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Biomedical subjects

M Sosa

Publications and source records attributed to M Sosa.

At least 37 records · Page 2Linked to original sources
PubMed2000

The effect of 25-dihydroxyvitamin D on the bone mineral metabolism of elderly women with hip fracture.

As there is little evidence of the efficacy of 25-hydroxyvitamin D3 (25-HCC) in reducing the risk of new fractures in osteoporotic women, we performed an open, prospective study with a follow-up of 1 yr in 58 females over 65 yr of age with osteoporosis and proximal femoral fractures. The patient group received 1 g calcium per day and 10 640 IU 25-HCC per week, while the control group received 1 g calcium daily. Biochemical markers of bone remodelling, serum calcium and parathyroid hormone were determined. Bone mineral density was assessed in the lumbar spine and in the proximal femur by two methods. After 1 yr of treatment, 25-HCC corrected secondary hyperparathyroidism, increased urine calcium excretion, and increased bone mass in the femoral neck, but had no effect upon the appearance of new fractures.

Absorptiometry, Photon↗
PubMed1998

The range of bone mineral density in healthy Canarian women by dual X-ray absorptiometry radiography and quantitative computer tomography.

Bone mass measurements play a crucial role in the diagnosis of osteoporosis. According to a World Health Organization (WHO) Working Group, osteoporosis in women can be diagnosed if the value for bone mineral density (BMD) is 2.5 or more standard deviations below the mean value of a young reference population. This definition obviously requires the availability of normal data, which should ideally be obtained locally. The objective was establish normal values of BMD in the female Canarian population, by dual X-ray absorptiometry (DXA) in the lumbar spine and the proximal femur, and by quantitative computed tomography (QCT) in the lumbar spine, and to study the correlation between the results of both techniques and the changes with age. Seven hundred forty-four Healthy Canarian women, from 20-80 yr old were examined. Measurement of bone density was performed by an Hologic QDR 1000 densitometer (DXA) in the lumbar spine and proximal femur, and by a Toshiba scanner model 600 HQ in the lumbar spine. Both methods show that the peak bone mass is achieved in the fourth decade (30-39 yr). Bone density decreases thereafter with age in the lumbar spine (r = -0.3364 DXA and r = -0.6988 for QCT) and in the femoral neck (r = -0.3988). Bone density mean values obtained by DXA are very similar to those described in Spain and in other European female populations, using the same densitometer. The correlations between both techniques (DXA and QCT) were high and statistically significant (p < 0.001 in every case). Normal values in the normal Canarian women for DXA and QCT are provided. Our results are very similar to those previously described. These two techniques have a close correlation.

Journal Article↗
PubMed1997

The 46-kDa mannose 6-phosphate receptor contains multiple binding sites for clathrin adaptors.

The two known mannose 6-phosphate receptors (MPR46 and MPR300) both mediate the transport of Man-6-P-containing lysosomal proteins to lysosomes. However, the MPRs cannot be detected in lysosomes, instead they recycle between the plasma membrane and endosomes and between endosomes and the trans-Golgi network. Both, endocytosis from the plasma membrane and budding of transport vesicles from the trans-Golgi network involves the interaction of the receptor with the clathrin-coated vesicles-associated protein complexes AP1 and AP2. We have analyzed this interaction between the Golgi-restricted AP1 complex and the plasma membrane-restricted AP2 complex with the MPR46 tail in vitro by using a biosensor. AP1 and AP2 both bind to and dissociate from the MPR46 tail with similar kinetics. Using synthetic peptides corresponding to different MPR receptor tail regions in inhibition and binding studies, a common high affinity binding site for AP1 and AP2 and two separate high affinity binding sites for AP1 and AP2, respectively, were identified.

Adaptor Protein Complex 1↗
PubMed1995

Methyl inosine monophosphate (MIMP) augments T-lymphocyte mitogen responses and reverses various immunosuppressants.

