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Biomedical subjects

G Pasternak

Publications and source records attributed to G Pasternak.

At least 19 recordsLinked to original sources
PubMed2006

Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.

BACKGROUND: Metformin is an oral anti-hyperglycemic agent used in the treatment of type 2 diabetes mellitus. The results of the UK Prospective Diabetes Study indicate that metformin treatment is associated with a reduction in total mortality compared to other anti-hyperglycemic treatments. Metformin, however, is thought to increase the risk of lactic acidosis, and is considered to be contraindicated in many chronic hypoxemic conditions that may be associated with lactic acidosis, such as cardiovascular, renal, hepatic and pulmonary disease, and advancing age. OBJECTIVES: To assess the incidence of fatal and nonfatal lactic acidosis with metformin use compared to placebo and other glucose-lowering treatments in patients with type 2 diabetes mellitus. A secondary objective was to evaluate the blood lactate levels for those on metformin treatment compared to placebo or non-metformin therapies. SEARCH STRATEGY: A search was performed of The Cochrane Library (up to 8/2005), MEDLINE (up to 8/2005), EMBASE (up to 11/2000), OLD MEDLINE, and REACTIONS (up to 8/2005), in order to identify all studies of metformin treatment from 1966 to August 2005. The Cumulated Index Medicus was used to search relevant articles from 1959 to 1965. The search was augmented by scanning references of identified articles, and by contacting principal investigators. Date of latest search: August 2005. SELECTION CRITERIA: Prospective trials in patients with type 2 diabetes that lasted longer than one month were included if they evaluated metformin, alone or in combination with other treatments, compared to placebo or any other glucose-lowering therapy. Observational cohort studies of metformin treatment lasting greater than one month were also included. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials to be included, assessed study quality and extracted data. The incidence of fatal and nonfatal lactic acidosis was recorded as cases per patient-years, for metformin treatment and for placebo or other treatments. The upper limit for the true incidence of cases in the metformin and non-metformin groups were calculated using Poisson statistics. In a second analysis lactate levels were measured as a net change from baseline or as mean treatment values (basal and stimulated by food or exercise) for treatment and comparison groups. The pooled results were recorded as a weighted mean difference (WMD) in mmol/L, using the fixed effect model for continuous data. MAIN RESULTS: Pooled data from 206 comparative trials and cohort studies revealed no cases of fatal or nonfatal lactic acidosis in 47,846 patient-years of metformin use or in 38,221 patients-years in the non-metformin group. Using Poisson statistics with 95% confidence intervals the upper limit for the true incidence of metformin-associated lactic acidosis was 6.3 cases per 100,000 patient-years, and the upper limit for the true incidence of lactic acidosis in the non-metformin group was 7.8 cases per 100,000 patient-years. There was no difference in lactate levels, either as mean treatment levels or as a net change from baseline, for metformin compared to placebo or other non-biguanide therapies. The mean lactate levels were slightly lower for metformin treatment compared to phenformin (WMD -0.75 mmol/L, 95% CI -0.86 to -0.15). AUTHORS' CONCLUSIONS: There is no evidence from prospective comparative trials or from observational cohort studies that metformin is associated with an increased risk of lactic acidosis, or with increased levels of lactate, compared to other anti-hyperglycemic treatments if prescribed under the study conditions.

Acidosis, Lactic↗
PubMed2002

Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus.

