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Biomedical subjects

G Gonzalez

Publications and source records attributed to G Gonzalez.

At least 19 recordsLinked to original sources
PubMed1996

Human immunodeficiency virus infection in children with tuberculosis in Santo Domingo, Dominican Republic: prevalence, clinical findings, and response to antituberculosis treatment.

We studied human immunodeficiency virus (HIV)-seroprevalence among children with clinically diagnosed tuberculosis (TB) and compared the clinical features and response to short-term anti-TB therapy of children with and without HIV infection in Santo Domingo, Dominican Republic. Children aged 18-59 months with new-onset, clinically diagnosed TB were tested for HIV antibodies, their clinical features were recorded and their response to a standard 6-month regimen of daily isoniazid and rifampicin with daily streptomycin and pyrazinamide for the first 2 months was assessed. To increase the number of HIV-infected children with TB available for study, we also included children previously known to be HIV infected who developed new-onset TB. Eleven (5.8%) of 189 consecutively enrolled children with clinically diagnosed TB were HIV infected. Fifteen other children with previously documented HIV infection and new-onset TB were available for study, yielding 26 HIV-positive and 178 HIV-negative children with TB. Of these 204 children with clinically diagnosed TB, 25 HIV-positive and 156 HIV-negative children were successfully followed for 6 months or until death. The proportion of HIV-positive children who failed treatment was 6 (29%) of 21 as compared with only 5 (3%) of 156 HIV-negative children [relative risk = 8.9; 95% confidence interval (CI) 2.9, 26.6; p = 0.0004]. HIV-infected children with clinically diagnosed TB are substantially more likely to fail standard treatment for TB than are HIV-uninfected children. If standard treatment regimens are used in such children, response to treatment must be monitored very closely and appropriate changes in the regimen must be made expeditiously.

AIDS Serodiagnosis↗
PubMed1996

Adenosine diphosphate as an intracellular regulator of insulin secretion.

Adenosine triphosphate (ATP)-sensitive potassium (KATP) channels couple the cellular metabolic state to electrical activity and are a critical link between blood glucose concentration and pancreatic insulin secretion. A mutation in the second nucleotide-binding fold (NBF2) of the sulfonylurea receptor (SUR) of an individual diagnosed with persistent hyperinsulinemic hypoglycemia of infancy generated KATP channels that could be opened by diazoxide but not in response to metabolic inhibition. The hamster SUR, containing the analogous mutation, had normal ATP sensitivity, but unlike wild-type channels, inhibition by ATP was not antagonized by adenosine diphosphate (ADP). Additional mutations in NBF2 resulted in the same phenotype, whereas an equivalent mutation in NBF1 showed normal sensitivity to MgADP. Thus, by binding to SUR NBF2 and antagonizing ATP inhibition of KATP++ channels, intracellular MgADP may regulate insulin secretion.

ATP-Binding Cassette Transporters↗
PubMed1996

In vitro antioxidant treatment recovers proliferative responses of anergic CD4+ lymphocytes from human immunodeficiency virus-infected individuals.

Oxidative stress has been proposed to be involved in the immunologic defeat observed in effector calls of the immune system as well as in lymphocyte cell death and viral replication in human immunodeficiency virus (HIV)-infected patients. Because thiol-containing antioxidants such as N-acetyl-L-cysteine have been shown to have beneficial effects on CD4+ lymphocyte survival and to inhibit programmed cell death and HIV-1 replication, they may play a role in therapeutic strategies of this disease. In this work we have studied the cellular thiol levels and the affect of in vitro antioxidant treatment of purified CD4+ lymphocytes from HIV-infected patients, and correlated these parameters to proliferative responses and programmed cell death. We show that CD4+ lymphocytes from HIV-infected patients display impaired proliferative responses and a significant decrease in cellular thiol levels, indicating a disturbed redox status. Interestingly, antioxidant treatment succeeded to restore defective proliferative responses to CD3-mediated activation in 8 of 11 patients (high antioxidant responders). In contrast to high responders, patients failing to respond to antioxidant treatment (low antioxidant responders), were characterized by an abnormal ratio of apoptotic cells, which was not affected by N-acetyl-L-cysteine and/or 2-beta-mercaptoethanol preincubation. These results demonstrate for the first time that antioxidant treatment is able to revert the impaired proliferative activity of CD4 cells from HIV-infected patients and could help designing therapeutic strategies with antioxidant drugs. However, this action is not observed in cells undergoing programmed cell death.

Acetylcysteine↗
PubMed1996

Osteoid osteoma with a multicentric nidus.

