[A young woman with fulminant pulmonary embolism]. / Fulminante Lungenembolie bei einer jungen Frau.

We describe the case of a 24-year-old woman who was admitted to the emergency department with dyspnea and sinus tachycardia. The suspected diagnosis of pulmonary embolism was confirmed by computed tomography (CT) scan. The patient lost consciousness soon afterwards and was found to be pulseless. Cardiopulmonary resuscitation was performed and high dosis thrombolysis was given. The patient survived without sequelae and was discharged on oral anticoagulation from the hospital 8 days after the initial admission. In our opinion unknown factor-V Leiden in combination with a local form of hormonal contraception (NuvaRing®) was responsible for the deep venous thrombosis of the left leg and the pulmonary embolism.

Primary cutaneous marginal zone B-cell lymphoma in a patient with chronic lymphocytic leukaemia.

Primary cutaneous marginal zone B-cell lymphoma (PCMZL) is a low-grade malignant lymphoma that presents in the skin with no evidence of extracutaneous localization at diagnosis. We present an 80-year-old woman with B-cell chronic lymphocytic leukaemia (CLL) who developed multifocal PCMZL lesions 14 months after CLL diagnosis. PCMZL was clonally similar to the original bone marrow (BM) CLL cells. The specific translocation t(14;18) (q32;q21) with breakpoints in IGH and BCL2 loci was found in a skin specimen, but was absent in BM and peripheral blood (PB) cells. In contrast, a 13q deletion was found in BM and PB CLL cells. The patient was treated with chlorambucil and complete response of PCMZL was achieved. To our knowledge this is the first patient with CLL in whom PCMZL has been diagnosed.

Ligand density modulates eosinophil signaling and migration.

Eosinophils are a major component of the inflammatory response in persistent airway inflammation in asthma. The factors that determine the retention of eosinophils in the airway remain poorly understood. Elevated levels of fibronectin have been observed in the airway of patients with asthma, and the levels correlate with eosinophil numbers. To determine if fibronectin density modulates eosinophil function, we investigated the effect of fibronectin and vascular cell adhesion molecule 1 (VCAM-1) density on eosinophil migration and signaling via the p38 and extracellular regulated kinase (ERK)-mitogen-activated protein kinase (MAPK) signaling pathways. There was a dose-dependent inhibition of eosinophil spreading and migration on increasing concentrations of fibronectin but not VCAM-1. In addition, activation of p38 MAPK was inhibited at high fibronectin but not high VCAM-1 concentrations, and ERK activity was slightly reduced at high VCAM-1 and fibronectin concentrations. Together, the results demonstrate that fibronectin but not VCAM-1 inhibits eosinophil migration and signaling.

[Investigation of polyamine interactions with the nuclear transcription factor NF-kappa B by computer modelling]. / Doslidzhennia vzaiemodiï poliaminiv z iadernym faktorom transkryptsiï NF-kappa B metodamy komp'iuternoho modeliuvannia.

Computer modelling is used to study interactions between polyamines and nuclear transcription factor NF-kappa B and NF-kappa B. specific DNA complex. It is shown that polyamines can regulate interaction between NF-kappa B and the specific DNA sequence by binding to p50 subunit of NF-kappa B. A possible polyamines binding site on the surface of p50 is found. Dissociation of polyamines to p50.DNA complex is modelled. Kd of spermine, spermidine and putrescine are calculated. Conformational transition of DNA.(p50)2-->DNA.p50 + p50 is simulated. Kd of complex p50.DNA is calculated in the presence and in the absence of polyamine in the binding site on the p50. It is shown that polyamines stabilizes the inter-domain interface of p50 protein due to appearance of additional electrostatic and hydrogen bonds. Shah, Thomas and Shirahata obtained the following sequence of efficiency in facilitating NF-kappa B--DNA binding: spermine > spermidine > putrescine. The sequence of affinities of polyamines to NF-kappa B that we obtained corresponds well to the former sequence from the cited work. Our results support the hypothesis that polyamines decreases the probability of spontaneous dissociation of DNA.p50 complex.

Fiber knob modifications overcome low, heterogeneous expression of the coxsackievirus-adenovirus receptor that limits adenovirus gene transfer and oncolysis for human rhabdomyosarcoma cells.

