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Biomedical subjects

A Robinson

Publications and source records attributed to A Robinson.

At least 397 records · Page 22Linked to original sources

Pituitary-gonadal function in Klinefelter syndrome before and during puberty.

Serum concentrations of follicle-stimulating hormone, luteinizing hormone, testosterone, and estradiol were determined at intervals before and during puberty in 40 individuals with Klinefelter syndrome (47,XXY karyotype), of whom 27 had been detected in neonatal cytogenetic screening programs. Prior to the appearance of secondary sexual changes, basal serum hormone concentrations and acute responses to stimulation with gonadotropin-releasing hormone and human chorionic gonadotropin were normal. The timing of the onset of clinical puberty was normal. Early pubertal boys showed initial testicular growth and normal serum testosterone levels, while serum follicle-stimulating hormone and estradiol concentrations were significantly elevated. By midpuberty, the Klinefelter subjects were uniformly hypergonadotropic and their testicular growth had ceased. Serum testosterone concentrations after age 15 remained in the low-normal adult range. Serum estradiol levels remained high, irrespective of the presence or absence of gynecomastia. Exaggerated responses to gonadotropin-releasing hormone are seen in pubertal subjects with elevated basal gonadotropin values.

Adolescent↗

The location of surface antigens of Bordetella pertussis by immuno-electron microscopy.

Immuno-electron microscopy using colloidal gold-tagged monoclonal antibodies (McAbs) has been used to detect antigens on the surface of Bordetella pertussis cells. McAbs to serotype-specific agglutinogens 2 and 3 labelled fimbriae in a serotype-specific manner. An attempt was made to determine whether individual fimbriae of serotype 1.2.3 cells bear both antigens 2 and 3. In double labelling experiments, individual cells were found to label with McAbs to antigen 2 (3 nm gold) and to antigen 3 (15 nm gold). Many fimbriae labelled with only one of these reagents, but there were instances where both labels could have been attached to the same fimbria. No fimbrial labelling was obtained with McAb to agglutinogen 1. Gold-tagged McAbs to filamentous haemagglutinin (FHA) labelled neither the fimbriae nor the surface of B. pertussis cells. Unfixed cells on electron microscope grids appeared to shed FHA readily. After fixation, a small proportion of cells bore aggregates of FHA which labelled specifically with anti-FHA McAb-gold. Results with one McAb to lymphocytosis promoting factor indicated that this antigen may be more intimately associated with the surface of B. pertussis than is FHA.

Antibodies, Monoclonal↗

Release and purification of fimbriae from Bordetella pertussis.

A competitive ELISA has been used to monitor the release of fimbriae from 1.2.3 serotype of B. pertussis after treatment by different methods and fimbriae have been purified from homogenates or KSCN extracts by chromatography. Fimbriae purified from different serotypes have been studied by inhibition of bacterial agglutination, immunodiffusion and SDS-polyacrylamide gel electrophoresis. Fimbriae purified from a 1.2 serotype have been labelled in immunoelectron microscopy with a IgM monoclonal antibody to agglutinogen 2 and evidence is presented that fimbriae purified from a 1.3 serotype also carry the agglutinogen 3 specificity. A difference in subunit molecular weight has been found between fimbriae purified from 1.2 and 1.3 serotypes.

Agglutinins↗

Protection against intranasal infection of mice with Bordetella pertussis.

Mice have been infected by intranasal instillation of Bordetella pertussis and the infection monitored by determining numbers of bacteria isolated from the lungs. Outer membrane proteins, filamentous hemagglutinin, toxoided-lymphocytosis promoting factor and agglutinogens (fimbriae) actively protect mice against intranasal infection and antibodies of the antigens neutralize infectivity. The neutralization of infection by agglutinins is serospecific. In general, antigens that actively protect mice against intracerebral infections also protect against intranasal infections but some antigens, such as filamentous hemagglutinin and agglutinogens, protect only against intranasal infections. The intranasal protective potency of antigens can be enhanced by including low levels of active lymphocytosis promoting factor in the preparations. The relevance of the intranasal test to the potency testing of pertussis vaccines is discussed.

Animals↗

The relationship between pertussis-toxin-induced ADP-ribosylation of a plasma-membrane protein and reversal of muscarinic inhibition of prolactin secretion in GH3 cells.