BACKGROUND: Metformin is an oral anti-hyperglycemic agent used in the treatment of type 2 diabetes mellitus. The results of the UK Prospective Diabetes Study indicate that metformin treatment is associated with a reduction in total mortality compared to other anti-hyperglycemic treatments. Metformin, however, is thought to increase the risk of lactic acidosis, and is considered to be contraindicated in many chronic hypoxemic conditions that may be associated with lactic acidosis, such as cardiovascular, renal, hepatic and pulmonary disease, and advancing age. OBJECTIVES: To assess the incidence of fatal and nonfatal lactic acidosis with metformin use compared to placebo and other glucose-lowering treatments in patients with type 2 diabetes mellitus. A secondary objective was to evaluate the blood lactate levels for those on metformin treatment compared to placebo or non-metformin therapies. SEARCH STRATEGY: A search was performed of the Cochrane Controlled Trials Register and the Database of Abstracts of Reviews of Effectiveness (up to 4/2000), Medline (up to 11/2000), Embase (up to 11/2000), Oldmedline, and Reactions (up to 5/2000), in order to identify all studies of metformin treatment from 1966 to November 2000. The Cumulated Index Medicus was used to search relevant articles from 1959 to 1965. The search was augmented by scanning references of identified articles, and by contacting principal investigators. Date of latest search: November 2000. SELECTION CRITERIA: Prospective trials in patients with type 2 diabetes that lasted longer than one month were included if they evaluated metformin, alone or in combination with other treatments, compared to placebo or any other glucose-lowering therapy. Observational cohort studies of metformin treatment lasting greater than one month were also included. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials to be included, assessed study quality and extracted data. The incidence of fatal and nonfatal lactic acidosis was recorded as cases per patient-years, for metformin treatment and for placebo or other treatments. The upper limit for the true incidence of cases in the metformin and non-metformin groups were calculated using Poisson statistics. In a second analysis lactate levels were measured as a net change from baseline or as mean treatment values (basal and stimulated by food or exercise) for treatment and comparison groups. The pooled results were recorded as a weighted mean difference (WMD) in mmol/L, using the fixed effects model for continuous data. MAIN RESULTS: Pooled data from 176 comparative trials and cohort studies revealed no cases of fatal or nonfatal lactic acidosis in 35,619 patient-years of metformin use or in 30,002 patients-years in the non-metformin group. Using Poisson statistics with 95% confidence intervals the upper limit for the true incidence of metformin-associated lactic acidosis was 8.4 cases per 100,000 patient-years, and the upper limit for the true incidence of lactic acidosis in the non-metformin group was 9 cases per 100,000 patient-years. There was no difference in lactate levels, either as mean treatment levels or as a net change from baseline, for metformin compared to placebo or other non-biguanide therapies. The mean lactate levels were slightly lower for metformin treatment compared to phenformin (WMD -0.75 mmol/L, 95% CI -0.86 to -0.15). REVIEWER'S CONCLUSIONS: There is no evidence from prospective comparative trials or from observational cohort studies that metformin is associated with an increased risk of lactic acidosis, or with increased levels of lactate, compared to other anti-hyperglycemic treatments if prescribed under the study conditions, taking into account contra-indications.

Acidosis, Lactic↗
PubMed2001

Strategies to manage the adverse effects of oral morphine: an evidence-based report.

Successful pain management with opioids requires that adequate analgesia be achieved without excessive adverse effects. By these criteria, a substantial minority of patients treated with oral morphine (10% to 30%) do not have a successful outcome because of (1) excessive adverse effects, (2) inadequate analgesia, or (3) a combination of both excessive adverse effects along with inadequate analgesia. The management of excessive adverse effects remains a major clinical challenge. Multiple approaches have been described to address this problem. The clinical challenge of selecting the best option is enhanced by the lack of definitive, evidence-based comparative data. Indeed, this aspect of opioid therapeutics has become a focus of substantial controversy. This study presents evidence-based recommendations for clinical-practice formulated by an Expert Working Group of the European Association of Palliative Care (EAPC) Research NETWORK: These recommendations highlight the need for careful evaluation to distinguish between morphine adverse effects from comorbidity, dehydration, or drug interactions, and initial consideration of dose reduction (possibly by the addition of a co analgesic). If side effects persist, the clinician should consider options of symptomatic management of the adverse effect, opioid rotation, or switching route of systemic administration. The approaches are described and guidelines are provided to aid in selecting between therapeutic options.

Administration, Oral↗
PubMed2001

Predominantly BCR-ABL negative myeloid precursors in interferon-alpha treated chronic myelogenous leukemia: a follow-up study of peripheral blood colony-forming cells with fluorescence in situ hybridization.

