Metallothionein Induction as Indicator of Low Level Metal Exposure to Aquatic Macroinvertebrates from a Relatively Unimpacted River System in South Africa.

The Marico River is relatively unaffected by anthropogenic activities. However, metal concentrations-mainly from natural sources-occasionally exceed environmental quality guidelines. Macroinvertebrates are capable to react to these metals through processes such as the induction of metallothioneins (MTs). The aims of this study were to determine whether the induction of MTs can be used as indicator of natural metal exposure in not anthropogenically impacted systems and whether there are relationships between metal concentrations in water, sediment and macroinvertebrates and concomitant MT levels. Positive correlations were found between metals in sediment and macroinvertebrates, while there were no correlations between metal concentrations in water and macroinvertebrates. Even in a not anthropogenically impacted system, a positive correlation existed between trace metal bioaccumulation (e.g. Ni, Pb, Zn) in macroinvertebrates and the induction of MTs. There were, however, no correlations between MTs and bioaccumulation of earth metals (e.g. Al, Fe, Mn, Ti).

Preclinical development of AMG 139, a human antibody specifically targeting IL-23.

BACKGROUND AND PURPOSE: AMG 139 is a human anti-IL-23 antibody currently in a phase II trial for treating Crohn's disease. To support its clinical development in humans, in vitro assays and in vivo studies were conducted in cynomolgus monkeys to determine the pharmacology, preclinical characteristics and safety of this monoclonal antibody. EXPERIMENTAL APPROACH: The in vitro pharmacology, pharmacokinetics (PK), pharmacodynamics and toxicology of AMG 139, after single or weekly i.v. or s.c. administration for up to 26 weeks, were evaluated in cynomolgus monkeys. KEY RESULTS: AMG 139 bound with high affinity to both human and cynomolgus monkey IL-23 and specifically neutralized the biological activity of IL-23 without binding or blocking IL-12. After a single dose, linear PK with s.c. bioavailability of 81% and mean half-life of 8.4-13 days were observed. After weekly s.c. dosing for 3 or 6 months, AMG 139 exposure increased approximately dose-proportionally from 30 to 300 mg·kg(-1) and mean accumulation between the first and last dose ranged from 2- to 3.5-fold. Peripheral blood immunophenotyping, T-cell-dependent antigen responses and bone formation markers were not different between AMG 139 and vehicle treatment. No adverse clinical signs, effects on body weight, vital signs, ophthalmic parameters, clinical pathology, ECG, organ weights or histopathology were observed in the monkeys with the highest dose of AMG 139 tested (300 mg·kg(-1) s.c. or i.v.). CONCLUSIONS AND IMPLICATIONS: The in vitro pharmacology, PK, immunogenicity and safety characteristics of AMG 139 in cynomolgus monkeys support its continued clinical development for the treatment of various inflammatory diseases.

Counting whales in a challenging, changing environment.

Estimating abundance of Antarctic minke whales is central to the International Whaling Commission's conservation and management work and understanding impacts of climate change on polar marine ecosystems. Detecting abundance trends is problematic, in part because minke whales are frequently sighted within Antarctic sea ice where navigational safety concerns prevent ships from surveying. Using icebreaker-supported helicopters, we conducted aerial surveys across a gradient of ice conditions to estimate minke whale density in the Weddell Sea. The surveys revealed substantial numbers of whales inside the sea ice. The Antarctic summer sea ice is undergoing rapid regional change in annual extent, distribution, and length of ice-covered season. These trends, along with substantial interannual variability in ice conditions, affect the proportion of whales available to be counted by traditional shipboard surveys. The strong association between whales and the dynamic, changing sea ice requires reexamination of the power to detect trends in whale abundance or predict ecosystem responses to climate change.

A perspective on efflux transport proteins in the liver.

Detailed knowledge regarding the influence of hepatic transport proteins on drug disposition has advanced at a rapid pace over the past decade. Efflux transport proteins located in the basolateral and apical (canalicular) membranes of hepatocytes play an important role in the hepatic elimination of many endogenous and exogenous compounds, including drugs and metabolites. This review focuses on the role of these efflux transporters in hepatic drug excretion. The impact of these proteins as underlying factors for disease is highlighted, and the importance of hepatic efflux proteins in the efficacy and toxicity of drugs is discussed. In addition, a brief overview of methodology to evaluate the function of hepatic efflux transport proteins is provided. Current challenges in predicting the impact of altered efflux protein function on systemic, intestinal, and hepatocyte exposure to drugs and metabolites are highlighted.

