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Biomedical subjects

D Gonzalez

Publications and source records attributed to D Gonzalez.

At least 19 recordsLinked to original sources
PubMed2006

Peritoneal macrophages suppress T-cell activation by amino acid catabolism.

T-lymphocyte activation triggered by anti-CD3, endogenous or exogenous superantigen, and mitogens was suppressed in a cell-dose-dependent fashion by peritoneal cavity (PerC) leucocytes. Study of lymphocyte-deficient mice and the use of multiparameter fluorescence-activated cell sorter analyses revealed that macrophages were responsible for this form of immune regulation. Interferon-gamma was essential to trigger suppression, which, by enzyme inhibition studies, was shown to be the result of tryptophan and arginine catabolism. These results illustrate that macrophages, which are classically defined by their innate effector function as antigen-presenting cells, have the potential to temper adaptive immunity.

Animals↗
PubMed2005

Comparative study of basiliximab treatment in lung transplantation.

OBJECTIVE: This study compared the incidence of acute or chronic rejection and adverse events in lung transplant patients receiving induction basiliximab versus controls not receiving treatment. MATERIALS AND METHODS: Basiliximab was administered to 15 patients with impaired renal function, advanced age, or high surgical risk, (group I). The mean age was 48.9 years; nine were double-lung and six single-lung grafts. They were compared to 13 lung transplants performed in 2001 (mean age 43.6 years, 11 double lung and two single lung [group II]). RESULTS: The incidence of acute rejection was 13.3% in group I versus 38.5% in group II (P = .19, OR 4.06), with chronic rejection in 20% and 38.5% of cases, respectively (P = .4, OR 2.5). No significant differences were observed in the incidence of infections or malignancies. Nor were there any direct adverse events due to the administration of the drug. The estimated 2-year survival was 80% for group I and 54% for group II (P = .14). CONCLUSIONS: Basiliximab has a trend to reduce the rate of acute and chronic rejection in lung transplant recipients, with no increased incidence of infections or malignancies. The 2-year survival for patients treated with basiliximab was better than the control group, despite including high risk transplant patients.

Adult↗
PubMed2004

HTLV-1 modifies the clinical and immunological response to schistosomiasis.

The immunological response in HTLV-1 infected individuals is characterized by a prominent Type-1 cytokine response with high production of IFN-gamma and TNF-alpha. In contrast, helminthic infections and in particular chronic schistosomiasis are associated with a predominant production of IL-4, IL-5, IL-10 and IL-13. Liver fibrosis is the main pathological finding in schistosomiasis that occurs after many years of infection. This pathology is T cell dependent but the immune response mechanisms are not completely understood. The North-east region of Brazil is endemic for both HTLV-1 and schistosomiasis. In the present study the immune response, clinical severity, and therapeutic response to praziquantel of patients with schistosomiasis coinfected with HTLV-1 were compared with patients infected only with S. mansoni. Patients with HTLV-1 and S. mansoni had lower levels of IL-5 (P < 0.05) and higher levels of IFN-gamma (P < 0.05) in cultures stimulated with S. mansoni antigen and decreased S. mansoni antigen specific IgE levels when compared with patients with schistosomiasis without HTLV-1 coinfection. Liver fibrosis was mild in all HTLV-1 coinfected patients and efficacy of praziquantel was lower in patients dually infected than in patients infected only with S. mansoni.

Adult↗
PubMed2003

Characterization of the RNA-binding activity of VP3, a major structural protein of Infectious bursal disease virus.

Infectious bursal disease virus (IBDV) is the agent of an immune-depressive disease affecting the poultry industry worldwide. Infection of IBDV leads to expression of five mature virus-encoded proteins. Proteolytic processing of the virus-encoded polyprotein generates VP3 which coats the inner surface of the IBDV capsid. In this report, we describe the characterization of the RNA-binding activity of VP3. For these studies, the VP3 coding region was fused to a histidine tag and expressed in insect cells using a recombinant baculovirus. The histidine-tagged VP3 was affinity-purified and used to study its ability to bind RNA molecules using three complementary methods: (i) Northwestern blotting; (ii) binding of VP3 protein-RNA complexes to nitrocellulose membranes; and (iii) electrophoretic mobility shift assays. The results demonstrated that VP3 efficiently bound ssRNA and dsRNA. Under the experimental conditions used in this study, the formation of VP3-RNA complexes did not depend upon the presence of specific RNA sequences. A series of histidine-tagged VP3 deletion mutants spanning the whole VP3 coding region were generated. The use of these mutants revealed that the VP3 RNA-binding domain layed in a highly conserved 69 aa stretch close to the N-terminus of the protein.

