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Biomedical subjects

R Alvarez

Publications and source records attributed to R Alvarez.

At least 109 records · Page 6Linked to original sources
PubMed1998

Bcl-2 overexpression is associated with resistance to dexamethasone, but not melphalan, in multiple myeloma cells.

Multiple myeloma (MM) is an incurable disease despite an initial response-rate of >60% with conventional or high-dose chemotherapy. Glucocorticosteroids such as dexamethasone (DEX) and alkylating agents such as melphalan (MEL) are capable of inducing complete responses (CR) in >50% of MM patients, however, resistance to these drugs develop rapidly, in >90% of patients, within 2 years of treatment. The exact mechanism of resistance to these drugs is not known. We investigated the mechanism of resistance to DEX and MEL. In particular, we investigated the role of bcl-2 in development of resistance to these two drugs. We tested the role of bcl-2 by transfecting 2 low bcl-2-expressing myeloma cell lines, ARP-1 and 8226, with a bcl-2 expression vector and compared the effects of DEX and MEL on apoptosis, cell cycle distribution and the levels of proapoptotic (bax) and antiapoptotic (bcl-2, bclx) proteins. The results indicate that the two drugs act by a different mechanism with respect to all the parameters tested. While DEX-induced apoptosis was dependent on the level of bcl-2 expression, MEL-induced apoptosis was independent of bcl-2 levels. Treatment with DEX of the low bcl-2-expressing cells (DEX-sensitive) resulted in a rapid apoptosis from all phases of the cell cycle. In contrast, treatment with MEL blocked the cells in late-S/G2 phase of the cell cycle and caused substantial apoptosis, regardless of bcl-2 expression. Major differences between DEX and MEL were also observed with respect to their effects on the levels of bcl-2 and p53. Whereas DEX induced an early (day 1) downregulation of bcl-2 (only in the cells with low bcl-2), treatment with MEL did not affect bcl-2 levels. The levels of bclx and bax remained unchanged following treatment with either MEL or DEX. These results, taken together, suggest that the two drugs target different cellular components and induce apoptosis by different pathways, and that resistance to DEX is associated with low levels of bcl-2, whereas resistance to MEL is independent of bcl-2, and therefore, in vivo resistance to MEL, observed in MM patients, might involve other mechanisms rather than bcl-2.

Antineoplastic Agents, Alkylating↗
PubMed1998

Characterization of a virus isolated from the cerebrospinal fluid of patients with epidemic neuropathy.

A previously unknown disease, termed epidemic neuropathy (EN), occurred in Cuba between 1991 and 1993. When samples of cerebrospinal fluid (CSF) from 45 patients with EN and 11 controls were inoculated into cultures of VERO cells, almost all (93%) of the samples from the cases of EN but only one (9%) of the control samples produced a slowly progressing cytopathological effect (CPE). Although the results of other studies indicated the presence of a picornavirus-like virus in CSF samples from EN cases, the CPE and other physico-chemical characteristics observed were not those expected of picorn-viruses. Several aetiological factors may have contributed to EN but at least one virus could have played a major role.

Adult↗
PubMed1998

[Cytomegalovirus: comparative study of diagnostic techniques].

BACKGROUND: The aim of this study was to undertake a comparative study of a series of diagnostic techniques of active infection by cytomegalovirus (CMV) in blood (isolation of CMV by shell vial, detection of specific anti-CMV IgG and IgM, antigenemia-detection of pp65 antigen by staining with peroxidase- and two variants of qualitative polymerase chain reaction [PCR]-conventional PCR or in one step and nested PCR-for detection of viral DNA). METHODS: Fifty kidney transplant patients were followed for the first 6 post transplant months. All except 6 were seropositive for CMV prior to transplantation and only one seronegative patient had a seronegative donor. RESULTS: A total of 750 blood samples were analyzed, 8 of which were positive by shell vial, 91 by specific IgM detection, 115 by antigenemia, 225 for conventional PCR and 440 for nested PCR. No positive sample was detected throughout follow up by any of the techniques used in only 4 patients (one being the seronegative receptor with a seronegative donor). CONCLUSIONS: Antigenemia was found to be the fastest, cheapest and simplest method of diagnosing CMV, presenting the advantage of providing quantitative results which allow the establishment of a relationship with the appearance of symptomatic infections. With the two variants used qualitative PCR was observed to be the earliest and most sensitive technique, while being the most difficult and the most expensive, with the disadvantage that its great sensitivity limits its clinical usefulness.

