Biomedical subjects

B Anderson

Publications and source records attributed to B Anderson.

At least 127 records · Page 7Linked to original sources

PubMed1996

Acceleration of spontaneous diabetes in TCR-beta-transgenic nonobese diabetic mice by beta-cell cytotoxic CD8+ T cells expressing identical endogenous TCR-alpha chains.

The role of target cell autoantigens and their repertoire vs those of foreign Ags, superantigens, or non-Ag-specific stimuli in the activation and recruitment of effector T cells in most spontaneous models of autoimmune diseases remains elusive. Here we report on the use of single TCR-beta transgenic mice to study the mechanisms that drive the accumulation of pathogenic T cells in the pancreatic islets of nonobese diabetic (NOD) mice, a model for insulin-dependent diabetes mellitus. Expression of the V(beta)8.1+ TCR-beta rearrangement of a diabetogenic H-2Kd-restricted beta cell cytotoxic CD8+ T cell (beta-CTL) clone in NOD mice caused a 10-fold increase in the peripheral precursor frequency of beta-CTL and a selective acceleration of the recruitment of CD8+ T cells to the pancreatic islets of prediabetic animals. This resulted in an earlier onset and a faster progression of beta cell depletion, and led to a dramatic acceleration of the onset of diabetes. Most islet-derived beta-CTL from diabetic transgenic NOD mice expressed an endogenously-derived TCR-alpha sequence identical to that of the clonotype donating the TCR-beta transgene, and a TCR-alpha-CDR3 sequence homologous to those expressed by most islet-derived beta-CTL from nontransgenic NOD mice. TCR-beta transgene expression did not change the peripheral frequency of beta cell-specific CD4+ T cells, the rate at which these cells accumulated in the pancreatic islets, or the incidence of diabetes. Taken together, our data indicate that retention of CD8+ and CD4+ T cells in the pancreatic islets of NOD mice is driven by beta cell autoantigens, rather than by local superantigens or non-Ag-specific stimuli, and that beta-CTL are major effectors of beta cell damage in spontaneous insulin-dependent diabetes mellitus.

Amino Acid Sequence↗

PubMed1996

Cloning, expression and sequence analysis of the Bartonella henselae gene encoding the HtrA stress-response protein.

A cloned fragment of Bartonella (Rochalimaea) henselae (Bh) DNA was found to direct synthesis of an immunoreactive protein in Escherichia coli (Ec). Sequence analysis revealed an open reading frame of 1509 nucleotides encoding a protein of 503 amino acids that exhibited extensive identity (over the entire protein) with the HtrA stress-response proteins of Brucella abortus (59%), Ec (37%) and Salmonella typhimurium (36%). When the putative htrA gene was amplified by polymerase chain reaction and used as template for in vitro transcription and translation, a protein with an apparent molecular mass of 62 kDa was synthesized from the plasmid template. These results suggest that the immunoreactive Bh protein is homologous to the HtrA class of stress-response proteins.

Bartonella henselae↗

PubMed1996

Paracetamol prescribing habits in a children's hospital.

AIM: Paracetamol is an analgesic/antipyretic widely used in children. The drug can cause hepatic and renal damage due to cumulative toxicity when used in excess of 90 mg/kg@day. There are no dosing guidelines for paracetamol use in children under 1 month of age. We wished to discern current paracetamol prescribing habits in order to establish safety of current practices and offer recommendations towards rational use. METHODS: An anonymous questionnaire was sent to all medical staff working in a university childrenís hospital. We sought information about paracetamol prescribing regimes for children 4 months and over, 3 months and under and neonates in the first 2 weeks of life. Pharmacists audited daily prescription charts of inpatients without hepatic or renal disease over a 2 month period. The maximum possible daily dose was calculated for each child and note was made if a dose in excess of 95 mg/kg was given. RESULTS: There were 53 respondents to the 80 questionnaires posted. There was a trend to use lower daily doses in the younger age group. Similarly, more practitioners either did not use or did not know safe dosing schedules in children 3 months and younger. During the 2 month period there were 823 prescriptions for children 4 months and over, 85 for infants 3 months and under and seven for under 2 week old neonates. In the children 4 months and over 25 of 140 prescriptions exceeding 95 mg/kg/day were given and two of six were given in infants 3 months and younger. CONCLUSION: Many medical staff were unsure of current safe dosing regimens, particularly in the younger age groups. Seventeen percent of prescriptions were above 95 mg/kg/day although only 3% of children were given these doses due to on demand charting and due to audit by pharmacy and nursing staff. There are few guidelines for children 3 months and under. The literature suggests 60-65 mg/kg/day in infants 1-3 months, although this dose was only charted in 16% of prescriptions and phamacokinetic data favours a higher dose. In neonates 30 mg/kg/day achieves effective therapeutic concentrations but further studies are needed.

