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Biomedical subjects

C Cruz

Publications and source records attributed to C Cruz.

At least 19 recordsLinked to original sources

Evidence that MutY and MutM combine to prevent mutations by an oxidatively damaged form of guanine in DNA.

It has been previously shown both in vivo and in vitro that DNA synthesis past an oxidatively damaged form of guanine, 7,8-dihydro-8-oxoguanine (8-oxoG), can result in the misincorporation of adenine (A) opposite the 8-oxodG. In this study we show that MutY glycosylase is active on a site-specific, oxidatively damaged A/8-oxoG mispair and that it removes the undamaged adenine from this mispair. Strains that lack active MutY protein have elevated rates of G.C----T.A transversions. We find that the mutator phenotype of a mutY strain can be fully complemented by overexpressing MutM protein (Fpg protein) from a plasmid clone. The MutM protein removes 8-oxoG lesions from DNA. In addition, we have isolated a strain with a chromosomal mutation that suppresses the mutY phenotype and found that this suppressor also overexpresses MutM. Finally, a mutY mutM double mutant has a 25- to 75-fold higher mutation rate than either mutator alone. The data strongly suggest that MutY is part of an intricate repair system directed against 8-oxoG lesions in nucleic acids and that the primary function of MutY in vivo is the removal of adenines that are misincorporated opposite 8-oxoG lesions during DNA synthesis.

Bacterial Proteins

HM-PAO spect in head trauma.

Single Photon Emission Computed Tomography (SPECT) after intravenous administration of Technetium-99m hexamethylpropylene-amine oxime (Tc-99m HM-PAO) makes possible the evaluation of cerebral perfusion. We have been assessing the diagnostic accuracy of SPECT in some groups of head trauma patients: the preliminary results of this study are presented. Fourteen patients have been selected, all of them showing some kind of focal neurological deficit; the Computed Tomography (CT) and Nuclear Magnetic Resonance (NMR) were normal, or showed lesions that could not be responsible for the neurological deficits. In all of the patients Tc-99m HM-PAO SPECT has been performed, showing changes in cerebral perfusion in areas correlated with the abnormalities elicited on clinical examination. These results show that Tc-99m HM-PAO SPECT is a better technique than CT or NMR in demonstrating the organic basis of some neurological deficits observed after head trauma.

Adolescent

Captopril magnifies the increase in angiotensin I-converting enzyme activity in rats with aminonucleoside nephrosis.

1. Serum, tissue and urine angiotensin I-converting enzyme (ACE) activity was estimated in the following groups of rats: saline-injected rats (controls); captopril-treated (CAP) control animals (CONTROL-CAP); puromycin aminonucleoside (PAN)-induced nephrotic syndrome (NS); and CAP-treated animals with NS (NS-CAP). 2. Serum ACE activity increased in the CONTROL-CAP, NS, and NS-CAP groups. The increase in the NS-CAP group was significantly higher compared with the NS or CONTROL-CAP groups. 3. In the CONTROL-CAP group, tissue ACE decreased in brain, heart and adrenal glands, and remained unchanged in the lung, testis, kidney, small intestine and liver. In the NS group, tissue ACE activity increased in the lung and testis, decreased in the brain and heart, and remained unchanged in the small intestine, adrenal glands, kidney and liver. Tissue ACE activity increased significantly in the NS-CAP group compared with the other groups. This increase in tissue ACE may contribute to an increase in the serum ACE activity in the NS-CAP group compared with the NS group. 4. Urine ACE activity increased in the NS and NS-CAP groups, although the rise in the NS-CAP group was significantly higher. The urine ACE correlated significantly with the circulating levels of this enzyme in the NS and NS-CAP groups. The loss of ACE in the urine in the presence of an increased serum ACE activity indicates that the biosynthesis of tissue ACE and its release into the bloodstream must be elevated.

Animals

Effect of captopril on urinary excretion of renin and angiotensinogen in aminonucleoside nephrosis.

