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Biomedical subjects

A Lash

Publications and source records attributed to A Lash.

At least 19 recordsLinked to original sources
PubMed1999

The Cancer Genome Anatomy Project: EST sequencing and the genetics of cancer progression.

As the process of tumor progression proceeds from the normal cellular state to a preneoplastic condition and finally to the fully invasive form, the molecular characteristics of the cell change as well. These characteristics can be considered a molecular fingerprint of the cell at each stage of progression and, analogous to fingerprinting a criminal, can be used as markers of the progression process. Based on this premise, the Cancer Genome Anatomy Project was initiated with the broad goal of determining the comprehensive molecular characterization of normal, premalignant, and malignant tumor cells, thus making a reality the identification of all major cellular mechanisms leading to tumor initiation and progression ([Strausberg, R.L., Dahl, C.A., and Klausner, R.D. (1997). "New opportunities for uncovering the molecular basis of cancer." Nat. Genet., 16: 415-516.], www.ncbi.nlm.nih.gov/ncicgap/). The expectation of determining the genetic fingerprints of cancer progression will allow for 1) correlation of disease progression with therapeutic outcome; 2) improved evaluation of disease treatment; 3) stimulation of novel approaches to prevention, detection, and therapy; and 4) enhanced diagnostic tools for clinical applications. Whereas acquiring the comprehensive molecular analysis of cancer progression may take years, results from initial, short-term goals are currently being realized and are proving very fruitful.

Databases, Factual↗
PubMed1999

A pilot study of interferon alpha-2a, fluorouracil, and leucovorin given with granulocyte-macrophage colony stimulating factor in advanced gastrointestinal adenocarcinoma.

We reported previously that the addition of recombinant Escherichia coli human granulocyte-macrophage colony stimulating factor (GM-CSF) to a 5-fluorouracil (5-FU) and leucovorin (LV) regimen seemed to ameliorate diarrhea and permit increased 5-FU dose intensity (J. L. Grem et al., J. Clin. Oncol., 12: 560-568, 1994). We then tested the effect of GM-CSF given with a more toxic regimen of 5-FU/LV/IFN-alpha (IFN alpha-2a). Thirty-one patients with a good performance status and no prior chemotherapy for systemic disease received IFN alpha(-2a (5 MU/m2 s.c., days 1-7), 5-FU (370 mg/m2 i.v., days 2-6), LV (500 mg/m2 i.v., days 2-6), and GM-CSF (Saccharomyces cerevisiae 250 microg/m2 s.c., days 7-18) every 3 weeks. Toxicities and 5-FU dose intensity were compared with that observed in our prior Phase II trial with 5-FU/LV/IFN alpha-2a (J. L. Grem et al., J. Clin. Oncol., 11: 1737-1745, 1993). In comparison with the prior Phase II study, the WBC and granulocyte nadirs in the present trial were significantly higher. When trends in toxicity grades for all cycles were compared, stratifying for 5-FU dose, the incidence and severity of mucositis, skin rash, WBC toxicity, and granulocyte toxicity were significantly lower in the present trial, whereas nausea/vomiting and fatigue were significantly worse. The delivered 5-FU dose intensity for all cycles of therapy appeared to be significantly higher in the present trial. Six of 28 evaluable patients had a partial response (21.4%), and 13 (46%) had stable disease for > or =12 weeks. Despite treatment-related toxicity, patient quality of life did not worsen during the study. No correlation was observed between thymidylate synthase content in primary tumor specimens and response, time to treatment failure, or survival. The addition of GM-CSF appeared to decrease the severity of leukopenia, granulocytopenia, mucositis, and skin rash when compared with our prior experience with this regimen of 5-FU/LV/IFN alpha-2a, at the cost of greater nausea/vomiting and fatigue. The potential impact of increased 5-FU dose intensity on clinical response, however, remains to be determined.

Adenocarcinoma↗
PubMed1997

Monoclonal origin of multicentric Kaposi's sarcoma lesions.

BACKGROUND: Kaposi's sarcoma has features of both hyperplastic proliferation and neoplastic growth. Multiple lesions, in which spindle cells are prominent, often arise synchronously over widely dispersed areas. We tested the hypothesis that the spindle cells in these multicentric lesions originate from a single clone of precursor cells. METHODS: To determine whether Kaposi's sarcoma is a monoclonal disorder, we assessed the methylation patterns of the androgen-receptor gene (HUMARA) in multiple lesions from women with the acquired immunodeficiency syndrome. In polyclonal tissues, about half the copies of each HUMARA allele are methylated, whereas in cells derived from a single clone all the copies of only one allele are methylated. To minimize contamination by normal DNA, we used microdissection to isolate areas composed primarily of spindle cells, the putative tumor cells. RESULTS: Eight patients with a total of 32 tumors were studied. Of these tumors, 28 had highly unbalanced methylation patterns (i.e., predominant methylation of one HUMARA allele). In all the tumors that had unbalanced methylation from a given patient, the same allele predominated. CONCLUSIONS: These data indicate that Kaposi's sarcoma is a disseminated monoclonal cancer and that the changes that permit the clonal outgrowth of spindle cells occur before the disease spreads.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Presence of Human Herpesvirus 8 Is Specific to Kaposi's Sarcoma Lesion.

