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Biomedical subjects

M Diez

Publications and source records attributed to M Diez.

At least 19 recordsLinked to original sources

Tuberculosis in Spain: epidemiological pattern and clinical practice.

SETTING: Thirteen Autonomous Regions in Spain. OBJECTIVE: To study the incidence of all forms of tuberculosis (TB) and investigate clinical practice in TB. DESIGN: Cases of all forms of tuberculosis diagnosed in the study setting from May 1986 to April 1997 were identified though active search of different databases. Clinical and epidemiological information on cases was collected from clinical records or by interview with physicians. RESULTS: The overall incidence of all forms of tuberculosis was 38.5/100,000 and the incidence of smear-positive disease was 13.83/100,000. Most cases (97.1%) were Spanish nationals, with rates higher in men than in women (52.7/100,000 vs. 24.87/100,000) and in groups aged 25-34 and 75 years and over (61.35/100,000 and 59.35/100,000, respectively). Disseminated forms were frequent (6.6%), and the most common risk factor was human immunodeficiency virus (HIV) infection (17.7% of cases). Hospitalisation was common (71.6%). Microbiological confirmation of diagnosis was sought for 87.7% of the cases (91.8% of pulmonary vs. 75.5% of extra-pulmonary cases), and 65.2% were culture-positive (73.8% of pulmonary vs. 39.7% of extra-pulmonary cases). HIV-infected patients were treated in almost equal proportions with three or four drugs (49.7% and 48.2%, respectively), while HIV-negative cases or those whose HIV status was unknown were usually treated with three drugs. CONCLUSION: The epidemiological pattern of TB in Spain is different to other industrialised countries in the age distribution of cases and the proportions of foreigners and cases with HIV infection. Microbiological confirmation of diagnosis is more common in pulmonary than in extra-pulmonary disease, and treatment with four drugs more frequent in HIV-positive cases.

Adolescent↗

Subcortical anarthria: a case report.

A 56-year-old right-handed male with a history of hypertension and diabetes presented two episodes of stroke: The first affected territory was the left anterior coroidal artery (capsular and paracapsular infarcts at the level of the genu and posterior arm of the internal capsule) and the second was the right thalamus, due to a hematoma. Following the first stroke, the patient developed severe dysarthria and after the second stroke remained anarthric. The pathophysiology of the disorder is discussed, and the role of the left and right thalamus as far as speech is concerned is reviewed.

Cerebral Infarction↗

Decreased MK-801 binding in discrete hippocampal regions of prion-infected mice.

The neurochemical alterations associated with neurodegeneration in prion diseases are not well defined. It is therefore of interest to study the influence of prion infection on messenger molecules and their receptors. In the present study we have analyzed the possible involvement of NMDA receptors in prion-infected mice using ligand binding autoradiography and iodinated MK-801, a noncompetitive NMDA antagonist. The results show a reduced binding of MK-801 in discrete regions of hippocampus at 110 days after infection, that is before the appearance of behavioral symptoms. In addition, early transient increases in MK-801 binding were observed in several layers. The exact neuroanatomical correlate of these changes in MK-801 binding, as well as its functional significance in relation to prion symptomatology, remain to be analyzed.

Animals↗

Determination of free and total sulfate and phosphate in glycosaminoglycans by column-switching high-performance size-exclusion and ion chromatography and single-column ion chromatography.

Analytical procedures for the determination of free and total sulfate and phosphate in glycosaminoglycans by high-performance liquid chromatography were studied. A column-switching method coupling high-performance size-exclusion chromatography (HPSEC) and ion chromatography (IC) is proposed for the determination of free anions. Good run-to-run and day-to-day precision values (RSD) of < 4.7% were obtained for both anions. Total anion contents were determined after wet acid hydrolysis with nitric acid-hydrogen peroxide (5 + 1) by single-column IC and ICP-AES elemental analysis in order to validate the results. Recoveries ranging from 94.6 to 99.0% for sulfate and from 80.8 to 94.0% for phosphate were obtained. Both HPSEC-IC and single-column IC methods were applied to the analysis of a low molecular mass heparin, a non-fractionated heparin and a chondroitin 4-sulfate. From the free and total sulfate determinations, the content of linked sulfur was calculated and ranged from 5.1 to 12.2% m/m.