Puromycin aminonucleoside (PAN)-nephrotic rats show high plasma renin, low plasma angiotensinogen (Angt), and increased urinary excretion of renin and Angt. In this work, we studied the effect of captopril on urinary excretion of total protein, renin, and Angt for 25 days after PAN injection. Captopril had no effect on total protein urinary excretion; however, captopril did enhance the urinary excretion of renin and did decrease the urinary excretion of Angt. This seems to be due to the fact that captopril magnifies the increase in renin and the decrease in Angt in the plasma of PAN-nephrotic rats.

Angiotensinogen

Activity of serum enzymes in puromycin aminonucleoside-induced nephrotic syndrome.

Total serum protein, serum albumin, total urine protein excretion, and the serum activity of several enzymes--aldolase (ALS), cholinesterase (CHS), leucine aminopeptidase (LAP), isocitrate dehydrogenase (ICD), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (HBD), creatine kinase (CK), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT)--were estimated in rats with nephrotic syndrome (NS) at 2, 4, 6, 8, 10, 12, 16, 20, and 30 days after a single injection of puromycin aminonucleoside (PAN). It was found that: (a) total serum protein and serum albumin diminished on day 4 and returned to control values on days 20 and 30, respectively; (b) total urine protein excretion rose on day 4, reached a peak value on day 8, and then fell substantially but still remained higher than control values on day 30; (c) ALS and CHS activities increased; (d) LAP, ICD, and AST activities showed a biphasic pattern, first increasing and then decreasing; (e) ALT, LDH, HBD, CK, and ALP activities decreased; and (f) GGT activity remained unchanged. The differences in the profiles of the enzyme activities suggest their independent regulation in experimental NS induced by PAN.

Animals

[Rearrangement of the bcl1 and bcl2 oncogenes in chronic lymphoid leukemia].

Oncogenes bcl1 and bcl2 are located in the rupture site of t(11;14) and t(14; 18), respectively. They have been found to rearrange in different B-cell malignancies. A molecular study of oncogenes bcl1 and bcl2 was carried out in 42 patients diagnosed of B-cell chronic lymphoid leukaemia. In 14.3% of the patients the rearrangement affected bcl1, but no differences were found with regard to stage and clinical course between these patients and those without any oncogen rearrangement. In all the patients studied bc12 was in a germinal configuration.

Aged

Single center success with a high risk peritoneal dialysis population.

A large end stage renal failure population treated by chronic ambulatory peritoneal dialysis (CAPD) was examined for rates of infection, CAPD modality failure and patient survival (N = 347). Nearly half were considered high risk for survival for reasons of age (39% older than 60 years), diabetes mellitus (33%), hemodialysis access failure (10%), poor cardiopulmonary reserve (16%) or technical challenges (30% had morbid obesity, history of abdominal aortic aneurysm repair or multiple abdominal surgeries). Hence, CAPD was often initiated by default rather than choice in the 347 patients studied (mean age: 51 +/- 17 years). Infections greatly outnumbered technical failures as grounds for cessation of CAPD. Over 5521 patient-months, 51% of patients developed infection with peritonitis predominating (80%) when compared to exit site infections (20%). The frequency of infections was 1.9 mean episodes per patient; however, 55% of these patients had only one episode of peritonitis. A rate of 0.75 infections per patient per year was seen with an average interval of 16 months between infections. Technique and patient survival rates at 4 years were 50% and 61% respectively. High risk status does not preclude successful CAPD and should not preclude its implementation.

Adolescent

Renal malignancy in peritoneal dialysis patients with acquired cystic kidney disease.

