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Biomedical subjects

M Diaz

Publications and source records attributed to M Diaz.

At least 37 records · Page 2Linked to original sources
PubMed2001

The translesion DNA polymerase zeta plays a major role in Ig and bcl-6 somatic hypermutation.

Ig somatic mutations would be introduced by a polymerase (pol) while repairing DNA outside main DNA replication. We show that human B cells constitutively express the translesion pol zeta, which effectively extends DNA past mismatched bases (mispair extender), and pol eta, which bypasses DNA lesions in an error-free fashion. Upon B cell receptor (BCR) engagement and coculture with activated CD4+ T cells, these lymphocytes upregulated pol zeta, downregulated pol eta, and mutated the Ig and bcl-6 genes. Inhibition of the pol zeta REV3 catalytic subunit by specific phosphorothioate-modified oligonucleotides impaired Ig and bcl-6 hypermutation and UV damage-induced DNA mutagenesis, without affecting cell cycle or viability. Thus, pol zeta plays a critical role in Ig and bcl-6 hypermutation, perhaps facilitated by the downregulation of pol eta.

B-Lymphocytes↗
PubMed2001

Bioelectrical impedance analysis of the body composition of Nigerian children with calcium-deficiency rickets.

Children with calcium-deficiency rickets experience increased urinary excretion of both essential and non-essential amino acids compared to non-rachitic children of the same age. Chronic wastage of amino acids into the urine could lead to a deficit in fat-free mass (FFM) in rachitic children. We therefore determined the FFM of children with calcium-deficiency rickets in northern Nigeria using bioelectrical impedance analysis. Because of the leg deformities present in the rachitic subjects, we calculated a 'corrected' height for each rachitic subject using the relationship between arm length and height in non-rachitic subjects over the same age range (r = 0.94). A total of 28 children (4 male and 24 female), 2-9 years of age with calcium-deficiency rickets and an equal number of age- and gender-matched controls were recruited into the study. Resistance and reactance measurements were obtained for all subjects and the total body water was calculated using age-specific equations. FFM was then calculated using age- and gender-specific hydration constants. No significant differences were found in the weights or FFM between the rachitic subjects and the controls (8.41 kg +/- 2.19 vs. 8.85 kg +/- 1.90, respectively). We conclude that chronic urinary wastage of amino acids by rachitic children does not result in a deficit in FFM.

Amino Acids↗
PubMed2001

Consecutive light microscopy, scanning-transmission electron microscopy and transmission electron microscopy of traumatic human brain oedema and ischaemic brain damage.

Cortical biopsies of 11 patients with traumatic brain oedema were consecutively studied by light microscopy (LM) using thick plastic sections, scanning-transmission electron microscopy ((S)TEM) using semithin plastic sections and transmission electron microscopy (TEM) using ultrathin sections. Samples were glutaraldehyde-osmium fixed and embedded in Araldite or Epon. Thick sections were stained with toluidine-blue for light microscopy. Semithin sections were examined unstained and uncoated for (S)TEM. Ultrathin sections were stained with uranyl and lead. Perivascular haemorrhages and perivascular extravasation of proteinaceous oedema fluid were observed in both moderate and severe oedema. Ischaemic pyramidal and non-pyramidal nerve cells appeared shrunken, electron dense and with enlargement of intracytoplasmic membrane compartment. Notably swollen astrocytes were observed in all samples examined. Glycogen-rich and glycogen-depleted astrocytes were identified in anoxic-ischaemic regions. Dark and hydropic satellite, interfascicular and perivascular oligodendrocytes were also found. The status spongiosus of severely oedematous brain parenchyma observed by LM and (S)TEM was correlated with the enlarged extracellular space and disrupted neuropil observed by TEM. The (S)TEM is recommended as a suitable technique for studying pathological processes in the central nervous system and as an informative adjunct to LM and TEM.

Adolescent↗
PubMed2001

Hormone replacement therapy. Knowledge, attitudes and practices of women attending a gynaecology outpatient clinic in Trinidad.