Journal Article↗

Prediction of protein digestibility in dog food by a multi-enzymatic method: a useful technique to develop.

The multi-enzymatic method with constant pH described by Dufour-Etienne et al. (Rec. Méd. Vét. 168, 789-796, 1992) was tested using 17 industrial dry dog foods and two ingredients, sodium caseinate and beef meat, which were used as references. The quantity of sodium hydroxide added to the enzymatic solution was measured after incubation times of 2, 5 and 10 min and the best prediction of the apparent protein digestibility was obtained with an incubation time fixed at 2 min. The volume of sodium hydroxide 0.1 N constantly added to maintain the pH of the solution at 8 was correlated to the value of in vivo digestibility of the protein measured in the dog. The correlation coefficient obtained was 0.90 with a standard error of the regression of 1.9 for all samples. The correlation coefficients calculated for incubation times of 5 and 10 min were lower than that at 2 min; thus an incubation period of 2 min provided the highest correlation coefficient for this multi-enzymatic method at constant pH. However, considering the lack of samples with an apparent protein digestibility ranging between 85 and 95%, the slope of the regression line and the correlation coefficient were strongly influenced by the ingredients, such that when the correlation coefficient was calculated for 17 dog foods without the reference ingredients, a coefficient of 0.71 (+/- 1.9) was obtained. These tests of in vitro digestibility are valuable to predict the apparent digestibility of the protein in the dog, but, it is essential to confirm the results by an in vivo test.

Animal Feed↗

Neuropeptides--an overview.

The present article provides a brief overview of various aspects on neuropeptides, emphasizing their multitude and their wide distribution in both the peripheral and central nervous system. Interestingly, neuropeptides are also expressed in various types of glial cells under normal and experimental conditions. The recent identification of, often multiple, receptor subtypes for each peptide, as well as the development of peptide antagonists, have provided an experimental framework to explore functional roles of neuropeptides. A characteristic of neuropeptides is the plasticity in their expression, reflecting the fact that release has to be compensated by de novo synthesis at the cell body level. In several systems peptides can be expressed at very low levels normally but are upregulated in response to, for example, nerve injury. The fact that neuropeptides virtually always coexist with one or more classic transmitters suggests that they are involved in modulatory processes and probably in many other types of functions, for example exerting trophic effects. Recent studies employing transgene technology have provided some information on their functional role, although compensatory mechanisms in all probability could disguise even a well defined action. It has been recognized that both 'old' and newly discovered peptides may be involved in the regulation of food intake. Recently the first disease-related mutation in a peptidergic system has been identified, and clinical efficacy of a substance P antagonist for treatment of depression has been reported. Taken together it seems that peptides may play a role particularly when the nervous system is stressed, challenged or afflicted by disease, and that peptidergic systems may, therefore, be targets for novel therapeutic strategies.

Animals↗

Time-dependency of the prognostic effect of carcinoembryonic antigen and p53 protein in colorectal adenocarcinoma.

