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Biomedical subjects

A Alba

Publications and source records attributed to A Alba.

At least 19 recordsLinked to original sources

Reg (regenerating) gene overexpression in islets from non-obese diabetic mice with accelerated diabetes: role of IFNbeta.

AIMS/HYPOTHESIS: The expression of IFNbeta in beta cells results in accelerated type 1 diabetes. The REG family of beta cell proliferation factors have been described as autoantigens in autoimmune diabetes. The aim of this study was to determine the effect of IFNbeta on Reg expression, and the implications of this in terms of autoimmunity. METHODS: Reg gene expression was determined in islets from non-obese diabetic (NOD) RIP-HuIFNbeta mice by cDNA microarray, quantitative real-time PCR and immunohistochemistry. The effect of IFNbeta on Reg1 and Reg2 expression was assessed in the NOD insulinoma cell line NIT-1. IL-6, known to induce Reg expression, was measured in the insulitis microenvironment. Morphological studies were carried out to determine islet enlargement in this model. RESULTS: Reg2 was upregulated in islets from the NOD RIP-HuIFNbeta mice at the onset of the autoimmune attack. IFNbeta upregulates Reg1 and Reg2 genes in NIT-1 cells. The expression of Il6 was increased in islets from transgenic mice and in NIT-1 cells exposed to HuIFNbeta. Moreover, islets from transgenic mice were enlarged compared with those from wild-type mice. CONCLUSIONS/INTERPRETATION: Reg overexpression correlates well with the acceleration of diabetes in this model. The upregulation of Reg suggests that islets try to improve hyperglycaemia by regenerating the cells lost in the autoimmune attack. Reg expression is regulated by several factors such as inflammation. Therefore, the overexpression of an IFNbeta-induced autoantigen (REG) in the islets during inflammation might contribute to the premature onset of diabetes.

Animals↗

Evidence of expression of endotoxin receptors CD14, toll-like receptors TLR4 and TLR2 and associated molecule MD-2 and of sensitivity to endotoxin (LPS) in islet beta cells.

CD14, a GPI-linked membrane protein, is a component of the lipopolysaccharide (LPS) receptor complex, one of the pattern-recognizing receptors (PRR) expressed by myeloid lineage cells. Here we report that CD14, the functionally linked toll-like receptor molecules, TLR2 and TLR4, and the associated molecule MD-2 are expressed in endocrine cells of the human pancreatic islets. CD14 expression in human pancreatic islets was determined by immunofluorescence staining of tissue sections and primary cultures, and confirmed by flow cytometry of dispersed normal islets and SV40-transformed islet cells (HP62). The latter cells synthesized and secreted CD14 in response to lipopolysaccharide (LPS) in a time- and dose-dependent manner. Reverse transcription polymerase chain reaction (RT-PCR)-Southern was positive for CD14, TLR2, TLR4 and MD-2 in human pancreas, purified islets and HP62 cells. In vitro experiments using rat islets (also positive for CD14 by RT-PCR) and HP62 cells showed that LPS regulates glucose-dependent insulin secretion and induces inflammatory cytokines [interleukin (IL)-1alpha, IL-6 and tumour necrosis factor (TNF)-alpha]. The functional expression of CD14 and associated molecules in islet beta cells adds a new pathway that islet cells may follow to adjust their function to endotoxaemia situations and become vulnerable to the inflammatory events that occur during diabetogenic insulitis.

Adolescent↗

Expression of LRP and MDR1 in locally advanced breast cancer predicts axillary node invasion at the time of rescue mastectomy after induction chemotherapy.