A questionnaire was used to assess the knowledge, attitudes, and practices of a sample of 218 outpatients attending the Port of Spain General Hospital Gynaecology Outpatient Clinic. The questionnaire investigated women's knowledge of menopause, risks and benefits of Hormone Replacement Therapy (HRT), their attitudes concerning HRT and menopause as well as practices of postmenopausal women with respect to HRT. Comparisons were made between women of differing menopausal status, educational background and ethnicity. The results showed that overall knowledge was lacking regardless of menopausal status, ethnicity or educational background. Less educated women were more inclined to believe that HRT was inappropriate principally because they regarded the menopause as a natural process (p = 0.023). Only 24% of postmenopausal women were practicing some form of HRT. A minority (7%) had previously been undergoing the therapy but had stopped. Most postmenopausal women (69%) simply never considered treatment because the majority had never heard about HRT. The main source of patient information was from the clinic they were attending. This study reveals low awareness of menopausal information and therapeutic options in a Trinidadian population. A targeted education programme may substantially fill this void.

Adult↗
PubMed2000

A selective optical sensor based on [9]mercuracarborand-3, a new type of ionophore with a chloride complexing cavity.

A highly selective optical sensor for chloride, based on the multidentate Lewis acid ionophore [9]mercuracarborand-3, is described herein. This sensor is constructed by embedding the mercuracarborand ionophore, a suitable pH-sensitive lipophilic dye, and lipophilic cationic sites in a plasticized polymeric membrane. The multiple complementary interactions offered by the preorganized complexing cavity of [9]mercuracarborand-3 is shown to control the anion selectivity pattern of the optical film. The film exhibits a significantly enhanced selectivity for chloride over a variety of lipophilic anions such as perchlorate, nitrate, salicylate, and thiocyanate. Furthermore, the optical selectivity coefficients obtained for chloride over other biologically relevant anions are shown to meet the selectivity requirements for the determination of chloride in physiological fluids, unlike previously reported chloride optical sensors. In addition, the optical film responds to chloride reversibly over a wide dynamic range (16 microM-136 mM) with fast response and recovery times.

Algorithms↗
PubMed2000

Insulin-like growth factor-I reverts testicular atrophy in rats with advanced cirrhosis.

The pathogenesis of hypogonadism in cirrhosis is not completely understood. The levels of insulin-like growth factor-I (IGF-I), an anabolic factor with trophic actions on testes, are reduced in cirrhosis. This study was undertaken to evaluate whether rats with advanced cirrhosis develop hypogonadism and whether the administration of IGF-I exerts beneficial effects on testicular structure and function. Wistar rats with ascitic cirrhosis induced with CCl(4) were allocated into 2 groups (n = 10, each) to receive recombinant IGF-I (20 microg x kg(-1) x d(-1), subcutaneously) or vehicle for 3 weeks. Healthy rats receiving vehicle were used as the control group (n = 10). At baseline, both cirrhotic groups showed similar deterioration of liver function tests. Compared with controls, nontreated cirrhotic rats showed decreased serum levels of IGF-I (P <.05), reduced testicular size and weight (P <.001), and intense histopathological testicular abnormalities, including reduced tubular diameters (P <.001), loss of the germinal line (P <. 001), and diminutions in cellular proliferation, spermatogenesis (P <.001), and testicular transferrin expression (P <.001). In addition, low serum testosterone (P <.01) and high serum LH (P <.01) were present in untreated cirrhotic animals. Cirrhotic rats that received IGF-I showed full recovery of testicular size and weight and of all histopathological abnormalities (P <.001 to <.01 vs. nontreated cirrhotic rats; P = ns vs. controls). Serum levels of sex hormones tended to normalize. In conclusion, IGF-I deficiency may play a pathogenetic role in hypogonadism of cirrhosis. Low doses of IGF-I for a short period of time revert testicular atrophy and appear to improve hypogonadism in advanced experimental cirrhosis.

Animals↗
PubMed2000

Maternal bone lead contribution to blood lead during and after pregnancy.

