Investigating the use of primary adult subventricular zone neural precursor cells for neuronal replacement therapies

With the relatively recent discovery that neurogenesis persists throughout life in restricted regions of the adult mammalian brain, including those of human beings, there has been great interest in the use of adult-derived neural stem cells for neuronal replacement. There are many great hurdles that must be overcome in order for such replacement strategies to succeed. In this review, we outline some of these hurdles and discuss recent experiments that investigate the potential of using neural precursor cells found in the subventricular zone of the adult brain for brain repair.     

Regulation of male sex hormone levels by soy isoflavones in rats

Several studies have suggested that soybean intake is associated with a lower risk of prostate cancer. However, the mechanism of prostate cancer prevention by soybeans remains unclear. Because prostate cancer is reported to have an association with an increased level of dihydrotestosterone (DHT) and soybean isoflavones are known to inhibit 5 alpha-reductase, which is involved in the conversion of testosterone to DHT, the effects of soybean extract and isoflavones on the plasma levels of male sex hormones were investigated using male rats. In Experiment I, Sprague-Dawley rats were fed diets with and without soy flour; in Experiment II, rats were fed diets containing 2% soy methanol extract or 0.2% semipurified isoflavones or a control diet. The study showed a reduction of plasma DHT along with an increase in total plasma androgen in rats fed soy flour or semipurified isoflavones for 1 wk. These results suggest that soy isoflavone intake may reduce plasma DHT level.     

Establishment and characterization of a schwannoma cell line from a patient with neurofibromatosis 2

By using retroviral mediated gene transfer technique, a primary schwannoma culture from a 56-year-old Neurofibromatosis type 2 (NF2) patient was immortalized with HPV E6-E7 genes. This cell line, HEI193, has a unique splice site mutation of the NF2 gene. Both immunocytochemistry and molecular biology techniques were used to demonstrate that this cell line is of Schwann cell origin. Comparison of the primary tumor with HEI193 revealed the same NF2 mutation and an identical pattern of allele loss at multiple loci, indicating that the established cell line had maintained many of the properties of the original tumor. The immortalized cell line was non-tumorigenic in both severe combined immunodeficient (SCID) mice and nude mice, but has altered growth properties such as higher proliferation rate and independence of Schwann cell growth factors. To our knowledge, this is the first attempt to establish permanent cell lines from human NF2 patients. This Schwann tumor-derived cell line may provide a useful model system for the study of familial NF2 tumor pathogenesis, for elucidating NF2 functions and for testing new gene-based therapeutic approaches.     

Malignant evolution of Schnitzler's syndrome--chronic urticaria and IgM monoclonal gammopathy: report of a new case and review of the literature

Schnitzler's syndrome, initially described in 1974 is an uncommon condition defined by chronic urticaria and monoclonal IgM gammopathy. Additional features include fever of unknown origin, elevated ESR, bone pain and frequently a benign clinical course. We conducted a literature search of Medline, EMBASE and Cancerlit and found 56 cases of Schnitzler's syndrome reported to date. The absence of lymphoproliferative disease in this condition is typical, but nine patients have progressed to develop lymphoplasmacytic neoplasias, particularly Waldenstrom's macroglobulinemia (WM). Malignant evolution of Schnitzler's syndrome is a rare complication, but emphasizes the importance of long term follow-up and the need for these patients to undergo periodic assessment of the bone marrow and lymph nodes. Treatment of this condition is difficult, with varying response to corticosteroids and largely unsuccessful results with standard chemotherapy used for WM. We describe a case of Schnitzler's syndrome in a 50-year old man with lymphocytic aggregates in the bone marrow after 9 years of chronic urticaria, fever, arthralgias and bone pain. We review the clinical features and treatment, with emphasis on the hematologic aspects of this unusual condition.     

Epigallocatechin-3-gallate decreases VEGF production in head and neck and breast carcinoma cells by inhibiting EGFR-related pathways of signal transduction

