Search PubMed⌕ Search

Biomedical subjects

D Cohen

Publications and source records attributed to D Cohen.

At least 289 records · Page 16Linked to original sources

[Finger fibrosarcoma. A case report].

The hand is a rare site of fibrosarcoma. We report one case in a fifty two year old female patient, presenting with a two-year history of an ulcerated tumor of the palmar aspect of the right index finger. The X Ray showed severe erosion of the 2nd phalanx. Because of the large volume of the tumor, a proximal amputation of the 2nd finger was performed. Histological examination concluded on a fibrosarcoma which was completely resected. No signs of recurrence or distant metastasis were seen after 8 months. The frequency of fibrosarcoma in the hand is 2.7 to 5.3%. These tumors are rarely located in the soft tissues of the hand. The treatment is essentially surgical based on a carcinological resection, which represents the only way to avoid recurrence, which is evaluated to be 12% after amputation.

Amputation, Surgical↗

The CIC library: a large insert YAC library for genome mapping in Arabidopsis thaliana.

A new Arabidopsis thaliana (ecotype Columbia) genomic library has been constructed in Yeast Artificial Chromosomes: the CIC library (for CEPH, INRA and CNRS). Optimization of plant culture conditions and protoplast preparation allowed the recovery of large amounts of viable protoplasts. Mechanical shearing of DNA was minimized by isolation of DNA from protoplasts embedded in agarose. Cloning of large inserts was favored by including two successive size fractionation steps (after partial EcoRI digestion and after ligation with the vector arms), which selected DNA fragments larger than 350 kb. The library consists of 1152 clones with an average insert size of 420 kb. Clones carrying chloroplast DNA and various nuclear repeated sequences have been identified. Twenty-one per cent of the clones are found to contain chloroplast DNA. Therefore, the library represents around four nuclear genome equivalents. The clones containing 5S rDNA genes, 18S-25S rDNA sequences and the 180 bp paracentromeric repeated element account for 3.6%, 8.9% and 5.8%, respectively. Only one clone was found to carry the 160 bp paracentromeric repeated element. Given the smaller size of clones carrying Arabidopsis repeated DNA, the average size of remaining clones is around 480 kb. The library was screened by PCR amplification using pairs of primers corresponding to sequences dispersed in the genome. Seventy out of 76 pairs of primers identified from one to seven YAC clones. Thus at least 92% of the genome is represented in the CIC library. The survey of the library for clones containing unlinked DNA sequences indicates that the proportion of chimeric clones is lower than 10%.

Arabidopsis↗

A high-fidelity physical map of human chromosome 21q in yeast artificial chromosomes.

Understanding of the human genome has been advanced significantly by the development of large DNA fragment libraries. To create a map of chromosome 21q that integrates the physical, cytogenetic, and linkage maps, we have characterized a subset of 127 chromosome 21 yeast artificial chromosome (YAC) clones for size, by pulsed field gel electrophoresis, for chimerism and cytogenetic location, by fluorescence in situ hybridization (FISH), and for sequence-tagged sites (STS) content, by PCR. It was found that 54% generated unique map locations on chromosome 21, and 45% detected sites on other chromosomes, of which 33% likely represented true chimerism. Using a simple algorithm, the data from nonchimeric clones have been combined to generate a size-corrected minimal tiling pathway including 58 chromosome 21q YACs that represent approximately 33 Mb and include 9 gaps. To confirm the resulting order and relationship to the cytogenetic map, the breakpoints from 23 cell lines partially aneuploid for chromosome 21 have been analyzed by quantitative Southern blot dosage analysis and FISH with a subset of the markers. As one way of investigating the relationship of the genetic to the physical map, the genetic map was superimposed on the physical map using a subset of well-defined markers common to both. The results suggest potential hot spots for recombination and/or gaps in the physical map. This integrated map will facilitate the search for the genes responsible for the Down syndrome phenotypes and provide a better understanding of genome organization and chromosome structure.

Aneuploidy↗

Intransal or intragastric immunization with proteosome-Shigella lipopolysaccharide vaccines protects against lethal pneumonia in a murine model of Shigella infection.

Mice immunized intransally or intragastrically with proteosome vaccines containing either Shigella sonnei or S. flexneri 2a lipopolysaccharide were protected against lethal pneumonia caused by homologous organisms in an experimental murine intranasal challenge model of Shigella infection. Histopathological analysis demonstrated that immunization also protected against the progressive lesions resulting from invasion of the pulmonary mucosa by S. sonnei. These data show that mucosal proteosome-lipopolysaccharide vaccines can protect against lethal bacterial pneumonia and indicate that such vaccines are promising candidates for protection against intestinal shigellosis.

