Search PubMed⌕ Search

Biomedical subjects

J Anderson

Publications and source records attributed to J Anderson.

At least 73 records · Page 4Linked to original sources
PubMed2001

Prefrontal cortex, negative symptoms, and schizophrenia: an MRI study.

The present study measured prefrontal cortical gray and white matter volume in chronic, male schizophrenic subjects who were characterized by a higher proportion of mixed or negative symptoms than previous patients that we have evaluated. Seventeen chronic male schizophrenic subjects and 17 male control subjects were matched on age and handedness. Regions of interest (ROI) were measured using high-resolution magnetic resonance (MR) acquisitions consisting of contiguous 1.5-mm slices of the entire brain. No significant differences were found between schizophrenic and control subjects in mean values for prefrontal gray matter volume in either hemisphere. However, right prefrontal white matter was significantly reduced in the schizophrenic group. In addition, right prefrontal gray matter volume was significantly correlated with right hippocampal volume in the schizophrenic, but not in the control group. Furthermore, an analysis in which the current data were combined with those from a previous study showed that schizophrenic subjects with high negative symptom scores had significantly smaller bilateral white matter volumes than those with low negative symptom scores. White matter was significantly reduced in the right hemisphere in this group of schizophrenic subjects. Prefrontal volumes were also associated with negative symptom severity and with volumes of medial-temporal lobe regions - two results that were also found previously in schizophrenic subjects with mostly positive symptoms. These results underscore the importance of temporal-prefrontal pathways in the symptomatology of schizophrenia, and they suggest an association between prefrontal abnormalities and negative symptoms.

Adult↗
PubMed2001

Complement inhibitor, complement receptor 1-related gene/protein y-Ig attenuates intestinal damage after the onset of mesenteric ischemia/reperfusion injury in mice.

Complement receptor 1-related gene/protein y (Crry) is a murine membrane protein that regulates the activity of both classical and alternative complement pathways. We used a recombinant soluble form of Crry fused to the hinge, CH2, and CH3 domains of mouse IgG1 (Crry-Ig) to determine whether inhibition of complement activation prevents and/or reverses mesenteric ischemia/reperfusion-induced injury in mice. Mice were subjected to 30 min of ischemia, followed by 2 h of reperfusion. Crry-Ig was administered either 5 min before or 30 min after initiation of the reperfusion phase. Pretreatment with Crry-Ig reduced local intestinal mucosal injury and decreased generation of leukotriene B(4) (LTB(4)). When given 30 min after the beginning of the reperfusion phase, Crry-Ig resulted in a decrease in ischemia/reperfusion-induced intestinal mucosal injury comparable to that occurring when it was given 5 min before initiation of the reperfusion phase. The beneficial effect of Crry-Ig administered 30 min after the initiation of reperfusion coincided with a decrease in PGE(2) generation despite the fact that it did not prevent local infiltration of neutrophils and did not have a significant effect on LTB(4) production. These data suggest that complement inhibition protects animals from reperfusion-induced intestinal damage even if administered as late as 30 min into reperfusion and that the mechanism of protection is independent of neutrophil infiltration or LTB(4) inhibition.

Animals↗
PubMed2001

Hyper-expression of human apolipoprotein E4 in astroglia and neurons does not enhance amyloid deposition in transgenic mice.

Recent studies in mice have clearly demonstrated that eliminating Apo E alters the rate, character and distribution of A beta deposits. In the present study, we asked whether elevating the levels of Apo E can, in a dominant fashion, influence amyloid deposition. We expressed human (Hu) Apo E4 via the mouse prion protein promoter, resulting in high expression in both astrocytes and neurons; only astrocytes efficiently secreted Hu Apo E4 (at least 5-fold more than endogenous). Mice hyper-expressing Hu Apo E4 developed normally and lived normal lifespans. The co-expression of Hu Apo E4 with a mutant amyloid precursor protein (APP) (Mo/Hu APPswe) or mutant APP and mutant presenilin (PS1dE9) did not lead to proportional changes in the age of appearance, relative burden, character or distribution of A beta deposits. We suggest that these data are best explained by proposing that the mechanisms by which Apo E influences A beta deposition involves an aspect of its normal function that is not augmented by hyper-expression.

Amyloid beta-Peptides↗
PubMed2001

Detection of the PAX3-FKHR fusion gene in paediatric rhabdomyosarcoma: a reproducible predictor of outcome?

