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Biomedical subjects

A Cross

Publications and source records attributed to A Cross.

At least 73 records · Page 4Linked to original sources

T cell receptor gene rearrangements in B-precursor acute lymphoblastic leukemia correlate with age and the stage of B cell differentiation.

Children with ALL diagnosed at less than 2 years of age have a poor prognosis when compared with older children. In an effort to identify biologic features of ALL in children less than 2 that might explain this difference, we performed extensive immunophenotypic and molecular genetic analyses on a series of patients. For comparison purposes patients were divided into four groups: CALLA- (CD10-) infants less than 2 years of age at diagnosis (n = 10), CALLA- children greater than 2 years of age at diagnosis (n = 10), CALLA+ infants (less than 2 years, n = 21) and CALLA+ children (older than 2 years, n = 21). No immunophenotyping differences in CALLA- or CALLA+ subgroups were identified when cases less than 2 were compared with cases greater than 2 years of age at diagnosis. The most interesting results were in the CALLA- group where 94% of the samples expressed the B cell antigen CD19 but 27% co-expressed CD7. Double labeling experiments confirmed leukemic blast cells co-expressed CD19 and CD7. The double-labeled cells represent either leukemic conversion of a precursor cell which has not yet committed to B or T cell lineage or aberrant expression of these antigens. Molecular genetic studies demonstrated that all samples, regardless of the patients' age or immunophenotype, had rearrangement of the Ig heavy chain gene. The most striking molecular results were in CALLA- patients; in patients less than 2 at diagnosis neither the beta- nor the gamma-chain gene of the T cell receptor (TCR) was rearranged, whereas DNA from 5 of 10 patients over the age of 2 demonstrated beta- or gamma-chain TCR gene rearrangements. The percentage of CALLA+ cases under the age of 2 years with rearrangements in TCR genes is less than that found in CALLA+ cases over the age of 2 years. The finding of no TCR rearrangements in CALLA- ALL and a decreased number of gamma-TCR rearrangements in CALLA+ cases under the age of 2 suggest that age may affect TCR gene rearrangements in lymphoblasts. The molecular differences in TCR gene rearrangements do not appear to correlate with the response to therapy.

Aging↗

Group B streptococcal sepsis in adults and infants. Contrasts and comparisons.

Group B streptococcal infection may result in significant morbidity and mortality in both infants and adults. The experience with group B streptococcal disease was analyzed at one medical center over a ten-year period from 1975 to 1984. Streptococcus agalactiae bacteremia was observed in 29 adults and 26 infants, with an attack rate of 0.2 cases per 1000 adult admissions and 3.2 cases per 1000 live births, respectively. The majority of adult infections apparently occurred as a result of nosocomial acquisition and was associated with a high mortality rate of 38%. Risk factors for group B streptococcal sepsis in adults include diabetes mellitus, malignancy, and hepatic failure. The majority (73%) of neonatal cases occurred within seven days of birth and occurred in a setting of maternal fever, prolonged rupture of membranes, or prematurity. The mortality rate in infants was remarkably low at only 15%. Fatalities occurred in both adults and infants, despite appropriate antimicrobial therapy. Infection control strategies against group B streptococcus must address potential nosocomial dissemination in adults as well as vertical transmission in infants.

Adult↗

Antibiotic-resistant isolates of Streptococcus pneumoniae from clinical specimens: a cluster of serotype 19A organisms in Brooklyn, New York.

Ten of 294 isolates of Streptococcus pneumoniae from patients enrolled in a Veterans Administration Cooperative Studies Program trial of pneumococcal vaccine efficacy were moderately resistant or resistant to penicillin. Nine of these organisms were serotype 19A isolated from patients at the Brooklyn (New York) V.A. Medical Center over an 18-month period (March 1983-November 1984). The minimal inhibitory concentration of penicillin for these pneumococci ranged from 1.0 to 2.0 micrograms/ml by the agar dilution technique and from 4.0 to 8.0 micrograms/ml by tube dilution. These organisms were resistant also to other beta-lactam antibiotics and to tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole. They were sensitive to erythromycin, clindamycin, vancomycin, and rifampin. The epidemiological source of these isolates was not discovered. However, it is possible that a focus of multiple antibiotic-resistant serotype 19A S. pneumoniae is present in Brooklyn.

Drug Resistance, Microbial↗

Binding sites for [3H]glutamate and [3H]aspartate in human cerebellum.

The binding of [3H]aspartate and [3H]glutamate to membranes prepared from frozen human cerebellar cortex was studied. The binding sites differed in their relative proportions, their inhibition by amino acids and analogues, and by the effects of cations. A proportion (about 30%) of [3H]glutamate binding was to sites similar to those labelled by [3H]aspartate. An additional component of [3H]glutamate binding (about 50%) was displaced by quisqualate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, and may represent a "quisqualate-preferring" receptor. Neither N-methyl-D-aspartic acid-sensitive nor DL-2-amino-4-phosphonobutyric acid-sensitive [3H]glutamate binding was detected.