Pertussis toxin (PT) caused the ADP-ribosylation of a Mr-41 000 protein in GH3-cell plasma-membrane preparations. This effect, and muscarinic inhibition of prolactin release, were reversed at similar rates by pretreatment of intact cells with PT. These results suggest that the Mr-41 000 protein is modified in intact GH3 cells, and that this protein (a component of the putative Ni unit of adenylate cyclase) is involved in the expression of muscarinic inhibition.

Adenosine Diphosphate Ribose↗

Pertussis toxin blocks the inhibitory effect of muscarinic cholinergic agonists on cyclic AMP accumulation and prolactin secretion in GH3 anterior-pituitary tumour cells.

The inhibition of prolactin secretion and cyclic AMP accumulation in GH3 cells by muscarinic agonists was blocked by preincubation of the cells with pertussis toxin (islet-activating protein). There was a lag of approx. 80 min in the onset of the effect on secretion. These results suggest that muscarinic agonists decrease prolactin secretion by inhibiting adenylate cyclase activity.

Adenylate Cyclase Toxin↗

The development of four unselected 47,XYY boys.

Four infants identified through neonatal screening programs are an unselected sample of 47,XYY boys. No consistent physical stigmata or medical disorders were identified. Three have increased height. All four demonstrated problems in motor and language development. Although their intelligence is within the average range, all four have language-related learning disorders requiring special education. Mild depression was apparent in all four, perhaps as a secondary result of their learning disorders. Some of the problems seen in the propositi are found in milder forms in other family members, leading to the hypothesis that their karyotype may heighten vulnerability to pre-existing familial conditions. Similarities between these findings and results from seven other study centers with a total of 42 47,XYY boys are noted. Parents of a prenatally diagnosed 47,XYY fetus seen in our center are informed that the extra Y chromosome represents a risk factor for these problems, but that environment remains a primary force in shaping their child's development.

Child Development↗

The combined effects of pregnancy and repeated plasma exchange on serum cholinesterase activity.

Fourteen patients are described in whom repeated plasma exchange was performed as part of their treatment for Rh alloimmunisation during pregnancy. Despite administration of fresh frozen plasma at frequent intervals during therapy, serum cholinesterase activity was shown to be reduced to levels sufficient to put many of them at risk from suxamethonium sensitivity. It is recommended that if short-acting muscle relaxants are intended to be used during the delivery of such patients, a careful investigation of cholinesterase status should be undertaken beforehand.

Anesthesia, Obstetrical↗

Isotypes of spontaneous and mitogen-induced autoantibodies in SLE-prone mice.

A common cellular abnormality of all murine strains prone to systemic lupus erythematosus (SLE) is an increased spontaneous polyclonal expansion of B cells. Our findings support the existence of this SLE-associated abnormality because the numbers of B lymphocytes secreting all the different IgG subclasses and IgM in spleens of all lupus-prone mice are elevated, compared to levels of normal splenic immunoglobulin-producing cells. We also report that 1) spontaneous polyclonal stimulation of immunoglobulin in autoimmune mice is preferential for subclass, and that the preferentially stimulated isotypes in each SLE strain consistently dominate both circulating and kidney-deposited immune complexes; 2) distinct patterns of isotype preference exist among the autoimmune strains determined by inherent B cell proliferative abnormalities or by B cell proliferation affected by thymus-derived lymphocytes; and 3) chronic administration of the TI B cell mitogen Lipid A in late-life SLE-prone mice induces an early-life glomerulonephritis with auto-antibodies of an isotype composition characteristic of those spontaneously produced by inherently abnormal B cells of early-life lupus mice.

Animals↗

Cognitive development of unselected girls with complete and partial X monosomy.

