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PubMed2001

Identification of trains of sleep sequences in adult rats.

In previous studies based on high resolution EEG analyses of the 7 h baseline session of 18 adult male Wistar rats [6,14], we have identified four sleep sequences initiating with slow wave sleep (SS) and terminating with waking (W) or paradoxical sleep (PS). Two of these sequences contained an intervening episode of transition sleep (TS). Several variables of these sequences (SS-->W, SS-->TS-->W, SS-->TS-->PS, and SS-->PS) were selectively correlated with the capacity of rats to learn a two-way active avoidance task the following day, and were differently distributed in fast learning, slow learning and non learning rats [21]. The temporal organization of different sleep components in sequences suggested that a comparable temporal organization might concern the different sleep sequences, albeit on a longer time scale. We have now used waking periods longer than 60 s to separate clusters of baseline sleep sequences (trains) in the same rats. Trains containing the same sleep sequence (homogeneous trains) have been distinguished from trains containing different sleep sequences (mixed trains). In addition, mixed trains including the SS-->TS-->W sequence (+TSW trains) have been separated from mixed trains lacking that sequence (-TSW trains). Mixed trains of the +TSW type were longest and most numerous, while homogeneous trains were shortest and least abundant. Mixed trains of the -TSW type displayed intermediate values. Several variables of sleep sequences and sleep components differed within mixed trains and among mixed and homogeneous trains. The data indicate that baseline sleep sequences aggregate in relatively long strings in a non random fashion. The mechanism of this association is discussed.

Animals↗
PubMed1999

Expression of Fas and Fas ligand in cutaneous B-cell lymphomas.

Primary cutaneous B-cell lymphomas (CBCLs) represent a rare, but distinct group of B-cell neoplasms with a different clinical behaviour to B-cell lymphomas secondarily involving the skin. Fas-Fas ligand (Fasl) expression was investigated in a group of primary and secondary CBCLs to gain an insight into the putative role of these apoptotic molecules in the clinical behaviour of these lymphomas. Frozen and paraffin sections from 32 patients with a CBCL were investigated for Fas and Fasl expression, using immunohistochemistry. This group included 24 primary CBCLs [14 primary cutaneous follicle centre cell lymphomas (PCFCCLs), six primary cutaneous large B-cell lymphomas (PCLBCLs) on the leg, and four primary cutaneous immunocytomas] and eight secondary CBCLs. The results were correlated with follow-up data, bcl-2, and ICAM-1 expression. High Fas expression and absent or low Fasl expression were detected in the vast majority of PCFCCLs and immunocytomas. The group of PCLBCLs on the leg, which have an intermediate prognosis, showed variable results with relatively higher Fasl expression. The highest Fasl expression was found in the more aggressive secondary CBCLs whereas in this group, Fas was undetectable in five of eight cases. Statistical analysis showed that Fas and ICAM-1 expression was strongly related to a favourable prognosis, whereas expression of Fasl and bcl-2 was related to a very poor prognosis. Although only type of CBCL and age, but not Fas, Fasl, bcl-2, and ICAM-1 expression, proved independent prognostic parameters using multivariate analysis, the results of this study suggest that differences in the expression of Fas and Fasl, as well as bcl-2 and ICAM-1, contribute to the differences in clinical behaviour between these different types of CBCL.

Adult↗
PubMed1993

Liver metastases with 10 human colon carcinoma cell lines in nude mice and association with carcinoembryonic antigen production.

