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S Diaz

Publications and source records attributed to S Diaz.

At least 19 recordsLinked to original sources
PubMed1999

Lysosomal and cytosolic sialic acid 9-O-acetylesterase activities can Be encoded by one gene via differential usage of a signal peptide-encoding exon at the N terminus.

9-O-Acetylation is one of the most common modifications of sialic acids, and it can affect several sialic acid-mediated recognition phenomena. We previously reported a cDNA encoding a lysosomal sialic acid-specific 9-O-acetylesterase, which traverses the endoplasmic reticulum-Golgi pathway and localizes primarily to lysosomes and endosomes. In this study, we report a variant cDNA derived from the same gene that contains a different 5' region. This cDNA has a putative open reading frame lacking a signal peptide-encoding sequence and is thus a candidate for the previously described cytosolic sialic acid 9-O-acetylesterase activity. Epitope-tagged constructs confirm that the new sequence causes the protein product to be targeted to the cytosol and has esterase activity. Using reverse transcription-polymerase chain reaction to distinguish the two forms of message, we show that although the lysosomal sialic acid-specific 9-O-acetylesterase message has a widespread pattern of expression in adult mouse tissues, this cytosolic sialic acid 9-O-acetylesterase form has a rather restricted distribution, with the strongest expression in the liver, ovary, and brain. Using a polyclonal antibody directed against the 69-amino acid region common to both proteins, we confirmed that the expression of glycosylated and nonglycosylated polypeptides occurred in appropriate subcellular fractions of normal mouse tissues. Rodent liver polypeptides reacting to the antibody also co-purify with previously described lysosomal sialic acid esterase activity and at least a portion of the cytosolic activity. Thus, two sialic acid 9-O-acetylesterases found in very different subcellular compartments can be encoded by a single gene by differential usage of a signal peptide-encoding exon at the N terminus. The 5'-rapid amplification of cDNA ends results and the differences in tissue-specific expression suggest that expression of these two products may be differentially regulated by independent promoters.

Acetylesterase↗
PubMed1998

A mutation in human CMP-sialic acid hydroxylase occurred after the Homo-Pan divergence.

Sialic acids are important cell-surface molecules of animals in the deuterostome lineage. Although humans do not express easily detectable amounts of N-glycolylneuraminic acid (Neu5Gc, a hydroxylated form of the common sialic acid N-acetylneuraminic acid, Neu5Ac), it is a major component in great ape tissues, except in the brain. This difference correlates with lack of the hydroxylase activity that converts CMP-Neu5Ac to CMP-Neu5Gc. Here we report cloning of human and chimpanzee hydroxylase cDNAs. Although this chimpanzee cDNA is similar to the murine homologue, the human cDNA contains a 92-bp deletion resulting in a frameshift mutation. The isolated human gene also shows evidence for this deletion. Genomic PCR analysis indicates that this deletion does not occur in any of the African great apes. The gene is localized to 6p22-p23 in both humans and great apes, which does not correspond to known chromosomal rearrangements that occurred during hominoid evolution. Thus, the lineage leading to modern humans suffered a mutation sometime after the common ancestor with the chimpanzee and bonobo, potentially affecting recognition by a variety of endogenous and exogenous sialic acid-binding lectins. Also, the expression of Neu5Gc previously reported in human fetuses and tumors as well as the traces detected in some normal adult humans must be mediated by an alternate pathway.

Amino Acid Sequence↗
PubMed1998

A structural difference between the cell surfaces of humans and the great apes.

The sialic acids are major components of the cell surfaces of animals of the deuterostome lineage. Earlier studies suggested that humans may not express N-glycolyl-neuraminic acid (Neu5Gc), a hydroxylated form of the common sialic acid N-acetyl-neuraminic acid (Neu5Ac). We find that while Neu5Gc is essentially undetectable on human plasma proteins and erythrocytes, it is a major component in all the four extant great apes (chimpanzee, bonobo, gorilla and orangutan) as well as in many other mammals. This marked difference is also seen amongst cultured lymphoblastoid cells from humans and great apes, as well as in a variety of other tissues compared between humans and chimpanzees, including the cerebral cortex and the cerebrospinal fluid. Biosynthetically, Neu5Gc arises from the action of a hydroxylase that converts the nucleotide donor CMP-Neu5Ac to CMP-Neu5Gc. This enzymatic activity is present in chimpanzee cells, but not in human cells. However, traces of Neu5Gc occur in some human tissues, and others have reported expression of Neu5Gc in human cancers and fetal tissues. Thus, the enzymatic capacity to express Neu5Gc appears to have been suppressed sometime after the great ape-hominid divergence. As terminal structures on cell surfaces, sialic acids are involved in intercellular cross-talk involving specific vertebrate lectins, as well as in microbe-host recognition involving a wide variety of pathogens. The level of sialic acid hydroxylation (level of Neu5Ac versus Neu5Gc) is known to positively or negatively affect several of these endogenous and exogenous interactions. Thus, there are potential functional consequences of this widespread structural change in humans affecting the surfaces of cells throughout the body.