We examined bone lead contribution to blood lead in a group of 311 immigrant women, 99% from Latin America, during the third trimester of pregnancy and 1 to 2 months after delivery. We measured in vivo tibia and calcaneus (heel) bone lead concentration in the postdelivery period with K shell X-ray fluorescence. Prenatal and postnatal geometric mean (range) blood lead level was 2.2 microg/dL (0.4 to 38.7) and 2.8 microg/dL (0.4 to 25.4), reflecting low current exposure. Postnatal blood lead level was significantly higher than prenatal (P<0.0001). Mean (range) tibia and calcaneus lead concentration was 6.7 microg/g (-33.7 to 62.2) and 8.4 microg/g (- 30.1 to 66.4), reflecting varying but elevated past lead exposure. Mean calcaneus lead concentration was significantly higher than mean tibia lead concentration (P = 0.055). Variance-weighted multiple regression and structural equation models showed that both calcaneus and tibia lead were directly associated with prenatal blood lead but only calcaneus lead was associated with postnatal blood lead. Increasing natural log years in the United States independently predicted decreasing calcaneus and third-trimester blood lead. The data suggest that while some exogenous lead sources and modulators of blood lead level, such as use of lead-glazed pottery and calcium in the diet, control lead exposure during and after pregnancy, endogenous lead sources from past exposure before immigration continue to influence blood lead levels in this sample.

Adolescent↗
PubMed2000

L-Carnitine effects on chemical composition of plasma lipoproteins of rabbits fed with normal and high cholesterol diets.

L-Carnitine plays an important role in the mitochondrial uptake of long-chain fatty acids in mammals. It has recently been shown that this compound has a marked hypo-cholesterolemic effect when used in conjunction with lipid-rich diets. The aim of this study was to investigate the effects of L-carnitine on the fatty acid composition of plasma lipoproteins in rabbits fed with different diets. Four different groups were investigated: group I (standard diet), group II (standard diet supplemented with L-carnitine at 80 mg/kg), group III (standard diet supplemented with 0.5% cholesterol), and group IV (standard diet supplemented with 0.5% cholesterol plus L-carnitine at 80 mg/kg). The feeding period was 126 d. Total plasma cholesterol was indistinguishable in groups I and II, but increased nearly 40-fold in group III. This increment was reduced by 50% in group IV. Correspondingly, total cholesterol content in lipoprotein fractions [very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) separated by agarose gel chromatography was the same for groups I and II, while for animals fed a cholesterol-rich diet (III) total cholesterol in VLDL + LDL increased nearly 100-fold when compared with groups I and II but, again, the increment was reduced by 50% in group IV. In contrast, total cholesterol in HDL increased only fivefold for both groups III and IV when compared with groups I and II, indicating no effects of L-carnitine on this parameter. The reduction of total cholesterol in VLDL + LDL particles in animals fed a cholesterol-rich diet plus L-carnitine was associated with a marked decrease in the ratio of cholesteryl ester to free cholesterol and a dramatic increase in their phospholipid content; opposite effects were observed for HDL. L-Carnitine induced a marked decrease in the saturated to unsaturated C16 + C18 fatty acid ratio in cholesteryl esters associated with VLDL and LDL from animals fed with both normal and cholesterol-rich diets. The opposite effect (a large increase in the saturated to unsaturated fatty acid ratio) was observed for both cholesteryl esters and phospholipids associated with HDL in animals fed with both diets. The results suggested that the hypocholesterolemic effects of L-carnitine could be associated with increased systemic breakdown of cholesteryl esters, a probable increase in reverse cholesterol transport, and the stabilization of a phospholipid-based structure of VLDL + LDL particles.

Animals↗
PubMed2000

Two MSA 2 peptides that bind to human red blood cells are relevant to Plasmodium falciparum merozoite invasion.

