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Biomedical subjects

H Cruz

Publications and source records attributed to H Cruz.

At least 19 recordsLinked to original sources
PubMed2006

Dynamic role of kallikrein 6 in traumatic spinal cord injury.

Kallikrein 6 (K6) is a member of the kallikrein gene family that comprises 15 structurally and functionally related serine proteases. In prior studies we showed that, while this trypsin-like enzyme is preferentially expressed in neurons and oligodendroglia of the adult central nervous system (CNS), it is up-regulated at sites of injury due to expression by infiltrating immune and resident CNS cells. Given this background we hypothesized that K6 is a key contributor to the pathophysiology of traumatic spinal cord injury (SCI), influencing neural repair and regeneration. Examination of K6 expression following contusion injury to the adult rat cord, and in cases of human traumatic SCI, indicated significant elevations at acute and chronic time points, not only at the injury site but also in cord segments above and below. Elevations in K6 were particularly prominent in macrophages, microglia and reactive astrocytes. To determine potential effects of elevated K6 on the regeneration environment, the ability of neurons to adhere to and extend processes on substrata which had been exposed to recombinant K6 was examined. Limited (1 h) or excess (24 h) K6-mediated proteolytic digestion of a growth-facilitatory substrate, laminin, significantly decreased neurite outgrowth. By contrast, similar hydrolysis of a growth-inhibitory substrate, aggrecan, significantly increased neurite extension and cell adherence. These data support the hypothesis that K6 enzymatic cascades mediate events secondary to spinal cord trauma, including dynamic modification of the capacity for axon outgrowth.

Adolescent↗
PubMed2001

Identification and total synthesis of novel fatty acids from the Siphonarid limpet Siphonaria denticulata.

The novel fatty acids 17-methyl-6(Z)-octadecenoic acid and 17-methyl-7(Z)-octadecenoic acid were identified for the first time in nature in the mollusk Siphonaria denticulata from Queensland, Australia. The principal fatty acids in the limpet were hexadecanoic acid, octadecanoic acid, and (Z)-9-octadecenoic acid, while the most interesting series of monounsaturated fatty acids was a family of five nonadecenoic acids with double bonds at either Delta(7), Delta(9), Delta(11), Delta(12), or Delta(13). The novel compounds were characterized using a combination of GC-MS and chemical transformations, such as dimethyl disulfide derivatization. The first total syntheses for the two novel methyl-branched nonadecenoic acids are also described, and these were accomplished in four to five steps and in high yields.

Animals↗
PubMed2000

Zinc-induced changes in ionic currents of clonal rat pancreatic -cells: activation of ATP-sensitive K+ channels.

The effects of zinc (Zn2+) on excitability and ionic conductances were analysed on RINm5F insulinoma cells under whole-cell and outside-out patch-clamp recording conditions. We found that extracellular application of 10-20 microM Zn2+ induced a reversible abolition of Ca2+ action potential firing, which was accompanied by an hyperpolarisation of the resting membrane potential. Higher concentrations of Zn2+, in the tens to hundreds micromolar range, induced a reversible reduction of voltage-gated Ca2+ and, to a lesser extent, K+ currents. Low-voltage-activated Ca2+ currents were more sensitive to Zn2+ block than high voltage-activated Ca2+ currents. The Zn2+-induced hyperpolarisation arose from a dose-dependent increase in a voltage-independent K+ conductance that was pharmacologically identified as an ATP-sensitive K+ (KATP) conductance. The effect was rapid in onset, readily reversible, voltage independent, and related to intracellular ATP concentration. In the presence of 1 mM intracellular ATP, half-maximal activation of KATP channels was obtained with extracellular application of 1.7 microM Zn2+. Single channel analysis revealed that extracellular Zn2+ increased the KATP channel open-state probability with no change in the single channel conductance. Our data support the hypothesis that Zn2+ binding to KATP protein subunits results in an activation of the channels, therefore regulating the resting membrane potential and decreasing the excitability of RINm5F cells. Taken together, our results suggest that Zn2+ can influence insulin secretion in pancreatic beta-cells through a negative feedback loop, involving both KATP and voltage-gated conductances.

Adenosine Triphosphate↗
PubMed1999

An integrated strategy for the process development of a recombinant antibody-cytokine fusion protein expressed in BHK cells.

Recombinant fusion proteins offer important new therapeutic approaches for the future. This report describes the use of three different genetic strategies (i.e. "mono-", "bi-" and "tri-cistronic" vectors) to achieve stable secretion from BHK cells of a glycosylated antibody-cytokine fusion protein designed for use in antitumour therapy. It describes selection of a robust and effective production cell line based on stability of secretion of the product, quality of mRNA and protein products and performance in in vitro bioassays for potency. The data obtained at this stage were utilised in the selection of a suitable candidate production cell line. The relative productivity and general performance of the cells in stirred tank and fixed bed culture systems indicated that a variety of cell culture technologies provided robust tools for production of a highly selected cell clone. Consistency of the product glycosylation was determined by analysis of released oligosaccharides using matrix-assisted laser desorption ionisation-time of flight mass spectrometry and high-performance anion exchange chromatography. These investigations showed consistent expression of three glycoforms of the fusion protein which varied in their relative proportions in different culture systems and at different time points in a fixed bed reactor with continuous perfusion. In conclusion, this study dealt with a range of important scientific and technical issues which are essential for regulatory approval and commercial success of a recombinant protein and elucidates some useful markers for process development for similar recombinant biologicals.

Animals↗
PubMed1999

Developing a managed care delivery system in New York State for Medicaid recipients with HIV.

