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Biomedical subjects

R Perez

Publications and source records attributed to R Perez.

At least 37 records · Page 2Linked to original sources

The endodontic cube: a system designed for evaluation of root canal anatomy and canal preparation.

An extensively redesigned muffle system is presented incorporating improved design features, such as rigid external fixation and machined internal indexing to enable a more accurate, clinically relevant, and reproducible evaluation of root canal anatomy before and after preparation. Given the ability to directly observe and quantify changes in the root canal system, the information obtained using this design is comprehensive. In each tooth pretreatment evaluation provides the ideal control, reinforcing the suitability of this technique.

Dental Pulp Cavity↗

Vestibular end-organ impairment in an animal model of type 2 diabetes mellitus.

OBJECTIVES/HYPOTHESIS: To define and assess the functional impairment of the vestibular part of the inner ear in a diabetic state, using a direct and objective test for evaluating the vestibular end-organ and an animal model for diet-induced type 2 diabetes mellitus. STUDY DESIGN: Prospective controlled animal study. METHODS: Two groups of sand rats (Psammomys obesus) were maintained on two different diets. The experimental group received a specially designed high-energy diet known to induce a diabetic state, and the control group a low-energy diet maintaining these animals in a normal metabolic state. After 1 month of documented hyperglycemia in the experimental group, recordings of vestibular evoked potentials (VsEPs) and recordings of auditory brainstem response (ABR) were conducted in all animals. The latency and the amplitude of the first wave of both responses, shown to reflect end-organ activity, were compared between the two groups. RESULTS: The mean latency of the first wave of the VsEPs was significantly (P = .002) prolonged and the amplitude was significantly (P = .005) decreased in the diabetic group in comparison to the control group. The latency of the first wave of ABR was significantly (P = .02) prolonged, the amplitude was not significantly decreased, and threshold was significantly elevated (P = .01) in the diabetic group. CONCLUSION: For the first time, using an objective assessment test, functional impairment of the vestibular part of the inner ear has been demonstrated in the diabetic metabolic state. Despite this being an animal study, these findings would seem to indicate that the vestibular-end-organ should be added to the long list of organs and tissues adversely affected by diabetes.

Animals↗

A purified GM3 ganglioside conjugated vaccine induces specific, adjuvant-dependent and non-transient antitumour activity against B16 mouse melanoma in vitro and in vivo.

The presence of substantial amounts of GM3 ganglioside on human melanomas and other tumours, together with its peculiar biological properties, makes this glycolipid a unique target for cancer immunotherapy. B16 mouse melanoma expresses GM3 and constitutes an appropriate model for the development of novel GM3-based vaccines. Recently, we hydrophobically incorporated purified GM3 into the outer membrane protein complex from Neisseria meningitidis to form very small size proteoliposomes (GM3/VSSP). We have examined the antitumour properties of GM3/VSSP vaccine and compared it with GM3 incorporated in very low density serum lipoproteins (GM3/VLDL). Immunization with four doses of GM3/VSSP vaccine (120 microg of ganglioside) plus Freund's adjuvant or Montanide ISA 51 significantly increased the overall survival of mice inoculated in the subcutis with 103 B16-F1 cells, whereas the GM3/VLDL immunogen was ineffective. The non-transient character of tumour protection was confirmed in animals surviving the first challenge and re-inoculated with 5 x 103 cells. GM3/VSSP vaccine also reduced the subcutaneous growth of highly aggressive B16-F10 cells. The importance of ganglioside structure in the tumour-protective effect of GM3/VSSP vaccine was confirmed using GM3 containing N-glycolylneuraminic acid, a ganglioside absent in melanoma cells. Immunostaining and enzyme-linked immunosorbent assay (ELISA) experiments showed a high specificity of immune sera against GM3 and the presence of all four IgG subclasses, with a preponderance of IgG2b and IgG3. In addition, a strong anti-B16 complement-mediated cytotoxicity was induced by vaccination with GM3/VSSP. The present data indicate the molecular specificity of GM3/VSSP vaccine as well as the adjuvant-dependent and non-transient character of tumour protection in the B16 mouse model. These findings suggest that an appropriate GM3 vaccine may be capable of inducing prolonged tumour protection in melanoma patients.

