Study protocol for a natural experiment in a lower socioeconomic area to examine the health-related effects of refurbishment to parks including built-shade (ShadePlus).

INTRODUCTION: Parks in disadvantaged suburbs often have low quality and few amenities, which is likely to result in them being underutilised for recreation and physical activity. Refurbishment of parks, including shade, walking paths and other amenities, may have broad health-related benefits. METHODS AND ANALYSIS: The study design, methods and planned analyses for a natural experiment examining the effects of refurbishments including built-shade added to parks in disadvantaged outer suburbs of Melbourne are described. Three intervention parks and three comparison parks matched for equivalence of park and neighbourhood characteristics were selected. Using mixed methods, the outcomes will be assessed during three consecutive spring-summer periods (T1: 2013-2014; T2: 2014-2015: T3: 2015-2016). Primary outcomes included: observed park use, physical activity and shade use. Self-reported social connectedness, community engagement and psychological well-being were assessed as secondary outcomes. ETHICS AND DISSEMINATION: This study was approved by Cancer Council Victoria's Human Research Ethics Committee. Studies such as ShadePlus can improve understanding of the broader effects of park refurbishments (including physical activity levels and sun protection behaviours, as well as social connectedness and psychological well-being). The study findings will be disseminated through established urban planning and parks and recreation networks, peer review publications and conference presentations.

The clinical and laboratory features of chronic sensory ataxic neuropathy with anti-disialosyl IgM antibodies.

The clinical and laboratory phenotype of a paraproteinaemic neuropathy syndrome termed chronic sensory ataxic neuropathy with anti-disialosyl IgM antibodies is described in a series of 18 cases. Previous single case reports have outlined some features of this syndrome. All 18 cases were defined by the presence of serum IgM antibodies which react principally with NeuAc (alpha2-8)NeuAc(alpha2-3)Gal-configured disialosyl epitopes common to many gangliosides including GDlb, GD3, GTlb and GQlb. In 17 out of 18 cases, the serum contained benign IgM paraproteins, and in four of these cases at least two IgM paraproteins were present. The IgM antibodies were also cold agglutinins in 50% of cases. The clinical picture comprised a chronic neuropathy with marked sensory ataxia and areflexia, and with relatively preserved motor function in the limbs. In addition, 16 out of 18 cases had motor weakness affecting oculomotor and bulbar muscles as fixed or as relapsing-remitting features. When present in their entirety, these clinical features have been described previously under the acronym CANOMAD: chronic ataxic neuropathy, ophthalmoplegia, IgM paraprotein, cold agglutinins and disialosyl antibodies. This distribution of clinical features is reminiscent of Miller Fisher syndrome, in which acute-phase anti-disialylated ganglioside IgG antibodies are found. Clinical electrophysiology and nerve biopsy show both demyelinating and axonal features. A partial response to intravenous immunoglobulin and other treatments is reported in some cases.

Full-spectrum fluorescent lighting: a review of its effects on physiology and health.

BACKGROUND: Full-spectrum fluorescent lighting (FSFL) has been credited with causing dramatic beneficial effects on a wide variety of behaviours, mental health outcomes and physical health effects, as compared to other fluorescent lamp types. These effects are hypothesized to occur because of similarity between FSFL emissions and daylight, which is said to have evolutionary superiority over other light sources. METHOD: This review, covering the period 1941-1999, critically considers the evidence for direct effects of FSFL through skin absorption as well as indirect effects on hormonal and neural processes. CONCLUSIONS: Overall, the evidence does not show dramatic effects of fluorescent lamp type on behaviour or health, neither does it support the evolutionary hypothesis.

Production, isolation and structure determination of novel fluoroindolocarbazoles from Saccharothrix aerocolonigenes ATCC 39243.