Plasmodium falciparum merozoite membrane surface antigen 2 (MSA2) has been associated with the development of protective immunity against malaria. MSA2 antibodies were able to inhibit in vitro merozoite invasion. In our search for experimental evidence concerning the participation of MSA2 in merozoite invasion, 40 peptides were synthesized according to sequences reported for the CAMP and FC27 prototype Plasmodium strains. These peptides were purified, 125I-radiolabeled and tested for their ability to bind to erythrocytes. Two MSA2 synthetic peptides with high specific binding to human erythrocytes were found. The peptide coded 4044 (KNESKYSNTFINNAYNMSIR), located in the MSA2 N-terminal conserved region, has an affinity coefficient of 72 nM and showed a positive cooperativity for the receptor-ligand interaction. The other peptide, coded 4053 (NPNHKNAETNPKGKGEVQKP) and located in the central variable region of MSA2, has an affinity coefficient of 49nM and also showed a positive cooperativity for the receptor-ligand interaction. The binding capacity of these peptides is affected by erythrocytes treated with neuraminidase and trypsin, but it is not affected by chymotrypsin. Both of these sequences inhibit in vitro erythrocyte parasite invasion by up to 95% suggesting that they have an important role in the parasite's invasion process. Furthermore, as published previously [A. Saul et al. (1992) J. Immunol., 148, 208-211], a protective B epitope is included in the 4044 peptide sequence.

Animals↗
PubMed2000

Inflammatory fibroid polyp of the esophagus.

The case of a 76-year-old woman with a submucosal tumor of the esophagus, whose principal symptoms were dysphagia and epigastric/retrosternal pain, is reported here. Endoscopy, barium swallow and a CAT scan all pointed to extramucosal localization. The lesion was located in the lower esophagus lying on the stomach fundus. An ulcer in the region of the cardia complicated the tumor. Two sets of conventional biopsies failed to detect malignancy, only inflammation and intestinal metaplasia were seen in the specimens of the mucosa surrounding the ulcer. The endoscopic ultrasonographic findings were an indistinct margin, hypoechogenicity, homogeneous appearance and location within the second and third echographic layer. The surgical resection of the tumor was complemented by an anterior partial fundoplication. The histologic study revealed an inflammatory fibroid polyp, which is a rare, benign, non-capsulated submucosal lesion composed mainly of loose connective tissue and vessels, with an eosinophilic inflammatory component. This lesion is seldom found in the esophagus.

Aged↗
PubMed2000

Liver transplantation in patients with homozygotic familial hypercholesterolemia previously treated by end-to-side portocaval shunt and ileal bypass.

Familial hypercholesterolemia is the result of mutations in the gene that encodes the synthesis of the cellular receptor for low density lipoprotein (LDL). In the homozygous form of the disease (HFHC), cellular LDL receptors either do not form, or, when present, cannot bond LDL and mediate its cellular uptake LDL, and the cholesterol that it transports accumulate in plasma, producing severe premature atherosclerosis and death from coronary artery disease usually before the age of 20. Currently, the only effective treatment is liver transplantation, which, alone or in association with medications, normalizes plasma cholesterol levels. The authors report the cases of 2 siblings with HFHC who underwent portocaval shunt at the ages of 2.5 and 1.5 years, respectively. Portocaval shunt produced an immediate, but insufficient decrease in cholesterol (by 40% and 35%, respectively), leaving them with cholesterol concentrations of about 500 mg/dL. One year later they each underwent ileal bypass without obtaining any significant response. Liver transplantation at the ages of 18 and 16 years, respectively, reduced plasma cholesterol concentrations to 129 and 225 mg/dL, respectively. The earlier operations seriously increased the technical difficulty of liver transplantation and did not produce a favorable effect on the natural course of the disease, so portocaval shunt and ileal bypass are not indicated in HFHC, not even for the purpose of delaying liver transplantation.

Adolescent↗
PubMed2000

Utility of tissue culture for detection of Toxoplasma gondii in vitreous humor of patients diagnosed with toxoplasmic retinochoroiditis.

Laboratory recovery and confirmation of the etiologic agent in necrotizing retinochoroiditis are problematic. Tissue culture and intraocular antibody titers were compared as adjuncts to clinical diagnosis for toxoplasmic retinochoroiditis: the correlations were 91 and 67%, respectively. Isolation of Toxoplasma gondii may establish a definitive diagnosis in patients with toxoplasmic retinochoroiditis.

Animals↗
PubMed2000

Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in subjects with schizotypal personality disorder: evidence of inhibitory deficits.

