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Biomedical subjects

A Ariza

Publications and source records attributed to A Ariza.

At least 19 recordsLinked to original sources

Rarity of JC virus DNA sequences and early proteins in human gliomas and medulloblastomas: the controversial role of JC virus in human neurooncogenesis.

JC virus (JCV), the agent of progressive multifocal leucoencephalopathy (PML), exerts an oncogenic effect in several laboratory animal models. Moreover, JCV genomic DNA and early viral protein T-antigen have been detected in various types of human central nervous system (CNS) neoplasms. To further explore this association we have studied paraffin-embedded brain biopsy tissue from 60 neoplasms (55 gliomas and five medulloblastomas) and 15 reactive gliosis cases for the presence of JCV DNA sequences and proteins. Four post mortem cases of HIV-associated PML were used as positive controls. Samples were assessed by polymerase chain reaction (PCR) amplification of early (large T antigen) and late (virion protein 3) sequences and immunohistochemistry (IHC) with both PAb 2024 and anti-SV40 large T antigen monoclonal antibodies. Five cases (three neoplasms and two reactive gliosis instances) showed low viral DNA levels when PCR-tested for VP3 or large T, while no case was immunoreactive for any of the two antibodies used. The four PML cases yielded positive results with both PCR and IHC. Additionally, IHC with both antibodies was applied to a tissue micro-array including 109 CNS tumours and 21 reactive gliosis samples. No immunoreactivity was detected in any of these tissue micro-array samples. The rarity of JCV DNA sequences and early proteins in our brain tumours enriches the controversy over the role of JCV in human neurooncogenesis, whose clarification is in need of further molecular and epidemiologic studies.

Adult↗

Antimalarial myopathy: an underdiagnosed complication? Prospective longitudinal study of 119 patients.

OBJECTIVES: To evaluate the prevalence and incidence of antimalarial myopathy in patients with rheumatic diseases treated with antimalarial drugs. METHODS: Over a three year period, all patients with rheumatic diseases who were taking antimalarial drugs were studied. Serum muscle enzymes were assessed at the time of inclusion and every six months thereafter. Muscle strength, electromyography (EMG), and muscle biopsy were assessed in patients with a persistent muscle enzyme disturbances. RESULTS: 119 patients were included (111 chloroquine, eight hydroxychloroquine). Of these, 22 (18.5%) had a persistent muscle enzyme disturbance: lactate dehydrogenase 19/22 (86%); creatine kinase 7/22 (32%), and aldolase 3/22 (14%). Findings of antimalarial myopathy were detected in 3/15 biopsied patients (20%) by light microscopy and in all 15 by electron microscopy. Eleven patients had myopathy at the time of inclusion (prevalence 9.2%) and four patients developed muscle injury during follow up (annual incidence 1.2%). Muscle weakness was observed in 8 of 15 patients with biopsy proven myopathy, giving a prevalence of clinical antimalarial myopathy of 6.7%. All these patients also had a myopathic pattern on electromyography. CONCLUSIONS: The prevalence of antimalarial myopathy is higher than previously recognised when muscle enzyme determination is used as a screening method. When a persistent muscle enzyme disturbance is observed, clinical and electromyographic studies should be undertaken periodically to detect the development of clinical myopathy. In cases of clinical myopathy, an anatomical-pathological tissue study, including an ultrastructural study, is mandatory to confirm the diagnosis.

Adult↗

Pathological gambling and age: differences in personality, psychopathology, and response to treatment variables.