A case is reported of a 16-year-old boy who presented with continuous pain in his right leg. Cortical thickening and diffuse medullary sclerosis was revealed on x-ray of the distal tibia. CT imaging showed a circumscribed annular pattern extending some 2.5 cm-s and indicating the multifocal nature of the lesion. The diagnosis of multifocal osteoid osteoma was confirmed after histological examination of the block of resected bone.

Adolescent↗
PubMed1996

Combined intensive chemoradiotherapy for organ preservation in patients with resectable and non-resectable oesophageal cancer.

From January 1990 to April 1993, 60 oesophageal cancer patients were enrolled in a protocol of non-surgical treatment that consisted of induction chemotherapy followed by concurrent chemoradiotherapy. Induction chemotherapy consisted of cisplatin 40 mg/m2 intravenous bolus days 1, 2, 14, 15; 24 h continuous infusion of 5-fluorouracil (5-FU) 1000 mg/m2 days 1 and 14; leucovorin 20 mg/m2 days 1 and 14 given before and with 5-FU; bleomycin 30 UI days 1 and 14; mitomycin C 10 mg/m2 day 14. Concurrent chemoradiotherapy consisted of 60 Gy (6 weeks) from day 21 and cisplatin 70 mg/m2 days 28, 42 and 56; leucovorin 20 mg/m2 followed by 5-FU 425 mg/m2 days 28, 35, 42, 49 and 56. Complete response occurred in 44 of 55 evaluable patients (80%). The median survival is 32 months; the actuarial survival at 40 months is 35% (CI 18-53). These results appear improved over those reported with surgery or radiation alone, and suggest that organ preservation as a secondary treatment goal should be vigorously investigated.

Adult↗
PubMed1996

Nonsteric factors dominate binding of nitric oxide, azide, imidazole, cyanide, and fluoride to the rhizobial heme-based oxygen sensor FixL.

BACKGROUND: The FixL protein is a heme-based sensor. Binding of oxygen to a unique heme domain inhibits a kinase domain of the type found in two-component regulators. Oxygen association is slow, but the dissociation rate is comparable to that of myoglobins. We have probed the size and chemistry of the FixL heme pocket by measuring the affinites, on rates and off rates for a wide variety of ferric heme ligands. Cyanide, but not fluoride, regulates the kinase activity. To examine how the sensory heme domain interacts with the kinase, we asked how the presence of the kinase domain affects ligand binding. RESULTS: The affinities of ferric FixL for heme ligands follow the same trend as their pKa values: cyanide > 4-methyl imidazole > imidazole > fluoride > azide >> thiocyanate. The association rates follow the reverse trend. Striking differences from myoglobin include a 6-fold greater affinity for, and faster binding to, the bulky ligand imidazole, a 14-fold faster on rate for nitric oxide, a 2 800-fold lower affinity for azide, and a complete failure to bind thiocyanate. The presence of the kinase domain does not alter the affinity or binding kinetics of the high-spin ligand fluoride, but affects the off rates of other ligands. The EPR spectrum shows a characteristic pentacoordinate nitrosyl heme, indicating that the Fe-His bond in FixL is strained. CONCLUSIONS: The importance of ligand deprotonation to the on rates and the fact that large ligands bind readily indicate that the heme pocket is open and apolar. Ligand basicity strongly influences the strength of binding. The destabilization of inhibitory ligands by the presence of the kinase domain is consistent with a 'load' imposed by coupling to the inactivating mechanism.

Azides↗
PubMed1996

Assignment of the hyperfine-shifted 1H-NMR signals of the heme in the oxygen sensor FixL from Rhizobium meliloti.

BACKGROUND: [corrected] The Rhizobial oxygen sensor FixL is a hemoprotein with kinase activity. On binding of strong-field ligands, a change of the ferrous or ferric heme iron from high to low spin reversibly inactivates the kinase. This spin-state change and other information on the heme pocket have been inferred from enzymatic assays, absorption spectra and mutagenesis studies. We set out to investigate the spin-state of the FixL heme and to identify the hyperfine-shifted heme-proton signals by NMR spectroscopy. RESULTS: Using one-dimensional NMR we directly observed the high- and low-spin nature of the met- and cyanomet-FixL heme domain, respectively. We determined the hyperfine-shifted 1H-NMR signals of the heme and the proximal histidine by one- and two-dimensional spectroscopy and note the absence of distal histidine signals. CONCLUSIONS: These findings support the spin-state mechanism of FixL regulation. They establish that the site of heme coordination is a histidine residue and strongly suggest that a distal histidine is absent. With a majority of the heme resonances identified, one- and two-dimensional NMR techniques can be extended to provide structural and mechanistic information about the residues that line the heme pocket.