Animals↗

Psammomys obesus and the albino rat--two different models of nutritional insulin resistance, representing two different types of human populations.

Animal models for insulin resistance and type 2 diabetes are required for the study of the mechanism of these phenomena and for a better understanding of diabetes complications in human populations. Type 2 diabetes is a syndrome that affects 5-10% of the adult population. Hyperinsulinaemia, hypertriglyceridaemia, decreased high-density lipoprotein (HDL) cholesterol levels, obesity and hypertension, all form a cluster of risk factors that increase the risk of coronary artery disease, and are known as insulin resistance syndrome or syndrome X. The gerbil, Psammomys obesus is characterized by primary insulin resistance and is a well-defined model for dietary induced type 2 diabetes. Weanling Psammomys and Albino rats were held individually for several weeks on high energy (HE) and low energy (LE) diets in order to determine the development of metabolic changes leading to diabetes. Feeding Psammomys on HE diet resulted in hyperglycaemia (303 +/- 40 mg/dl), hyperinsulinaemia (194 +/- 31 microU/ml) and a moderate elevation in body weight, obesity and plasma triglycerides. Albino rats on HE diet demonstrated an elevation in plasma insulin (30 +/- 4 microU/ml), hypertriglyceridaemia (170 +/- 11 mg/dl), an elevation in body weight and obesity, but maintained normoglycaemia (98 +/- 6 mg/dl). Psammomys represent a model that is similar to human populations, with primary insulin resistance expressed in young age, which leads to a high percentage of adult type 2 diabetes. Examples for such populations are the Pima Indians, Australian Aborigines and many other Third World populations. The results indicate that the metabolism of Psammomys is well adapted towards life in a low energy environment, where Psammomys takes advantage of its capacity for a constant accumulation of adipose tissue that will serve for maintenance and breeding in periods of scarcity. This metabolism known as 'thrifty metabolism', is compromised at a high nutrient intake.

Animal Nutritional Physiological Phenomena↗

In vivo visualization of pyloric mucosal hypertrophy in infants with hypertrophic pyloric stenosis: is there an etiologic role?

OBJECTIVE: Infantile hypertrophic pyloric stenosis (IHPS) is a common condition which presents in infants at 2-12 weeks of postnatal life, and whose cause remains obscure. Multiple associated abnormalities have been recognized within the external hypertrophied pyloric muscle layer, but the internal component of the pyloric mucosa has received scant attention in the literature to date. Our purpose in this study was to show that pyloric mucosal redundancy is a constant finding in infants with IHPS, to discuss its possible cause, and to explore the hypothesis of a relationship between pyloric mucosal redundancy and the development of IHPS. MATERIALS AND METHODS: We identified 102 consecutive infants with surgically confirmed IHPS and determined the thickness of the pyloric mucosa compared with the thickness of the surrounding hypertrophied muscle. Fifty-one infants who did not have pyloric stenosis served as controls. RESULTS: Mean mucosal thickness in patients with IHPS approximated mean muscle thickness, with a ratio of 0.89. In infants with IHPS, the pyloric mucosa constitutes approximately one third of the cross-sectional diameter of the pyloric mass and fills and obstructs the pyloric canal. CONCLUSION: Mucosal redundancy is a constant associated finding in IHPS. Although the origin of the redundancy and a cause-and-effect relationship are difficult to establish, our findings support the hypothesis that hypergastrinemia may be implicated in the pathogenesis of IHPS, and suggest that mucosal thickening could be implicated as one of the initiating factors in its development.

Female↗

Binocular interaction and sensitivity to horizontal disparity in visual cortex in the awake monkey.

