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Biomedical subjects

C Cruz

Publications and source records attributed to C Cruz.

At least 55 records · Page 3Linked to original sources

Circadian temperature rhythms in clockwise and counter-clockwise rapidly rotating shift schedules.

The purpose of this study was to examine the circadian temperature rhythm in clockwise (CW) and counter-clockwise (CCW) rapidly rotating shift schedules. Arguments against the CCW rotation of shifts are that they result in shortened sleep and promote greater disruption of circadian rhythms. The 3-week study included a week of day shifts (0800-1600) and 2 weeks of shiftwork. The CW 2-2-1 schedule rotated from two early mornings (0600-1400) to two evenings (1400-2200) to one midnight shift (2200-0600) allowing 24 hours off at each shift rotation and a 48-hour weekend. The CCW schedule rotated from two evenings to two early mornings to one midnight shifts allowing only 8 hours off at each shift rotation and an 80-hour weekend. Analysis of the 72-hr periods at the end of each workweek, including the midnight shifts and recovery periods during weeks 2 and 3 were compared to the same 72-hour period at the end of week 1 (baseline). A cosine function that fit the temperature curves by minimizing the sums of squares produced parameters that underwent analysis of covariance procedures. Significant differences were found between rotation conditions for amplitude and acrophase. An attenuation of amplitude and a delay in the acrophase was the found for the counter-clockwise condition. Features inherent in this schedule might explain these effects, particularly, the increased opportunity for "sleeping in" at the beginning of the week and an expanded (2-shift) workday at the end of the week.

Adult↗

Immunohistochemical detection of mismatch repair gene proteins as a useful tool for the identification of colorectal carcinoma with the mutator phenotype.

There are two well-defined pathways for colorectal carcinogenesis, the suppressor and the mutator pathways. The latter is characteristic of hereditary non-polyposis colorectal cancer (HNPCC), but can also be found in a subset of sporadic colorectal cancer (SCC) possessing distinctive clinical and pathological features, namely early age of onset, location in the right colon, poor differentiation, and a predominant mucinous component. This mutator pathway results from inactivation of mismatch repair (MMR) genes, namely MSH2 and MLH1. The aim of this study was to ascertain if abnormal MMR protein gene expression is a good indicator for identifying tumours from the mutator pathway. Seventy-six cases of SCC were studied by immunohistochemistry using two monoclonal mouse antibodies that react against MSH2 and MLH1 protein gene products. Immunoexpression was assessed both in tumour and in non-neoplastic, adjacent and distant mucosa. Microsatellite instability (MSI) was detected by evaluating the length of poly(CA) repeated sequences at seven loci, or by the detection of small unstable alleles in a poly(A) repeat - BAT-26. Except for BAT-26, in which only tumour DNA was used, MSI analysis was performed in both tumour and normal mucosal DNA. MSI was classified as high (MSI-H), low (MSI-L) or stable (MSS). Abnormal protein expression was found in 9/76 (12%) tumours. Immunohistochemistry for hmlh1 and hmsh2 detected 75% of MSI-H. There was also a highly significant correlation between the observed immunoexpression and several clinical and pathological characteristics described as the phenotypic profile of the mutator pathway, such as right-sided location (p=0.003), mucin production (p=0.008), and a peritumoural lymphoid infiltrate (p=0.009). Non-neoplastic adjacent mucosa showed normal hMSH2 expression in all cases, but in ten cases there was no hMLH1 expression in this transitional mucosa, which is known to display an alterated mucin pattern and a high proliferative rate. These results demonstrated a good correlation between hMLH1 and hMSH2 gene immunoexpression and the clinico-pathological features characteristic of the mutator phenotype and support the use of this method as a rapid and efficient way to detect tumours arising from this pathway.

Adult↗

Tyrosine phosphorylation mediates both activation and downmodulation of the biological activity of Vav.

Vav works as a GDP/GTP exchange factor for Rac GTPases, thereby facilitating the transition of these proteins from the inactive (GDP-bound) into the active (GTP-bound) state. The stimulation of Vav exchange activity during cell signaling is mediated by tyrosine phosphorylation. To understand the roles of phosphorylation in the regulation of Vav activity, we have initiated the characterization of the residues of Vav that are phosphorylated during signal transduction. Here we show that a Y-to-F mutation in one of these residues, Y174, leads to the oncogenic activation of Vav and to the enhancement of other Vav-mediated signals such as those for cytoskeletal reorganization, JNK activation, and stimulation of the nuclear factor of activated T cells. The effect induced by the Y174F mutation is further accentuated by mutations in residue Y142 or Y160. The Y174F mutation has no effect on the exchange activity of Vav in vitro but results in higher levels of phosphorylation in vivo. Using a phosphospecific antibody, we found that Y174 is phosphorylated following stimulation of mitogenic and antigenic receptors. This phosphorylation event is conserved in Vav-2 and Vav-3, the other two members of the Vav family. These results identify a previously unknown mechanism for the oncogenic activation of Vav and suggest that the activity of this exchange factor is modulated by two antagonistic phosphorylation events, one involved in Vav activation and a second one implicated in Vav inactivation.

