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Biomedical subjects

P Graves

Publications and source records attributed to P Graves.

At least 19 recordsLinked to original sources
PubMed1998

Education for children with disabilities: the rationale for inclusion.

OBJECTIVE: To discuss issues in the education of children with disabilities, particularly with respect to inclusion in mainstream classes. METHODOLOGY: Review of the literature on education for children with disabilities, focusing on the inclusion versus segregation debate. RESULTS: The literature provides no support for segregation and some support for the view that segregated children are disadvantaged. What seems to be important is the way the child is educated rather than where the education takes place. In addition, there are ethical, sociological, and legal arguments in favour of an inclusive educational system. CONCLUSIONS: There are good arguments to encourage inclusive education for children with disabilities. In advising parents, doctors should focus on how rather than where the child with a disability should be educated.

Child↗
PubMed1997

Development of oral hygiene self-efficacy and outcome expectancy questionnaires.

In order to measure social cognitive constructs in the oral hygiene domain, questionnaires containing self-efficacy and outcome expectation items were developed. Items were generated to measure personal beliefs in brushing and flossing ability under a variety of circumstances, and expected outcomes from performing oral hygiene behaviors that might be positive, negative, primary and secondary. In the first study, factor scales were developed on the basis of the responses from 90 subjects awaiting dental treatment. Principal components analyses with varimax rotation revealed two self-efficacy and four outcome expectations dimensions that explained 73% and 51% of the variance, respectively. A second study that utilized 103 government employees was conducted to evaluate the psychometric properties of the questionnaires. All scales demonstrated good internal consistency and test-retest stability. Correlations with extra test measures provided preliminary evidence for the validity of the instruments.

Adult↗
PubMed1996

Mortality from intentional and unintentional injury among infants of young mothers in Colorado, 1986 to 1992.

OBJECTIVES: To investigate the association between maternal age and other risk factors and infant injury deaths in the state of Colorado from 1986 to 1992. DESIGN: A retrospective cohort design was used to compare rates of unintentional and intentional infant injury mortality by maternal age group. A case-control design explored the importance of various risk factors, particularly maternal age, using multivariate logistic regression. PARTICIPANTS: The 2 case groups comprised all unintentional and intentional injury deaths in the first year of life. The control group was a random sample of both survivors and noninjury deaths selected from the entire birth cohort. RESULTS: The infant injury mortality rate for the 322766 live births in Colorado from 1986 to 1992 was 3.1 per 10000. Intentional injury death rates were highest for infants of teenaged mothers, peaking at 10.5 per 10000 live births for mothers aged 16 years. Unintentional injury death rates were highest for infants of mothers aged 20 to 24 years, peaking at 3.7 per 10000 live births for 22-year-old mothers. For intentional injury death, maternal marital status had a significant impact on maternal age; compared with the baseline group of married mothers older than 24 years, significantly higher risks were observed for infants of teenagers who were married (odds ratio [OR] = 32.0; 95% confidence interval[CI], 9.9-104.0) but also in infants of older mothers who were unmarried (OR = 3.6; 95% CI, 1.0-13.0 for unmarried mothers aged 20-24 years and (OR = 7.7; 95% CI, 2.4-25.0 for those > 24 years). Black race (OR = 3.5; 95% CI, 1.4-9.4) was also associated with intentional injury death. For unintentional injury death, the highest risk was for infants of mothers aged 20 to 24 years and unmarried (OR = 3.9; 95% CI, 1.7-9.3). Risk was also elevated for infants of married teenaged mothers (OR = 3.5; 95% CI, 0.7-17.8) but was not significantly different from the baseline group for unmarried teenagers, married 20- to 24-year-old mothers, or unmarried mothers aged 25 years or older. Risk was increased by the presence of older siblings (OR = 1.5 per sibling; 95% CI, 1.2-2.0). CONCLUSIONS: Maternal age and marital status significantly affect the rate of both unintentional and intentional infant injury mortality. These results suggest that child abuse prevention strategies should be targeted to teenaged mothers, and that strategies designed to prevent unintentional injuries should focus particularly on parents or caretakers of infants born to unmarried mothers in their early 20s as well as married teenagers.

Adult↗
PubMed1996

Monoclonal antibodies to the human TSH receptor: epitope mapping and binding to the native receptor on the basolateral plasma membrane of thyroid follicular cells.