The mechanism and target cell of the life-prolonging effect of interferon-alpha (IFN-alpha) in chronic myelogenous leukemia (CML) are controversial. We studied the influence of IFN-alpha treatment on the frequency of malignant hematopoietic precursor cells in the peripheral blood (PB) of CML patients during the course of the disease. PB 10-day colony-forming cells (PB-CFCs) were assessed with regard to their quantity, lineage distribution, and BCR-ABL status, as determined by fluorescence in situ hybridization (FISH). PB-CFC numbers were determined in 39 patients (29 in the chronic phase, 6 in an advanced stage, and 4 with progression to an advanced stage during follow-up). Thirty-one patients were evaluated either once or several times to determine the BCR-ABL status of the colonies. BCR-ABL negative PB-CFCs were detectable at diagnosis in 5 of 11 patients. A major reduction of BCR-ABL positive colonies to <25% of PB-CFCs was observed in 10/13 determinable IFN-alpha treated patients in early and late chronic phases, indicating a high proportion of BCR-ABL negativity at the clonogenic cell level. In contrast, only 3 of these patients had a cytogenetic response of <25% Philadelphia chromosome (Ph1)-positive metaphases in bone marrow cytogenetics. Treatment with IFN-alpha and/or hydroxyurea (HU) during chronic phase was accompanied by a reduction of PB-CFCs to subnormal levels (median 24 CFCs/ml) compared to controls (median 207 CFCs/ml), untreated patients in chronic phase (median 25,979 CFCs/ml), and patients with advanced disease (median 6,047 CFCs/ml). In blast crisis (6 patients), all colonies tested were BCR-ABL positive. Our results show that IFN-alpha treatment leads to a marked reduction of malignant myeloid precursor cells in the PB of CML patients, which exceeds the degree of cytogenetic remission. This offers an explanation for the good therapeutic efficacy and even life-prolonging effect of IFN-alpha, which is also observed in cytogenetic non-responders.

Fusion Proteins, bcr-abl↗
PubMed2000

CD14+ peripheral blood mononuclear cells from chronic myeloid leukemia and normal donors are inhibitory to short- and long-term cultured colony-forming cells.

Monocyte-induced cell-cytotoxicity has been implicated in the mechanism of suppression of normal haematopoietic progenitors in chronic myeloid leukemia (CML). We examined here the in vitro effect of CML-derived and normal peripheral blood (PB) monocytes on short- and long-term cultured haematopoietic progenitor cells. Short-term coculture (5 days) of CML or normal monocytes with CML or normal peripheral blood mononuclear cells (PBMNC)/CD34+ cells as targets resulted in a significant inhibition of colony-forming cell (CFC) growth. Coculture conditioned medium (CCM) from 5-days cocultures of normal or CML CD14+ monocytes with CD34+ cells were likewise inhibitory to CFC. In 5-week long-term cocultures of monocytes in direct contact with normal bone marrow (BM) progenitors, CML monocytes reduced the proportion of long-term cultured CFC (LTC-CFC) significantly to 52% of the controls, while normal monocytes had a less pronounced inhibitory effect (89% of the controls) on LTC-CFC. Reduction of LTC-CFC was great when CML monocytes and target cells were separated by a transwell membrane as compared to control cultures in the absence of CD14+ cells (53.5 vs. 9%). CCM from 5-week cocultures of normal or CML CD14+ monocytes with CD34+ progenitors from bone marrow (BM) cells were also inhibitory to CFC. No difference in cytokine levels for TNF-alpha, IFN-gamma, G-CSF, IL-10, IL-6 was detectable between CML CD14+ CCM and control CCM derived from short- and long-term cocultures. Our results suggest that CML monocytes may play a role in the inhibition of normal haematopoiesis through a yet not defined soluble factor supporting the expansion of the malignant clone in CML.

Adult↗
PubMed2000

Interferon-alpha-treated patients with chronic myelogenous leukemia show BCR/ABL-positive peripheral blood progenitor cells surviving long-term culture.