3T3 Cells↗

Effects of quick rotating shift schedules on the health and adjustment of air traffic controllers.

INTRODUCTION: Many Air Traffic Control Specialists (ATCSs) in the United States work shift schedules that involve counterclockwise rapid rotations. Researchers have reported negative health effects associated with shiftwork, suggesting that workers on rotating shift schedules suffer the greatest consequences. The purpose of this study was to assess the extent of health, sleep, and shiftwork adaptation problems experienced by ATCSs. HYPOTHESIS: It was hypothesized that shiftwork-related problems would be identified. METHODS: A total of 210 ATCSs completed a modified version of the National Institute for Occupational Safety and Health (NIOSH) General Health and Adjustment Questionnaire (25). The questionnaire included a broad range of health, sleep, job, and lifestyle questions. Health and sleep pattern index scores were computed for this paper. Comparisons were conducted based on the following shift characteristics: length of shift (8- vs. 9-h), number of early morning shifts, number of midnight shifts, and schedule preference. RESULTS: Over half of the sample in this study reported periods of severe fatigue or exhaustion and symptoms of gastrointestinal disturbance typically found among shift workers. Better health and sleep pattern index scores were reported by those who preferred rotating schedules and by those who did not work night shifts. DISCUSSION: The ATCSs in this sample were relatively young and are required to pass a yearly physical to maintain employment. Thus, this may have resulted in low frequencies of reported medical problems. However, reports of sleepiness, fatigue, and falling asleep seem to indicate that countermeasures for sleepiness at work and on the drive home could benefit ATCSs.

Adult↗

Isolation of steroidal sapogenins implicated in experimentally induced cholangiopathy of sheep grazing Brachiaria decumbens in Brazil.

As part of an experimental study, crystal-associated cholangiopathy was induced in 9 sheep by grazing pure pastures of Brachiaria decumbens in Brazil. One of these sheep showed characteristic lesions of photosensitization. The analysis of the B decumbens samples by acidic hydrolysis followed by TLC and infrared spectrum revealed diosgenin as the principal sapogenin present in the plant. In the rumen contents samples from the B decumbens-grazing group were identified by TLC, 1H and 13C NMR and EIMS as epismilagenin, episarsasapogenin, and a mixture of smilagenin and sarsasapogenin. In the bile samples from the B decumbens-grazing group, TLC analysis demonstrated 2 compounds similar to epismilagenin and episarsasapogenin. However, by this same method, those compounds were not observed in the rumen contents and bile from 2 sheep which served as control animals. The P chartarum spore counts remained very low during the experimental period.

Animals↗

Baccharis megapotamica var Weirii poisoning in Brazilian cattle.

Three Holstein heifers died after consumption of Baccharis megapotamica var weirii in southern Brazil. Main histologic lesions included degeneration and necrosis of the epithelium from the forestomachs and of the lymphoid tissue of the spleen and lymph nodes.

Animals↗

Emergence of vancomycin resistance in Staphylococcus aureus. Glycopeptide-Intermediate Staphylococcus aureus Working Group.

BACKGROUND: Since the emergence of methicillin-resistant Staphylococcus aureus, the glycopeptide vancomycin has been the only uniformly effective treatment for staphylococcal infections. In 1997, two infections due to S. aureus with reduced susceptibility to vancomycin were identified in the United States. METHODS: We investigated the two patients with infections due to S. aureus with intermediate resistance to glycopeptides, as defined by a minimal inhibitory concentration of vancomycin of 8 to 16 microg per milliliter. To assess the carriage and transmission of these strains of S. aureus, we cultured samples from the patients and their contacts and evaluated the isolates. RESULTS: The first patient was a 59-year-old man in Michigan with diabetes mellitus and chronic renal failure. Peritonitis due to S. aureus with intermediate resistance to glycopeptides developed after 18 weeks of vancomycin treatment for recurrent methicillin-resistant S. aureus peritonitis associated with dialysis. The removal of the peritoneal catheter plus treatment with rifampin and trimethoprim-sulfamethoxazole eradicated the infection. The second patient was a 66-year-old man with diabetes in New Jersey. A bloodstream infection due to S. aureus with intermediate resistance to glycopeptides developed after 18 weeks of vancomycin treatment for recurrent methicillin-resistant S. aureus bacteremia. This infection was eradicated with vancomycin, gentamicin, and rifampin. Both patients died. The glycopeptide-intermediate S. aureus isolates differed by two bands on pulsed-field gel electrophoresis. On electron microscopy, the isolates from the infected patients had thicker extracellular matrixes than control methicillin-resistant S. aureus isolates. No carriage was documented among 177 contacts of the two patients. CONCLUSIONS: The emergence of S. aureus with intermediate resistance to glycopeptides emphasizes the importance of the prudent use of antibiotics, the laboratory capacity to identify resistant strains, and the use of infection-control precautions to prevent transmission.