OBJECTIVE: Patients with schizophrenia spectrum disorders have been shown to have deficits in sensorimotor gating as assessed by prepulse inhibition of the startle response. The authors hypothesized that nonschizophrenic relatives of patients with schizophrenia would also have prepulse inhibition deficits, thereby reflecting a genetically transmitted susceptibility to sensorimotor gating deficits. METHOD: Twenty-five comparison subjects, 23 patients with schizophrenia, 34 relatives of the schizophrenic patients, and 11 subjects with schizotypal personality disorder were assessed in an acoustic startle paradigm. The eye-blink component of the startle response was assessed bilaterally by using electromyographic recordings of orbicularis oculi. RESULTS: The patients with schizophrenia, their relatives, and subjects with schizotypal personality disorder all had reduced prepulse inhibition relative to comparison subjects, and these deficits were more evident in measures of right eye-blink prepulse inhibition. Comparison subjects demonstrated greater right versus left eye-blink prepulse inhibition, whereas the probands, their relatives, and subjects with schizotypal personality disorder showed less asymmetry of prepulse inhibition. CONCLUSIONS: These data suggest a genetically transmitted deficit in prepulse inhibition (sensorimotor gating) in patients with schizophrenia spectrum disorders, including subjects with schizotypal personality disorder and relatives of patients with schizophrenia.

Acoustic Stimulation↗
PubMed2000

Relative roles of somatic and Darwinian evolution in shaping the antibody response.

The need for a highly specific system of recognition in immunity has resulted in the evolution of several somatic mechanisms such as V(D)J recombination, to diversify the repertoire of B cells. Therefore, repertoire diversification is the driving force for the cells that constitute the bulk of the response to unpredictable pathogens, the B2 naive B cells. Predictability of antigen, on the other hand, has played a major role in shaping the neonatal repertoire, in which evolution to recognize commonly encountered pathogens has driven the germline sequence of several VH segments that are used frequently in the neonatal repertoire. A third population, the memory B cell population, is generated to respond to a known pathogen, but predictability of the pathogen is not acquired until after a first exposure. Therefore, it is somatic evolution in germinal centers that drives the generation of high-affinity memory B cells.

Animals↗
PubMed2000

Long-term survival expectancy after liver transplantation in children.

PURPOSE: The aim of this study was to assess the long-term survival rate in children who have undergone orthotopic liver transplantation (OLT) in the last 13 years. METHODS: The records of 198 consecutive patients under 18 years of age who underwent 249 OLTs between 1986 and 1998 were reviewed. Actuarial patient survival rates were assessed at 1, 3, 5, and 10 years in the whole series, in the last 5 years, and in patients surviving more than 1 year. Age, weight, and indications were analyzed, as well as type and incidence of posttransplant complications. The median follow-up period was 41 months (0 to 154 months). RESULTS: Biliary atresia was the most common indication (41.9%) followed by alpha-1 antitrypsin deficiency (8.1%), Alagille syndrome (7.6%), and fulminant hepatic failure (6.6%). One hundred forty-six patients (58.6%) were below 5 years, and 46 patients were (18.5%) younger than 1 year at operation. Sixty-eight patients (27.3%) weighed less than 10 kg. One hundred seventy whole organs and 70 reduced, 5 living-related donor, and 4 split-liver allografts were used. Hepatic artery thrombosis (n = 18), primary nonfunction (n = 15), and chronic rejection (n = 14) were the most common causes for allograft failure. Fourteen patients (7%) had posttransplant lymphoproliferative disorders (PTLD) at a median time of 28 months (4 to 124 months) postoperation (3 died). The 1-, 3-, 5-, and 10-year actuarial patient survival rates are 80%, 76%, 74%, and 74%, respectively; over the last 5 years it is 88% at 1 year and 82% at 3 and 5 years. For patients surviving more than 1 year, 3-, 5-, and 10-year actuarial survival rates are 95%, 93%, and 93%, respectively. CONCLUSIONS: (1) Overall results of OLT improve with increasing experience. (2) Children who survive more than 1 year after OLT have an excellent prognosis, although long-term complications of immunosuppression can be expected.

Child↗