Animals↗
PubMed1998

Impairment and disability: their relation during stroke rehabilitation.

OBJECTIVES: To describe the association between impairment and disability during stroke rehabilitation and to examine the effects of rehabilitation by studying the degree of disability reduction experienced by stroke patients who did not have significant reductions in impairment levels. DESIGN: Statistical analysis of items from a database of prospectively collected information on stroke patients admitted for rehabilitation. SETTING: Large urban academic freestanding rehabilitation facility. PARTICIPANTS: Four hundred two patients consecutively admitted for comprehensive acute stroke inpatient rehabilitation. MAIN OUTCOME MEASURES: The National Institutes of Health Stroke Scale (NIHSS) was used to measure impairment and the Functional Independence Measure (FIM) was used to measure disability. Motor and cognitive subscales of the FIM instrument were evaluated. Raw NIHSS and FIM scores were converted to linear measures using Rasch analysis. METHODS: Relationships were studied between converted NIHSS and the two FIM subscales for admission, discharge, and change scores using linear regression analysis. In a second analysis, two groups of patients were identified; the 342 patients who experienced no substantial reduction of impairment comprised the "no impairment reduction (NIR) group," and the 60 patients who had a significant reduction of impairment level comprised the "impairment reduction (IR) group." Multivariate analysis of variance was used to determine and compare the amount of change in motor and cognitive FIM measures over time for each of the two groups. RESULTS: NIHSS correlated significantly with motor and cognitive FIM subscores for admission, discharge, and change measures; R2 values ranged between .02 and .36. Both the NIR group and the IR group experienced significant decreases in disability during rehabilitation. The differences in discharge FIM measures between the two groups were relatively small. CONCLUSIONS: Although stroke-related impairment and disability are significantly correlated with each other, reduced impairment level alone does not fully explain the reduced disability that occurs during rehabilitation. Even patients without substantial impairment reduction demonstrate disability reduction during rehabilitation, suggesting that rehabilitation has an independent role in improving function beyond that explained by neurologic recovery alone.

Aged↗
PubMed1998

Stroke rehabilitation: clinical predictors of resource utilization.

OBJECTIVE: To identify predictors of rehabilitation hospital resource utilization for patients with stroke, using demographic, medical, and functional information available on admission. DESIGN: Statistical analysis of data prospectively collected from stroke rehabilitation patients. SETTING: Large, urban, academic freestanding rehabilitation facility. PARTICIPANTS: A total of 945 stroke patients consecutively admitted for acute inpatient rehabilitation. MAIN OUTCOME MEASURES: Resource utilization was measured by rehabilitation length of stay (LOS) and mean hospital charge per day (CPD). METHODS: Independent variables were organized into categories derived from four consecutive phases of clinical assessment: (1) patient referral information, (2) acute hospital record review and patient history, (3) physical examination, and (4) functional assessment. Predictors for LOS and CPD were identified separately using four stepwise multiple linear regression analyses starting with variables from the first category and adding new category data for each subsequent analysis. RESULTS: Severe neurologic impairment, as measured by Rasch-converted NIH stroke scale and lower Rasch-converted motor measure of the Functional Independence Measure (FIM) instrument predicted longer LOS (F2,824 = 231.9, p < .001). Lower Rasch-converted motor FIM instrument measure, tracheostomy, feeding tube, and a history of pneumonia, coronary artery disease, or renal failure predicted higher CPD (F6,820 = 90.2, p < .001). CONCLUSION: Stroke rehabilitation LOS and CPD are predicted by different factors. Severe impairment and motor disability are the main predictors of longer LOS; motor disability and medical comorbidities predict higher CPD. These findings will help clinicians anticipate resource needs of stroke rehabilitation patients using medical history, physical examination, and functional assessment.