Cytomegalovirus Infections↗
PubMed1998

Novel 3'-spiro nucleoside analogues of TSAO-T. Part II. A comparative study based on NMR conformational analysis in solution and theoretical calculations.

The structures of two novel 3'-spiro nucleosides analogues of the potent human immunodeficiency virus type 1 (HIV-1) reverse trancriptase (RT) inhibitor TSAO-m3T, in solution, as derived from NMR spectroscopy are described. In these TSAO analogues the spiro amino oxathioledioxide moiety has been replaced by spiro amino oxazolone or spiro amino oxathiazoledioxide moieties. A comparative study based on theoretical calculations of the hydrophobicity, the solvation free energies and molecular electrostatic potentials (MEP) of the three compounds is also described. No significant conformational differences were detected in solution between TSAO-m3T and its analogues that might account for the differences observed in their inhibitory activity against HIV-1 RT. The calculated hydrophobicity (log P) values, dipole moments and the electrostatic contributions to the solvation free energies of the three spiro ring systems were also similar. However, the differences found in the calculated MEPs of the spiro systems between TSAO-m3T and its analogues suggest that the different electrostatic surroundings of the 4"-amino group of the spiro moiety in the analogues may be responsible for a detrimental electrostatic interaction of the spiro rings with the Glu-B138 of RT.

Anti-HIV Agents↗
PubMed1997

Cloned and native guinea pig 5-ht7 receptors. Characterization using an integrated approach.

Structural criteria, i.e., primary sequence homology, indicates a unique 5-HT subtype. Operational criteria suggest that this is also true, although no selective agonist or antagonist is available to fully define the receptor, and thus its function in vivo. Transductional data provide perhaps the weakest criterion to define the receptor, since at least two other subtypes (5-HT4 and 5-ht6) signal via the same second messenger. These criteria, taken together, suggest that the cloned sequence represents an endogenously expressed 5-HT receptor and should be referred to as "5-HT7" receptors, rather than "5-ht7".

Amino Acid Sequence↗
PubMed1997

Autoimmune hepatitis type 2 and hepatitis C virus infection: study of HLA antigens.

BACKGROUND/AIMS: Markers for hepatitis C virus are often detectable in patients suffering chronic hepatitis with liver-kidney microsomal type 1 antibodies. Several authors have suggested that two subsets of those patients can be defined: a) hepatitis C virus negative and b) hepatitis C virus positive. The aim of this work was to further analyze the possible genetic association, HLA class I and II, in these two groups of patients. METHODS: HLA was analyzed in 49 patients. Class I was studied using a standard lymphocytotoxicity test and in class II a reverse hybridization-based test for DRB1 typing and PCR-SSO for DQB1 typing were used. Sixty healthy Spanish subjects and 39 chronic hepatitis C subjects without anti-LKM1 antibodies were used as control groups for the "a" and "b" subsets, respectively. RESULTS: No significant association was found with class I specificities in either group. DQB1 typing showed a very significant increase of DQ2 in the "a" group (93.3% vs. 48%; RR = 15; Pc = 0.0025), and DRB1 typing from the "b" group revealed a high association with DR7 (82.3% vs. 43.6%; RR = 6; Pc = 0.0086). CONCLUSIONS: Our studies revealed a strong association with DQ2 for the "a" group and for the first time an extremely high association with DR7 antigen for the "b" subset. Hence it is possible to establish a different genetic profile in these two patient groups.

Adolescent↗
PubMed1997

Hamster origin of metaphases with multiple chromosome rearrangements in first cleavage human-hamster embryos.

Laboratories using the human sperm-hamster egg fertilization system to analyse sperm chromosomes obtain, sporadically, metaphases with multiple aberrations. Due to the high number of aberrations, these metaphases cannot be fully karyotyped. In some of them, one or several human chromosomes can be identified, guaranteeing the human origin of the whole metaphase. However, in others, none of the chromosomes can be recognized as human. This latter type of grossly rearranged metaphases is characterized by complex chromatid exchanges, multifragmented chromosomes and pulverized chromosome material. Using fluorescent in-situ hybridization techniques (FISH) with either human or hamster genomic DNA probes, we examined the origin of this second type of metaphase with multiple chromatid exchanges and fragmented chromosomes. Our study demonstrates that all of them hybridize with hamster genomic DNA probes and not with human DNA, proving their hamster origin. Since some of these metaphases seem to be diploid, we suggest that they may arise from hamster eggs that have failed to complete meiosis and have not extruded the second polar body.