We have characterized four murine monoclonal antibodies (mAbs) to the extracellular domain of the human TSH receptor (TSH-R.E), the target autoantigen of Graves' disease. Recombinant TSH-R.E used as immunogen, was produced in E. coli as a fusion protein with glutathione-S-transferase or in a baculovirus-insect cell system, as a non-fusion glycoprotein. To increase the epitope specificity of the mAbs, two different strains of mice (H-2(b) and H-2(d)) were immunized. The epitopes recognized by the mAbs were characterized by immunoblotting with various recombinant constructs of TSH-R.E and by binding to overlapping synthetic peptides of the receptor. The four IgG mAbs characterized recognized epitopes localized to different regions on the TSH-R.E; amino acids 22-35 (A1O and A11, both IgG2b from H-2(b) animals), amino acids 402-415 (A7, IgG2b from H-2(b) animals) and amino acids 147-228 (A9, IgG1 from H-2(d) animals). Immunolocalization studies showed that mAb A9 recognized TSH-R.E on unfixed cryostat sections, where binding was localized to the basolateral plasma membrane of thyroid follicular cells, suggesting that this antibody reacts with the native receptor on thyroid cells. The binding of the mAbs A7, A10 and A11 was also restricted to the basal surface of thyroid cells, but only after acetone fixation of the sections, implying that the epitopes recognized on the amino and carboxyl terminus of the extracellular region of the receptor are not accessible on the native molecule. None of the mAbs stimulated cyclic AMP responses in COS-7 cells transiently transfected with full-length functioning TSH-R.E, whilst weak inhibition of binding of radiolabelled TSH to porcine membranes in a radioreceptor assay was apparent with mAb A10 and A11, but only at high concentrations of IgG. The ability of mAb A9 to bind to the native receptor without stimulating activity or inhibition of TSH binding suggests that antibody can bind to the central region of the TSH-R.E without perturbing receptor function. The availability of mAbs that recognize epitopes on different regions of the extracellular domain of TSH-R will lead to a better understanding of the autoantigenic regions on TSH-R implicated in disease activity.

Amino Acid Sequence↗
PubMed1995

White matter signal hyperintensities in the brains of patients with late paraphrenia and the normal, community-living elderly.

We determined the prevalence and anatomical location of areas of white matter hyperintensity visualized by magnetic resonance imaging in the brains of 38 late paraphrenic patients with an onset of psychotic illness after the age of 60 and 31 healthy aged community volunteers. All degrees of white matter signal hyperintensity were very common in both groups, and there was no excess of such changes in the brain of patients. Periventricular white matter and subcortical grey matter hyperintensities were significantly associated with both measured diastolic and systolic blood pressure in patients and control subjects. Periventricular and deep white matter, together with subcortical grey matter hyperintensities, were significantly associated with increased age. The excess of such presumed brain-imaging abnormalities previously reported in patients with an onset of psychosis late in life may be a consequence of earlier authors' failure to include examination of appropriate community control populations and to carefully exclude patients with evidence of stroke.

Aged↗
PubMed1995

Therapy methods for cerebral palsy.

OBJECTIVE: Current approaches to therapy for cerebral palsy tend to be child-focussed and claim functional improvements. Such approaches lead to demands for more therapy and more services as the solution for problems associated with cerebral palsy. This report suggests an alternative approach. METHODOLOGY: The literature on therapy methods for cerebral palsy is reviewed and compared with the literature on early intervention for children with intellectual disabilities. RESULTS: The claims for functional improvements resulting from therapy methods cannot be substantiated. The literature on early intervention for children with cognitive impairments indicates a shift in emphasis from the child's impairments to the whole child, the family and the wider community. CONCLUSIONS: Demands for more and better therapy are, at best, simplistic and tend to detract from the real needs of the child and family. An ongoing ecological approach is more likely to produce positive outcomes.

Cerebral Palsy↗
PubMed1994

Thyroglobulin-induced murine thyroiditis assessed by intrathyroidal T cell receptor sequencing.