Aspartic Acid↗

Identification of Escherichia coli K1 antigen.

We compared the use of bacteriophage sensitivity, seroagglutination with polyclonal antisera raised in rabbits or horses, seroagglutination with murine monoclonal antibody, and the serum agar precipitin technique for the detection of K1 capsular polysaccharide among clinical isolates of Escherichia coli obtained from blood stream infections. Some E. coli isolates failed to yield agreement among these tests, indicating that reliable detection of K1 antigen may require the use of multiple tests.

Agglutination Tests↗

Dopamine D-1 and D-2 receptors in Huntington's disease.

Dopamine receptors were studied in post-mortem brains from control and Huntington's disease patients, using the specific binding of [3H]spiperone to dopamine D-2 receptors and [3H]piflutixol to dopamine D-1 receptors. Both [3H]spiperone binding and [3H]piflutixol binding were reduced by 45-50% in Huntington's disease putamen. The loss of [3H]spiperone and [3H]piflutixol binding sites correlated with decreased GABA concentrations observed in Huntington's disease putamen. A selective loss (48%) of [3H]piflutixol binding was observed in Huntington's disease substantia nigra pars reticulata, [3H]piflutixol binding was unchanged in substantia nigra pars compacta. No differences in [3H]spiperone binding were observed between the groups in either region of substantia nigra. The results are discussed in relation to the pathophysiology of Huntington's disease, and to the presence of distinct dopamine receptors in human brain.

Aged↗

Effectiveness of the neonatal transport team.

This study was performed to determine the effectiveness of a hospital-based transport team in lowering mortality in newborns. The medical records of 603 outborn infants weighing from 500 to 2500 g and having primary respiratory disorders were reviewed. The infants were admitted to 1 of 3 regional neonatal centers between January 1, 1977 and September 30, 1980. The 2 centers without transport teams admitted 304 outborn infants, of whom 62 (20%) expired by 120 h of age. The center with a transport team admitted 184 team-transported infants and 115 nonteam-transported infants, of whom 38 (13%) expired by 120 h of age. Outborn infants admitted to the hospitals without a neonatal transport team had a 60% (p less than 0.01) greater mortality compared to those admitted to the hospital with a transport team. At the onset of intensive care, the babies transported to the nonteam hospitals had a greater incidence of hypothermia and acidosis which may be related to their increased mortality. We conclude that hospitals without the services of a neonatal transport team may have significantly more deaths among low birth weight infants with respiratory disease than comparable hospitals with neonatal transport teams.

Humans↗

Processing of herpes simplex virus type 1 glycoproteins: two-dimensional gel analysis using monoclonal antibodies.

The number of discrete species of glycoprotein induced by herpes simplex virus type 1 (HSV-1, strain 17 syn+) and their processing has been examined by a combination of immunoprecipitation with monoclonal antibodies and analysis of immune precipitates by two-dimensional (2D) gel electrophoresis. Seventeen different monoclonal antibodies directed against glycoproteins A/B, C, D and E were used. Polypeptides intermediate in the synthesis of gA/B, C and D were visualized and two early intermediates of glycoprotein A/B (pgA/B1 and pgA/B2), both mannose-containing, were identified. Comparison on 2D gels of polypeptides synthesized in vitro from HSV-1-infected cell mRNA with those synthesized in pulse-chase experiments in vivo has allowed identification of early precursors of pgA/B and pgD. Their apparent mol. wt. were 105000 and 47000 respectively. The 2D gel analysis of glycoproteins induced in HFL cells infected with 17 syn+ revealed a number of previously unreported glycoprotein species. One had mobility on both gradient and single concentration SDS-polyacrylamide gels similar to that of gC but was resolved from gC on non-equilibrium pH gradient gels. This glycoprotein was produced in relatively large amounts and was not precipitated by any of the monoclonal antibodies used in this study. The data suggest that this glycoprotein either has a polypeptide chain unrelated to those of glycoproteins A/B, C, D or E or alternatively is derived from one of them and modified in such a way as to mask or remove the antigenic sites with which the monoclonal antibodies interact. Sixteen other previously unreported glycoprotein species not obviously related, as judged by their electrophoretic mobility, to gA/B, C, D or E were also identified: two reacted with gA/B-specific monoclonal antibodies and five with glycoprotein C-specific monoclonal antibodies. The origin of the remaining nine new glycoproteins has still to be ascertained.

Antibodies, Monoclonal↗

K antigen and serum sensitivity of rough Escherichia coli.

We prepared bacterial hybrids which express both K1 and K27 antigens and examined the relative contributions of these capsules to serum resistance. Escherichia coli Hfr strain F639 (rough, K27+, serum sensitive) was conjugated with E. coli recipient strain E412 (rough, K1+, His- Trp- Strr, serum resistant). Transconjugants which inherited both the his and trp linked genes for K27 antigen synthesis were analyzed. These hybrids retained and expressed the K1 antigen since the K1 locus is nonallelic with K27 gene loci. Hybrid strains which express both K1 and K27 antigens exhibit serum resistance, but not at the level of the K1+ parental strain. An isogenic K1 derivative of a hybrid which expressed only K27 antigen was serum sensitive (greater than 99% kill, 60 min). These findings indicate that the presence of the K1 capsular antigen can protect some rough strains of E. coli from serum bactericidal activity, whereas K27 and perhaps other K antigens fail to provide such a protective effect.