Aged↗
PubMed1998

Norplant consensus statement and background review.

This review has highlighted the attributes of a very important new method of contraception. The signatories to this document agree that, with the provision of appropriate information and instruction for the user, Norplant is a good contraceptive choice to be made available worldwide in family planning programs that have the resources for appropriate training and counseling. The signatories to this document are acting in their own personal capacity and not as representatives of any particular organization.

Contraceptive Agents, Female↗
PubMed1998

The performance of levonorgestrel rod and Norplant contraceptive implants: a 5 year randomized study.

A new contraceptive (LNG rod implants, Jadelle, Leiras Oy's registered trademark for rod implants) was prospectively evaluated in randomized 5 year comparison with Norplant (Population Council's registered trademark for contraceptive implants releasing levonorgestrel) capsule implants. The study involved 1198 women at seven centres. No pregnancies occurred in the first 4 years. At 5 years, the cumulative pregnancy rate was 1 per 100 users or less for each regimen. Annual discontinuation rates averaged 11-12 per 100 users (P > 0.05), corresponding to 5 year continuation rates of 55.1 for rods and 53.0 per 100 for capsules. Mean annual discontinuation rates for menstrual disturbances were 3.5 and 4.2 per 100 for rod and capsule implants respectively (P > 0.05), and mean annual removal rates for medical problems were 3.5 and 3.0 per 100 (P > 0.05) respectively. Apart from menstrual problems, headache, weight gain and acne were the principal medical reasons for removal. In proportional hazard analyses, family formation variables, age, parity and desire/non desire for another child, recorded at admission, significantly affected discontinuation rates for major decrement categories and for all reasons combined. Mean rod removal time was half that of Norplant (P < 0.01); complications of rod removal were at a lower rate. With these contraceptives indistinguishable in performance except for ease and speed of removal, LNG rod implants appear to be preferable to Norplant for use through 5 years by virtue of relative ease of removal.

Adult↗
PubMed1998

Interactive case challenge. Dysphoric disorders in women: a case of premenstrual syndrome.

When this woman's long-standing PMS grows progressively more severe over the 3 years following the birth of her third child, what pharmacologic and nonpharmacologic treatments would you recommend? Symptoms of mood swings, irritability, and anxiety occur in many women during the premenstrual phase of the menstrual cycle. Several promising treatment options now exist for women whose symptoms are severe and interfere with daily functioning. These include nonpharmacologic as well as pharmacologic interventions, such as serotonergic antidepressants, anxiolytics, and hormones that suppress ovulation. When PMS becomes intolerably severe for this 36-year-old mother of 3 children--all under 10 years of age--she seeks treatment.

Adult↗
PubMed1997

Clinical performance of a new two-rod levonorgestrel contraceptive implant: a three-year randomized study with Norplant implants as controls.

In a randomized three-year clinical trial at seven clinics, the performance of levonorgestrel rod (LNG ROD) implants used by 600 women was compared with that of soft tubing NORPLANT implants used by 598 women. No pregnancies occurred in either group of women and, accordingly, body weight did not affect the efficacy of either type of implant. There were neither statistically significant nor important differences in termination rates for any reason over the three years. Complaint and illness rates during use of either of the two implant types were statistically indistinguishable and were attributable to the same set of conditions. Seventy-one per 100 of the women using each implant regimen continued to the three-year point, for an average annual continuation rate of 89 per 100. Removals of LNG ROD implants were accomplished in about half the time required for removal of Norplant capsule implants (p < 0.001).

Adolescent↗
PubMed1997

Levonorgestrel concentrations during use of levonorgestrel rod (LNG ROD) implants.

In a three-year randomized trial that included 398 women, blood samples were collected for the purpose of assaying levonorgestrel concentrations in women using a new two-rod contraceptive implant system or an earlier implant formulation, Norplant-2 implants. Sample collection was at 1, 3, 6, 9, and 12 months after placement and semiannually thereafter through three years. Resulting assays and analyses showed that levonorgestrel concentrations of each implant formulation decreased significantly with time after placement, with increasing body weight, and with ponderal index. In the third year, several measures indicated that concentrations of the contraceptive drug were higher in women using the LNG ROD implants than in users of the original formulation. No pregnancies occurred among women in either group in the three years. This study provides evidence that the minimum levonorgestrel concentration needed to protect against pregnancy is below 200 pg/ml, and possibly is below 175 pg/ml.