Saccharothrix aerocolonigenes ATCC 39243 produces an indolocarbazole antitumor agent rebeccamycin under submerged fermentation conditions. Adding DL-6-fluorotryptophan to culture of S. aerocolonigenes ATCC 39243 induces the formation of two novel indolocarbazoles, fluoroindolocarbazoles A and B. Feeding DL-5-fluorotryptophan to culture of S. aerocolonigenes ATCC 39243 induces the production of a novel indolocarbazole, fluoroindolocarbazole C. These fluoroindolocarbazoles have been isolated from culture broth and purified to homogeneity by vacuum liquid chromatography and column chromatography. All three fluoroindolocarbazoles are more potent than rebeccamycin against P388 leukemia by ip route in murine model.

Peripheral neuropathy associated with anti-GM2 ganglioside antibodies: clinical and immunopathological studies.

GM2 ganglioside is a potential peripheral nerve antigen for neuropathy-associated autoantibodies. However little data are available on their pathogenic effects, if any. In this study we have screened both neuropathy-associated and control sera for anti-GM2 antibodies and subsequently used high titre sera for immunohistological and complement mediated cytotoxicity studies. We identified abnormally elevated anti-GM2 antisera in the normal population, as well as in patients with peripheral neuropathies and other neurological diseases. GM2 antibodies were either mono-reactive, cross-reactive with GM1a, or cross-reactive with GalNAc-GM1b and/or GalNAc-GD1a. All GM2 antisera from neuropathy subjects and normal controls bound to, and were capable of complement-mediated lysis of the NSC-34 cell line which expresses high levels of membrane-associated GM2. However, in immunohistological studies on human and rodent peripheral nervous system tissues, no specific binding was seen with GM2 antisera, either cross-reactive with GalNAc-GM1b and GalNAc-GDla, or with GM1a. These data indicate that although GM2 antisera can lyse neural membranes containing GM2, this antigen(s) is not detectable by standard immunohistological techniques in human or rodent peripheral nerve. This raises doubts about their pathophysiological significance in human autoimmune neuropathy.

Long-term clinical and neurophysiological follow-up of patients with peripheral, neuropathy associated with benign monoclonal gammopathy.

The incidence of hematological malignancy in patients with monoclonal gammopathy of undetermined significance (MGUS) has been assessed as 17% to 25%. To ascertain whether this is true of neuropathy associated with MGUS, a long-term (5-42 years) retrospective clinical and neurophysiological follow-up was conducted in 50 cases (immunoglobulin M [IgM], n = 38; IgG, n = 11; IgA, n = 1). Only three patients developed hematological malignancy. Of 25 survivors with IgM paraproteinemia, 7 had myelin-associated glycoprotein antibodies with typical clinical features. Evoked distal muscle amplitudes were significantly smaller than for the other paraprotein classes. Preferential distal demyelination manifested by relative prolongation of distal motor latency was not apparent in the cases of long duration. Two patients with IgM antidisialosyl antibodies and cold agglutinating activity had a large fiber neuropathy with intermittent oculofacial involvement. Both responded to intravenous immunoglobulin. Findings in the remaining patients were varied. Recognition of IgM subgroups is important both for prognosis and possible response to treatment.

Physical inactivity and other health risks among Australian males in less-skilled occupations.

Male workers in less-skilled occupations have higher rates of cardiovascular disease, compared with higher-skilled workers. A representative population sample of Australian male workers was used to compare physical activity levels and selected cardiovascular disease risk factors in less-skilled versus professional and skilled workers. Workers in the less-skilled occupational categories reported significantly more vigorous work and home-based activity than did those in the professional and skilled categories. In multivariate comparisons, cigarette smoking was the only factor that discriminated between the less-skilled versus the professional and skilled employees. Although worksites can potentially provide health-promoting physical activity options for higher-risk groups, our findings suggest that smoking and possibly overweight are risk factors that are more strongly present in less-skilled occupations.

Glutathione S-transferases in human renal cortex and neoplastic tissue: enzymatic activity, isoenzyme profile and immunohistochemical localization.