Antigens↗

High-resolution magnetic resonance imaging of normal porcine cartilaginous epiphyseal maturation.

The aim of this study was to determine whether high-resolution magnetic resonance (MR) imaging could differentiate epiphyseal and articular cartilage in the cartilaginous epiphysis and demonstrate its developmental changes. T1- and T2-weighted (T1W and T2W) spin-echo sequences at 50-mm field of view (FOV) of hip joints were obtained from 14 piglets (newborn to 6 months). Subsequently, high-resolution MR images (15-mm FOV) of a biopsy core of the proximal femoral cartilaginous epiphysis were correlated with histology. Newborn cartilaginous epiphysis demonstrated homogeneous signal intensity on T1W and T2W imaging with abundant cartilage canals. From 2 weeks of age, the cartilaginous epiphysis showed a diminution of cartilage canals, with three zones evident on T2W imaging consisting of a low-signal middle zone separating two higher signal zones. Histologic evaluation demonstrated four distinct morphologic laminas with a decrease in overall cartilage thickness with age. The laminas were not as well defined in the newborn compared with the older piglets. No simple correlation was found between the MR zonal pattern and the morphological laminas on histology. No distinct demarcation between the articular cartilage and epiphyseal cartilage was present. MR can visualize cartilage canals and demonstrate changes in the cartilaginous epiphysis that occur with maturation. What component of the cartilaginous epiphysis that accounts for the MR differences seen between newborn and older piglets remains unclear.

Animals↗

Nosocomial infections due to Pseudomonas aeruginosa: review of recent trends.

The role of Pseudomonas aeruginosa in nosocomial infections occurring since 1975 is reviewed. Data from the National Nosocomial Infections Study conducted by the Centers for Disease Control, from individual medical centers, and from the literature were used to compare the relative frequency of occurrence of nosocomial infection caused by P. aeruginosa with that of infection caused by other gram-negative bacilli. The relative frequency of P. aeruginosa as a nosocomial pathogen has increased, although wide variations are seen among individual medical centers. P. aeruginosa continues to be a major pathogen among patients with immunosuppression, cystic fibrosis, malignancy, and trauma. While Staphylococcus aureus has become the predominant pathogen in some large burn centers, P. aeruginosa is the most important gram-negative pathogen. Periodic review of the epidemiology of P. aeruginosa infection is warranted in view of the changing incidence of infection caused by this organism.

Agranulocytosis↗

Accessibility of antigenic sites recognized by AUA1, HMFG1 and HMFG2 monoclonal antibodies: its influence on antibody binding of live cells.

We assessed the immunoreactivity of live and alcohol-fixed monolayers of HRA-19, a rectal adenocarcinoma cell line, to the monoclonal antibodies AUA1, HMFG1 and HMFG2. Differences in staining patterns between live and alcohol-fixed colonies were found. The well-polarized cells forming the centers of the monolayer colonies showed strong membrane staining when the cells were alcohol-fixed prior to AUA1 incubation, but showed no staining when the cells were alive during the incubation. When AUA1 incubation was done both before and after alcohol fixation, membrane staining was again seen, ruling out the possibility of antigenic modulation. Incubation of live cells with AUA1 together with EDTA showed strong staining of dissociating cells. It is concluded that AUA1 antigenic sites, which on polarized cells are basolateral in location, are inaccessible to the antibody-containing culture fluid, which bathes the apical aspects of the cells, but they become accessible after alcohol fixation, or treatment with EDTA. HMFG1 antigenic sites are located on the apical cell membrane, and accordingly, no differences were seen between incubation of live and alcohol-fixed cells when incubated with HMFG1. The antigenic sites of HMFG2 are partly intracellular, and in our monolayer model, the staining of live cells was weaker and more scarce than on alcohol-fixed cells. It is concluded that immunostaining of cytological and histological material of tumours may not adequately predict antibody binding on live cells, and thus, these findings are of importance in the context of selection of monoclonal antibodies for clinical radio-immunotargeting.

Adenocarcinoma↗

131I-labelled monoclonal antibody H17E2 in the detection of subcutaneous metastasis from gestational choriocarcinoma.

Subcutaneous metastasis is an uncommon finding in gestational choriocarcinoma. We detected such a lesion by external radioimmunoscintigraphy in a patient with gestational choriocarcinoma using 131-I labelled H17E2 monoclonal antibody raised against placental alkaline phosphatase. On the contrary, no positive image of the same metastasis was taken using 131-I labelled non-specific 11.4.1 monoclonal antibody. The successful detection of occult metastatic deposits in choriocarcinoma, which have become resistant to chemotherapy, may be of value for the potential use of curative surgery in these patients.

Adult↗