Adolescent↗
PubMed1997

First week drug concentrations in women with levonorgestrel rod or Norplant capsule implants.

Forty-two healthy women volunteered to have blood samples drawn at 2, 4, 8, 24, 48, and 168 h (7 days) following placement of levonorgestrel-releasing rod (LNG rod) or of Norplant capsule implants to permit measurement of drug concentrations. Three clinics recruited 10 women each, half of whom used each type of implant. Twelve additional subjects were later enrolled at one site to provide greater detail for the capsule implants. Throughout the week, women with Norplant implants had apparently higher mean drug concentrations than did women with LNG rod implants, but the differences were significant only in the first 48 h after placement (p < 0.05). Maximum levels for capsule implants were found at the 24-h sample (mean, 1358 to 1474 pg/mL) and for the LNG rod implants at 48 h (772 pg/mL). Body weight was negatively correlated with levonorgestrel concentrations at all times (p < 0.05). For several sampling times, differences between clinics in mean concentrations were statistically significant after weight adjustment. Despite differences by implant type, weight, or clinic location, drug concentrations compatible with contraceptive effect were attained within 24 h in users of LNG rod or of Norplant implants, insofar as all women had levonorgestrel concentrations above 250 pg/mL at the 24-h sample.

Adolescent↗
PubMed1997

Renal effects of chronic exposure to malathion in Octodon degus.

We studied the effects of chronic exposure to malathion in the kidney of Octodon degus, a caviomorph whose habitat may be exposed to pesticides currently used in Chilean agriculture. A group of adult female animals received malathion (200 ppm) as sole drinking fluid for 90 days. Kidneys showed signs of histologic damage, marked by hyperplasia and hypertrophy of tubular cells. Exposed animals had unchanged glomerular filtration rates and renal handling of sodium and chloride, but a significant increase in fractional excretion of potassium resulted from this treatment. The activities of Na+/K(+)-ATPase and Mg(2+)-ATPase in renal cortex and outer medulla were not affected by malathion exposure. This study provides evidence of both morphologic and functional renal damage elicited by chronic exposure of O. degus to a low dose of malathion. Morphologic alterations in glomerulus were accompanied by either morphologic and functional impairments of the distal nephron.

Animals↗
PubMed1997

New sialic acids from biological sources identified by a comprehensive and sensitive approach: liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) of SIA quinoxalinones.

Sialic acids are a family of 9-carbon carboxylated sugars, where different substitutions of the backbone define over 30 members. Biological roles of these substitutions have been missed until recently because of their low abundance and lability to conventional isolation/purification methods. This new approach characterizes sialic acids using electrospray ionization-mass spectrometry (ESI-MS) to monitor the HPLC separation of their DMB (1,2-diamino-4,5-methylenedioxy-benzene) derivatives (quinoxalinones). A combination of retention times and spectra characteristics allows definition of the type and position of the various substituents. This approach requires no previous purification, involving a simple derivatization reaction followed by direct injection on the microbore HPLC column. A complete spectrum, including molecular ions and CAD fragments of a sialic acid quinoxalinone, is obtained by injecting 10-20 pmol of the compound. Individual quinoxalinones can be purified by regular RP-HPLC and analyzed by direct-injection ESI-MS or LSIMS. Using this approach, we identified 28 different sialic acids, including the following new species: Neu5Gc9Lt (BSM), anhydro derivatives of Neu5Ac other than the 4,8-anhydro (horse serum hydrolyzates), KDN5(7)Ac and KDN5(7),9Ac2 (amphibian Pleurodeles waltl), four isomers of Neu5Gc8MexAc and three anhydro derivatives of Neu5Gc8Me (glycolipids of the starfish Pisaster brevispinus), and Neu5Ac8S (in addition to Neu5Gc8S, in the glycolipids of the sea urchin Lovenia cordiformis). Results show the usefulness of LC-ESI-MS to study sialic acid diversity, and identification of small amounts of unexpected sialic acids or new members of their family.