BACKGROUND: Axillary node status after induction chemotherapy for locally advanced breast cancer has been shown on multivariate analysis to be an independent predictor of relapse. However, it has been postulated that responders to induction chemotherapy with a clinically negative axilla could be spared the burden of lymphadenectomy, because most of them will not show histological nodal invasion. P-glycoprotein expression in the rescue mastectomy specimen has finally been identified as a significant predictor of patient survival. MATERIALS AND METHODS: We studied the expression of the genes encoding multidrug resistance associated protein (MDR1) and lung cancer associated resistance protein (LRP) in formalin-fixed, paraffin-embedded tumor samples from 52 patients treated for locally advanced breast cancer by means of induction chemotherapy followed by rescue mastectomy. P-glycoprotein expression was assessed by means of immunohistochemistry before treatment in 23 cases, and by means of reverse-transcriptase-mediated polymerase chain reaction (RT-PCR) after treatment in 46 (6 failed). LRP expression was detected by means of immunohistochemistry, with the LRP-56 monoclonal antibody, in 31 cases before treatment. Immunohistochemistry for detecting the expression of c-erb-B2, p53, Ki67, estrogen receptor and progesterone receptor are routinely performed in our laboratory in every case, and the results obtained were included in the study. All patients had received between two and six cycles of standard 5-fluorouracil, doxorubicin and cyclophosphamide (FAC) chemotherapy, with two exceptions [one patient received four cycles of a docetaxel-adriamycin combination, and the other four cycles of standard cyclophosphamide-methotrexate-5-fluorouracil (CMF) polychemotherapy]. Response was assessed in accordance with the Response Evaluation Criteria In Solid Tumors (RECIST). By these, 2 patients achieved a complete clinical response, 37 a partial response, and the remaining 13 showed stable disease. This makes a total clinical response rate of 75.0%. None achieved a complete pathological response. RESULTS: MDR1 mRNA expression detected by RT-PCR was associated with the presence of invaded axillary nodes at surgery in 18/22 cases (81.8%), compared with 13/24 (54.2%) in the group with undetectable MDR1 expression. This difference was statistically significant (P < 0.05). LRP expression in more than 20% of tumor cells before any treatment was associated with axillary nodal metastasis after chemotherapy and rescue mastectomy in 17/23 cases, compared with 3/8 in nonexpressors. Again, this difference was highly significant (P < 0.01). LRP expression before treatment and MDR1 mRNA expression after treatment were significantly interrelated (P < 0.001), which might reflect the presence of chemoresistant clones liable to metastasize to the regional nodes. Persistence of previously detected MDR1-positivity after treatment (7/9 compared with 0/2 cases) was significantly associated with axillary node metastasis (P < 0.05). Finally, in a logistic regression multivariate model, histology other than ductal, a Ki67 labeling index of at least 20% and the combination of LRP and MDR1 positivity emerged as independent predictors of axillary node invasion at the time of rescue mastectomy. CONCLUSION: The expression of different genes involved in resistance to chemotherapy, both before and after treatment with neoadjuvant, is associated with the presence of axillary node invasion at rescue surgery in locally advanced breast cancer. This might reflect the presence of intrinsically resistant clones before any form of therapy, which persist after it, and could be helpful both for prognosis and for the choice of individual treatment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Expression of CD3 and CD11b antigens on blood and mammary gland leukocytes and bacterial survival in milk of cows with experimentally induced Staphylococcus aureus mastitis.

OBJECTIVES: To differentiate early (1 to 8 days) from late (9 to 14 days) inflammatory phases and assess relationships between leukocyte phenotype and bacterial recovery in cows with Staphylococcus aureus-induced mastitis. ANIMALS: 10 first-lactation Holstein cows. PROCEDURE: Blood and milk samples were collected from 4 or 6 cows before and after intramammary infusion of sterile broth or S. aureus, respectively. Flow cytometric expression of CD3 and CD11b antigens on blood and milk leukocytes, leukocyte differential counts, bacterial counts in milk, and somatic cell counts were determined longitudinally. RESULTS: Density of CD3 molecules decreased on blood lymphocytes and increased on milk lymphocytes after infusion of bacteria. Density of CD11b molecules on lymphocytes and phagocytes and percentage of CD11b+ lymphocytes in milk increased significantly after infusion; maximum values were achieved during the early inflammatory phase. Density of CD3 and CD11b molecules on milk lymphocytes and macrophages, respectively, 1 day after inoculation were negatively correlated with bacterial recovery on day 1 and days 9 to 14, respectively. Density of CD11b molecules on milk macrophages and the ratios of phagocyte to lymphocyte percentages and polymorphonuclear cell to macrophage percentages in milk differentiated the early from the late inflammatory phase. CONCLUSIONS AND CLINICAL RELEVANCE: Activation of bovine mammary gland macrophages and T cells in response to intramammary infusion of S. aureus was associated with an inability to culture this bacterium from milk. Identification of specific inflammatory phases of S. aureus-induced mastitis in cows may allow for the design of more efficacious treatment and control programs.

