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Biomedical subjects

B Ghosh

Publications and source records attributed to B Ghosh.

At least 73 records · Page 4Linked to original sources
PubMed1995

Physiological potential of beta-carotene in prolonging the survival of the host bearing transplantable murine lymphoma.

beta-Carotene, when supplemented in diet, has been found to increase the survival period of mice bearing a transplantable tumor, Dalton's lymphoma. Tumor cell-count, body weight pattern, hematological parameters like total count showed marked alterations in a dose-responsive manner with beta-carotene administration when compared to their untreated counterparts. Decreased tumor cell proliferation is also reflected by increased hemoglobin levels of the host.

Animals↗
PubMed1994

Linkage analysis of IL4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations.

Sib-pair analysis of 170 individuals from 11 Amish families revealed evidence for linkage of five markers in chromosome 5q31.1 with a gene controlling total serum immunoglobulin E (IgE) concentration. No linkage was found between these markers and specific IgE antibody concentrations. Analysis of total IgE within a subset of 128 IgE antibody-negative sib pairs confirmed evidence for linkage to 5q31.1, especially to the interleukin-4 gene (IL4). A combination of segregation and maximum likelihood analyses provided further evidence for this linkage. These analyses suggest that IL4 or a nearby gene in 5q31.1 regulates IgE production in a nonantigen-specific (noncognate) fashion.

Adolescent↗
PubMed1994

Immunologic and molecular characterization of Amb p V allergens from Ambrosia psilostachya (western Ragweed) pollen.

We have purified and characterized the Amb p V allergen (A1 variant) from western ragweed (Ambrosia psilostachya) pollen. This allergen was found to be highly cross-reactive with the Amb a VA1 allergen from short ragweed (A. artemisiifolia) pollen in a competitive double-Ab radioimmunoassay (DARIA) and the two allergens showed concordant allergenic potency in histamine-release experiments. We cloned and sequenced several Amb p V genes from western ragweed pollen and flowers by direct PCR of genomic DNA. The amino acid sequences deduced from the nucleotide sequences indicated the presence of multiple forms of Amb p V that could be broadly classified into two groups: Amb p VA and Amb p VB variants. The sequences of the Amb p VA variants are highly homologous to Amb a V (about 90% identity) and very similar to the protein sequence that we obtained. The Amb p VB variants share approximately 65% amino acid homology with Amb a V and have five to seven cysteine residues as compared with the eight found in Amb a V and Amb t V. Two cysteine residues that form disulfide bonds in other Amb Vs (positions 19 and 43 in Amb a V) are replaced by serine and alanine in the Amb p VB1 and Amb p VB2 variants. We have generated model structures of Amb p VA1, VA2, VA3, and VB1 variants from the nuclear magnetic resonance-derived structure of Amb a VA1 by homology modeling. Comparison of antigenic epitopes predicted for the structures of Amb p V variants and Amb a VA1 explains the observed cross-reactivity of the two ragweed proteins and suggests the epitopes likely to be involved in Ab recognition.

Allergens↗
PubMed1994

Integrated clinical and basic studies related to circumventing non-small cell lung cancer drug resistance.

Consideration of a range of clinical and basic studies conducted at the National Cancer Institute which explore the nature of the tumor biology of lung identify the limitations of using chemotherapy for the treatment of advanced lung cancer. No single mechanistic explanation for lung cancer's chemoresistance is apparent, although considerable information about the biology of lung cancer and some of its clinical consequences have been elucidated. In contrast to previous works from our group, this presentation will focus principally on studies of the nature of drug resistance with non-small cell cancer. An alternative combined modality strategy for lung cancer control is to focus on epithelial progression of lung cancer using local modalities while it is still confined to the bronchial epithelium. Particular high risk populations may be appropriate to determine if local tools such as photodynamic laser therapy can be effective in this application. To deal with the underlying biochemical perturbations resulting from critical exposure of the bronchial epithelium to carcinogens, rational biochemical intervention with 13 cis retinoic acid are being evaluated in several clinical trials. An evolution towards more effective lung cancer control may involve the combined modalities of laser ablation of accessible dysplastic epithelium and chronic administration of intervention agents, such as retinoids, to neutralize cancer promotion dynamics in the more remote areas of the lung epithelium.

Antineoplastic Agents↗
PubMed1994

A dose intensity study of FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy and Escherichia coli-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) in advanced breast cancer patients.