Methyl inosine monophosphate (MIMP) augments preferentially the in vitro responses of human and murine lymphocytes to a T-cell mitogen such as phytohemagglutinin (PHA) and inconsistently to a B-cell mitogen such as pokeweed or lipopolysaccharide (LPS). In a normal interleukin-2-dependent cell line (CTLL), MIMP showed little or no effect on IL-2 action; however, in a murine CTLL line exhibiting impaired responses to IL-2, MIMP stimulated thymidine incorporation and restored the response to IL-2. MIMP augments the PHA responses of both CD4+ and CD8+ human peripheral blood T-cells. The effect of MIMP to augment the PHA response of human lymphocytes is paralleled by the parent molecule, IMP. MIMP, but not IMP, is resistant to hydrolysis by 5'nucleotidase; thus, MIMP appears to be a protected analogue of IMP which is capable of in vivo action. MIMP (100 micrograms/ml) augments the PHA responses of 15 to 24 elderly humans. MIMP also augments the PHA responses of eight HIV-infected pre-AIDS patients but not of eight AIDS patients. When PHA responses of human lymphocytes are suppressed in vitro by an HIV-derived immunosuppressive peptide, interferon alpha, or prostaglandin PGE2, MIMP (0.1-100 micrograms/ml) progressively restores the depressed response; however, when the suppression is severe (greater than 50%), MIMP cannot restore the response. These data indicate that MIMP potentiates normal T-lymphocyte mitogen responses and restores those impaired by a variety of inflammatory and immunosuppressive influences.

Animals↗
PubMed1995

Immunotherapy with natural interleukins and/or thymosin alpha 1 potently augments T-lymphocyte responses of hydrocortisone-treated aged mice.

Cytokines and thymic hormones are thought to play critical roles in the regulation of T-lymphocyte development and function. In an effort to determine the effectiveness of such agents in an immunotherapeutic strategy, we employed aged mice in a hydrocortisone treatment model to generate an immunodeficient state and to study its reconstitution. Mice were given five daily injections of a natural cytokine mixture (NCM), recombinant interleukins (rIL-1, rIL-2) or their combination, thymosin alpha 1 or fraction 5 (T alpha 1, TF5), or the combinations of NCM plus T alpha 1 and of NCM plus TF5. Spleen and thymus weights were obtained and the cellular responses to stimulation in vitro with NCM, IL-1, IL-2 and mitogens (PHA and Con A) were assayed. Both NCM and T alpha 1 in vivo treatment augmented thymocyte and splenocyte in vitro responses to both interleukins and mitogens. Neither treatments with equivalent doses of rIL-1, rIL-2 nor their combination, nor TF5 achieved similar results. Of all the treatments, only NCM plus T alpha 1 augmented spleen weight; none augmented thymus weight. Surface marker analyses of T-lymphocytes and subsets indicate that treatment of mice with NCM plus T alpha 1 increased spleen T-cell numbers of both CD4 and CD8 positive cells significantly. These data indicate that NCM and T alpha 1 alone and in combination may be therapeutically useful to restore T-lymphocyte number or function in secondary immunodeficiency.

Age Factors↗
PubMed1994

Heterologous transformation of Zalerion arboricola.

A heterologous DNA-mediated transformation system was developed for the pneumocandin-producing fungus Z. arboricola that was based on either conferral of hygromycin B resistance or complementation of a nitrate reductase mutant. Hygromycin-resistant transformants were selected with plasmid pCSN43 which contains the E. coli hygromycin B phosphotransferase gene under the control of Aspergillus nidulans trpC transcription signals. Transformation frequencies were about four transformants per microgram of circular DNA and could be improved four- to six-fold by linearizing the transforming DNA. The transformants differed from one another with respect to the copy number of the integrated plasmid and the site of integration. Adding an autonomously-replicating sequence (AMA1) from A. nidulans to pCSN43 enhanced transformation three-fold and produced, in addition, numerous abortive transformants. However, it is unlikely that the AMA1 sequence promoted plasmid replication in Z. arboricola. Nitrate reductase mutants of Z. arboricola were isolated by positive selection on chlorate-containing medium, and one mutant was subsequently transformed with pSTA700 which contains the nitrate reductase gene (niaD) from Cephalosporium acremonium. Introduction of the niaD gene restored sensitivity to chlorate in the mutant; therefore, using the niaD gene as a selectable marker provides a system for both positive and negative selection. To our knowledge, this is the first report describing transformation of a member of the genus Zalerion.