1. Glutathione S-transferase (GST) activity in the cytosol of renal cortex and tumours from eight men and eight women was measured using 1-chloro-2,4-dinitrobenzene (CDNB) as a substrate. GST activities ranged from 685 to 2192 nmol/min/mg protein in cortex (median 1213) and from non-detectable (minimum 45) to 2424 nmol/min/mg protein in tumours (median 469). The activities in the tumours were lower than those in the normal cortices (p < 0.05). 2. In men, the activity in the cortical cytosol was in all cases higher than that measured in the corresponding tumours (p < 0.05). In women, the difference in activity between cortices and tumours was not significantly different (p > 0.05). 3. The age of the patients ranged from 42 to 81 years (median 62) and was not found to play a role in the levels of GST activity observed in cortex or in renal tumours from either sex. 4. Immunoblotting and immunohistochemical studies confirmed that GST-alpha was the predominant form expressed both in normal cortex and tumour and probably accounted for most of the GST activity present in these samples. GST-mu and GST-phi were expressed in both tumours and normal cortex and, while in some cases the level of expression in the cortices was higher than that found in the tumours, the reverse was also observed. Within the GST-mu class, GST M1/M2 was only detected in one sample (tumour), which showed the highest overall expression of GST-mu. GSTM3 was the predominant isoenzyme of the mu class in normal and tumour tissue, whereas GTM4 and GSTM5 were not detected. 5. These differences could have functional significance where xenobiotics or cytotoxic drugs are specific substrates for the different classes of GSTs.

1-Methoxy-agroclavine from Penicillium sp. WC75209, a novel inhibitor of the Lck tyrosine kinase.

A high-throughput screen was developed and implemented to identify inhibitors of the Lck tyrosine kinase. This report describes the identification of a specific inhibitor of this enzyme from the solid fermentation culture of the Penicillium sp., WC75209. The active compound was isolated and structurally characterized as 1-methoxy-5R, 10S-agroclavine, a new member of the ergot alkaloid family.

Human IgM paraproteins demonstrate shared reactivity between Campylobacter jejuni lipopolysaccharides and human peripheral nerve disialylated gangliosides.

IgM paraproteins from patients with CANOMAD (chronic ataxic neuropathy, ophthalmoplegia, M-protein, agglutination, anti-disialosyl antibodies) react with NeuAc(alpha 2-8)NeuAc epitopes on a wide range of gangliosides including GQ1b, GT1a, GD1b and GD3. The tissue distribution of reactive antigens in human peripheral nerve has not been addressed in detail. In addition, the origin of these antibodies is unknown. Here we report that purified anti-disialosyl paraproteins from two affected patients bind a wide array of human peripheral nerve structures including dorsal root ganglia, dorsal and ventral root axons, femoral and oculomotor nerves. We also show that these paraproteins bind lipopolysaccharides of Campylobacter jejuni isolates from 3/3 cases of Miller Fisher syndrome, and to a less frequent extent, from cases of Guillain-Barré syndrome and enteritis controls. In conjunction with our previous studies, these data provide a possible causal link between the origin and pathogenic effects of anti-disialosyl antibodies in human paraproteinaemic neuropathy.

Bripiodionen, a new inhibitor of human cytomegalovirus protease from Streptomyces sp. WC76599.

Bripiodionen (1), a new natural product, was isolated from Streptomyces sp. WC76599 during the screening of microbial fermentation extracts for their ability to inhibit human cytomegalovirus protease. The structure of 1 was elucidated by spectroscopic methods. Compound 1 displayed inhibitory activity against human cytomegalovirus protease with an IC50 value of 30 microM.

BMS-182123, a fungal metabolite that inhibits the production of TNF-alpha by macrophages and monocytes.

