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Biomedical subjects

R Hernandez

Publications and source records attributed to R Hernandez.

At least 37 records · Page 2Linked to original sources

Immunostaining of heat shock proteins in the retina and optic nerve head of normal and glaucomatous eyes.

PURPOSE: To examine immunostaining of 60-kd and 27-kd heat shock proteins (HSP 60 and HSP 27), which are known to increase cell survival in response to stress, in glaucomatous retina and optic nerve head. METHODS: Six postmortem eyes from patients with primary open-angle glaucoma, 6 eyes from patients with normal-pressure glaucoma, and 6 eyes from age-matched normal subjects were studied by immunohistochemistry. The sections of the retina and optic nerve head were examined after immunostaining with antibodies to HSP 60 and HSP 27. RESULTS: The intensity of the immunostaining and the number of labeled cells for heat shock proteins (HSPs) were greater in retina sections from glaucomatous eyes than in sections from normal eyes from age-matched donors. Retinal immunostaining of HSP 60 was prominent in the retinal ganglion cells and photoreceptors, whereas immunostaining of HSP 27 was prominent in the nerve fiber layer and ganglion cells as well as in the retinal vessels. In addition, retinal immunostaining of these HSPs exhibited regional and cellular differences. Optic nerve heads of glaucomatous eyes exhibited increased immunostaining of HSP 27, but not HSP 60, which was mostly associated with astroglial cells in the lamina cribrosa. CONCLUSION: The increased immunostaining of HSP 60 and HSP 27 in the glaucomatous eyes may reflect a role of these proteins as a cellular defense mechanism in response to stress or injury in glaucoma. CLINICAL RELEVANCE: These findings suggest that immunoregulation is an important component of glaucomatous optic neuropathy.

Aged↗

Identification of a point mutation in an esterase gene in different populations of the southern cattle tick, Boophilus microplus.

Two esterase cDNA sequences were obtained from susceptible and organophosphorus resistant strains of Boophilus microplus. Both sequences have a high degree of homology to carboxylesterase B. One gene has identical sequences in both strains and the other showed two point mutations. One mutation produces an amino acid substitution when the amino acid sequence is deduced, this mutation was detected in six different populations susceptible and resistant to insecticides, but a pyrethroid resistant strain was the only one that showed only the mutant allele. Identification of this mutation and the strong signal detected in southern blot with this strain, suggest that esterases are contributing to detoxification of pyrethroid compounds, as a resistant mechanism in Mexican strains of the southern cattle tick.

Amino Acid Sequence↗

Allogeneic peripheral blood cell transplantation for hypereosinophilic syndrome with myelofibrosis.

Patients with hypereosinophilic syndrome (HES) display a very heterogeneous clinical picture ranging from asymptomatic cases to very aggressive forms. We report a 38-year-old woman with progressive HES who developed severe myelofibrosis and was treated by allogeneic stem cell transplantation, using peripheral blood (PBSCT) instead of bone marrow as the source of progenitor cells, after conditioning with cytoxan and busulphan. To the best of our knowledge, this is the first case of HES with myelofibrosis treated with PBSCT. The patient remains alive 8 months post-PBSCT, and bone marrow fibrosis has significantly decreased following transplantation. Bone Marrow Transplantation (2000) 25, 217-218.

Adult↗

Effect of bilateral ovariectomy and ovarian steroid hormones on the antioxidant systems and plasma malondialdehyde levels in Wistar rats.

We studied in the Wistar rat the effect of bilateral ovariectomy and of the administration of estradiol (E2) alone or together with medroxyprogesterone (MPA) on the lipid peroxidation (MDA) and the enzymatic (SOD and catalase) and non-enzymatic (vitamins A and E) antioxidant systems. At 15 days after castration, we observed no variations in the lipid peroxidation levels (MDA), with there being a slight increase in vitamins A and E (p<0.05), catalase (p<0.01), and SOD (n.s.) activity. The addition of estradiol led to a decline (n.s.) in the MDA values and in the catalase and SOD activity, with no modification of the vit. A and E concentrations. The combined (E2+MPA) therapy did not modify the results obtained with E2 alone, although the catalase decline did now reach significance (p<0.05).

