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Biomedical subjects

M F Brown

Publications and source records attributed to M F Brown.

At least 37 records · Page 2Linked to original sources
PubMed1999

Plasmon resonance spectroscopy: probing molecular interactions within membranes.

Surface plasmon resonance (SPR) has become a popular method for investigating biomolecular interactions. A new variant of this technique, coupled plasmon-waveguide resonance (CPWR) spectroscopy, allows the characterization of anisotropic biological membranes. Plasmon resonance can therefore be used to study the molecular events involved in a wide variety of membrane processes, including energy conversion and signal transduction.

Animals↗
PubMed1999

Role of P-selectin expression in hepatic ischemia and reperfusion injury.

BACKGROUND: Researchers have shown that reperfusion of ischemic tissues initiates a complex series of reactions that paradoxically injure tissues. Although several mechanisms have been proposed to explain the pathobiology of ischemic/reperfusion (I/R) injury, much attention has focused on adhesion molecules. Our research is intended to show the kinetics of P-selectin in the liver in response to I/R injury. METHODS: Left-lobar hepatic ischemia was induced for 30 min in 35 C57BL-6 mice and 20 P-selectin-deficient (K-O) mice. P-selectin expression was measured in these mice at 20 min, 2, 5, 12 and 24 h reperfusion times, as well as in control and sham animals. The animals were injected with radio-labeled P-selectin monoclonal antibody and the organs were harvested for counts/g tissue, expressed as the percentage injected dose. Serum liver enzymes were measured and pathological sections of ischemic and control livers were performed. The unpaired t-test was used for statistical analysis. RESULTS: P-selectin expression showed two peaks in this animal model. The first peak was at 20 min and the second peak at 5 h of reperfusion (p < 0.001). We documented an 8-fold increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) levels 10 h following I/R injury. Pathological specimens showed periportal necrosis consistent with an ischemic event. P-selectin K-O mice showed no up-regulation as a separate control group, and the liver enzymes were significantly lower than the wild-type mice at 10 h (p < 0.001). CONCLUSION: P-selectin has a bimodal expression following hepatic I/R injury. The first peak is attributed to the Weibel-Palade bodies and the second to new translational P-selectin. We noted no difference in the up-regulation of P-selectin in the ischemic and non-ischemic liver lobes in the same animal.

Alanine Transaminase↗
PubMed1999

Identification of a herpes simplex virus-induced dendrite in an eye-bank donor cornea.

PURPOSE: To demonstrate the presence of an active herpetic dendrite in an eye-bank cornea. METHODS CASE REPORT: One eye-bank cornea was studied. Viral cultures and polymerase chain reaction (PCR) testing were performed 4 days after tissue preservation. The presence or absence of herpes simplex virus (HSV) type 1 was investigated. RESULTS: The presence of an active HSV dendrite in an eye-bank cornea was verified. HSV type 1 was confirmed using PCR amplification and restriction endonuclease DNA fragment analysis. CONCLUSION: This case suggests that HSV may remain viable in stored corneal tissue at 4 degrees C.

Cornea↗
PubMed1999

Wildcat World: simulation programs for teaching basic concepts in psychological science.

A series of computer programs is described that allows beginning psychology students to design, conduct, analyze, and interpret virtual (computer-simulated) psychological studies. This technique allows the instructor more control over the outcome of student experiments, increases the scope of experiments that can be done by students, decreases the amount of class time that must be devoted to conducting experiments, and eliminates concerns about student experimenters using human or animal subjects.

Computer-Assisted Instruction↗
PubMed1998

N-carbamoyl analogs of Zafirlukast: potent receptor antagonists of leukotriene D4.

Exploration of the indole nitrogen region of Zafirlukast (1) has uncovered a potent series of cysteinyl leukotriene D4 (LTD4) antagonists. These studies showed that a variety of functionality could be incorporated in this region of the molecule without sacrificing potency. Efforts to exploit this site in order to improve oral efficacy are discussed.

Animals↗
PubMed1998

Chromophore orientation in bacteriorhodopsin determined from the angular dependence of deuterium nuclear magnetic resonance spectra of oriented purple membranes.