Acetaminophen↗

PubMed1996

Usefulness of tumor volumetry by magnetic resonance imaging in assessing response to radiation therapy in carcinoma of the uterine cervix.

PURPOSE: Clinical evaluation of tumor size in cervical cancer is often difficult, and clinical signs of radiation therapy failure may not be present until well after completion of treatment. The purpose of this study is to investigate early indicators of treatment response using magnetic resonance (MR) imaging for quantitative assessment of tumor volume and tumor regression rate before, during, and after radiation therapy. METHODS AND MATERIALS: Thirty-four patients with cervical cancer Stages IB [5], IIB [8], IIIA [1], IIIB [14], IVA [3], IVB [1], and recurrent [2] were studied prospectively with four serial MR examinations obtained at the start of radiation therapy, at 2-2.5 weeks (20-24 Gy), at 4-5 weeks (40-50 Gy), and 1-2 months after treatment completion. Tumor volume was assessed by three-dimensional volumetric measurements using T2-weighted images of each MR examination. The volume regression rate was generated based on the four sequential MR studies. These findings were correlated with local control, metastasis rate, and disease-free survival. Median follow-up was 18 months (range: 9-43 months). RESULTS: The tumor regression rate after a dose of 40-50 Gy correlated significantly with treatment outcome. The actuarial 2-year disease-free survival was 88.4% in patients with tumors regressing to < 20% of the initial volume compared with 45.4% in those with > or = 20% residual (p = 0.007). The incidence of local recurrence was 9.5% (2 out of 21) and 76.9% (10 out of 13), respectively (p < 0.001). Analysis by initial tumor volume showed that this observation was valid in patients with initial volumes between 40 and 100 cm3. Analysis by FIGO stage confirmed this observation in all patients except those with Stage IB. CONCLUSION: Sequential tumor volumetry using MR imaging appears to be a sensitive measure of the responsiveness of cervical cancer to irradiation. Treatment response can be assessed as early as during the course of radiation therapy by measurement of initial tumor volume and regression rate at 40-50 Gy. In patients with large (> 40 cm3) and advanced (Stage > or = IIIA) tumors, this technique may be helpful in supplementing the clinical examination for response assessment. The identification of patients at high risk for treatment failure may ultimately lead to improved clinical outcome.

Adult↗

PubMed1996

Alterations in cortical thickness and neuronal density in the frontal cortex of Albert Einstein.

Neuronal density, neuron size, and the number of neurons under 1 mm2 of cerebral cortical surface area were measured in the right pre-frontal cortex of Albert Einstein and five elderly control subjects. Measurement of neuronal density used the optical dissector technique on celloidin-embedded cresyl violet-stained sections. The neurons counted provided a systematic random sample for the measurement of cell body cross-sectional area. Einstein's cortex did not differ from the control subjects in the number of neurons under 1 mm2 of cerebral cortex or in mean neuronal size. Because Einstein's cortex was thinner than the controls he had a greater neuronal density.

Aged↗

PubMed1996

Management of severe bronchiolitis: indications for ventilator support.

