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Biomedical subjects

R S Chapman

Publications and source records attributed to R S Chapman.

At least 37 records · Page 2Linked to original sources

Verb use by individuals with Down syndrome.

Production of grammatical and lexical verbs in narratives from 29 individuals with Down syndrome and 29 typically developing control subjects matched on linguistic level (Brown's Stages 3, 4, and 5) was examined. We addressed recent theories proposing that verbs are central to syntactic development (Tomasello & Merriman, 1995). Consistent with predictions from the child talk model (Chapman et al., 1992), the individuals with Down syndrome produced fewer lexical or grammatical verbs per utterance compared to the control group but produced a greater diversity of lexical verbs. The findings suggest that the well-documented syntactic deficits evidenced by individuals with Down syndrome may reflect difficulty in accessing verbs when constructing utterances. This difficulty may stem from deficits in auditory short-term memory.

Child↗

Second-trimester echogenic bowel and intraamniotic bleeding: association between fetal bowel echogenicity and amniotic fluid spectrophotometry at 410 nm.

OBJECTIVE: Our purpose was to determine whether the presence of heme pigments in amniotic fluid is associated with the ultrasonographic findings of increased fetal bowel echogenicity in the second trimester. STUDY DESIGN: Spectrophotometric analysis of amniotic fluid for optical density at 410 nm was prospectively performed to study the presence of heme pigments in (1) 104 pregnancies undergoing second-trimester amniocentesis for routine cytogenetic indications and (2) in 14 pregnancies undergoing amniocentesis for prenatal karyotyping because of fetal strongly echogenic bowel. In the routine amniocentesis group the fetal small bowel echogenicity was assessed immediately before amniocentesis and classified as nonechogenic (n = 64), mildly echogenic (n = 36), or hyperechogenic (n = 4) with the fetal iliac wing and liver used as references. Only amniotic fluid specimens that were obtained at the first attempt and that were not blood-stained were included in this study, with the first milliliter being discarded in all samples. RESULTS: In the routine amniocentesis group abnormal amniotic fluid optical density readings were significantly more frequent in fetuses with increased bowel echogenicity compared with those with nonechogenic bowel (8/40 [20%] vs 3/64 [5%], respectively; p < 0.001). In the hyperchogenic bowel group abnormal amniotic fluid optical density readings were found in four samples (29%). Overall, 12 of 54 fetuses (22%) with increased bowel echogenicity had a detectable peak at 410 nm. Three of the 12 (25%) fetuses with echogenic bowel and positive readings for hemoglobin were chromosomally abnormal. CONCLUSIONS: Fetal small bowel echogenicity is associated with the presence of heme pigments in amniotic fluid as determined by amniotic fluid optical density at 410 nm. Swallowing of amniotic fluid after intraamniotic bleeding seems implicated in the etiology of second-trimester echogenic bowel in both euploid and aneuploid fetuses.

Amniocentesis↗

Further characterisation of the in situ terminal deoxynucleotidyl transferase (TdT) assay for the flow cytometric analysis of apoptosis in drug resistant and drug sensitive leukaemic cells.

Apoptosis, originally defined by specific morphological changes, is characterised biochemically by non-random cleavage of DNA. Depending on cell type, this DNA cleavage proceeds from 300 and 50kbp fragments prior to, concomitantly with, or in the absence of 180bp integer fragmentation. Incorporation into fragmented DNA of biotin-labelled nucleotides by terminal deoxynucleotidyl transferase (TdT) has recently become a standard flow cytometric assay for the identification and quantitation of apoptosis. Nucleotide incorporation is visualized using avidin-tagged fluorescein isothiocyanate (FITC) (Gorczyca et al.: Cancer Res 53:1945-1951, 1993; Jonker et al.: Cytometry (Suppl 13):Abstr 99A, 1993). Here, we characterise this assay further in three different haemopoietic cell lines. Drug-induced DNA damage is not identified by the TdT assay unless it is coupled to the apoptotic response. This was demonstrated using cells in which activation of the oncogenic Abelson-encoded protein tyrosine kinase suppressed drug-induced apoptosis, but did not inhibit drug-induced DNA damage (by melphalan, hydroxyurea, or etoposide). Furthermore, the TdT assay identifies DNA fragments formed during apoptosis induced by etoposide and N-methylformamide in HL60 and MOLT-4 cells, including those high molecular weight DNA fragments formed in MOLT-4 cells which were not further cleaved to 180-200bp integer fragments. Our results support the use of flow cytometry and the TdT assay to reliably measure apoptotic cells in heterogeneous cell samples.

