Biomedical subjects

M Rodriguez

Publications and source records attributed to M Rodriguez.

At least 73 records · Page 4Linked to original sources

PubMed2002

Effect of electric and magnetic fields (60 Hz) on production, and levels of growth hormone and insulin-like growth factor 1, in lactating, pregnant cows subjected to short days.

Electric and magnetic fields (EMF) are generated by the transmission of electricity through high tension lines traversing rural areas. Previous studies showed increased dry matter intake (DMI) and fat corrected milk in dairy cows exposed to EMF. Because EMF exposure has been shown to suppress pineal release of melatonin in some species, it was hypothesized that EMF effects resemble those of exposure to long days. Previous studies have shown that DMI and milk production increase in dairy cattle in response to long day photoperiods, and this has been observed in association with increased circulating insulin-like growth factor 1 (IGF-1), but not growth hormone (GH). The hypothesis that EMF act by modifying the response to photoperiod was tested by subjecting dairy cows to controlled EMF exposure while keeping them under short-day conditions. Sixteen lactating, pregnant Holstein cows were exposed to a vertical electric field of 10 kV/m and a horizontal magnetic field of 30 microT in a crossover design with treatment switchback. Two groups of eight cows each were exposed to EMF for 16 h/d in either oftwo sequences. Each sequence consisted of three consecutive 28-d periods. All animals were maintained under short day conditions (8 h light, 16 h dark) during the trial. DMI and plasma IGF-1 were increased (P < 0.01) during EMF exposure (17.03 vs.16.04 kg/d, SE = 0.4; 137 +/- 6 ng/ml vs 126 +/- 6, respectively). The mean GH concentration was not affected, but a treatment x hour interaction was detected, with GH lower for the EMF exposed animals during the first 16 h of the sampling period, and higher for the last 8 h. Overall, the yield of milk or its components was not affected by EMF exposure, but milk yield was significantly higher for the exposed animals during wk 4 of treatment.

Animals↗

PubMed2002

Natural history of acute HCV infection in hemodialysis patients.

AIMS: Chronic liver disease develops in the majority of non-uremic patients with hepatitis C virus (HCV) infection. The aim of this study was to analyze the evolution towards chronic hepatopathy in 19 cases of acute hepatitis C observed in hemodialysis patients from 1990 to 2001. METHODS: A prospective follow-up study on HCV infection was conducted in 3 HD units from April 1990 to June 2001 to study clinical outcomes after acute hepatitis C. A total of 781 patients were tested monthly for alanine aminotransferase and anti-HCV in serum. In this period, 19 patients suffered from acute hepatitis C. Evolution to chronic liver disease in the follow-up was evaluated by means of biochemical (increased ALT) and virological criteria (HCV-RNA+). The transmission mechanism, the apparition of anti-HCV, clinical manifestations and mortality were also investigated. RESULTS: In 15 (78.9%) of the 19 patients, the viremia remained positive (chronic viremia) and 11 patients (57.8%) evolved to chronic liver disease (chronic viremia and high transaminase levels) with a median follow-up of 3 years (range 1 - 6). Five of them who underwent liver biopsies had histologic signs of chronic active hepatitis. One of them (5.2%) evolved to liver cirrhosis in the follow-up. In 4 out of 19 patients (21%) the HCV infection resolved. Although 7 (36.8%) of them died in the follow-up, acute hepatitis C infection was not a short-term independent risk factor of death. CONCLUSIONS: Three years after acute hepatitis C, 87.5% of the hemodialysis patients remained HCV-RNA positive and 56.2% evolved to chronic liver disease. It is important to stress that HCV infection spontaneously cleared in 4 out of 19 patients (21%).

Acute Disease↗

PubMed2001

Antithrombin III prevents early pulmonary dysfunction after lung transplantation in the dog.

