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Biomedical subjects

M Rizzo

Publications and source records attributed to M Rizzo.

At least 127 records · Page 7Linked to original sources
PubMed1997

Integrin activation protects pulmonary endothelial cells from the genotoxic effects of bleomycin.

Integrin activation promotes the survival of endothelial cells undergoing diverse forms of stress. Here we determined the ability of integrins to inhibit DNA strand breakage by bleomycin (BLM), a DNA-cleaving antitumor antibiotic that causes acute endothelial injury and subsequent pulmonary fibrosis. We found that BLM produced DNA breakage in cultured murine lung endothelial cells (MLEC) within 45 min of treatment as measured by DNA sedimentation and in situ labeling of 3'-OH by nick translation (ISNT). Two hours after the removal of BLM, we found a marked but incomplete reduction in DNA strand breakage as measured by ISNT, indicating that the damage was reversible. DNA sedimentation and ISNT demonstrated that strand breakage due to BLM was inhibited in MLEC cultured on fibronectin, and no evidence of breakage was found 2 h after removal of the drug in ISNT experiments. Gelatin, type IV collagen, laminin, and the integrin ligand peptide Gly-Arg-Gly-Asp-Ser-Pro, but not the inactive Gly-Arg-Ala-Asp-Ser-Pro peptide, also inhibited DNA strand breakage. Activation of integrins, either by coating surfaces with antibodies to alpha 5-, beta 1-, or beta 3-integrin subunits or by receptor clustering with the soluble antibodies, inhibited BLM-induced DNA breakage. Inhibition of BLM-induced DNA strand breakage by soluble beta 1-integrin antibody increased with increasing antibody concentration and duration of receptor clustering before BLM treatment. Thus integrin activation protects pulmonary endothelial cells from the genotoxic effects of BLM.

Animals↗
PubMed1997

Localization of endothelin-converting enzyme-1 in human kidney.

The distribution of endothelin-converting enzyme-1 (ECE-1) mRNA and protein was investigated in human kidney excised because of renal tumors. ECE-1 immunoreactivity was detected by immunohistochemistry throughout the different areas of the kidney in the vascular and tubular structures. In the cortex, ECE-1 immunostaining was present in the endothelial surface of arcuate and interlobular arteries and in arterioles. Weak specific immunoreactivity was present over some proximal and distal tubules. Few endothelial glomerular cells contained ECE-1 protein. In the medulla, ECE-1 immunoreactivity was observed in the vasa recta bundles and capillaries. ECE-1 immunostaining was also detected in the outer and inner medullary collecting ducts and thin limbs of Henle's loops. Immunohistochemical detection of the von Willebrand factor on adjacent sections confirmed the endothelial nature of the vascular cells that exhibited ECE-1 immunostaining. The distribution patterns of ECE-1 mRNA, investigated by in situ hybridization, appeared similar to that obtained by immunohistochemistry in the cortical and medullary vasculature and in different portions of the nephron. Northern blot and densitometric analyses demonstrated that ECE-1 mRNA levels were quantitatively similar in both the renal cortex and medulla. These results demonstrate that vascular endothelial and tubular epithelial cells in the cortex and medulla of the human kidney synthesize ECE-1, which, in turn, may play an important role in regulating endothelin production in physiological and pathological conditions.

Adult↗
PubMed1997

Cowper's gland duct cyst in an adult male. Radiological and clinical aspects.

A 48-year-old man presenting with perineal pain, weak stream and dysuria was found to have a Cowper's gland duct cyst measuring 1.8 x 3.5 cm, which was investigated with retrograde and voiding urethrography, cavernosography and perineal MRI, which was the single most useful imaging technique. Treatment consisted in complete surgical excision, which allowed an anatomical reconstruction of the urethra. This condition is typical of the pediatric age group, and seldom diagnosed in adults.

Adult↗
PubMed1997

Driving with Alzheimer disease: the anatomy of a crash.

Alzheimer disease (AD) affects several abilities that are crucial to automobile driving and can thereby increase the risk for a crash. The specific driver safety errors that lead up to crashes in this driver population, however, remain largely unknown. We developed a graphical means for dissecting these safety-related behaviors for application to car crashes of AD drivers. These crashes occurred in collision avoidance scenarios implemented on the Iowa Driving Simulator. Crash plots were produced by "rewinding" the data stream, then graphing the vehicle speed, path, steering wheel position, pedal positions, and driver gaze up to the very moment of impact. In this way, we were able to display in detail the patterns of vehicle and driver control to determine exactly how a crash occurred. Several different types of antecedent safety errors were noted, ranging from responding inappropriately with the hand and foot controls to not responding at all. In this paper we focus on the performance of a single impaired driver to demonstrate our technique and findings. Understanding the "anatomy" of crashes in cognitively disabled drivers with AD can help guide future efforts at injury prevention and control.

