxia, handedness, family history of Down's syndrome, or number of children, brothers, and sisters. CONCLUSIONS: The association of faster course and family history of psychiatric disorders in the patients with a family history of dementia is consistent with the hypothesis of heterogeneity, but the overall results could also be explained by a genetic-environmental model of Alzheimer's disease.

Age Factors↗
PubMed1992

The potential role of custody facilities in controlling sexually transmitted diseases.

BACKGROUND: The National Commission on Correctional Health Care recommends that medical screening, including tests for syphilis and other sexually transmitted diseases, be performed by the 14th day after initial booking procedures. Because the average length of stay in detention is usually less than 14 days, most detainees are not screened or treated for asymptomatic communicable diseases. METHODS: In order to determine the incidence and prevalence of syphilis among those booked through a large county jail, a rapid screening procedure to test newly incarcerated inmates and treat those infected was implemented over a 3-week period. RESULTS: Among 6309 detainees eligible for testing during the 3-week period of the study, 129 (2%) were diagnosed with syphilis. During the preceding month when only those reporting symptoms or high-risk behaviors were screened, 20 cases were diagnosed. The sensitivity and predictive value of self-reported risk factors for syphilis infection were low. Among the first 110 diagnosed cases, 17 (15.5%) were released within 3 days and 86 (78%) were released within 6 days. CONCLUSIONS: If screening and treatment for syphilis are delayed until the 14th day after booking, the majority of infected inmates will be released prior to evaluation and treatment. Rapid screening and treatment for selected sexually transmitted diseases are likely to be an effective public health measure when implemented in custody settings.

Adolescent↗
PubMed1992

Neuroleptic medication and prescription practices with sheltered-care residents: a 12-year perspective.

OBJECTIVES: Most adult residents of sheltered-care facilities (board and care, family care, psychosocial rehabilitation, and other supported housing arrangements) for the chronically mentally ill receive neuroleptics. These facilities house over 300,000 mentally ill residents, but neuroleptic prescription practices with this population have not been studied. METHODS: A probability sample (n = 393) of all adult former psychiatric patients in sheltered care in California was surveyed in 1973; 94% of the located survivors (n = 243) were reinterviewed 12 years later. RESULTS: In 1973, 79% received neuroleptics; in 1985, 76%. Polypharmacy decreased, and the elderly remained less medicated than adults. Yet, mean daily neuroleptic doses doubled, more persons received higher doses, and 62% reported adverse effects. Furthermore, high dosing was attributed to psychiatrists rather than other physicians, even when controlling for residents clinical and sociodemographic characteristics. CONCLUSIONS: Neuroleptic drugs became the staple pharmacological treatment for mentally ill sheltered-care residents. While physicians more cautiously medicated the elderly, they had not reduced doses by 1985, even after a decade of treatment. The specialty of the prescriber was an important factor in preference for high-dose treatment.

Adolescent↗
PubMed1992

[Surgery of idiopathic epimacular membranes. Prognostic factors].

Seventy consecutive cases of idiopathic epimacular membrane removal were reviewed in order to evaluate the prognosis factors of this surgery. The characteristics analyzed where the duration of the symptoms, pre and postoperative visual acuity and the macular changes on fluorescein angiography. The mean follow-up after surgery was 9 months. Mean preoperative visual acuity was 0.17 and the mean best postoperative visual acuity 0.43. Visual acuity improved by 2 lines or more in 81% of the cases and the mean improvement was 3.5 lines. The complications of epimacular membrane surgery included nuclear cataract (10 eyes underwent cataract surgery), peripheral retinal breaks (3%), and retinal detachment (3%) successfully operated. Three of the main preoperative data were related to better postoperative visual outcome: preoperative visual acuity: eyes with visual acuity of 0.16 or more tended to have better postoperative vision than eyes with poorer preoperative vision (mean postoperative visual acuity 0.5 and 0.34 respectively; p < or = 0.05); duration of visual impairment before surgery: eyes with a visual impairment of less than 2 years had better postoperative vision than the others (mean postoperative visual acuity, 0.5 and 0.3 respectively; p < or = 0.05); the absence of preoperative angiographic macular edema: eyes without preoperative macular edema had better postoperative vision than the others (mean postoperative visual acuity: 0.5 and 0.4 respectively; p < or = 0.05). The normal postoperative pattern of macular vessels and foveolar shape was also a statistically significant factor of good vision recovery.

Adult↗
PubMed1992

The CEPH YAC library.

Because of their large size, YACs provide is a powerful tool for physical mapping studies of complex genomes. As it will be advantageous to have genomic libraries of clones with large inserts for analyzing megabase sized regions of the human genome, we have investigated a number of parameters in order to increase the insert size of the YACs. We constructed a genomic library currently containing more than 85,000 YAC clones. Mean sizes of YACs produced at several stages of construction of the library range from 430 kb to 1,200 kb, representing 13 haploid equivalents of the human genome. This library was organized in order to allow rapid screen of YACs for large scale physical mapping of the human genome.

Chromosome Walking↗
PubMed1992

Increased plasma interleukin-6 concentrations in alcoholic hepatitis.