AIM: Bronchiolitis is a common respiratory illness in children. We reviewed our experience of children under one year presenting to an intensive care unit with a clinical diagnosis of bronchiolitis in order to determine if ethnicity, prematurity, arterial carbon dioxide tension or nasopharyngeal aspirates positive for respiratory syncytial virus were related to the need for ventilator assistance. METHOD: A review of the charts of all infants with bronchiolitis admitted to the paediatric intensive care unit from December 1991 to February 1994 was undertaken. RESULTS: There were 94 infants. Ventilator assistance was given to 24 children--nine children had nasopharyngeal continuous positive airway pressure and 15 children required intermittent positive pressure ventilation. There was no difference in ethnic mix between the respiratory support group (Maori 45%, Pacific Islands 30%, other 25%) and those children managed conservatively (Maori 40%, Pacific Islands 36%, other 24%). Fifteen of the 24 infants who needed ventilator support were born prematurely. The mean (corrected) age of infants who required respiratory support was 1.79 (SD2.98) months compared to 3.32 (SD2.58) months for those infants who did not (p < 0.01). We were able to match 19 of the 24 infants who required ventilator support by age, sex and ethnicity with a nonventilated child. There was no significant difference in admission PaCO2 between groups (7.7 SD 1.5 vs 8.1 SD 1.5 kPa) or highest PaCO2 in the first 24 hours for nonventilated children and preintubation PaCO2 in ventilated children (8.6 SD1.3 vs 8.9 SD 1.9kPa). Nasopharyngeal aspirates were positive for respiratory syncytial virus in 39 patients. Respiratory support was required for 13 children who had positive RSV aspirates and for nine children who were not RSV positive (NS). CONCLUSION: Infants with bronchiolitis that were premature were not likely to need respiratory support. Ethnicity, arterial PaCO2 and positivity for RSV were not related to the need for ventilator assistance.

Age Factors↗

PubMed1996

p53 allelotypes and enhanced detection of allelic loss in ovarian cancer: lack of correlation with familial and clinical factors.

To develop a mapping strategy for improved detection of p53 allelic loss associated with ovarian carcinoma, we utilized multiple intragenic polymorphisms and single-strand conformation polymorphism (SSCP) analysis. p53 allelotype distributions were defined for 80 ovarian cancer patients from germ-line DNA. All polymorphic sites studied had polymorphism information content (PIC) rates of greater than 0.25. Tumor loss of heterozygosity (LOH) was determined from informative polymorphisms and migratory shifts on SSCP screening of exons 5-9. Of the four polymorphisms analyzed, the intron 1 (alu) was the most informative (PIC = 0.66). A novel allele of 110 base pairs was found in 4.4% of our ovarian cancer cohort at this site. The intron 3 (16-base pair repeat) and intron 6 (MSP1) polymorphisms were in relative equilibrium; thus, we chose to use only the intron 3 polymorphic site in the mapping strategy. Family cancer history did not influence the allelotype distribution frequencies. Overall, 56 of 61 tumors (91.8%) were informative for allelic loss, and LOH was observed in 66.1 %. A reduction to homozygosity at the p53 locus did not correlate with familial or clinical factors. These observations are consistent with the multiple mechanisms by which p53 dysfunction can occur.

Adult↗

PubMed1996

Surgical management of cervical cancer complicating pregnancy: a case-control study.

A retrospective, case-control analysis of 30 women with cervical cancer associated with pregnancy, surgically managed at the University of Iowa between 1960 and 1994, was performed. Controls were matched with cases based on age, histology, stage, treatment, and year of treatment. Patients were divided into two groups: Group I, radical hysterectomy (26 patients) and group II, simple hysterectomy (4 patients). Eleven patients underwent surgical treatment in the third trimester with a mean planned delay in therapy of 16 weeks. None of the patients with a planned delay in therapy developed recurrent disease. No neonatal morbidity was encountered in these patients. Among group I patients, there was longer anesthesia time (P < 0.03), but there were no differences in the mean operative time. There was more blood loss at the time of surgery among pregnant patients (1493 cc vs 1065 cc for group I, P = 0.005; 812 cc vs 362 cc for group II, P = 0.03); however, there was no difference in the frequency of blood transfusion. The percentage of patients receiving a transfusion decreased significantly after 1991 (33% versus 90%, P = 0.01 for pregnant patients and 33% versus 85%, P = 0.03 for nonpregnant patients). There were no differences in the time required for postoperative bladder drainage, mean hospital stay, febrile morbidity, incidence of wound infection, wound separation, pelvic abscess, thromboembolic disease, or urinary tract infection. One case patient and 3 control patients died of disease, but this difference was not statistically significant. Based upon our data, in selected cases of early-stage cervical cancer, surgical management of cervical cancer is safe during pregnancy. For early Stage I squamous cancers, planned delay in therapy is safe.