We evaluated the binocular interaction and horizontal disparity sensitivity in neurons recorded from macaque visual cortex. Neurons from V1 of three awake Macaca mulatta monkeys were isolated by means of extracellular recording and tested for disparity sensitivity with dynamic random dot stereograms. Neurons sensitive to horizontal disparities were stimulated both monocularly and binocularly with flashing bars and their responses quantified. ANOVA and regression tests were used for data analysis. Sixty-six cells out of 185 (66/185, 36%) showed sensitivity to horizontal disparity. Disparity sensitive cells were grouped into near (25/66, 38%), tuned inhibitory (16/66, 24%), far (13/66, 20%) and tuned excitatory (12/66, 18%). Receptive fields of tuned cells were located more centrally in the visual field than those of near and far cells. The binocular interaction in tuned inhibitory cells increased linearly along with ocular unbalance. Most of tuned excitatory cells (10/12, 83%) showed facilitatory binocular interaction, characterized by a stronger response to binocular stimulation than to the stimulation of the dominant eye. On the contrary, most of tuned inhibitory cells (14/16, 88%) showed suppressory binocular interaction, characterized by a weaker response to binocular stimulation than to the stimulation of the dominant eye. Near and far cells showed both types of interaction in similar percentages. The binocular response showed a linear relationship with the sum of both monocular responses in tuned excitatory, tuned inhibitory and near cells, but not in far cells. Sensitivity to horizontal disparity may be a result of facilitatory and suppressive interactions between left and right inputs.

Animals↗

Heterogeneous nuclear ribonucleoprotein complexes from Xenopus laevis oocytes and somatic cells.

HnRNP proteins have been implicated in most stages of cellular mRNA metabolism, including processing, nucleocytoplasmic transport, stability, and localization. Several hnRNP proteins are also known to participate in key early developmental decisions. In order to facilitate functional studies of these pre-mRNA- and mRNA-binding proteins in a vertebrate organism amenable to developmental studies and experimental manipulation, we identified and purified the major hnRNP proteins and isolated the hnRNP complex from Xenopus laevis oocytes and somatic cells. Using affinity chromatography and immunological methods, we isolated a family of >15 abundant single-stranded nucleic acid-binding proteins, which range in apparent molecular weight from approximately 20 kDa to >150 kDa, and with isoelectric points from <5 to >8. Monoclonal antibodies revealed that a subset of these proteins are major hnRNP proteins in both oocytes and somatic cells in culture, and include proteins related to human hnRNP A2/B1/B2 and hnRNP K. UV crosslinking in living cells demonstrated that these proteins bind poly(A)+ RNA in vivo. Immunopurification using a monoclonal antibodyto X. aevishnRNPA2 resulted in the isolation of RNP complexes that contain a specific subset of single-stranded nucleic acid-binding proteins. The protein composition of complexes isolated from somatic cells and from oocyte germinal vesicles was similar, suggesting that the overall properties and functions of hnRNP proteins in these two cell types are comparable. These findings, together with the novel probes generated here, will also facilitate studies of the function of vertebrate RNA-binding proteins using the well characterized X. laevis oocyte and early embryo as experimental systems.

Animals↗

Directional anisotropy in the cleavage fracture of silicon

Total-energy pseudopotential calculations are used to study the cleavage anisotropy in silicon. It is shown that cracks propagate easily on 111 and 110 planes provided crack propagation proceeds in the <1;10> direction. In contrast, if the crack is driven in a <001> direction on a 110 plane the bond breaking process is discontinuous and associated with pronounced relaxations of the surrounding atoms, which results in a large lattice trapping. The different lattice trapping for different crack propagation directions can explain the experimentally observed cleavage anisotropy in silicon single crystals.

Journal Article↗

Exclusive Th2 primary effector function in spleens but mixed Th1/Th2 function in lymph nodes of murine neonates.

Recent studies have shown that neonatal mice are competent to develop mature, Ag-specific Th1 function in situ. However, under many conditions, Th2 responses dominate in the neonate, while Th1 responses are more prevalent in adults. To compare further the immune responses of neonates and adults, we used the enzyme-linked immunospot method to measure the frequencies of primary Th1/Th2 effectors generated in situ in the spleens and lymph nodes. As assessed by the detection of IFN-gamma- or IL-4-producing cells, adults developed mixed Th1/Th2 responses in both organs. Neonatal lymph nodes contained mature frequencies of IFN-gamma- and IL-4-producing cells. In striking contrast, while mature frequencies of Th2 cells developed in neonatal spleens, virtually no IFN-gamma-secreting cells were detected. Exclusive Th2 function was observed in both BALB/c and C57BL/6 neonates, strains in which the Th2 and Th1 lineages, respectively, are favored in adults. Although Th1 effectors were virtually undetectable, the addition of rIL-12 boosted the frequency of IFN-gamma-secreting cells to adult levels. Therefore, Th1 effectors apparently developed in situ, but Th1 effector function either was not promoted or was inhibited upon subsequent exposure to the Ag in culture. Together, these results indicate that the quality of a primary Th response in neonates is strongly dependent on the site of initial Ag exposure; responses initiated in the lymph nodes are mixed Th1/Th2, whereas responses occurring in the spleen are heavily Th2 biased.