Thyroid glands from CBA/J (H-2k) mice, with human thyroglobulin (Tg)-induced thyroiditis, were removed and total cellular RNA was prepared and reverse transcribed as target cDNA for PCRs to detect 17 murine T cell receptor (mTCR) V beta families. Southern analysis of the resulting PCR fragments showed a marked bias in the intrathyroidal expression of mTCR V beta gene families with only 10 detectable V beta gene families of the 17 tested. Four Tg-specific CBA/J T cell lines also showed a biased use of mTCR V beta gene families with only 7 V beta gene families detected of the 17 tested. Sequence analysis showed evidence of oligoclonal expansion of the intrathyroidal T cell populations, and some of the CDR3 sequences found in the thyroid infiltrates were identical, or similar, to examples of the patterns of CDR3 sequences seen in the Tg-specific lines. Overall, however, there was marked N-D-N sequence variation in both the lines and thyroid infiltrates. These data indicated that 1) mTcR V gene analysis of intact thyroid tissue reflected the thyroid Ag-specific T cells infiltrating the thyroid gland; 2) confirmed the phenomenon of oligoclonal expansion in early thyroiditis; 3) showed that certain V beta gene families may be overemployed in the T cell recognition of Tg in the context of H-2k; and 4) revealed, by the varied patterns of the CDR3 sequences, that the V gene itself may be more important in thyroid Ag recognition than N-D-N region motifs.

Amino Acid Sequence↗
PubMed1994

Quantitative magnetic resonance imaging volumetry distinguishes delusional disorder from late-onset schizophrenia.

BACKGROUND: Late paraphrenia is recognised as a heterogeneous disorder. This is reflected by the division of such patients into schizophrenia and delusional disorder in ICD-10. Earlier imaging studies have suggested that major structural abnormalities may be associated with the onset of psychosis in later life. METHOD: Fifty late paraphrenics and 35 age-matched healthy controls underwent structural magnetic resonance imaging of the whole brain in the coronal plane. Measurements were made of intracranial and brain volumes and the volumes of the intracerebral and extracerebral cerebrospinal fluid spaces. RESULTS: No differences in intracranial, brain or extracerebral cerebrospinal fluid volumes between patients and controls were found. Late paraphrenic patients had greater lateral and third ventricle volumes than controls and the left lateral ventricle was larger than the right. When the patients were divided into appropriate ICD-10 diagnoses: paranoid schizophrenia (n = 31) and delusional disorder (n = 16), lateral ventricle volumes in the delusional disorder patients were much greater than those of the schizophrenics and almost twice those of controls. CONCLUSIONS: Structural brain differences underly diagnostic heterogeneity within late paraphrenia. The brains of late onset schizophrenics are only subtly different from those of healthy elderly individuals.

Age of Onset↗
PubMed1993

HLA-DR alpha gene regulation in immortalized human thyroid cancer cells.

The induction of HLA class II antigens on human thyroid epithelial cells has been shown to be an intimate part of the pathology of autoimmune thyroid disease and may also be relevant to the natural history of thyroid neoplasia since thyroid cancer cells may show spontaneous HLA class II antigen expression. We have, therefore, analyzed the regulation of HLA-DR-alpha-specific mRNA transcripts, as a model for HLA class II antigen induction, in three established human thyroid cancer cell lines (papillary thyroid cell line NPA, and follicular thyroid cell lines RO-82-W1 and MRO-87-1). Each of the lines expressed 1.4 kb HLA-DR-alpha-specific mRNA transcripts, either constitutively or after cytokine induction, but showed markedly different regulatory characteristics. For example, the induction of HLA-DR alpha mRNA in response to recombinant human interferon-gamma (IFN-gamma) was inversely proportional to the degree of constitutive DR alpha mRNA expression; when there was constitutive absence there was a greater degree of induction. Similarly, the half-lives of the HLA-DR alpha mRNA transcripts varied from 80 to 420 min with the longest degradation time occurring in those cells lacking constitutive expression of HLA-DR alpha mRNA. These data indicated that the degradation rate was not a determinant of their constitutive expression. We also sequenced the 5' promoter region of the HLA-DR alpha gene (nucleotides -88 to -277 with respect to the translation start site) in each of the three cell lines. Sequence analyses revealed identity to the previously published normal human genomic sequence. Taken together, therefore, these data indicate that transactivating factors, rather than changes in mRNA degradation or promoter abnormalities, are the likely causes of variation in constitutive and cytokine-induced HLA-DR alpha gene expression in human thyroid cancer cells.

