The potential impact of new generation transgenic methods on creating rabbit models of cardiac diseases.

Since the creation of the first transgenic rabbit thirty years ago, pronuclear microinjection remained the single applied method and resulted in numerous important rabbit models of human diseases, including cardiac deficiencies, albeit with low efficiency. For additive transgenesis a novel transposon mediated method, e.g., the Sleeping Beauty transgenesis, increased the efficiency, and its application to create cardiac disease models is expected in the near future. The targeted genome engineering nuclease family, e.g., the zink finger nuclease (ZFN), the transcription activator-like effector nuclease (TALEN) and the newest, clustered regularly interspaced short palindromic repeats (CRISPR) with the CRISPR associated effector protein (CAS), revolutionized the non-mouse transgenesis. The latest gene-targeting technology, the CRISPR/CAS system, was proven to be efficient in rabbit to create multi-gene knockout models. In the future, the number of tailor-made rabbit models produced with one of the above mentioned methods is expected to exponentially increase and to provide adequate models of heart diseases.

Recombinant human tissue non-specific alkaline phosphatase successfully counteracts lipopolysaccharide induced sepsis in mice.

Sepsis is a life threatening condition that arises when the body's response to an infection injures its own tissues and organs. Sepsis can lead to shock, multiple organ failure and death especially if not recognized early and treated promptly. Molecular mechanisms underlying the systemic inflammatory response syndrome associated with sepsis are still not completely defined and most therapies developed to target the acute inflammatory component of the disease are insufficient. In this study we investigated a possibility of combating sepsis in a mouse model by intravenous treatment with recombinant human tissue non-specific alkaline phosphatase (rhTNAP) derived from transgenic rabbit milk. We induced sepsis in mice by intraperitoneal injection of LPS and three hours later treated experimental group of mice by intravenous injection with rhTNAP derived from transgenic rabbits. Such treatment was proved to be physiologically effective in this model, as administration of recombinant rhTNAP successfully combated the decrease in body temperature and resulted in increased survival of mice (80 % vs. 30 % in a control group). In a control experiment, also the administration of bovine intestinal alkaline phosphatase by intravenous injection proved to be effective in increasing survival of mice treated with LPS. Altogether, present work demonstrates the redeeming effect of the recombinant tissue non-specific AP derived from milk of genetically modified rabbits in combating sepsis induced by LPS.

Cerebellar developmental venous anomalies with associated vascular pathology.

Cerebellar developmental venous anomalies (CDVA) are benign conditions, although sometimes they are associated with haemorrhages and reported to be symptomatic. This is the largest follow-up study to investigate the symptomatology of CDVAs and their association with other malformations. Thirty-two patients were followed for 2 - 9 years. Twenty-eight had isolated asymptomatic CDVA without any neurological condition during follow-up, which might be linked to the CDVA. Four patients had CDVA and an associated vascular pathology: two pontine cavernomas, one asymptomatic arteriovenous malformation (this is the first published case in the literature) and one cerebellar infarct with a developmental variation of the posterior fossa venous circulation. One patient had two CDVAs, while another had a unique draining vein from the upper part of the brainstem too. In conclusion, CDVAs are benign, asymptomatic conditions, but they are sometimes associated with pathogenic malformations requiring detailed neuroradiological investigations.

High level expression of tissue-nonspecific alkaline phosphatase in the milk of transgenic rabbits.

Alkaline phosphatase is a promising therapeutic agent in the Gram-negative bacterial lipopolysaccharide (LPS) mediated acute and chronic diseases. Contrary to other alkaline phosphatase isozymes, purified tissue-nonspecific alkaline phosphatase (TNAP) is not available in large quantities from tissue sources, which would enable to analyse its efficacy in animal sepsis models. Two transgenic rabbit lines were created by pronuclear microinjection with the whey acidic protein promoter-humanTNAP minigene (WAP-hTNAP). Lactating females of both lines produced biologically active human TNAP. As indicated by fractionation of milk samples the recombinant alkaline phosphatase was associated with the membrane of milk fat globules. Alkaline phosphatase enzymatic activity was two orders of magnitude higher compared to normal human serum levels. The demonstration that this TNAP is physiologically active would provide the clue to use transgenic animals as bioreactor for bulk production of the human tissue-nonspecific alkaline phosphatase in milk. This may be a valuable and possibly viable option with important implication in attenuating LPS mediated inflammatory responses.