Animals↗

The dental prosthesis used for intraoral muscle therapy in the rehabilitation of the stroke patient. A preliminary research study.

The dentist can maximize the oral rehabilitation of the stroke patient's weak or paralyzed oral musculature, resulting in dysfunctional speech, swallowing and deglutition, with the use of palatal lift and palatal augmentation prostheses. The study described here evaluates functional changes using these prostheses for three post-stroke patients with left hemiparesis. Clinical tests indicated decreased nasal emission and hypernasality, and improved speech articulation. Videofluoroscopy evaluation showed improvement in the oral phase of swallowing. Patient self-assessment indicated improved satisfaction with treatment.

Adult↗

[Epidemic rhabdomyolysis due to the eating of quail. A clinical, epidemiological and experimental study].

BACKGROUND: Few toxic outbreaks by quails ingestion have been described, none in Spain, and the toxic hasn't been identified. A toxic outbreak, by quails ingestion that ate Galeopsis ladanum seeds, is described and an animal model is developed. PATIENTS AND METHODS: A rhabdomyolysis outbreak by quails ingestion is studied clinical and epidemiologically. Quails crops were analyzed and 20 patients were studied. A murine model was developed. Alcaloid content in Galeopsis ladanum seeds and quail meat was measured. RESULTS: Twenty patients suffered from rhabdomyolysis (myalgia, increase of muscular enzymes and myoglobinuria) by ingestion of quails that ate Galeopsis ladanum seeds as it could be seen at their crops. Six patients needed hospital care but evolution was benign. Rats fed with quails that ate Galeopsis ladanum seeds had higher creatinkinase (CK) levels than controls rats (near significance, p = 0.0588). Several alcaloids, stachydrine included, was detected in seeds. Another alcaloid no identified was detected in quails meat. CONCLUSIONS: Quails that eat Galeopsis ladanum seeds are toxic for human beings, causing rhabdomyolysis. A plant alcaloid could be the toxic involved in the outbreak.

Alkaloids↗

Localization of TIMP-1, TIMP-2, TIMP-3, gelatinase A and gelatinase B in pathological human corneas.

PURPOSE: Determine the tissue distribution patterns for tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2, TIMP-3), gelatinase A and gelatinase B in normal and pathologic corneas. METHODS: Corneas were examined by immunohistochemistry, using antibodies to TIMP-1, TIMP-2, TIMP-3, gelatinase A or gelatinase B. RESULTS: In normal corneas, TIMP-1 antibody stained the epithelium and endothelium. TIMP-2 and TIMP-3 stained the epithelium, keratocytes and endothelium. Gelatinase A staining was weak and restricted to the epithelial cells. Radial keratotomy scars showed increased staining for TIMP-1 and TIMP-2 around the epithelial cell plug and along the incision. Bullous keratopathy corneas showed TIMP staining patterns similar to normal corneas and increased gelatinase A staining in regions of subepithelial fibrosis. Stromal scars of keratoconus corneas also had increased staining with TIMP-1 and TIMP-2 antibodies. In many keratoconus corneas, the TIMP-3 staining pattern was similar to normal corneas. However, in some keratoconus corneas, when Bowman's layer was missing, the stroma beneath was completely devoid of TIMP-3 antibody staining. No gelatinase B was seen in either the normal or diseased corneas. CONCLUSION: These data suggest that TIMP-1 and TIMP-2 are important for scar formation and corneal remodeling, since they were found in increased amounts at radial keratotomy incision sites and keratoconus scars. The significance of the focal stromal defects in TIMP-3 staining, associated with absence of Bowman's layer on keratoconus corneas, needs to be elucidated. At the stages of disease examined in this study, gelatinase B may not play a significant role in these pathological processes, since it was not seen in any of the corneas examined.

