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Biomedical subjects

A Robinson

Publications and source records attributed to A Robinson.

At least 19 recordsLinked to original sources
PubMed1992

Prognosis of prenatally diagnosed children with sex chromosome aneuploidy.

Sex chromosome aneuploidy (SCA) occurs in about 1/250 amniocenteses, and the significance of the long-term prognosis of fetuses with SCA is of concern to prospective parents and health care providers. Longitudinal studies in an unselected group of newborn infants with SCA diagnosed postnatally have refuted allegations of mental retardation but have documented an increased risk for developmental problems. Of the 530 phone consultations with parents faced with a prenatal diagnosis of SCA, 68% continued the pregnancy. Twenty of the oldest subsequently born children (now 7-14 years old) were available for follow-up. In this small sample and age group, the propositi are progressing developmentally at a rate comparable to their sibs and are doing better at school and in peer relations than the SCA group diagnosed postnatally. Only 2 have documented IQs as low as 90. The documented IQs of the remainder, none of whom are sex chromosome mosaics, are all over 110. The parent population in this prenatally diagnosed group is unique and different from that of the postnatally diagnosed group in that over 85% of them are college graduates, often professionals, and upper socioeconomic individuals. The developmental competence of this SCA sample may be attributable to the supportive environment provided by these families, all of whom made a conscious decision to continue the pregnancy.

Adolescent↗
PubMed1992

Effects of guanidinium hydrochloride on the structure and immunological properties of Bordetella pertussis fimbriae.

Denaturation of Bordetella pertussis fimbrial preparations by guanidinium hydrochloride (GdnHCl) has been characterized using static light scattering, c.d., fluorescence and antibody recognition. The susceptibility of Fim2 + 3 (a mixed preparation of two fimbrial types) to GdnHCl was found to be highly dependent on pH; as the pH was increased from pH 7.2 to 10.5, the concentration of GdnHCl required to induce 50% denaturation was decreased. At pH 10.5, Fim2 + 3 was denatured by GdnHCl in a three-step pathway comprising: (1) formation of a pre-denaturational intermediate at less than 1.0 M-GdnHCl; (2) dissociation of the fimbrial polymer into subunits between 2 M- and 3.2 M-GdnHCl; and (3) subunit unfolding between 2.8 M- and 3.6 M-GdnHCl. A similar pathway was also found for the denaturation of the individual fimbrial types, Fim2 and Fim3, except that unfolding of either subunit commenced at a lower GdnHCl concentration (2.2 M) than that found for the mixture of fimbriae, Fim2 + 3. The second step in the denaturation pathway, dissociation into subunits, was partially reversible, but the renaturation and reassociation of fully unfolded subunits to form fimbriae-like structures was not achieved. These findings demonstrate that the GdnHCl denaturation of complex polymeric proteins is unlikely to follow a reversible two-state denaturation pathway, and support the involvement of a chaperone-like protein in the folding and assembly of the fimbriae in vivo. Measurement of the ability of anti-fimbrial monoclonal antibodies to recognize intermediates in the denaturation pathway enabled the identification of two types of epitope which were dependent on different aspects of fimbrial tertiary/quaternary structure.

Animals↗
PubMed1992

Hypocalcemia during sepsis. Relationship to resuscitation and hemodynamics.

The ionized calcium (IC) and parathyroid hormone response to polymicrobial intra-abdominal sepsis and the relationship between IC and hemodynamic alterations with and without crystalloid resuscitation were investigated. Thirty swine underwent cecal ligation and incision (n = 19) or sham laparotomy (n = 11), with seven animals that had cecal ligation and incision administered Ringer's solution (50 mL/kg) after each set of measurements recorded on days 0, 1, 2, 4, and 8. An early decrease in mean arterial pressure and cardiac index in animals that had cecal ligation and incision reversed with resuscitation. The IC also fell early and parathyroid hormone level increased in both the unresuscitated and resuscitated septic groups. However, correlation coefficients of mean arterial pressure and cardiac index with IC ranged from .034 to .287 in the septic animals and were lower in the group that had sham laparotomy. We conclude that polymicrobial intra-abdominal sepsis results in decreased IC and an elevated parathyroid hormone level. Hemodynamics do not correlate with IC levels, and resuscitation can be achieved without calcium administration.