Animals↗
PubMed1997

Arthritis severity and spirochete burden are determined by serotype in the Borrelia turicatae-mouse model of Lyme disease.

Immunodeficient mice infected with Borrelia turicatae, a relapsing fever agent, have a disorder that resembles disseminated Lyme disease. Two serotypes, A and B, differed in their arthritogenicity in both CB-17 SCID and C3H SCID mice. In CB-17 SCID mice infected with serotype A or B, arthritis was assessed by measurement of tibiotarsal diameter, functional ability on a beam walk test, and microscopic assessment of joint inflammation. Serotype B-infected mice had greater joint swelling, functional disability, and leukocytic infiltration in the joints than serotype A-infected mice. Joint swelling and disability peaked at 2 weeks of infection and then decreased, while leukocyte infiltration in the joints persisted. To investigate the basis for the differences in arthritogenicity of serotypes A and B, spirochete burdens in infected mice were measured by quantitative PCR of spirochete DNA in joints, direct immunofluorescence of spirochetes in joints, and counts of spirochetes in the blood. At 2 weeks of infection there were seven times more spirochetes in the joints of serotype B-infected mice than in those of serotype A-infected mice, measured by both quantitative PCR and direct enumeration. Although serotypes A and B had the same infectivity and growth rate in vivo, serotype B spirochetes were eightfold more abundant in the blood than serotype A spirochetes and produced greater fatality in newborn mice. These findings indicate that differences in disease severity in mice infected with serotype A or B are attributable to differences in the spirochete burden in the joints and blood.

Animals↗
PubMed1997

Effectiveness of immunomodulating treatment (thymostimulin) in chronic obstructive pulmonary disease.

We conducted a prospective randomized study to assess the effect of thymostimulin in patients with long-standing chronic obstructive pulmonary disease (COPD) during a 1-year follow-up. A total of 38 patients in the intervention group and 40 in the control group received standard treatment for COPD. Patients in the intervention group were also given thymostimulin intramuscularly (1 mg/kg day for the 1st week followed by once a week for 6 months). At the end of the study period, patients treated with thymostimulin showed a statistically significant lower number of exacerbations and hospital admissions as compared with controls. However, there were no changes in the number of patients with severe or moderate impairment of respiratory function throughout the study period. No significant differences were found by Multitest or in serum concentrations of immunoglobulins and T-cell subsets before and after thymostimulin treatment. We conclude that treatment with thymostimulin is effective in the prevention of COPD exacerbations acting on the cellular immune response involved in bronchopulmonary defense.

Adjuvants, Immunologic↗
PubMed1997

[Clinico-pathological correlation in the main types of dementia].

INTRODUCTION: Dementia has became a serious health problem in developed countries. The objective of this study was to establish the possible correlation between the initial clinical diagnosis and the anatomopathological criteria. Pathological confirmation of the cases clinically diagnosed as Alzheimer disease/senile dementia Alzheimer type (AD/SDAT) and multi-infarct dementia (MID) was carried out. MATERIAL AND METHODS: Twelve brains from demented patients were studied. Brains were removed at post-mortem intervals of 1-3 hours to guarantee an adequate conservation of the tissue. The brains were weighed, fixed for 4 weeks in 10% buffered neutral formalin and coronally sectioned at intervals of approximately 1 cm. Bilateral sections of neocortex from frontal, temporal, parietal lobes, cingulate gyrus, amygdala, hippocampus, thalamus, cerebellum and unilateral sections of locus ceruleus and substantia nigra were taken. Five micrometer sections of the paraffin embedded material were stained by the following methods: hematoxylin-floxine, Congo red and Bielschowsky silver impregnation. RESULTS: Our neuropathological results showed a high correlation with the initial clinical classification and confirmed the diagnosis of AD/ SDAT in 6 cases, MID in 3 cases and mixed dementia in 1 case. Two cases did not exhibited morphological evidence of dementia. CONCLUSIONS: We concluded that the methodology applied for the morphologic diagnosis of dementia was feasible, useful and reproducible. Further studies will be necessary using a larger number of sample.

Aged↗
PubMed1997

Dose-response relationship for the induction of chromosomal abnormalities in gamma-irradiated human spermatozoa.