Acetylation↗
PubMed1996

Molecular cloning and characterization of lysosomal sialic acid O-acetylesterase.

O-Acetylation and de-O-acetylation of sialic acids have been implicated in the regulation of a variety of biological phenomena, including endogenous lectin recognition, tumor antigenicity, virus binding, and complement activation. Applying a strategy designed to identify genes preferentially expressed in active sites of embryonic hematopoiesis, we isolated a novel cDNA from the pluripotent hematopoietic cell line FDCPmixA4 whose open reading frame contained sequences homologous to peptide fragments of a lysosomal sialic acid O-acetylesterase (Lse) previously purified from rat liver, but with no evident similarity to endoplasmic reticulum-derived acetylesterases. The expressed Lse protein exhibits sialic-acid O-acetylesterase activity that is not attributable to a typical serine esterase active site. lse expression is spatially and temporally restricted during embryogenesis, and its mRNA levels correlate with differences in O-acetylesterase activity described in adult tissues and blood cell types. Using interspecific backcross analysis, we further mapped the lse gene to the central region of mouse chromosome 9. This constitutes the first report on the molecular cloning of a sialic acid-specific O-acetylesterase in vertebrates and suggests novel roles for the 9-O-acetyl modification of sialic acids during the development and differentiation of mammalian organisms.

Acetylesterase↗
PubMed1996

Overdiagnosis of depression in the general hospital.

To test the hypothesis that depression is often inaccurately detected in medical settings, we examined the psychiatric consultations performed at two medical-surgical teaching hospitals. All records for the 4396 consultations seen in a 3-year period were retrospectively reviewed. Consultations were categorized by the reason for referral. These reasons were compared with the consulting psychiatrist's diagnosis. Diagnoses were grouped into "Depressed" and "Not Depressed" categories, depending on whether the psychiatric diagnoses implied any form of depressive illness (alone or in combination with other diagnoses). The majority of the referrals for psychiatric consultation (about 25% and 30% at the respective sites) were for presumed depression. Of these referrals for depression, approximately 40% were judged by the consultant to have no depressive diagnosis. Of the referrals for depression judged not to be depressed, the majority had other undiagnosed illnesses, particularly delirium, dementia, and anxiety disorders. The authors conclude that although numerous studies report that depression is unrecognized in medical patients, it may also be inappropriately suspected. This is of most concern when the presumption of depression delays other medical, neurological, or psychiatric evaluation.

Adolescent↗
PubMed1995

Solar ultraviolet B radiation and photoproduction of vitamin D3 in central and southern areas of Argentina.

The incidence of nutritional rickets in the southern part of Argentina is 8-12 times higher than in the rest of the country. Winter 25(OH)D serum levels in normal population of southern areas are lower than in central and northern areas. To elucidate these differences, we compared the photoconversion of provitamin D3 (7-DHC) to previtamin D3 in two cities: Ushuaia (latitude 55 degrees S) and Buenos Aires (34 degrees S). Ampules containing 7-DHC were exposed to sunlight one day in the middle of each month either from 10:30 a.m. to 2:30 p.m. or from 8:00 a.m. to 5:00 p.m. The percentages of photoproducts formed were determined by high performance liquid chromatography (HPLC). Previous studies have proved that this is a valid model to assess "in vitro" the photoproduction of vitamin D3 in human skin. Previtamin D3 + vitamin D3 formed in Ushuaia were less (p < 0.02) than those found in Buenos Aires during all seasons: summer, (X +/- SEM) 6.4 +/- 0.8% vs. 13.2 +/- 1.8%; autumn, 1.2 +/- 0.7% vs. 6.3 +/- 1.3%; winter, 0.8 +/- 0.7% vs. 3.6 +/- 0.7%; spring, 3.4 +/- 0.5% vs. 9.1 +/- 1.1%. The photoproducts produced from 10:30 a.m. to 2:30 p.m. were similar for each month and latitude to those formed when the ampules were exposed from 8:00 a.m. to 5:00 p.m. We conclude that in Ushuaia there is a prolonged "vitamin D winter" during which cutaneous synthesis of vitamin D is absent, leading to lower serum values of 25(OH)D and contributing to the higher incidence of rickets.

Argentina↗