Aged↗

Opioid peptide systems following a subconvulsant dose of pentylenetetrazol in rats.

The development of epilepsy and a progressive increase in susceptibility to seizures may involve changes in inhibitory and excitatory systems from the beginning of the process. The present study was focused to analyze the opioid peptide changes induced by a chemical sub-convulsant stimulation. Experiments were carried out to determine opioid peptide release, mu receptor binding and proenkephalin expression in rat brain, as well as nociceptive responses, following the administration of a sub-convulsant dose of pentylenetetrazol (PTZ) (30 mg/kg, i.p.). Membrane binding experiments revealed reduced number of mu binding sites (Bmax) in cortex and amygdala, but not in striatum and hippocampus, an effect that was evident only 24 h, but not 28 days, after PTZ treatment. In situ hybridization experiments suggested a significant enhancement of proenkephalin mRNA expression in specific brain regions 24 h after PTZ treatment. Microdialysis combined with a universal opioid peptide radioimmunoassay revealed extracellular opioid peptide levels to be elevated in the amygdala (137%) 90 min after PTZ administration. Evaluation of nociceptive responses using the Randall-Selitto test showed an analgesic effect short term (30-90 min) after PTZ injection. Collectively, these data provide evidence for a significant activation of opioid peptide systems as a consequence of the administration of a sub-convulsant dose of PTZ. These neurochemical changes may play an important role in the progression of epileptogenesis.

Animals↗

Frequent co-expression of the HOXA9 and MEIS1 homeobox genes in human myeloid leukemias.

There is increasing evidence that HOX homeobox genes play a role in leukemogenesis. Recent studies have demonstrated that enforced co-expression of HOXA9 and MEIS1 in murine marrow leads to rapid development of myeloid leukemia, and that these proteins exhibit cooperative DNA binding. However, it is unclear whether co-activation of HOXA9 and MEIS genes is a common occurrence in human leukemias. We surveyed expression of HOXA9 and MEIS1 in 24 leukemic cell lines and 80 patient samples, using RNase protection analyses and immunohistochemistry. We demonstrate that the expression of HOXA9 and MEIS1 in leukemia cells is uniquely myeloid, and that these genes are commonly co-expressed in myeloid cell lines and in samples of acute myelogenous leukemia (AML) of all subtypes except in promyelocytic leukemia. While HOXA9 is expressed in most cases of chronic myelogenous leukemia, MEIS1 is weakly expressed or not at all. Immunohistochemical staining of selected AML samples showed moderate to high levels of HOXA9 protein, primarily cytoplasmic, in leukemic myeloblasts, with weaker and primarily nuclear staining for MEIS1. These data support the concept that co-activation of HOXA9 and MEIS1 is a common event in AML, and may represent a common pathway of many different oncogenic mutations.

Genes, Homeobox↗

Reproductive function in male rats with chronic nephrosis.

Endocrine dysfunction has been associated with renal diseases. The present study was conducted to explore reproductive function in male rats with chronic nephrosis. Experimental chronic nephrosis was induced by the administration of 7.5, 5.0 and 5.0 mg per 100 g body weight of puromycin aminonucleoside on days 0, 21 and 35, respectively. Reproductive function was evaluated on the basis of hormonal concentrations, mass of accessory sex organs and fertility during an 84 day period. Circulating LH, FSH, testosterone and oestradiol concentrations were measured by specific radioimmunoassays, while fertility was estimated by the rate of pregnancy induction. Samples were collected on days 7, 14, 28, 56 and 84. The results showed an important endocrine dysfunction characterized by low concentrations of LH and FSH during the first month, after which concentrations were similar to control values or even increased on days 56 and 84. Testosterone and oestradiol decreased significantly at all time points evaluated. The mass of the testes did not alter. However, the mass of the prostate and seminal vesicle decreased only during the first 2 weeks, and became essentially normal thereafter. The reproductive capacity of nephrotic males was eliminated on day 7, whereas on day 14, 16% of the group was able to mate successfully and subsequently most animals recovered their normal reproductive function. This study demonstrates for the first time that rats with experimental chronic nephrosis develop an important endocrine dysfunction, characterized mainly by persistent reduction in testosterone concentrations, which impairs reproductive capacity only transiently.