BACKGROUND: The secretion of carcinoembryonic antigen (CEA) by many colorectal tumors is associated with a worse prognosis and a greater likelihood of metastases. The exact biologic function of CEA is not known. In the literature, it has been postulated CEA may be a tumorigenicity-enhancing factor. METHODS: Ten different human colonic adenocarcinoma cell lines (RW-7213, RW-2982, LS174T, SW1116, RW-5928, DLD-2, SW-48, DLD-1, SW-480, and HCT-8) with a wide range of CEA production (from undetectable to 5200 ng/ml in culture medium) were injected into the spleens of groups of nude mice as a model for experimental hepatic metastasis. RESULTS: There was a wide range in local tumorigenicity in the spleen (from 0-90%) and in liver metastases (from 0-70%). The capacity to grow in both liver and spleen was associated with CEA production. The four cell lines that secreted the highest amounts of CEA produced the highest tumorigenicity in the spleen (67-90%) with frequent liver colonization (25-70%). The two cell lines that secreted no detectable CEA produced neither splenic tumors nor hepatic colonies. Low-level CEA production was associated with intermediate and more variable tumorigenicity. CONCLUSIONS: There was an association between CEA secretion and the ability of 10 different colorectal cell lines to grow in nude mouse spleen and liver models.

Adenocarcinoma↗
PubMed2005

Main accessory sulcus of the liver.

It has been proposed that the superficial part of the portal fissures weakens the surface hepatic parenchyma, allowing the development of accessory sulci caused by diaphragmatic pressure. To evaluate the relationship of the sulci in the antero-superior surface of the right liver with the right portal fissure, macroscopic post mortem examination of 85 livers was carried out and radio-opaque resins were injected into the portal and hepatic venous systems to obtain vascular casts. After formalin fixation, the 85 livers also underwent CT and MR scans and 3D image elaboration. Diaphragmatic sulci were found in 32 cases. We studied the sulci located in the right liver, i.e., those that lay to the right of the line of Cantlie. They were found in 28 instances and in 16 cases they were multiple. In the livers with a single sulcus, it extended between the anterior and right surfaces of the right liver and showed a curved course downward and forward, toward the inferior margin. In the cases with multiple sulci, one sulcus always showed a course similar to that of the single sulci. The 28 sulci, with similar position and course, showed variable characteristics (mean length=7.6 +/- 2.7 cm, mean width=0.8 +/- 0.7 cm, mean depth=1.4 +/- 0.8 cm). Both radiological images and corrosion casts showed a correspondence between these sulci and the right hepatic vein and the right portal fissure in 71% of cases. These sulci may represent the variable expression (cranial, intermediate, or caudal portions) of a potential sulcus, the main accessory sulcus (MAS), that develops along a theoretically predictable course corresponding to the superficial part of the right portal fissure. The high prevalence of location of the MAS at the level of the upper part of the right portal fissure can be ascribed to the presence at this level of the watershed between the roots of the tributaries of the hepatic veins coming from segments VIII and VII, draining respectively into the middle and right hepatic veins. Thus, the coexistence of the two portal and hepatic venous boundaries may represent a further predisposition to the effects of diaphragmatic pressure. The MAS may represent a marking for the right portal fissure, and hence a superficial reference for the deep course of the right hepatic vein.

Adult↗
PubMed1980

The ependyma of the saccular pineal gland in the non-eutherian mammal Trichosurus vulpecula. A scanning electron microscopic study.

The pineal gland in the possum is represented by a thickening in the wall of the pineal recess. A superficial pineal body and a pineal stalk are characteristically lacking. The ependyma related to the gland is specialized but differs markedly from the lining in other circumventricular organs in form and in surface morphology. Two distinct topographic zones have been recognized. In the middle is a mass of cells which form a prominent knobby-surfaced central zone. These cells are characterized by the absence of cilia, the paucity of microvilli and blebs and the presence of processes which overlap adjacent cells. A surface pattern formed of cell outlines was lacking. it is suggested that the central zone is lined by pinealocytes, supporting cells and the processes of both cell types. Most of the central zone is surrounded by an intermediate zone of variable width. The latter region has been observed to possess a circumventricular organ-type surface morphology. It is sparsely ciliated, almost totally covered by a carpet of microvilli and it exhibits a variety of surface specializations. Supraependymal cells and various transitory supraependymal cell processes are also present. Outside the specialized ependyma is the peripheral zone which like the regular ventricular lining is densely ciliated. Supraependymal processes are found among the clusters of cilia, or rarely, on the surface of the ciliary bed. Season and sex related differences in surface ultrastructure were not observed.