Adult↗

PubMed1996

In vitro selection and molecular characterization of human immunodeficiency virus type 1 with reduced sensitivity to 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA).

9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA) is an acyclic nucleotide with potent in vitro activity against human immunodeficiency virus type 1 (HIV-1). The present study was undertaken to determine whether HIV-1 resistance to PMEA could be generated by in vitro selection and if so, to determine which mutations in reverse transcriptase (RT) were responsible. HIV-1LAI was serially passaged for 10 months in the presence of increasing concentrations of PMEA up to a maximum of 40 microM. After 40 passages, the 50% inhibitory concentration (IC50) of PMEA had increased almost 7-fold from 4.45 to 30.5 microM. Some cross-resistance to 2',3'-dideoxycytidine (ddC, zalcitabine), 2',3-dideoxyinosine (ddI, didanosine), and 3'-thiacytidine (3TC, lamivudine) was also observed, but no cross-reactive resistance to 3'-azido-3'-thymidine (AZT, zidovudine). Sequencing of the RT encoding region of each of eight pol clones from resistant isolates revealed a Lys-65-->Arg (K65R) substitution. HIV with the K65R mutation inserted by site-directed mutagenesis also had decreased sensitivity to PMEA in H9 cells and a similar cross-resistance profile. Thus, HIV can develop decreased sensitivity to PMEA after long-term in vitro exposure and this change is associated with a K65R substitution. Additional studies will be needed to determine whether a similar mutation in HIV RT develops in patients receiving PMEA or its orally bioavailable prodrug adefovir dipivoxil (bis-POM PMEA).

Adenine↗

PubMed1996

Obesity and prognosis in endometrial cancer.

OBJECTIVE: We tested the null hypothesis that morbid obesity as measured by the Quetelet index has no influence on survival in endometrial cancer. STUDY DESIGN: A retrospective study of 492 women with endometrial carcinoma was performed. Age, height, weight, Quetelet index, stage, cell type, grade, node status, peritoneal cytologic findings, and depth of myometrial invasion were analyzed for influence on survival. RESULTS: Mean Quetelet index was 34 (range 16 to 89). Quetelet index was < 30 in 45% of patients, 30 to 40 in 33%, and > 40 in 22%. Five percent of those with a Quetelet index > 40 had positive nodes, but 64% of patients with a Quetelet index > 40 did not have lymph node sampling done. Lack of sampling of lymph nodes in the entire group had no adverse effect on survival. In a proportional hazards regression model for time from diagnosis to death from disease, grade, node status, myometrial invasion, and stage had highly significant effects. When Quetelet index was analyzed as a continuous variable, as Quetelet index increased, time to recurrence was significantly increased (p = 0.0136), and significance was approached for survival (p = 0.0645). Quetelet index was strongly related to grade (p = 0.013), depth of myometrial invasion (p = 0.031), negative cytologic findings (p = 0.004), and stage (p = 0.011) with obese patients having better differentiated, less invasive tumors of lower stage with negative washings. CONCLUSIONS: Morbid obesity positively affects survival in endometrial carcinoma. This effect is accounted for by the association of obesity with less aggressive disease. Morbid obesity is not associated with increased death from other causes. Lack of sampling of negative lymph nodes does not adversely affect survival.

Adult↗

PubMed1996

Comparison of virus burden in blood and sequential lymph node biopsy specimens from children infected with human immunodeficiency virus.