Amino Acid Sequence↗
PubMed2001

The World Trade Center attack. Doctors in the fire and police services.

The World Trade Center attack cast some physicians in roles outside their usual hospital practice. The incident required several physicians to function in the dangerous environment of the disaster. Priorities and triage strategies established by the police, emergency medical service and fire departments, while adhered to, required instantaneous modification and upgrading given the vast loss of civilian and rescue personnel lives. Many civilian medical staff presented themselves with good intentions but needed to be placed out of the collapse zone for fear of incurring additional casualties. In addition, problems with re-establishment of command and control, communications, personnel and equipment replacement all impacted on the rescue effort. This article recounts the roles played by the two coauthors during the World Trade Center attack.

Aircraft↗
PubMed2001

Is routine fetal karyotyping necessary for patients undergoing amniocentesis for elevated maternal serum alpha-fetoprotein?

OBJECTIVE: The object of the study was to determine the necessity of routine fetal karyotyping in patients undergoing amniocentesis for elevated maternal serum alpha-fetoprotein (AFP). METHODS: Data were collected retrospectively on patients under age 35 who underwent amniocentesis for elevated maternal serum AFP at the University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey, between 1 January 1986 and 31 March 1995. A total of 537 patients with maternal serum AFP values greater than 2.5 multiples of the median were included in the study. RESULTS: Of 509 patients in the group with normal amniotic fluid AFP, 505 had a normal karyotype (specificity 94.9%, negative predictive value 99.2%). One of 28 patients in the group with an elevated amniotic fluid AFP demonstrated an abnormal karyotype (sensitivity 20%, positive predictive value 3.6%). CONCLUSIONS: Routine fetal chromosomal analysis of amniotic fluid amniocytes may not be necessary in patients with a normal level of amniotic fluid AFP. A fetal karyotype is recommended in those patients with an elevated amniotic fluid AFP.

Adult↗
PubMed2001

Chronic subcutaneous octreotide decreases gastrointestinal blood loss in blue rubber-bleb nevus syndrome.

BACKGROUND: A patient affected by blue rubber-bleb nevus syndrome had chronic gastrointestinal bleeding requiring weekly blood transfusions. Despite multiple surgical and endoscopic procedures to treat the venous malformations, the patient continued to bleed primarily from lesions in the small bowel. Therefore, this patient was treated with octreotide, a somatostatin analog known to decrease splanchnic blood flow and that is used for acute and chronic gastrointestinal bleeding. METHODS: Octreotide therapy, 5.7 microg/kg subcutaneously twice daily, was initiated, and the patient was followed up clinically. Complete blood counts, blood glucose concentration, pancreatic enzyme concentration, liver function tests, and growth hormone concentration were monitored during treatments. RESULTS: During the 4 weeks after initiation of octreotide therapy, hemoglobin concentration was maintained without the need for transfusions. Octreotide decreased the patient's monthly need for blood transfusion from 52 +/- 7 mL. kg-1. mo-1 of packed red blood cells to 23 +/- 7 mL. kg-1. mo-1. She had no detectable side effects or growth inhibition. Other medical interventions including -epsilonaminocaproic acid, nadolol, and total parenteral nutrition with bowel rest were not as effective as octreotide alone. CONCLUSION: Octreotide decreased the patient's need for blood transfusions. Possible mechanisms include altering blood flow to the gastrointestinal tract and direct effects on the venous malformations.

Anemia, Iron-Deficiency↗
PubMed2000

The in vitro inhibitory action of antiprogestin RU486 on LH and FSH secretion in the absence of progesterone in rats is estrogen-dependent.