In the state of New York, models of care known as HIV Special Needs Plans (HIV SNPs) are being developed to meet the unique health and medical needs of Medicaid recipients with HIV. Establishing managed care plans for the 80,000 to 100,000 HIV-infected Medicaid recipients residing in the state has required considerable effort, including distributing planning grants to solicit information and recommendations regarding program and fiscal policy; convening a workgroup to facilitate discussions between the state and the provider and consumer communities; conducting a longitudinal survey to assess the impact of managed care on persons with HIV; and developing a longitudinal, person-based, encounter-level database representing the clinical and service utilization histories of more than 100,000 patients for state fiscal years 1990 to 1996. The key fiscal issues identified and discussed were capitation rates, initial capitalization levels, and risk-adjustment mechanisms. Other pertinent issues included the importance of a benefits package supporting a comprehensive, integrated continuum of state-of-the-art services; marketing and enrollment; attention to provider and consumer training and education needs; and interdependence of financial reimbursement and benefits packages. From our experience in New York State, we conclude that a successful model of Medicaid managed care for persons with HIV should build on the existing infrastructure of services, using a collaborative process among government agencies, healthcare providers, and HIV/AIDS consumer communities. A future challenge lies in the implementation of the HIV SNP model and evaluation of its soundness and ability to ensure quality healthcare services.

Capitation Fee↗
PubMed1996

Timing of surgery after acute myocardial infarction.

OBJECTIVE: We wished to determine if timing of surgery, when other co-morbid variables are controlled, influenced outcome after operations for acute myocardial infarction. DESIGN: Between 3/20/1990 and 6/17/1994, data was prospectively collected on 338 patients undergoing operation for either evolving infarcts (n=73) or up to 21 days after infarction (mean 7.9 days). SETTING: Tertiary hospital referral center. PATIENTS: Infarction was diagnosed by CK enzymes or EKG Q-waves preoperatively in 338 patients undergoing surgery. The mean age of the patients was 66.1 years (SD+/-10.5 years), 76 had emergency operations immediately after catheterization (50 following PTCA complications), 223 had urgent operations, and 39 were elective. INTERVENTIONS: Seventy-three had preoperative ballon pumps, and 259 had one or more mammary artery bypasses with a mean of 3.27 (SD+/-1.0) distal anastomoses. RESULTS: In-hospital and 30-day survival rate was 95.6% (323/338). Of the 73 variables evaluated by step-wise logistic regression analysis, the multivariate independent preoperative predictors of death were: aortic valve regurgitation, chronic pulmonary disease, preoperative diuretic administration, preoperative balloon pump, preoperative inotropes, and the need for additional concomitant noncardiac surgery. Including the operative variables, the predictors were: preoperative balloon pump, preoperative inotropes, the presence of left main stenosis, preoperative renal failure, chronic pulmonary disease, valve disease, ischemic arrhythmia, pump perfusion time, valve surgery, and homologous blood transfusion volume required. When the postoperative variables were included, the predictors were: preoperative inotropes, postoperative balloon pump, postoperative epinephrine, postoperative permanent stroke, and postoperative acute renal failure. The time between infarction and operation was not an independent prediction (p>0.4) in any of the logistic regression models. CONCLUSION: Early operation after acute infarction is not in itself a risk factor, rather comorbid disease and preoperative hemodynamic status determine outcome after surgery.

Hemodynamics↗
PubMed1995

Silent giant left atrium. A case report.

A sixty-two-year-old white woman with a 14.5 cm (145 mm) silent giant left atrial enlargement secondary probably to rheumatic heart disease is presented. Aside from mild progressive shortness of breath during the past year, the patient had been asymptomatic all her life. Her clinical picture was manifested for the first time by syncope secondary to slow atrial fibrillation, for which a permanent pacemaker was required. The correct diagnosis of the enlarged chamber was not possible through the routine chest roentgenogram. In this case, the echocardiogram, nuclear angiogram, and computed tomography were the pertinent studies needed to reach the diagnosis.

Cardiomegaly↗
PubMed1994

Sequence of the Streptomyces albus G lipase-encoding gene reveals the presence of a prokaryotic lipase family.

An extracellular lipase (Lip)-encoding gene from Streptomyces albus G has been cloned and sequenced. It encodes a Lip with 82% sequence identity to another previously cloned Lip from a Streptomyces species not closely related. These two sequences can be aligned with 33% identity to the sequence of Lip1 from the antarctic psychrotroph Moraxella TA144 [G. Feller et al., Nucleic Acids Res. 18 (1990) 6431]. An alignment of the three sequences revealed amino-acid substitutions which might be responsible for the greater thermal stability of the Streptomyces lipases. The presence of this lip gene family in several members of the Streptomyces genus was also shown.

Amino Acid Sequence↗
PubMed1992

Late evaluation of glomerular filtration rate, proteinuria, and urinary acidification after acute tubular necrosis.

Fourteen patients were studied 2 to 36 months after acute tubular necrosis. It was observed that 43% of the patients had decreased glomerular filtration rate. These patients were older and had lower urinary excretion of ammonium and titratable acidity. Proteinuria greater than 150 mg/day, without reaching a nephrotic level, was found in 92% of the patients. The presence of oliguria, the demand of dialysis, and the acute tubular necrosis etiology were not statistically different among the patients who recovered their glomerular filtration rate either totally or partially.

Adult↗
PubMed1991

Ventricular tachycardia as a first manifestation of right ventricular myxoma--a case presentation.

The authors present a case of a thirty-nine-year-old white man in good health who developed episodes of ventricular tachycardia as a first manifestation of a right ventricular myxoma, which was diagnosed by two-dimensional echocardiogram and then resected with no complications and total disappearance of the cardiac arrhythmia. After reviewing the literature they consider the present case as a rare manifestation of an infrequent location of an uncommon disease.

Adult↗