The aim of this study was to ascertain the possible differences in personality, psychopathology, and response to treatment in pathological gambling according to age. The sample, comprising 67 participants, was divided into three groups: 32.6% with ages ranging between 17 and 26 years, 31.3% between 27 and 43 years, and 35.8% over 44 years of age. The participants were administered the following tests, Minnesota Multiphasic Personality Inventory [MMPI; Hathaway, S.R. & McKinley, J.C. (1943, 1961). Cuestionario de personalidad MMPI. Madrid Seccion de Estudios de TEA ed. 1970, 1975], sensation-seeking questionnaire [SSS; Zuckerman, M. (1979). Sensation seeking; beyond the optimal level of arousal. Hillsdale, NJ: Lawrence Erlbaum Associates], and the Symptom Check List Revised [SCL-90-R; Derogatis, L.R. (1977). Symptom check list-90 revised. Administration scoring and procedures manual. Baltimore]. All underwent a group treatment programme that was carried out in the Pathological Gambling Unit at Ciutat Sanitaria i Universitaria de Bellvitge (CSUB), Teaching hospital, Barcelona, Spain. The findings show differences depending on age in the participants' personality and in psychopathology and in their response to treatment.

Adolescent↗

Development of a rat model of spinal cord injury and cellular transplantation.

BACKGROUND AND PURPOSE: Intravenously or intraspinally delivered human umbilical cord blood (UCB) cells and mesenchymal stem cells have been previously shown to improve the functional recovery of spinal cord-injured rats. Obtaining an animal model in the laboratory setting is critical for the development of experimental therapies. We have established a rat model of spinal cord injury (SCI) with basic histological and functional evaluations, ready to use for cell transplantation experiments. METHODS: In the first phase 10 Sprague-Dawley (SD) rats were used to standardize the laminectomy at D9-D10 without secondary lesions. In a second phase, 28 SD rats were laminectomized and injured at D9 by spinal cord compression for 3 to 5 seconds with an aneurysmal clip. Open-field behavior was assessed at days 2 and 7 postoperatively, and weekly until their sacrifice, using the Basso, Beattie, and Bresnahan locomotor rating scale. Two weeks postinjury, 14 immunosuppressed rats received a double intraspinal cell transplant of previously frozen UCB mononuclear cells (MNCs). Using a Hamilton syringe, 2.5 x 10(5) unlabelled MNCs in 10 microL medium were transplanted, rostrally and caudally to the lesion site. Rats were sacrificed at 4 weeks posttransplant by transcardial perfusion with 4% paraformaldehyde, and spinal cords were dissected and further fixated for histological analysis. RESULTS: No wound infections were observed. Thirteen rats developed urinary tract infections and two animals showed autophagia grade 3. We observed a common spontaneous mobility improvement until a certain limit, depending on the degree of lesion and intrinsic characteristics of the animal. CONCLUSIONS: An animal model of SCI has been established. Critical parameters in the survival and correct functional analysis are continuous animal care postinjury, urinary tract infections, autophagia, and weight loss. In addition, electrophysiological measures might be necessary to properly assess functional modifications.

Animals↗

Prognostic significance of p27Kip1, p45Skp2 and Ki67 expression profiles in Merkel cell carcinoma, extracutaneous small cell carcinoma, and cutaneous squamous cell carcinoma.

AIMS: To compare the immunohistochemical expression of prognostic markers p27(Kip1), p45(Skp2) and Ki67 in Merkel cell carcinoma (primary neuroendocrine carcinoma of the skin, MCC), small cell neuroendocrine carcinoma of lung and urinary bladder (SNC), and cutaneous squamous cell carcinoma (SCC). METHODS AND RESULTS: Immunohistochemistry was performed using antibodies directed against p27(Kip1), p45(Skp2) and Ki67 on 72 tumour cases: 24 MCC, 25 SCC, and 23 SNC (15 from the lung and eight from the urinary bladder). Percentages of positive cells were determined for each marker and statistically analysed. Expression profiles on MCC and SCC were significantly different for all three markers. MCC and SNC exhibited significant similarities in their p27(Kip1) and p45(Skp2) expression profiles. In contrast, MCC and SNC differed significantly in their Ki67 proliferation indices, which were much higher in SNC. Additionally, MCC cases showed an association between increased proliferation indices and the appearance of local recurrence(s) and/or metastases. CONCLUSION: The immunohistochemical profile of MCC differs from that of SCC, in spite of their common oncogenesis and the supposed metaplastic origin of MCC, and resembles that of SNC, except for Ki67 levels, which were higher in the latter (characterized by greater biological aggressiveness). High levels of Ki67 also appear to be a prognostic factor in MCC.