The orientation of prosthetic groups in membrane proteins is of considerable importance in understanding their functional role in energy conversion, signal transduction, and ion transport. In this work, the orientation of the retinylidene chromophore of bacteriorhodopsin (bR) was investigated using 2H NMR spectroscopy. Bacteriorhodopsin was regenerated with all-trans-retinal stereospecifically deuterated in one of the geminal methyl groups on C1 of the cyclohexene ring. A highly oriented sample, which is needed to obtain individual bond orientations from 2H NMR, was prepared by forming hydrated lamellar films of purple membranes on glass slides. A Monte Carlo method was developed to accurately simulate the 2H NMR line shape due to the distribution of bond angles and the orientational disorder of the membranes. The number of free parameters in the line shape simulation was reduced by independent measurements of the intrinsic line width (1.6 kHz from T2e experiments) and the effective quadrupolar coupling constant (38. 8-39.8 kHz from analysis of the line shape of a powder-type sample). The angle between the C1-(1R)-1-CD3 bond and the purple membrane normal was determined with high accuracy from the simultaneous analysis of a series of 2H NMR spectra recorded at different inclinations of the uniaxially oriented sample in the magnetic field at 20 and -50 degrees C. The value of 68.7 +/- 2.0 degrees in dark-adapted bR was used, together with the previously determined angle of the C5-CD3 bond, to calculate the possible orientations of the cyclohexene ring in the membrane. The solutions obtained from 2H NMR were then combined with additional constraints from linear dichroism and electron cryomicroscopy to obtain the allowed orientations of retinal in the noncentrosymmetric membrane structure. The combined data indicate that the methyl groups on the polyene chain point toward the cytoplasmic side of the membrane and the N-H bond of the Schiff base to the extracellular side, i.e., toward the side of proton release in the pump pathway.

Bacteriorhodopsins↗
PubMed1998

Septic complications after splenectomy for sickle cell sequestration crisis.

Patients with sickle cell disease (SCD) are predisposed to infections. There is a paucity of recent information on the incidence of post-splenectomy infectious complications in these patients. The purpose of this study was to determine whether splenectomy increases infectious complications in SCD. Twenty-nine patients with SCD had splenectomy for sequestration crises at our hospital between 1988 and 1992; 16 of them received all of their follow-up care at our institution. These 16 charts were reviewed for infectious-related admissions, hospital days, days of i.v. antibiotics, positive cultures, and episodes of sepsis. For each patient, these parameters in the pre- and postoperative period were compared and expressed as number per year. The mean age at time of splenectomy was 2.5 +/- 0.4 years and the mean follow-up was 4.5 +/- 0.4 years. There was no significant difference in the pre- and postoperative periods for admissions, hospital days, days of i.v. antibiotics, positive cultures, or episodes of sepsis per year. There were also no operative deaths. The incidence of pre-splenectomy sepsis was 0.04 +/- 0.03 episodes per year compared to 0.09 +/- 0.04 (P = ns) episodes/year after splenectomy. Sepsis occurred at an average of 20.8 (range 2-30) months postoperatively; Streptococcus pneumoniae was the most common causative organism. The total mortality after splenectomy in SCD patients was 3.4% (1/29) over a nearly 5-year period. Although infections are common in children with SCD, there was no increase in infections or episodes of sepsis in SCD patients who underwent splenectomy.

Child↗
PubMed1998

Corneal lenticular wrinkling after automated lamellar keratoplasty.

PURPOSE: To report complications of automated lamellar keratoplasty in two eyes of two patients. METHODS: Case reports. Two eyes of two patients underwent automated lamellar keratoplasty for myopia. Both patients complained of visual distortion and glare in the postoperative eye. RESULTS: The postoperative eye of both patients showed evidence of wrinkling of the corneal lenticule accompanied by irregular astigmatism. Patient 1 showed persistent lenticular wrinkling and corneal scarring 2.5 years later. Patient 2 showed evidence of interface scar and overcorrection. CONCLUSION: The use of a microkeratome can be complicated by lenticular displacement and wrinkling, resulting in visual aberration for the patient.

Adult↗
PubMed1998

ICAM-1 upregulation in distant tissues after hepatic ischemia/reperfusion: a clue to the mechanism of multiple organ failure.