BACKGROUND: This study examined the prognostic information regarding the risk of postoperative tumor recurrence obtained by simultaneous determination of preoperative serum carcinoembryonic antigen (CEA) and immunohistochemical expression of p53 protein in tumor tissue from patients with colorectal carcinoma. METHODS: A retrospective study of 174 patients (AJCC/UICC Stages I, II and III) was conducted. Serum CEA levels were determined by an enzyme-linked immunoadsorbent assay. Immunohistochemical expression of nuclear p53 protein was assessed in formalin fixed, paraffin embedded archival tumor tissue. The results of both factors were categorized by clinical and histopathologic variables. The relative prognostic significance of all factors with regard to disease free survival was assessed by Cox proportional hazards regression analysis. The stability of the predictive value of both markers was assessed: 1) by splitting the follow-up into three intervals and performing separate analyses for each period and 2) graphically by plotting the corresponding cumulative hazards ratio along the follow-up. RESULTS: Eighty-two (47%) tumors manifested overexpression of p53 protein and 60 tumors (34.4%) exhibited elevated serum CEA levels (cutoff value of 5 ng/mL). p53 positive immunostaining and elevated CEA levels were associated with low cumulative disease free survival at 60 months' of follow-up, and proved to have independent prognostic significance. Analysis performed in different time periods of follow-up showed that the prognostic effect of both markers was not stable over time. The predictive significance of CEA and p53 changed along the study periods. An elevated preoperative CEA level was an indicator of a high risk of recurrence only during the first 2 years after surgery (hazards ratio, 3.26; 95% confidence interval 95% CI, 1.65-6.42). The presence of p53 immunoreactivity in the primary tumor was an indicator of a high risk of recurrence only after the first year of follow-up (hazards ratio, 4.02; 95% CI, 1.68-9.6). CONCLUSIONS: The serum CEA level and expression of p53 protein provide complementary prognostic information. Time-dependency of the prognostic influence of both parameters should be taken into consideration when establishing postoperative predictive estimations.

Adenocarcinoma↗

Neuropeptides in hippocampus and cortex in transgenic mice overexpressing V717F beta-amyloid precursor protein--initial observations.

Immunohistochemistry was used to analyse 18- and 26-month-old transgenic mice overexpressing the human beta-amyloid precursor protein under the platelet-derived growth factor-beta promoter with regard to presence and distribution of neuropeptides. In addition, antisera/antibodies to tyrosine hydroxylase, acetylcholinesterase, amyloid peptide, glial fibrillary acidic protein and microglial marker OX42 were used. These mice have been reported to exhibit extensive amyloid plaques in the hippocampus and cortex [Masliah et al. (1996) J. Neurosci. 16, 5795-5811]. The most pronounced changes were related to neuropeptides, whereas differences between wild-type and transgenic mice were less prominent with regard to tyrosine hydroxylase and acetylcholinesterase. The main findings were of two types; (i) involvement of peptide-containing neurites in amyloid beta-peptide positive plaques, and (ii) more generalized changes in peptide levels in specific layers, neuron populations and/or subregions in the hippocampal formation and ventral cortices. In contrast, the parietal and auditory cortices were comparatively less affected. The peptide immunoreactivities most strongly involved, both in plaques and in the generalized changes, were galanin, neuropeptide Y, cholecystokinin and enkephalin. This study shows that there is considerable variation both with regard to plaque load and peptide expression even among homozygotes of the same age. The most pronounced changes, predominantly increased peptide levels, were observed in two 26-month-old homozygous mice, for example, galanin-, enkephalin- and cholecystokinin-like immunoreactivities in stratum lacunosum moleculare, and galanin, neuropeptide Y, enkephalin and dynorphin in mossy fibers. Many peptides also showed elevated levels in the ventral cortices. However, decreases were also observed. Thus, galanin-like immunoreactivity could not any longer be detected in the diffusely distributed (presumably noradrenergic) fiber network in all hippocampal and cortical layers, and dynorphin-like immunoreactivity was decreased in stratum moleculare, cholecystokinin-like immunoreactivity in mossy fibers and substance P-like immunoreactivity in fibers around granule cells. The significance of generalized peptide changes is at present unclear. For example, the increase in the mainly inhibitory peptides galanin, neuropeptide Y, enkephalin and dynorphin and the decrease in the mainly excitatory peptide cholecystokinin in mossy fibers (and of substance P fibers around granule cells) indicate a shift in balance towards inhibition of the input to the CA3 pyramidal cell layer. Moreover, it may be speculated that the increase in levels of some of the peptides represents a reaction to nerve injury with the aim to counteract, in different ways, the consequences of injury, for example by exerting trophic actions. Further studies will be needed to establish to what extent these changes are typical for Alzheimer mouse models in general or are associated with the V717F mutation and/or the platelet-derived growth factor-beta promoter.