Animals↗
PubMed1989

Predictors of sustained ventricular tachycardia inducibility in patients with nonsustained ventricular tachycardia and chronic coronary artery disease.

To assess the likelihood of inducing sustained ventricular tachycardia, we analyzed a cohort of 58 retrospective and 18 prospective patients with chronic coronary artery disease who underwent electrophysiologic study because of spontaneous nonsustained ventricular tachycardia (three or more beats, lasting less than 30 seconds, at a rate greater than 100/min). In 24 of the 58 retrospective patients (41%) sustained ventricular tachycardia was inducible. Stepwise logistic regression identified two "major" variables--left ventricular aneurysm/dyskinesis/akinesis (p = 0.0001; relative risk = 11.88) and ejection fraction less than 40% (p = 0.0002; relative risk = 9.69)--and one "minor" variable--nonsustained ventricular tachycardia longer than 10 beats (p = 0.0151; relative risk = 4.21)--as significant predictors of inducibility. Nineteen patients with both major variables had a high probability of inducibility (greater than 90%). Nineteen patients with neither major variable had a low probability of inducibility (less than 5%). The remaining 20 patients with only one of the major variables had an intermediate probability of inducibility (14% to 75%). The significance of the third minor factor, nonsustained ventricular tachycardia longer than 10 beats, was confined to this intermediate group, in which it could be used to segregate relatively high (65% to 75%) and relatively low (14% to 20%) probability of inducibility. Prospective application of the predictor function stratified 18 additional patients into three groups with high (six patients), intermediate (seven patients), and low (five patients) probability of inducibility. The observed rate of inducibility in each group was 5 of 6 (83%), 2 of 7 (29%), and 0 of 5 (0%), respectively. These data suggest that patients with nonsustained ventricular tachycardia and chronic coronary artery disease can be stratified into subgroups with high, intermediate, and low probability of inducibility of sustained ventricular tachycardia on the basis of ejection fraction and regional ventricular wall motion defects alone.

Aged↗
PubMed1995

Clinicians and patients with hypertension: unsettled issues about compliance.

Ambulatory treatment of hypertension depends largely on long-term oral medications to lower blood pressure and delay or prevent cardiovascular morbidity and mortality. Failure to achieve the therapeutic goal may reflect biologic, pharmacologic, or behavioral factors. Ignoring behavioral factors may result in unnecessary or even dangerous regimen escalation. More than half of patients with insufficient reductions in blood pressure display suboptimal medication compliance as assessed by pill count or bioassay. Once-daily dosing may be an important part of enhancing compliance, patient convenience, and regimen simplification; however, drug concentrations may be subtherapeutic when dosing delays or omissions occur. Electronic monitoring data in hypertension, glaucoma, seizure disorders, and other diseases indicate that 50% to 60% of patients adhere well to prescribed regiments, that 5% to 10% adhere poorly, and that the 30% to 45% adhere to an intermediate but markedly variable degree. A growing body of literature offers empirical support for focused and personalized interventions.

Ambulatory Care↗
PubMed1990

Comparison of norethindrone and medroxyprogesterone acetate with natural progesterone and estradiol in stimulating prolactin production from cultured endometrial stromal cells.

Progestins stimulate prolactin production from endometrial stromal cells in culture. We compared the potencies of the synthetic progestins norethindrone and medroxyprogesterone acetate to natural progesterone in inducing stromal prolactin production. Modifications of the culture system provided an increase in stromal cell yield, thus permitting multiple comparisons from the treatment of cells from a common endometrial sample. The effects of high-dose estradiol also were evaluated in this system. The findings suggest relative potencies of 50:1 for medroxyprogesterone acetate and progesterone. Norethindrone gave intermediate and more variable responses. Estradiol potentiated prolactin production from only submaximal progestins doses. The differences between the progestin effects, in large measure, were due to differential culture growth as reflected by culture mass. Compared to controls and estradiol alone, all the progestins induced much greater prolactin production. Thus during decidualization, progestins probably promote both stromal growth and intracellular prolactin production. High-dose estradiol may not interfere with these events.