Several groups have shown that Ph-progenitors reappear in LTC of CML bone marrow or PBMNC when the cell preparations were derived from newly diagnosed Ph-positive patients or after induction chemotherapy. We have tested the hypothesis whether LTC may further decrease CML progenitors if the cells to be cultured were from IFN-treated patients. In our experiments, PBMNC were cultured from 7 IFN- and 5 HU-treated patients in stable chronic phase of the disease, and from 9 patients at diagnosis. Progenitor cells in PBMNC were quantitatively analyzed before and after 35 days of LTC by combining the clonogenic assay in semisolid medium with dual-color interphase FISH for identification of the BCR/ABL status of colony-forming progenitor cells. A median of 22 colonies (range 7-88) before and 30 colonies (5-71) after LTC were analyzed per patient. Our results show that the number of BCR/ABL-positive CFC before and after LTC was approximately the same. This was independent of IFN or HU therapy. In the IFN group there were 58% (median) BCR/ABL-positive CFC before and 54% (median) after LTC of PBMNC. In the HU group, 80% of CFC were BCR/ABL-positive before and 85% after LTC. A complete elimination of BCR/ABL-positive cells was not achieved. We conclude that CML early progenitors in PBMNC of IFN-treated CML patients may survive LTC.

Antineoplastic Agents, Alkylating↗
PubMed2000

BCR/ABL-negative clonogenic hematopoietic cells do not accumulate in the plastic-adherent fraction of peripheral blood mononuclear cells from patients with chronic myeloid leukemia in stable chronic phase.

PBMNC from patients with CML and healthy control persons were separated into plastic-adherent and nonadherent cell fractions. A colony assay in semi-solid medium was used to estimate the number and lineage commitment of CFC in each of the fractions. The CML blood-derived colonies were isolated and analyzed by FISH for BCR/ABL sequences. Thus, we were able to test the hypothesis whether a selective enrichment is possible of normal progenitor cells in the blood of CML patients in stable chronic phase after HU and/or IFN. Although the number of leukocytes differed considerably between patients at diagnosis and in stable chronic phase, the proportion of adherent and nonadherent cells was about the same in all preparations tested. There were also only minor differences of adherence between MNC of CML and normal origin. Furthermore, BCR/ABL-positive and negative colonies were equally distributed among unseparated, adherent, and nonadherent PBMNC fractions. In conclusion, an accumulation of BCR/ABL-negative CFC was not found in any of the PBMNC fractions. CFC from PBMNC of the same lineage commitment were simultaneously present in plastic-adherent and nonadherent cell fractions, indicating that their surface charges might be different and, on the other hand, that different lineage commitment precursors can be present in either of the fractions irrespective of CML or blood origin.

Antineoplastic Agents, Alkylating↗
PubMed1999

Does long-term culture favor normal clonogenic cells from interferon-treated patients with chronic myelogenous leukemia?

We have tested whether peripheral blood mononuclear cells (PBMNCs) from interferon (IFN)-treated patients may lose residual BCR-ABL sequence-positive progenitor cells when long-term cultured for 35 days on allogeneic stromal cells. IFN-treated patients have low white blood cell counts and a fair number of BCR-ABL-negative colony-forming cells in the peripheral blood. Particularly, IFN responders show increased numbers of normal hematopoietic cells. We have quantitatively analyzed progenitor cells in PBMNCs of IFN-treated patients by combining the clonogenic assay in semisolid medium with interphase fluorescent in situ hybridization (FISH). Thus, the identification is possible of the BCR-ABL status of colony-forming progenitor cells. In IFN-treated patients, the number of BCR-ABL-positive CFCs is considerably decreased and BCR-ABL-negative CFCs appear in the peripheral blood. We could show that after LTC for 35 days of the same PBMNCs on irradiated allogeneic normal stromal cells residual BCR-ABL sequence-positive CFCs were still present. In some cases the relative number of BCR-ABL sequence-positive CFCs was found to be increased after LTC. A minor proportion of blood samples from IFN-treated patients did not give rise to CFCs after LTC on allogeneic stromal cells (three of 10 patients). Inter- and intraindividual variations can be found with regard to loss or gain of BCR-ABL sequence-positive colonies after LTC. We conclude that early CML progenitor cells persist in the peripheral blood of IFN-treated patients and that a certain proportion may survive long-term culture.

Biomarkers, Tumor↗
PubMed1998

Chronic myelogenous leukemia: molecular and cellular aspects.