Animals↗

A single deletion in the membrane-proximal region of the Sindbis virus glycoprotein E2 endodomain blocks virus assembly.

The envelopment of the Sindbis virus nucleocapsid in the modified cell plasma membrane involves a highly specific interaction between the capsid (C) protein and the endodomain of the E2 glycoprotein. We have previously identified a domain of the Sindbis virus C protein involved in binding to the E2 endodomain (H. Lee and D. T. Brown, Virology 202:390-400, 1994). The C-E2 binding domain resides in a hydrophobic cleft with C Y180 and W247 on opposing sides of the cleft. Structural modeling studies indicate that the E2 domain, which is proposed to bind the C protein (E2 398T, 399P, and 400Y), is located at a sufficient distance from the membrane to occupy the C protein binding cleft (S. Lee, K. E. Owen, H. K. Choi, H. Lee, G. Lu, G. Wengler, D. T. Brown, M. G. Rossmann, and R. J. Kuhn, Structure 4:531-541, 1996). To measure the critical spanning length of the E2 endodomain which positions the TPY domain into the putative C binding cleft, we have constructed a deletion mutant, DeltaK391, in which a nonconserved lysine (E2 K391) at the membrane-cytoplasm junction of the E2 tail has been deleted. This mutant was found to produce very low levels of virus from BHK-21 cells due to a defect in an unidentified step in nucleocapsid binding to the E2 endodomain. In contrast, DeltaK391 produced wild-type levels of virus from tissue-cultured mosquito cells. We propose that the phenotypic differences displayed by this mutant in the two diverse host cells arise from fundamental differences in the lipid composition of the insect cell membranes which affect the physical and structural properties of membranes and thereby virus assembly. The data suggest that these viruses have evolved properties adapted specifically for assembly in the diverse hosts in which they grow.

Amino Acid Sequence↗

Mycotic pseudoaneurysm associated with aortic coarctation.

Development of a mycotic aneurysm or pseudoaneurysm after subacute bacterial endarteritis is uncommon. Nonetheless, patients with coarctation of the aorta are more likely to develop this complication. We describe a case of a large pseudoaneurysm discovered in a child with a previously undiagnosed aorta coarctation. Successful repair was performed with the aid of partial left heart bypass and the use of an interposition graft. A high index of suspicion is necessary to accurately diagnose this rare but life-threatening entity.

Aneurysm, False↗

Faculty perspectives of health promotion in allied health curricula: results of a national survey.

More knowledge and skills related to health promotion/disease prevention are being required of health professionals. Allied health graduates entering the workforce will need academic preparation in these areas. This study assessed faculty perspectives on the status of health promotion content in allied health programs by a survey of 524 program directors. A questionnaire gathered information about perception of importance, level of representation, and method of delivery of health promotion content. Response rate was 41%. The majority of participants thought this content area was important for their programs and was highly or moderately represented in their curricula. Level of representation was significantly associated with requirement for accreditation. Programs in the Northeast were more likely to think health promotion was important and those in the West were more likely to have it integrated into their curricula. The most common delivery modality was guest lecture. Allied health is adopting health promotion curricular content, but further study is needed to assess programs and faculty expertise and identify strategies to ensure greater consistency of delivering material.

Allied Health Occupations↗

Propensity and mechanisms of restenosis in different coronary stent designs: complementary value of the analysis of the luminal gain-loss relationship.