Rhabdomyosarcoma has 2 major histological subtypes, embryonal and alveolar. Alveolar histology is associated with the fusion genes PAX3-FKHR and PAX7-FKHR. Definition of alveolar has been complicated by changes in terminology and subjectivity. It is currently unclear whether adverse clinical behaviour is better predicted by the presence of these fusion genes or by alveolar histology. We have determined the presence of the PAX3/7-FKHR fusion genes in 91 primary rhabdomyosarcoma tumours using a combination of classical cytogenetics, FISH and RT-PCR, with a view to determining the clinical characteristics of tumours with and without the characteristic translocations. There were 37 patients with t(2;13)/PAX3-FKHR, 8 with t(1;13) PAX7-FKHR and 46 with neither translocation. One or other of the characteristic translocations was found in 31/38 (82%) of alveolar cases. Univariate survival analysis revealed the presence of the translocation t(2;13)/PAX3-FKHR to be an adverse prognostic factor. With the difficulties in morphological diagnosis of alveolar rhabdomyosarcoma on increasingly used small needle biopsy specimens, these data suggest that molecular analysis for PAX3-FKHR will be a clinically useful tool in treatment stratification in the future. This hypothesis requires testing in a prospective study. Variant t(1;13)/PAX7-FKHR appears biologically different, occurring in younger patients with more localised disease.

Adolescent↗
PubMed2001

Neuroblastoma in monozygotic twins--a case of probable twin-to-twin metastasis.

Concordance for neuroblastoma in monozygotic twins has been reported only rarely, and the cause of the shared pathology has not been established. We describe a case of infant monozygotic twins developing tumours that were morphologically, clinically and molecularly indistinguishable, but with a delay of 6 months between times of presentation. Both tumours were metastatic and had amplification of MYCN and deletion at 1p36. Twin 1, who developed neuroblastoma first, had constitutional karyotype abnormalities in at least 5% of peripheral blood mononuclear cells involving 1p and 3p, and a deletion of 1q44 in 21% of cells. Twin 2 had a normal constitutional karyotype and lacked rearrangement or deletion of these regions. We propose an acquired neuroblastoma predisposition specific for twin 1, and in utero metastatic spread of tumour cells to twin 2 via the shared placental circulation.

DNA, Neoplasm↗
PubMed2001

Plasma levels of soluble CD14 and tumor necrosis factor-alpha type II receptor correlate with cognitive dysfunction during human immunodeficiency virus type 1 infection.

The relationship between monocyte immune responses and cognitive impairment during progressive human immunodeficiency virus type 1 (HIV-1) infection was investigated in 28 subjects receiving highly active antiretroviral therapy. The mean+/-SEM CD4(+) T lymphocyte count and virus load for all patients were 237+/-41 cells/mm(3) and 77,091+/-195,372 HIV-1 RNA copies/mL, respectively. Levels of soluble tumor necrosis factor-alpha type II receptor (sTNF-RII) and soluble CD14 (sCD14) were measured in plasma by ELISA and were correlated with results from neuropsychological, magnetic resonance imaging, and magnetic resonance spectroscopy tests. Plasma sCD14 and sTNF-RII levels were elevated in subjects with cognitive impairment and in those with brain atrophy. Furthermore, both factors were correlated with spectroscopic choline:creatine ratios. These findings support the idea that peripheral immune responses are linked to cognitive dysfunction during advanced HIV-1 disease.

Adult↗
PubMed2001

BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implications for Alzheimer's disease therapeutics.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by accumulation of amyloid plaques and neurofibrillary tangles in the brain. The major components of plaque, beta-amyloid peptides (Abetas), are produced from amyloid precursor protein (APP) by the activity of beta- and gamma-secretases. beta-secretase activity cleaves APP to define the N-terminus of the Abeta1-x peptides and, therefore, has been a long- sought therapeutic target for treatment of AD. The gene encoding a beta-secretase for beta-site APP cleaving enzyme (BACE) was identified recently. However, it was not known whether BACE was the primary beta-secretase in mammalian brain nor whether inhibition of beta-secretase might have effects in mammals that would preclude its utility as a therapeutic target. In the work described herein, we generated two lines of BACE knockout mice and characterized them for pathology, beta-secretase activity and Abeta production. These mice appeared to develop normally and showed no consistent phenotypic differences from their wild-type littermates, including overall normal tissue morphology and brain histochemistry, normal blood and urine chemistries, normal blood-cell composition, and no overt behavioral and neuromuscular effects. Brain and primary cortical cultures from BACE knockout mice showed no detectable beta-secretase activity, and primary cortical cultures from BACE knockout mice produced much less Abeta from APP. The findings that BACE is the primary beta-secretase activity in brain and that loss of beta-secretase activity produces no profound phenotypic defects with a concomitant reduction in beta-amyloid peptide clearly indicate that BACE is an excellent therapeutic target for treatment of AD.