Chronic myelogenous leukemia (CML) originates in a pluripotent hematopoietic stem cell of the bone marrow and is characterized by greatly increased numbers of granulocytes in the blood. Myeloid and other hematopoietic cell lineages are involved in the process of clonal proliferation and differentiation. After a period of 4-6 years the disease progresses to acute-stage leukemia. On the cellular level, CML is associated with a specific chromosome abnormality, the t(9; 22) reciprocal translocation that forms the Philadelphia (Ph) chromosome. The Ph chromosome is the result of a molecular rearrangement between the c-ABL proto-oncogene on chromosome 9 and the BCR (breakpoint cluster region) gene on chromosome 22. Most of ABL is linked with a truncated BCR. The BCR/ABL fusion gene codes for an 8-kb mRNA and a novel 210-kDa protein which has higher and aberrant tyrosine kinase activity than the normal c-ABL-coded counterpart. Phosphorylation of a number of substrates such as GAP, GRB-2, SHC, FES, CRKL, and paxillin is considered a decisive step in transformation. An etiological connection between BCR/ABL and leukemia is indicated by the observation that transgenic mice bearing a BCR/ABL DNA construct develop leukemia of B, T, and myeloid cell origin. CML cells proliferate and expand in an almost unlimited manner. Adhesion defects in bone marrow stromal cells have been proposed to explain the increased number of leukemic cells in the peripheral blood. However, findings of our laboratory have shown that the BCR/ABL chimeric protein that is expressed in transfected cells may, under certain conditions, also increase the adhesion to fibronectin via enhanced expression of integrin. Our previous immunocytological studies on the expression of beta1 and beta2 integrins have found no qualitative differences between normal and CML hematopoietic cells in vitro. Even long-term-cultured CML bone marrow or blood cells continuously express those adhesion molecules that are characteristic of the cytological type. Recent experiments indicate that certain early CML progenitors may adhere to the stromal layer in vitro similarly to their normal counterparts. They cannot be completely removed by long-term culture on allogeneic stromal cells. At present, the only curative therapy is transplantation of allogeneic hematopoietic stem cells. Based on the molecular and cellular state of knowledge of CML, new therapies are being developed. BCR/ABL antisense oligonucleotides, inhibitors of tyrosine kinase, peptide-specific adoptive immunotherapy or peptide vaccination, and restoration of hematopoiesis by autologous stem cell transplantation following CML cell purging are examples of important approaches to improving CML treatment.

Animals↗
PubMed1997

A statistically significant sex difference in the number of colony-forming cells from human peripheral blood.

The number of colony-forming cells (CFC) in the peripheral blood (PB) of 43 volunteers was examined using a semisolid clonogenic culture assay. In all, 22 male (age 21-39 years) and 21 female individuals (age 21-39 years) were tested, ten of each group twice to examine the intraindividual variability of colony-forming cells in PB. A statistically significant sex difference in the number of CFC, erythroblastic colonies (BFU-E), and granulocyte/macrophage colonies (CFU-GM) in PB was detected in favor of male individuals. No significant difference between female and male PB was found for the number of CFU-GEMM. The intraindividual variability of CFC and BFU-E was significantly higher in female donors. These results support previous reports by others on a potential influence of sex steroids on hematopoiesis.

Androgens↗
PubMed1994

Persistence of bcr-abl mRNA-expressing cells in long-term cultures established from chronic myeloid leukemic bone marrow or blood.

Long-term cultures (LTC) established from chronic myeloid leukemic (CML) bone marrow or blood contain bcr-abl mRNA-expressing cells, as demonstrated by the polymerase chain reaction (PCR). Bcr-abl sequences were detectable in cultures from all of nine patients investigated. In LTC from two patients, in which a cytogenetic conversion from Ph+ to Ph- was noted at day 20 and 40, respectively, the PCR for bcr-abl remained positive, at least up to day 112 and 245, respectively, in vitro. The differences between the results of cytogenetic and PCR analyses was explained by the fact that the metaphases studied were obviously derived from spontaneously EBV-transformed bcr-abl mRNA-negative B cells, which may become the dominating cell type very early in LTC from bone marrow or blood. LTCs cloned for EBV-transformed B cells which no longer harbor admixed macrophages are bcr-abl mRNA negative. In conclusion, bcr-abl mRNA-expressing cells may show long-term persistence in LTC established from CML bone marrow or blood.

Adult↗
PubMed1994

Behavior in vitro of long-term cultured bone marrow or blood cells from chronic myeloid leukemia: adhesion molecules and differentiation antigens as detected by immunocytochemistry.