Animals↗
PubMed1992

Molecular studies of parental origin and mosaicism in 45,X conceptuses.

The present report summarizes molecular studies of parental origin and sex chromosome mosaicism in forty-one 45,X conceptuses, consisting of 29 spontaneous abortions and 12 liveborn individuals with Turner syndrome. Our studies indicate that most 45,X conceptuses have a single, maternally derived X chromosome, regardless of whether the conceptus is liveborn or spontaneously aborted. In studies of mosaicism, our identification of X- and Y-chromosome mosaics among 45,X spontaneous abortions indicates that mosaicism does not ensure survival to term of 45,X fetuses. However, the incidence of sex chromosome mosaicism is substantially higher in liveborn than in aborted 45,X conceptuses, indicating that the presence of a second cell line increases the likelihood of survival to term.

Abortion, Spontaneous↗
PubMed1992

The role of CD45 in T-cell activation--resolving the paradoxes?

CD45 is one of the most abundant transmembrane glycoproteins expressed on the surface of haematopoietic cells. Despite the striking advances of the past few years in the understanding of the actions of CD45 at a molecular level, several paradoxes remain. This article argues that these paradoxes are more apparent than real, and suggests that CD45 plays a key role on the T-cell surface in regulating coupling of the antigen-receptor complex to intracellular signalling pathways.

CD3 Complex↗
PubMed1992

Potency testing of acellular pertussis vaccines.

The laboratory assessment of the potential of acellular pertussis vaccines to protect against human disease is a major problem. The mouse intracerebral challenge test, which is the accepted potency assay for whole cell pertussis vaccines, is not suitable for testing acellular vaccines, and more recently developed murine respiratory infection assays have methodological drawbacks and doubtful relevance to the human infection. We have found that the ability of several Bordetella pertussis antigens to protect mice against lung colonization correlates with their ability to raise murine antibodies which inhibit the adhesion of the bacteria to Vero cells. In this report we consider the applicability of such in vitro assays, and the in vivo assays, to the potency testing of acellular pertussis vaccines.

Animals↗
PubMed1992

Intranasal infection of infant mice with Neisseria meningitidis.

In human meningococcal infection the mechanism of the transition from asymptomatic carriage to invasive disease is unknown, partly due to the lack of an effective animal model that mimics all stages of the human disease. Therefore, we have endeavoured to develop a model for the human infection by instilling a suspension of Neisseria meningitidis into the nostrils of infant mice and subsequently determining the numbers of organisms in the nasal passages, lungs, blood and brains. Intranasal (i.n.) instillation resulted in consistent nasal colonisation which usually developed into a lung infection. In many cases the lung infection preceded bacteraemia, which occasionally resulted in death of the mice. The severity of the infection and the transition to bacteraemia were enhanced by intraperitoneal (i.p.) treatment of the mice with iron dextran or human transferrin. A N. meningitidis strain that was avirulent in an i.p. infection was also avirulent following i.n. infection. The requirement for lung colonisation to precede bacteraemia and the need for i.p. injection of iron compounds limit the use of i.n. infection of the infant mouse as a model for human meningococcal disease. However, various aspects of meningococcal virulence can be examined using this model.

Animals↗
PubMed1992

A phase II trial of goserelin (Zoladex) in relapsed epithelial ovarian cancer.

Thirty patients with advanced epithelial ovarian cancer were treated with the luteinising hormone releasing agonist, goserelin. There were two partial responses lasting 40 and 105 weeks respectively. In addition five patients had disease stabilisation lasting 25, 35, 40, 66 and 70 weeks respectively and 23 patients had progressive disease. No significant or unexpected toxicities occurred. This minimally toxic therapy halted disease progression for 6 months or more in 23% of patients, the majority of whom were heavily pretreated. There were five early deaths due to disease progression. The use of goserelin in patients with epithelial ovarian cancers resistant to or relapsing soon after first line platinum based chemotherapy needs to be further evaluated.