Analysis of Variance↗

Hepatitis B immunisation status among health care workers in two Kuala Lumpur hospitals.

Health care workers (HCW) are at higher risk of acquiring blood borne infections such as hepatitis B virus, hepatitis C virus and human immunodeficiency virus from patients. To minimise exposure, Universal Precautions Policy guidelines were introduced. This study looked into one of the aspects of hepatitis B prevention among HCW in the Malaysian context. The objective of this study was to assess hepatitis B vaccine coverage among HCW. A cross sectional study involving pre-tested questionnaires was undertaken from February 2001 to August 2001. Hospital staff in Hospital Kuala Lumpur and Hospital Universiti Kebangsaan Malaysia as well as undergraduate students undergoing clinical attachments were randomly chosen. A total of 625 subjects were enrolled. Only 58.4% had taken a complete hepatitis B vaccination. However, 82.2% have taken at least one dose of the hepatitis B vaccine and were supposed to complete the schedule in due course. Not all HCW were protected against hepatitis B. Preventing hepatitis B in HCW should be one of the priorities of the hospital management as it is definitely cheaper than managing chronic hepatitis B cases.

Adult↗

Evaluation and utility of new CE marked containers (CELLFLEX-MacoPharma) for bone bank.

In order to guarantee the required level of quality for our Bone &Tissue Banking, we evaluated a new CE marked container (CELLFLEX MacoPharma), for packing, transport, processing and storage of bones for therapeutic use. The use of CE marked containers is mandatory for organ and tissue containers (Medical Device Directive 93/42). We carried out a three-phase study: (1)Evaluation, (2) Implementation, (3)Audit The product was evaluated for the following criteria:Dash mechanical resistance, Dash air tightness, Dash fragility, Dash capacity. No damage was observed after the storage period, even after immersion in liquid nitrogen. No breakages were observed after provoked impact tests (pots dropped onto the floor). The pot capacity evaluation showed that the inner pot volume (approximately 500 ml) permits adequate storage of tendons and the majority of bone allografts. In conclusion, this evaluation has shown that the CELLFLEX kit is suitable for long duration preservation of bone allografts even at very low temperature conditions (vapour phase nitrogen). Its format and structure permit preservation of most bone allografts.

Bone Transplantation↗

Differential expression of alpha-synuclein isoforms in dementia with Lewy bodies.

Dementia with Lewy bodies (DLB) is characterized by the widespread presence of Lewy bodies (LBs) in the brain. alpha-Synuclein, the main component of LBs, is expressed as two main isoforms (112 and 140), but little is known about their differential expression in the brain. We compared alpha-synuclein 112 and alpha-synuclein 140 expression levels in the prefrontal cortices of six DLB patients, eight Alzheimer disease (AD) patients, and six control subjects. Relative alpha-synuclein 112 and alpha-synuclein 140 expression levels were determined by real-time polymerase chain reaction with competimer technology using a LightCycler System. Whereas total alpha-synuclein levels were just marginally elevated in DLB in comparison with the other groups, alpha-synuclein 112 was seen to be markedly increased in DLB compared with AD cases and controls. In contrast, alpha-synuclein 140 levels were significantly diminished in both neurodegenerative disorders in comparison with controls. These results show differential overexpression of alpha-synuclein 112 in DLB, a finding that could be of importance in DLB pathogenesis.

Aged↗

Neisseria meningitidis isolates with moderate susceptibility to penicillin.

Neisseria meningitidis is one of the important cause of meningitis and has been extremely susceptible to penicillin. Nevertheless, moderately penicillin resistant strains have been reported in some parts of the world. To our knowledge, there is no such report in Malaysia. We report two clinical isolates that were found to have MICs of decreased susceptibility to penicillin by the agar dilution method.

Humans↗

Determination of five nitroimidazoles in water by liquid chromatography-mass spectrometry.

