In vitro properties of a newly established medulloblastoma cell line, MCD-1

Medulloblastomas are poorly differentiated brain tumors believed to arise from primitive pleuripotential stem cells, and tend to express mixed neuronal and glial properties. In the present study, we examined immunohistochemical and neurotransmitter phenotypic properties in a newly established medulloblastoma cell line, MCD-1. MCD-1 cells were immortal, not contact-inhibited, but did not grow in soft agar. Immunohistochemical studies showed positive staining for neurofilament protein (NF), neuron-specific enolase (NSE), synaptophysin, MAP 2, τ, NCAM 180, vimentin, and S-100 protein. The cells expressed specific uptake of glutamate, serotonin, and choline, but not GABA or dopamine. A significant increase in process extension was seen in response to agents that enhance intracellular cyclic AMP, especially 3-isobutyl-1-methylxanthine (IBMX). Process formation induced by IBMX was associated with a decrease in cell proliferation as evidenced by a reduction in numbers of cells incorporating 5-bromo-2-deoxyuridine (BrdU). No increase in process extension was observed following exposure to NGF or retinoic acid. MCD-1 cells were shown to produce transforming growth factor beta (TGFβ), and were immunopositive for mutant p53. Transfection assays with the PG13-Luc reporter plasmid, which contains a p53-responsive enhancer element and a luciferase reporter gene, suggested MCD-1 cells are deficient in wild-type p53 and do not activate p53 on treatment with the anticancer agent adriamycin. The MCD-1 cell line is suggested to represent an abnormally differentiated cell type, which has some properties consistent with a multipotent neuronal phenotype while retaining some properties of immature cells of a glial lineage. The MCD-1 cell line can be used to provide a model of a medulloblastoma cell line that is resistant to growth-controlling and anticancer agents.     

Production and Enhanced Anti-tumor Activity of Tumor Necrosis Factor in Mice Treated with Cyclophosphamide

We demonstrated recently that the production of tumor necrosis factor (TNF) is induced in normal mice and in the immunosuppressed nude mouse model by the administration of muramyl dipeptide (MDP) derivatives followed by endotoxin (lipopolysaccharide). In the present study, the ability of this treatment to induce the production of TNF in mice receiving cyclophosphamide (CY) was examined. Two days following treatment with high-dose CY (250 mg/kg), mice exhibited leukocytopenia and drastically reduced splenic weight. However, these animals remained capable of producing TNF, albeit at lower levels, when treated with MDP derivatives and lipopolysaccharide (LPS), particularly when the lipophilic analogue MDP-dipalmitoyl glycerol (GDP) was utilized. TNF was also induced by the administration of MDP-GDP and LPS to Meth A sarcoma-bearing mice treated with this dose of CY. Furthermore, in all animals receiving this combination therapy, sarcoma necrosis and complete regression were obtained without any sign of tumor regrowth. A dose of 100 mg/kg CY was not effective for inhibiting tumor regrowth under the same experimental conditions. These results demonstrated that the anti-tumor activity of endogenously induced TNF is potentiated by combined therapy with a high dose of CY.     

Major cerebral vessels injury caused by a seatbelt shoulder strap: case report

Major cerebral arterial injury may result from penetrating or blunt trauma. In blunt trauma, clinical suspicion of such injury may not be raised, especially if the cranial CT scan is negative. We report a case of a seatbelt shoulder strap to the neck resulting in injury to three major cerebral vessels as demonstrated by cerebral angiography. Although the initial cranial CT scans were negative, a cerebral infarction ultimately developed. The patient was managed conservatively and recovered most of her functions. The importance of clinical suspicion and cerebral angiography is stressed.     

Hereditary pituitary prolactinomas: a new rat model

Pituitary adenomas are known to occur spontaneously in several rat strains, especially during aging. Here we report the occurrence of adenomas (prolactinomas) in a new rat model at an early age. The adenomas were characterized by light and electron microscopy and histochemically by immunoperoxidase methods using specific antisera. Of the 53 pituitaries examined, one was normal, two were hyperplastic and the remainder were adenomas. Among the latter, there were 37 prolactinomas (70%), 3 GH-producing tumours and 2 ACTH-containing neoplasms. One microadenoma produced both PRL and GH. The remaining 8 adenomas were histochemically negative for all pituitary hormones. Serum PRL levels were elevated in both sexes while serum testosterone was high in females and low in the males. The serum estrogen levels were elevated in the males with prolactinomas. The prolactinomas appear to be transmitted as an autosomal dominant characteristic with incomplete penetrance and a greater incidence in the male.     