Aged↗
PubMed1997

Long-term results of anterior and posterior urethroplasty with actuarial evaluation of the success rates.

PURPOSE: We analyzed the long-term results of different urethroplasty techniques. MATERIALS AND METHODS: We performed a retrospective review of 98 patients who underwent different procedures for anterior (78) and posterior (20) urethral strictures. Mean followup was 53 months. A total of 20 patients underwent end-to-end anastomosis (group 1), 30 underwent 1-stage procedures (group 2), 28 underwent 2-stage procedures (group 3), and 20 underwent bulboprostatic anastomosis (group 4). The results were analyzed using Kaplan-Meier curves and log rank test. RESULTS: The success rate was 95% for group 1, 93.4% for group 2, 78.6% for group 3, and 70% for group 4. Statistical evaluation of the actuarial success rates failed to show significant differences among the 4 groups. CONCLUSIONS: The stricture recurrences were uniformly distributed over time. Urethroplasty patients must be followed for the rest of their lives.

Actuarial Analysis↗
PubMed1997

Update on renal acidification: a physiological view.

The kidney plays a major role in the regulation of acid-base balance. This process is mainly dependent on H+ secretion in the tubular lumen. Two acid extruder proteins are involved: the Na+/H+ exchanger and H(+)-ATPase. Studies using in vivo and in vitro microperfusion and isolated membrane vesicles have clearly demonstrated that the Na+/H+ exchanger is the main mechanism regulating H+ secretion/HCO3- reabsorption along the proximal nephron. Moreover, several reports indicate that this protein is involved in intracellular pH (pHi) regulation. Newer studies using molecular biology techniques have identified at least five isoforms of the Na+/H+ exchanger: NHE-1 is the housekeeping isoform, while NHE-3 seems to be implicated in transepithelial acid-base transport, although other isoforms could be involved too. H(+)-ATPase is the major acid extruder protein along the distal nephron, but it is also expressed along the proximal tubule, where a Na(+)-independent bicarbonate reabsorption has been described. There are a few studies indicating that the proton pump participates in pHi regulation, particularly in the presence of a large acid load. Its absence along the distal nephron may be one of the causes of distal tubular acidosis.

Acid-Base Imbalance↗
PubMed1997

Increased concentration of soluble human leukocyte antigen class I levels in the bronchoalveolar lavage of human pulmonary allografts.

BACKGROUND: Human leukocyte antigen (HLA) class I antigens, are glycoproteins expressed on the cell surface and are also secreted (sHLA) into the surrounding fluids. This study investigates whether pulmonary allograft rejection is associated with an increased amount of sHLA class I in the bronchoalveolar lavage (BAL) fluid. METHODS: Enzyme-linked immunosorbant assays were used to measure sHLA class I levels in BAL samples from 66 lung transplant recipients. RESULTS: Analysis of pulmonary allograft recipients revealed that the mean concentration of sHLA class I was significantly higher in samples from recipients with acute rejection than in recipients with no evidence of rejection. Seventy-two percent of the patients with rejection had sHLA levels above the normal range for patients with infection or rejection. Conversely, sHLA levels were within normal limits in 94% of the control population. Time kinetic analysis revealed that in subjects with rejection, sHLA class I levels peaked in the first 2 weeks after transplantation and decreased thereafter. Increased levels of sHLA were found in patients with acute rejection but not in those with chronic rejection. Fifty-nine percent (n = 10) of the patients with infection had sHLA levels within the normal (no infection or rejection) range. The remaining 41% (n = 7) with infection had sHLA above the normal range. Fifty-seven percent (n = 4) of the latter group had cytomegalovirus infection. These results were confirmed in a prospective study carried out by analyzing paired samples obtained during and after rejection. Eight of the nine patients had high BAL sHLA class I during acute rejection, and low BAL sHLA class I levels after resolution of the acute rejection. CONCLUSION: Our data demonstrate that measurement of sHLA class I levels in BAL samples is a sensitive indicator of acute rejection.

