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Biomedical subjects

J Berry

Publications and source records attributed to J Berry.

At least 19 recordsLinked to original sources

Environment of infants during sleep and risk of the sudden infant death syndrome: results of 1993-5 case-control study for confidential inquiry into stillbirths and deaths in infancy. Confidential Enquiry into Stillbirths and Deaths Regional Coordinators and Researchers.

OBJECTIVE: To investigate the role of sleeping arrangements as risk factors for the sudden infant death syndrome after a national risk reduction campaign. DESIGN: Two year population based case-control study. Parental interviews were conducted for each infant who died and for four controls matched for age and date of interview. SETTING: Three regions in England with a total population of 17 million people. SUBJECTS: 195 babies who died and 780 matched controls. RESULTS: Prone and side sleeping positions both carried increased risks of death compared with supine when adjusted for maternal age, parity, gestation, birth weight, exposure to smoke, and other relevant factors in the sleeping environment (multivariate odds ratio = 9.00 (95% confidence interval 2.84 to 28.47) and 1.84 (1.02 to 3.31), respectively). The higher incidence of side rather than prone sleeping led to a higher population attributable risk (side 18.4%, prone 14.2%). More of the infants who died were found with bed covers over their heads (21.58; 6.21 to 74.99). The use of a dummy had an apparent protective effect (0.38; 0.21 to 0.70). Bed sharing for the whole night was a significant risk factor for infants whose mothers smoked (9.25; 2.31 to 34.02). No protective effect of breast feeding could be identified on multivariate analysis. CONCLUSIONS: This study confirms the importance of certain risk factors for the sudden infant death syndrome and identifies others-for example, covers over the head, side sleeping position-which may be amenable to change by educating and informing parents and health care professionals.

Bedding and Linens

Smoking and the sudden infant death syndrome: results from 1993-5 case-control study for confidential inquiry into stillbirths and deaths in infancy. Confidential Enquiry into Stillbirths and Deaths Regional Coordinators and Researchers.

OBJECTIVE: To investigate the effects of exposure to tobacco smoke and of parental consumption of alcohol and illegal drugs as risk factors for the sudden infant death syndrome after a national risk reduction campaign which included advice on prenatal and postnatal avoidance of tobacco smoke. DESIGN: Two year population based case-control study. Parental interviews were conducted for each infant who died and four controls matched for age and date of interview. SETTING: Three regions in England with a total population of 17 million people. SUBJECTS: 195 babies who died and 780 matched controls. RESULTS: More index than control mothers (62.6% v 25.1%) smoked during pregnancy (multivariate odds ratio = 2.10; 95% confidence interval 1.24 to 3.54). Paternal smoking had an additional independent effect when other factors were controlled for (2.50; 1.48 to 4.22). The risk of death rose with increasing postnatal exposure to tobacco smoke, which had an additive effect among those also exposed to maternal smoking during pregnancy (2.93; 1.56 to 5.48). The population attributable risk was over 61%, which implies that the numbers of deaths from the syndrome could be reduced by almost two third if parents did not smoke. Alcohol use was higher among index than control mothers but was strongly correlated with smoking and on multivariate analysis was not found to have any additional independent effect. Illegal drug use was more common among the index parents, and paternal use of illegal drugs remained significant in the multivariate model (4.68; 1.56 to 14.05). CONCLUSIONS: This study confirms the increased risk of the sudden infant death syndrome associated with maternal smoking during pregnancy and shows evidence that household exposure to tobacco smoke has an independent additive effect. Parental drug misuse has an additional small but significant effect.

Alcohol Drinking

Localization and expression of osteopontin in mineralized and nonmineralized tissues of the periodontium.