A known complication of long-term hemodialysis, acquired cystic kidney disease (ACKD) has been reported infrequently in association with chronic ambulatory peritoneal dialysis (CAPD). The duration of end stage renal failure (ESRF) is thought to correlate with the development of ACKD. Renal cell carcinoma has been reported in 4-10% of patients with ACKD. Two patients on CAPD for more than 6 years without prior hemodialysis treatment developed renal malignancy in the setting of ACKD. Flank and abdominal pain was the presenting symptom in both patients neither of whom had hematuria. Renal ultrasound detected cystic lesions consistent with ACKD; malignant masses were ultimately identified by CT scan. Both patients underwent flank radical nephrectomy, resumed CAPD early in the postoperative period and continue on CAPD 9 and 4 months after surgery. One patient has since developed hepatic metastasis. ACKD is an important risk factor for the development of renal cell carcinoma not only in maintenance hemodialysis patients but also in the CAPD population. A high index of suspicion and serial ultrasound screening for ACKD is warranted in patients with long-term dialysis-dependence.

Carcinoma, Renal Cell

Improved nutritional follow-up of peritoneal dialysis patients with bioelectrical impedance.

A threat to survival in renal failure, malnutrition in continuous ambulatory peritoneal dialysis patients (CAPD) is often occult as CAPD patients often gain weight masking actual protein malnutrition. Bioelectrical impedance (BEI) accurately assesses body composition in CAPD patients and uncovers subtle changes in lean body mass (LBM) that escape indirect anthropometric detection. Segregating parameters of body composition is crucial to nutritional management of CAPD patients in whom fat may account for overall weight gain. While both skin-fold methods and BEI correctly distinguished thin and overweight patients in terms of fat mass, only BEI accurately segregated these patients by LBM (P = 0.007). Serial weights of 39 CAPD patients followed longitudinally for three or more months did not correlate with BEI-measured changes in LBM. LBM was lost in 49% of patients as determined by BEI, while serial weights detected a loss of LBM in 36% of these patients. Strikingly, by serial weights, 64% of patients demonstrated weight gain; however, in 24% of these an actual loss of LBM was demonstrated by BEI. BEI provides specific quantitation of LBM in CAPD patients with changing body habitus and unrecognized nutritional derangement.

Adult

Enhanced peritoneal dialysis delivery with PD-PLUS.

We prospectively studied the effects of enhanced continuous ambulatory peritoneal dialysis (CAPD) on the normalized protein catabolic rate (NPCR) and Kprt/V of two patients with zero residual renal function and marginal or below minimal HCFA values on urea kinetic modeling (Kprt/V = 0.21). Predictable increases in NPCR (from 0.61 to 0.76 and from 0.73 to 0.81 gm/kg/day, respectively) were seen after two weeks of enhanced CAPD achieved by the addition of a fifth nighttime exchange by a portable, easily operable, automated device (PD-PLUS).

Creatinine

Evolution of lipid profiles in long-term peritoneal dialysis.

Serial lipid profiles of 102 patients starting chronic ambulatory peritoneal dialysis (CAPD) in our renal unit from January 1985 to December 1990 were collected retrospectively. Transient triglyceride elevation was noted during the first two years of CAPD but declined to normal levels even lower than those at baseline by 60 months. Total cholesterol, HDL and LDL cholesterol levels did not change significantly. Lipid-lowering agents were begun in 17 patients before initiating CAPD, 5 of whom achieved lipid profiles warranting cessation of therapy. Five other patients started treatment while on CAPD. No statistical difference in patient mortality was found when patients hyperlipidemic at the initiation of CAPD were compared to their normolipemic counterparts. We conclude that the return to normal plasma triglyceride levels after transient triglyceride elevation during long-term CAPD implies that adaptative mechanisms of triglyceride production in response to chronic glucose overload may ensue.

Adolescent

[Health technology in Mexico].

The features of the health technology cycle are presented, and the effects of the demographic, epidemiologic and economic transition on the health technology demand in Mexico are discussed. The main problems of science and technology in the context of a decreasing scientific and technological activity due to the economic crisis and the adjustment policies are also analyzed: administrative and planning problems, low impact of scientific production, limitations of the Mexican private sector, and the obstacles for technology assessment. Finally, this paper also discusses the main support strategies for science and technology implemented by the Mexican government during the 1980s and the challenges and opportunities that lie ahead.

