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Biomedical subjects

D Benjamin

Publications and source records attributed to D Benjamin.

At least 199 records · Page 11Linked to original sources

Expression of normal myeloid-associated antigens by acute leukemia cells.

Monoclonal antibodies that react with hematopoietic cells and their precursors in a stage and lineage restricted fashion were used in indirect immunofluorescence assays to examine leukemic cells from 105 pediatric age patients. The differentiative states of blasts from 42 patients with acute nonlymphocytic leukemia (ANLL) were defined by these antibodies. When these were compared to their morphologic and histochemical levels of differentiation as defined by the French-American-British (FAB) classification, no direct relationship was found. The reactivity of these antibodies with leukemic cells from 63 patients with acute lymphocytic leukemiA (ALL) was also investigated, and the usefulness of these antibodies in distinguishing leukemias of myeloid from those of lymphoid origin was demonstrated.

Acute Disease↗

B-cell-derived interleukin-1 (IL-1)-like factor. II. Sources, effects, and biochemical properties.

A variety of types of human B-cell lines were evaluated for their ability to produce interleukin 1 (IL-1)-like factors. All of the eight Epstein-Barr virus (EBV)-transformed B lymphocyte lines, three of four of the EBV+ lymphoma lines, only three of seven of the EBV- lymphoma lines, and none of the three tested myeloma lines secreted some IL-1 activity. The IL-1-like factor produced by the cell lines was detected on the basis of its thymocyte comitogenic and/or fibroblast proliferative activities. Injections of partially purified IL-1-like factor from one of the EBV-transformed B-lymphocyte lines also induced the appearance of an acute phase protein (haptoglobin) in the serum of C3H/HeJ mice. These biological activities are identical with those of monocyte-derived IL-1. Thymocyte comitogenic activity and fibroblast proliferation activity from one of the EBV-B cell line-derived IL-1-like activities were not dissociable by biochemical procedures, including HPLC gel filtration and HPLC anion-exchange chromatography. However, the IL-1-like factor from one of the EBV-B lymphocyte cell lines was larger in size (25 kDa) and more acidic (pI 5.5) than monocyte-derived IL-1.

Animals↗

Immunodiagnosis of childhood ALL with monoclonal antibodies to myeloid and lymphoid associated antigens.

Sixty-five cryopreserved leukemic samples from children diagnosed and treated as having acute lymphocytic leukemia (ALL) were retrospectively examined for the presence of lymphoid and myeloid associated antigens by indirect immunofluorescence using monoclonal antibodies. Expectedly, the majority of these specimens expressed antigens known to be expressed on lymphoid, and not myeloid malignancies. These included the common acute lymphoblastic leukemia antigen (CALLA), the p32 B-cell associated antigen, and T-cell associated antigens. Leukemic cells from the 8 remaining patients expressed antigens known to be present on both myeloid and lymphoid leukemias. These included HLA/DR, and the antigens identified by BA-1 and BA-2. Cells from 2 of these 8 patients reacted with antibodies that define antigens present on normal and malignant myeloid cells. Both specimens reacted with 1G10, an anti-granulocyte antibody, and one reacted with 5F1 which reacts with monocytes, nucleated red blood cells, megakaryocytes and platelets. One of these patients relapsed while receiving ALL therapy, and the morphology of her leukemic cells became characteristic of acute monocytic leukemia (AMoL). The second patient failed ALL therapy but responded to standard acute nonlymphocytic leukemia (ANLL) therapy, clearing her peripheral blasts. Thus these studies confirm that cell surface phenotyping with monoclonal antibodies can recognize ALL cells that express myeloid rather than lymphoid associated antigens and demonstrate that the malignant cells display a clinical behavior consistent with the diagnosis of ANLL.

Adolescent↗

The value of the radionuclide angiogram in the prediction of perioperative myocardial infarction in patients undergoing lower extremity revascularization procedures.