OBJECTIVES: This study sought to investigate the influence of stent design on the long-term angiographic outcome. BACKGROUND: The proportional relationship between vessel injury and late luminal loss in percutaneous revascularization should be best appreciated in coronary stenting, where recoil and shrinkage are theoretically minimal. It is unclear whether all stent designs can counterbalance this reactive loss by achieving a large initial luminal gain (bigger is better). METHODS: In 523 lesions successfully stented, the long-term angiographic results of slotted-tube (n = 331), coil (n = 85), multicellular (n = 70) and self-expandable mesh (n = 37) stent designs were compared using the angiographic gain-loss relationship (GLR). RESULTS: Restenosis rate was 10% for multicellular, 20% for slotted-tube, 46% for coil and 49% for self-expandable designs (p = 0.001). At a difference with other designs, no significant GLR was found in coil stents, suggesting additional mechanisms of luminal loss (i.e., plaque protrusion, stent compression) to neointimal proliferation. Significant differences in late loss between stents were found within each quartile of luminal gain, suggesting a specific role of design in luminal loss. Multivariate analysis identified use of coil and self-expandable stents, vessel size, minimal luminal diameter preintervention, luminal gain and stent length as variables with independent predictive value for several indices of angiographic long-term outcome. CONCLUSIONS: The analysis of GLR: 1) demonstrates that stent design influences late luminal loss; 2) challenges the applicability of the widely accepted "bigger is better" approach to all stent designs; and 3) appears as a valuable tool in assessing long-term stent performance.

Coronary Angiography↗

Albinism and agenesis of the corpus callosum with profound developmental delay: Vici syndrome, evidence for autosomal recessive inheritance.

We report on two sibs and two other unrelated patients with agenesis of corpus callosum, oculocutaneous albinism, repeated infections, and cardiomyopathy. All manifested postnatal growth retardation, microcephaly, and profound developmental delay. Additional central nervous system anomalies present in at least one patient included hypoplasia of the cerebellar vermis, white matter neuronal heterotopia, or bilateral schizencephaly. Repeated viral, bacterial, and fungal infections were consistent with a primary immunodeficiency. However, immunological studies showed variable, nonspecific findings. Cardiomyopathy with progressive heart failure or infection led to death before age 2 years in three of the patients. This syndrome was first described by Vici et al. [1988: Am. J. Med. Genet. 29:1-8]. The four patients reported herein confirm this unique disorder. Affected sibs of both sexes born to unaffected parents provide evidence for autosomal recessive inheritance.

Adult↗

Initial results and long-term clinical and angiographic implications of coronary stenting in elderly patients.

Results of 378 consecutive elderly patients (> or = 65 years) undergoing coronary stenting were compared with those of 601 younger patients. Although the restenosis rate was similar in the 2 groups, age > or = 65 years was an independent predictor of in-hospital mortality (relative risk 5.4, 95% confidence interval 1.2 to 20.1) and follow-up mortality (relative risk 2.8, 95% confidence interval 1.3 to 6.1).

Aged↗

Long-term clinical and echocardiographic follow-up after percutaneous mitral valvuloplasty with the Inoue balloon.

BACKGROUND: The objective of this study was to assess the long-term clinical outcome and valvular changes (area and regurgitation) after percutaneous mitral valvuloplasty (PMV). METHODS AND RESULTS: After PMV, 561 patients were followed up for 39 (+/-23) months and clinical/echocardiographic data obtained yearly. Kaplan-Meier and Cox regression analyses were performed to estimate event-free survival, its predictors, and the relative risks of several patient subgroups. There were several nonexclusive events: 19 (3.3%) cardiac deaths, 55 (9.8%) mitral replacements, 6 (1%) repeated PMVs, 56 (10%) cases of restenosis, and 108 (19%) cases of clinical impairment. Survival free of major events (cardiac death, mitral surgery, repeat PMV, or functional impairment) was 69% at 7 years, ranging from 88% to 40% in different subgroups of patients. Wilkins score was the best preprocedural predictor of mitral opening, but the procedural result (mitral area and regurgitation) was the only independent predictor of major event-free survival. Mitral area loss, though mild [0.13 (+/-0.21)cm2], increased with time and was >/=0.3 cm2 in 12%, 22%, and 27% of patients at 3, 5, and 7 years, respectively. Regurgitation did not progress in 81% of patients, and when it occurred it was usually by 1 grade. CONCLUSIONS: Seven years after PMV, more than two thirds of patients were in good clinical condition and free of any major event. The procedural result was the main determinant of long-term outcome, although a high score had also negative implications. Mitral area decreased progressively over time, whereas regurgitation did not tend to progress.