Interleukin-6 (hepatocyte stimulating factor) is a 26 kd cytokine that plays a major role in the acute phase response, especially the hepatic aspects of the acute phase response. Patients with alcoholic hepatitis manifest many aspects of the acute phase response. In this 6-month study we evaluated serial plasma interleukin-6 levels in 30 consecutive patients with moderate to severe alcoholic hepatitis. Mean admission plasma interleukin-6 activity was markedly increased (49.8 +/- 8.5 U/ml, normal less than 5 U/ml) in patients with alcoholic hepatitis, and levels decreased with clinical improvement to 15.6 +/- 6.1 U/ml at 6 months. Admission interleukin-6 activity correlated significantly (r = 0.82) with the severity of liver disease as assessed by the discriminant function of Maddrey. Also measured were selected assays postulated to be regulated by interleukin-6, including serum albumin (2.3 +/- 0.1 gm/dl), which was significantly depressed; alpha 1-acid glycoprotein (52 +/- 5 mg/dl), which was within normal limits; and IgA (827 +/- 70 mg/dl) and C-reactive protein (3.03 +/- 0.51 mg/dl), which were significantly elevated. Interleukin-6 activity fell over time in a pattern similar to that of bilirubin and C-reactive protein. We suggest that plasma interleukin-6 may not only regulate many aspects of the acute phase response but also may be a marker of inflammation and severity of disease in alcoholic hepatitis.

Hepatitis, Alcoholic↗
PubMed1992

A new Streptococcus group A M-29 variant isolated during a suspected common-source epidemic.

In the summer of 1988, a large epidemic of acute pharyngitis occurred in an Israeli military base. The clinical features were those of acute pharyngitis. The epidemic curve was characteristic of a common-source outbreak, possibly food-borne. Throat swabs from a sample of cases were positive for group A streptococci. Nine isolates from the epidemic were further evaluated at the local reference laboratory and serotyping showed that all were of the same strain with a distinct M protein that is a hitherto undescribed variant of M-29. We discuss the significance of unusual strains of beta-hemolytic Streptococcus appearing in food-borne outbreaks.

Acute Disease↗
PubMed1991

Theoretical analysis of library screening using a N-dimensional pooling strategy.

A solution to the problem of library screening is analysed. We examine how to retrieve those clones that are positive for a single copy landmark from a whole library while performing only a minimum number of laboratory tests: the clones are arranged on a matrix (i.e in 2 dimensions) and pooled according to the rows and columns. A fingerprint is determined for each pool and an analysis allows selection of a list containing all the positive clones, plus a few false positives. These false positives are eliminated by using another (or several other) matrix which has to be reconfigured in a way as different as possible from the previous one. We examine the use of cubes (3 dimensions) or hypercubes of any dimension instead of matrices and analyse how to reconfigure them in order to eliminate the false positives as efficiently as possible. The advantage of the method proposed is the low number of tests required and the low number of pools that require to be prepared [only 258 pools and 282 tests (258 + 24 verifications) are needed to screen the 72,000 clones of the CEPH YAC library (1) with a sequence-tagged site]. Furthermore, this method allows easy and systematic screenings and can be applied to a large physical mapping project, which will lead to an interesting map with a low, precisely known, rate of error: when fingerprinting a 150 Mb chromosome with the CEPH YAC library and 1750 sequence-tagged sites, 903,000 tests would be necessary to obtain about 20 contigs of an average length of 6.7 Mb, while only about one false positive would be expected in the resultant map. Finally, STSs can be ordered by dividing a clone library into sublibraries (corresponding to groups of microplates for example) and testing each STS on pooled clones from each sublibrary. This allows to dedicate to each STSs a fingerprint that consists in the list of the positive pools. In many cases these fingerprints will be enough to order the STSs. Indeed if large YACs (greater than 1 Mb) can be obtained, the combined screening of DNA families and YAC DNA pools would allow an integrated construction of both genetic and physical maps of the human genome, that will also reduce the optimal number of meioses needed for a 1 centimorgan linkage map.

Chromosome Mapping↗
PubMed1991

The candidate gene for the X-linked Kallmann syndrome encodes a protein related to adhesion molecules.

Kallmann syndrome associates hypogonadotropic hypogonadism and anosmia and is probably due to a defect in the embryonic migration of olfactory and GnRH-synthesizing neurons. The Kallmann gene had been localized to Xp22.3. In this study 67 kb of genomic DNA, corresponding to a deletion interval containing at least part of the Kallmann gene, were sequenced. Two candidate exons, identified by multiparameter computer programs, were found in a cDNA encoding a protein of 679 amino acids. This candidate gene (ADMLX) is interrupted in its 3' coding region in the Kallmann patient, in which the proximal end of the KAL deletion interval was previously defined. A 5' end deletion was detected in another Kallmann patient. The predicted protein sequence shows homologies with the fibronectin type III repeat. ADMLX thus encodes a putative adhesion molecule, consistent with the defect of embryonic neuronal migration.

Amino Acid Sequence↗