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Biomedical subjects

T Lopez

Publications and source records attributed to T Lopez.

At least 37 records · Page 2Linked to original sources
PubMed1999

Vaccination with the extracellular domain of p185neu prevents mammary tumor development in neu transgenic mice.

The HER2/neu oncogene product, p185(HER2/neu), is overexpressed on the surface of many human breast cancers. Strains of transgenic mice have been developed that express the rat neu oncogene in mammary epithelial cells and develop spontaneous mammary tumors that overexpress p185neu. This model provides an ideal system for testing interventions to prevent tumor development. In this study, we immunized neu-transgenic mice with a vaccine consisting of the extracellular domain of p185neu (NeuECD). Immunized mice developed Neu-specific humoral immune responses, as measured by circulating anti-Neu antibodies in their sera, and cellular immune responses, as measured by lymphocyte proliferation to NeuECD in vitro. In addition, the subsequent development of mammary tumors was significantly lower in immunized mice than in controls and vaccine treatment was associated with a significant increase in median survival.

3T3 Cells↗
PubMed1999

Lumbar transplant of neurons genetically modified to secrete galanin reverse pain-like behaviors after partial sciatic nerve injury.

The use of cell lines as biologic "minipumps" to chronically deliver antinociceptive molecules such as the peptide galanin near the pain processing centers of the spinal cord after nerve injury is a newly developing technology for the treatment of neuropathic pain. The neuronal rat cell line, RN33B, derived from E13 brainstem raphe and immortalized with the SV40 temperature-sensitive allele of large T antigen (tsTag), was transfected with rat preprogalanin (GAL) cDNA and the galanin-synthesizing and -secreting cell line, 33GAL.19, was isolated [1]. The 33GAL.19 cells transfected with the GAL gene expressed immunoreactivity (ir) for the GAL protein and synthesized low levels of GAL-ir at permissive temperature (33 degrees C), when the cells were proliferating, and increased GAL-ir during terminal differentiation at non-permissive temperature (39 degrees C) in vitro. A control cell line, 33V.1, RN33B cells transfected with the pCEP4 vector alone and similarly isolated by subcloning, contained no detectible GAL-ir at either temperature in vitro. These cell lines were used as grafts in a model of chronic neuropathic pain induced by unilateral chronic constriction injury (CCI) of the sciatic nerve. Pain-related behaviors, including cold and tactile allodynia and thermal and mechanical hyperalgesia, were evaluated in the affected hindpaw after CCI and transplants. The 33GAL.19 and 33V.1 cells transplanted in the lumbar subarachnoid space near the spinal cord one week after CCI, survived at least seven weeks on the pial surface around the spinal cord and only the 33GAL.19 cells expressed GAL-ir in vivo after transplant. Furthermore, the tactile and cold allodynia and tactile and thermal hyperalgesia induced by CCI was significantly reduced or eliminated during the two to seven week period after grafts of 33GAL.19 cells. The maximal effect on chronic pain behaviors with the GAL grafts occurred one to three weeks after transplantation. Transplants of 33V.1 control cells had no effect on the allodynia and hyperalgesia induced by CCI. These data suggest that a chronically applied, low local dose of galanin supplied by transplanted cells near the lumbar spinal dorsal horn was able to reverse the development of chronic neuropathic pain following CCI. The use of transplants of genetically modified neural cell lines that are able to deliver antinociceptive molecules, such as galanin, offers a safe and novel approach to pain management.

Animals↗
PubMed1997

Effects of aspirin or basic amino acids on collagen cross-links and complications in NIDDM.

OBJECTIVE: To determine if long-term therapy with aspirin or basic amino acids for subjects with NIDDM reduces the severity of clinical complications and/or reduces tissue levels of markers of glycooxidative damage. RESEARCH DESIGN AND METHODS: Subjects with NIDDM were administered either aspirin (100 mg/day) or a combination of basic amino acids consisting of L-arginine (2 g/day) plus L-lysine (0.5 g/day) for 1 year. The study was double-blind and placebo-controlled. The presence and severity of retinopathy, nephropathy, and neuropathy were assessed in all subjects at 4-month intervals, as were serum blood glucose, glycohemoglobin levels, and presence of albuminuria. Collagen cross-linking and collagen glycation were measured in skin collagen obtained by biopsy at the beginning and the end of the study. Skin biopsies were also obtained from age-matched control subjects. RESULTS: Skin samples obtained from NIDDM subjects at the beginning of the study had significantly increased levels of glucitolyllysine, pentosidine, and hydroxypyridinium, as compared with age-matched control subjects. Pentosidine levels were significantly correlated with severity of retinopathy and neuropathy, but not nephropathy. Subjects receiving aspirin, but not amino acids or placebo, had significantly decreased levels of skin pentosidine after 1 year of therapy. CONCLUSIONS: It is concluded that 1) low-dose aspirin may reduce glycooxidative damage in people with NIDDM, and 2) treatment may need to continue for more than 1 year before clinical status improves.