A rapid liquid chromatography-mass spectrometric method for the determination of five nitroimidazoles in water from different sources is described. The extraction procedure was based on HLB solid-phase extraction with acetonitrile followed by an evaporation step. Ternidazol, another nitroimidazole, was used as the internal standard. The liquid chromatographic separation was made on a C18 bonded silica column applying a gradient with an ammonium acetate buffer solution and acetonitrile. Following electrospray ionisation, the protonated molecular ions [M+H]+ were obtained. Quantification for each nitroimidazole was carried out by monitoring its molecular ion. Calibration functions, quantification and detection limits, intra- and inter-day reproducibility and accuracy were estimated. For the confirmatory assay, several fragment ions from each nitroimidazole were obtained and monitored. The method was applied successfully to determine and identify nitroimidazoles in water from different sources at a level of 0.2 microg l(-1).

Chromatography, High Pressure Liquid↗

Over-expression of p45(SKP2) in Kaposi's sarcoma correlates with higher tumor stage and extracutaneous involvement but is not directly related to p27(KIP1) down-regulation.

F-Box protein p45(SKP2) is the substrate-specific receptor of ubiquitin-protein ligase SCF/p45(SKP2) and is involved in the degradation of p27(Kip1) through the ubiquitin/proteasome pathway. In addition, p45(SKP2) facilitates proteolysis of other molecules related to the cell cycle, is frequently over-expressed in transformed cells, and induces S phase in quiescent cells. The aim of this study was to determine whether p45(SKP2) expression is altered in aggressive lesions of Kaposi's sarcoma and its relation to p27(KIP1)down-regulation. We performed immunohistochemistry using antibodies directed to p45(SKP2), p27(KIP1), and Ki67 on paraffin blocks corresponding to 47 cases of Kaposi's sarcoma (8 macules, 10 plaques, 12 tumors, and 15 extracutaneous lesions). p45(SKP2) nuclear over-expression was present in all Kaposi's sarcoma stages, being significantly increased in skin tumors (mean +/- 95% confidence interval: 39.2 +/- 18.8) and extracutaneous lesions (25.8 +/- 17.3) as compared with macules (18.9 +/- 8.2) and plaques (29.2 +/- 12.0; P =.0199). On the other hand, Kaposi's sarcoma progression was associated with a decrease in p27(KIP1) expression and Ki67 immunoreactivity was independent of disease stage. No statistically significant differences were found in regard to patients' sex and human immunodeficiency virus status and regression analysis failed to show a correlation among p45(SKP2), p27(KIP1) and Ki67 immunostaining scores. These findings suggest that p45(SKP2) is involved in Kaposi's sarcoma progression, not only by promoting the degradation of p27(KIP1) but also through other mechanisms still unknown.

Cell Cycle Proteins↗

Alzheimer's disease and the cystatin C gene polymorphism: an association study.

Cystatin C is an amyloidogenic protein that colocalizes with beta-amyloid (Abeta) within arteriolar walls in Alzheimer disease (AD) brains. Recently, a coding polymorphism in the cystatin C gene (CST3) has been claimed to confer risk for the development of late-onset AD. In the present work we have tested the frequencies of CST3-A and CST3-G alleles and used chi-square and logistic regression analyses to assess the association among the CST3 polymorphism, apolipoprotein E4 (APOE4), and AD in a series of 159 AD patients and 155 controls. The CST3-A allele was seen to be an accumulation risk factor for early-onset AD. Furthermore, a synergistic association among the CST3-A allele, APOE4 and AD was found in AD patients whose ages were between 60 and 74 years.

Aged↗

Proliferating trichilemmal tumour: p53 immunoreactivity in association with p27Kip1 over-expression indicates a low-grade carcinoma profile.