Epidemiology

Serum and urinary ceruloplasmin in experimental nephrotic syndrome.

The levels of ceruloplasmin (Cp) and total protein were measured in serum and urine from rats with experimental nephrotic syndrome (NS) for 20 days after a single injection of puromycin aminonucleoside (PAN). Control values for Cp in serum and urine were: 0.23 +/- 0.01 mg/ml and 0.063 mg/day, and those for total protein were: 7.1 +/- 0.14 g/dl and 2.1 +/- 0.6 mg/day, respectively. It was found that: a) serum Cp decreased on day 6, remained low until day 10 (0.07 +/- 0.01 to 0.08 +/- 0.01 mg/ml), and returned to control levels on day 12; b) total serum protein decreased on day 4, reached the lowest value on day 6 (3.3 +/- 0.3 g/dl) and returned to control levels on day 16; c) Cp in urine increased on day 6, reached a peak value on day 8 (0.62 +/- 0.07 mg/day), then decreased but remained high on day 20; and d) total protein in urine increased on day 5, reached a peak value on day 10 (692 +/- 59 mg/day) and returned to control values on day 20. There was a close association between the levels of Cp and total protein in serum and urine. The decrease of circulating Cp indicates that a typical acute phase response does not occur in the PAN-nephrotic rats. The loss of Cp in the urine of the nephrotic rats may contribute to the decrease in the serum levels of this protein.

Animals

MutM, a protein that prevents G.C----T.A transversions, is formamidopyrimidine-DNA glycosylase.

We have cloned chromosomal DNA bordering an insert that inactivates mutM. Sequencing of this clone has revealed that the insertion element is located between the promoter and structural gene for formamidopyrimidine-DNA glycosylase (Fapy-DNA glycosylase). An overproducing clone of Fapy-DNA glycosylase complements the original mutM strain that had been isolated after EMS mutagenesis. Thus, we conclude that MutM is actually Fapy-DNA glycosylase. mutM has previously been characterized as a mutator strain that leads specifically to G.C----T.A transversions. This in vivo characterization correlates well with the mutagenic potential of one of the lesions Fapy-DNA glycosylase removes, 8-oxo-7,8-dihydro-2'-deoxyguanine (8-OxodG).

8-Hydroxy-2'-Deoxyguanosine

Traumatic interhemispheric subdural haematomas.

According to reports in the literature traumatic interhemispheric subdural haematomas (I.S.H.) are supposed to present acutely or subacutely with contralateral monoparesis of a lower extremity or hemiparesis or in bilateral haematomas even with paraparesis, and to need early operative evacuation. In our series of 5 cases none of them followed this "classical" clinical picture, and three of them recovered without operation. We conclude that the indication for operative evacuation depends on the clinical course and that in patients with spontaneously improving symptomatology non-surgical management under close supervision may be the better solution. Also the C.T. finding of open convexity cisterns may be possible indication for conservative management.

Adolescent

Comparative study of the fatty acid composition of sponges of the genus Ircinia. Identification of the new 23-methyl-5,9-tetracosadienoic acid.

1. The phospholipid fatty acid compositions of the sponges Ircinia strobilina, Ircinia felix, Ircinia campana, Ircinia sp., Spongia tubulifera and Dysidea etherea were studied, revealing the presence, besides other common fatty acids, of considerable amounts (2-5%) of the novel 23-methyl-5,9-tetracosadienoic acid (1). 2. The demospongic acids 5,9-tetracosadienoic acid, 23-methyl-5,9-tetracosadienoic acid (1), and 5,9-pentacosadienoic acid, were particularly abundant in sponges of the genus Ircinia, in contrast to the most common 5,9-hexacosadienoic acid found in other species. These findings are discussed in terms of the taxonomy of the Dictyoceratida. 3. The complete characterization of the novel phospholipid fatty acid 23-methyl-5,9-tetracosadienoic acid (1) is presented.

Animals