To summarize results from various studies focusing on determining the expression/localization of BSP and OPN during tooth root development, there is general agreement that OPN is expressed/localized to the root surface during cementogenesis and is also seen throughout the PDL region. The expression/localization of OPN to odontoblasts and its role in dentinogenesis is less apparent. Recent studies directed at establishing odontoblast cell lines should help to resolve this conflict. Studies on BSP expression during tooth root formation indicate a very precise expression and localization of this molecule during cementogenesis indicating that this molecule may play an important role in the formation of this mineralized tissue. However, as with OPN, the expression of BSP and its role in dentin formation is not clearly defined.

Animals

Changes of mitochondrial mass in the hemopoietic stem cell line FDCP-mix after treatment with etoposide: a correlative study by multiparameter flow cytometry and confocal and electron microscopy.

FDCP-Mix, a pluripotent murine hemopoietic stem cell line which undergoes typical internucleosomal cleavage of DNA when induced to apoptosis by either drugs or withdrawal of growth factor (interleukin-3) was studied after treatment with the topoisomerase II inhibitor etoposide (0.5-4 microM). An increase in autolytic activity was the major early morphological change within the cytoplasm, with mitochondria as the main target for autolytic digestion. Despite this macroautophagy, thin sections showed a high number of mitochondria, suggesting mitochondrial proliferation as a result of drug treatment. This observation of an increase in the number of mitochondria was confirmed by flow cytometric studies of mitochondrial overall mass. Multiparameter flow cytometry of cells double stained with propidium iodide and nonyl-acridine orange gave an accurate assay for mitochondrial mass in relation to cell cycle stages. The increase in mitochondrial mass was found in all cell cycle stages. The results suggest a drug-induced proliferation of mitochondria separate from the processes involved in the doubling of mitochondrial mass during the cell cycle and a decline of mitochondria in the later stages of apoptosis.

Acridine Orange

A case of experiential hallucinations of unknown origins, or the mystery of the mime.

A case is described of repetitive familiar activities apparently accompanied by a hallucinated physical environment in an older brain-injured man with an amputation of the left temporal lobe. A parallel is drawn to the 'experiential hallucinations' described in psychomotor seizures and direct stimulation of the cortex.

Activities of Daily Living

Role of two mineral-associated adhesion molecules, osteopontin and bone sialoprotein, during cementogenesis.

Adhesion molecules and their cell membrane receptors are known to play important regulatory roles in cell differentiation. Consequently, the following experiments were conducted to determine the role of two adhesion molecules, bone sialoprotein (BSP) and osteopontin (OPN) in tooth root formation. Developing murine molar tooth germs at sequential stages of development (developmental days 21-42) were analyzed using immunohistochemical and in situ hybridization techniques. While BSP was localized to alveolar bone and odontoblasts early in development, BSP was distinctly localized to the cemental root surface at latter periods coincident with the initiation of root formation and cementogenesis. Conversely, OPN was distributed in a nonspecific fashion throughout the PDL and the eruption pathway of the forming tooth. In situ hybridization confirmed that cells lining the root surface express BSP. The fact that BSP is specifically localized to the cemental surface suggests that this protein is involved in cementoblast differentiation and/or early mineralization of the cementum matrix. Localization of OPN to non-mineralized tissues further suggests that OPN functions as an inhibitor of mineralization during periodontal ligament formation. These findings collectively suggest that BSP and OPN are intimately involved in the sequence of cellular and molecular events accompanying cementogenesis.

Alveolar Process

Mutations in Ig V(D)J genes are distributed asymmetrically and independently of the position of V(D)J.

To study the distribution of somatic mutations in the DNA flanking the 5' side of rearranged Ig V genes, the 5' region of 14 to 21 mutant forms of three different V(D)J were sequenced. These were compared with a fourth V(D)J for which the flanking sequences of 10 mutant forms are known. The leader intron of these four V genes varied from 82 to 365 nucleotides in length. Analysis of the data showed that: 1) The mutation frequency is distributed asymmetrically with respect to the V(D)J exon with skewing in the 3' direction. 2) The distribution of mutations 5' of V(D)J seems to be related to the size of the leader intron. The significance of these findings for models of hypermutation is discussed.