Background: Human herpesvirus 8(HHV8) has previously been shown to be associated with Kaposi's sarcoma (KS) skin lesions in HIV-positive and negative patients. This study was designed to test, on a microscopic level, using the microdissection technique in frozen and formalin-fixed tissue, whether HHV8 DNA is specific to the KS lesion. Methods and Results: Thirty-seven evaluable KS lesions were microdissected and DNA extracted, and HHV8-specific polymerase chain reaction (PCR) was performed. All of the KS lesions showed a PCR product; none of the microscopically adjacent normal tissue samples showed a PCR product. One of the PCR products was sequenced, confirming the presence of HHV8 DNA. Conclusions: HHV8 was shown to be specific to the KS lesion at the microscopic level.

Journal Article↗
PubMed1990

Neurotoxicological evaluation of hospital sterilizer workers exposed to ethylene oxide.

Ethylene oxide is now frequently used to chemically sterilize heat-sensitive materials in the hospital setting. Previous reports of neurotoxic effects of ethylene oxide have been described in animals and humans. Recent reports suggest that cognitive deficits may be associated with chronic low-level ethylene oxide exposure. We undertook this study of hospital workers with chronic ethylene oxide exposure and compared them with a non-exposed control group in an attempt to detect neurological and neuropsychological abnormalities. Ethylene oxide breathing zone levels of up to 250 ppm in exposed subjects were reported. All evaluations were done without examiners' knowledge of exposure status of the subjects. The exposed group was found to have a statistically significant lower P300 amplitude, bilaterally hypoactive distal deep tendon reflexes and poorer performance on neuropsychological tests involving psychomotor speed. Exposed subjects acknowledged more symptoms and higher levels of depression and anxiety. Nerve conduction velocities and EEG spectral analysis were similar in both exposed and control groups as were scores on most psychological tests. Based upon this information and prior reports, ethylene oxide should be considered in a differential diagnosis of neuropsychological, peripheral and central nervous system dysfunction in workplace settings associated with ethylene oxide exposure.

Adult↗
PubMed1990

Neuropsychologic "impairment" in a cohort of hospital workers chronically exposed to ethylene oxide.

Ethylene Oxide is widely used to sterilize heat-sensitive materials. Acute and chronic neurogenic effects to the central and peripheral nervous system in man and animals have been described. To assess the chronic, subtle neuropsychologic effects of ethylene oxide, we performed a cross-sectional study of 25 hospital central supply workers exposed to low levels of ethylene oxide and 24 unexposed control workers. Subjects were tested using a neuropsychological screening battery by examiners blinded to exposure status. Testing results were reviewed independently by two neuropsychologists without knowledge of exposure. Subject status was categorized as normal, "impaired," or disagreement (between the two neuropsychologists). There were significantly more subjects concordantly judged as impaired in the exposed group versus the control group (chi 2 (2) = 6.0861, p less than 0.05). Although limited by the cross-sectional study design and the global categorization, these findings suggest that CNS dysfunction and cognitive impairment may result from chronic ethylene oxide exposure in hospital central supply units.

Adult↗
PubMed1989

Cross-sectional neurotoxicology study of lead-exposed cohort.

Although the toxic effects of lead have been known for centuries, lead intoxication is still widespread in the United States. Without baseline tests of neuropsychological, neurobehavioral and neurophysiological testing it may be difficult to detect subtle changes in neurological function after lead exposure. This may be further confounded by partial chelation treatment and exposure to neurotoxic mixtures or inability to quantitate alcohol consumption. We undertook a cross-sectional study to address these problems in 24 exposed and 29 control subjects in a plant that manufactured electrical components using fritted leaded glass to coat capacitors and transistors. Potentially exposed workers had blood lead levels ranging between 3 micrograms/dL to 135 micrograms/dL. Industrial hygiene monitoring revealed the plant's air lead levels ranged from 61 micrograms/m3 to 1,700 micrograms/m3 in excess of OSHA permissible exposure limits of 40 micrograms/m3/10 hr day. Using a specially designed battery of neurophysiological, neurobehavioral and neuropsychological screening tests, we demonstrated a significant difference from controls in measures of psychomotor speed, motor strength and verbal memory. Although limited by the cross-sectional design, these findings support the hypothesis that the battery of neurophysiological, neuropsychological and neurobehavioral tests can detect a significant inter-group differences between lead-exposed and control subjects.