AIMS: Alterations of cell-cycle regulatory molecules in tumorigenesis may predict the biological behaviour of neoplasms and greatly contribute to their proper classification. Since the behaviour of proliferating trichilemmal tumour (PTT) is controversial, we decided to explore the possible significance of altered p53 and p27Kip1 immunohistochemical expression patterns in PTT. METHODS AND RESULTS: We evaluated the percentage and distribution of positive tumour cells and compared the results with those obtained from usual trichilemmal cysts (TC) and squamous cell carcinomas with trichilemmal differentiation (SCCT). PTT showed p53 immunoreactivity (50.4 +/- 29.6, mean +/- standard deviation) that was not statistically different from that seen in SCCT (75.2 +/- 36.3). On the other hand, p53 immunostaining was virtually absent in TC cases (positivity for p53 was observed in only one instance in < 1% of cells). As for p27Kip1, the mean percentage of positive cells in PTT (82.7 +/- 9.9) was slightly lower than in TC (90.6 +/- 4.6) but significantly higher than in SCCT (53.4 +/- 30). CONCLUSIONS: The similar p53 immunoreactivity in both PTT and SCCT favour the interpretation of the former as carcinoma, albeit one whose behaviour would be tempered by the well-known regulatory effect exerted by p27Kip1 on the cell cycle.

Carcinoma, Squamous Cell↗

Towards a 'human-like' model of tuberculosis: intranasal inoculation of LPS induces intragranulomatous lung necrosis in mice infected aerogenically with Mycobacterium tuberculosis.

It is well known that one of the differences between murine and human tuberculosis is the lack of intragranulomatous necrosis in the former. The aim of this study was to create a feasible and reproducible model of an experimental model of murine tuberculosis in which this necrosis should be present. Considering the Shwartzman reaction as a possible explanation for intragranulomatous necrosis in human tuberculosis, C57Bl/6 mice, infected aerogenically with a virulent strain of Mycobacterium tuberculosis, were intranasally inoculated with lipopolysaccharide (LPS) on day 19 postinfection (p.i.). Twenty-four hours later, neutrophils infiltrated the lung parenchyma in a significant level, and 10 days after necrosis could be detected in the centres of primary granulomas, that showed scanty macrophages and large amounts of collagen on an eosinophilic background. On the other hand, a significant decrease in the concentration of colony forming units (CFU) could be appreciated 24 h after the LPS inoculation. Afterwards, nonbronchogenic spreading of granulomas increased and higher levels of interferon (IFN)-gamma mRNA were detected. These results lend support to the Shwartzman reaction as the origin of the intragranulomatous necrosis in the M. tuberculosis infection, and provides a useful tool to improve experimental murine models in tuberculosis.

Administration, Intranasal↗

Cutaneous angiolymphoid hyperplasia with high endothelial venules is characterized by endothelial expression of cutaneous lymphocyte antigen.

Two cases in which the presence of cutaneous lesions with a characteristic admixture of lymphoid hyperplasia and vascular proliferation lead to the diagnosis of so-called acral pseudolymphomatous angiokeratoma (APA) of children are reported. Owing to the prominence of its blood vessels, so striking as to be reminiscent of high endothelial venules (HEVs), APA was initially interpreted as a vascular lesion rather than a pseudolymphoma. This resemblance is further compounded by our finding that cutaneous lymphocyte antigen (CLA), an HEV marker, is also expressed in APA epithelioid blood vessels. Consequently, we believe that "cutaneous angiolymphoid hyperplasia with high endothelial venules" (ALH-HEV), which alludes to the dual nature of proliferating elements and the HEV-like phenotype of the vascular component, would be a better denomination for this entity. Additionally, we speculate that ALH-HEV lymphoid hyperplasia self-perpetuates through the transformation of dermal capillaries into HEVs, which would bind non-skin homing lymphocytes expressing L-selectin and promote their local recruitment and recirculation.

Angiokeratoma↗

Decreased immunoreactivity for cell-cycle regulator p27(Kip1) in Kaposi's sarcoma correlates with higher stage and extracutaneous involvement.