Previous in vivo findings show that in the virtual absence of progesterone (P), the antiprogestin RU486 reduces LH and FSH secretion in proestrous rats, indicating that activation of P receptor (PR) can occur in the absence of the cognate ligand. The present study investigates, in vitro, whether or not the inhibitory effect of antiprogestin RU486 on gonadotropin secretion in the absence of P is estrous cycle dependent, and whether its specific expression in proestrus mirrors the high estrogen (E2) background. In the first experiment we investigated the effect of RU486 (10 nM) and/or LHRH (10 nM) on LH and FSH secretion in incubated pituitaries collected on each day of the estrous cycle of the rat. In the second experiment, we determined the effect of RU486 and/or LHRH on preovulatory LH and FSH release by pituitaries from female rats that were ovariectomized (OVX), treated with the antiestrogen LY117018-HCL (Eli Lilly & Co.), or injected with 20 micrograms of estradiol benzoate (EB). The third experiment investigated the effect of RU486 and/or LHRH on LH and FSH release by pituitaries collected from intact or EB-treated (0.1 mg/kg over three consecutive days) male rats. RU486 reduced both basal and LHRH-stimulated LH and FSH secretion in proestrous pituitaries from normal 4-day cyclic rats. By contrast, in diestrous pituitaries, RU486 increased both parameters of LH secretion but was without effect on FSH release. RU486 was also without effect in pituitaries collected from rats in estrus or metestrus, or from OVX or antiestrogen-treated rats. Moreover, EB injection or treatment induced the full inhibitory effect of RU486 in pituitaries from female and male rats, respectively. The above results suggested that P occupancy of the receptor is not required for the formation or function of the active receptor and hence for preovulatory LH and FSH secretion, and that this form of PR activation at pituitary level is E2-dependent and not genetically determined.

Animals↗
PubMed2000

Risk of fractures in celiac disease patients: a cross-sectional, case-control study.

OBJECTIVES: Although osteopenia and osteoporosis are well-recognized complications of celiac disease, no controlled studies have been done to assess the prevalence of fractures in a large cohort of patients. The objectives of this study were to determine the prevalence of bone fractures and vertebral deformities in celiacs and to analyze the relationship between fractures and clinical data of patients. METHODS: We studied 165 patients with a well-established diagnosis of celiac disease. A similar number of age- and gender-matched control subjects with functional GI disorders were evaluated. The design of the study was cross-sectional, with a retrospective historical review through a personal interview of all subjects. All patients underwent bone mineral density measurement by dual-energy, x-ray absorptiometry and spinal x-ray. Vertebral deformities were determined by visual inspection of spinal x-rays and by morphometric analysis. RESULTS: Among celiacs, 41 patients (25%) referred have had from one to five fractures in the peripheral skeleton. On the contrary, only 14 (8%) control subjects experienced fractures. This difference was highly significant (odds ratio, 3.5; 95% confidence interval [CI], 1.8-7.2; p<0.0001). Although inspection of spinal x-rays showed evidence of vertebral deformities in the lumbar spine in only two patients, a more detailed examination of lateral x-rays using morphometric criteria detected lumbar spine vertebral deformities in nine (five also had fractures in the peripheral skeleton) and in four controls (odds ratio, 2.8; 95% CI, 0.7-11.5; p = NS). Eighty percent of fractures were detected before the diagnosis of celiac disease or in patients who were noncompliant with the gluten-free diet; only 7% of patients experienced fractures after starting treatment. Regression analysis adjusted for multiple comparisons showed that patients with fractures were diagnosed with celiac disease later (p<0.06) and remained undiagnosed for more prolonged periods (p<0.05). There was a trend, which did not reach statistical significance, for a lower bone mineral density in the lumbar spine and total skeleton among patients with fractures. CONCLUSIONS: This study has demonstrated that patients with celiac disease had a high prevalence of bone fractures in the peripheral skeleton. Most of these events occurred before diagnosis or while patients were noncompliant with gluten-containing diet. Our results suggest that early diagnosis and effective treatment of celiac disease were the most relevant measures to protect patients from the risk of fractures.

Adolescent↗
PubMed1999

The role of nitric oxide in the control of basal and LHRH-stimulated LH secretion.