BACKGROUND: Ischemia-reperfusion injury with the resulting inflammatory response is a devastating complication of lung transplantation; much of the tissue damage could be diminished by control of the inflammatory response. Recent studies have show that antithrombin III (AT III) has an anti-inflammatory effect in addition to its established role in the regulation of blood coagulation. Thus, we hypothesized that the administration of AT III might help to prevent ischemia-reperfusion injury after lung transplantation. METHODS AND RESULTS: The study was performed in a dog model of orthotopic lung transplantation. Dogs were randomly assigned to receive either vehicle (controls) or AT III. We observed that in control dogs, during the 180-minute period after lung transplantation, the arterial O(2) partial pressure decreased and both the alveolar-arterial O(2) difference and the pulmonary vascular resistance increased. By contrast, these parameters remained unchanged in the group of dogs receiving AT III. Dogs with transplants receiving AT III did not show an increase in cell adhesion molecules, and histological examination revealed almost an absence of inflammatory response. The administration of AT III produced a marked increase in serum prostacyclin (PGI(2)) levels, whereas in control dogs, the PGI(2) levels did not change. The beneficial effect of AT III was not observed when dogs received indomethacin to prevent the stimulation of PGI(2) release by AT III. CONCLUSIONS: Our results demonstrate that AT III prevents ischemia-reperfusion injury in a dog model of lung transplantation and that this effect is conditioned by an increase in PGI(2) production.

6-Ketoprostaglandin F1 alpha↗

PubMed2001

Surgical therapy for tremor in multiple sclerosis: an evaluation of outcome measures.

OBJECTIVE: To assess the reliability, validity, and sensitivity of outcome measures that might be used in a clinical trial of surgery for the treatment of severe tremor associated with MS (MS tremor). METHODS: Nine patients with MS tremor were evaluated before and 3 and 12 months after thalamic surgery (six thalamotomy, three deep brain stimulation). A clinical tremor rating scale (CTRS), a novel quantitative movement analysis technique (QMA), and a variety of measures of disability, neurologic impairment, and quality of life was utilized. RESULTS: Both the CTRS and QMA were reliable measures of tremor and both were sensitive to the improvement in tremor following surgery. However, QMA correlated with disability measures and corresponded better to patient and examiner assessment of surgical results. The disability scales used were insensitive to functional improvements that may follow surgery. The box and blocks test clearly separated three patients who had excellent results from three who had poor results. Baseline QMA values predicted improvement on the box and blocks test. CONCLUSIONS: 1) QMA is a reliable, objective and valid measure of MS tremor that could be used in a clinical trial. 2) The box and blocks test can detect the improvement in prehensile function that follows surgery, but standard disability scales are poorly responsive to this change. 3) Preoperative QMA values may predict which patients are most amenable to functional improvement after surgery.

Adult↗

PubMed2001

Preservation of motor function by inhibition of CD8+ virus peptide-specific T cells in Theiler's virus infection.

Central nervous system-infiltrating CD8+ T cells are potential mediators of neuropathology in models of multiple sclerosis induced by Theiler's murine encephalomyelitis virus (TMEV) infection. C57BL/6 mice mount a vigorous cytotoxic T lymphocyte (CTL) response against the immunodominant virus peptide VP2121-130 and clear TMEV infection. Interferon-g (IFN-g)R-/- mice also mount a strong CTL response against the VP2121-130 epitope, but because of genetic deficiencies in critical IFN-g signaling pathways, they do not clear TMEV infection and develop prominent neurological deficits within 6 wk. This pronounced disease process, coupled with a defined CTL response, provides an ideal model for evaluating the importance of antiviral CTL activity in the development of severe demyelination and loss of motor neuron function. By administering the VP2121-130 peptide before and during TMEV infection, 99% of the VP2121-130-specific CD8+ T cell response was inhibited. No decrease in virus infection was observed. Peptide treatment did result in significantly less motor dysfunction, even when no differences in levels of demyelination were observed. Although most investigators focus on the role of CD4+ T cells in demyelinating disease, these studies are the first to demonstrate a clear contribution of antiviral CD8+ T cells in neurological injury in a chronic-progressive model of multiple sclerosis.

Animals↗

PubMed2001

Progressive depletion of peripheral B lymphocytes in 4-1BB (CD137) ligand/I-Ealpha)-transgenic mice.