BACKGROUND: It has been demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) can ameliorate chemotherapy-induced neutropenia. The extent to which GM-CSF can increase the actual delivered dose intensity of combination chemotherapy over multiple cycles of therapy to patients with advanced breast cancer has not been well defined. We conducted a phase I/II study of dose-intensive FLAC chemotherapy (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) in combination with GM-CSF in patients with locally advanced and metastatic breast cancer to study the acute and cumulative toxicities, anti-tumor activity and dose-intensity achievable with this regimen. METHODS: Eighty-one patients with newly diagnosed stages IIB, III and IV breast cancer who were previously untreated with chemotherapy and who had measurable disease received multiple cycles of FLAC chemotherapy plus E. coli-derived GM-CSF administered every three weeks. RESULTS: FLAC plus GM-CSF as associated with significant cumulative hematologic toxicity. Ninety-eight percent of patients developed grade 4 neutropenia; 29% of all cycles administered required hospitalization for fever and neutropenia; 41% and 22% of cycles required red blood cell and platelet transfusions, respectively. Other significant toxicities with E. coli-derived GM-CSF included mild to moderate first dose effects (hypotension, dyspnea, abdominal cramping) in 30% of patients; late occurring anaphylactoid reactions in 11% of patients; and vascular thromboses. The average delivered dose intensities over all cycles were cyclophosphamide, 210 mg/m2/week; doxorubicin, 14.8 mg/m2/week and 5-fluorouracil, 342 mg/m2/week. The overall clinical response rates were 100% and 83% for LABC and metastatic patients, respectively. There were 23% (6/26) pathologic CR's in the LABC patients given neoadjuvant FLAC and 22% (12/54) clinical CR's in the stage IV patients. The median survival of the LABC patients has not been reached (> 26 months) and is 30 months for the stage IV patients. CONCLUSIONS: The administration of multiple cycles of FLAC plus E. coli-derived GM-CSF therapy is associated with cumulative, dose-limiting myelosuppression, especially thrombocytopenia, as well as significant clinical toxicity. A modest increase in FLAC dose intensity over the starting doses was achievable with the addition of GM-CSF. FLAC chemotherapy has substantial antitumor activity in the treatment of advanced breast cancer. The potential usefulness of FLAC plus GM-CSF must be balanced by its considerable cost and alteration in patients' quality of life due to toxicity. Combination hematopoietic growth factor strategies may be able to reduce the toxicity of FLAC and to allow further increase dose intensity.

Adult↗
PubMed1993

Cloning and expression of immunologically active recombinant Amb a V allergen of short ragweed (Ambrosia artemisiifolia) pollen.

We have cloned and sequenced Amb a V, an Ambrosia artemisiifolia (short ragweed) pollen allergen that has proved to be particularly useful in the genetic analysis of human immune responsiveness. The amino acid sequence deduced from the cloned cDNA sequence corresponds to the published sequence of the protein, except that the cDNA sequence encodes an extra 10 amino acids at the C-terminus. The expressed 55-residue protein is then presumably cleaved enzymatically at the C-terminal lysine found in the 45-residue protein isolated from the pollen. The cloning and sequencing of Amb a V genomic DNA confirmed the cDNA sequence and showed that the Amb a V gene has no introns. Recombinant Amb a V allergen, expressed in Escherichia coli, bound to IgG and IgE antibodies in all Amb a V-allergic individuals tested and inhibition studies demonstrated that the recombinant protein contains a subset of the antigenic epitopes found on native Amb a V. In addition, recombinant Amb a V released histamine efficiently from basophils from Amb a V-allergic patients. The recombinant Amb a V allergen and mutants of Amb a V should, therefore, be useful in studies of allergen epitopes in humans, as well as providing a diagnostic tool.

Allergens↗
PubMed1993

Computed tomography-guided needle localization of suspicious breast lesions.

Non-palpable breast lesions, suspicious for carcinoma, are usually localized prior to biopsy using standard mammographic techniques. We report two patients in whom computed tomography was used to localize suspicious non-palpable breast lesions that could not be readily localized using standard mammographic techniques.

Biopsy, Needle↗
PubMed1992

Expression and analysis of recombinant Amb a V and Amb t V allergens. Comparison with native proteins by immunological assays and NMR spectroscopy.

The Amb V allergens are small, highly disulfide-bonded ragweed pollen allergens that serve as useful models for understanding the molecular basis of the human immune response. We have produced recombinant Amb a V and Amb t V (from short and giant ragweed pollens, respectively) in Escherichia coli and have compared their structural and functional characteristics to those of the native proteins. Recombinant Amb t V was indistinguishable from native Amb t V as determined by NMR spectroscopy and antibody-binding studies. Whereas inhibition analysis showed that recombinant Amb a V possessed only approximately 50% of the antibody-binding activity of native Amb a V, the two proteins were similarly effective in stimulating Amb a V-specific T-cells. Our results demonstrate that even highly homologous proteins exhibit different abilities to fold into their native three-dimensional conformations and establish the potential and limits of expressing the recombinant Amb V allergens intracellularly in E. coli.

Allergens↗
PubMed1992

The correct dose: pharmacologically guided end point for anti-growth factor therapy.