Analysis of Variance↗
PubMed1984

Transformation of fibre types in muscular dystrophies.

In the normal human skeletal muscle, slow and fast forms of troponin I are segregated in type I and type II cells, respectively. Muscle biopsies from different dystrophies showed a large number of intermediate cells that stained with antibodies to both fast and slow troponin I. Intermediate cells of variable size were scattered at random and did not show a motor unit distribution as generally seen in some neuromuscular disorders. The preponderance of a particular cell type depended on the type of dystrophy. Except for dystrophia myotonica, all cases showed presence of small cells that looked like regenerating cells.

Adult↗
PubMed1992

A multivariate study of protective effects of Zn and Cu against nephrotoxicity induced by cadmium metallothionein in rats.

Factorial experimental design was used to study the protective effects of Zn and Cu on cadmium-metallothionein(CdMT)-induced nephrotoxicity in male Wistar rats. In the factorial design two levels of Zn (0 and 25 mg/kg body weight), two levels of Cu (0 and 12.5 mg/kg), and two levels of CdMT (0.1 and 0.4 mg of Cd/kg) were used as varied factors. The factorial design was complemented with a center point with all three variables at an intermediate setting, i.e., Zn at 12.5 mg/kg, Cu at 6.25 mg/kg, and CdMT at 0.25 mg Cd/kg. Each of the nine combinations of settings was administered to one of nine groups with six rats in each. Zn and Cu were injected sc 24 hr prior to the injection of CdMT. The concentrations of protein and Ca in urine and Ca in renal cortex were used as effects. The relationship between the experimental design settings and the effects were modeled with multiple regression. The multiple regression analysis revealed that for the high dose of CdMT (i) the enhanced values of protein in urine caused by CdMT injection could be more efficiently reduced by Zn than by Cu, and (ii) excessive Ca in urine and renal cortex could be more efficiently reduced by Cu than by Zn. No significant synergism or antagonism between Cu and Zn was found. These models can be used to estimate the dose levels of Zn and Cu which will reduce the toxic effects of CdMT. The treatment of 20.4 mg/kg Zn, for example, will reduce the effects of 0.4 mg Cd/kg as CdMT on protein in urine, and 2.8 mg/kg Cu will reduce the Ca in urine to the levels of those caused by 0.25 mg Cd/kg (no Zn and Cu). Similarly, the effect of 0.4 mg Cd/kg on Ca level in renal cortex can be reduced to that of 0.28 mg Cd/kg as CdMT by 7.98 mg Cu/kg, which is three times as efficient as Zn. The obtained results might be of importance in understanding the mechanism of cadmium toxicity and the potential risk to the health of the population exposed to cadmium occupationally or environmentally.

Animals↗
PubMed1981

Auditory event-related potentials in schizophrenia and depression.

Event-related potentials in two auditory target detection paradigms and two auditory paradigms without overt tasks were studied in 22 schizophrenic, 21 depressed, and 28 matched control subjects meeting Research Diagnostic Criteria. In the target detection paradigms, schizophrenics showed a pattern of reduced N120 amplitude and shorter P200 latency to frequently occurring tones, and reduced P300 and Slow Wave amplitude to infrequent target and nontarget tones. This pattern is consistent with impaired selective attention for stimuli. For depressed patients these variables were generally intermediate between those of schizophrenics and controls. In the other paradigms N120 latency was greater for schizophrenics, and P200 amplitude was less for depressed patients.

Adult↗
PubMed1994

Age changes in mastication in the pig.