BACKGROUND: Lymph nodes serve as reservoirs for the replication of human immunodeficiency virus (HIV) type 1. Comparison of serial measurements of virus burden in lymph nodes and peripheral blood after a change in antiretroviral therapy may provide insights into pathogenic mechanisms and permit a more accurate assessment of a therapeutic response. STUDY DESIGN: Nevirapine was added to the drug regiment of eight children with HIV infection treated with the combination of zidovudine and didanosine who had increasing levels of serum p24 antigen. Lymph node biopsies were performed at entry and after 12 weeks of therapy. RESULTS: Neither CD4 counts nor p24 antigen level correlated with the degree of viremia as measured by ribonucleic acid copy numbers in plasma. Correlations were found between HIV DNA copy number in peripheral blood mononuclear cells and HIV DNA copy number in lymph nodes (p = 0.02), as well as between peripheral blood CD4 counts and lymph node architecture. The HIV signals in the lymph nodes conformed to the anatomic organization of apical light zones in the germinal centers; however, in more advanced disease stages, organized germinal centers disappeared as evidence by a decline in the extent of the follicular dendritic network. CONCLUSIONS: Lymph node biopsies in this small number of HIV-infected children revealed a progressive loss of an organized architecture, especially of the follicular dendritic network. This correlated with a progressive loss of CD4+ cells but not with other measures of disease stage, including viral load, as measured by ribonucleic acid copy numbers.

Antiviral Agents↗

PubMed1996

Analysis of sertraline-only overdoses.

Sertraline is an antidepressant for which preliminary data suggest a low inherent toxicity. Previously reported case series have included coingestants or had small numbers of patients. This study was undertaken to determine the toxicity of overdoses of sertraline alone. A 2-year retrospective and 6-month prospective study was conducted at a regional poison center. There were 52 patients with a mean age of 19.3 +/- 13.8 years and a mean dose of 727 +/- 686 mg. There were no symptoms in 34 cases. Symptomatic patients experienced mild central nervous system, cardiovascular, and gastrointestinal effects. Two patients developed bradycardia which resolved without therapy. While all but 3 of 38 adolescents and adults were treated in a health care facility, 10 of 14 children were managed at home. Gastrointestinal decontamination was performed in 37 cases. No other specific therapy was required. Serious toxicity would not be expected following sertraline-only overdoses.

1-Naphthylamine↗

PubMed1996

Effects of positive and negative life events on time to depression onset: an analysis of additivity and timing.

While the relationship of life events to depression onset has occupied researchers for almost a quarter of a century, few studies have attempted to account for either the temporal patterning of events relative to episode onset, or, the effect of multiple events in a study period. In this report, we attempt to address the issues of timing of events, multiple events (both positive and negative) and multiple aspects (both positivity and negativity) of single events on latency time to depression onset, while simultaneously accounting for possible decay in the effects of events over time. We use the proportional hazards approach to model the effects of life events and consider modelling the change in impact of events with the passage of time. After interviewing 142 recurrent unipolar patients using the Life Events and Difficulties Schedule, we rated severity and positivity of life events reported during the 6-month period prior to onset. As we hypothesized, additional life events occurring after an initial provoking agent level event significantly alter the risk of illness onset. Additional severely threatening events decrease the time to onset, but positive events do not appear to delay onset. Interestingly, seemingly neutral events had a highly significant effect in shortening the time to onset. We note the many limitations imposed on the interpretation of these findings related to the selected group of subjects studied and encourage those who have more generalizable data to apply these methods of analysis.

Adult↗

PubMed1996

T-cell lymphoma in Hashimoto's thyroiditis.

An elderly Caucasian woman with a 2-year-history of hypothyroidism, treated with thyroxine, presented with a rapidly growing mass in the thyroid. The morphological and immunological features of this thyroid tumour were those of a peripheral T-cell lymphoma with an immunophenotype commonly associated with HTLV-1 positive-adult T-cell leukaemia/lymphoma, although serology for HTLV1 antibody was negative. Monoclonal gene rearrangements were demonstrated with T-cell receptor beta- and gamma-specific primers. There are several interesting features in this case (i): although primary B-cell lymphomas (MALT-associated lymphomas) of thyroid are a well-recognized sequel to thyroiditis, primary T-cell lymphomas are rare, even in areas of the world where adult T-cell lymphomas predominate; (ii) the tumour showed the typical immunophenotype of an HTLV-1 positive T-cell lymphoma but the patient is English, has not visited endemic areas, and is serologically negative for HTLV-1; (iii) the residual thyroid gland showed a florid lymphocytic thyroiditis with Hürthle cell change, typical of Hashimoto's thyroiditis; (iv) unlike other reports of thyroid T-cell lymphoma, which have presented with stage III-IV disease, this tumour presented in the favourable clinical stage of IE.