Animals↗

Comprehensive tuberculosis control for patients at high risk for noncompliance.

The current tuberculosis epidemic in the United States is marked, in many areas, by high rates of noncompliance with antituberculous regimens. In response to this, a comprehensive program of medical, nursing, social services, and supervised therapy was developed at Bellevue Hospital. Most patients were referred to the on-site directly observed therapy program (DOT) located in the hospital. Patients on DOT received daily or twice weekly therapy, and were given incentives to enhance compliance. Outreach was used to track patients who missed appointments. From November 1992 through July 1993, 113 patients were referred. HIV infection, homelessness, illicit drug use, and alcoholism were common. Follow-up revealed that 11 patients were noncompliant and completely lost to follow-up; of the remaining 102, 99% achieved bacteriologic cure. Of the 102 patients who received therapy, 74 attended the Bellevue DOT clinic, 16 attended other DOT programs in the city or received medication at home, and three died of HIV-related, nontuberculous illness. Nine patients were self-medicated and judged treatment successes. We conclude that a comprehensive hospital-based tuberculosis control program is capable of achieving a high degree of success, even in a population at high risk for noncompliance.

Adult↗

Day-program-based treatment in the Amsterdam City Center.

The Social Psychiatric Services Center (SPDC C/OW) is the acute psychiatric clinic for the Amsterdam city center. The unit, originally an integrated part of a General Psychiatric Hospital located outside Amsterdam, was transferred to the city center in 1988. Since then, the unit has been transformed into a fully operational institute for day-program-based treatment, both as a substitute for 24 hours hospitalization and as an extension of community treatment programs. The SPDC's organization, the format and contents of the treatment program and the integrated cooperation with the district mental health care partners proceed directly from the consistently applied key concepts: day-program-based treatment, continuity of care and tailor-made care. After an overview of some relevant developments in the Netherlands in general and in Amsterdam more specifically the SPDC is described in detail. Some conclusions, based on the experience of 6 years work in this organisation, are drawn, focussing on long term treatment strategies and the differences and merits of community-based versus hospital-based care.

Adult↗

The metanephric blastema differentiates into collecting system and nephron epithelia in vitro.

The kidney forms from two tissue populations derived from intermediate mesoderm, the ureteric bud and metanephric mesenchyme. It is currently accepted that metanephric mesenchyme is committed to differentiating into nephrons while the ureteric bud is restricted to forming the renal collecting system. To test this hypothesis, we transferred lacZ into pure metanephric mesenchyme isolated from gestation day 13 rat embryos. The fate of tagged mesenchymal cells and their progeny was characterized after co-culture with isolated ureteric buds. When induced to differentiate by the native inducer of kidney morphogenesis, lineage-tagged mesenchymal cells exhibit the potential to differentiate into collecting system epithelia, in addition to nephrons. The fate of cells deriving from isolated ureteric buds was also examined and results of these lacZ gene transfer experiments indicate that the majority of ureteric bud cells differentiate into the renal collecting system. These cell fate studies combined with in situ morphological observations raise the possibility that collecting system morphogenesis in vivo occurs by growth of the ureteric bud and recruitment of mesenchymal cells from the metanephric blastema. Thus, metanephric mesenchyme may be a pluripotent renal stem population.

Animals↗

Age-related ANP release in response to acute vs. chronic sodium loading.

Atrial natriuretic peptide (ANP) levels were studied in young (2-week-old) and old (age 20 months) rats following acute (20 mL/kg bolus of normal saline i.v.) vs. chronic sodium loading (high-salt diet for 21 days). In both groups serum ANP rose significantly 1 h post i.v. loading. However, the increment was greater in the old animals. On chronic sodium load, in the young group, ANP rose significantly on days 3 and 7, subsequently declining to baseline. In the old animals, no increase in ANP was noted throughout the chronic experiment. Twenty-four-hour urinary sodium excretion was similar in the two groups following acute or chronic salt load. The results suggest that: (1) The old kidney requires a greater ANP stimulus to excrete a given acute i.v. sodium load. (2) The relatively diminished elasticity of the old heart plays a major role in the exaggerated ANP release in response to a bolus i.v. load of saline. (3) The role of ANP in maintaining homeostatic renal sodium excretion during short-term sodium oral loading is different in the two age groups.

Aging↗

Generation of 28 sequence-tagged sites (STSs) from yeast artificial chromosome (YAC) clones anchored at human chromosome 21q22.1 region.