Aged↗

Long-term angiographic results of stenting in chronic total occlusions: influence of stent design and vessel size.

BACKGROUND: Although coronary stenting has decreased the high restenosis rate associated with percutaneous transluminal coronary angioplasty of chronic total occlusions (CTOs), the results are still less satisfactory than those found in nonoccluded lesions, at least as reported with the Palmaz-Schatz stent. The present work compares the restenosis rate of other stent designs with that of the Palmaz-Schatz stent. METHODS: We studied the long-term angiographic outcome of 120 CTOs successfully recanalized with balloon-expandable stents and without concomitant debulking techniques. Angiographic follow-up and full quantitative coronary angiography analysis was prospectively performed in all patients. Three different stent designs were compared: Palmaz-Schatz (n = 47), coil (n = 24), and multicellular (n = 49). Particular attention was paid to their performance in vessels of 3 mm or less and greater than 3 mm in diameter. Restenosis was defined as a 50% or greater diameter stenosis at follow-up. RESULTS: Multicellular stents were implanted more frequently in the left anterior descending artery and in patients with multivessel disease. No other significant differences in clinical or angiographic baseline characteristics, including vessel size, were noted between groups. At follow-up, multicellular stents presented a lower restenosis rate (22% vs 36% and 58% in the Palmaz-Schatz and coil stent groups, respectively; P =.01 ) and larger minimal luminal diameters (1.92 +/- 0.85 mm vs 1.73 +/- 0.98 and 1.38 +/- 0.83 mm in the Palmaz-Schatz and coil stent groups, respectively; P = 0.0). The superiority of the multicellular stent design resulted from a lower restenosis rate in vessels of 3.0 mm or less in diameter (20% vs 47% and 79% in the Palmaz-Schatz and coil stent groups, respectively; P =.006). CONCLUSIONS: These results suggest that the restenosis rate after stent recanalization of CTOs is influenced by both stent design and vessel size and may indicate a superiority of multicellular over Palmaz-Schatz and coil stent designs for this purpose.

Coronary Angiography↗

Cloning and sequencing of a putative acetylcholinesterase cDNA from Boophilus microplus (Acari: Ixodidae).

Using a strategy based on degenerate primers derived from acetylcholinesterase (AChE) from other species, we cloned and sequenced a putative AChE cDNA from the southern cattle tick, Boophilus microplus (Canestrini). The sequence has a high degree of homology to sequences of AChE from other species reported in the GenBank. The open reading frame of 1,689 bp, corresponding to a deduced sequence of 563 amino acids, has conserved regions and features shared by the AChE family, necessary for its catalytic activity. No differences were found in the putative cDNA sequences from organophosphorus acaricide (OP) resistant and susceptible strains. The results suggest that this putative AChE gene is not involved in resistance to OP compounds as a mutated gene in the resistant strain studied. However, differences were detected, with a probe derived from this cDNA, in DNA fragments after digestion of genomic DNA from different strains with restriction nucleases. This indicates polymorphism in this gene in B. microplus.

Acetylcholinesterase↗

Double stenting as a treatment for stent collapse in the left main coronary artery.

We report on a case of double stent implantation in the left main coronary artery due to collapse of the first implanted stent. The case illustrates a complication of stenting presumably dictated by the specific characteristics of left main disease, and the feasibility and good long-term results of double stenting in this situation.

Aged↗

Quantitative and ultrastructural changes in glia and pericytes in the parietal cortex of the aging rat.