Long-term cultures (LTC) were established from chronic myeloid leukemic bone marrow or blood. As detected by immunocytochemistry using 25 different monoclonal antibodies, the in vitro cultured cells express a variety of adhesion molecules and differentiation antigens. beta 1 and beta 2 integrins are constantly present on long-term cultured cells. CD4, CD54, CD58, and CD71 markers become highly expressed on the cells after about 10 days in vitro while CD56 is permanently lacking. Only 5 of the 17 patients studied had between 25 and 85 per cent CD33 and CD34 differentiation antigen-positive cells initially in the bone marrow or blood. There was a decrease to less than 10 per cent after six to eight weeks in culture. In later stages of long-term culture, monocytes/macrophages become the dominating cell types. Blast cells are admixed to these cells in varying numbers. In 4 of the 17 cases studied long-term cultures converted to cell lines showing indefinite cell growth. The cells were identified as B cell blasts spontaneously transformed by Epstein Barr virus (EBV). The permanent myeloid and monocytic leukemia cell lines K-562, HL-60, KG-1, RC-2a, CTV-1, THP-1, and U-937 were likewise tested for adhesion molecules and differentiation antigens. A stable marker expression was found, the pattern of which is characteristic of each cell line. CD4 is frequently present on myeloid and monocytic leukemia cell lines (HL-60, RC-2a, THP-1, and U-937). Exceptionally, CD2 and CD34 were shown on KG-1. CD49e, CD49f, CD44, and CD71 are expressed on all cell lines tested.

Antigens, CD↗
PubMed1991

Identification and characterization of receptors for tumor necrosis factor-alpha in the brain.

Specific receptors for murine TNF have been identified in homogenates of rodent brain. These receptors are saturable and bind TNF with sufficient affinity to ensure occupancy by cytokine elaborated during infection. 125I-mTNF was detected in four specific complexes of Mr 130,000, 90,000, 66,000 and 60,000 after affinity labeling. Solubilization of brain membranes into detergent increased binding capacity 4-fold which indicates the presence of latent receptors for mTNF in the brain. Specific binding was greatest in the brainstem, least in the cerebellum and was also detected in the cortex, thalamus and basal ganglia.

Animals↗
PubMed1990

Patterns of expression of tumor markers on non-transformed human mammary epithelial cells cultured in vitro.

We have examined the expression of 7 well defined tumor markers/tumor associated antigens (H type 2, X, Y, sialyl-Lea, CEA, MAM-6, and Tn) and a tumor associated antigen defined by a new own monoclonal antibody on non-transformed human epithelial cell lines derived from reduction mammoplasties by means of immunocytochemistry with monoclonal antibodies. Two cell types are discernible: slowly or non-proliferating, lumenal derived (I), and proliferating, stem cell-like, basal cell-derived cells (II). Five out of the 8 tumor markers were expressed on type I cells, and all 8 on type II cells. The number of positive cells varied considerably from a few to 100 per cent depending on the individual markers. The observed patterns proved to be characteristic and reproducible; they appear to reflect the developmental stage of the cells cultured in vitro rather than a direct influence of the culture conditions.

Biomarkers, Tumor↗
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↗
PubMed1988

A new monoclonal antibody (A46-B/B10) highly specific for the blood group H type 2 epitope: generation, epitope analysis, serological and histological evaluation.

A monoclonal antibody recognizing the blood group H type 2 antigen has been obtained from a BALB/c mouse immunized with MCF-7 (human mammary carcinoma) cells. The specificity of this antibody (A46-B/B10, IgM, kappa) has been identified by haemagglutination tests, immunohistochemistry, binding inhibition studies, and absorption experiments performed with synthetic oligosaccharides. The antibody is virtually nonreactive with H type 1 antigen or with closely related type 2 structures (e.g., Y antigen). A46-B/B10 strongly agglutinates human erythrocytes according to the amount of H substance expressed and can, therefore, easily discriminate between blood groups A1 and A2 as well as A1B and A2B (A1 and A1B are not or only weakly agglutinated). In immunohistochemistry, this antibody seems to provide a highly specific reagent for a restricted number of carcinomas and epithelial lineages in tissue sections and in vitro.

ABO Blood-Group System↗