Animals↗

Audiometric configurations following exposure to explosions.

OBJECTIVE: To determine the configurations in pathologic audiograms obtained in patients shortly after exposure to an explosion. DESIGN, SETTING, AND PATIENTS: Audiograms were performed in 143 patients (286 ears; 76 males and 67 females, with a mean age of 34.6 years [range, 11-79 years]) sent to the Department of Otolaryngology and Head and Neck Surgery in a city hospital located in the center of Jerusalem, Israel, after being injured in 4 severe explosions occurring in Jerusalem during 1995-1997. Most of the audiograms were obtained within 4 hours after the explosion, and the remaining were obtained within 4 days of the explosion. RESULTS: Of 200 pathologic audiograms, 93 (46%) showed a downward slope configuration, 82 (41%) showed a dip configuration, and 25 (12%) were flat. There were 38 audiograms (19%) with 6-kHz dips. In 82% of the patients, the audiometric configurations were similar in both ears. Patients with a slope configuration on the audiogram were significantly older than those with a dip configuration (mean age, 40.8 vs 32.8 years; P<.01). CONCLUSIONS: There does not appear to be a single typical audiometric configuration in patients exposed to explosions. The slope and dip configurations are most frequently seen and are approximately equal in their incidence. This observation may lead to better understanding damage to the inner ear as a result of an explosion. This study is distinctive because of the large number of audiograms obtained and the fact that most of them were obtained immediately after the explosion.

Adolescent↗

An ERP study of the temporal course of the Stroop color-word interference effect.

The electrophysiological correlates of the Stroop color-word interference effect were studied in eight healthy subjects using high-density Event-Related Potentials (ERPs). Three response modalities were compared: Overt Verbal, Covert Verbal, and Manual. Both Overt Verbal and Manual versions of the Stroop yielded robust Stroop color-word interference as indexed by longer RT for incongruent than congruent color words. The Incongruent vs Congruent ERP difference wave presented two effects. A first effect was a medial dorsal negativity between 350-500 ms post-stimulus (peak at 410 ms). This effect had a significantly different scalp distribution in the Verbal and Manual Stroop versions, with an anterior-medial focus for overt or covert speech, and a broader medial-dorsal distribution for the manual task. Dipole source analysis suggested two independent generators in anterior cingulate cortex. Later on in time, a prolonged positivity developed between 500-800 ms post-stimulus over left superior temporo-parietal scalp. This effect was present for all the three response modalities. A possible interpretation of these results is that Stroop color-word interference first activates anterior cingulate cortex (350-500 ms post-stimulus), followed by activation of the left temporo-parietal cortex, possibly related to the need of additional processing of word meaning.

Adult↗

Nonlinear mechanical behavior of piezocomposites for ultrasonic transducers

A comparative study is carried out between the nonlinear behavior of a composite and the piezoceramic used to obtain it. This characterization is necessary for using the composite in power transducer applications. A study of the losses and the resonator stiffness variations has also been done. Both these effects, as well as the possibility of the frequency hysteresis, show different behavior in the composites, since the increases in the ceramics are different from those in the composites. In this study two measurement methods are used: principally the motional impedance increase with the motional current measurements. The results obtained are normalized in order to make them independent of the resonator size, and thus make the comparison between the composite and the ceramic easier. The figure of the mechanical loss tangent tan delta m versus the mean strain shows that the losses can be greater in the ceramic than in the composite for soft ceramics. The dependence behavior of the losses and stiffness variations versus the mean strain is studied for both resonators.

Journal Article↗

Paclitaxel exposure time determines the nature of the interaction with radiation in HeLa cells. the role of apoptosis.