Bacterial Proteins↗
PubMed1996

CD4+ lymphocytes from HIV-infected patients display impaired CD45-associated tyrosine phosphatase activity which is enhanced by anti-oxidants.

It has been proposed that signal transduction defects may, at least partially, account for the functional impairment of CD4+ lymphocytes during HIV-1 infection. Recently, we have demonstrated that unresponsive CD4+ lymphocytes from these patients had reduced protein tyrosine phosphorylation after CD3 engagement, and that this defect was associated with constitutively altered levels of p56lck and p59fyn kinases. Since CD45 is essential for T cell receptor (TCR) and CD2-mediated activation of protein tyrosine kinases, we study here CD45-associated tyrosine phosphatase activity in resting and activated CD4 T cells from HIV-infected patients. We found a significant decrease in the basal and post-activation phosphatase activity of CD45 which correlated well with impairment of proliferative responses. In addition, decreased levels of cellular thiols observed in resting CD4+ lymphocytes from these patients suggested a disturbed redox status. Although expression levels of CD45 were decreased in most patients, a significant recovery of phosphatase activity and proliferative responses was observed in most patients by preincubating cells with N-acetyl-L-cysteine and beta2-mercaptoethanol. In some patients, anti-oxidant treatment failed to significantly enhance phosphatase activity and proliferative responses. The low responses of purified CD4+ lymphocytes from these patients were associated with a high ratio of apoptotic cell death which did not appear to be influenced by anti-oxidant treatment.

Apoptosis↗
PubMed1996

Pericardial cyst. Surgical resection in two symptomatic cases.

Two cases of surgical resection of symptomatic pericardial cysts are reported. Pathological aspects, diagnostic methods and alternatives of management in these benign lesions are discussed. Other excised cases are also mentioned. The authors recommend excision of these cysts in all patients with a low risk in order to: 1) eliminate the tumour mass, 2) relieve symptoms and 3) allow histological examination.

Adolescent↗
PubMed1996

Biofilm formation by Acinetobacter baumannii.

Acinetobacter baumannii, an important nosocomial pathogen is usually found on various surfaces in the hospital environment. In this work, the ability to form biofilms on the surface of sterile coverslips by one clinical isolate of A. baumannii was studied. Sessile cells which adhered to coverslips after being immersed in a nutrient-deficient mineral medium were observed by epifluorescence and scanning electron microscopy at various times of incubation. A rapid increase in the number of sessile cells in young biofilms, followed by a slower increase of such cells was found. At 48 h biofilms were clearly visible and an amorphous material similar to the exopolysaccharide described in some other bacteria covered sessile cells was evident. Biofilm formation by A. baumannii probably favours its maintenance on solid surfaces in the hospital environment and protects the micro-organism against some antibacterial factors.

Acinetobacter↗
PubMed1995

Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor.

A member of the inwardly rectifying potassium channel family was cloned here. The channel, called BIR (Kir6.2), was expressed in large amounts in rat pancreatic islets and glucose-responsive insulin-secreting cell lines. Coexpression with the sulfonylurea receptor SUR reconstituted an inwardly rectifying potassium conductance of 76 picosiemens that was sensitive to adenosine triphosphate (ATP) (IKATP) and was inhibited by sulfonylureas and activated by diazoxide. The data indicate that these pancreatic beta cell potassium channels are a complex composed of at least two subunits--BIR, a member of the inward rectifier potassium channel family, and SUR, a member of the ATP-binding cassette superfamily. Gene mapping data show that these two potassium channel subunit genes are clustered on human chromosome 11 at position 11p15.1.

ATP-Binding Cassette Transporters↗
PubMed1995

Remodelling of lipoproteins in transgenic mice expressing human cholesteryl ester transfer protein.

Cholesteryl ester transfer protein (CETP) facilitates the transfer of reciprocal exchange of neutral lipids between lipoproteins. To better understand the function of CETP and its role in atherogenic pathways, transgenic mice which express human CETP were generated. The transgene encoding human CETP was under the control of the mouse alpha-fetoprotein enhancer and mouse albumin gene promoter and was expressed exclusively in the liver. The level of human CETP activity in transgenic mouse plasmas was found to be 1- to 5-fold greater than in normolipidemic human plasma. Human CETP induced an approx. 30 and 40% reduction of HDL cholesterol levels in plasma from female and male transgenic mice, respectively, when compared to controls. In addition, multiple alterations in mouse lipoprotein composition were observed in the transgenic mice. Diminished HDL cholesterol levels and disappearance of the apo E-rich HDL1 moiety account for the dramatic reduction in plasma cholesterol. The decrease in HDL cholesterol was accompanied by a marked reduction in HDL particle size and apo A-I content. The cholesterol content and the size of LDL particles increased, but only modestly, in transgenic mouse plasma. In conclusion, human CETP induces a significant remodelling of mouse lipoproteins which results in dramatic reduction in plasma cholesterol levels.