Base Sequence↗

Carbon monoxide trend, meteorology, and three-way catalysts in Mexico City.

From the analysis of data of the Inspection/Maintenance (I/M) program, and of the long-term trend of ambient CO concentrations in Mexico City, it is inferred that three-way catalysts (TWCs) have a 45% efficiency, well below the expected 90% value. The most probable causes are sulfur poisoning, lead contamination, and ceramic breakage due to bumps and potholes on the streets. Also, we have found a ratio between the average daily peak value of atmospheric CO and gasoline consumption: (11 +/- 1) ppbCO/MLm (million liters of gasoline per month) in 1988 decaying to (10 +/- 1) in 1991 for Mexico City before the introduction of TWCs. In addition, we found a correlation between the monthly averages of CO daily peak and meteorological variables, explaining most of the seasonal changes using only the intensity of the inversion layer and surface wind speed.

Air Movements↗

[Prevalence of human immunodeficiency virus infection in drug addicts assisted from 1991 to 1996 at a detoxification center in Castilla y Leon].

BACKGROUND: The Word Health Organization (WHO) has recommended epidemiologic surveillance of infection by the human immunodeficiency virus (HIV) in high risk populations. An important decrease has recently been observed in the prevalence of HIV infection in drug addicts in different regions in Spain with notable differences being found. The evolution of the prevalence of HIV infection in intravenous drug addicts initiating detoxication in Castilla and Leon was analyzed. METHODS: Six hundred forty-seven drug addicts (535 males and 112 females) were studied over 6 years (1991-1996) analyzing HIV seropositivity, demographic variables, drug use, age of initiation in drug consumption and route used. RESULTS: Most of the drug addicts were males (83%) with a mean age of initiation in the use of drugs of 19.6 years. Heroine was most frequently consumed in 95% of the patients. The mean length of consumption on admission was 8.6 years with no significant differences being observed in sexes. A relationship was observed between HIV infection and the lower age of initiation in drug usage with the greater the age of admission to detoxication the longer the time having consumed drugs. The prevalence of HIV infection significantly decreased in males and females from 36.8% in 1991 to 17.4% in 1996 (p < 0.0005), with this decrease being related to the change from the intravenous to the smoked route of drug intake. On multivariate analysis by logistic regression the odds ratio at one year of admission was significant (OR = 0.80), years of drug addiction (OR = 1.15), intravenous route (OR = 3.04) and female sex (OR = 2.75). CONCLUSIONS: A significant decrease has been observed in the prevalence of HIV infection in drug addicts in Castilla and León attending a therapeutic center for detoxication from 1991-1996.

Adult↗

[The rapid specific characterization of clinical isolates of the genus Mycobacterium by the polymerase chain reaction and restriction enzyme analysis].

BACKGROUND: Typing at species level of Mycobacterium is usually performed by microbiological and biochemical methods that require a long time and/or sufficient amount of bacteria. Molecular biology can avoid these problems using different techniques. METHODS: A colony growth of the following mycobacteria has been analyzed: M. tuberculosis, M. kansasii, M. avium, M. intracellulare, M. gordonae, M. phlei, M. aurum, M. fortuitum, M. flavescens, M. marinum, M. xenopi, M. nonchromogenicum, M. terrae and M. chelonei. Strains were grown in Löwenstein-Jensen medium. DNA was obtained by proteolytic digestion and fenol extraction. The 16S rRNA gen was amplified by polymerase chain reaction (PCR) and the amplification was digested by HaeIII, HpaII, RsaI and AluI restriction enzymes. Restriction fragment patterns were analyzed by agarose gel electrophoresis and UV transillumination. RESULTS: The combination of the patterns obtained with HpaII and RsaI was sufficient to generate 13 different combined ones. The patterns of M. intracellulare and M. avium were the same. CONCLUSIONS: PCR and restriction enzyme analysis is an useful method for typing at species level of clinical isolates of mycobacteria.