The purpose of the present study was to investigate further the mechanisms underlying subadditive and superadditive interactions of radiation and paclitaxel treatments in vitro. The protocol studied was a fixed radiation treatment (7 Gy) followed either immediately or after a 10 h delay by paclitaxel treatment. Paclitaxel treatment was exposure to either a fixed dose of paclitaxel (10 nM) for varying time intervals up to 25 h, or varying doses of paclitaxel up to 20 nM for a fixed exposure time of 24 h. The cells used were HeLa. Cell survival was assessed by colony forming ability and apoptosis was measured by flow cytometry. The results show that when the paclitaxel exposure time was 24 h superadditive interactions were observed at all paclitaxel doses. A reasonable correlation between surviving fraction as measured by colony forming ability and apoptosis in the attached cells at the end of paclitaxel treatment was observed. The nature of the interaction of radiation and subsequent paclitaxel treatment is critically dependent on the duration of the paclitaxel treatment.

Antineoplastic Agents, Phytogenic↗

Minimally invasive treatment for localized adenocarcinoma of the prostate: review of 1048 patients treated with ultrasound-guided palladium-103 brachytherapy.

PURPOSE: To assess the effectiveness of palladium-103 brachytherapy in stage T1 and T2 adenocarcinoma of the prostate. PATIENTS AND METHODS: The charts of 1048 patients treated between 1991 and 1999 with transperineal realtime ultrasound-guided (103)Pd (Theraseed) implants were reviewed to assess the effects on serum prostate specific antigen (PSA) values and tissue (biopsy). Of the 1048 patients, 780 had sufficient data for this report. Preoperative total androgen blockade (leuprolide and flutamide) was used selectively in patients whose prostate size was >50 cc and those whose tumors had a Gleason score of >7. RESULTS: At 1 year, 86% of the evaluable 766 patients had stable PSA concentration <1.5 ng/mL; at 5 years, 86% of the 166 patients with data available had stable PSA values <1.5 ng/mL. Biopsies were negative in 92% of the patients studied at 2 years. Patients with pretreatment PSA values <10 ng/mL had the best outcomes, and those treated with (103)Pd plus hormone ablation achieved PSA reduction more rapidly than those treated with radioisotope monotherapy. There was one disease-related death; the principal morbidity was short-term bladder and bowel irritation without permanent sequelae. Impotence occurred in approximately 15% of patients, and incontinence occurred in 5% of those who had undergone prior transurethral resection of the prostate. CONCLUSION: The technique used in this study proved effective in reducing PSA concentrations to <1.5 ng/mL and in producing negative biopsies 1 and 2 years postoperatively. These results are comparable to those of external-beam radiation therapy and radical prostatectomy while demonstrating a significant reduction in morbidity.

Adenocarcinoma↗

Vestibular and cochlear ototoxicity of topical antiseptics assessed by evoked potentials.

OBJECTIVES/HYPOTHESIS: To evaluate and compare the effect of chlorhexidine gluconate, povidoneiodine, and alcohol-three antiseptics used before ear surgery-on the function of the vestibular and cochlear parts of the sand rat's inner ear. The assessment of damage is based on the recording of vestibular evoked potentials (VsEPs) and auditory brainstem response (ABR). STUDY DESIGN: Prospective controlled animal study. METHODS: Fat sand rats were randomly assigned to five different groups, each receiving topical application of a different agent: saline (control), gentamicin (ototoxic control), chlorhexidine, povidone-iodine, and alcohol. Right-side total labyrinthectomy was performed, and a polyethylene tube was inserted into the left (contralateral) middle ear. After baseline recordings were taken of VsEPs and ABR, each animal received five consecutive daily applications of the specific agent into the left middle ear. Three days after the fifth application, evoked potential recordings (VsEPs and ABRs) were repeated and compared with baseline measurements. RESULTS: Administration of saline affected neither VsEPs nor ABR. In contrast, as expected, neither of these responses could be recorded after gentamicin application. After application of chlorhexidine all waves disappeared in all sand rats. Alcohol caused the waves to disappear in some of the animals only. Povidone-iodine did not affect VsEP recordings and had only a small effect on ABR. CONCLUSIONS: Chlorhexidine and alcohol had a clear toxic effect on the vestibular and cochlear function of the inner ear of the sand rat, whereas povidone-iodine did not. Thus, taking into consideration that this is an animal study, it appears that povidone-iodine might be preferable to the other agents tested in disinfecting ears with a perforated tympanic membrane.