Acetylcholine↗

Probable evidence of scurvy in subadults from archeological sites in Peru.

Subadult scurvy is not well documented in archeological human remains despite the existence of many biomedical references indicating that bone changes do occur in some cases and, because of this, should be observable in human burials. There are several potential reasons for this gap in our knowledge of scurvy. Not all children who suffered from scurvy died of the disease or from other causes when they had scurvy. Scurvy may not leave characteristic bone changes in every case of the disease. Some of the pathological conditions associated with scurvy have been known for many years, but these features may be rare or difficult to differentiate from other pathological conditions. Recently a lesion of the skull has been described that is probably pathognomonic for scurvy, specifically porous and sometimes hypertrophic lesions of the greater wing of the sphenoid. This lesion is bilateral and highly associated with evidence of inflammation at other anatomical sites in the skull. A survey of subadult skulls (N = 363) in the human skeletal collection from Peru at the National Museum of Natural History, Smithsonian Institution, reveals a prevalence of 10% of skulls that exhibit plausible evidence of scurvy. Some cases of scurvy also have cribra orbitalia that has been attributed to anemia. In most of the Peruvian scurvy cases, anemia is an unlikely possibility because there is no evidence of marrow hyperplasia. This highlights the need for caution in using lesions of the orbit as an indicator of anemia when there is no other evidence of this disease elsewhere in the skeleton. Anatomical evidence of scurvy offers the potential of providing new and important evidence of diet in archeological human populations.

Adolescent↗

Galanin and NPY, two peptides with multiple putative roles in the nervous system.

In the present brief overview we summarize results from several studies focusing on two neuropeptides, galanin and neuropeptide Y (NPY) in discrete neuronal systems, where they coexist with classic transmitters. On the basis of studies in different animal models we propose that these peptides may be involved in regulation of certain CNS functions and that drugs acting on their receptors may be of use in new therapeutic strategies. At the spinal level galanin and NPY are regulated in DRG neurons by nerve injury and in dorsal horn neurons by inflammation. It is possible that this leads to attenuation of pain sensitivity. Moreover, both peptides may exert trophic effects, for example to enhance regeneration. In the hypothalamic arcuate nucleus NPY and its receptors are part of the feeding circuitry, and we suggest that derangement of these NPY neurons may at least in part underlay the lethal phenotype of anorectic mice, which die 22 days postnatally after showing decreased food intake and growth retardation. Expression of NPY and NPY receptors is changed in the hippocampus of mice comparatively early after prion inoculation, indicating that this peptide system is affected in this spongiform degenerative disease in a region of importance for learning and memory. Finally, galanin is co-localized with classic monoamine transmitters in two central systems, the dorsal raphe serotonin neurons and the locus coeruleus noradrenergic neurons. In both cases galanin causes hyperpolarization (at high concentrations) and prolongs monoamine-induced outward currents (at low concentrations), thus modulating activity in two systems of importance for many brain functions including mood regulation. It may therefore be interesting to analyse to what extent drugs affecting galaninergic transmission also may be efficient in the treatment of, for example, depression.

Animals↗

Neuropeptide Y: some viewpoints on a multifaceted peptide in the normal and diseased nervous system.