Interaction of 4-1BB (CD137) and its ligand (4-1BBL) is thought to positively regulate cell-mediated and humoral immune responses. We have prepared transgenic mouse strains that express 4-1BBL cDNA under the control of MHC class II I-Ealpha promoter. The 4-1BBL-transgenic mice show progressive splenomegaly and selective depletion of B220(+) B cells accompanied with low levels of circulating IgG and defective humoral responses to Ag challenge. In addition, splenocytes from the transgenic mice fail to provide stimulation for allogeneic T cells in both lymphoproliferative and CTL responses in vitro, whereas their T cells remain functionally normal. Our results reveal unexpected functions of 4-1BBL in the regulation of humoral immune responses and Ag presentation.

4-1BB Ligand↗

PubMed2001

Vortices in trapped superfluid fermi gases.

We consider a superfluid of trapped fermionic atoms and study the single vortex solution in the Ginzburg-Landau regime. We define simple analytical estimates for the main characteristics of the system, such as the vortex core size, temperature regimes for the existence of a vortex, and the effects of rotation and interactions with normal fermions. The parameter dependence of the vortex core size (healing length) is found to be essentially different from that of the healing length in metallic superconductors or in trapped atomic Bose-Einstein condensation in the Thomas-Fermi limit. This is an indication of the importance of the confining geometry for the properties of fermionic superfluids.

Journal Article↗

PubMed2001

Synthesis and evaluation of oxodioxolenylmethyl carbamate prodrugs of pseudomycins.

With the aim of increasing therapeutic indexes of novel cyclic depsinonapeptide pseudomycins, we synthesized and evaluated a series of mono-, di-, and trioxodioxolenylmethyl carbamate prodrugs (2 and 4) of pseudomycin B 1 and pseudomycin C' 3. It is rather encouraging to note that several members of the newly synthesized prodrugs described herein (e.g., 2a, 2e, and 4e) exhibited comparable in vivo efficacy to that achieved by the parent compounds, yet free of tail vein irritation and histamine induced toxicity in vivo.

Animals↗

PubMed2001

Prodrugs of 3-amido bearing pseudomycin analogues: novel antifungal agents.

With the aim of identifying safer pseudomycin derivatives, we synthesized and evaluated a number of N-acyloxymethyl carbamate linked prodrugs of 3-amido pseudomycin analogues. To our satisfaction, all of the prodrug-amide combinations prepared exhibited good in vivo efficacy against murine Candidiasis. When evaluated in a dose elevation study, all of the newly synthesized combinations (e.g., 4A, 6A, 8A, and 8B) demonstrated improved toxicity profiles in comparison to their corresponding 3-amides as well as the parent pseudomycin B.

Amides↗

PubMed2001

A randomized trial of intravenous immunoglobulin in inflammatory demyelinating optic neuritis.

OBJECTIVE: To determine whether IV immunoglobulin (IVIg) reverses chronic visual impairment in MS patients with optic neuritis (ON). METHODS: In this double-blind, placebo-controlled Phase II trial, 55 patients with persistent acuity loss after ON were randomized to receive either IVIg 0.4 g/kg daily for 5 days followed by three single infusions monthly for 3 months, or placebo. RESULTS: The trial was terminated by the National Eye Institute because of negative results when 55 of the planned 60 patients had been enrolled. Fifty-two patients completed the scheduled infusions, and 53 patients completed 12 months of follow-up. Analysis of this data indicated that a difference between treatment groups was not observed for the primary outcome measure, improvement in logMAR visual scores at 6 months (p = 0.766). Exploratory secondary analyses suggested that IVIg treatment was associated with improvement in visual function (including logMAR visual scores at 6 months and visual fields at 6 and 12 months) in patients with clinically stable MS during the trial. CONCLUSIONS: IVIg administration does not reverse persistent visual loss from ON to a degree that merits general use.

Adult↗

PubMed2001

Syntheses and antifungal activities of novel 3-amido bearing pseudomycin analogues.