Exploiting the lytic life cycle of viruses has gained recent attention as an anticancer strategy (oncolysis). To explore the utility of adenovirus (Ad)-mediated oncolysis for rhabdomyosarcoma (RMS), we tested RMS cell lines for Ad gene transduction and infection. RMS cells were variably transduced by Ad. Compared with control cells, RMS cells were less sensitive or even resistant to oncolysis by wild-type virus. RMS cells expressed the Ad internalization receptors, alpha(v) integrins, but had low or undetectable expression of the major attachment receptor, coxsackievirus-Ad receptor (CAR). Mutant Ads with ablated CAR binding exhibited only 5-20% of transgene expression in RMS cells seen with a wild-type vector, suggesting that residual or heterogeneous CAR expression mediated the little transduction that was detectable. Immunohistochemical analysis of archived clinical specimens showed little detectable CAR expression in five embryonal and eight alveolar RMS tumors. Stable transduction of the cDNA for CAR enabled both efficient Ad gene transfer and oncolysis for otherwise resistant RMS cells, suggesting that poor CAR expression is the limiting feature. Gene transfer to RMS cells was increased >2 logs using Ads engineered with modified fiber knobs containing either an integrin-binding RGD peptide or a polylysine peptide in the exposed HI loop. The RGD modification enabled increased oncolysis for RMS cells by a conditionally replicative Ad, Ad delta24RGD, harboring a retinoblastoma-binding mutation in the E1A gene. Thus, the development of replication-competent vectors targeted to cell surface receptors other than CAR is critical to advance the use of Ad for treating RMS.

Nociceptive responsiveness during slow-wave sleep and waking in the rat.

Brainstem neurons that are thought to modulate pain are reported to have state-dependent discharge rates. Yet, the effect of behavioral state upon nociceptive transmission has not been well studied. Therefore, we examined responses to noxious thermal stimulation of the rat hindpaw presented during different behavioral states. Noxious thermal stimuli were applied to rats as they spontaneously cycled through waking and sleeping states. Two different methods of heating the paw - a focused light bulb ("radiant heat") and a CO2 laser ("laser heat")-were employed. Regardless of the heating method used, rats withdrew from noxious thermal stimulation when it was applied in each behavioral state tested. When rats were tested with radiant heat, the withdrawal latency from noxious heat was shorter during slow-wave sleep than during waking. In contrast, when tested with laser heat, there was no difference in either the response latency or magnitude evoked by noxious heat across sleep/wake states. Despite the fact that rats withdrew from noxious heat (using either method of application) applied during sleep, the rats quickly returned to sleep afterwards. The latency to sleep after noxious stimulation was significantly greater during waking than during sleeping. The behavioral response to noxious thermal stimulation includes both an initial motor withdrawal which is enhanced during sleep and arousal or alerting which is suppressed during sleep. Therefore, pain evokes at least two distinct reactions that are differentially modulated across sleep/wake cycles.

Temporal population code of concurrent vocal signals in the auditory midbrain.

Unique patterns of spike activity across neuron populations have been implicated in the coding of complex sensory stimuli. Delineating the patterns of neural activity in response to varying stimulus parameters and their relationships to the tuning characteristics of individual neurons is essential to ascertaining the nature of population coding within the brain. Here, we address these points in the midbrain coding of concurrent vocal signals of a sound-producing fish, the plainfin midshipman. Midshipman produce multiharmonic vocalizations which frequently overlap to produce beats. We used multivariate statistical analysis from single-unit recordings across multiple animals to assess the presence of a temporal population code. Our results show that distinct patterns of temporal activity emerge among midbrain neurons in response to concurrent signals that vary in their difference frequency. These patterns can serve to code beat difference frequencies. The patterns directly result from the differential temporal coding of difference frequency by individual neurons. Difference frequency encoding, based on temporal patterns of activity, could permit the segregation of concurrent vocal signals on time scales shorter than codes requiring averaging. Given the ubiquity across vertebrates of auditory midbrain tuning to the temporal structure of acoustic signals, a similar temporal population code is likely present in other species.

The crystal structure of phosphoribulokinase from Rhodobacter sphaeroides reveals a fold similar to that of adenylate kinase.