Biomarkers↗

PubMed1996

A mathematical model of line bisection behaviour in neglect.

Subjects with left hemispatial neglect frequently demonstrate an array of abnormal behaviours on line bisection tasks. They misbisect long horizontal lines to the right of true midline. They bisect short lines to the left of true midline. They exaggerate the left-sided length of lines when placing the endpoints for 'invisible' lines, and they underestimate the length of the left side of long lines that are shown to them bisected accurately. No current theory of neglect explains all these features of line bisection behaviour. A mathematical model of line bisection behaviour in neglect is presented that proposes that subjects bisect lines at the point where they perceive the 'salience' of the two line segments created by their bisection mark to be equal. Salience is determined by the brain's attentional systems which map salience amplitude to spatial position following a bell shaped distribution. Right hemisphere strokes simulated by decreasing the 'height' and "breadth' of the right hemisphere salience to position function produced all of the above features of clinical neglect subjects' line bisection behaviour. Neglect may be conceived of as damage to brain systems performing mappings between stimulus characteristics (such as spatial location) and salience.

Attention↗

PubMed1996

Age and hemisphere effects on dendritic structure.

The dendritic structures of 187 small supragranular pyramidal neurons of the posterior superior temporal gyrus were studied with rapid Golgi impregnations in postmortem samples from 10 men aged 21-71 years. The number of primary basilar dendritic branches, the total number of basilar dendritic endings, the total basilar dendritic length, the total number of visible basilar dendritic spines and the cell soma sizes were all positively inter-correlated and all features were correlated to age (r = -0.77, -0.88, -0.82, -0.72, -0.86, respectively; all P < 0.05). These neuronal measures all correlated with brain weight (r = 0.79*, 0.65*, 0.51, 0.45, 0.55, respectively; *denotes P < 0.05). A first principle component derived from the inter-correlations of the neuronal features plus brain weight correlated almost perfectly with age (r = -0.93). The neuronal features differed between the right and left hemispheres (Wilks' Lambda = 0.91, P < 0.01). Post hoc tests showed that the dendritic trees of the right hemisphere were longer (P = 0.002), more branched (P = 0.008) and possessed more dendritic spines (P = 0.0009; Sheffe's tests). In conclusion, there are hemispheric differences in the dendritic structure of the small pyramidal neurons of presumptive human speech cortex and its right hemisphere analogue. Generalized neuronal atrophy is highly correlated with both brain weight and age, and is a candidate process to explain the decline in cognition with age.

Adult↗

PubMed1996

Isolation and characterization of rice R genes: evidence for distinct evolutionary paths in rice and maize.

R and B genes and their homologues encode basic helix-loop-helix (bHLH) transcriptional activators that regulate the anthocyanin biosynthetic pathway in flowering plants. In maize, R/B genes comprise a very small gene family whose organization reflects the unique evolutionary history and genome architecture of maize. To know whether the organization of the R gene family could provide information about the origins of the distantly related grass rice, we characterized members of the R gene family from rice Oryza saliva. Despite being a true diploid, O. sativa has at least two R genes. An active homologue (Ra) with extensive homology with other R genes is located at a position on chromosome 4 previously shown to be in synteny with regions of maize chromosomes 2 and 10 that contain the B and R loci, respectively. A second rice R gene (Rb) of undetermined function was identified on chromosome 1 and found to be present only in rice species with AA genomes. All non-AA species have but one R gene that is Ra-like. These data suggest that the common ancestor shared by maize and rice had a single R gene and that the small R gene families of grasses have arisen recently and independently.

Amino Acid Sequence↗

PubMed1996

Semantic neglect?

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Aphasia, Wernicke↗