As a result of our core SAR effort, we discovered a large number of 3-amido pseudomycin B (PSB) analogues (e.g., 4e LY448212 and 5b LY448731) that retain good in vitro and in vivo (IP) activities against Candida and Cryptococcus without inherent tail vein irritation. Several dimethylamino termini bearing 3-amides (e.g., 5b) also exhibited improved potency against Aspergillus in vitro. When evaluated in a two-week rat toxicology study, it was found that all animals receiving 4e (up to 75 mg/kg) were found to be normal. On the basis of these observations, we are convinced that it is possible to broaden the antifungal spectrum and improve the safety profile of pseudomycin analogues at the same time.

Amides↗

PubMed2001

Binding of prostaglandins to human PPARgamma: tool assessment and new natural ligands.

The peroxisome proliferator-activated receptors (PPAR) form a family of nuclear receptors with a wide variety of biological roles from adipogenesis to carcinogenesis. More ligands (agonist and antagonist) are needed to explore the multiple functions of PPAR, particularly PPARgamma. In order to complete such ligand screening, a binding test should be assessed versus the classical transactivation reporter gene assay. In the present work, the full-length human PPARgamma protein as well as its ligand binding domain portion were expressed in Escherichia coli. Bacterial membrane preparations expressing those constructs were characterized using a classical binding competition assay [3H]rosiglitazone as the radioligand. When the receptor preparations were soluble, binding had to be measured with a new alternative method. The systems were assessed using a series of reference PPAR (alpha, beta and gamma) ligands. The full-length human PPARgamma fused to glutathione-S-transferase, expressed in E. coli and tested as a bacterial membrane-bound protein led to the most accurate results when compared to the literature. Furthermore, in an attempt to complete the panel of natural PPARgamma ligands, 29 commercially available prostaglandins were screened in the binding assay. Prostaglandins H(1) and H(2) were found to be modest ligands, however as potent as 15Delta(12-14 )prostaglandin J(2). These results were confirmed in the classical transactivation assay. The fact that these three prostaglandins were equally potent, suggests new pathways of PPARgamma-linked gene activation.

Binding Sites↗

PubMed2001

MSP, a trypsin-like serine protease, is abundantly expressed in the human nervous system.

The goal of the present investigation was to determine the regional and cellular specific expression patterns of the newly identified serine protease, myelencephalon-specific protease (MSP), in the adult human brain (Scarisbrick et al. [1997b] J. Neurosci. 17:8156-8168). To assess the potential scope of MSP activity, Northern blot techniques were used to determine the relative abundance of MSP mRNA in 16 different adult human brain regions, and in the brain and peripheral tissues of the midgestation human fetus. The regional and temporal specific expression patterns of MSP mRNA were directly compared with those of tissue plasminogen activator (tPA), a serine protease strongly implicated in the development, ongoing plasticity, and response of the nervous system to injury and disease. mRNA encoding each protease was distributed widely throughout the normal adult human central nervous system (CNS), but the expression of each was only partially overlapping. Additionally, compared with tPA, MSP exhibited a more restricted distribution and delayed developmental onset. By immunohistochemical localization, MSP was present at moderate to high levels in neurons and oligodendroglia of the adult human brain, at a level closely resembling the relative abundance indicated by Northern blot. MSP was most abundantly expressed in the spinal cord, hippocampus, substantia nigra, and basal ganglia. The robust expression of MSP in clinically significant regions of the adult human CNS indicates that further study of this protease in terms of both normal brain physiology and neurodegenerative disorders is warranted.

Adult↗

PubMed2001

Cloning and structural characterization of ECTACC, a new member of the transforming acidic coiled coil (TACC) gene family: cDNA sequence and expression analysis in human microvascular endothelial cells.