Alzheimer Disease↗
PubMed2001

Localization of a gene (MCUL1) for multiple cutaneous leiomyomata and uterine fibroids to chromosome 1q42.3-q43.

Dominant transmission of multiple uterine and cutaneous smooth-muscle tumors is seen in the disorder multiple leiomyomatosis (ML). We undertook a genomewide screen of 11 families segregating ML and found evidence for linkage to chromosome 1q42.3-q43 (maximum multipoint LOD score 5.40). Haplotype construction and analysis of recombinations permitted the minimal interval containing the locus, which we have designated "MCUL1," to be refined to an approximately 14-cM region flanked by markers D1S517 and D1S2842. Allelic-loss studies of tumors indicated that MCUL1 may act as a tumor suppressor. Identification of MCUL1 should have wide interest, since this gene may harbor low-penetrance variants predisposing to the common form of uterine fibroids and/or may undergo somatic mutation in sporadic leiomyomata.

Chromosome Mapping↗
PubMed2001

Congenital alveolar rhabdomyosarcoma: clinical and molecular distinction from alveolar rhabdomyosarcoma in older children.

BACKGROUND: Congenital alveolar rhabdomyosarcoma (RMS) is extremely rare and invariably fatal with current therapy. Its clinical presentation is unusual and is distinct from RMS in older children, with > 50% of patients presenting with multiple cutaneous metastases. To the authors' knowledge, the biology of this condition has not been studied to date. METHODS: The clinical and pathologic findings of four cases of congenital RMS are presented along with those of other cases found in the literature. Molecular analysis was undertaken to detect the characteristic chromosomal translocations of alveolar RMS in three cases with suitable material. RESULTS: To the authors' knowledge, there are no recorded survivors of congenital alveolar RMS. Clinical and histopathologic findings in four patients with congenital alveolar RMS are detailed along with treatment responses. It now is recognized that tumor specific translocations can be detected in the majority of cases of alveolar RMS using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. However, detailed molecular analysis using RT-PCR was unable to detect the presence of either the classic t(2;13) or variant t(1;13) translocation in three cases analyzed at the molecular level. CONCLUSIONS: To the authors' knowledge the optimal treatment for this rare tumor is not known. The longest survivor in the current series underwent myeloablative therapy with peripheral stem cell support, suggesting that more intensive treatment may be of value in this rare condition. None of the three tumors analyzed by RT-PCR harbored characteristic RMS translocations. The molecular biology of this highly malignant and aggressive congenital tumor appears to be different from alveolar RMS in older children and warrants further investigation.

Female↗
PubMed2001

Treatment of orbital rhabdomyosarcoma: survival and late effects of treatment--results of an international workshop.

PURPOSE: Orbital rhabdomyosarcoma (RMS) historically has been associated with an excellent survival rate. The majority of patients are cured with the use of both chemotherapy and radiation therapy, but a significant number experience important late sequelae of treatment. In an attempt to determine optimal therapy in relation both to cure and to sequelae, the experience of the four international collaborative groups (Intergroup Rhabdomyosarcoma Study Group [IRSG], International Society of Paediatric Oncology [SIOP] Sarcoma Committee, German Collaborative Soft Tissue Sarcoma Group [CWS], and Italian Cooperative Soft Tissue Sarcoma Group [ICG] studies) was shared at an international workshop. PATIENTS AND METHODS: A total of 306 eligible patients were identified from group records (186 from IRS, 43 from SIOP MMT, 40 from CWS, and 37 from ICG). Median age was 6.8 years, and median follow-up was 6.5 years. Eighty percent of patients received radiation therapy (RT) as part of primary therapy, but there were significant differences in the use of RT between the individual groups (93% in IRSG, 76% in ICG, and 70% in CWS, but only 37% in the SIOP MMT group). RESULTS: At 10 years, event-free and overall survival for the whole cohort were 77% (range, 71% to 81%) and 87% (range, 82% to 92%), respectively. There was no difference in overall survival between the collaborative groups regardless of differences in the use of initial RT. In total, 34 (12%) of 273 survivors had not received RT, although this varied between the different groups (41% in the SIOP MMT group, 20% in CWS, 7% in ICG, and 6% in IRSG). There was no difference in overall survival for the whole cohort regardless of whether radiotherapy was used as part of initial therapy (86% at 10 years for both). CONCLUSION: These data suggest that a subset of patients with orbital RMS can be cured without systematic local therapy, although the total burden of treatment (primary therapy and treatment for relapse) must be taken into account when assessing the implications for late sequelae.