Adenocarcinoma↗
PubMed1992

Magnetic resonance imaging of hearts with atrioventricular valve atresia or double inlet ventricle.

OBJECTIVE: To investigate the effectiveness and limitations of magnetic resonance imaging in defining cardiac anatomy in patients with double inlet ventricle or atrioventricular valve atresia. DESIGN: Magnetic resonance images were reviewed retrospectively without reference to other morphological data. SETTING: A tertiary referral centre for paediatric cardiology. PATIENTS: 18 patients (aged 8 days to 27 years) with a suspected univentricular atrioventricular connection. METHODS: Imaging by a 1.5 T whole body magnetic resonance system with imaging planes adjusted to individual patient anatomy to best define the cardiac morphology. A complete sequential diagnosis obtained from an independent interpretation of the images was compared with the diagnosis obtained from cross sectional echocardiography and angiocardiography. RESULTS: There was substantial accord between the diagnosis from magnetic resonance alone and that from other methods. In the six instances where there was not accord the magnetic resonance diagnosis was considered to be correct in two cases and incorrect in three cases. In the remaining case no consensus could be reached. In eight patients magnetic resonance imaging provided anatomical information additional to that from other methods. The strengths of magnetic resonance were in imaging the pulmonary arteries and their abnormalities and identifying juxtaposed atrial appendanges but there were some deficiencies in identifying Blalock-Taussig shunts. CONCLUSION: Magnetic resonance imaging provided detailed information about all aspects of cardiac morphology in patients with a suspected diagnosis of univentricular atrioventricular connection. Often it provided additional information to echocardiography. Its use in selected patients should give valuable complementary information.

Adolescent↗
PubMed1992

Evidence for selective accumulation of intrathyroidal T lymphocytes in human autoimmune thyroid disease based on T cell receptor V gene usage.

We have investigated the T cell receptor V alpha and V beta gene family usage by T lymphocytes infiltrating affected thyroids in patients with autoimmune thyroid disease. We show that the intrathyroidal T lymphocytes from patients (n = 6) with autoimmune thyroid disease display a widespread usage of V beta gene families with an average of 14.4/19 V beta gene families similar to the peripheral T lymphocytes of the same patients. Because we recently reported that the utilization of V alpha gene families is markedly reduced within these mitogen-stimulated intrathyroidal T cell populations, as well as within intact tissue from similar patients (n = 4) (overall mean of 4.0/18 families detected), these results indicate that in thyroids of patients with autoimmune thyroid disease the lymphocytes are selectively accumulating based on their V alpha rather than V beta elements. This preferential hTcR V alpha and widespread V beta gene usage was not mimicked in most 7-d autologous mixed lymphocyte reactions using non-T cell stimulators (n = 6) or EB-virus immortalized autologous B cell lines (n = 3). Hence, the selective V gene utilization by intrathyroidal T cells is likely to be secondary to multiepitopic thyroidal autoantigens activating thyroid infiltrating T cells or to the presence of a superantigenlike thyroidal self-antigen, capable of determining a selective infiltration or activation of a variety of T lymphocytes on the basis of their V alpha gene usage.

Autoantibodies↗
PubMed1991

Evidence of limited variability of antigen receptors on intrathyroidal T cells in autoimmune thyroid disease.

BACKGROUND: Patients with autoimmune thyroid diseases, including Graves' disease and Hashimoto's disease, have marked lymphocytic infiltration in their thyroid glands. We examined the gene for the variable regions of the alpha-chain of the human T-cell receptor (the V alpha gene) in intrathyroidal T cells to determine whether the infiltration is a secondary heterogeneous immune response or a more restricted, and therefore primary and presumably pathogenetic, reaction to thyroid autoantigens. METHODS: We used the polymerase chain reaction to detect small numbers of T cells expressing the variable region of the V alpha gene. Different oligonucleotides were used to amplify complementary DNA for the 18 known families of the V alpha gene in intrathyroidal T cells from 9 patients with autoimmune thyroid disease. We compared the findings with the results in patients with nonautoimmune thyroid disease as well as those in normal subjects. RESULTS: We found marked restriction in the expression of T-cell-receptor V alpha genes by T cells from the thyroid tissue of patients with autoimmune thyroid disease. An average of only 5 of the 18 V alpha genes were expressed in such samples, as compared with 17 V alpha genes expressed in peripheral-blood T cells from the same patients. No such restriction was found in thyroid tissue from patients with nonautoimmune thyroid disease. The predominantly expressed V alpha genes differed from patient to patient, however, with no clear association with the type of disease. CONCLUSIONS: Intrathyroidal T-cell accumulation in autoimmune thyroid disease is highly restricted and points to the primacy of T cells in causing thyroid disorders. These results present the possibility of using antibodies to the T-cell receptor for the specific inhibition of abnormal T-cell function in autoimmune thyroid disease.