Animals

Conformational mimicry of a chlamydial neutralization epitope on filamentous phage.

Conformational constraints were imposed on a peptide epitope from Chlamydia trachomatis to improve its ability to elicit antibodies that cross-react with native antigen. Appropriate constraints were discovered by a strategy that required no prior knowledge of the epitope's native conformation. First, we constructed a library of 3.2 x 10(5) peptides in which the epitope's contact residues were subject to random conformational constraints, each constrained peptide being fused genetically to the surface of a filamentous phage vector. Next, we selected phage displaying the most native-like peptides in the library by affinity purification with antibodies that bind the epitope only in its native conformation. Finally, we immunized mice with the selected phage and titered the resulting antisera against both whole cells and unconstrained peptide. The ratio of anti-cell titer to anti-peptide titer, which reflects the channeling of the antibody response to the native epitope, was up to five times higher for affinity-selected phage than for unselected peptide phage. In this case, therefore, "antigenic fitness," the ability of a peptide to bind antibodies specific for native epitope, correlated with "immunogenic fitness," its ability to elicit antibodies that are effective against the native antigen on an invading pathogen. If the correlation is general, surveying thousands or millions of peptides for antigenic fitness with phage display technology may be a simple but effective pre-screen for immunogenic fitness, which is costly to assess directly.

Amino Acid Sequence

Local intramural drug delivery using an infusion balloon following angioplasty in normal and atherosclerotic vessels.

Local intramural delivery of various pharmacologic agents following angioplasty has been proposed as a means of reducing restenosis. This study tested whether local intramural delivery of aqueous solutions using an infusion balloon could be accomplished safely in normal vessels and whether such infusion was safe following standard angioplasty in diseased vessels. Infusion of aqueous agents into normal canine arteries had no adverse effect. Infusion of several aqueous agents (< or = 4 cc at 4 atm) into diseased swine iliac arteries following balloon angioplasty did not worsen existing or create new dissections. Histologically, infusion treated vessels did not differ in either model from vessels treated with angioplasty alone. We conclude that local intramural drug infusion does not create new, or worsen existing, dissections produced during standard balloon angioplasty in diseased vessels.

Angioplasty, Balloon, Coronary

E-SHAP: an effective treatment in selected patients with relapsed non-Hodgkin's lymphoma.

BACKGROUND: The optimal treatment of relapsed or refractory non-Hodgkin's lymphoma is unknown. The reported encouraging results of a salvage regimen, E-SHAP (etoposide 40 mg/m2/day x 4, methyl prednisolone 500 mg daily x 4, cytosine arabinoside 2 gm/m2 one dose and cisplatinum 25 mg/m2/day x 4), at the M.D. Anderson Hospital in Texas, which resulted in a 65% response rate, could not be reproduced in the United Kingdom (0% response). PATIENTS AND METHODS: Twenty-six patients with relapsed (n = 16) or refractory (n = 10) non-Hodgkin's lymphoma were treated at our Centre by a modified E-SHAP regimen (cytosine arabinoside 1 gm/m2 one dose). The treatment was intended as remission induction before BMT (n = 16), as salvage by itself (n = 5) and for palliation of symptoms (n = 5). RESULTS: The overall response rate was 72% (CR = 7 and PR = 11). A comparison of Kaplan-Meier curves showed a statistically significant improvement in median relapse-free survival in patients who had previously achieved CR (p = 0.0012), no bulky disease (P = 0.0006) and no B-symptoms (P = 0.0004). The toxicity was acceptable: 8 instances of febrile neutropenia, 2 of reversible renal impairment and 2 symptomatic electrolyte abnormalities. No fatal toxicities were encountered. The median time to treatment failure was 191 days and median overall survival was 190 days. CONCLUSIONS: E-SHAP is an active combination chemotherapy when used as a salvage regimen or for remission induction before bone marrow transplantation in selected patients with relapsed non-Hodgkin's lymphoma. Patients who previously achieved CR, with low tumour burden and no B-symptoms are the best candidates for this treatment. It has a limited palliative effect.