Adolescent↗
PubMed2001

Cytogenetic abnormalities in 42 rhabdomyosarcoma: a United Kingdom Cancer Cytogenetics Group Study.

BACKGROUND: Rhabdomyosarcomas are the most common type of pediatric soft tissue sarcoma. The cytogenetic literature on RMS is biased towards the less common alveolar subtype (ARMS), which is frequently associated with specific translocations and the PAX3/7-FKHR fusion genes. Relatively few karyotypes are reported for the embryonal subtype (ERMS). The aim of this study was to further cytogenetic knowledge of RMS subtypes. PROCEDURE: Representative examples of all karyotypes from UKCCG; member laboratories were reexamined and their histopathologies reviewed through the United Kingdom Children's Cancer Study (Group) (UKCCSG). Molecular evidence for the PAX3/7-FKHR fusion genes was available for five ERMS and seven ARMS cases and compiled with the karyotypes. RESULTS: Clonal chro mosome aberrations were characterized for 25 ERMS and 17 ARMS cases. Thirty-six percent of the ERMS cases involved translocation breakpoints in the 1p11-q11 region. Ten of the seventeen cases of ARMS showed cytogenetic evidence for the t(2;13)(q35;q14), consistent with molecular data available from four of these. Two further ARMS cases revealed a PAX3-FKHR and a variant PAX7-FKHR fusion gene product that were not detected cytogenetically. CONCLUSIONS: Many of the karyotypes from both subtypes were complex. The frequent involvement of the 1p11-1q11 region and gain of chromosomes 2, 8, 12, and 13 in ERMS may be functionally significant. There was no evidence for involvement of the PAX3/7-FKHR genes in ERMS, and cryptic involvement was found in some ARMS. There were no consistent chromosomal rearrangements associated with apparently translocation negative ARMS cases.

Adolescent↗
PubMed2001

Early lumen loss after repeat coronary intervention for in-stent restenosis.

The purpose of this study was to compare the effects of balloon angioplasty versus repeat stenting on the early angiographic outcome in patients with in-stent restenosis. The treatment of in-stent restenosis using balloon angioplasty alone often yields excellent early results, but is associated with a high rate of late recurrence. In the SCRIPPS trial, patients with restenosis were treated either with balloon angioplasty alone or placement of additional stents to optimize angiographic results before randomization and exposure of the restenotic segment to gamma radiation or placebo. In patients undergoing repeat catheter based intervention for the treatment of in-stent restenosis, quantitative coronary angiography was used to compare the results of balloon angioplasty alone versus repeat stenting on early lumen loss. After a mean delay time interval of 71 min, the early loss was 0.35 +/- 0.34 mm in the balloon angioplasty alone group compared to 0.01 +/- 0.34 mm in the repeat-stenting group (P = 0.004). The early loss index in the balloon angioplasty alone group (12.8 +/- 12.9%) was significantly greater than in the repeat stenting group (0.7 +/- 12.1%; P = 0.003). Although balloon angioplasty for in-stent restenosis often provides excellent immediate angiographic results, luminal diameters are significantly reduced in the early time period after balloon dilatation. Repeat stenting nearly abolishes this early luminal loss.

Aged↗
PubMed2001

Passive stiffness is increased in soleus muscle of desmin knockout mouse.

The effects of an absence of desmin on passive stiffness of skeletal muscle were analyzed using soleus muscles from desmin knockout mice. Stiffness was evaluated by analyzing the passive tension induced by a ramp-and-hold extension test. This test showed that passive resistance to stretch was largely increased for muscles lacking desmin. This study could facilitate interpretation of changes in muscle mechanics observed in humans affected by desmin-related myopathies.