MR imaging technology: maximizing the signal-to-noise ratio from a single tissue

The pulse-sequence equations for spin-echo magnetic resonance imaging were used to determine interpulse delay times that give the highest signal-to-noise ratio from a single tissue. This theoretical result was then verified experimentally using 1-, 2-, and 5-mM/l copper sulfate solutions imaged on a 0.15-T resistive system. Theoretical analysis determined the spin-echo interpulse delay times that maximize the signal-to-noise ratio from a single tissue as TEopt = TEmin, the minimum echo delay time permitted by the system, and, to a good approximation, TRopt = 1.27 T1 + 1.90 TEmin, with T1 the longitudinal magnetic relaxation time of the tissue. Phantom measurements of the signal-to-noise ratio in a typical imaging system confirmed the theoretically determined TRopt values to within 7%.     

Phosphorus intake in preterm babies and variation of tubular reabsorption for phosphate per liter glomerular filtrate.

Inadequate low intake of phosphorus can induce a hypophosphatemic depletion syndrome resulting in hypercalcemia, hypercalciuria, hypophosphatemia, and rickets. Tubular reabsorption for phosphate per liter glomerular filtration rate (TP/GFR) has been proposed as a reliable index of renal phosphate handling for all age groups. In the present study, carried out in 12 healthy premature babies fed unmodified pooled human milk and then a preterm formula for two periods of 10 days, we demonstrated clearly that TP/GFR as well as calciuria can reflect the poor phosphorus intake and that the kidney of preterm babies is able to rapidly adapt itself to an increase in phosphorus diet content.     

Abnormal US appearance of the cerebellum (banana sign): indirect sign of spina bifida

Certain fetal cranial abnormalities found on second-trimester sonograms can be signs of an open spina bifida. In particular, an abnormal configuration of the cerebellum, known as the banana sign, has been associated with neural tube defects. To further evaluate the usefulness of this sign, the authors compared images of the posterior fossa in 23 fetuses who had documented neural tube defects with those of 38 control fetuses who underwent sonography because of an elevated maternal serum alpha-fetoprotein level. Twenty-two of the 23 fetuses with neural tube defects had compression and anterior alignment of the cerebellar hemispheres (the banana sign), and follow-up confirmed the presence of an open neural tube defect. One fetus had a normal-appearing posterior fossa; however, the neural tube defect at birth was completely covered with skin. Four of the neural tube defects were difficult to see sonographically, and the abnormal configuration of the cerebellum, as well as the flattening of the frontal bone (lemon sign), was instrumental in suggesting the correct diagnosis. The 38 control fetuses had normal-appearing posterior fossae.     

One Hundred Consecutive Liver Transplants Using Institutes Georges Lopez-1 Preservation Solution: Outcomes and Prognostic Factors

Background

There are only 4 prior studies reporting on outcomes of liver transplantation (LT) using Institutes Georges Lopez-1 (IGL-1) preservation solution. Detection of negative predictors of LT using IGL-1 may help finding strategies to protect selected recipients at higher risk of graft failure and death.

Relamorelin for the treatment of gastrointestinal motility disorders

Introduction: Current treatments for gastroparesis are limited. Chronic idiopathic constipation (CIC) has more treatment options, but none are efficacious for severe cases.

Areas covered: Molecular targets to accelerate GI motility are being identified, and relamorelin, a synthetic ghrelin analog, has been promising. In humans, relamorelin increases growth hormone levels and accelerates gastric emptying. Relamorelin was superior to placebo for symptom relief in phase IIA studies for diabetic gastroparesis (DG) and CIC. In phase IIB studies in DG, relamorelin did not significantly reduce vomiting frequency when compared to placebo, but it reduced four symptoms of DG (nausea, fullness, bloating and abdominal pain) and accelerated gastric emptying. To date, relamorelin has been well tolerated and safe in humans without cardiac or neurologic adverse effects. It is still in clinical trial stages and not yet approved by the Food and Drug Administration. Phase III studies are underway.

Expert opinion: Relamorelin shows promise in treating DG, with a reduction in core symptoms. Relative to available treatments, it appears to be efficacious and well tolerated. The absence of neurological or cardiovascular adverse effects places it at an advantage over other available therapies. Once approved, it will likely become the drug of first choice for DG.