Animals↗
PubMed1995

[Infectious complications of implantable catheters in HIV infected patients. Retrospective study of 46 patients].

OBJECTIVES: Investigate the rate of infection in HIV positive patients with an implantable venous access device. METHODS: Forty-six totally implantable venous access devices (port-a-cath, PAC) were inserted in 46 HIV infected patients between January 1990 and May 1992. We analyzed the rate of infectious complications and tried to find predictive factors. RESULTS: There were five infectious complications in five patients. The total complication rate was 0.06 per 100 catheter days. Staphylococcus aureus was responsible in two cases, Staphylococcus epidermidis was responsible in one case and Acinetobacter in one case. No predictive factor was recognized. CONCLUSION: The rate of PAC infection was lower than in other published studies concerning HIV-infected patients. Totally implantable central venous access devices play an increasingly important role in the clinical management of HIV-related diseases. We have shown that the PAC device is safe and convenient in HIV-infected patients.

AIDS-Related Opportunistic Infections↗
PubMed1995

Identification and biotyping of Acinetobacter spp. isolated in Chilean hospitals.

Two hundred and eighty-one isolates of Acinetobacter spp. obtained from clinical specimens in hospitals from five Chilean cities were identified to species level and biotyped. Respiratory tract and wound secretions were the main sources of the isolates. Acinetobacter baumannii was the most frequent species (96.8%), followed by Acinetobacter genospecies 3 (2.8%). Twelve different biotypes of A. baumannii strains were found of which biotypes 9, 8 and 6 were the most frequent. Isolates of other biotypes were rare. These results differ from most other Latin American and European countries.

Acinetobacter↗
PubMed1995

Comparison of newer laparoscopic port closure techniques in the porcine model.

Obtaining a precise fascial closure of larger laparoscopic port sites presents an ongoing challenge for even the most experienced laparoscopic surgeons. To this end, we evaluated five new methods for closing laparoscopic port sites and compared these with the standard technique of a hand-sutured repair using a 0 absorbable suture in the pig. The new devices studied were the Carter-Thomason Needle-Point Suture Passer (CTNSP), the eXit Disposable Puncture Closure (EDPC) device, the Maciol suture needle (MSN) set, the Endoclose suture carrier, and a nonpropreitary technique using a long 14-gauge Angiocatheter and a looped Prolene suture. Unlike the typical clinical situation, the fascia of the pig lies extremely close to the skin; hence, the sutured closure could be routinely performed most quickly of all. Among the newer techniques, the CTNSP provided the quickest closure. The Endoclose, MSN, and 14-gauge Angiocatheter techniques required the use of an auxiliary grasper, which appeared to slow the closure. Only the EDPC provided an airtight closure in 100% of cases. Of the new techniques, the 14-gauge Angiocatheter technique was the least expensive ($3). The efficacy of these techniques in the clinical realm needs to be assessed by a randomized trial.

Animals↗
PubMed1995

[Medical treatment of 44 patients with anal canal carcinoma. Argentinian Intergroup for the treatment of gastrointestinal tumors (IATTGI)].

In order to investigate the medical treatment of anal canal carcinoma (ACC), 27 patients (pts) were treated with cisplatin, fluorouracil and radiotherapy, in an alternating schedule. Eleven pts received mitomycin C, fluorouracil and radiotherapy, in a concurrent scheme. Finally, six pts were included in a new outpatient scheme with cisplatin, fluorouracil, leucovorin, mitomycin C and concurrent radiotherapy. Within the first schedule, 25 pts were evaluable and 18 achieved complete response. All of them are disease free until now. With the second scheme, 7/10 pts had a complete response and 5 of them are alive and disease free. All the pts included in the last schedule (6/6) achieved complete remission. There were no deaths related to toxicity. Our experience is one of the earliest in oncology using cisplatin as a first line drug, in the non-surgical treatment of ACC. We think that the use of cisplatin is feasible, its toxicity is manageable, and its effectivity is similar to other schedules, as observed in our last scheme.

Adult↗