Abelson murine leukemia virus↗

Maternal serum human chorionic gonadotrophin during early pregnancy resulting in boys with hypospadias or cryptorchidism.

OBJECTIVE: To compare maternal serum human chorionic gonadotrophin (hCG) samples before 18 weeks gestation in mothers of boys with cryptorchidism or hypospadias with that in mothers of normal boys. The effect of season on maternal hCG was also assessed. SUBJECTS AND METHODS: Stored serum samples from mothers of singleton male fetuses born between January 1988 and December 1992 were assayed for total hCG, using a Delfia assay. There were 153 eligible samples from 96 mothers of normal boys, 31 of those with cryptorchidism, and 26 of those with hypospadias. RESULTS: The data from mothers of normal boys were used to construct a time-specific reference range for hCG. Plotting the hCG levels of the other groups and superimposing the reference range showed no significant difference between them (P = 0.09). Maternal hCG was not significantly different between cryptorchid boys requiring orchidopexy and those experiencing early spontaneous descent. An analysis of covariance allowing for gestational age showed that maternal hCG is significantly higher during the peak summer than peak winter months (P = 0.046). CONCLUSION: While a seasonal effect on maternal hCG was demonstrated our data does not suggest this to be the sole cause for cryptorchidism or hypospadias or to account for the observation that both have a seasonal frequency.

Chorionic Gonadotropin↗

Characterization of drug resistance mediated via the suppression of apoptosis by Abelson protein tyrosine kinase.

Constitutive activation of the Abelson (Abl) protein tyrosine kinase (PTK) is a causative event in chronic myeloid leukemia, where intense chemotherapy currently fails to eradicate the leukemic clone. Using a mouse mast cell line (IC.DP), we previously showed that v-Abl PTK induced resistance to the anti-cancer drugs melphalan and hydroxyurea by the suppression of apoptosis. Here, using this cell line, we demonstrate by alkaline elution that v-Abl PTK did not affect the levels of DNA damage induced by either drug. This confirms that v-Abl PTK acts downstream of the drug-target interaction to prevent the coupling of drug-induced damage to the apoptotic pathway. Although Abl PTK- and interleukin-3 (IL-3)-stimulated signaling events share common signaling pathways, a similar level of drug resistance was not provided by IL-3, implying that Abl PTK does not merely mimic an IL-3 survival signaling pathway. Previously we demonstrated translocation of protein kinase C-beta II stimulated by activation of Abl PTK. Drug sensitivity was restored in cells with active v-Abl PTK by simultaneous addition of calphostin C, an inhibitor of protein kinase C, suggesting a role for protein kinase C in the suppression of drug-induced apoptosis by v-Abl PTK. One novel strategy for the treatment of chronic myeloid leukemia could therefore include the use of a downstream modifier of the Abl PTK-mediated survival signaling pathway to render leukemic cells more sensitive to a second drug, such as a cytotoxic agent.

Abelson murine leukemia virus↗

The suppression of drug-induced apoptosis by activation of v-ABL protein tyrosine kinase.