The gaseous transmitter nitric oxide (NO) appears to be involved in the control of LH secretion and in the modulation of LH responses after stimulation with luteinizing hormone releasing hormone (LHRH), excitatory amino acids (EAAs) and leptin. The regulatory action of NO in the control of LH secretion includes modulation of LHRH release, changes in hypothalamic-pituitary blood flow and direct effects at pituitary level. To determine the net balance of these actions we evaluated (1) the effects of systemic administration of sodium nitroprusside (SNP, a NO donor) and Nw-nitro-L-arginine methyl ester (NAME, a blocker of NO synthase) on basal and LHRH-stimulated LH secretion in intact and ovariectomized females; and (2) the effects of SNP and NAME on LH secreted by dispersed pituitary cells. Finally, since NO is involved in the stimulatory effect of excitatory amino acids (EAAs) on LH secretion, we analyzed the effects of different inhibitors of NO synthase (NOS) in the LH response to kainic acid (KA), an agonist of kainate receptors, in male and female rats, neonatally injected with estradiol that show an increased sensitivity to EAAs. We found that NAME (40 and 60 mg/kg) increases LH secretion in intact and ovariectomized females, while SNP had no effect. The effect of NAME was not mediated through a direct action at pituitary level, since the basal and LHRH-stimulated LH release remained unchanged in presence of NAME. Similarly, basal and LHRH-stimulated LH secretion from dispersed pituitary cells were unaffected by NAME. Finally, the stimulatory effects of KA on LH release were not abolished by NOS inhibitors. In conclusion, our results provide evidence that the global action of NOS inhibitors is an increase in basal LH secretion, through a mechanism that remains to be fully characterized. In addition, our data demonstrate that the KA-stimulated LH secretion is not mediated by an increase in NO generation.

Animals↗
PubMed1999

Mechanism of the stimulatory action of antisteroid RU486 on follicle-stimulating hormone secretion in the cyclic Rat.

These experiments explored the mechanism underlying FSH hypersecretion on estrous afternoon in rats injected with RU486 (RU) on proestrus. Four-day cyclic rats were injected with RU at 12:00 h on proestrus (1 or 4 mg/0.2 ml oil; s.c.), and its effects on LH and FSH secretion at 18:30 h on estrus were compared with those of antiprogestagens ZK299 (ZK) (1 or 4 mg/0.2 ml oil; s.c.) and Org31806 (OR) (2 or 8 mg/0.2 ml oil; s.c.). Additionally, rats treated with RU or nembutal (PB) (60 mg/kg; i.p. at 13:00 h on proestrus) were injected with an LHRH antagonist (LHRHa) at 10:00 h on estrus (1 mg/0.2 ml saline; s.c.) or progesterone (P) (7.7, 15.5 or 30.9 mg/0.2 ml oil; s.c.) on proestrus at 10:00 h in RU-injected rats and at 14:00 h in PB-injected rats. Animals were killed by decapitation at 18:30 h on estrus and serum LH and FSH concentrations were determined. Rats treated with 1 or 4 mg of RU or Org or 4 mg of ZK recorded increased serum FSH on estrous afternoon, while 1 mg ZK had no effect. PB increased mainly serum LH levels and, to a lesser extent, FSH levels. P decreased serum FSH concentrations in both RU- and PB-injected rats. LHRHa reversed the effects of PB on FSH secretions, but reduced FSH hypersecretion induced by RU only. These results are interpreted to mean that, in the absence of proestrous afternoon P-inhibitory action of the neural stimulus controlling LHRH release, FSH secretion on estrous afternoon involves two components: one is LHRH dependent while, in contrast to LH secretion, the other is LHRH independent, and only expressed in a low estrogen background.

Animals↗
PubMed1999

The antiprogestin RU486 dissociates LH and FSH secretion in male rats: evidence for direct action at the pituitary level.

