Berberine sensitizes human glioma cells, but not normal glial cells, to ionizing radiation in vitro

The identification of nontoxic agents that can enhance the efficacy of postoperative radiotherapy for patients with glioblastoma multiforme (GBM) remains a challenge in oncology. We evaluated human GBM cell lines for their responsiveness to berberine, an alkaloid compound used commonly in Asia as an antibiotic. In experiments measuring clonogenic survival, treatment with a nontoxic dose of berberine rendered GBM cells more sensitive than vehicle-treated control cells to x-rays. Such radiosensitization was not observed in parallel experiments with primary human glial cultures. These data suggest that berberine could be integrated with postoperative radiotherapy to selectively promote residual GBM tumor cell death     

Liver transplant for giant cell hepatitis with autoimmune haemolytic anaemia

Giant cell hepatitis (CGH) with autoimmune haemolytic anaemia (AHA) is a distinct entity with an aggressive course. Immunosuppression may help early disease. A case is reported of a child with GCH and AHA with early disease recurrence after liver transplantation for end stage liver disease.     

Liver transplantation for homozygous familial hypercholesterolaemia

Homozygous familial hypercholesterolaemia is a rare inherited condition with an incidence of approximately one in a million. It is associated with severe premature atherosclerosis and early death from cardiovascular complications. The results of liver transplantation reported to date have suggested only partially effective reduction of the hypercholesterolaemia. Three boys with familial hypercholesterolaemia, aged 10.0 to 15.1 years, received liver grafts at Addenbrooke's Hospital. Their untreated fasting lipid concentrations were grossly raised. All three had angiographic evidence of coronary atheroma and two had exertional angina. One child had such severe atheroma that coronary artery bypass surgery was considered necessary before liver transplantation. All three had straightforward operative and postoperative courses and their lipid concentrations returned rapidly to normal. One boy developed chronic rejection requiring retransplantation. Currently all three boys are well, on normal diets, and with normal liver function. It is concluded that (1) liver transplantation offers highly effective treatment for this lethal condition, (2) timing the operation is difficult but it should be undertaken before coronary artery disease has progressed too far (when combined liver and heart transplantation may be the only possibility), and (3) in well grown children with no previous abdominal surgery the immediate risks of liver transplantation are low but chronic rejection remains a danger.     

Stapedectomy and vertigo

The relationship between vestibular and cochlear function in Stapedectomy was investigated in 722 patients (925 ears). There were no differences in hearing between patients with and without pre-operative complaints of vertigo. Post-operatively patients with long lasting vertigo obtained equally good hearing results as the others. The direction of spontaneous nystagmus post-operatively in relation to the operated ear was of no prognostic significance regarding short term hearing results. However, at follow-up an average of 15 years after the operation, hearing was somewhat poorer in those having spontaneous nystagmus towards the operated ear. At follow-up 17% had an abnormal caloric test.     

Spontaneous osteonecrosis of the knee and medial meniscal tears

Several factors may play a role in the etiology of "spontaneous" osteonecrosis of the medial femoral condyle. Corticosteroids are known to induce osteonecrosis, and 45% of the patients in this study received steroids parenterally or by intra-articular injection. Another factor, heretofore given little attention, is the association of medial meniscal tears and "spontaneous" osteonecrosis. Twenty-one (78%) of 27 knees examined by arthrography demonstrated meniscal tears. Stress concentration over the edge of the meniscal fragment may result in ischemic necrosis of the femoral condyle. Early detection of a medial meniscal tear by arthrography in older patients and prompt treatment may be important in avoiding the late changes of "spontaneous" osteonecrosis.     

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In summary, the naturopathic approach would treat this patient with dietary modification, nutritional and herbal supplements, regular preventive nasal irrigation, and adjunctive therapies such as homeopathy and osteopathic manipulation as indicated. Hopefully, this preventive approach will reduce or eliminate the need for the use of antibiotics to treat the acute exacerbations of what is really a chronic, lifestyle-related condition. As illustrated here, the Naturopathic Therapeutic Order can both guide us in treating a specific condition and assist us in assessing our patients on an individual, prevention-oriented basis.     

Site-directed mutagenesis of the human D antigen: definition of D epitopes on the sixth external domain of the D protein expressed on K562 cells

BACKGROUND: The antigens of the human Rh system are of great clinical significance in transfusion medicine and pregnancy. Of the Rh system antigens, D is clinically the most important, being one of the most immunogenic structures arising from human cells. The human D antigen represents a collection of epitopes expressed on a red cell membrane protein that is predicted to have 12 membrane-spanning segments giving rise to six exofacial domains. STUDY DESIGN AND METHODS: By site-directed mutagenesis using the method of inverse polymerase chain reaction, cE and D cDNA mutant constructs were generated with changes to the RHD-specific residues 350, 353, and 354 in the predicted sixth exofacial loop. Each mutant cDNA was subcloned into the pBabe puromycin retroviral vector, and supernatants were used to transduce K562 cells. Puromycin-resistant K562 clones were screened by flow cytometric analysis using a panel of monoclonal antibodies with specificities to ep (epitope) D1 through epD9. RESULTS: De novo expression of epD3 and epD9 was generated in the K562 cell lines expressing the mutated cE polypeptide (cE-Asp350His, Gly353Trp, Ala354Asn). Expression of c and E was unaffected. Conversely, the cells expressing the mutated D polypeptide demonstrated loss of expression of epD1, epD2, epD3, epD4, and epD9. CONCLUSION: The data provide strong evidence for the critical involvement of three amino acids, Asp₃₅₀, Gly₃₅₃, and Ala₃₅₄, in the expression of epD3 and epD9 on the predicted sixth external domain of the D protein. This domain also appears to be essential for the expression of epD1, epD2, and epD4, as a loss of expression of these epitopes was observed in K562 cells transduced with the D_mut construct (encoding His₃₅₀, Trp₃₅₃, and Asn₃₅₄). The K562/D_mut, cell line has an identical molecular and serologic profile as the red cell D^IVb pheno-type, which confirms that retroviral gene transfer of Rh cDNA into K562 cells provides us with a powerful means by which to further map epitopes of D.