Cells with a temperature-sensitive mutant of the v-abl oncoprotein (IC.DP) were treated with the anticancer drugs melphalan or hydroxyurea. At the restrictive temperature for v-ABL protein tyrosine kinase activity, drug-treated IC.DP cells died by apoptosis. In contrast, apoptotic cell death induced by either drug was suppressed when v-ABL was active. However, melphalan-induced accumulation of cells in the S and G2-M phases of the cell cycle was unaffected by v-ABL activation. Moreover, the continuous presence of v-ABL activity was necessary to suppress apoptosis. This suggested that melphalan had interacted with DNA and that v-ABL activity prevented the coupling of drug-induced damage to the apoptotic pathway. IC.DP cells exhibited similar levels and subcellular localization of the BCL-2 protein irrespective of v-ABL activation status, thus v-ABL-mediated cell survival appeared to be independent of BCL-2.

Animals↗

Evaluation of a home-based intervention program to reduce infant passive smoking and lower respiratory illness.

We conducted a randomized controlled trial to determine whether a home-based intervention program could reduce infant passive smoking and lower respiratory illness. The intervention consisted of four nurse home visits during the first 6 months of life, designed to assist families to reduce the infant's exposure to tobacco smoke. Among the 121 infants of smoking mothers who completed the study, there was a significant difference in trend over the year between the intervention and the control groups in the amount of exposure to tobacco smoke; infants in the intervention group were exposed to 5.9 fewer cigarettes per day at 12 months. There was no group difference in infant urine cotinine excretion. The prevalence of persistent lower respiratory symptoms was lower among intervention-group infants of smoking mothers whose head of household had no education beyond high school: intervention group, 14.6%; and controls, 34.0%.

Adult↗

Sequential recall in individuals with Down syndrome.

This study investigated whether memory for item order is selectively impaired in a group of individuals with Down syndrome. The ability to recall correctly ordered information was examined using two auditory tasks--narrative recall (Time 1) and digit span (Time 2)--and a nonverbal, visual task (Time 2) on which mental age (MA) matching was partially determined. Although subjects with Down syndrome recalled significantly less information than MA-matched controls on both auditory tasks, replicating previous findings of auditory memory span deficits, no differences in the ordering of recalled information were found. Nor did the groups differ in the relative frequency of ordering errors in the visual task. Neither a pervasive deficit in sequential processing nor a specific difficulty in recalling the order of information is supported. Alternative accounts are discussed.

Adolescent↗

Papuloerythroderma and cutaneous T cell lymphoma.

An 83-year-old man had the typical cutaneous features of papuloerythroderma of Ofuji. There were reduced numbers of lymphocytes and platelets in his peripheral blood but the eosinophil count was normal. Skin biopsy showed a nondiagnostic infiltrate of T lymphocytes in the dermis. Treatment with topical steroids and UVB phototherapy was ineffective. Twelve months after presentation, a further skin biopsy revealed atypical lymphoid cells invading the epidermis and the skin adnexae. A diagnosis of malignant lymphoma was made; no evidence of extracutaneous spread was found. Photochemotherapy produced rapid resolution of the skin eruption and clearance of the cutaneous infiltrate. Papuloerythroderma may be a manifestation of a cutaneous lymphoma.

Aged↗

Skin pigmentation due to minocycline treatment of facial dermatoses.

Fifty-four patients taking minocycline for acne or rosacea were assessed for adverse effects. Their mean duration of treatment was 17 months, and their average cumulative dose was 47 g. No symptoms attributable to the therapy were reported. Biochemistry and haematology profiles were normal. There was no evidence of an adverse effect on thyroid function. Skin pigmentation was detected in eight patients (14.8%). Five patients had diffuse facial pigmentation, and three patients had localized pigmentation at the site of a scar or injury. Diffuse pigmentation occurred only in patients who had been on treatment for 3 years or more; 50% of such patients were affected. Age and solar damage may also have been factors in this type of pigmentation. Localized pigmentation occurred at sites of previous tissue damage, and was not directly related to the duration of therapy. Patients who receive long-term minocycline therapy should be regularly monitored for the development of pigmentation.