Administration of 4 mg of the antisteroid RU486 over 8 consecutive days to adult male rats dissociated in vivo and in vitro gonadotrophin secretion, increasing FSH and decreasing LH secretion. In subsequent experiments we evaluated the involvement of testicular or adrenal secretory products, as well as hypothalamic LHRH, in the effects of 4 consecutive days of RU486 treatment on the secretion of gonadotrophins. The first day of RU486 injection was designated day 1, subsequent days being numbered consecutively. Groups of rats injected with oil (0.2 ml) or RU486 (4 mg) were: (i) injected s.c. from day 1 to day 4 with the antiandrogen flutamide (10 mg/kg); (ii) bilateral orchidectomized (ORCH) on day 1; and (iii) bilateral adrenalectomized (ADX) on day 1. Controls were given flutamide vehicle or were sham operated. To ascertain whether the secretion of LHRH is involved in the effects of RU486 on gonadotrophin secretion, we measured the LHRH secretion into the pituitary stalk blood vessels at 1100 h on day 5 in oil- or RU486-treated rats. Additional oil- and RU486-treated rats were injected i.p. with 100 ng LHRH at 1000 h on day 5, or s.c. with 1 mg LHRH antagonist (LHRH-ANT) at 1000 h on days 2 and 4. Controls were given saline. All animals were decapitated at 1100 h on day 5, trunk blood collected and serum stored frozen until FSH, LH and testosterone assays.%While ADX had no effect on FSH and LH secretion in either oil- or RU486-treated rats, the removal of androgen negative feedback with flutamide treatment or by ORCH substantially increased serum levels of FSH and LH in both oil- and RU486-treated rats, and thus annulled the effects of RU486. No differences in pituitary stalk plasma LHRH concentrations were found between oil- and RU486-treated rats. Injection of LHRH increased serum FSH and LH concentrations in oil-treated rats but only, and to a lesser extent, LH concentrations in RU486-treated rats. Treatment with LHRH-ANT decreased serum concentrations of FSH and LH in both oil- and RU486-treated rats. These results suggest that RU486 inhibited LHRH-stimulated LH secretion at the pituitary level, and that FSH secretion increased in response to a reduction in the negative feedback of androgen.

Adrenalectomy↗
PubMed1999

Antiprogestins RU486 and ZK299 suppress basal and LHRH-stimulated FSH and LH secretion at pituitary level in the rat in an oestrous cycle stage-dependent manner.

We have previously shown that administration of antiprogestin (AP) type II RU486 to ovariectomized (OVX) rats on the morning of pro-oestrus decreases the magnitude of preovulatory gonadotrophin surge. This suggests that the effect of RU486 on LHRH-dependent gonadotrophin release may be independent of its ability to block progesterone actions. The aim of the present research was to study the possible site of RU486 action and to determine whether the gonadotrophin suppressive effect of APs RU486 and ZK299 is dependent on the oestrogen background. Intact or OVX rats in the morning of pro-oestrus were injected s.c. with 4 mg of RU486 or ZK299 (AP type I) at 0900 h on pro-oestrus. At 1830 h, serum concentration of FSH and LH and median eminence (ME) content of LHRH were determined. In the second experiment, the effect of RU486 and ZK299 on pituitary responsiveness to LHRH (100 ng, i.p.) and ME content of LHRH at 1830 h pentobarbital-blocked intact or OVX rats was evaluated. In the last study, the anterior pituitary release of FSH and LH from pro-oestrus or metoestrus donors incubated with or without LHRH (1, 10 or 100 nM) in the presence or absence of APs (20 nM) was evaluated. Both APs reduced serum FSH and LH levels at 1830 h on pro-oestrus in intact and OVX rats. The suppressive effect on gonadotrophin release brought about by AP treatment was also evidenced in PB-blocked intact and OVX rats. This suggested that the inhibitory effect of APs occurred, at least in part, at pituitary level. Furthermore, in the absence of the natural ligand, APs significantly reduced basal and LHRH-stimulated FSH and LH release from pro-oestrous but not from metoestrus pituitaries. In conclusion, these experiments have shown, both 'in vivo' and 'in vitro', that APs RU486 and ZK299 have suppressive effects at pituitary level on basal and LHRH-stimulated FSH and LH secretion, regardless of their antiprogestagenic activity, in pro-oestrus but not in metoestrus.

Analysis of Variance↗
PubMed1998

Partial laryngectomy as salvage surgery for radiation failures in T1-T2 laryngeal cancer.