Administration, Topical↗

Plasma C-reactive protein in hemodialysis patients: a cross-sectional, longitudinal clinical survey.

In hemodialysis patients, C-reactive protein (CRP), an acute-phase reactant, is a sensitive and independent marker of malnutrition, anemia, and amyloidosis. The aim of the present studies was to evaluate CRP and interleukin 6 levels in plasma samples from long-term hemodialysis patients on different extracorporeal modalities associated with or without backfiltration. Two hundred and forty-seven patients were recruited in eight hospital-based centers. All patients had been on their dialytic modality for at least 6 months. At enrollment, 46 hemodialysis patients out of 247 (18.6%) had clinical evidence of pathologies known to be associated with high CRP values. The 201 remaining patients were defined as clinically stable and were on conventional hemodialysis (34%), hemodiafiltration with infusion volumes <10 liters/session (10%), hemodiafiltration with infusion volumes <20 liters/session (32%), and double-chamber hemodiafiltration with infusion volumes <10 liters/session (22%). Analysis of CRP values in the clinically stable patients showed that an unexpectedly high proportion (47%) of the patients had CRP values higher than 5 mg/l (taken as the upper limit in normal human subjects). The values of CRP and interleukin 6 were significantly higher in hemodiafiltration with infusion volumes <10 liters/session than in hemodiafiltration with infusion volumes >20 liters/session, in hemodialysis and in double-chamber hemodiafiltration. The same pattern occurred after 6 months of follow-up in 171 out of 201 clinically stable patients. Hemodialytic conditions that expose to the risk of backfiltration such as low exchange volume hemodiafiltration may induce a chronic inflammatory state as reflected by increased plasma values of both CRP and interleukin 6, thus suggesting the need for hemodialytic strategies that reduce (hemodialysis with low-permeability membranes or hemodiafiltration with infusion volumes >20 liters) or eliminate (double-chamber hemodiafiltration) backfiltration of bacteria-derived contaminants.

Acute-Phase Proteins↗

Radiotoxicity of h-R3 monoclonal antibody labeled with 188Re administered intracerebrally in rats.

Brain tumors are often incurable despite current aggressive treatment modalities. Regional intracerebral administration of labeled monoclonal antibodies (Mabs) can maximize the radioisotope and Mab concentration to tumor sites while reducing systemic toxicity. h-R3 is a humanized antiepidermal growth factor receptor Mab that successfully targets the epidermal growth factor receptor, which is overexpressed in glioblastomas. We studied the acute local and systemic toxicity effects of intraventricular 188Re-h-R3 in rats. Forty rats were distributed into four groups with five animals of each sex in each group. A single 5 -microl dose (2.5 microl into the left and 2.5 microl into the right lateral ventricles) of neutral solution containing 50 microg of h- R3 labeled with 49.5 +/- 1.7,284 +/- 13.7 or 579 +/- 23.7 muCi of 188Re were stereotactically administered to each animal. Control animals received vehicle alone. Each animal was observed twice daily for detection of toxicity signs. Body weights were recorded on days 0, 7 and 14. Blood samples for analysis of hematological and clinical chemistry parameters were taken on days 0 and 14. Necropsy and histopathological studies were carried out after completion of the study. All animals, but one, remained clinically stable. Toxicities included local radionecrosis, discrete increase in ALAT and creatinine blood values at higher dose level. We concluded that a single intraventricular administration of relatively large doses of 188Re-h-R3 is tolerable and causes minimal local and systemic toxicity effects in rats. Nevertheless, further studies are necessary to discard learning and behavioral problems.

Adenocarcinoma↗

Use of evoked potentials to objectively differentiate between selective vulnerability of cochlear and vestibular end organ function.

Auditory nerve brainstem evoked responses (ABR) have been used for several decades to investigate cochlear function. Recently techniques have been developed to elicit similar recordings from the vestibular end organs - short latency vestibular evoked potentials (VsEPs). Both ABR and VsEP reflect appropriate end organ function and may therefore be used to investigate the vulnerability of these end organs to various experimental insults, such as noise exposure and ototoxic drugs.

Animals↗