Joubert–Boltshauser syndrome with polydactyly in siblings

Two siblings are described with clinical features of the Joubert–Boltshauser syndrome. Both had polydactyly and one had fleshy tumours of the tongue. Computed tomography of the brain showed hypoplasia of the cerebellar vermis, associated in one case with a cyst of the fourth ventricle.     

In-vitro studies on intestinal malabsorption of amino-acids in young chicks infected with Eimeria acervulina

In vitro uptake of L. histidine by intestinal tissue from chicks infected with E. acervulina was slightly reduced. This was confirmed using radio-actively labelled mixed amino-acid substrates in the form of a Chlorella protein hydrolysate.     

Studies on malaria and Anopheles balabacensis in Cambodia

During the past few years Anopheles balabacensis has come to be recognized as a very important human malaria vector in Thailand and the Indochinese area, but little has been published on its bionomics except from North Borneo.     

Trombone tongue: a new clinical sign for significant medullary compression at the craniovertebral junction. Case report

The authors describe a previously unreported clinical sign that may indicate the onset of significant compression of the medulla oblongata in cases of craniovertebral junction abnormalities. This 17-year-old boy presented with mild bilateral leg weakness. Imaging studies revealed severe basilar invagination and a marked Chiari malformation. While awaiting surgery, his tongue developed an involuntary constant protrusion-intrusion repetitive motion. The onset of this so-named "trombone tongue" sign was followed shortly afterward by rapidly progressive spastic tetraparesis. After the authors performed a transmaxillary clivectomy, foramen magnum decompression, and occipitocervical fusion, they noted that the abnormal tongue motion promptly resolved and the tetraparesis gradually improved. The authors discuss their current understanding of the central control of tongue movements and present a hypothesis on the pathogenesis of trombone tongue based on the neuroanatomical basis of another abnormal tongue movement sign, lingual myoclonus.     

p16(Ink4a) in melanocyte senescence and differentiation

BACKGROUND: The Ink4a-Arf tumor suppressor locus encodes two growth inhibitors, p16 and Arf, both of which are also implicated as effectors in cellular senescence. Because human germline defects in the INK4A-ARF locus are associated with familial melanoma, melanocytes may have unusual INK4A-ARF functions or controls of cell senescence. Because senescence is believed to be an anticancer mechanism, we investigated the role of Ink4a-Arf and its individual components in melanocyte senescence. METHODS: Melanocytes were cultured from littermate mice with zero, one, or two functional copies of the Ink4a-Arf locus. Senescence was evaluated by cumulative population doubling curves and by the assessment of acidic beta-galactosidase (an indicator of senescence) expression. Pigmentation and cell size were evaluated by spectrophotometry and microscopy. p16 and Arf expression in primary and spontaneously immortalized melanocyte or melanocyte precursor cell lines were evaluated by immunoblotting. Retroviral vectors containing normal p16 and Arf complementary DNAs were used to restore expression of these genes in Ink4a-Arf(-/-) melanocytes. RESULTS: Wild-type melanocytes (i.e., Ink4a-Arf(+/+)) senesced within 4-5 weeks of culture. Ink4a-Arf(-/-) melanocytes did not senesce and readily became immortal. Ink4a-Arf(+/-) melanocytes showed defective senescence. Senescent Ink4a-Arf(+/+) melanocytes were heavily pigmented, but Ink4a-Arf(+/-) and Ink4a-Arf(-/-) melanocytes were less pigmented. All of six spontaneously immortalized melanocyte or melanocyte precursor lines from Ink4a-Arf(+/+) mice lacked p16 protein expression, although most retained Arf protein expression. After restoration of p16 but not Arf expression, Ink4a-Arf(-/-) melanocytes stopped growing, became highly melanized, and expressed acidic beta-galactosidase. By contrast, restoration of Arf but not p16 expression led to cell death without evidence of senescence. CONCLUSION: Normal mouse melanocyte senescence and associated pigmentation require both copies of Ink4a-Arf and appear to depend more on p16 than on Arf function. Mutations of the INK4A-ARF locus may favor tumorigenesis from melanocytes by impairing senescence, cell differentiation, and (where ARF is disrupted) cell death.     

Long-term bone marrow culture-derived stromal fibroblasts as a potential target for gene therapy in acute myelogenous leukemia

As a part of our continuing efforts to develop gene therapy for acute myelogenous leukemia (AML), this study was undertaken to evaluate the possibility of using autologous bone marrow stromal fibroblasts (BMSFs) as a target cell population. Autologous BMSFs in AML were isolated from the stromal layers of long-term bone marrow culture (LTBMC) using immunomagnetic beads. BMSFs exhibited rapid proliferation even in the absence of growth factors. Cultures stimulated with bFGF produced significantly increased numbers of BMSFs than cultures without added growth factors. Using LNC/LacZ retroviral vector, the transduction efficiency of BMSFs was 13+/-4% at a 5 multiplicity of infection (MOI). LNC/interleukin-2 (IL-2)-transduced BMSFs produced between 1200 and 4800pg of IL-2/10(6) cells per 24h. Using adenoviral vector AdV/LacZ, the transduction efficiency was 84+/-10% at 100, and 92+/-8% at a MOI of 1000. Although the addition of basic fibroblast growth factor, epidermal growth factor, or platelet-derived growth factor did not affect the transduction efficiency, they increased the numbers of transduced cells significantly (P<0.01). AdV/IL-2-treated BMSFs produced high levels of IL-2 over the course of 7 days between 9820 and 22,700pg of IL-2/10(6) cells per 24h. Our finding that the genetically engineered autologous BMSFs of AML could be successfully established in vitro implies that BMSFs obtained from LTBMC might be considered as a target cell population for certain types of clinical gene therapy in AML.