Duplication of 7q36.3 encompassing the Sonic Hedgehog (SHH) gene is associated with congenital muscular hypertrophy.

Muscular hypertrophy is a very rare finding on foetal ultrasonography. We present a case with recurrent muscular hypertrophy, liver enlargement and polyhydramnios in two pregnancies. One pregnancy was terminated due to suspicion of a storage disease, whereas the other led to delivery of a boy with muscular hypertrophy and mildly retarded psychomotor development. Array-CGH identified a small duplication of 7q36.3 including the Sonic Hedgehog (SHH) gene in both the aborted foetus and the live born male sib. Neither of the parents carried the 7q36.3 duplication. The consequences of overexpression of SHH in humans are not elucidated, but animal studies have suggested its importance in muscular hypertrophy. We suggest that the clinical findings in the presented case might be explained by the duplication and presumed overexpression of SHH.

The Influence of Health Education on the Prevalence; Intensity and Morbidity of Schistosoma haematobium Infections in Children over a Two-Year Period in the Limpopo Province; South Africa

The influence of health education on the prevalence and intensity of Schistosoma haematobium infections; as well as on the related morbidity; was studied in schoolchildren between the ages of 4 and 14. Three groups of children were selected for this investigation. The 67 children in the experimental group received chemotherapy before health education was implemented; as well as when they got re-infected during the study. Health education was presented in mother tongue by means of a puppet show. The 99 children in one of the control groups received treatment only after the study while the 80 children in the remaining control group were treated as those in the experimental group; except that no intervention by means of education was applied. Health education; parasitological screens and snail surveys were done during the rainy; cold-dry and hot-dry seasons between 2004 and 2006. The prevalence and intensity of infection; as well as the morbidity (degree of haematuria) due to the infections; were determined after the urine samples; collected from each child; were screened. Significant differences (p0.05) were found between the initial prevalence of infection (100) and all the values recorded from survey 2 to survey 7. With regard to the intensity of infection; significant differences were found in all cases between the experimental and the treated control groups except in the heavy category (p=0.84). Statistical comparisons between the mean percentages calculated for corresponding categories of haematuria between the different groups revealed significant differences in all cases except between the experimental and treated control groups in the heavy category (3+) of haematuria

Restriction of GAGE protein expression to subpopulations of cancer cells is independent of genotype and may limit the use of GAGE proteins as targets for cancer immunotherapy.

The GAGE cancer testis antigen gene family encodes products that can be recognized by autologous T cells, and GAGE proteins have been suggested as potential targets for cancer immunotherapy. Analysis of GAGE expression in tumours has primarily been performed at the level of gene transcription, whereas little is known about GAGE expression at the protein level. To evaluate the potential of GAGE proteins as targets for cancer-specific immunotherapy, we studied the expression of these proteins in normal and malignant cells/tissues using a novel panel of monoclonal antibodies. Immunohistochemical analysis of more than 250 cancer specimens demonstrated that GAGE proteins were frequently expressed in numerous cancer types and correlated with the expression of the cancer testis antigens MAGE-A1 and NY-ESO-1. Significant intercellular and subcellular differences in GAGE protein levels were observed, and most GAGE-positive tumours also contained cancer cells lacking GAGE expression. Studies of genetically homogenous cell lines with similar intercellular heterogeneous GAGE expression showed that GAGE expression was not associated with a specific genotype, but defined a phenotypically distinct population of cells. Surprisingly, in normal tissues we found that GAGE proteins were not restricted to testis, but were also present in a subset of oocytes of resting primordial follicles and in maturing oocytes. This is the first time that a cancer testis antigen has been reported in postfoetal oocytes. The lack of GAGE expression in a subset of cancer cells within GAGE-positive tumours has decisive implications for the development of GAGE-targeted cancer therapy.

Distribution, habitats and role as intermediate host of the freshwater snail, Bulinus forskalii, in South Africa.