Twenty-eight sequence-tagged sites (STSs) were newly generated from the DNA sequences of vector-insert junctions from yeast artificial chromosomes (YACs) anchored at chromosome 21q22.1 region. The insert DNAs adjacent to vector arms were specifically amplified through inverse PCR method to clone into pUC19 vector for sequencing. Sixty DNA junctions from 44 CEPH YAC clones were cloned and sequenced. Of these DNA sequences of junctions between vector-arms and DNA inserts, twenty-eight STSs were finally obtained to show the accurate amplification, which is specific for human chromosome 21. The sets of 28 STSs were useful to build fine YAC contigs by STS-mediated YAC walking at the 21q22.1 region.

Animals↗

The effects of HIV on cognitive and motor development in children born to HIV-seropositive women with no reported drug use: birth to 24 months.

OBJECTIVE: This study documents delays in the mental and motor functioning of infants perinatally infected with human immunodeficiency virus (HIV) while controlling for confounding effects of prenatal drug exposure, ethnicity, socioeconomic status, and maternal separation and death. METHODS: The cognitive and motor development of 126 infants born to nondrug-using, HIV-seropositive Haitian women was assessed at 3-month intervals through 24 months of age using the Bayley Scales of Infant Development. By 18 months of age, 28 of the infants were diagnosed as HIV-infected, and the 98 uninfected infants served as a control group. The infected and uninfected infants did not differ with respect to mean gestational age, birth weight, ethnicity, or rates of maternal separation and death. RESULTS: By 3 months of age, the mean mental and motor scores of the infected infants were significantly lower than those of the uninfected controls. Furthermore, the initial differences between the two groups increased over time, as many of the infected infants became increasingly delayed. Although the infected infants tended to perform more poorly than the uninfected infants, nearly one third of the infected infants exhibited relatively normal cognitive development and half demonstrated relatively normal motor development. CONCLUSIONS: Over the first 24 months of life, the mean rate of development of HIV-infected infants is significantly slower than that of noninfected infants born to seropositive mothers. This occurs even when the effects are not confounded with those of prenatal drug exposure.

Adult↗

[Cellular senescence and survival of T lymphocytes].

In order to study cellular senescence in T lymphocytes and its link with aging, we have undertaken long-term cultures from adult individuals (aged from 20 to 40) and centenarians. The proliferative advantage of CD4+ over CD8+ T cells is reversed after the second stimulation. Periodically stimulated cultures remained exponentially growing during nearly 200 days, whereas 2 of them that were continued for 300 days stopped proliferating. However, once this phase of senescence is reached, the cells do not die out. Six other cultures remained viable for 34 months without proliferation but with conservation of the cell number. Three of these cultures have clonal karyotypic abnormalities: trisomy 2 and telomeric fusions.

Adult↗

Compliance with public sector HIV medical care.

Despite the availability of free or low-cost public sector human immunodeficiency virus (HIV) health-care services, important inequities in utilization exist. This study examined two measures of compliance with HIV medical care: attendance of scheduled outpatient visits and use of the emergency room. Clients of two public HIV outpatient clinics were followed from time of health-care initiation to either death or the end of the study. The association of race, sex, age, and injection drug use (IDU) with these measures were examined in multivariate logistic regression. Models were adjusted for disease staging at time of entry and for length of follow-up time in clinic. Of 1824 clients followed, 15% failed to attend scheduled visits and 18.1% had at least one emergency room visit. Clients who missed visits were more likely to be African American, to have a history of IDU, and to have a CD4 cell count < 500/mm3 or an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection at entry. They were also more likely to have > or = 12 months of follow-up time in the HIV clinic, but were less likely to have entered into health care from an early intervention clinic. Clients who had at least one emergency room visit were more likely to be African American, female, IDU, and under 22 years of age; these clients were also more likely to have entered with CD4 < 200/mm3 or with an opportunistic infection, and to have > or = 12 months of follow-up in the clinic.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Analysis of the interactions of SDZ PSC 833 ([3'-keto-Bmt1]-Val2]-Cyclosporine), a multidrug resistance modulator, with P-glycoprotein.