In a recent study on head and neck squamous cell carcinoma (HNSCC) cells we found that epigallocatechin-3-gallate (EGCG), a major biologically active component of green tea, inhibited activation of the epidermal growth factor receptor (EGFR) and related signaling pathways. Since activation of EGFR signaling pathways is associated with angiogenesis, we examined the effects of EGCG on vascular endothelial growth factor (VEGF) production by YCU-H891 HNSCC and MDA-MB-231 breast carcinoma cell lines, because we found that both of these cell lines display autocrine activation of transforming growth factor-alpha (TGF-alpha)/EGFR signaling and produce high levels of VEGF. Treatment with EGCG inhibited the constitutive activation of the EGFR, Stat3, and Akt in both cell lines. These changes were associated with inhibition of VEGF promoter activity and cellular production of VEGF. Mechanistic studies indicated that inhibition of Stat3, but not mitogen-activated protein kinase kinase (MEK)1 or phosphatidylinositol 3'-kinase (PI3K), significantly decreased VEGF promoter activity. However, the inhibitory effects of a dominant negative Stat3 on VEGF expression was not as strong as that produced by EGCG. An analysis of alternative pathways indicated that EGCG strongly inhibited the constitutive activation of NF-kappa B in both cell lines, and an NF-kappa B inhibitor strongly inhibited VEGF production. These results suggest that EGCG inhibits VEGF production by inhibiting both the constitutive activation of Stat3 and NF-kappa B, but not extracellular-signal-regulated kinase (ERK) or Akt, in these cells. Therefore, EGCG may be useful in treating HNSCC and breast carcinoma because it can exert both antiproliferative and antiangiogenic activities.     

SunghyangJungki-San Ga Pogongyoung inhibits IL-1 mediated tumour necrosis factor-alpha secretion in astrocytes

Astrocytes play an important role in initiating and modulating inflammatory responses within the central nervous system (CNS). Extensive studies in rodents have shown that substance P induces inflammatory cytokine production in astrocytes. In this study we have examined whether an aqueous extract of SunghyangJungki-San Ga Pogongyoung (SSGP) inhibits the secretion of TNF-alpha from primary cultures of rat astrocytes. SSGP (10-1,000 microg/mL) significantly inhibited the TNF-alpha secretion by astrocytes stimulated with lipopolysaccharide (LPS) and substance P (SP). Interleukin-1 (IL-1) has been shown to elevate TNF-alpha secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore examined whether IL-1 mediated inhibition of TNF-alpha secretion from primary astrocytes by SSGP. Treatment with SSGP (10-1,000 microg/mL) to astrocytes stimulated with both LPS and SP decreased IL-1 secretion significantly. Moreover, the secretion of TNF-alpha by LPS and SP in astrocytes was progressively inhibited with an increasing amount of IL-1 neutralizing antibody. Our results suggest that SSGP may inhibit TNF-alpha secretion by inhibiting IL-1 secretion and that SSGP has an antiinflammatory activity in the CNS.     

Personality profiles of patients with dissociative trance disorder in Singapore

This report studies the personality of individuals who suffer from dissociative trance disorder and examines whether the personality profiles could predict the individual's frequency of trance states. A total of 58 cases were given the Eysenck Personality Questionnaire (EPQ) and their personal information harvested from the case notes and through subsequent interviews. The subjects were also reassessed 1 year later to obtain their frequency of trance states. For both sexes, there were lower extraversion scores and higher psychoticism, neuroticism, and lie scores in the sample compared to the Singapore norms. Of the 47 subjects traced, total episodes of trances that occurred over the 1-year period was positively correlated with neuroticism and negatively with extraversion scores. The high lie scores in individuals with dissociative trance disorder could be a reflection of their concern of how others perceive them. The motivation could be that of restoration of self-esteem or "face." The profiles in the EPQ could be used to predict the individual's frequency of trance states. Subjects with personality traits like nervousness, excitability, and emotional instability were more likely to have a higher frequency of trance states.     

Migraine and isolated recurrent vertigo of unknown cause

Chronic recurrent attacks of vertigo, not associated with any auditory or neurological symptoms, are a common reason for referral to our neurotology clinic. Even after an extensive neurotological evaluation, some cases remain undiagnosed. We prospectively evaluated 72 consecutive patients who presented to the clinic with isolated recurrent vertigo of unknown cause. All patients underwent diagnostic evaluation to exclude identifiable causes of isolated recurrent vertigo. We compared the prevalence of migraine, according to the International Headache Society (IHS) criteria, in the isolated recurrent vertigo group, with a sex- and age-matched control group of orthopedic patients. The prevalence of migraine according to IHS criteria was higher in the isolated recurrent vertigo group (61.1%) than in the control group (10%; p < 0.01). Only 16.7% of patients had an abnormal vestibular function test. The most common abnormal finding was a unilateral vestibular weakness to caloric stimulation. Our results suggest that migraine should be considered in the differential diagnosis of isolated recurrent vertigo of unknown cause.