Adult↗
PubMed1992

Effects of haemorrhage on bacterial antigen specific pulmonary plasma cell function.

Nosocomial pneumonia is frequent after haemorrhage and trauma, and often contributes to multiple organ system failure, morbidity and mortality in this setting. Although the percentages and numbers of bacterial polysaccharide antigen-specific pulmonary B cell clonal precursors are markedly decreased after haemorrhage, the effects of haemorrhage on pulmonary plasma cells actually producing antibody to these antigens are unknown. To investigate this question, the numbers of intraparenchymal pulmonary plasma cells producing antibody against the bacterial polysaccharide antigen levan (from Aerobacter levanicum) as well as bacterial antigen specific secretory IgA (sIgA) titres in the lungs were determined at various time points after 30% blood volume haemorrhage. Reduced numbers of bacterial antigen specific pulmonary plasma cells were found for more than 21 days following haemorrhage. An almost complete disappearance from the lungs of levan specific plasma cells occurred between 3 and 21 days after blood loss. Titres of bacterial antigen specific sIgA in the lungs were decreased starting at 3 days post-haemorrhage and remained significantly depressed for more than 35 days after blood loss. These results demonstrate that haemorrhage produces profound and long-lasting suppression in bacterial antigen-specific pulmonary plasma cell function. Because these effects do not occur immediately post-haemorrhage, immunization techniques able to enhance bacterial antigen specific sIgA titres at pulmonary surfaces may be able to increase resistance to nosocomial pneumonia if administered shortly after injury and blood loss.

Animals↗
PubMed1992

H2-receptors mediate histamine-induced variations in the permeability of the blood-brain barrier of rats.

Earlier investigations suggested that histamine H2-receptors mediate alterations in cerebrovascular permeability in mammals. The objective of this study was to observe the effects of the H2-receptor antagonist ranitidine on histamine-stimulated alterations in the permeability of the blood-brain barrier (BBB) of rats. Normotensive Wistar-Kyoto (WKY) (control) and spontaneously hypertensive (SHR) rats were premedicated with ranitidine (1 mg/kg), followed by histamine (1.25, 2.5 or 5.0 micrograms/kg) or saline. Animals were anesthetized and permeability of the BBB was evaluated with 99mTc-labeled sodium pertechnetate (TcO4-) or with 131I-labeled human serum albumin (RISA). In both control and hypertensive rats, ranitidine blocked histamine-induced changes in cerebrovascular permeability, but did not inhibit histamine-stimulated systemic hypotension. The alterations in the permeability of the BBB did not correlate with variations in blood pressure produced by histamine.

Animals↗
PubMed1992

Swirls, wrinkles and the whole ball of wax (the source of keratin in cerumen).

Recent work carried out at the Ear Pathology Research Laboratory has demonstrated that cerumen plugs consist of a large amount of keratin debris. In this study the site of origin of this keratin was investigated. This was done by histologically examining these cerumen plugs without disturbing the natural relationship between the plug and the surrounding epithelium. We have clearly demonstrated that a cerumen plug consists of keratin arising from the migratory epithelium of the deep external auditory canal and epithelium of the superficial external auditory canal.

Cadaver↗
PubMed1992

Prognostic factors in juvenile chronic granulocytic leukaemia.