The essential photosynthetic enzyme phosphoribulokinase (PRK) is responsible for the conversion of ribulose 5-phosphate (Ru5P) to ribulose 1,5-bisphosphate, the substrate for the CO2 fixing enzyme ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco). We have determined the structure of the octameric bacterial form of PRK to a resolution of 2.5 A. The protein is folded into a seven-member mixed beta-sheet surrounded by alpha-helices, giving the overall appearance of the nucleotide monophosphate family of kinases. Homology with the nucleotide monophosphate kinases suggests a number of amino acid residues that are likely to be important in catalysis and suggests the roles of some amino acid residues that have been mutated prior to the determination of the structure. Further, sequence identity across eukaryotic and prokaryotic species and a calculation of the buried surface area suggests the identity within the octamer of a dimer conserved throughout evolution. The width of the groove leading to the active site is consistent with an oriented molecule of thioredoxin controlling the oxidation state of two cysteines that regulate activity in the eukaryotic enzymes. Although neither Asp 42 nor Asp 169 can be definitively assigned as the catalytic base, the crystal structure suggests the location of a ribulose 5-phosphate binding site and suggests a role for several of the conserved basic residues.

[Veterinary medicine in the modern world]. / Zverolékarství v dnesním svete.

Present veterinary medicine is the result of a global scientific effort. Unknown are ideological or national barriers. However, the conditions for its realization vary from country to country with a changing clientele as well. The number of farm animals is increasing, as well as interest in the health of animals not in the care of man. There are about 600,000 veterinarians in the world, globally unevenly distributed. Relatively speaking, the least are in areas with greater agricultural population, and the most, in societies of the postindustrial age. In recent years many regions of the world have been going through an avalanche of changes. Even though the concepts of these consequence to the health care of animals far from agree, the direction of veterinary responsibility is shifting from public to private sector. In this regard the care of animal health on an international, national or regional level has been repeatedly analyzed and intricately evaluated from the early '80s. A generally accepted policy has been that in the care of animal health both sectors, public and private, play a significant role. However, under discussion are their relative proportions which differ in various parts of the world. The market is increasingly permeating into health care. In our country up to now the critical break in the development of veterinary medicine has not been objectively evaluated. We are still too concerned with the past, passing on disinformation, persisting in old dogmas and moss-grown myths. The way into a world of new priorities and the hierarchy of values in today's turbulent times is uneasy, all the more to be tentaciously sought.

[Changes in hydration in chicken and duck eggs during incubation]. / Zmeny hydratace slepicích a kachních vajec behem inkubace.

Water loss was determined during incubation in 80 eggs of the domestic fowl, White Leghorn-LB and New Hampshire-NH (between the 1st and 20th day), and in 80 eggs of Beijing White ducks (between the 1st and 25th day). Our data have shown that, the lowest actual water content was found in NH eggs, the highest in the duck eggs. Water content decreased absolutely and relatively during incubation; 365 in LB, 500 in NH and 312 mg/d in ducks. Water loss was higher in the first half of hatching. In the second half it was probably partly offset by water originating from fats oxidized for energetic purposes; the offset made a third in LB and NH, and still more in the ducks. Our results are somewhat different from the literature data, the variability of which is considered to be rather high in general. There were large shifts of water among the egg components during incubation. Water totally disappeared from the albumen, although it contained approximately three quarters of water was at the beginning of hatching. Already in the first half of incubation, more than a third of water was transported to the embryo, fetal membranes and fluids. In the subsequent ten days, water accumulation in the body of the developing and growing embryo was especially rapid; the water amount increased eight times in the fowl, seven times in the duck bodies. Water losses and its shifts show not only interspecific differences related to different lengths of incubation, but also intraspecific ones, between BL and NH.

[Sows and piglets--nutritional interactions]. / Prasnice a selata--nutricní interakce.

Nutrition energy transfer from sows to piglets is unusually intensive in the suckling period. Due to this transfer, the sows increase their relative standard energy metabolism up to four times, that means to the boundary of the long-term sustainable maximum. They cannot cover these large energy outputs by feed intake, therefore they are catabolizing their own body tissues during suckling and lose about 15% of their live weight. Through milk, which is an energy-rich high-fat diet, up to 1.76 MJ/kg and day of energy (in the first week) are transferred to piglets, and/or up to 2.26 MJ/kg0.75 and day of energy (in the second week), which enables them to double their live weight at birth within the first 7 to 10 days. Milk transfer is of behavioral character in the system dam and litter. In a short time, it assumes a form of cyclic, collective synchronized suckling which is repeated more than twenty times a day and consists of several phases. But the piglets are able to feed not only on genuine milk but also from other sources from the second week of life. Then their weaning begins. They enter from the suckling period to a long, several-week period of weaning, in which some of their functional characteristics are changed fluently, others in a cascade manner. Proper, and to all participants adequate development of this transfer is depending on numerous circumstance which need not always be real. One of the reasons is that birth is such a large load for piglets that they cannot be competitive partners to their less loaded mates in the competition for sources of nutrition. Their participation in the unusually intensive, episodic, delicate transfer of nutrients conditioned by many factors is insufficient, full of failures. Hence they do not sufficiently utilize their growth potential, and do not often survive. Nevertheless, they are so functionally adaptable so that they can live without mothers, in isolation, being able to drink a liquid diet.