Acremonium↗
PubMed1993

Epidemiology of proximal femoral fracture in Gran Canaria (Canary Islands).

An epidemiological survey of proximal femoral fracture (PFF) was carried out in Gran Canaria (Canary Islands) in 1990. We identified 211 cases of PFF affecting residents, which gave an incidence of 161 per 100,000 per year (92 per 100,000 per year for men and 176 for women). Three quarters of all fractures occurred to residents of urban areas and nearly all fractures were caused by falls indoors. There was a higher incidence in winter than in summer months.

Africa, Western↗
PubMed1992

Mixed interleukins and thymosin fraction V synergistically induce T lymphocyte development in hydrocortisone-treated aged mice.

Analysis of the role of interleukins in T cell ontogeny in vitro indicates that the regulation of T cell development involves interleukins (ILs) as well as thymic hormones (THs). In order to assess their respective roles in T lymphocyte development in vivo, chemically thymectomized mice were treated with ILs and THs. After 2 days of hydrocortisone treatment, aged mice showed acute thymic involution (weight was less than 30% of control) and reduced spleen size (less than 80% of control) with progressive recovery to 8 days. After 2 days of hydrocortisone treatment, adult mice were injected for 5 days with mixed buffy coat interleukins (BC-IL; 50 units IL2 equivalence), purified IL2 (50 units), rIL1 beta (4 ng), and thymosin fraction V (TF5; 100 micrograms). The animals were sacrificed and spleens and thymuses were analyzed for weight, cellularity, T cell number, subsets, and function as determined by proliferative responses to concanavalin A and ILs. BC-IL treatment increased the recovery of spleen and thymus weights and cellularity with corresponding augmentation of number and function of T lymphocytes; neither IL1 or IL2 or their combination had this effect. TF5 had no effect alone but strongly potentiated the effect of BC-IL on T lymphocyte function. These data indicate that BC-IL in combination with thymic peptides potently promotes T lymphocyte development. The combination may be therapeutically relevant for immunorestoration.

Aging↗
PubMed1992

Potentiation of immune responses in mice by a new inosine derivative--methyl inosine monophosphate (MIMP).

Inosine 5'-methyl monophosphate (MIMP) is a new immunomodulator designed to improve upon the activity of other thymomimetic purines. In Balb/c mice, MIMP was assessed for toxicity and activity on immune responses. The lethal dose for half the mice (LD50) exceeded 500 mg/kg of body weight by both the parenteral and oral routes. At doses of 1-100 mg/kg, the mice showed no visible untoward effects. The antibody response of splenocytes to sheep erythrocytes (SRBC) was measured by IgM plaque-forming cells (PFC) in soft agar under optimal conditions of immunization and challenge. MIMP (1-100 mg/kg) was given by both the intraperitoneal and oral routes (gavage) at the time of SRBC injection and 4 days thereafter. The PFC response was found to be significantly augmented. The maximum effect (approximately 2x) was observed at 50 and 100 mg/kg, via intraperitoneal (i.p.) and oral routes, respectively. Increases (maximally 1.5x) in the responses of splenic lymphocytes to mitogen stimulation with phytohemagglutinin (PHA) and concanavalin A (Con A) were observed under similar conditions of MIMP treatment. SRBC-induced delayed-hypersensitivity (DTH) was also measured under optimal conditions. By both i.p. and oral routes, enhancement of DTH response was produced by the lower doses of MIMP (0.01-1 mg/kg). Again, a second peak of optimum stimulation of DTH response was produced by 50 mg/kg of MIMP when administered by both routes. The effect was observed mainly on the sensitization rather than on the expression phase. MIMP qualifies as an effective immunopotentiator in normal mice.