Antigens, CD↗
PubMed1991

The little riddle maker. A case presentation.

This report describes the intensive psychoanalytic psychotherapy of a 7-year-old girl diagnosed as suffering from childhood schizophrenia. The treatment, lasting for 3 years, took place in an inpatient setting and followed a conflict-resolution model. The treatment process revealed an unusually orderly unfolding of a psychosexual zonal configuration: oral, anal, and phallic-oedipal. The child's style of communicating with her therapist by way of riddles is illustrated and examined in relation to her self-other experience in each emerging psychosexual phase.

Child↗
PubMed1991

Rapid detection of type A influenza viruses with monoclonal antibodies to the M protein (M1) by enzyme-linked immunosorbent assay and time-resolved fluoroimmunoassay.

Monoclonal antibodies (MAbs) to the M protein (M1) were used in the development of direct detection systems for type A influenza viruses in clinical specimens. Optimal detection by an enzyme-linked immunosorbent assay was achieved when MAbs were used as capture antibodies and rabbit polyclonal antibodies were used as sandwich antibodies. Detection by the enzyme-linked immunosorbent assay required amplification of the virus. direct detection in clinical specimens (nasopharyngeal aspirates) was accomplished when MAbs recognizing two distinct antigenic sites of M1 were used in a time-resolved fluoroimmunoassay. Type A influenza viruses could be detected equally well in specimens obtained during epidemics of both H3N2 and H1N1 influenza viruses.

Antibodies, Monoclonal↗
PubMed1991

Registration of MR and CT images for skull base surgery using point-like anatomical features.

We have developed a registration technique for combining magnetic resonance imaging (MRI) and computed tomography (CT) images of the skull base for use in surgical planning. The technique is based on user identification of point-like landmarks visible in both modalities. The combination of images involves a small amount of expert interaction, is relatively quick and preliminary evaluation indicates that it is accurate to within 1.5 mm. Registered or fused images can be viewed either on an image processing workstation, or fused images can be printed onto conventional film for convenience in clinical use. We present one patient in order to demonstrate the technique's indications and advantages.

Humans↗
PubMed1991

Conserved and variant epitopes of target antigens of transmission-blocking antibodies among isolates of Plasmodium falciparum from Malaysia.

Monoclonal antibodies (MAbs) directed against different epitope regions on three sexual stage-specific gamete surface proteins of Plasmodium falciparum, Pfs 25, Pfs 230, and Pfs 48/45, were used to study the genetic diversity of these epitopes among fresh isolates of P. falciparum from Malaysia, using immunofluorescence microscopy (IFA). Among 45 Malaysian isolates, one epitope of Pfs 25, designated region I, showed evidence of variable reactivity with MAbs among different isolates; the Pfs 25 epitope, region II, was universally recognized by MAbs in all isolates. Two apparently distinct epitope regions of Pfs 230 were defined by MAbs, one of which was universally recognized by MAbs among the 45 isolates; the other was conserved in all but three isolates. The epitope regions of gamete-surface protein Pfs 48/45, designated regions I, IIa, IIb, IIc, III, and IV, were examined for reactivity by IFA in 33 isolates. Epitope regions I, IIb, III, and IV were conserved in all isolates; regions IIa and IIc existed in variant forms.

Adolescent↗
PubMed1990

Refractoriness of erythrocytes infected with Plasmodium falciparum gametocytes to lysis by sorbitol.

Unlike erythrocytes infected with mature asexual parasites of Plasmodium falciparum, those infected with gametocytes are not lysed by 5% sorbitol solutions. This observation was used to devise a method for producing synchronized cultures of gametocytes, free of asexual stage parasites. The refractoriness to sorbitol suggests that the major anion transport pathway, which appears in the membrane of erythrocytes infected with asexual stage parasites, is not present in cells infected with gametocytes.

Animals↗