To better define the group of patients at high risk of myocardial infarction (MI) and death associated with lower extremity revascularization procedures, resting gated blood pool studies were obtained in 100 such patients before surgery and results were correlated with the prevalence of perioperative MI. The results indicated that three patient groups could be distinguished on the basis of cardiac ejection fraction. Group I (n = 50) had preoperative ejection fractions ranging from 56% to 83%. None of the patients in group I suffered an acute perioperative MI. Group II (n = 42) comprised patients with ejection fractions ranging from 36% to 55%. There was a 19.0% prevalence of MI in group II, with one cardiac death. Group III included eight patients with ejection fractions ranging from 26% to 35%. There was a 75% prevalence of perioperative MI in these patients, with one cardiac death. All perioperative MIs occurred within the first 48 hr after surgery. Statistical analysis demonstrated a significantly higher prevalence of perioperative MI in patients with gated pool ejection fractions of 35% or less compared with the prevalence in patients with one or more of the other widely used clinical signs of increased cardiac operative risk (p less than .02).

Aged↗

Herpes simplex viral pneumonitis in childhood.

We report two cases of herpes simplex pneumonia in children. One patient had Down syndrome, and the other was immunosuppressed by cancer therapy. Both had interstitial pneumonitis with nonspecific physical, radiographic, and laboratory findings, and both died. The diagnosis of herpes simplex pneumonia was made by isolation of herpes simplex virus from autopsy lung cultures as well as by demonstration of antigen in the tissue with an immunoperoxidase procedure. Inasmuch as herpes simplex pneumonia is a potentially treatable infection, early virologic studies are recommended in immunocompromised children with progressive pneumonitis of undetermined cause.

Antigens, Viral↗

The value of radionuclide angiography as a predictor of perioperative myocardial infarction in patients undergoing abdominal aortic aneurysm resection.

To define the group of patients at high risk for myocardial infarction (MI) and death associated with abdominal aortic aneurysm repair, resting gated blood pool studies were obtained on 50 such aneurysm patients preoperatively. The results indicated that three groups could be distinguished among these patients by cardiac ejection fraction. Group I (n = 25) had preoperative ejection fractions ranging from 56% to 85%. None of the patients in group I suffered an acute perioperative MI. Group II (n = 20) comprised patients with ejection fractions ranging from 36% to 55%. There was a 20% incidence of MI in group II but no cardiac deaths. Group III included five patients with ejection fractions ranging from 27% to 35%. There was an 80% incidence of perioperative MI in these patients, with one cardiac death and one cardiac arrest. All perioperative MIs occurred within the first 48 hours after surgery. In addition there was a 50% incidence of perioperative MI among all those patients who were 80 years of age or older. These results indicate guidelines for the management of patients undergoing abdominal aortic aneurysm repair based on their preoperative ejection fraction. The data further suggest that the noninvasive gated blood pool method of determining ejection fraction may serve a more broadly useful function in helping to determine which of those patients about to undergo major surgical procedures are at high risk for perioperative MI.

Aged↗

Induction of plasmacytoid differentiation by phorbol ester in B-cell lymphoma cell lines bearing 8;14 translocations.

At nanomolar concentrations, phorbol 12-myristate 13-acetate induced differentiation in a human Epstein-Barr virus-negative B-cell line, JD 38, derived from an undifferentiated lymphoma and containing an 8;14 translocation. The changes induced by phorbol 12-myristate 13-acetate were consistent with differentiation towards plasma cells and included (i) a marked increase (30-fold) in IgM secretion; (ii) a decrease in the nuclear/cytoplasmic ratio associated with the development of a single prominent nucleolus instead of multiple nucleoli; (iii) the development of parallel arrays of rough endoplasmic reticulum, eccentric nuclei, and marginated heterochromatin; (iv) a reduction in the expression of surface markers, including common acute lymphoblastic leukemia antigen, IgM, and C3 receptors. Essentially all cells showed plasmacytoid differentiation, although the degree varied. Rare cells (less than 1%) appeared to be terminally differentiated into plasma cells. The increase in secreted IgM was preceded by a small increase in mu-chain RNA, with an increase in the ratio of secreted to membrane form. A small increase in c-myc RNA was also detected with differentiation. This might reflect coordinate regulation of the transcription of immunoglobulin and the translocated c-myc gene. Thus, the maturational arrest of this lymphoma cell line can be overcome with phorbol 12-myristate 13-acetate, indicating that translocation of the c-myc gene does not permanently block the capacity for differentiation. Further, this gene continues to be expressed to at least the same level during cell maturation. Similar ultrastructural changes were induced by phorbol 12-myristate 13-acetate in four of seven additional lines studied.