This paper focuses on the geographical distribution and habitats of Bulinus forskalii, the snail intermediate host of the conical fluke of equids, Gastrodiscus aegyptiacus as reflected by the 1209 samples in the database of the National Freshwater Snail Collection of South Africa. The 362 different loci on record represent an extensive distribution in KwaZulu-Natal Province, the Limpopo Province, the coastal areas of the Eastern Cape Province and the south-eastern part of the North West Province. Although it was recorded from all types of water-body represented in the database, the highest percentages of samples were recovered from dams (30.4%) and brooks (28.2%). The majority of samples came from perennial habitats (59.1%), 60.7% from habitats with standing water, 54.0% from habitats with clear water and 71.8% from habitats of which the water was described as fresh. The majority of samples (39.5%) were collected in habitats of which the substratum was recorded as muddy. The highest percentage of samples, by far (81.5%), was collected in habitats that fell within the mean yearly temperature interval ranging from 15-20 degrees C. An integrated decision tree constructed from the data in the database indicated that temperature and type of water-body played a decisive role in determining the presence of B. forskalii in a given area. The results of experimental exposure to miracidia of a local strain of both Schistosoma haematobium and Schistosoma mattheei in the laboratory indicated that a local strain of B. forskalii was incompatible with both these strains of parasite. Research to clarify the role of B. forskalii in the transmission of both Calicophoron microbothrium and G. aegyptiacus in South Africa, is recommended.

Declining autopsy rates in stillbirths and infant deaths: results from Funen County, Denmark, 1986-96.

OBJECTIVE: The aim of this study was to describe the development of the autopsy rate in stillbirths and infant deaths in an 11-year period and evaluate the information gained by performing an autopsy. METHODS: Included in the study were all stillbirths and infant deaths in Funen County, Denmark, in 1986-96. Data sources were death certificates and autopsy reports. RESULTS: The study included 273 stillbirths and 351 deaths in infancy. The rates of stillbirth and infant death did not change significantly during the period. The overall autopsy rate for stillbirths was 70% and for infant deaths 57%. There was a significant decline in autopsy rate during the years 1991-96 as compared with 1986-90 for stillbirths, infant deaths and infant deaths excluding sudden infant death syndrome. In stillbirth, the autopsy changed the diagnosis in 9% of the cases. In 22%, the clinical diagnosis was maintained, but additional information was obtained. In infant death, the numbers were 10% and 40%, respectively. CONCLUSION: In 10% of the autopsies the diagnosis was changed completely, with an impact on genetic counseling as well as on statistical records of causes of death in fetuses and infants. With additional information in 22-40% of the autopsies, the study emphasizes autopsy as a useful investigation.

The respiratory properties of Biomphalaria glabrata exposed to Schistosoma mansoni infection, starvation, CO, and choices of different oxygen concentrations.

The oxygen consumption rate (VO(2)) of Biomphalaria glabrata populations, using polarometric and manometric methods, when plotted against dried body mass as logarithmic co-ordinates, respectively, fell on a regression line with a slope between 0.933 and 1.02. The slope of the regression line for non-infected Schistosoma mansoni populations was found to be 1.04 with no differences in the VO(2) between infected and non-infected snails. The VO(2) of CO-treated snails was the same as for the control snails. The VO(2) of starved snails declined after 3 days and was half the original value after 10 days starvation at 27 degrees C. The P(50) value for snail haemolymph containing haemoglobin suspended in a Tris-HCl buffer was 5.57(+/-0.73)mmHg at a pH of 7.51 and 25 degrees C. For Sephadex-75 cleaned haemolymph the P(50) value was 1.72(+/-0.07)mmHg at 25 degrees C and pH 7.51. Snails exposed to oxygen fs and to choices of different oxygen concentrations in water did not exclusively prefer high (130mmHg), low (15mmHg), or normal (80mmHg) oxygen tensions. The oxygen consumption rate of 782 cercariae at 27 degrees C was measured as 0.0092 microl O(2)/h per single cercaria. The results, when compared with the data in the literature [Z. Vergl. Physiol. 46 (1963) 467;; S. A. J. Zool. 14 (1979) 202], indicate that the mantle cavity gas bubble plays an insignificant or no role at all when pulmonate snails are kept in water with high partial pressures of oxygen and at low temperatures.

Distribution and habitats of the snail Lymnaea truncatula, intermediate host of the liver fluke Fasciola hepatica, in South Africa.