A comparative study of chewing in miniature pigs at three stages of dental development was carried out using electromyography and movement analysis. The mastication of the youngest pigs was characterized by longer burst durations of jaw muscles, particularly closing muscles, and greater relative jaw opening. Chewing side alternated irregularly and burst durations were variable. Between the intermediate and oldest ages, the parameters remained almost unchanged. Because the amount of dental development that occurred between the second two stages was just as extensive as that between the first two, progressive eruption cannot account for the age changes observed in mastication.

Age Factors↗
PubMed2001

The influence of plaque orientation (pericardial or myocardial) on coronary arterial remodeling.

BACKGROUND: Many systemic, regional and lesion factors have been identified which may influence arterial remodeling, but little is known about the importance of extravascular resistance to vessel enlargement. As myocardial systolic splinting may significantly affect vessel expansion the effect of plaque orientation on arterial remodeling in eccentric coronary atherosclerotic lesions was examined. METHODS: Using intravascular ultrasound imaging to obtain cross-sectional vessel area (VA), plaque area (PA) and lumen area (LA), remodeling in eccentric left anterior descending coronary artery lesions was compared which predominantly involved the pericardial or free arc (P, n=25) and the myocardial side (M, n=40) of the vessel wall. Normalized vessel area (NVA, VA(lesion)/VA(reference)) was compared as a continuous and categorical variable (positive>1.05, intermediate 0.95-1.05, negative<0.95) as well as remodeling index (RI, VA(lesion)-VA(reference)/PA(lesion)-PA(reference)). RESULTS: The two groups were well matched for clinical and lesion characteristics known to affect remodeling. Reference segments areas were similar in the two groups; while lesion LA was also similar, in the pericardial group there was significantly greater lesion PA (P 12.78+/-0.72, M 10.26+/-0.50 mm(2), P<0.05) and VA (P 15.71+/-0.90, M 12.82+/-0.57 mm(2), P<0.05) demonstrating enhanced compensatory remodeling. Outward remodeling was significantly greater in P than in M by both NVA (P 1.03+/-0.03, M 0.86+/-0.03, P<0.01) and RI (P 0.02+/-0.07, M -1.10+/-0.32, P<0.01). Positive, intermediate and negative remodeling occurred in nine, nine and seven lesions in P and in four, ten and 26 lesions in M (P<0.01). CONCLUSIONS: Remodeling compensates more for plaque growth in eccentric coronary lesions which are surrounded by the pericardium than those surrounded by the myocardium. Extravascular resistance appears to influence arterial remodeling.

Aged↗
PubMed1996

Randomised controlled trial of a reduced-visits programme of antenatal care in Harare, Zimbabwe.

BACKGROUND: Many of the individual components of antenatal care have been studied in randomised controlled trials, but few studies have compared whole programmes of antenatal care. Our aim was to test the hypothesis that a new programme of antenatal care with fewer goal-oriented visits would give an equivalent or better result in the outcomes associated with pregnancy and delivery. METHODS: In a randomised clinical trial in Harare, Zimbabwe, we compared a new programme of antenatal care with the standard programme. The new programme consisted of fewer but more objectively oriented visits and fewer procedures per visit. Seven primary care clinics were randomly assigned to the two programmes-three to the standard programme and four to the new programme. FINDINGS: Over a 2-year period, 15,994 women were recruited into the study at the time they booked antenatal care. 97% of the women were followed up, 9,394 who had followed the new programme, and 6,138 from clinics with the standard one. Women allocated to the new programme made, as planned, fewer visits than those in the standard programme (median 4 vs 6 visits, respectively). The proportion of antenatal referrals was also lower (13.6 vs 15.3%; odds ratio 0.87 [95% CI 0.79-0.95]) because of significantly fewer referrals for pregnancy-induced hypertension (2.5 vs 3.8%; 0.66 [0.55-0.79]). Nevertheless, there were significantly fewer labour referrals for severe hypertension or eclampsia (2.1 vs 2.6%; 0.81 [0.66-1.00]). The risk for preterm (< 37 weeks) delivery was significantly lower for women on the new programme (10.1 vs 11.5%; 0.86 [0.78-0.96]). There were no other significant differences between the programmes in other major indices of pregnancy outcome, including antenatal referrals for other causes, labour referrals, obstetric interventions, low birthweight, and perinatal and maternal mortality and morbidity. INTERPRETATION: An antenatal care programme with fewer more objectively oriented visits can be introduced without adverse effects on the main intermediate outcome pregnancy variables.