[Anagrelide--new antiplatelet drug]. / Anagrelide--nowy lek przeciwplytkowy.

Anagrelide is a quinazoline compound developed as a potent inhibitor of platelet aggregation. During studies in human it has produced rapid and selective thrombocytopenia and has therefore been evaluated for use in conditions associated with thrombocythaemia. Anagrelide significantly inhibits human megakaryocyte colony development in vitro by preventing full megakaryocyte maturation, and inhibits platelet aggregation as a result of potent inhibition of cyclic adenosine monophosphate (cAMP) phosphodiesterase activity. In 60 to 93% of patients with essential or myeloproliferative thrombocythaemia anagrelide produces sustain reductions in platelet counts and also reduces the incidence of disease-related symptoms. Most adverse effects are related to its vasodilatory or positive inotropic properties. This new agent appears promising in the treatment of thrombocytosis in patients with chronic myeloproliferative diseases, especially in younger persons in whom the risk of leukaemogenic transformation with some alternative drugs is of particular concern.

The effects of diarrhoea on food intake in piglets weaned on the day of birth.

Large White x Landrace piglets (23 animals) weaned on the first day after birth were reared individually in a thermoneutral environment on a liquid diet having a macronutrient content similar to that of sow's milk. They were offered the diet from sucking bottles nine times a day at 2-h intervals. According to the appearance of the faeces the animals were divided into two groups: diarrhoeic piglets and clinically healthy animals. Their consumption of the diet, energy (GE) and macronutrients was assessed from the 3rd to the 10th day after birth; a total of 514 and 441 measurements were made in diarrhoeic piglets and healthy controls, respectively. With advancing age the intake of the diet by animals of the two groups changed in the same way as we described in previous studies. In diarrhoeic piglets, however, both the actual and the relative food intake, expressed in relation to live body mass and metabolic mass, was lower on days 3, 5 and 6 than in the healthy controls. In the period of the earlier described transient decrease in food consumption this difference disappeared and was observed again in piglets 9 (actual diet intake) and 10 (both actual and relative diet intake) days of age. Impairment of their enteral functions manifested by decreased ingestion of the liquid diet, GE, N substances and lipids was also observed after ontogenic shift of regulatory mechanisms of food intake control to a higher integrative level.

[Water consumption in piglets weaned early at various ages and fed a liquid diet]. / Konzum vody selaty casne odstavovanými v rûzném veku na tekutou dietu.

Water consumption was recorded in 72 piglets of the Lorge White breed, weaned either on the second, sixth, tenth day or on the fourteenth day of age, this parameter was followed till the age of four weeks. The piglets were kept individually in a thermoneutral zone and they received a milk diet with macronutrient content, similar to sow's milk and water content of from 78.47%. The diet was offered to suck nine times a day in two-hour intervals. The piglet age at weaning was found to influence significantly water intake. Daily water ingestion is higher in piglets separated from the sows at a younger age than in piglets weaned later on; it reaches as much as 29% in the first group, 26% in the second group, 28% and 20% of live weight in the third and fourth groups, respectively. If converted to the metabolic weight, the percentage is still higher: more than 40% in the first group at the end of the fourth week. Although the spans of weaning beginnings were always identical in particular groups of piglets (four days), the differences in the water consumption were not the same. The differences were smaller between the first and second group, and the third and fourth group, in comparison with those between the second and third group. This fact confirms previous general statements about the periodization of early postnatal life of piglets. The beginning of weaning of the first two groups belongs to the "suckling" period, while the beginning of weaning of the other groups is within the "weaning" period.(ABSTRACT TRUNCATED AT 250 WORDS)