Adjuvants, Immunologic↗
PubMed1992

Methyl inosine monophosphate: a potential immunotherapeutic for early human immunodeficiency virus (HIV) infection.

MIMP is a new thymomimetic purine under development for immunorestorative therapy. Lymphocytes were obtained from eight patients with acquired immunodeficiency disease (AIDS), eight with symptomatic pre-AIDS (ARC), and 22 normal controls and were stimulated in vitro with phytohemagglutinin (PHA). AIDS patients (mean CD4 counts of 40) showed PHA responses less than 10% of control while ARC patients (mean CD4 counts of 544) showed responses approximately 50% of the control responses. MIMP (0.1, 1, 10 and 100 micrograms/ml) progressively augmented the PHA responses in all these groups. The augmentation of the responses of the leukocytes of AIDS patients while statistically significant was minimal. The augmentation of the responses of ARC patients was significant and their maximal responses approached control levels. The effect of 1 micrograms/ml MIMP was comparable with that observed with indomethacin (10(-6) M) and interleukin-2 (IL2 - 4 units/ml) and was additive with each of these stimulants. In a parallel manner, MIMP restored the suppression of control lymphocytes induced by the immunosuppressive 17 amino acid fragment of the P41 peptide of HIV. In vivo experiments showed that MIMP significantly delayed death in a murine FLV AIDS model at a dose of 1 mg/kg by the oral or parenteral route. MIMP is under preclinical development for early HIV disease to forestall progression to AIDS by attenuating virus-induced immunosuppression.

Adjuvants, Immunologic↗
PubMed1985

Influence of trophic substances in the regulation of resting membrane potential and ionic concentration in skeletal muscle.

We studied the ionic and water content and the resting membrane potential of rat extensor digitorum longus EDL muscles at different times after unilateral nerve crush. Intracellular potassium concentration decreased progressively during the 1st week after nerve crush whereas intracellular sodium concentration increased significantly. At about day 10, when functional reinnervation (presence of end-plate potentials and miniature end-plate potentials) was detected, the above changes tended to return to control values. In addition, there was a significant difference between muscles with long and short nerve stumps. These results suggest a neurogenic dependency of muscle hydroelectrolytic composition. The decrease in resting membrane potential was greatest after 6.5 days of denervation when changes in the internal ionic concentration were maximum; however, these ionic changes contributed little to the decrease. The recovery of the resting membrane potential commenced at least 48 h before the first signs of functional reinnervation (10th day). This finding suggested an important contribution of some neurotrophic material in early stages of the reinnervation when nerve-muscle contacts were already established. Later, the contribution of mechanical activity to the restoration of the RMP became apparent (20th day); fibrillation potentials had disappeared by that time.

Animals↗
PubMed1985

[The importance of HLA antigens in alcoholic cirrhosis].

The existence of a relationship between HLA and the possibility of the development of an alcoholic cirrhosis is researched in this paper. This work was done from 1982 to 1984, by the staff of four clinics of the Medicine School of the University of Uruguay. We studied 47 alcoholics with portal cirrhosis, 19 non-cirrhotic alcoholics and 250 healthy nonalcoholic controls. We confirmed with liver biopsy the cirrhosis in the first group and in the second, liver biopsy was performed in order to assure that they had no cirrhosis. Table I shows the histocompatibility antigens which were tested in the 3 groups. Levels of significance were obtained from exact Fisher test with Yates correction for discontinuity; Pc (corrected P) and RR (relative risk) were also determined. In the alcoholics with portal cirrhosis, the HLABW40 showed a Pc less than 0,005 (RR = 3,93). In the non-cirrhotic alcoholics no significative association was found. We conclude that the carrier of the genetic marker HLABW40, has almost 4 times more chances to develop a cirrhosis as consequence of chronic alcoholic abuse. The presence of this marker, in our patients, has no association with the possibility that an individual becomes an alcoholic abuser. We think that if this data are confirmed in a wider study, some guidelines for the prevention of alcoholic cirrhosis may be established.

Adult↗