Analysis of Variance↗
PubMed1996

Effect of copper ion on the motility, viability, acrosome reaction and fertilizing capacity of human spermatozoa in vitro.

The objective of this study is to provide additional information on the effect of copper ion (Cu2+) in preventing pregnancy. Human spermatozoa, selected by the swim-up method, were incubated for 0, 5 or 24 h in the presence of 10 ng, 1 microgram, 10 micrograms or 100 micrograms of Cu2+ mL-1 in BWW culture medium, and then evaluated in terms of their motility, viability, acrosome reaction (AR) and the capacity to penetrate zona-free hamster eggs. AR and penetration in zona-free hamster eggs were assessed at 5 h of incubation. Motility, viability and AR in sperm incubated for 5 h were significantly affected by Cu2+ at a concentration of 100 micrograms mL-1, but not at the lower concentrations. Incubation for 24 h did not affect motility and viability of sperm incubated in the presence of concentrations of Cu2+ ranging from 10 ng mL-1 to 10 micrograms mL-1, but a concentration of 100 micrograms mL-1 caused a significant decrease in both parameters. In contrast, the penetration rate of zona-free hamster oocytes significantly decreased compared with that of controls, when only sperm were incubated in the presence of concentrations of Cu2+ ranging from 10 ng mL-1 to 10 micrograms mL-1, and no penetration was observed in the presence of 100 micrograms mL-1 of Cu2+ . When only oocytes were exposed to Cu2+, the penetration rate dropped to 50% of that of the controls. Finally, when both gametes were exposed to Cu2+ before co-incubation, the penetration rate fell to zero for every concentration tested. Results showed that copper, at concentrations similar to those released from intrauterine devices (IUD), affects the fertilizing capacity of human gametes in vitro and interferes with the sperm-oocyte interaction leading to fertilization. These effects suggest that the principle action of Cu2+ released from Cu-IUD is to act as a preconception contraceptive agent when delivered in endometrial and oviducal fluids.

Acrosome↗
PubMed1996

The equivalent renal urea clearance: a new parameter to assess dialysis dose.

BACKGROUND: Currently the total (dialytic plus renal) urea clearance (KT) is computed as Kt/V plus the equivalent Kt/V (KT/VKR) provided by the renal urea clearance (KR). However, KT/VKR is computed with two different formulae, by Gotch and Keshaviah respectively. Moreover Teschan suggested a weekly KT, that is a multiple of Keshaviah's KT. We suggest the equivalent renal urea clearance (EKR), that kinetically quantifies the "time-averaged KT' and is independent of treatment type and schedule. METHODS: Computer simulation has been used to analyse the relationship between EKR, as corrected for urea volume (EKRc), and Kt/V. Data from 66 HD patients, of whom eight were on once-weekly and 11 on twice-weekly HD, had been used to compare EKR with current KTs. RESULTS: For each individual schedule, the relationship between EKRc and Kt/V is linear and each ml/min of KR increases EKR by the same amount. For instance, for thrice-weekly HD patients, EKRc = 1 + 10 x Kt/V: so that, the critical Kt/V values of 0.8 and 1.0 correspond to EKRc values of 9.0 and 11 ml/min respectively, independently from treatment type and schedule. As to the clinical data, all once- and twice-weekly patients had a significant KR and excellent clinical status, but most of them had 9 < or = EKRc < 11 ml/min. After appropriate reconciliation of units, it has been found that kinetic KT was overestimated by about 10-12% (range, 2-23%) by Keshaviah and Teschan's KT, and by about 2-7% (range, 0.3-15%) by Gotch's KT. CONCLUSIONS: EKRc can account for KR and provide guidelines for all types of dialysis treatments: as far as urea is concerned, dialysis adequacy should require EKRc > or = 11 ml/min. However, it is likely that EKRc > or = 9 ml/min could suffice for patients with a substantial residual renal function.

Adult↗
PubMed1995

The empty follicle syndrome: a pharmaceutical industry syndrome.