The cytogenetic effects of in vitro irradiation on human spermatozoa have been studied by the interspecific in vitro fertilization system between human sperm and hamster oocytes. Semen samples from three healthy men were irradiated at doses of 0.00, 0.10, 0.25, 0.50, 1.00, 2.00, and 4.00 Gy. A total of 340 chromosome complements derived from non-irradiated human spermatozoa and 987 complements from irradiated spermatozoa were analyzed after sequential uniform stain-G banding. Both the frequency of spermatozoa with structural chromosome abnormalities, and the incidence of such abnormalities per cell, showed strong dose-effect relationships that were best expressed by linear-quadratic equations: Y = 0.06413(+/-0.00475) + 0.1982(+/-0.00833)D - 0.00763(+/-0.00204)D2 and Y = 0.07385(+/-0.00838) + 0.23329(+/-0.03124)D + 0.02317(+/-0.00955)D2, respectively. When analyzing separately unrejoined and rejoined structural abnormalities, we found that the incidence of unrejoined lesions was four times higher than the incidence of rejoined anomalies. The induction of unrejoined abnormalities showed a linear, dose-dependent increase, whereas the incidence of rejoined abnormalities showed a quadratic, dose-dependent increase. The distribution of radiation-induced breakpoints was also analyzed. Breakpoints were found to be randomly distributed among chromosomes, but a clustering of breakpoints in G-negative bands was found: 71.5% of breakpoints were located in G-negative bands, and 28.5% in G-positive bands.

Adult↗
PubMed1997

Squamous cell carcinoma, malignant melanoma and malignant fibrous histiocytoma arising in burn scars.

The most common cancer arising from an old burn scar is squamous cell carcinoma, while malignant melanoma is rare. There are only four reports in the literature on the combination of the more common tumour with a malignant melanoma and only two cases of malignant fibrous histiocytoma alone. This paper reports the first occurrence of the combination of all three types of cancer in burn scars of the same patient. The factors that promote malignant transformation, such as immunological factors and karyotype, are discussed. We also performed an immunohistochemical study using anti-p53 antibodies.

Burns↗
PubMed1997

[Sclerosing hepatocarcinoma not associated with hypercalcemia].

The sclerosing hepatocellular carcinoma is an unusual subtype of hepatocellular carcinoma characterized by an intense fibrous stroma in which the tubular structures are embedded. Histological diagnosis is difficult, and misinterpretation as cholangiocarcinoma or metastatic adenocarcinomas may occur. It usually presents on non-cirrhotic livers. Metastases located outside of the liver are frequent as well as hypercalcemia and low levels of serum phosphate. We report a case of this rare histopathologic subtype of hepatocellular carcinoma in a 35-year-old woman, asymptomatic and with no previous history of chronic liver disease. It was detected by a routine gynaecological ultrasonography. An important increase of serum alpha-fetoprotein was noted. Extension studies showed bilateral lung metastases. Several palliative therapies were tried out, including epirrubicin, with partial response. Twenty months after the diagnosis the patient's situation is nearly terminal.

Adult↗
PubMed1996

Brain stem reflexes in patients with Wallenberg's syndrome: correlation with clinical and magnetic resonance imaging (MRI) findings.

In spite of the general clinical uniformity of Wallenberg's syndrome (WS), individual patients present with a slightly different clinical picture, and detailed studies with magnetic resonance imaging (MRI) show differences in the topography of the brain stem lesion. Neurophysiological characterization of the lesion in WS has been known for a long time, but there are no studies on the possible correlation between lesion topography and neurophysiological deficit. Assuming that afferents from the three branches of the trigeminal nerve reach different parts of the trigeminal nuclei, we examined the possible correlation between the lesion topography assessed by the MRI and the neurophysiological deficit, assessed by studying the brain stem reflexes in patients with WS within 2 weeks after stroke. Neurophysiological abnormalities were always located in the afferent branch of the reflexes examined, but not all patients exhibited abnormalities in all responses. The ophthalmic branch was involved in 92.8% of patients, and the mandibular branch in 57.1% of patients. The patients with MRI lesions located in the lower medulla had normal responses with infraorbital or mental nerve stimulation. The results of this neurophysiological study confirm the heterogeneity of WS. Whether the neurophysiological identification of different subgoups of patients is relevant for clinical outcome needs further studies.

Action Potentials↗