Multidrug resistance (MDR) is considered to be an important impediment to the effective treatment of cancer. P-glycoprotein, the drug efflux pump that mediates this resistance, can be inhibited by a wide variety of pharmacological agents, resulting in the circumvention of the MDR phenotype. SDZ PSC 833 ([3'-keto-Bmt1]-Val2]-cyclosporine), a nonimmunosuppressive cyclosporine D derivative, was identified to be a potent MDR modulator (Gaveriaux et al. J. Cell Pharmacol. 2:225-234; 1991). In this study, the interactions of P-glycoprotein with two cyclosporine derivatives, SDZ PSC 833 and cyclosporine A (CsA, Sandimmune), were analyzed. SDZ PSC 833 enhanced the sensitivity of the MDR cells to anticancer drugs by increasing the accumulation and inhibiting the efflux of cytotoxic agents from resistant cells more efficiently than CsA. The two cyclosporine analogs competed with the labeling of P-glycoprotein by a photoactive cyclosporine derivative. In addition, membrane vesicles derived from resistant cells bound SDZ PSC 833. However, CsA was transported by P-glycoprotein, whereas SDZ PSC 833 was not actively transported. This resulted in a prolonged inhibitory effect by SDZ PSC 833. The studies suggest that the binding of SDZ PSC 833 to P-glycoprotein in the absence of its transport from MDR cells mediated its high potency as an MDR reversing agent. In addition, the comparison of the two cyclosporine analogs indicated that limited chemical modifications of MDR reversing agents can affect their potential to inhibit P-glycoprotein function.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Changing pattern of expression of the epidermal growth factor receptor and transforming growth factor alpha in the progression of prostatic neoplasms.

The autocrine/paracrine interaction of the epidermal growth factor receptor (EGFr) and transforming growth factor alpha (TGF-alpha) has been implicated in prostate cancer cell growth and proliferation. To evaluate the role of EGFr and TGF-alpha in prostate cancer progression, we studied the immunohistochemical staining pattern of EGFr and TGF-alpha in malignant primary and hormone-independent metastatic prostate lesions. The specimens evaluated included 37 primary carcinomas (34 hormone-naive and 3 hormone-refractory tumors) and 22 metastases. For each specimen, the pattern of expression was evaluated and staining reactivities graded from 0-3, with 0 representing no staining and 3 representing homogeneous and intense staining. Primary malignant prostate epithelial cells in areas with discrete gland formation showed strong EGFr immunostaining, while stromal cells were generally nonreactive. In untreated primary tumors, TGF-alpha expression was primarily in the stroma, while epithelial cells were weakly positive in several cases. Malignant epithelial cells adjacent to neural elements that stained positive for TGF-alpha was frequently observed. A homogeneous staining pattern for EGFr was noted in 17 (89%) of 19 evaluable androgen-independent-refractory metastases, while TGF-alpha expression was found in 14 (78%) of 18 evaluable cases. Overall, 14 of 18 androgen-independent metastases coexpressed the receptor and the ligand. These results suggest that, unlike primary prostate tumors where a paracrine relationship between EGFr and TGF-alpha appears to predominate, the potential for autocrine stimulation may exist in the majority of metastatic androgen-independent tumors. Furthermore, the changing pattern of expression as the disease evolves from the localized hormone-naive to metastatic androgen-independent condition suggests that strategies aimed at blocking this growth factor pathway may be of therapeutic importance for androgen-independent disease.

Adrenal Gland Neoplasms↗

NF-IL6, a member of the C/EBP family of transcription factors, binds and trans-activates the human MDR1 gene promoter.

Revealing the regulatory mechanisms involved in P-glycoprotein expression is important to our understanding of multidrug resistance (MDR) in tumor cells. The MDR1 gene encoding P-glycoprotein contained a promoter sequence (-157 to -125) that was found to be homologous with other mdr gene promoters and that specifically interacted with a nuclear protein. The nuclear protein was identified, using a HeLa lambda gt11 cDNA expression library, to be the transcriptional regulator nuclear factor for interleukin-6 (NF-IL6), a member of the C/EBP family of transcription factors that bound an NF-IL-6-like consensus element 5'-TTTCGCAGT-3'. Furthermore, a glutathione S-transferase fusion protein (10.1-glutathione S-transferase) containing the partial NF-IL6 cDNA was also found to specifically interact with the MDR1 promoter sequence. Co-transfection of an NF-IL6 expression vector with a chloramphenicol acetyltransferase reporter gene driven by 1018 base pairs of MDR1 5'-flanking sequences demonstrated that NF-IL6 trans-activated the MDR1 promoter. This trans-activation was significantly reduced when the NF-IL6 element in the reporter gene construct was deleted or mutated. Identification of NF-IL6 as an important transcriptional regulator and the implications of its potential role in MDR1 gene induction in response to a variety of stimuli are discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