BACKGROUND: Radiotherapy is the treatment of choice for early glottic carcinoma. Thirteen percent to 24% of patients require salvage surgery. To evaluate time of recurrence, site, and locoregional control, we retrospectively reviewed 29 patients treated from 1981 to 1996. METHODS: There were 28 men and 1 woman. Mean age was 63 years. Twenty were T1 (69%) and 9 were T2 (31%). Median time of recurrence was 14.5 months. In 14 patients (52%), a partial laryngectomy was done, and 13 patients had a total laryngectomy. Two refused surgery. RESULTS: One patient relapsed after salvage surgery. Five-year survival after salvage surgery was 92%, with no difference between partial and total laryngectomy (p = 0.2). CONCLUSIONS: Recurrences after failure to radiotherapy in T1-T2 glottic carcinoma could be salvaged with partial laryngectomy in 52% of patients, preserving laryngeal function, with adequate tumor control and acceptable morbidity. The selection of the surgical procedure is based on the tumor extension.

Adult↗
PubMed1998

Molybdenum intake of adults in Germany and Mexico.

Molybdenum is an essential micronutrient. It plays a complex role in the ecosystem, because the metal is a part of a cofactor for several important enzymes in human, animal and plant metabolism. The physiological requirement for this element is relatively low. Our investigations were aimed at determining the Mo intake of adults in Germany and Mexico by means of duplicate portion technique. Molybdenum was estimated in the food duplicate samples by inductively coupled plasma atomic emission spectrometry. In 1988, 1992 and 1996 the Mo consumption of humans was investigated in 14 test groups of persons with mixed diets. Each test population consisted of seven men and seven women. Furthermore, in 1996 the Mo intake of 10 female and 10 male vegetarians and of two Mexican test groups was also determined. Different factors, such as sex, time of investigation, location and eating habits have an effect on the individual Mo intake, Molybdenum intake of adults with mixed diets has increased significantly from 1988 to 1996. Furthermore, results of our study showed that Mo intake of German adults differs depending on location and the kind of diet. German women with a mixed diet consumed 89 micrograms d-1 in 1996 and men 100 micrograms d-1. In comparison, female and male vegetarians consumed 179 micrograms d-1 and 170 micrograms d-1, respectively. There was a significant difference in Mo consumption between German and Mexican test persons. Mexican women consumed on average 162 micrograms d-1 and Mexican men 208 micrograms d-1. The Mo requirement of adults amounts to about 25 micrograms d-1. Our investigations showed that the Mo requirement is met by normal intake. An intake of 150 micrograms kg-1 body weight may be toxic for humans. Therefore, people in Germany and Mexico are not endangered by Mo exposure.

Adult↗
PubMed1997

Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin.

BACKGROUND: We conducted a randomized, prospective trial comparing external irradiation with external irradiation plus goserelin (an agonist analogue of gonadotropin-releasing hormone that reduces testosterone secretion) in patients with locally advanced prostate cancer. METHODS: From 1987 to 1995, 415 patients with locally advanced prostate cancer were randomly assigned to receive radiotherapy alone or radiotherapy plus immediate treatment with goserelin. The patients had a median age of 71 years (range, 51 to 80). Patients in both groups received 50 Gy of radiation to the pelvis over a period of five weeks and an additional 20 Gy over an additional two weeks as a prostatic boost. Patients in the combined-treatment group received 3.6 mg of goserelin (Zoladex) subcutaneously every four weeks starting on the first day of irradiation and continuing for three years; those patients also received cyproterone acetate (150 mg orally per day) during the first month of treatment to inhibit the transient rise in testosterone associated with the administration of goserelin. RESULTS: Data were available for analysis on 401 patients. The median follow-up was 45 months. Kaplan-Meier estimates of overall survival at five years were 79 percent (95 percent confidence interval, 72 to 86 percent) in the combined-treatment group and 62 percent (95 percent confidence interval, 52 to 72 percent) in the radiotherapy group (P=0.001). The proportion of surviving patients who were free of disease at five years was 85 percent (95 percent confidence interval, 78 to 92 percent) in the combined-treatment group and 48 percent (95 percent confidence interval, 38 to 58 percent) in the radiotherapy group (P<0.001). CONCLUSIONS: Adjuvant treatment with goserelin, when started simultaneously with external irradiation, improves local control and survival in patients with locally advanced prostate cancer.

Adenocarcinoma↗