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Biomedical subjects

J Kurek

Publications and source records attributed to J Kurek.

9 recordsLinked to original sources

Acute isolated tuberculous appendicitis.

Non-pulmonary tuberculosis is found with different frequencies in different countries of the world. It is said to constitute about 4% of all tuberculosis cases in Poland, about 25% in England and Wales and about 17% in the USA. It seems that these differences are the result of differences in rates of diagnosis and registration of new tuberculosis cases. This in turn is influenced by public health funding in the individual countries. In this work, we present a case of acute, isolated, tuberculous inflammation of the appendix. We call attention to the fact that pre-operative diagnosis is practically impossible. Clinical symptoms do not point to inflammatory changes. Only surgical evaluation, and especially the result of histopathological examination make it to possible to establish the final diagnosis to initiation of anti-tuberculous treatment.

Adult↗

Cytotoxicity of paclitaxel or cisplatin on carcinoma cell lines is not inhibited by leukemia inhibitory factor (LIF).

We have established a reliable, reproducible and objective growth assay to measure whether leukemia inhibitory factor (LIF) was able to protect tumour-derived cell lines from toxic effects of the chemotherapy agents, cisplatin and paclitaxel. Using this assay, we demonstrated that LIF did not alter the cytotoxic action of these drugs, on a panel of seven cancer cell lines. This was not because of the inactivity of the LIF or because the cell lines did not express components of the LIF receptor. These findings suggest that the potential clinical use of LIF, as a neuroprotective agent, in conjunction with chemotherapy will not interfere with the anti-tumour treatment.

Antigens, CD↗

Leukemia inhibitory factor by systemic administration rescues spinal motor neurons in the SOD1 G93A murine model of familial amyotrophic lateral sclerosis.

Leukemia inhibitory factor (LIF) is a survival factor for motoneurons. In this study we investigated whether intense systemic LIF therapy prevents the loss of lumbar motoneurons in the transgenic SOD1 G93A mouse model of familial amyotrophic lateral sclerosis. Treatment involved daily 25 microg/kg intraperitoneal injection for a period of 6 weeks starting at 70 days of age. Using the unbiased optical dissector technique, significant rescue of motoneurons in the LIF-treated group (3809+/-455) was found compared to the vehicle group (1085+/-140).

Amyotrophic Lateral Sclerosis↗

AM424: history of a novel drug candidate.

1. Leukaemia inhibitory factor (LIF) is a 180 amino acid single-chain protein, named after its effect on haematopoietic cells. Leukaemia inhibitory factor belongs to a group of cytokines that includes ciliary neurotrophic factor, interleukin (IL)-6, IL-11, cardiotrophin-1 and oncostatin M. All group members use the gp130 signal transducing subunit for intracellular signalling, but show differences in biological effect. 2. Research over the past 6-8 years has shown LIF to have potent neuromuscular activity. In vitro and in vivo studies on axotomy and nerve crush models demonstrate a powerful effect of LIF in enhancing the survival of both motor and sensory neurons, while reducing denervation-induced muscle atrophy. In models of both axotomy induced neuronal death and in the wobbler mouse, LIF is active at doses as low as 1 microgram/kg delivered systemically. 3. In muscle, LIF will increase the rate of muscle regeneration in vivo when applied exogenously after injury and will stimulate intrinsic muscle repair following its targeted release to dystrophic muscle in the mdx mouse. Leukaemia inhibitory factor may also have a role as an adjunct to myoblast transfer therapy, with studies showing that the transplantation of genetically competent myoblasts into mdx mouse muscle is enhanced when cells are injected with LIF. 4. Distribution and pharmacokinetic studies have been conducted in primates with doses of 20 micrograms/kg recombinant human LIF given subcutaneously over 2 weeks tolerated without major side effects. 5. A pharmaceutical form of recombinant human LIF (AM424; AMRAD Operations, Richmond, Victoria, Australia) entered human clinical trials during 1997 and a phase I clinical trial in healthy volunteers has been completed. A phase I repeat dose study has also been completed in cancer patients undergoing chemotherapy. The primary indication for a phase II study is the treatment of chemotherapy induced peripheral neuropathy. Other potential indications include muscle wasting diseases, acute nerve trauma and motor neuron disease. 6. The role of LIF in modulating nerve loss should make it an ideal candidate for the treatment of a number of neurological conditions. The phase I study represents the first trial in a programme for the clinical development of AM424.