Using immunohistochemical and in situ hybridization methodologies the localization of neuropeptide tyrosine (NPY) and two of its receptors, the Y1- and the Y2-receptor (R), has been analysed in various tissues in normal animals and animals subjected to different experimental procedures as well as animals with a genetic and an acquired disease. (1) Dorsal root ganglion (DRG) neurons are discussed with special focus on the effect of peripheral nerve injury. In normal DRG neurons NPY cannot be detected, whereas Y1-R mRNA and Y1-R-like immunoreactivity (LI) are strongly expressed. The Y1-Rs decorate the membrane of the cell soma and are not transported peripherally into the axonal branches. Y2-R mRNA levels are low. After axotomy there is a marked increase in NPY, a decrease in Y1-Rs and an increase in Y2-Rs. The Y2-R is transported centrifugally. These findings suggest that NPY-ergic mechanisms participate in the adaptive changes of sensory neurons in response to injury. (2) Using specific antibodies the cellular and subcellular localization of the Y1-R protein have been analysed in cerebral blood vessels. The results demonstrate high concentrations of receptors in smooth muscle cells around pial arterioles with lower numbers in large vessels on the basal surface of the brain. In many regions the receptors 'disappear' after the arterioles have entered the brain tissue. At the ultrastructural level the receptors are found both on the endothelial and peripheral side of the muscle cells as well as laterally, where muscle cells oppose each other. The receptor protein is often associated with small vesicles. No NPY-positive nerve fibers were found around the Y1-R-rich arterioles, but they were only seen around the arteries with low Y1-R levels. The Y1-R-rich arterioles were, however, seen close to numerous NPY-positive fibers originating from central interneurons. These findings raise the possibility that centrally originating NPY can influence cerebral blood flow, possibly by stimulating NPY-Rs on the peripheral side of the muscle cells. However, also blood borne NPY, released under special conditions, such as stress from sympathetic nerves and the adrenal medulla and transported with blood, may stimulate receptors on the endothelial side of the smooth muscle cells. (3) In the arcuate nucleus Y1- and Y2-Rs are found, whereby the Y1-Rs are located in its ventro-medial portion and co-localized with POMC peptides, and the Y2-R in its ventromedial part, partly co-localized with NPY. NPY nerve endings makes synaptic contact with the POMC/Y1-R-positive neurons. In a mouse model for genetic anorexia very high levels of NPY were observed in arcuate neurons as compared to control mice. However, NPY mRNA levels were not different between the two groups. Taken together these findings are in good agreement with the view that NPY in the arcuate nucleus plays an important role in regulating feeding behaviour. (4) After intracerebral prion inoculation in mice an upregulation of NPY mRNA levels was observed in CA3 pyramidal neurons, and this effect was seen at a time point just before the first behavioural symptoms were manifested. At approximately the same time there was a dramatic decrease in Y2-R binding in strata oriens and radiatum of the CA1 region of the hippocampus, whereas in other regions no changes or much smaller changes were observed. Also, there was only a very slight decrease in Y2-R mRNA levels in CA3 neurons. It thus appears as if the prion disease prevents ligand binding to the Y2-R, perhaps by influencing traffic of receptor proteins, possibly at the level of cell membrane-associated caveolae, which have been implicated in the conversion of normal protein to scrapie protein. It is possible that these changes in NPY-ergic mechanisms may underlie some of the central symptoms associated with the prion disease. (ABSTRACT TRUNCATED)

Animals↗

Akinetic mutism: a report of three cases.

OBJECTIVES: To report 3 new cases of akinetic mutism, a clinical syndrome defined by silent immobility with preserved visual alertness not accountable by lesion of the areas and/or effector pathways of speech and voluntary movements. MATERIAL AND METHODS: Anatomopathological studies were performed in Cases 1 and 2; clinical follow-up, EEG, angiography and CT scans in Case 3. RESULTS: Case 1: Bipallidal necrosis; Case 2: Left pallidal necrosis with right frontoparietal cortico-subcortical infarction; Case 3: Striato-capsular infarction on the left side, involving the caudate nucleus and the anterior arm of the internal capsule, together with obstructive hydrocephalus. CONCLUSION: The roles of both globus pallidus and prefrontostriatal circuits in the onset of voluntary movements are discussed.

Adult↗

Different periods of feed restriction before compensatory growth in Belgian Blue bulls: I. animal performance, nitrogen balance, meat characteristics, and fat composition.