Animals↗
PubMed2001

PAX3-FKHR induces morphological change and enhances cellular proliferation and invasion in rhabdomyosarcoma.

Alveolar rhabdomyosarcoma (ARMS) is consistently associated with the characteristic translocations t(2;13)(q35;q14) and t(1;13)(p36;q14), which encode for the PAX3-FKHR and PAX7-FKHR fusion oncoproteins respectively. We have investigated the relationship between PAX3-FKHR expression and ARMS histogenesis in primary tumors and cell culture systems. In a blinded histological review of discrepant primary tumors in which there was PAX3-FKHR expression but embryonal histology, we found small areas of alveolar histology in 6 of 11 cases. This suggests that histology alone may under-represent the association between PAX3-FKHR and ARMS, and we investigated this link by examining the effect of ectopic PAX3-FKHR expression on RMS cells. Two cell lines, RD and HX170C, were stably transfected with a PAX3-FKHR expression construct. In cloned transfectants derived from both lines, PAX3-FKHR expression resulted in increased proliferative rate in vitro and promoted cell growth in the absence of added growth factors. Tumors that formed as xenografts in immunodeficient mice were faster growing, more locally invasive, and had a denser, more pleomorphic architecture than untransfected or empty vector transfected tumors. The characteristic clefts and alveolar spaces of ARMS, however, were not seen. In contrast, tumors grown as xenografts from individual clones derived from ARMS cell lines showed all of the classical morphological features of ARMS suggesting divergence in vivo from precursor cells propagated in culture.

Animals↗
PubMed2001

Human immunodeficiency virus and assisted reproduction: reconsidering evidence, reframing ethics.

OBJECTIVE: To review the advances in the treatment of human immunodeficiency virus (HIV) infection and revisit the medical, ethical, and legal issues surrounding infertility management in HIV-infected couples. DESIGN: Analytic review. RESULTS(S): HIV infection continues to be a serious public health and reproductive issue. However, present policies which allow for the categorical exclusion of HIV-infected individuals from infertility services should be reconsidered in light of improvements in the prognosis of infected individuals and a dramatic decrease in the risk of vertical transmission. An analysis of the ethical cogency of the arguments against the provision of services does not substantiate the exclusion of HIV-infected individuals; rather, the principle of justice requires that HIV-infected women be treated the same way as a woman who might have an increased risk of conceiving a child with a disability or a may have a decreased life expectancy due to a chronic illness such as diabetes. Ethical disagreement notwithstanding, with the precedents recently established by the Americans with Disabilities Act (ADA), discrimination based on HIV status would also likely be unlawful under most circumstances. CONCLUSIONS(S): With advances in the treatment of HIV infection, contextualized counseling and a respect for patients' decisions regarding infertility treatment should be adopted as public policy. It is neither ethically nor legally justifiable to categorically exclude individuals from infertility services on the basis of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Adenosarcoma in a patient with vaginal endometriosis.

BACKGROUND: Adenosarcoma in a patient with extraovarian endometriosis is a rare event and can be easily overlooked. CASE: A woman with a history of endometriosis underwent multiple resections of a vaginal mass and medical treatment for presumed recurrent endometriosis. Eventually, a vaginal adenosarcoma was diagnosed. CONCLUSION: The possibility of adenosarcoma should be considered if an enlarging mass occurs at the site of extraovarian endometriosis.

Adenosarcoma↗
PubMed2001

Clinical and pathological features of posttransplant lymphoproliferative disorders: influence on survival and response to treatment.

PURPOSE: To review the clinical and pathological characteristics of patients with posttransplant lymphoproliferative disorders (PTLD) occurring after solid organ transplantation and determine the influence of these characteristics on response to treatment and survival. PATIENTS AND METHODS: Retrospective review of 32 patients. RESULTS: Overall five-year survival was 59%. Forty-five percent of patients diagnosed within the first year after transplant had advanced disease. Characteristics that were associated with poorer survival were diagnosis within the first year posttransplant, monoclonal tumors and presentation with an infectious mononucleosis-like syndrome. Six of eight patients treated with surgery are alive and disease-free. CONCLUSION: Patients with PTLD can achieve long-term survival. Surgery can play an important role in selected patients. Characteristics that may be associated with poorer survival are diagnosis within the first year after transplant, presence of a monoclonal tumor or an infectious mononucleosis-like presentation.

Adolescent↗