Erythropoietin (Epo) transduces mitogenic and chemoattractant signals to human endothelial cells. Identifications of Epo-responsive genes are important for understanding the molecular nature of Epo signaling in endothelial cells. The effects of Epo on differential expression of various genes were examined in human microvascular endothelial cells (HMVEC) by differential display reverse transcriptase polymerase chain reaction (RT-PCR). In the current study we obtained from Epo-treated HMVEC a cDNA fragment with characteristics of the 3' end of mRNA. Using the cDNA fragment, we then selectively isolated a full-length clone by screening an unamplified endothelial cell cDNA library followed by 5' rapid amplification of cDNA ends by polymerase chain reaction (RACE-PCR). The nucleotide sequence of the longest cDNA revealed an open reading frame of 3311 nucleotides that encodes a protein consisting of approximately 906 amino acids with a predicted MW of approximately 100 kDa. The nucleotide sequence of the cDNA is nearly identical to that of transforming acidic coiled coil-containing (TACC2) and anti-zuai-1 (AZU-1) cDNA clones except at the 5'- and 3'-ends. Northern blot analysis showed an increase in endothelial-TACC-related mRNA levels in Epo-treated cells in comparison to that of the control cells. Endothelial-TACC-related mRNA was highly expressed in heart and skeletal muscle tissue. Placenta and brain tissue exhibited low levels of expression of endothelial-TACC-related gene. Southern blot analysis of genomic DNA from somatic cell hybrids showed that endothelial-TACC-related cDNA maps to chromosome 10. Immunofluorescence microscopy and the occurrence of several putative phosphorylation and SH3 binding sites on the deduced protein suggest that endothelial-TACC-related protein may be involved in Epo signaling cascades in endothelial cells.

Amino Acid Sequence↗

PubMed2001

Structure-activity relationship studies of melanin-concentrating hormone (MCH)-related peptide ligands at SLC-1, the human MCH receptor.

Melanin-concentrating hormone (MCH) is a cyclic nonadecapeptide involved in the regulation of feeding behavior, which acts through a G protein-coupled receptor (SLC-1) inhibiting adenylcyclase activity. In this study, 57 analogues of MCH were investigated on the recently cloned human MCH receptor stably expressed in HEK293 cells, on both the inhibition of forskolin-stimulated cAMP production and guanosine-5'-O-(3-[(35)S]thiotriphosphate ([(35)S]- GTPgammaS) binding. The dodecapeptide MCH-(6-17) (MCH ring between Cys(7) and Cys(16), with a single extra amino acid at the N terminus (Arg(6)) and at the C terminus (Trp(17))) was found to be the minimal sequence required for a full and potent agonistic response on cAMP formation and [(35)S]- GTPgammaS binding. We Ala-scanned this dodecapeptide and found that only 3 of 8 amino acids of the ring, namely Met(8), Arg(11), and Tyr(13), were essential to elicit full and potent responses in both tests. Deletions inside the ring led either to inactivity or to poor antagonists with potencies in the micromolar range. Cys(7) and Cys(16) were substituted by Asp and Lys or one of their analogues, in an attempt to replace the disulfide bridge by an amide bond. However, those modifications were deleterious for agonistic activity. In [(35)S]- GTPgammaS binding, these compounds behaved as weak antagonists (K(B) 1-4 microm). Finally, substitution in MCH-(6-17) of 6 out of 12 amino acids by non-natural residues and concomitant replacement of the disulfide bond by an amide bond led to three compounds with potent antagonistic properties (K(B) = 0.1-0.2 microm). Exploitation of these structure-activity relationships should open the way to the design of short and stable MCH peptide antagonists.

Alanine↗

PubMed2001

Clonal evolution in Waldenstrom macroglobulinemia highlights functional role of B-cell receptor.

The course of clonal evolution of 2 related clones in the blood of a patient with Waldenstrom macroglobulinemia (WM) indicates the functional importance for the expression of the B-cell receptor for the survival of these malignant cells. Protein and nucleotide sequencing of the paraproteins' variable regions revealed 2 predominant Vlambda and 2 VH sequences, each set comprised in the ratio 1:1.5. The 2 VH sequences and 2 Vlambda sequences shared the same VDJ and VJ junctional sequences, respectively, indicating that 2 malignant clones had evolved from a common ancestor. This is the first report on intraclonal heterogeneity in WM. Comparison of the Vlambda and VH sequences with the closest matching known germline genes showed that they contained approximately 10 somatic mutations each. The distribution and type of mutations demonstrate that mutations have continued to accumulate in the malignant clones and that selection has been operating to preserve immunoglobulin structure.