This paper focuses on the geographical distribution and habitats of Lymnaea truncatula, the intermediate, snail host of the liver fluke, Fasciola hepatica, as reflected by the 723 samples in the database of the National Freshwater Snail Collection, Potchefstroom, South Africa. The 221 different loci (1/16-degree squares) on record reflect an extensive but discontinuous distribution, except in Lesotho and in parts of the Mpumalanga, Gauteng and North West provinces of South Africa. Although recorded from 12 different types of waterbody, it was mostly (42.0%) recovered from swamps. Most samples (45.8%) were collected in habitats with slow-flowing water. A muddy substratum was recorded for 62.5% of the samples. Most samples (86.3%) were collected in habitats with a mean annual air temperature of 10-20 degrees C, and more than 69% came from localities with a mean annual rainfall of 600-900 mm. An integrated decision tree constructed from the data indicated that temperature and types of waterbody play a decisive role in determining the presence of L. truncatula in a given area. A temperature index calculated for all mollusc species ranked L. truncatula second in a total of 53 species according to its association with low temperatures. It remains to be established whether its distribution is indeed discontinuous, and whether its preference for a particular habitat, amphibious habits and ability to aestivate could have resulted in some populations having been overlooked during surveys.

Daily emergence of Schistosoma mansoni and S. haematobium cercariae from naturally infected snails under field conditions.

The daily emergence of Schistosoma mansoni and S. haematobium cercariae was investigated under field conditions. Intermediate host snails of both schistosome species were collected during the rainy season, cold dry season and warm dry season and kept separately in test tubes in habitat water. Shed cercariae were collected from each of the test tubes at two hourly intervals, transferred to Petri dishes and counted. Mice were exposed to these cercariae to establish the identity of the schistosome parasites. Peak shedding for both species was observed at 1100 h during the rainy and warm dry seasons and at 0900 h during the cold dry season. Shedding before 0900 h was found only for S. haematobium in the rainy season while shedding after 1700 h occurred only during this season at both species. Shedding observed during 1900 h observation period was in the low category for both species. No shedding was observed during the 2100 h observation period for any of the species and the investigation was discontinued after this period. Only S. haematobium ova were found in the exposed mice.

Infection control in South African oral hygiene practice.

OBJECTIVE: The aim was to gain information about the practice of infection control in oral hygiene practice. METHODS: A questionnaire based on OSHA and CDC guidelines was submitted to oral hygienists who attended a refresher course followed by a second posted questionnaire seeking information about hand hygiene practice. The questions were directed to observance of personal protection by oral hygienists and the application of procedures required for infection control in the surgery. RESULTS: 87.5% wore face masks but the proper use of facial protection, overcoats and disposable overcoats was reported by fewer than 50%. A total of 97% wore gloves and 88% changed gloves between patients. Skin reactions to gloves were reported by 26%. Only 7% had not been vaccinated against hepatitis B. The correct procedures for sterilising equipment and instruments were carried out by fewer than 50%, and 57% of participants wanted an improvement of infection control arrangements in their workplace. CONCLUSION: It is concluded that a need exists for proper practice of infection control by oral hygienists which can be remedied by interceptive and preventive education and peer pressure.

[Granulosa cell tumors in children]. / Granulosacelletumorer hos børn.

Juvenile granulosa cell tumours (JGCT) are rare. They may develop in ovarian or testicular tissue. In childhood a special histological type called juvenile granulosa cell tumour (JGCT) is seen. Four cases are described: Congenital JGCT in a child with sex chromosomal abnormity (45 XO/46 XdicYq) and tumour arising from immature testicular tissue, JGCT in the testis of a four month old boy, JGCT associated with a hypothalmic hamartoma in a 18 month-old girl, and JGCT in an eight year-old girl. In all cases the tumours were benign.

Interannual variation in condition of the mackerel icefish

Mackerel icefish Champsocephalus gunnari are widespread on the South Georgia (54° S, 36° W) shelf. Analysis of condition indicated a strong interannual variation. High condition indices, indicative of good feeding conditions, were present when krill were abundant in the region. Years when krill were scarce and condition index was consequently low, were consistent with years when indices from land-based krill predators also indicated that krill were scarce.

Organ weights in healthy and apparently healthy Danish infants.

The weights of brain, heart, liver, kidneys, spleen, lungs, and thymus were registered in 222 forensic autopsies of Danish infants aged 1 week to 0.99 year (137 males, 85 females), who prior to death were healthy or apparently healthy based on clinical evidence. Variability of organ weights was estimated, and the relationship between individual organ weights and age, body weight, and body length, and the sum of organ weights was evaluated in relation to age, body weight, and body length. No significant differences were found between males and females, and between the healthy and apparently healthy infants. There was a positive, significant correlation of the individual organ weights with age, body weight, and body length. It was most pronounced for the weight of the brain and least pronounced for the thymus. Am. J. Hum. Biol. 9:35-38 © 1997 Wiley-Liss, Inc.