The frequency of astrocytes, microglia plus oligodendrocytes, and pericytes displaying nuclei was analyzed and quantified in 160-microm-wide strips of the parietal cortex (Par1 region) from young and aged Wistar rats. The study was performed on two groups of rats aged 3-4 and 32-36 months. Quantifications of the glial cell types and pericytes were made in 1-microm-thick sections stained with toluidine blue. Ultrathin sections were also made to analyze the ultrastructural features of these cells during aging. Astrocytes and pericytes increased in number by about 20% and 22%, respectively, with age. These increases were most significant in layers II-IV and V for both cellular types. Clusters of astrocytes were common in these layers of aging rats. The ultrastructural analysis also indicated changes in all cell types that stored inclusions and vacuoles with age, which were particularly abundant in microglial cells. End-feet astrocytes and pericytes surrounding the vascular wall also contained vacuoles and inclusions, and consequently the vascular wall increased in thickness. In conclusion, the aging process increased astrocyte and pericyte populations, but not microglia plus oligodendrocyte populations, in the rat parietal cortex. Although no significant change in nuclear size could be observed in any cell type, all glial cells as well as pericytes underwent morphological ultrastructural changes. These modifications may result from the need to correct possible homeostatic imbalances during aging.

Aging↗

Differences in cytotoxicity of native and engineered RIPs can be used to assess their ability to reach the cytoplasm.

Ricin is a heterodimeric cytotoxin composed of RTB, a galactose binding lectin, and RTA, an enzymatic N-glycosidase. The toxin is endocytosed, and after intracellular routing, RTA is translocated to the cytoplasm where it inactivates ribosomes resulting in a loss of host cell protein synthesis and cell death. We show for the first time that the cytotoxicity against cultured T cells by several RTA mutants is directly proportional to the enzyme activity of RTA, suggesting this is a reliable system to measure translocation effects. Large discrepancies between cytotoxicity and enzyme action for a given pair of toxins are therefore attributable to differences in cell binding, uptake, or membrane translocation. Fluid phase uptake and cytotoxicity of isolated RTA are essentially identical to that of the single chain toxin PAP. This important finding suggests that RTA, and the A chain of class 2 RIPs in general, has not evolved special translocation signals to complement the increased target cell binding facilitated by RTB. Experiments with the lectin RCA and with ebulin suggest those toxins have diminished cytotoxicity probably mediated by comparative deficiencies in B chain binding. Addition of a KDEL sequence to RTA increases fluid phase uptake, consistent with the notion that transport to the ER is important for cytotoxicity. Fusion of MBP or GST to the amino terminus of RTA has little effect on enzyme action or cytotoxicity. This result is not altered by protease inhibitors, suggesting the fusion proteins are probably not cleaved prior to translocation of the toxic A chain and implying that the toxins can carry large passenger proteins into the cytoplasm, an observation with interesting potential for analytical and therapeutic chemistry.

Amino Acid Sequence↗

Chemotherapy as a part of each treatment fraction in a twice-a-day hyperfractionated schedule: a new chemoradiotherapy approach for advanced head and neck cancer.

BACKGROUND: Using chemotherapy as a part of each treatment fraction remains unexplored. This study integrates the concomitant administration of carboplatin with hyperfractionated irradiation by optimizing chemopotentiation through carboplatin administration with each irradiation fraction. METHODS: From February 1993 to August 1996, 52 patients with advanced head and neck cancer were treated on a twice-a-day chemoradiotherapy schedule. Each fraction consisted of 115 cGy preceded by 5 mg/m2 of carboplatin. Treatment was given 5 days a week up to total doses of 350 mg/m2 of carboplatin + 8050 cGy in 7 weeks. RESULTS: All (100%) of patients tolerated the treatment (83% as scheduled). Acute and late toxicities were moderate. Rates of 96% complete response (CR) and 4% partial response (PR) were achieved. At 52 months, local control and cause-specific survival rates are 72% and 59%, respectively. Nodal control rate is 95%. CONCLUSION: These results show potential for improvement upon hyperfractionated radiotherapy alone and compare favorably with those of most reported trials.

Adult↗