Base Sequence↗

PubMed2001

Liposomal doxorubicin in ovarian, peritoneal, and tubal carcinoma: a retrospective comparative study of single-agent dosages.

PURPOSE: The aim of this study was to evaluate the relative activity and tolerance of liposomal doxorubicin in recurrent ovarian, peritoneal, and tubal carcinoma at an initial dose of 40 or 50 mg/m(2) every 4 weeks. METHODS: A retrospective single-institution study was performed on patients who received liposomal doxorubicin from 1/97 to 12/00. Demographic data, liposomal doxorubicin dose, dose reductions, response, and progression-free and overall survival were recorded. RESULTS: Seventy-eight patients, 38 treated at 40 mg/m(2) and 40 treated at 50 mg/m(2), were identified. There was no difference with respect to patient age, performance status, percentage of patients who were platinum resistant or paclitaxel resistant, or tumor bulk. The response rate in this highly resistant population was 13.5 and 7.7% for liposomal doxorubicin at 40 and 50 mg/m(2) every 4 weeks, respectively. Stable disease was observed in 49 and 51% of patients treated with liposomal doxorubicin at a dose of 40 and 50 mg/m(2) every 4 weeks, respectively. The progression-free survival for patients with responding and stable disease was similar. Dose reductions were required in 27.5% of patients treated at 50 mg/m(2) versus no patients treated at 40 mg/m(2) (P < 0.001). Treatment delays due to toxicity were required in 32.5% of patients treated at 50 mg/m(2) versus 16% of patients treated at 40 mg/m(2) (P = 0.14). CONCLUSION: Liposomal doxorubicin at a dose of 40 mg/m(2) appears to be as active as liposomal doxorubicin at a dose of 50 mg/m(2) in ovarian, peritoneal, and tubal carcinoma and is better tolerated based on the frequency of dose reductions and treatment delays.

Adult↗

PubMed2001

Improved therapeutic index of lower dose topotecan chemotherapy in recurrent ovarian cancer.

OBJECTIVE: Topotecan (1.5 mg/m(2)) administered daily for 5 consecutive days of a 21-day cycle is an established chemotherapeutic regimen in recurrent ovarian cancer. However, noncumulative myelosuppression has limited its use by many clinicians. We sought to determine whether a lower dose of topotecan could provide comparable tumor activity and higher tolerability in pretreated ovarian cancer patients. METHODS: A retrospective chart review was conducted on recurrent ovarian, peritoneal, or fallopian tube cancer patients with measurable disease or elevated cancer antigen 125 levels (evaluable disease). Patients were treated with topotecan (1.0 mg/m(2)) given by 30-min intravenous infusion for 5 consecutive days every 21 days until disease progression or unacceptable toxicity. RESULTS: Treatment records from 37 women who had been treated with a median of 3 courses (range, 1 to 17) of lower dose topotecan were evaluated; all were evaluable for tolerability and 36 were evaluable for response. Patients had received a median of 3 (range, 1 to 6) previous treatments. The overall response rate was 22% (8/36); the response rates for patients with evaluable disease and measurable disease were 35.7 (5/14) and 13.6% (3/22), respectively. An additional 8 patients (22%) achieved stable disease. Grade 4 neutropenia, thrombocytopenia, and anemia occurred in 48.6, 5.4, and 5.4% of patients, respectively. Granulocyte colony-stimulating factor support was used in 37% of patients, including 5 who experienced febrile neutropenia. CONCLUSION: Topotecan at 1.0 mg/m(2) x 5 days every 21 days is active in platinum- and paclitaxel-resistant ovarian cancer, with significant improvements in hematologic toxicity. In heavily pretreated patients-topotecan can be safely given at reduced doses without apparent loss of efficacy.

Adult↗