B-Lymphocytes↗

Synthesis of kappa light chains by cell lines containing an 8;22 chromosomal translocation derived from a male homosexual with Burkitt's lymphoma.

Three cell lines were derived from a homosexual patient with probable acquired immunodeficiency syndrome and Burkitt's lymphoma. The cell lines produce an unusual strain of Epstein-Barr virus which will both transform cord blood lymphocytes and induce early antigens in Raji cells. Translocations between chromosomes 8 and 22 have occurred in all three lines, but the cells synthesize immunoglobulin M with light chains of the kappa type, in contrast to the usual concordance between a translocation involving chromosome 22 and lambda chain synthesis. Both kappa genes and one lambda gene are rearranged. These findings indicate either that translocation may occur as a separate event from immunoglobulin gene rearrangement or that the proposed hierarchical sequence of immunoglobulin gene rearrangements is not always adhered to. The data also imply that in cells containing a translocation between the long arm of chromosome 8 and a chromosome bearing an immunoglobulin gene, alteration of cellular myc expression may occur regardless of the immunoglobulin gene that is expressed.

Acquired Immunodeficiency Syndrome↗

Use of fluoresceinated complement-coated bacteria and sheep erythrocyte-antibody-complement complexes for identification of complement receptors on lymphoid cell lines: differences in binding characteristics between cell lines of normal and malignant origin.

Twenty-four lymphoma-derived cell lines, 11 cord blood lymphocyte lines, and 3 lymphoblastoid cell lines derived from normal adults were examined for complement (C) receptors utilizing fluoresceinated C-coated bacteria (FBC) to determine the optimal conditions for each type of cell line. Incubation of FBC with lymphoma-derived cell lines at 37 and 0.5 degrees C showed that maximal FBC binding at both temperatures was after 120 minutes, and peak reactivity was invariably higher at 37 degrees C. These temperature-dependent differences were similar, both in Epstein-Barr virus nuclear antigen (EBNA)-positive and EBNA-negative lines. EBNA-positive lines, however, expressed higher levels of FBC rosettes than EBNA-negative lines at both temperatures. In contrast, FBC binding to cord blood cell lines after 120-minute incubation was maximal at 0.5 degrees C. Although similar numbers of FBC rosettes were formed after 30 minutes at both 37 and 0.5 degrees C in cord blood cell lines, rosette formation deteriorated after longer periods of incubation at 37 degrees C. The optimal temperature for FBC binding to lymphoblastoid cell lines could not be determined, since bacteria bound spontaneously to these lines at 37 degrees C. Cell lines were also tested simultaneously for sheep erythrocyte-antibody-complement complex (EAC)M and FBC binding at 37 and 0.5 degrees C. FBC reactivity under optimal conditions for each type of cell line correlated well with EACM reactivity at 37 degrees C. The significance of these results is discussed.

Burkitt Lymphoma↗

Apparent meningococcemia: clinical features of disease due to Haemophilus influenzae and Neisseria meningitidis.

To determine the etiology of apparent meningococcemia, all cases of sepsis with coagulopathy, purpura, and/or adrenal hemorrhage (Waterhouse-Friderichsen syndrome) with and without shock occurring over a 12-year period were reviewed. A total of 42 cases were identified; 30 cases were caused by Neisseria meningitidis and 12 cases were caused by Haemophilus influenzae. Compared with patients with disease caused by H influenzae, patients with meningococcal disease were older, more often male, more often contracted the disease in winter-spring, and had a longer duration of antecedent symptoms; however, none of these differences was statistically significant. All patients were febrile (greater than 38 degrees C) and appeared toxic. Similar proportions in each group had shock and disseminated intravascular coagulopathy at the time of admission. Ten of 12 patients with H influenzae infection compared with 15/30 (P less than .05) with meningococcal infection were lethargic or comatose at the time of admission. Nine of 12 patients with H influenzae infection died compared with 5/30 with meningococcal disease (P less than .005); the mean time from onset of symptoms to death with H influenzae infection (20.7 +/- 11.4 [SE] hours) was significantly shorter (P less than .05) than with meningococcal infection (120 +/- 74.4 hours). Children with clinical signs of sepsis and with purpura, petechiae, or coagulopathy may have N meningitidis or H influenzae as etiologic agents. Initial antibiotic therapy should be directed against these pathogens.