Acute Disease↗
PubMed1996

Specific blockade of slowly activating I(sK) channels by chromanols -- impact on the role of I(sK) channels in epithelia.

Chromanols, which were recently shown to inhibit cAMP-mediated Cl- secretion in colon crypts via a blockade of a cAMP-activated K+ conductance, were analyzed for their effects on distinct cloned K+ channels expressed in Xenopus oocytes. The lead chromanol 293B specifically inhibited I(sK) channels with an IC50 of 7 micromol/l without affecting the delayed rectifier Kv1.1 or the inward rectifier Kir2.1. Moreover, several other chromanols displayed the same rank order of potency for I(sK) inhibition as demonstrated in colon crypts. Finally, we tested the effects of the previously described I(sK) blocker azimilide on cAMP mediated Cl- secretion in rat colon crypts. Similar to 293B azimilide inhibited the forskolin induced Cl- secretion. These data suggest that I(sK) protein induced K+ conductances are the targets for the chromanol 293B and its analogues, and azimilide.

Animals↗
PubMed1996

The relative efficacy of cues for two-dimensional shape perception.

The visual system uses a variety of cues for form perception, including motion, color, binocular disparity, texture, and luminance. Physiological evidence suggests that these cues are processed by different neural mechanisms. Do the cues processed by some mechanisms convey any advantage for form perception when compared to cues processed by another? In response to this question we assessed the relative efficiency of several cues in conveying two-dimensional form from background noise. For the sake of comparison, every cue type used the same experimental design and stimulus set. Our results confirm that movement is one of the most efficient cues for shape perception. Also, a simple transient cue (an instantaneous flashing on or off) is equally useful. In comparison, local dot density (a type of texture cue) was the least efficient. The efficiencies of most other cues, such as color, stereopsis, and relative movement in noise, were conspicuously similar.

Adult↗
PubMed1996

Optical blur and the perception of global coherent motion in random dot cinematograms.

We evaluated the effect of +3.25 dioptres of optical blur on the discrimination of motion direction in random dot cinematograms. Dot displacement between frames varied from 2.1 to 63' of visual angle while the temporal interval was held constant. Optical blur worsened discrimination in three normal subjects at displacements below 16', but improved discrimination at displacements of 21' or more. In a second experiment, two subjects viewed equivalent velocity stimuli constructed with different combinations of temporal interval and spatial displacement. Results showed that the effect of blur was specific to displacement and not velocity. Furthermore, varying the dot density of the display showed that the effect of blur correlated with dot displacement and not the probability of dot mismatches. Since optical blur attenuates high spatial frequencies, this suggests that high spatial frequencies are important for motion perception when dot displacements are less than 16' to 21', but reduce motion perception at larger dot displacements. The use of random dot cinematograms in populations must take into account stimulus displacement and optical causes of reduced spatial acuity.

Contrast Sensitivity↗
PubMed1996

1,4-Benzodiazepine derivatives as anticonvulsant agents in DBA/2 mice.

1. The behavioural and anticonvulsant effects of 10 1,4-benzodiazepine derivatives were studied after intraperitoneal administration in DBA/2 mice, a strain genetically susceptible to sound-induced seizures. 2. The anticonvulsant effects were evaluated on seizures evoked by means of auditory stimulation (109 dB, 12-16 kHz) in animals placed singly under a perspex dome. The rank order of potency for anticonvulsant activity was alprazolam > clonazepam > flunitrazepam > diazepam > pinazepam > desmethyldiazepam > oxazepam > prazepam > halazepam > camazepam. 3. The impairment of locomotor performance following IP administration of the above reported derivatives was also evaluated by means of the rotarod test. 4. Hypothermic activity was observed after the highest doses of the benzodiazepines studied. 5. The potency of various 1,4-benzodiazepines as inhibitors of specific [3H] flumazenil binding to membranes from cerebellum or cortex was evaluated. In general, 1,4-benzodiazepines were active as anticonvulsants at micromolar range and inhibited [3H] flumazenil binding at nanomolar range. 6. The different degree of anticonvulsant activity and impairment of coordinated motor movements cannot be directly related to the benzodiazepine binding affinity or to the lipophilicity of the compounds studied.

Animals↗
PubMed1996

Structure-activity relationships of 2-aryl-2,5-dihydropyridazino [4,3-b]indol-3(3H)-ones at the benzodiazepine receptor.