BACKGROUND/PURPOSE: Endothelial cell adhesion molecules (ECAMs) are felt to play an important role in ischemia/reperfusion (I/R) injury by causing adhesion of leukocytes to endothelial cells. It is possible that ECAMs play a role in multiple organ system failure. ICAM-1 is one of the adhesion molecules that has been shown to be upregulated in response to cytokines. This upregulation leads to leukocyte endothelial cell interaction (adhesion) and to neutrophil infiltration of the affected tissue. The purpose of our study was to measure ICAM-1 expression in the liver and other organs after hepatic ischemia/reperfusion (I/R). METHODS: A laparotomy was performed on 14 Sprague-Dawley rats; 45 minutes of occlusive ischemia to the left lateral lobe was followed by 5 hours of reperfusion. The rat was injected with I125-labeled ICAM-1 MAb and I131-labeled nonbinding MAb (to control for nonspecific accumulation of ICAM-1 MAb). Entire organs were harvested and accumulated activity was measured in each organ. ICAM-1 levels were expressed as percent injected dose per gram of tissue. Control animals underwent sham laparotomy. RESULTS: ICAM-1 was upregulated in the ischemic lobe of the liver, nonischemic lobe of the liver, heart, kidney, intestine, and pancreas. Up-regulation in the lung was not significant. Both the lung and liver had high constitutive levels of ICAM-1. CONCLUSIONS: These data show that (1) significant hepatic upregulation of ICAM-1 after hepatic ischemia/reperfusion and (2) significant ICAM-1 upregulation in other tissues (heart, kidney, and intestine) after hepatic ischemia/reperfusion. The ICAM-1 upregulation in distant organs is likely mediated by cytokines such as tumor necrosis factor (TNF). These data show that leukocyte endothelial cell interactions in distant organs may be mediated by hepatic ischemia/reperfusion. This is a possible explanation for how failure of one organ can lead to failure of others in multiple organ system failure.

Animals↗
PubMed1998

Delayed external compression reduction of an omphalocele (DECRO): an alternative method of treatment for moderate and large omphaloceles.

BACKGROUND/PURPOSE: Standard treatment of large hepatoomphaloceles has been SILASTIC (Dow Corning, Midland, MI) silo placement followed by closure. This requires two operations, and complications from the silo may occur. The authors have looked for a safe and simpler alternate method of closure. Delayed external compression reduction of an omphalocele (DECRO), appears to have a low complication rate and a rapid time to closure. METHODS: The authors reviewed retrospectively the records of six patients with hepato-omphaloceles treated with DECRO from August 1993 to July 1997. All defects were evaluated by the attending surgeon and could not be closed primarily. All data are expressed as mean +/- SEM. RESULTS: The average gestational age was 36.5 +/- 0.67 weeks with mean weight of 2,780 +/- 256 g. Two patients had congenital cardiac disease. The mean size of the defects was 6.2 x 5.7 cm. All defects had the liver out of the abdomen. No patients required silo placement. The mean time to reduction and final closure was 5.6 +/- 0.49 days. The average postoperative time on the ventilator was 7.1 +/- 3.5 days. Mean time to full feeds was 18.8 +/- 3.4 days. One patient had superficial necrosis of the skin flap. Mean time to discharge was 30.5 +/- 5.5 days. All patients had DECRO completed without complications. CONCLUSIONS: This procedure decreases the number of operations needed from two to one. No complications were seen from the procedure and the time of mechanical ventilation required was low. The abdominal compartment syndrome developed in none of the patients. DECRO is a safe and very effective alternative to SILASTIC silo placement in moderate and large omphaloceles that cannot be closed primarily.

Bandages↗
PubMed1998

Zoonotic Onchocerca (Nematoda:Filarioidea) in the cornea of a Colorado resident.

OBJECTIVE: A female patient, resident in the state of Colorado, presented with iritis of the right eye. Slit-lamp examination showed the presence of a thin, threadlike worm entwined in the cornea. The patient was taken to surgery for removal of the parasite. DESIGN: A case report. INTERVENTION: A 3-mm-long supertemporal incision was made in the cornea and further dissected until the worm could be grasped and removed by gentle traction. RESULTS: The worm, a filarial nematode, was identified as a member of the genus Onchocerca, most likely Onchocerca cervicalis, a natural parasite of horses. The patient had an uneventful recovery, and 1 week after surgery, her visual acuity, intraocular pressure, and corneal edema were all resolving. CONCLUSION: In the United States and elsewhere, most cases of zoonotic filarial infection involving the eye are caused by Dirofilaria or Dipetalonema-like worms. However, the current case was caused by a species of Onchocerca. This is the first case of zoonotic Onchocerca from the eye to be reported, only the second case of zoonotic Onchocerca in the United States, and the seventh case worldwide. The worm was removed surgically, and the patient had an uneventful recovery.

Animals↗
PubMed1997

Quantification of P-selectin expression after renal ischemia and reperfusion.