Age Factors↗

Serum monoclonal immunoglobulin bands in undifferentiated lymphomas of Burkitt and non-Burkitt types.

Using an improved electroimmunofixation technique that combines the sensitivity of high resolution agarose gel electrophoresis with the specificity of immunoprecipitation, we have demonstrated monoclonal immunoglobulin bands in the serum of patients with undifferentiated lymphomas of Burkitt and non-Burkitt types. Monoclonal bands were detected in the serum of 12 of 21 patients with extensive tumor, and 1 of 10 patients with minimal tumor. All of the bands were identified as IgM of a single light chain class. Such bands were not detected in the serum of patients with lymphoblastic lymphoma (7) or African Burkitt's lymphoma (6). There was disappearance of the bands after therapy and reappearance at relapse. These findings, coupled with previously reported in vitro information, indicate that undifferentiated lymphoma cells secrete immunoglobulin of IgM isotype. Therefore, such monoclonal bands may be of potential value as tumor markers.

Adolescent↗

Derivation of lymphoma cell lines from microscopically normal bone marrow in patients with undifferentiated lymphomas: evidence of occult bone marrow involvement.

Evidence is presented that at least 17% of microscopically normal bone marrow samples obtained from patients with undifferentiated lymphomas contain occult tumor cells. Of 19 microscopically normal bone marrow samples tested, continuous tumor cell lines were obtained from 4. A tumor cell origin was confirmed by the presence of an 8;14 chromosomal translocation in each case, and HLA typing confirmed the patient origin of the cell line. In two other patients, direct cytogenetic examination of microscopically normal bone marrow samples revealed karyotypes containing 8:14 translocations or a 14q+ chromosome. These findings indicate that undifferentiated lymphomas are often more widespread than is clinically appreciated. The presence of submicroscopic marrow involvement is also of significance to the design and analysis of treatment protocols involving autologous marrow infusion.

Adult↗

Immunoglobulin secretion by cell lines derived from African and American undifferentiated lymphomas of Burkitt's and non-Burkitt's type.

As part of an investigation of the cellular origins of undifferentiated lymphomas of the Burkitt's and non-Burkitt's types, we have examined immunoglobulin secretion by cell lines and biopsy samples from these tumors and have compared it with other lymphoblastoid cell lines. The majority of American lymphoma cell lines and a smaller fraction of African lymphoma cell lines secreted monoclonal IgM. No other Ig classes were secreted. Ig secretion by the tumor samples was also found to be exclusively IgM. The secreted IgM was polymeric and associated with J chain. Secretion of free light chain by most of the tumor cell lines was observed. Quantitation by immunoassay demonstrated that the American lymphoma cell lines secreted significantly more IgM than the African lymphoma cell lines. We have proposed that the lymphoma cells represent an early stage of B cell differentiation, during which antigen-independent secretion occurs.

Africa↗

Is the CSF lactate measurement useful in the management of children with suspected bacterial meningitis?

The role of the cerebrospinal fluid lactate measurement was evaluated for the management of children with suspected bacterial meningitis. Although CSF lactate can be precisely measured, it provided no additional information over that which can be obtained from a CSF cell count. Reliance on the CSF lactate concentration alone would have increased the number of children being treated unnecessarily with antibiotics. There was neither clinical nor experimental evidence to suggest that the test should be used in the early diagnosis of meningitis. In patients with equivocal clinical and CSF findings, it failed to differentiate bacterial from nonbacterial infection. The data do not support the view that the measurement of CSF lactate has significant role in the management of children with suspected meningitis.

Adolescent↗

The effect of polybrominated biphenyl on infants and young children.

The effects of PBB on 33 children born between September 1, 1973, and December 31, 1975, were evaluated in September, 1977. These children, born to families who lived on quarantined farms, were compared to 20 children who were not exposed to PBB. The birthdate interval was selected to obtain children who were exposed in utero or in early infancy or both, the two time periods when damage to developing tissues and organ systems should have been maximal. The results of these studies failed to identify any effects on physical growth, physical examination, or neurologic assessment, although the parents indicated by historical review that the exposed children had had more illnesses, especially respiratory, than had the control children. There were some indications of an inverse relationship between PBB fast level and performance on selected developmental tests.

Biphenyl Compounds↗