Adolescent

Antibody recognition of a neutralization epitope on the major outer membrane protein of Chlamydia trachomatis.

Two BALB/c mice were immunized with serovar C Chlamydia trachomatis elementary bodies, and 63 hybridomas producing monoclonal antibodies to C. trachomatis were recovered. Eight hybridomas which were specific for an identical peptide epitope (AGLQND) in serovar C major outer membrane protein variable domain I were identified. Detailed immunochemical study of the antigen-antibody interaction and genetic characterization of the antibody variable-region gene sequences showed that distinct B-cell clonal lineages were elicited by the epitope sequence. Since each antibody had a distinct pattern of fine specificity for recognition of the epitope and displayed different degrees of cross-reactivity with a related serovar (serovar A), we conclude that B-cell recognition of an immunodominant neutralization epitope can be pleiotropic. Differences in B-cell recognition of a neutralization epitope may delay the emergence by mutation of antigenic-drift variants of the C. trachomatis major outer membrane protein.

Amino Acid Sequence

Influence of membrane Ig receptor density and affinity on B cell signaling by antigen. Implications for affinity maturation.

We have initiated a series of experiments to explore the effect of changes in density of the surface Ig receptor (mIg) on Ag:mIg interactions. We transfected into the surface Ig-negative B cell line M12.4 H and L chain constructs known to effect a 10-fold change in antibody binding affinity for the naturally occurring hapten phosphocholine (PC). Two sets of stable transfectants were generated and those expressing levels of mIg comparable to the range normally seen on splenic B cells were studied. One set expressed an unmutated VH and an unmutated VL. The second set expressed the same pair of V regions except for a single somatic change in CDR3 of VH; this substitution increases the affinity of antibody for PC from 3 x 10(4) M-1 to 3 x 10(5) M-1. Ag:mIg interactions were assessed in the transfected cell lines by measuring calcium mobilization induced by stimulation with soluble PC Ag. As expected, the mutation that increased affinity for PC increased the sensitivity of transfectants to PC Ag. Relatively small changes in receptor number had a dramatic effect in the quantity and quality of a calcium response. Significantly, we found that Ag-specific signaling could occur with only a few thousand receptors per cell. Signaling differences were most noticeable with PC protein Ag (T-dependent form) compared with PC polysaccharide Ag (T-independent form). These results suggest that the down-regulation of mIg that follows B cell activation may have evolved to assist in the selection of B cell clones with higher affinity for Ag. Furthermore, the results also provide an explanation for why selection of higher affinity clones can occur with protein Ag but only poorly so with polymeric Ag.

Animals

Neuropsychological deficits in abstinent cocaine abusers: preliminary findings after two weeks of abstinence.

Sixteen subjects hospitalized for treatment of cocaine dependence were administered a battery of neuropsychological tests within 72 h of last cocaine use and again approximately 2 weeks later. Twenty-one non-cocaine using control subjects, matched for age, gender, ethnicity and education, also received neuropsychological testing. Abstinence from mood altering substances during the 2-week study period was verified for both groups on three occasions using quantitative urine analysis. The results suggest that recent cocaine use is associated with impairment in memory, visuospatial abilities, and concentration during the acute phase of withdrawal, independent of withdrawal-related depression. Furthermore, many of these deficits appear to persist at least 2 weeks beyond cessation of cocaine use.

Adult

Hamartoma of the tongue.

A female infant nine months of age presented with a bilobed swelling at the base of her tongue. Histological examination showed it to be a hamartoma of the tongue. Lingual hamartomas are rare. There are fifteen case reports of lingual hamartoma in the world literature. Our case is presented and the previous case reports are reviewed.

Female