Animals↗

[Analysis of productivity, quality and cost of first grade laboratories: blood biometry].

OBJECTIVE: Assessment of productivity, quality and production costs and determination of the efficiency of top grade clinical laboratories in Mexico. METHODS: Ten laboratories were selected from among the total number (52) existing in Mexico City, and the Donabedian model of structure, process and results were applied. Blood count was selected as a tracer. RESULTS: The principal problems found were: inadequate distribution of trained human resources, poor glass material, inadequate analytic process and low productivity. These factors are reflected in the unit costs, which exceed reference laboratory costs by 200%. Only 50% of the laboratories analyzed generate reliable results. Only 20% of the laboratories studied operate efficiently. CONCLUSIONS: To solve the problems identified requires integral strategies at different levels. A specific recomendation for the improvement of quality and productivity is an assessment of the cost/benefit of creating a central laboratory and using the remaining sites exclusively for the collection of samples.

Biometry↗

Experimental traumatic cerebral contusion: morphological study of brain microvessels and characterization of the oedema.

Several experimental brain oedema models are currently available, but most of them are very different from what happens in clinical practice. As it is simple and seems to replicate the range of injuries seen in man we decided to evaluate Marmarou's model of head injury in order to test physiopathogenic and therapeutic hypotheses. Three groups of Wistar rats weighting 360-400 gr, anaesthetized with sodium pentobarbitone and breathing spontaneously, without tracheal intubation, were studied. In the first group six animals were killed two hours after injury and the brain's water content compared with that of nine controls. In another group Evans blue (100 mg/kg) was injected one hour before trauma and dye's extraction ratio determined at various times after injury: five animals at 15 minutes, six at 30 minutes, five at 60 minutes and nine at 120 minutes. A total of twenty-eight animals served as controls. In the last group morphological studies with light and electron microscopy were performed in the traumatized brain tissue from rats killed 5 and 120 minutes after injury and in brain tissue from control rats. Results showed that Marmarou's brain trauma model induced perivascular brain oedema, already visible at the ultrastructural level 5 minutes after the injury. Endothelial cells themselves were "oedematiated", rich in pinocytotic vesicles and membrane blebs, and presented intact tight junctions. Two hours after trauma the perivascular oedema was more marked. At this time the brain water content was significantly higher than that in controls. Evans blue extraction ratio increased linearly with time, being significantly higher than in controls 120 minutes after injury. We conclude that Marmarou's model is a suitable model for the study of brain oedema induced by trauma, and that this oedema, assessed by three different methodologies, was statistically significant two hours after injury.

Animals↗

Effect of mechanogated membrane ion channel blockers on experimental traumatic brain oedema.

Traumatic head injury leads to marked swelling of endothelial cells, both in human patients and in Marmarou's rat model. We used this model to test the hypothesis of mechanogated ion channels being involved in the formation of traumatic brain oedema. All mechanogated channel blockers tested (gadolinium, amiloride, gentamicin) significantly reduced traumatic brain oedema evaluated by Evans blue extraction ratio, either when given 15 minutes before or 30 minutes after induction of trauma (evaluation 2 hours after trauma). These results clearly support our hypothesis, opening a new way for the investigation of the treatment of a clinical situation endowed with high morbidity and mortality.

Amiloride↗

Cerebral edema associated with meningiomas: the role of peritumoral brain tissue.

We undertook a morphological study of small pieces of peritumoral brain tissue removed from seven patients with meningiomas submitted to surgery. All patients had cerebral edema, as shown by preoperative C.T. and N.M.R.. Control specimens were obtained from five patients undergoing ventriculo-peritoneal shunt. The tissue fragments were fixed in glutaraldehyde-osmium and embedded in Epon. In semi-thin sections observed under light microscopy peritumoral endothelial cells exhibited voluminous cytoplasm and nucleus. Morphometrical evaluation confirmed that these endothelial cell nuclei were significantly larger than controls. Under the electron microscope those cells showed nuclei rich in euchromatin and cytoplasm rich in pinocytotic vesicles. The morphological changes observed suggest a process of dedifferentiation of brain peritumoral capillary cells and are compatible with an increase in permeability. Both events, which may be due to diffusion of a tumoral vascular permeability factor, favour the hypothesis that peritumoral brain tissue contributes to edema fluid that accumulates around meningiomas.

Adult↗