A retrospective analysis of the clinical and haematological characteristics of patients diagnosed as having juvenile chronic granulocytic leukaemia between 1971 and 1986 was carried out. Thirty-three children were identified who were between the ages of 18 weeks and 8.8 years at diagnosis. The disease was more frequent in boys than girls (23:10). The most common presenting symptoms were skin rash (58%) and bleeding manifestations (45%). All patients had some degree of splenomegaly and in 88% this was more than 3 centimetres below the costal margin. Hepatomegaly and lymphadenopathy were also frequent findings. Anaemia was common and leucocytosis an invariable finding with a white cell count above 50 x 10(9) 1-1 in 42%. Monocytosis was found in 78%. Haemoglobin F measurements were available in 31 children and above 10% in 22 (67%). No child had the Philadelphia chromosome or monosomy 7. Thirty children were treated with chemotherapy, with a variable degree of symptomatic improvement. Twenty-nine patients had died with a median survival time of 5 months. The commonest cause of death was complications of bone marrow failure and no child developed acute leukaemia. Presenting characteristics associated with a longer survival period were age less than 6 months (P = 0.02), female sex (P = 0.02), HbF less than 10% (P = 0.0004) and the absence of bleeding manifestations (P = 0.03). We conclude that the prognosis for children aged over 6 months, with a raised HbF level is very poor, and that, in the absence of possible bone marrow transplantation, consideration should be given to novel treatment approaches for these patients.

Antineoplastic Agents↗
PubMed1991

Phase II trial of whole-cell pertussis vaccine vs an acellular vaccine containing agglutinogens.

An acellular pertussis vaccine containing agglutinogens 2 and 3, pertussis toxin, and filamentous haemagglutinin was developed by the Centre for Applied Microbiology and Research in the UK. 188 infants were entered into a randomised blind trial and received either the acellular or a whole-cell vaccine, combined with diphtheria and tetanus toxoids, in a 3, 5, and 8-10 month schedule. Local reactions were similar in the two groups but significantly fewer infants had systemic symptoms after the acellular vaccine. Mean log-antibody titres to the agglutinogen and toxin components were higher with the acellular than with the whole-cell vaccine. Persistence of antibodies one year after the third dose was also better in the acellular group.

Antibodies, Bacterial↗
PubMed1991

A comparison of fibrillation in denervated skeletal muscle of the anaesthetized rat and guinea-pig.

We have used intracellular recording in vivo to study fibrillation (spontaneous repetitive membrane activity) in extensor digitorum longus (fast twitch) and soleus (slow twitch) muscles of the anaesthetized rat and guinea-pig denervated for periods of about 10 to 60 days. The proportion of fibres fibrillating in the guinea-pig soleus was greater than 50% in most animals up to the longest period of denervation (65 days). Fibrillation was rarely found in rat soleus after three weeks of denervation. Its incidence in the extensor digitorum longus muscles of both species was intermediate. The mean frequency of fibrillation was higher in guinea-pig extensor digitorum longus (16 Hz) and soleus (8 Hz) than in the rat extensor digitorum longus (3 Hz) and soleus (2 Hz). The resting membrane potentials of the denervated muscles were less than normal and correlated inversely with the frequency of fibrillation but not with the incidence of fibrillation: in rat soleus, many fewer fibers were fibrillating at a given membrane potential than in the other three muscles. The incidence of fibrillation was compared with previously reported tensions of the four denervated muscles and was found to have the same rank order. We suggest that fibrillation may reduce atrophy (and hence tension loss) of denervated muscle, which may have implications for artificial stimulation. Fibrillation frequency was directly related to changes in twitch speed of the four muscles after denervation.

Animals↗
PubMed1991

An exploration of family and individual profiles following father-daughter incest.

This paper presents the results of a range of psychometric assessments which attempted to identify family and individual variables associated with father-daughter incest. Psychometric self-report measures were used to examine differences between families in which incest had been confirmed and a matched comparison group. Significant differences between the members of the incest and the comparison groups included behavioral and self-esteem problems in the daughters and differences in the familial environments of the two groups. Daughters who had been sexually abused reported lower levels of self-esteem about their intellectual and school status. Mothers in the incest group reported that their daughters had more conduct problems than the comparison mothers. The incest families were generally reported to be higher in conflict and organization and lower in cohesion, expressiveness, and active recreation. No differences between groups were found for levels of marital adjustment, self-esteem in mothers, or overall level of psychopathology in the perpetrators.

Adaptation, Psychological↗