Acne Vulgaris↗

Lower respiratory illness in infants and low socioeconomic status.

OBJECTIVES: Infants from families of low socioeconomic status are said to suffer higher rates of lower respiratory illness, but this assertion has not been carefully examined. METHODS: We studied the frequency and determinants of lower respiratory illness in infants of different socioeconomic status (n = 393) by analyzing data from a community-based cohort study of respiratory illness during the first year of life in central North Carolina. RESULTS: The incidence of lower respiratory illness was 1.41 in the low socioeconomic group, 1.26 in the middle group, and 0.67 in the high group. The prevalence of persistent respiratory symptoms was 39% in infants in the low socioeconomic group, 24% in infants in the middle group, and 14% in infants in the high group. The odds of persistent respiratory symptoms in infants of low and middle socioeconomic status were reduced after controlling for environmental risk factors for lower respiratory illness. Enrollment in day care was associated with an increased risk of persistent symptoms among infants of high but not low socioeconomic status. CONCLUSIONS: Infants of low socioeconomic status are at increased risk of persistent respiratory symptoms. This risk can be partly attributed to environmental exposures, most of which could be changed.

Acute Disease↗

Production and characterisation of monoclonal antibodies to parathyroid hormone (1-34).

Monoclonal antibodies to the biologically active N terminal region of parathyroid hormone (PTH) suitable for use in the measurement of circulating PTH concentrations have proved difficult to produce. In this study, no serum PTH antibody titres could be detected in mice using synthetic human PTH (1-34) (free or coupled to albumin) or PTH (1-10) (coupled to keyhole limpet haemocyanin) as immunogen. A consistent response to PTH (1-34) peptide was obtained in DA rats. We have produced five monoclonal antibodies to PTH (1-34) derived from the fusion of DA rat spleen cells and the mouse myeloma line X63 Ag.8.653. Bulk production of the antibodies was achieved using congenitally athymic mice for ascites production. Antibody assessment studies revealed the antibodies to be sensitive to the oxidation state of the methionine residues in PTH (1-34). Two of the antibodies, 3B3 and 6E3, were shown to be of potential use in measuring circulating PTH (1-84) when used in combination with available antibodies to C terminal PTH. A third antibody, 4G3, which failed to recognise PTH (1-84) when used in combination with 3B3, formed the basis of a specific assay for PTH (1-34).

Animals↗

Papuloerythroderma. Another case of a new disease.

We describe a case of papuloerythroderma. This is a distinctive clinical entity characterized by pruritus, red-brown flat-topped papules exhibiting the "deck-chair" sign, eosinophilia, and lymphopenia. We propose that the Langerhans cell may have a central role in the pathogenesis of papuloerthroderma and we describe an excellent response to photochemotherapy.

Aged↗

Language skills of children and adolescents with Down syndrome: I. Comprehension.

This study investigates the development of vocabulary and syntax comprehension skills cross-sectionally in 48 children and adolescents with Down syndrome (Trisomy 21), aged 5-20 years, in comparison to 48 control children aged 2-6 years matched statistically for nonverbal mental age and mother's years of education. Age-equivalent scores on vocabulary (PPVT-R) and syntax (TACL-R) comprehension tests differed in the Down syndrome group but not the control group; vocabulary comprehension was relatively more advanced than syntax. Age-equivalent scores on nonverbal cognitive subtests of pattern analysis and short-term memory for bead arrangements (Stanford-Binet, 4th ed.) also differed for the Down syndrome group but not the control group, indicating an unusual pattern of nonverbal cognitive function in the Down syndrome group. Stepwise multiple regression analyses showed that chronological age and mean mental age, collectively, accounted for 78% of the variability in vocabulary comprehension and 80% of the variability in syntax comprehension in the Down syndrome group, with total passes on a hearing screening accounting for an additional 4% in each case. Implications for research are discussed.

Adolescent↗