The purpose of this study is to provide evidence that empty follicle syndrome (EFS) is a result of an abnormality in the in-vivo biological activity of some batches of commercially available human chorionic gonadotrophin (HCG). This is a comparative study between six consecutive in-vitro fertilization (IVF) cases with EFS (study group) and 10 IVF pregnancy cycles (control group). Both groups received the same ovarian stimulation protocol consisting of leuprolide acetate and human menopausal gonadotrophin (HMG). An i.m. injection of 10,000 IU of HCG was administered once follicles had reached 18-20 mm and oestradiol/follicle > or = 16 mm was at least 900 pmol/l. Transvaginal aspiration was performed 36 h later. Plasma HCG prior to and 12 h after i.m. injection as well as the follicular fluid (FF) concentrations of oestradiol, progesterone, luteinizing hormone (LH) and HCG were determined in the study group and controls. The in-vitro biological activity of the batch of HCG used by the EFS cases and the control group was determined using a Leydig cell preparation from adult rats. Furthermore, the plasma clearance rate after i.v. injection of 5000 IU of HCG, from the same batches, was studied in three male volunteers. In the IVF cycles, no HCG was detected in plasma prior to the injection of commercial HCG. After 12 h, no HCG was detected in the study group compared to a mean of 207.5 IU/l (110-360) in controls. Mean FF concentration of LH, HCG, progesterone and oestradiol was 0.9 IU/l, 0 IU/l, 3.1 nmol/ml and 4.4 nmol/ml in EFS compared to 1.0, 98.3, 32.0 and 3.7 in pregnancy cycles. The in-vitro biological activity in both HCG batches was not significantly different; however, immunoreactive HCG used in EFS cases was undetectable in plasma of male volunteers as soon as 10 min after i.v. injection of 5000 IU of HCG. The endocrine abnormalities found in follicular fluids of EFS are not a consequence of an ovarian problem but the result of a lack of exposure to biologically active HCG. The rapid clearance of the drug after i.v. injection and the high affinity of desialylated HCG to liver cells suggest this to be a possible explanation for this infrequent but unfortunate event.

Adult↗
PubMed1995

A modified Two-BUN method for routine urea modeling: clinical validation in 120 patients on a free diet.

Recently, a modified algorithm of the Two-BUN method (MA2p), avoiding dialyzer clearance measurement, was presented for routine assessment of Kt/V and NPCR. To validate MA2p in patients on a free diet (FDP), we studied 120 stable dialysis FDP by measuring Kt/V and NPCR with both MA2p and a modified version of the standard Three-BUN method (MA3p), for the 3 weekly sessions. The NPCR values (g/kg/day), calculated by MA3p for the 3 interdialyses were: 1.286 +/- 0.274, 1.256 +/- 0.276, and 1.116 +/- 0.230, respectively. The correlation coefficient (r) for averaged Kt/V values obtained by the two methods was 0.999 and the percent error (Error%) for MA2p vs. MA3p results ranged from -1.5 to +0.78%. The respective results for NPCR were: r = 0.967, Error% range from -11.7 to +13.9%. In conclusion, MA2p can be safely used in patients on a free diet. The lowest NPCR values were observed during the long interdialysis.

Adult↗
PubMed1994

Major histocompatibility complex-encoded antigen processing gene polymorphism in IDDM.

Susceptibility to insulin-dependent diabetes mellitus (IDDM) is greatly influenced by polymorphisms in the genes of the class II region of the human leukocyte antigen (HLA) complex. The complexity of this genetic association and the lack of a direct proof of involvement of HLA class II genes in human IDDM have continued to support speculation on a possible role of genes encoded in the close vicinity of these loci in IDDM. Because the recently discovered transporter associated with antigen processing (TAP) and large multifunctional protease (LMP) genes are encoded in the HLA class II region and are implicated in the processing of antigenic proteins for presentation by HLA class I molecules, they are additional candidates for a role in IDDM pathogenesis. We have analyzed genomic and coding sequence polymorphisms in the LMP2, TAP1, and TAP2 genes of 77 Danish IDDM patients and 102 control subjects. Although patients and control subjects did not differ in TAP1 and LMP2 alleles, we found a striking absence of the TAP2 allele B (long form) in IDDM patients. An analysis of the TAP2 alleles in individual DR types, however, revealed that this phenomenon is likely to be caused by linkage disequilibrium between the two loci. Thus, polymorphisms in the TAP and LMP genes are unlikely to be associated with IDDM.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Pyrrolizidine alkaloidosis in Argentinian cattle caused by Senecio selloi.

A herd of 135 Aberdeen Angus cows were grazing on pastures containing abundant Senecio selloi in the eastern region of Buenos Aires Province, Argentina. Some undiagnosed deaths were observed during 1989. In 1990 the death count raised to 38 animals, all of them showing the same clinical signs and gross and histopathological lesions. The time from the start of signs to death varied from 2 to 6 d. The most conspicuous signs were distention of the abdominal cavity and moderate icterus of mucous membranes. At necropsy, large amounts of fluid were in the abdominal cavity, there were lesions in the digestive tract, kidneys and mesenteric lymph nodes, and the liver was enlarged and fibrous. Histopathology showed the hepatic parenchyma replaced by fibrous tissue with marked megalocytosis. The signs and lesions were consistent with those produced by pyrrolizidine alkaloids. An abundance of Senecio selloi resulted in a diagnosis of poisoning from this plant. This is the first report of toxicity due to this plant species in Argentina.