Neutrophils are important in ischemia and reperfusion injury. Multiple factors may be responsible for the adhesion of granulocytes to endothelial cells. P-selectin is a carbohydrate-binding glycoprotein that is stored preformed in endothelial cells as Weibel-Palade bodies. This preformation implies a very early role of P-selectin in the leukocyte adhesion process. Previous studies of P-selectin have not quantified its expression. The purpose of this study is to quantitate the expression and time course of P-selectin in response to renal ischemia and reperfusion injury. P-selectin was measured in 34 C57BL-6 mice after 30 minutes of occlusive left renal ischemia followed by 20 minutes, 2, 5, 10, and 24 hours of reperfusion. This was also performed in control and sham laparotomy groups. P-selectin was quantified using a new double radiolabeled 125I/131I monoclonal antibody technique and reported as percent injected dose per gram of tissue. P-selectin expression peaked at 20 minutes, plateaued up to 5 hours, and fell at 10 hours. Additionally, genetically altered mice that do not express P-selectin showed no up regulation after 5 hours of reperfusion. Pathology results confirmed significant renal injury. Renal ischemia and reperfusion injury caused significant upregulation of P-selectin. Expression of P-selectin at the short reperfusion time of 20 minutes reinforces the premise that P-selectin is one of the earliest adhesion molecules expressed. This early peak is probably caused by the release of preformed P-selectin. The delineation of these mechanisms of injury may be important in understanding and preventing renal injury in transplantation, sepsis, and shock.

Animals↗
PubMed1997

Sensory and sympathetic innervation of the vertebral endplate in patients with degenerative disc disease.

We obtained intervertebral discs with cartilage endplates and underlying cancellous bone at operation from patients with degenerative disc disease and then used immunohistochemical techniques to localise the nerves and nerve endings in the specimens. We used antibodies for the ubiquitous neuronal protein gene product 9.5 (PGP 9.5). Immunoreactivity to neuropeptide Y was used to identify autonomic nerves and calcitonin gene-related peptide (CGRP) and substance P to identify sensory nerves. Blood vessels were identified by immunoreactivity with platelet-endothelial cell-adhesion molecule (CD31; PECAM). In a control group with no known history of chronic back pain, nerve fibres immunoreactive to PGP 9.5 and neuropeptide Y were most closely related to blood vessels, with occasional substance P and CGRP immunoreactivity. In patients with severe back pain and markedly reduced disc height, proliferation of blood vessels and accompanying nerve fibres was observed in the endplate region and underlying vertebral bodies. Many of these nerves were immunoreactive to substance P or CGRP, and in addition, substance P- and CGRP-immunoreactive nociceptors were seen unrelated to blood vessels. Quantification by image analysis showed a marked increase in CGRP-containing sensory nerve fibres compared with normal control subjects. We speculate that a chemotactic response to products of disc breakdown is responsible for the proliferation of vascularity and CGRP-containing sensory nerves found in the endplate region and vertebral body adjacent to degenerate discs. The neuropeptides substance P and CGRP have potent vasodilatory as well as pain-transmitting effects. The increase in sensory nerve endings suggests increase in blood flow, perhaps as an attempt to augment the nutrition of the degenerate disc. The increase in the density of sensory nerves, and the presence of endplate cartilage defects, strongly suggest that the endplates and vertebral bodies are sources of pain; this may explain the severe pain on movement experienced by some patients with degenerative disc disease.

Adolescent↗
PubMed1997

Hepatic ischemia/reperfusion affects leukocyte rolling and velocity.

Mechanisms of injury in hepatic ischemia/reperfusion injury are poorly defined. Leukocytes are thought to be important in the final mechanism of hepatic damage. We intend to show the time course of abnormal leukocyte activity in the liver after ischemia/reperfusion (I/R) injury. Left lobar hepatic ischemia was induced for 20 min in anesthetized C57B1-6 mice. Measurements were taken at control, reperfusion, and matching sham times (no ischemia) of 2, 5, 12, and 24 h. Measurements were taken using rhodamine and fluorescein enhanced intravital microscopy. Post sinusoidal venules were evaluated for numbers of rolling leukocytes, leukocyte saltation, and leukocyte velocity. Data are expressed as number of rolling leukocytes per 100 microns venule length (2 min). Statistical analysis was by ANOVA. The number of rolling leukocytes at 5, 12, and 24 h of reperfusion (p < 0.001) was significantly higher than control and sham-operated animals. Leukocyte velocities were significantly slower in the 12 h I/R group when compared to sham animals (p < 0.001). These data show that there are definable and quantifiable changes in leukocyte kinetics in the liver after ischemia/reperfusion. These changes, which lasted for 24 h, are likely due to upregulation of various endothelial cell adhesion molecules. Delineation of these mechanisms may be important in disease states such as shock, sepsis, and hepatic transplantation.

Analysis of Variance↗