[Neurofibromatosis with abdominal and severe central nervous system complications]. / Neurofibromatosis hasi és súlyos központi idegrendszeri szövódményekkel.

A young male patient suffered in cutaneous neurofibromatosis was followed during four years. He developed tissue proliferations of various histological structures manifested in the skin, central nervous system and different splanchnic organs. The classification criteria of neurofibromatosis as well as the diagnostic and therapeutic recommendations are discussed.

[Testosterone-dihydrotestosterone ratio in the differential diagnosis of pancreatic disease]. / A testosteron-dihydrotestosteron hányados a pancreas betegségek elkülönítö diagnosztikájában.

Serum testosterone (T), dihydrotestosterone (DT) and androstendione (AD) concentration were determined in male patients with pancreatic cancer (n = 14), chronic pancreatitis (n = 26), other malignancies of the gastrointestinal tract (n = 19) and in control subjects (n = 16). The T level was decreased in patients with pancreatic cancer relative to other groups of patients but the difference was not statistically significant. The T/DT ratio was significantly lower in pancreatic cancer (2.5 +/- 1.0) compared to chronic pancreatitis (9.6 +/- 2.3, p 0.01). The specificity of the ratio is 84%, while the sensitivity was found to be 92%. The discriminative value was found to be 4. The T/DT ratio seems to be a valuable marker in the differentiation of pancreatic cancer from chronic pancreatitis.

Screw fixation of odontoid fractures: preliminary report.

In the period from 1981 to 1985, 32 odontoid fractures were treated in the National Institute of Traumatology. In four cases anterior stabilization was provided with compression screws inserted from the front. Two cases of odontoid fracture are shown, one accompanied by ventral, the other by dorsal dislocation. A brief review is provided of the results obtained with different methods of treatment drawing on the international literature.

Up-to-date method of treatment of most frequent axis-injuries: screw-fixation of the odontoid fractures.

In the period from 1981 to 1985, 32 odontoid fractures were treated in the National Institute of Traumatology. In 4 cases anterior stabilization was made with compression-screws from the ventral approach. Two cases of odontoid fractures are shown, one accompanied by ventral, the other by dorsal dislocation. A brief review of the results with different methods of treatment is given on the basis of the international literature.

Relationship between serum dehydroepiandrosterone sulphate and urinary 17-ketosteroid values.

To assess the validity of serum dehydroepiandrosterone sulphate (DS) radioimmunoassay instead of urinary total 17-ketosteroid (17-KS) or individual metabolite (dehydroepiandrosterone + etiocholanolone + androsterone; D + E + A) determination to control adrenal androgen function, a comparative study has been performed. Mathematical analysis of simultaneous estimates revealed significant correlation when normal or above normal 17-KS or D + E + A excretion relative to serum DS were considered. Poor correlation was observed when below normal metabolite excretion and serum DS were related. Furthermore, there was a significant correlation between estimates of 17-KS (or D + E + A) and those of serum unconjugated D also determined by radioimmunoassay. The serum DS radioimmunoassay appeared to be a reliable tool to assess adrenal androgen function, at least in patients exhibiting normal or high 17-ketosteroid values.

A comparative study of steroid concentrations in human adipose tissue and the peripheral circulation.

Using radioimmunological methods, levels of cortisol, dehydroepiandrosterone, androstenedione, testosterone, oestrogens (oestradiol + oestrone), progesterone and 17 alpha-hydroxyprogesterone were determined in adipose tissue and peripheral blood obtained during surgical treatment of patients with non-endocrine diseases. The steroid content of human adipose tissue was observed to be extremely high relative to that in the general circulation, giving a tissue/serum ratio of 0.4 to 13.2. The concentration of steroids decreased in the following order: dehydroepiandrosterone greater than cortisol greater than androstenedione greater than progesterone greater than testosterone greater than 17 alpha-hydroxyprogesterone greater than oestradiol + oestrone. This sequence is different from that found in blood. When anthropometric variables were taken into consideration, the adipose tissue mass of severely obese subjects contained a steroid pool far greater than that in the total blood volume.