Adult↗
PubMed1987

The immunological consequences of challenge with bovine tubercle bacilli in badgers (Meles meles).

Optimal conditions were determined for performing antibody measurements (ELISA), lymphocyte transformation tests and, to some extent, skin tests in badgers. These parameters, together with the bacteriological and pathological studies reported previously (Pritchard et al. 1987), were used to follow the course of intradermal and intratracheal challenge of badgers with bovine tubercle bacilli. Two challenge doses were used for each route of infection and two animals received each dose. None of the four animals challenged by the intratracheal method showed any evidence of infection, suggesting that adult badgers may have some resistance to challenge by this method. All four animals challenged intradermally developed lesion of tuberculosis. Immunologically the disease passed through three phases. There was an early phase in which lymphocyte transformation to whole BCG steadily and significantly increased, and skin tests to tuberculin became positive but there was little change in antibody levels. This was followed by an intermediate phase of variable skin responses, fluctuating lymphocyte transformation and significant increase in antibody levels. The final phase, which was only seen in two animals with extensive disease, was associated with changing skin reactions and falling lymphocyte responses, together with a sudden increase in antibody levels. This paper presents the first formal evidence of cell-mediated immunity to tuberculosis in the badger, which may delay onset and prolong the survival of challenged animals.

Animals↗
PubMedDate not supplied

Fast intracrystalline hydration of beta-chitin revealed by combined microdrop generation and on-line synchrotron radiation microdiffraction.

Water microdrops of about 50 microm in diameter, generated by an ink-jet system, have been used to hydrate fragments of Pogonophora tubes. In situ X-ray microdiffraction with a beam size of 10 microm was used to follow the structural transformations that affected the crystalline beta-chitin part of the specimens. Starting from anhydrous chitin, the formation of a full beta-chitin dihydrate was observed within about 90 s. A disordered intermediate phase with variable d-spacing that could be due to a mixture of anhydrous and hydrated beta-chitin layers was also detected.

Chitin↗
PubMed1997

Entropy detection by pigeons: response to mixed visual displays after same-different discrimination training.

Pigeons were trained to peck 2 different buttons in response to 16-icon Same versus Different arrays. In Same arrays, the icons were identical to one another, whereas in Different arrays, the icons were different from one another. In Experiment 1, pigeons discriminated Same from Different arrays and transferred their discriminative responding to arrays of novel icons. In Experiments 2-4, pigeons exhibited sensitivity to the degree of display variability when shown intermediate Mixture arrays. Entropy, an information theoretic measure, systematically described these results while outperforming rival accounts.

Animals↗
PubMed2000

The two faces of mutation: extinction and adaptation in RNA viruses.

From a population standpoint, two main features characterize the replication of RNA viruses and viruses that use RNA as a replicative intermediate: high genetic variability, and enormous fluctuations in population size. Their genetic variability mainly reflects a lack of the proof-reading and post-replicative error correction mechanisms that operate during cellular DNA replication, but recombination and segment exchange can also play an important role. Viral population size can change tremendously as a consequence of transmission between hosts or between different tissues within an infected host. A new infection can be initiated with very few particles that subsequently expand many trillion-fold. Repeated bottleneck events can lead to drastic fitness losses or even to viral extinction, whereas continuously large population sizes result in fitness gains and adaptation. Here we review experimental evidence for the effects of mutation, selection, and genetic drift on the adaptation and extinction of RNA viruses.

Adaptation, Physiological↗