Thirty double-muscled Belgian Blue bulls were maintained at a rate of gain of .5 kg/d during four periods of time, 115 (G2), 239 (G3), or 411 (G4) d (low growth period, LGP), before fattening (rapid growth period, RGP). Ten control animals (CG) were fed a diet rich in energy and protein. The G2, G3, and G4 were fed a diet low in energy and protein and the same diet as CG during RGP. Live weight was recorded biweekly, feed intake (FI) daily, and nitrogen balance at three times for each group. At the slaughterhouse, the 7, 8, and 9th ribs were removed to determine carcass composition, meat quality, and meat and fat composition. Compensatory growth reached a maximum 2 mo after refeeding and then decreased rapidly, leading to a sharp increase in the feed conversion ratio. Nitrogen balance was higher in compensating groups ( P < .05). Compensating animals had higher carcass connective and adipose tissue contents (P < .05) but lower meat fat content (P < .05). Cattle exhibiting compensatory growth had higher redness, yellowness, cooking losses, and drip losses, but had lower Warner-Bratzler peak shear force values. The saturated fatty acid content of the fat decreased with the duration of the LGP. During the first 2 mo after refeeding, compensatory growth in double-muscled bulls was ascribed to one or more of the following mechanisms: higher FI, lower maintenance requirements, or better efficiency of lean meat production. Compensatory growth at the expense of higher FI increased peripheral fat but decreased intramuscular fat deposition.

Abattoirs↗

Different periods of feed restriction before compensatory growth in Belgian Blue bulls: II. Plasma metabolites and hormones.

Plasma metabolites and hormones were studied in 16 double-muscled Belgian Blue bulls maintained at low growth (.5 kg/d) for 114 (G2), 243 (G3), or 419 (G4) d (low growth period, LGP) before fattening (rapid growth period, RGP). Animals from the control group (CG) were fed a diet high in energy and protein. The animals from G2, G3, and G4 were fed a restricted amount of a diet low in energy and protein during LGP and the same diet as CG during RGP. Plasma glucose, alpha-amino nitrogen (AAN), NEFA, urea, creatinine, thyroxine (T4), 3,3',5'-triiodothyronine (T3), and IGF-I were measured in blood samples taken fortnightly. Plasma GH and insulin (I) profiles were measured in serial blood samples obtained at three times during growth. The RGP was characterized by an initial compensatory growth, by higher plasma glucose, AAN, and urea levels, and by lower plasma NEFA and creatinine levels. Plasma GH concentration decreased after refeeding. Plasma T4 increased linearly during refeeding, as opposed to T3, which showed a different profile in each group. Plasma IGF-I showed a curvilinear increase during RGP and reached a plateau after 3 mo in each compensating group. In G4, changes of plasma metabolites and hormones differed often distinctly from G2 or G3. During refeeding, higher nutrient supply improved the functionality of the somatotropic axis and increased the concentration of anabolic hormones, allowing rapid muscle deposition. However, animals underfed the longest period behaved differently from the other groups, possibly because they reached a more complete sexual maturity.

Aging↗

In vitro genotoxicity of polycyclic musk fragrances in the micronucleus test.

The synthetic polycyclic musk fragrance compounds galaxolide (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-(g)-2-b enzopyrane), tonalide (7-acetyl-1,1,3,4,4,6-hexamerthyltetraline), celestolide (4-acetyl-1,1-dimethyl-6-tert-butylindane), phantolide (6-acetyl-1,1,2,3,3,5-hexamethylindane), cashmeran (6,7-dihydro-1,1,2,3,3-pentamethyl-4-(5H) indanone) and traseolide (5-acetyl-1,1,2,6-tetramethyl-3-isopropylindane) were examined for their genotoxicity in the micronucleus test (MNT) with human lymphocytes in vitro in the presence and absence of an exogenous metabolizing system containing rat liver S9 and the metabolically competent human hepatoma cell line Hep G2. Compound concentrations were employed up to cytotoxic doses. Galaxolide, tonalide, celestolide, phantolide, cashmeran and traseolide revealed no genotoxicity in the micronucleus test with human lymphocytes and with the human hepatoma cell line Hep G2.