Base Sequence↗

Chronic ventilator use in osteogenesis imperfecta congenita with basilar impression: a case report.

Osteogenesis imperfecta, a rare connective tissue disorder, is known to be associated sometimes with the invagination of the basilar skull. This deformity may disturb respiratory function secondary to brain stem compression and hydrocephalus. In addition, the deformed thoracic cage and fragile ribs make pulmonary care more complicated. A case of 24-year-old man is presented with brain stem compression syndrome secondary to osteogenesis imperfecta congenita with basilar impression. He developed respiratory failure and became tracheostomy positive-pressure ventilator dependent at the age of 21 years. He also suffered multiple skeletal abnormalities and mental retardation, and following the brain stem compression, severe quadriparesis. The patient's condition is stable since he has been using the ventilator and he is currently living in the community.

Adult↗

[Changes in the spectrum of the diseases in patients hospitalized with HIV infection].

BACKGROUND: Infections in subjects with HIV-1 infection are a frequent cause of hospital admission. Knowledge of the entities which most often motivate hospitalization may aid in designing the most appropriate diagnostic and prophylactic strategies. The causes of hospital admission in individuals with risk practices for HIV-1 infection attended in a Department of Infectious Diseases in Madrid over a period of 4 years were analyzed. METHODS: The records of the patients admitted from 1989 to 1992 were retrospectively reviewed. The principal and associated diagnoses which led to hospitalization were considered. The admissions of the two years were compared. RESULTS: Bacterial pneumonias were the principal cause of hospitalization in the 2 years studied. Forty-five percent of the infections leading to hospital admission were not included among those defining AIDS. Tuberculosis was the most frequent opportunistic infection. Admissions due to pulmonary pneumocystosis, tuberculosis, toxoplasmosis, esophageal candidiasis and Kaposi's sarcoma decreased from 1989-1992. To the contrary, disseminated Mycobacterium avium complex infection and systemic infection by cytomegalovirus significantly increased over the same period. The incidence of other diseases such as endocarditis or leishmaniasis remained stable. More than half of the diseases were diagnosed in association with another entity during the same admission. Likewise, an increase in atypical forms of infections thus making diagnosis and treatment more difficult was observed. The first cases of multiresistant tuberculosis, all of rapidly fatal evolution, were identified in 1992. Mean hospital stay increased 30% and the rate of mortality was of 9% in 1989 and rose to 20% in 1992. CONCLUSIONS: The spectrum of infections which led to hospital admission of patients with HIV-1 infection has significantly modified over the last 4 years being related with the generalization of prophylactic medication for some opportunistic infections, the improvement of certain diagnostic techniques and more frequent ambulatory treatment of some diseases. The mean length of stay and hospital mortality have increased in the HIV+ population.

AIDS-Related Opportunistic Infections↗

Influence of exercise on a heart transplant patient.

A treadmill training protocol was implemented to examine the effects of a 12-week exercise program on the physiologic status of a patient who had a heart transplant in 1980. The patient was tested for exercise tolerance before programming, midway through the study, and immediately upon completing endurance training. Maximal METS levels achieved were 3.2 METS, 5.6 METS, and 6.3 METS, respectively. The subject began an anaerobic program consisting of 48 exercise sessions over a three-month period. Exercise sessions were interval in nature, walking at 2.5 mph, 0% grade, three repetitions, five minutes each and increasing to 3.0 mph, 2.5% grade, two repetitions, 15 minutes each. The patient improved from Class III (METS = 3.0), where less than ordinary physical activity causes fatigue, to Class I (METS = 6.5), where ordinary physical activity can be sustained without undue fatigue. These findings suggest that selected heart transplant patients may achieve up to 85% maximum oxygen consumption and maximum heart rate which demonstrates the need for endurance training programs in this population. This form of cardiovascular conditioning has enabled the participant to engage in higher levels of activities of daily living within the community.

Blood Pressure↗