Animals↗

[The application of biodegradable anastomosis ring Valtrac for intestinal anastomosis].

UNLABELLED: In 1985 a biofragmentable anastomosis ring (BAR) Valtrac was introduced for intestinal anastomoses. From August 1994 trough March 1998, 49 intestinal anastomoses were performed in 44 patients: there were 28 jejunoileostomies, 8 colocolostomies and 3 gastrojejunostomies. In 5 patients after total gastrectomy, two anastomoses with the use of Valtrac ring were made during the same operation. The patient group consisted of 26 women and 18 men, aged 14 to 81 years (mean age: 54 years); there were 13 emergency and 31 elective procedures. The reasons for the operations were: cancer--35 cases, pancreatic cyst drainage--4 cases and reconstructive procedures in the digestive tract--5 cases. First intestinal gas passage and defecation were monitored in all patients; control X-ray was performed on the 10th postoperative day. No mortality nor serious complications were observed in the postoperative period. In an 81-year old patient, an inconsiderable leakage was found at the anastomotic site. This was successfully managed in the second operation. CONCLUSIONS: 1. Valtrac is an alternative method for intestinal anastomoses. 2. The anastomotic technique is atraumatic and easy even for an unexperienced surgeon.

Adolescent↗

Leukaemia inhibitory factor treatment stimulates muscle regeneration in the mdx mouse.

A number of growth factors are involved in coordinating muscle cell proliferation and differentiation, particularly after injury and in disease. Leukaemia inhibitory factor (LIF) strongly stimulates the proliferation of myoblasts in vitro and in vivo and its expression in muscle after injury suggests that LIF may have a role as a trauma factor. The mdx mouse was used to study the effects of LIF on in vivo muscle regeneration during disease. The rationale for using trophic factors such as LIF to treat neuromuscular disease includes the understanding that these molecules show some degree of selectivity for the population of cells in which they are effective. LIF was administered to muscle of the mdx mouse using osmotic pumps implanted subcutaneously in unrestrained mice. The growth factor was continuously delivered into the vastus lateralis muscle at 7 U/mu 1 for 7 days via a catheter. The results show that LIF increased the rate of muscle regeneration in mdx mice by stimulating the formation of larger myotubes. LIF treatment also increased the number of regenerating myotubes in the perfused area. This myotrophic action indicates that LIF contributes to muscle regeneration. Together with its known neurotrophic action, LIF is a potential therapeutic agent for the treatment of neuromuscular disease.

Animals↗

Effects of leukaemia inhibitory factor and other cytokines on murine and human myoblast proliferation.

It has been shown previously that leukaemia inhibitory factor (LIF) and transforming growth factor-alpha (TGF-alpha) stimulate proliferation of primary cultures of murine myoblasts. We now show that human myoblasts respond in a similar manner to LIF and TGF-alpha. These responses occur over a range of growth conditions. There are total additive effects in both human and murine myoblasts between LIF and TGF-alpha and LIF and fibroblast growth factor-beta (FGF-beta), but not between LIF and interleukin-6 (IL-6) or insulin-like growth factor 1 (IGF-1). The LIF response is initiated by a short exposure to the cytokine and is maintained for prolonged periods in its absence.

Animals↗

Preparation of monoclonal antibodies to C3b by immunization with C3b(i)-sepharose.

We have prepared and characterized four monoclonal antibodies (MAbs) to human C3b of high specificity and affinity. Our procedure did not require a purified source of C3b for immunization. Instead, C3b and C3bi were deposited on Sepharose 4B via the alternative pathway of complement activation in normal human serum, and this C3b(i)-Sepharose served as the immunogen. C3b(i)-Sepharose was also prepared from a number of primate and non-primate sources, and this allowed us to demonstrate that the anti-human C3b MAbs cross-reacted with primate-derived C3b, but not with C3b from non-primates. The procedures we have developed may be useful in the further investigation of species-specific C3 fragment-binding proteins from both primate and non-primate sources.

Animals↗