A fungal metabolite, BMS-182123, which inhibited bacterial endotoxin-induced production of tumor necrosis factor (TNF-alpha) in murine macrophages and human peripheral blood monocytes (in vitro), was isolated from the culture broth of Penicillium chrysogenum strain V39673. The effective BMS-182123 concentration (IC50) resulting in 50% inhibition of lipopolysaccharide-induced TNF-alpha production in murine macrophages and human monocytes was 600 ng/ml and 4.0 microgram/ml, respectively. BMS-182123 suppressed the lipopolysaccharide-induced TNF-alpha promoter activity and did not affect the stability of posttranscriptional mRNA. Addition of hydrophobic resin, Amberlite XAD-8 (1%), to the fermentation enhanced the production of BMS-182123 by 5.5 fold. A total of 577 mg pure BMS-182123 was recovered from a 250-liter fermentation supplemented with 1% Amberlite XAD-8.

Large scale production and semi-purification of kedarcidin in a 1000-L fermentor.

Actinomycete strain ATCC 53650 was grown in a 1000-L fermentor containing 680 L of medium and the production of kedarcidin was monitored by HPLC. The titers of kedarcidin in the fermentor cultures were 0.49-0.53 mg ml-1. A quick and efficient purification method involving the use of anion exchange resin DE23 (batch adsorption-desorption) and an ultrafiltration system yielded high recovery (65% yield) of kedarcidin from the fermentor culture. Over 200 grams of lyophilized kedarcidin of 70% purity was recovered from each of two 1000-L fermentor cultures using this process.

AAEM minimonograph #42: intraoperative monitoring of peripheral and cranial nerves.

Intraoperative studies of focal neuropathies have become increasingly common both as an aid to the localization of the neuropathy and a means of monitoring the integrity of the nerve in the course of surgery. Success very often depends on careful attention to the technical problems presented by working in the operating theater. Despite these difficulties, assessment of conduction directly from the exposed nerve offers opportunities for better understanding the pathophysiology of these neuropathies and correlating these findings with conventional electrodiagnostic studies.

The effect of cerulenin on the production of esperamicin A1 by Actinomadura verrucosospora.

Addition of cerulenin (0.25-1.0 mM) to cultures of Acinomadura verrucosospora before the onset of esperamicin synthesis inhibited the production of esperamicin A1 by the microorganism. This result indicates that esperamicin A1 is biosynthesized in part by the polyketide pathway. Addition of cerulenin to the cultures during the active production phase led to a net decrease in esperamicin A1 production. The 14C-acetate labeling pattern of esperamicin A1 in the cultures with or without addition of cerulenin at the active production phase also demonstrated the instability of esperamicin A1 in the fermentation. This suggests that esperamicin A1 is unstable and degradation occurs during the active production phase. Addition of the neutral resin Diaion HP-20 (1%) to the fermentation enhanced the production of esperamicin A1 by 53%.

Improved processes for the production and isolation of dynemicin A and large-scale fermentation in a 10,000-liter fermentor.

Supplementing the culture of Micromonospora chersina sp. nov. No. M956-1 with NaI (0.5 mg/l) enhanced the production of dynemicin A by 35-fold in shake flask culture. Homogeneous dynemicin A was obtained from the whole broth extract by Dicalite chromatography, Sephadex LH-20 chromatography and vacuum liquid chromatography. Gram quantities of dynemicin A were obtained from the fermentation of M. chersina sp. nov. No. M956-1 in a 10,000-liter fermentor.

Isolation of a bromo analog of rebeccamycin from Saccharothrix aerocolonigenes.

When grown in a defined medium containing 0.05% KBr, Saccharothrix aerocolonigenes ATCC 39243 produces a novel bromo analog of rebeccamycin. This new analog, designated bromorebeccamycin, has been isolated from the culture broth and purified by vacuum liquid chromatography and column chromatography. Spectroscopic data demonstrated that bromorebeccamycin has the same structure as rebeccamycin, except for the replacement of the two chlorine atoms by bromine atoms in the molecule. Bromorebeccamycin and rebeccamycin have a similar potency and activity against P388 leukemia in the murine model.