Animals↗
PubMed1993

Effect of dietary viscosity on energy intake by breast-fed and non-breast-fed children during and after acute diarrhea.

To determine the effect of dietary viscosity on energy consumption by young children, 56 Peruvian children 9-20 mo of age with acute diarrhea were randomly assigned to either a liquid or semisolid diet, with or without added amylase to reduce viscosity. Intakes of the study diet, breast milk, and other foods were measured for 2 consecutive d during and again after illness. Total 24-h energy intake (chi +/- SD) during diarrhea, 349.4 +/- 121.8 kJ/kg (83.6 +/- 29.1 kcal/kg) was 18% less than intake after recovery, 428.9 +/- 141.0 kJ/kg (102.6 +/- 33.7), P < 0.001. In the ANOVA breast-fed children consumed significantly less total energy (P = 0.008) and energy from the study diet (P = 0.02) than non-breast-fed children. Breast milk intake did not change with illness. There was no significant relationship between viscosity of the study diet and either total energy intake or intake of energy from the study diet. Energy intake by these children was primarily determined by health status and breast-feeding practice, not by dietary viscosity.

Acute Disease↗
PubMed1993

Ryegrass staggers in heifers: a new mycotoxicosis in Argentina.

Aberdeen Angus (AA) and crossbred AA x Hereford 8-9 mo old heifers (560 animals) showed a typical perennial ryegrass (PRG) staggers syndrome after grazing 26 d in a 25-hectare paddock of pure Lolium perenne. Effects were observed in about 50% of the herd. When forced to move, the animals showed incoordination, weakening of the forelimbs, falling on the chest and neck, and moving in this position during the first steps before recovering a normal gait. In severely affected animals all of the 4 limbs had extreme rigidity. All the affected animals had generalized tremors. Twelve days after removal from this pasture the animals had no symptoms. The symptoms described, the pasture conditions (mostly PRG stubble and short PRG green plants in slow growth), a positive mouse bioassay of extracts obtained from the basal part of the PRG plants, and the microscopic finding of Acremonium lolii hyphae in the leaf sheaths of the same plant material produced diagnostic evidence to confirm this as a PRG staggers case, the first reported in Argentina.

Animal Feed↗
PubMed1992

Pregnancy rate in an oocyte donation program.

Oocyte donation programs offer an alternative treatment for infertile women with ovarian failure or abnormal ovarian function. Seventeen cycles of in vitro fertilization and embryo transfer with donated oocytes were performed in 13 women, with a mean age of 34.8 years. The hormonal replacement therapy consisted of a fixed dose of oral estradiol valerate, 6 mg daily, and intramuscular progesterone in oil, 100 mg daily. Estrogen and progesterone were continued for 10 more weeks after embryo transfer if pregnancy was established. After 13 embryo transfers, 8 pregnancies were obtained, for a pregnancy rate per transfer of 61.5%. Today seven pregnancies are progressing normally, including one set of twins. This results suggest that an oocyte donation program using a fixed and simple hormonal replacement therapy is an adequate treatment for these infertile couples.

Adult↗
PubMed1992

Reconciliation between urea kinetics and direct dialysis quantification.

Previous studies comparing urea kinetic model (UKM) and direct dialysate quantification technique (DDQ) found statistically different results as far as the urea distribution volume (V) and protein catabolic rate (PCR) are concerned. In these studies, however, the true values for both the dialyser urea clearance (K) and urea concentration (C) were not used. The aim of this study was to compare UKM and DDQ using for both methods a variable-volume single-pool (VVSP) model as well as plasma water C and effective K. The study was performed during paired filtration dialysis (PFD) sessions because this technique allows bloodless measuring of K. Twenty dialysis patients were studied during a single PFD session. Dialysate and ultrafiltrate C and urea mass transfer rate were measured every 15 min to compute averaged K and total urea removal. Blood samples were obtained as for a three-point UKM, and an iterative technique was used for both methods. The results (means +/- SD) obtained with UKM were as follows: K = 176 +/- 23 ml/min; V = 29986 +/- 7620 ml, PCR = 65 +/- 15 g/day, Kt/V = 1.04 +/- 0.17. These results were not statistically different from those obtained using DDQ. In conclusion, when methodological errors are avoided, DDQ and UKM provide very similar results. This study shows also that PFD is very useful for studying solute kinetics during dialysis.

Female↗