Strategies to block the effects of tumor growth factors, such as estrogen, and to recruit other regulatory elements, such as with retinoids, have focused interest on the possibility of successful tumor intervention approaches. Approaches that neutralize the effects of critical molecules that drive tumor promotion are attractive targets for evaluation as new intervention agents. Clinical intervention trials with early stage patients or with subjects from "high risk" populations impose stricter types of constraints than conventional chemotherapy approaches in advanced stage patients. The potential for short-term toxicity has to be considered, as it may affect subject accrual or compliance. The longer expected survival of intervention subjects mandates closer attention to the possibilities of unexpected long-term toxicities with chronic administration of an intervention agent. As part of a Phase I clinical trial evaluating the utility of a monoclonal antibody directed against the autocrine growth factor, gastrin-releasing peptide to block the growth of small cell lung cancer, we developed a mathematical model to predict the requisite amount of antibody to neutralize growth factor effect. This model requires knowledge of the equilibrium concentration of the secreted growth factor, specific receptor, and bioavailability of the antibody in the tumor interstitium. A range of possible target doses of antibody can be developed to address the potential for heterogeneity frequently encountered in such systems, including a range of levels for peptide production and specific receptor expression. This approach could be applied to rationally derive treatment or intervention in which specific information regarding the relevant binding parameters is available. Through refinement of this modeling approach more context-specific dosing of agonist/antagonists could be determined which may decrease side effects associated with the drug administration.

Antibodies, Monoclonal↗
PubMed1992

Dose dependence of acetylcholinesterase activity in neuroblastoma cells exposed to modulated radio-frequency electromagnetic radiation.

Radio-frequency electromagnetic radiation (RFR) at 915 and 147 MHz, when sinusoidally amplitude modulated (AM) at 16 Hz, has been shown to enhance release of calcium ions from neuroblastoma cells in culture. The dose-response relation is unusual, consisting of two power-density "windows" in which enhanced efflux occurs, separated by power-density regions in which no effect is observed. To explore the physiological importance of these findings, we have examined the impact of RFR exposure on a membrane-bound enzyme, acetylcholinesterase (AChE), which is intimately involved with the acetylcholine (ACh) neurotransmitter system. Neuroblastoma cells (NG108), exposed for 30 min to 147-MHz radiation, AM at 16 Hz, demonstrated enhanced AChE activity, as assayed by a procedure using 14C-labeled ACh. Enhanced activity was observed within a time window between 7.0 and 7.5 h after the cells were plated and only when the exposure occurred at power densities identified in a previous report as being effective for altering the release of calcium ions. Thus RFR affects both calcium-ion release and AChE activity in nervous system-derived cells in culture in a common dose-dependent manner.

Acetylcholinesterase↗
PubMed1992

Serum alpha-1 acid glycoprotein levels in patients with idiopathic peripheral retinal vasculitis (Eales' disease).

Serum alpha-1 acid glycoprotein levels were measured in 27 patients with idiopathic peripheral retinal vasculitis (Eales' disease) and 31 healthy subjects by single radial immunodiffusion technique. The levels were found to be significantly increased in both moderate and severe types of the disease. The serum levels of this protein paralleled the severity of the disease. The increased alpha-1 acid glycoprotein in serum showed a significant fall to near normal levels during the quiescent stage. Our observations support the hypothesis that idiopathic peripheral retinal vasculitis is an immune mediated disease. It is proposed that serum alpha-1 acid glycoprotein may be considered as a reliable parameter of the activity and the degree of severity of the disease, as well as an useful tool for monitoring the efficacy of treatment.

Adolescent↗
PubMed1992

East-West migration: the European perspective. Current trends and prospects beyond 1992.

"This...paper seeks to discern the current situation in East-West migration, including migratory movements within, and towards East Europe, and its possible trends beyond 1993. In so doing it takes into account some of the major policy and operational measures which are being taken or are contemplated by the governments of East and West Europe." Consideration is given to the determinants of East-West migration, sources of possible future migratory pressures, the impact of the formation of the European Community on migratory flows, and movements to and within Eastern Europe.

Demography↗
PubMed1992

Early detection of breast carcinoma: a comparison of palpable and nonpalpable lesions.

A retrospective study of 536 needle-localization biopsies of nonpalpable breast lesions and 623 excisional biopsies of palpable breast lesions was performed. Carcinoma was present in 17.9% of needle-localization biopsy specimens and in 11.1% of excisional biopsy specimens. Noninvasive carcinoma constituted 50% of carcinomas detected by needle-localization biopsy and only 7.3% of carcinomas detected by excisional biopsy (p less than 0.005). Invasive carcinoma detected by needle-localization biopsy was associated with axillary lymph node metastasis in 9.8% of patients who had axillary dissection, compared with 37.7% of patients with invasive carcinoma detected by excisional biopsy of a palpable mass (p less than 0.005). Invasive carcinoma detected by needle-localization biopsy was less than 2 cm in size (T1) in 93.5% of biopsy specimens; in contrast, invasive carcinoma detected by excisional biopsy was less than 2 cm in size in only 54.7% of biopsy specimens (p less than 0.005). Nonpalpable breast lesions that proved to be invasive carcinoma were pathologic stage I in 82.9% of patients. Palpable breast lesions that proved to be invasive carcinoma were pathologic stage I in only 47.2% of patients. Survival benefits of mammographic screening and biopsy of nonpalpable lesions are likely the result of detection of invasive carcinoma at an early stage and detection of noninvasive carcinoma that may later develop into or mark increased risk of invasive carcinoma.

Axilla↗