Adult↗
PubMed1987

Studies on human blood lymphocytes with iC3b (type 3) complement receptors: III. Abnormalities in patients with active systemic lupus erythematosus.

Lymphocytes displaying iC3b (Type 3) complement receptors (CR3) were quantified by flow cytometry in patients with systemic lupus erythematosus. The percentages and absolute numbers were compared to age and sex matched controls. Total CR3+ lymphocytes identified by the monoclonal antibodies OKM1 or Leu 15 were significantly decreased in patients with symptomatic arthritis, serositis or vasculitis and those with lupus nephritis, whereas values for CR3+ lymphocytes in patients with inactive disease were similar to normal donors. The phenotype of CR3+ lymphocytes was markedly different in patients with active SLE. In normals granular lymphocytes bearing Fc receptors for IgG (L cells) comprised two-thirds of CR3+ lymphocytes. However, in SLE this subset was reduced to 20% and there was a corresponding increase in CR3+ lymphocytes co-expressing the T3 marker. Percentages of CR3 T4+ but not CR3+ T8+ lymphocytes were significantly increased in SLE. Although patients with active disease were lymphopenic, absolute numbers of CR3+ lymphocytes co-expressing T cell markers were similar to normal controls. Since L cells are non-specific suppressors of Ig production, the reduction of this subset along with the increase in CR3 T4+ cells could contribute to unregulated antibody production characteristic of SLE.

Adult↗
PubMed1986

Studies on human blood lymphocytes with iC3b (type 3) complement receptors. I. Granular, Fc-IgG receptor positive and negative subsets in healthy subjects and patients with systemic lupus erythematosus.

By using the OKM1 monoclonal antibody and the fluorescence-activated cell sorter to identify lymphocytes bearing iC3b (type 3) complement receptors, two principal populations of OKM1+ lymphocytes have been identified in human peripheral blood. One subset exhibited azurophilic granules and Fc receptors for IgG stained by Leu-11. The other population did not display FcR, but was enriched in cells reacting with OKT3 and OKT8 (low intensity). In healthy subjects, approximately 60% of CR3+ lymphocytes were granular FcR-bearing cells and only 18% co-expressed OKT3 determinants. In patients with systemic lupus erythematosus (SLE), CR3+ lymphocytes were predominantly FcR negative cells and 71% lacked granules. Only 33% reacted with Leu-11, but 50% co-expressed OKT3, 44% reacted with OKT8+, and 15% were OKT4+. We tested the hypothesis that agranular OKT3+ Leu-11- lymphocytes, such as those found in SLE patients, contained the precursors of natural killer (NK) cells. Leu-11+ cells were removed from normal lymphocytes by complement lysis, and the remaining cells were treated with recombinant IFN-alpha, IFN-gamma, or IL 2. These procedures were ineffective in generating typical NK effector cells. Our studies do not support the hypothesis that CR3+ Leu-11- lymphocytes are the precursors of granular Leu-11+ NK cells.

Antibodies, Monoclonal↗
PubMed1985

Immunologic studies in patients with chyluria.

Patients with chyluria, postoperative chylothorax, or surgical thoracic duct drainage are depleted of lymphocytes, IgA, and C3 as a result of the loss of lymphatic cellular and humoral elements, but the specific defects have not been well characterized. Therefore, we investigated the immunologic status of three patients with longstanding chyluria who were lymphopenic but did not have evidence of opportunistic infections. All patients had normal levels of immunoglobulins except for a moderate decrease in the IgA fraction, a normal antibody response to viral agents, and a normal hypersensitivity response to at least one of six recall antigens. Their complement levels were essentially normal. All were leukopenic because of decreased numbers of circulating lymphocytes. Two had depressed relative and absolute numbers of OKT4 (helper/inducer) T cells and normal or increased relative numbers of OKT8 (cytotoxic/suppressor) T cells, resulting in a marked reversal of the OKT4 to OKT8 ratio. The third was severely depleted of both OKT4 and OKT8 cells. The response of their peripheral blood mononuclear cells to mitogen stimulation was reduced, but they all had normal or increased absolute and relative numbers of natural killer (NK) cells as defined by HNK-1 or OKM-1. Their NK activity was less than that of normal controls unless stimulated by interferon, suggesting that many of the NK cells were immature. Normal delayed hypersensitivity, reduced but effective mitogen stimulation, and a normal NK response after interferon may be factors that protect these patients against opportunistic infections and neoplasms.

Antibodies, Monoclonal↗