Adult↗

Marked decrease of neuropeptide Y Y2 receptor binding sites in the hippocampus in murine prion disease.

Using autoradiographic binding methodology with monoiodinated peptide YY together with the agonists neuropeptide Y (NPY) and NPY (13-36), as well as in situ hybridization with oligonucleotide probes complementary to the NPY Y2 receptor (Y2-R) mRNA, we have studied whether or not intracerebral prion inoculation affects Y2-Rs in male CD-1 mice. Monoiodinated peptide YY binding, mainly representing Y2-Rs, was down-regulated by 85% in the CA1 strata oriens and radiatum and by 50-65% in the CA3 stratum oriens 110-140 days postinoculation. In the CA3 stratum radiatum, where the mossy fibers from the dentate granule cells project, there was a significant decrease in PYY binding at 110-120 days. Y2-R mRNA, moderately expressed both in the CA1 and CA3 pyramidal cell layers and the granule cell layer in the dentate gyrus, showed a slight, but not significant, decrease in CA3 neurons 130 days postinoculation. The results indicate that the accumulation of the scrapie prion protein in the CA1-3 region strongly inhibits NPY binding at the Y2-Rs, which, however, is only marginally due to reduced Y2-R mRNA expression. The loss of the ability of NPY to bind to inhibitory Y2-Rs may cause dysfunction of hippocampal circuits and may contribute to the clinical symptoms in mouse scrapie.

Animals↗

Genomic organization of the yeast Yarrowia lipolytica.

We produced electrophoretic karyotypes of the reference strain E150 and of seven other isolates from different geographical origins to study the genomic organization of the dimorphic yeast Yarrowia lipolytica. These karyotypes differed in the number and size of the chromosomal bands. The karyotype of the reference stain E150 consisted of five bands of between 2.6 and 4.9 Mb in size. This strain contained at least five rDNA clusters, from 190 to 620 kb in size, which were scattered over most of the chromosomes. The assignment of 43 markers, including rRNA genes and three centromeres, to the E150 bands defined five linkage groups. Hybridization to the karyotypes of other isolates with pools of markers of each linkage group showed that linkage groups I, II, IV and V were conserved in the strains tested whereas group III was not and was split between at least two chromosomes in most strains. Use of a meganuclease I-SceI site targeted to one locus of E150 linkage group III showed that two chromosomes actually comigrated in band III of this strain. Our results are compatible with six chromosomes defining the haploid complement of strains of Y. lipolytica and that, despite an unprecedented chromosome length polymorphism, the overall structure of the genome is conserved in different isolates.

Ascomycota↗

Prediction of recurrence by quantification of p185neu protein in non-small-cell lung cancer tissue.

The concentration of c-erbB-2 oncogene-encoded protein (p185neu) in fresh tumour samples obtained at the time of surgery from 94 non-small-cell lung cancer patients (NSCLC) was determined by an enzyme immunoassay. The relative prognostic importance was estimated, and the influence of other predictors was assessed by means of a Cox's proportional regression model. Median concentration of p185 in tumour tissues was 206 U mg(-1) (range 21-1050 U mg(-1)). p185 level did not differ significantly among subgroups defined by TNM classification, histological type, sex and age. Categorization of patients by p185 level, with 206 U mg(-1) and 343 U mg(-1) taken as cut-off values (corresponding to the 50th and 80th percentiles of the frequency distribution), showed that the recurrence rate, cumulative disease-free likelihood at the 36-month follow-up and median time from surgery to the diagnosis of recurrence worsened progressively as the level of p185 increased. Multivariate analysis confirmed the independent prognostic value of p185 level. Risk of recurrence increased by 1.304 for every increase of 100 units in p185 concentration (95% CI 1.141-1.490) (P<0.001). These findings encourage the inclusion of p185 concentration assay in a future predictive multifactorial prognostic index in NSCLC.

Adult↗