A consistent relationship has been established between the development of Kaposi's sarcoma (KS) and human herpes virus-8 (HHV8) infection. HHV8-encoded v-cyclin, through its complexing with cyclin-dependent kinase 6, contributes to the phosphorylation and proteasome-mediated degradation of p27(Kip1). On the other hand, down-regulation of p27(Kip1) expression seems to facilitate metastatic dissemination in a variety of human neoplasms. Although the neoplastic nature of KS remains controversial, it has been repeatedly demonstrated that in some patients KS may behave as a malignant neoplasm and follow an ominous course, especially in HIV-positive patients and when associated with extracutaneous involvement. To determine whether decreased p27(Kip1) levels are also related to more aggressive behaviour in KS, it was decided to investigate p27(Kip1) immunoreactivity in KS biopsy specimens and its possible changes in relation to cutaneous versus extracutaneous involvement and HIV serological status. Forty-nine cases of KS (29 AIDS-related and 21 classical) corresponding to 30 cutaneous biopsy specimens (ten macules, seven plaques, and 13 tumours) and 19 extracutaneous biopsy specimens were immunostained to determine the expression of p27(Kip1) and the proliferation marker Ki-67 antigen. The mean percentages of p27(Kip1)-positive cells were significantly higher in biopsy specimens from skin lesions (77.8+/-21.1) than in those from extracutaneous locations (42.0+/-26.0). Amongst cutaneous lesions, p27(Kip1) expression was significantly higher in macules (83.8+/-18.5) and plaques (91.4+/-6.4) than in tumours (65.8+/-22.6). Ki-67 immunoreactivity showed no correlation with any of the variables studied. These results lend support to the hypothesis that decreased levels of p27(Kip1), which may have been brought about by HHV8 infection, play a role in KS progression through its various histopathological stages, to its eventual extracutaneous spread.

Cell Count↗

Immunohistochemical detection of Bcl-2 in Kaposi's sarcoma lesions varies according to histopathologic stage, whereas expression of Bcl-x and Mcl-1 differs according to human immunodeficiency virus serologic status of patients.

Expression of Bcl-2, Bcl-x, and Mcl-1 was immunohistochemically evaluated in 33 cases of Kaposi's sarcoma (KS) of the skin. Of these, classic KS (C-KS) accounted for 17 cases (10 in plaque stage and 7 in tumor stage) and acquired immunodeficiency syndrome-associated KS (AIDS-KS) accounted for 16 cases (8 in plaque stage and 8 in tumor stage). In both C-KS and AIDS-KS, Bcl-2 immunoreaction correlated with progression stage, its average score intensity being more than 2-fold in tumors than in plaques. In contrast, Bcl-x and Mcl-1 staining intensity was unrelated to progression stage but was dependent on human immunodeficiency virus infection status. Thus, whereas Bcl-x expression was stronger in C-KS cases, Mcl-1 immunostaining was more intense in AIDS-KS instances. These findings indicate that in cutaneous KS, some Bcl-2 family proteins exhibit differential expressions that are dependent on either progression stage or human immunodeficiency virus infection status.

Acquired Immunodeficiency Syndrome↗

Palisading and verocay body-prominent dermatofibrosarcoma protuberans: a report of three cases.

UNLABELLED: The aim of this report is to draw attention to nuclear palisading and Verocay body formation as peculiar, previously undescribed histological findings in rare instances of dermatofibrosarcoma protuberans (DFSP). METHODS AND RESULTS: Three indurated, nodular or plaque skin lesions were diagnosed as DFSP on the basis of their storiform proliferation of spindle-shaped cells diffusely infiltrating the dermis and subcutaneous tissue. Sclerosing and giant cell areas were also identified. Unexpectedly, conspicuous nuclear palisading was also noted in all cases and Verocay body formation was present in two. Immunostains were positive for CD34 and negative for S100 protein in every instance. Proliferating cells were seen to display fibroblast-like features by ultrastructural study of one case. CONCLUSIONS: DFSP may rarely show a schwannoid histological appearance as the result of nuclear palisading and even Verocay body formation. In this setting, both the search for DFSP characteristic morphologic features and the performance of CD34 and S100 protein immunohistochemistry will facilitate the correct diagnosis.

Antigens, CD34↗