A large series of 2-aryl-2,5-dihydropyridazino[4,3-b]indol-3(3H)ones (PIs) carrying properly selected substituents at the indole and N2-phenyl rings was prepared and tested as central benzodiazepine receptor (BZR) ligands and potential (anti)convulsant agents. Stereoelectronic requirements for high receptor affinity were detected by means of 2-D and 3-D QSAR analyses. BZR affinities and pharmacological profiles of the compounds were examined in comparison with some other pyridazinoindolones recently described by us and with pyrazoloquinoline (PQ) analogues. An anticonvulsant activity greater than PQs was generally observed for PIs. Notably, in the test of audiogenically induced seizures, one compound showed a potency comparable to that of diazepam.

Animals↗
PubMed1996

Overexpression and activation of hepatocyte growth factor/scatter factor in human non-small-cell lung carcinomas.

Hepatocyte growth factor/scatter factor (HGF/SF) stimulates the invasive growth of epithelial cells via the c-MET oncogene-encoded receptor. In normal lung, both the receptor and the ligand are detected, and the latter is known to be a mitogenic and a motogenic factor for both cultured bronchial epithelial cells and non-small-cell carcinoma lines. Here, ligand and receptor expression was examined in 42 samples of primary human non-small-cell lung carcinoma of different histotype. Each carcinoma sample was compared with adjacent normal lung tissue. The Met/HGF receptor was found to be 2 to 10-fold increased in 25% of carcinoma samples (P = 0.0113). The ligand, HGF/SF, was found to be 10 to 100-fold overexpressed in carcinoma samples (P < 0.0001). Notably, while HGF/SF was occasionally detectable and found exclusively as a single-chain inactive precursor in normal tissues, it was constantly in the biologically-active heterodimeric form in carcinomas. Immunohistochemical staining showed homogeneous expression of both the receptor and the ligand in carcinoma samples, whereas staining was barely detectable in their normal counterparts. These data show that HGF/SF is overexpressed and consistently activated in non-small-cell lung carcinomas and may contribute to the invasive growth of lung cancer.

Adenocarcinoma↗
PubMed1996

Bilateral effects of unilateral visual cortex lesions in human.

We studied the vision of 12 patients with unilateral lesions of the visual cortex. All had a VI-type scotoma located in the contralateral visual fields, as expected, and visual acuity of 20/30 or better. Our aim was to test the hypothesis that they also had a visual deficit in their ipsilesional or 'good' visual fields. The first experiment tested the subjects' ability to respond to transient signals presented at unpredictable temporal intervals and spatial locations amongst many spatially random and identical distracter elements. The results showed that, compared with controls, the lesion group had a significantly reduced sensitivity to signal and increased response times affecting both hemifields. In a second experiment, we tested the useful field of view (UFOV) in two of the patients under conditions of differing attention demand. Both showed bilateral constriction, compatible with the results of the first experiment. One possible explanation for the bilateral effects of unilateral occipital lobe lesions is damage to interhemispheric connections along their presplenial course, affecting the synthesis of visual information from both hemifields (i.e. the interhemispheric diaschisis effects put forth by von Monakow). The trouble is task dependent and can be construed as a global reduction in visual attention capacity. It is subtle in comparison with the contralesional V1-type scotoma that Holmes measured, yet may account for unexplained complaints of reduced performance in some patients, particularly in tasks with high visual information processing demands, such as reading and automobile driving.

Adult↗
PubMed1996

Lomefloxacin versus ciprofloxacin in the treatment of complicated urinary tract infections: a multicenter study.

The efficacy and safety of lomefloxacin 400 mg daily in the treatment of complicated urinary tract infections were confirmed in a randomized multicenter study that enrolled 294 patients from 16 centers in Italy. A total of 155 patients were treated with 400 mg lomefloxacin once daily for 15 days while a total of 139 patients received 500 mg of ciprofloxacin twice daily for 15 days. Eradication of the initial pathogen was observed in 87% of patients treated with lomefloxacin and in 81% of ciprofloxacin-treated patients while clinical success was achieved in 85% of lomefloxacin-treated patients and in 76% of patients treated with ciprofloxacin. The differences in outcome between the two treatment groups were not statistically significant (chi 2 = ns). Both drug regimens were well tolerated and no patients discontinued treatment due to adverse events. In conclusion, once-daily lomefloxacin was as effective as twice-daily ciprofloxacin in the treatment of complicated urinary tract infections.

Administration, Oral↗