The cognitive development of nine girls with 45,X and 45,X variant karyotypes, seven 45,X mosaics, and nine 46,XX control subjects (ages 8 to 17 years) followed since birth was evaluated. The nonmosaic group was slightly delayed in walking, had a moderately decreased full-scale and performance IQ, demonstrated a striking deficit in perceptual organization and fine motor execution, but had generally average language skills. Three nonmosaic girls with low intelligence were identified and one subject had above average intelligence. Intelligence was not correlated with the presence of physical stigmata. No obvious developmental differences were found between the three girls with 45,X variant, two with partial Xq deletions and one with a ring X chromosome, and the six girls with 45,X genotype. The 45,X mosaic group did not experience early developmental delays and was not significantly different from control subjects on any IQ score. A large amount of variability between subjects was noted, which could be partially attributed to family characteristics and socioeconomic conditions. Whereas this study corroborates previous findings of specific intellectual deficits in 45,X populations, it emphasizes the need for caution in estimating the cognitive development of any X and partial X monosomic infant.

Adolescent↗

Antigens in whooping cough vaccine and antibody levels induced by vaccination of children.

The content of 3 antigens--filamentous haemagglutinin, lymphocytosis-promoting factor, and serotype-specific agglutinogens (fimbriae)--was determined in the current UK whole-cell whooping cough vaccine. Antibodies to these antigens and to outer membrane proteins and lipopolysaccharide of Bordetella pertussis were measured in the serum of unvaccinated children and children who had received 1, 2, or 3 doses of the vaccine. Children who had received one dose of vaccine had varied low antibody titres. Children who had received two or three doses had significantly higher antibody titres to all the antigens tested, as did some unvaccinated children with no history of whooping cough. This study shows that filamentous haemagglutinin, lymphocytosis promoting factor, and outer membrane proteins are immunogenic constituents of the whole-cell vaccine. Their inclusion in a subcellular vaccine would not involve novel antigens.

Antibodies, Bacterial↗

Parents' adaptation to early diagnosis of sex chromosome anomalies.

In 56 structured psychiatric interviews parents were asked to describe their experience as participants in the Denver prospective study of children with sex chromosome anomalies in order to assess its impact on attitudes toward the identified child and on family relationships. It was found that most achieved satisfactory understanding of the diagnosis with minimal disturbance, preferred early disclosure, denied its influence on parent-child and parent-parent relationships, and were reasonably comfortable in sharing diagnostic information with the child. Environmental and cultural factors did not correlate with the responses obtained. Emphasis directed toward obstacles in the adaptive process permitted evaluation of reported parental anxieties arising from faulty or delayed communication of the diagnosis, a child's adjustment to problems of growth and development, and, for parents of children with 45,X and 47,XXY chromosome constitutions, anxiety regarding anticipated difficulty in sexual maturation and fertility. The assessment interviews afforded additional opportunity for clinical discussion and counseling with parents on issues of concern to them.

Adaptation, Psychological↗

Prognosis in acute lymphoblastic leukemia of childhood as determined by cytogenetic studies at diagnosis.

Fifty-one children with acute lymphoblastic leukemia on a common protocol of treatment were classified according to presence or absence of chromosomal abnormalities found at the time of diagnosis in bone marrow and/or blood. Twenty-two or 43% had normal karyotypes while 29 (57%) had clonal abnormalities using the Giemsa-trypsin banding technique. Thirteen of the 29 (45%) chromosomally abnormal patients relapsed while only three of 21 (14%) with normal karyotypes have relapsed with a median follow-up of 49.5 months (42-76 months). (One child with a normal karyotype did not respond to therapy.) Several hypotheses have been offered to attempt to explain the significantly better prognosis of patients with no observable initial chromosomal aberrations.

Adolescent↗

Membrane and cytoplasmic changes in 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU)-sensitive and resistant human malignant glioma-derived cell lines.

Human glioma-derived cell lines previously determined by a microtiter chemotherapy assay to be either 'sensitive' or 'resistant' to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) were treated with BCNU (1-80 micrograms/ml) and observed using microcinematography, scanning electron microscopy, and transmission electron microscopy. Striking bleb formation and cell retraction were observed to occur in a dose-dependent relationship within minutes in the cells known to be BCNU-sensitive. At 15 micrograms/ml, 69% of cells showed blebs by 30 min, 87% by 90 min, and 100% by 4 hr. This activity was not seen in BCNU-resistant cells. These morphological changes occur at a time too early to be accounted for by the known BCNU mechanism of DNA alkylation and cross-link formation and suggest that cytoplasmic and/or membrane events may be significant initial events in the cytotoxic actions of BCNU.

Adult↗