Denatonium bitter tasting among transgenic mice expressing rat von Ebner's gland protein.

Von Ebner's gland protein (VEGP) is a secretory protein, which is abundantly expressed in the small von Ebner's salivary glands of the tongue. VEGP as component of the perireceptor environment around taste papillae might function as transporter of hydrophobic molecules, for example bitter substances. Here we report a new approach to investigate the physiological role of VEGP by expression of the cloned rat VEGP gene in transgenic mice. Taste papillae of mice, in contrast to rats, do not contain VEGP. The founder mouse 4345 and three offspring carry the transgene as shown by PCR analysis and saliva of the transgenic mice contains high amounts of VEGP. In two-bottle preference tests, transgenic and nontransgenic siblings show significantly different capabilities to taste the bitter compound denatonium benzoate at 10 microM. The reduced sensitivity of transgenic mice to denatonium benzoate points to a clearance function of VEGP the specificity of which for taste compounds and other molecules remains to be seen.

Armanni-Ebstein lesions of the kidney: diagnostic of death in diabetic coma?

In the period from January 1986 through April 1993, 47 cases with diabetes mellitus were autopsied at the Institute of Forensic Medicine, Odense University. In 26 cases, the diabetes had been treated with insulin, in 21 cases with oral medication or diet only. In eight insulin-dependent cases, tubular vacuolation was found in the kidneys, the so-called Armanni-Ebstein lesions. The circumstances of death and postmortem analyses of blood, urine and/or vitreous humor supported a presumed diabetic coma as the cause of death in these eight cases. Of the remaining 39 cases, six were too putrefied for histologic examination. In the remaining 33 cases and in a series of 20 non-diabetics, the cause of death was ascertained as illness (other than diabetes), traffic accidents, drowning or intoxication. In none of these cases was a diabetic coma suspected, and none of these cases showed tubular vacuolation in the kidneys. The authors conclude that tubular vacuolation of the kidneys strongly indicates death in diabetic coma.

Structural organization of the genes for rat von Ebner's gland proteins 1 and 2 reveals their close relationship to lipocalins.

The rat von Ebner's gland protein 1 (VEGP 1) is a secretory protein, which is abundantly expressed in the small acinar von Ebner's salivary glands of the tongue. Based on the primary structure of this protein we have previously suggested that it is a member of the lipocalin superfamily of lipophilic-ligand carrier proteins. Although the physiological role of VEGP 1 is not clear, it might be involved in sensory or protective functions in the taste epithelium. Here, we report the purification of VEGP 1 and of a closely related secretory polypeptide, VEGP 2, the isolation of a cDNA clone encoding VEGP 2, and the isolation and structural characterization of the genes for both proteins. Protein purification by gel-filtration and anion-exchange chromatography using Mono Q revealed the presence of two different immunoreactive VEGP species. N-terminal sequence determination of peptide fragments isolated after protease Asp-N digestion allowed the identification of a new VEGP, named VEGP 2, in addition to the previously characterized VEGP 1. The complete VEGP 2 sequence was deduced from a cDNA clone isolated from a von Ebner's gland cDNA library. The VEGP 2 cDNA encodes a protein of 177 amino acids and is 94% identical to VEGP 1. DNA sequence analysis of the rat VEGP 1 and 2 genes isolated from rat genomic libraries revealed that both span about 4.5 kb and contain seven exons. The VEGP 1 and 2 genes are non-allelic distinct genes in the rat genome and probably arose by gene duplication. The high degree of nucleotide sequence identity in introns A-C (94-100%) points to a recent gene conversion event that included the 5' part of the genes. The genomic organization of the rat VEGP genes closely resembles that found in other lipocalins such as beta-lactoglobulin, mouse urinary proteins (MUPs) and prostaglandin D synthase, and therefore provides clear evidence that VEGPs belong to this superfamily of proteins.

[Safety in using metal tracheostomy tubes]. / Sikkerheden ved brug af metaltrakealkanyler.

The breakage of a stainless steel tracheostomy tube resulted in the death of a 19-year old man. Technical investigations identified corrosion as the mechanism of degradation of the braced joint between the plate and the external tube. Examination of a stock of 112 sterling silver tubes showed corrosive attacks on four tubes. Recommendations are presented concerning the production, maintenance and control of metal tracheostomy tubes.