Massive bone destruction in a human proximal femur from ancient Nubia.

Massive bone destruction in a human right proximal femur is described and differentially discussed in this case study. The individual was an older adult female buried at the ancient Nubian site of Tombos (modern-day Sudan) dating to the early Napatan/Third Intermediate Period (c. 1069-750 BCE). The right femur displayed a pathologic fracture with extensive lytic destruction and resorption of the entire femoral neck, most of the femoral head, and trochanters. Macroscopic and radiographic analyses revealed cortical thinning of the proximal diaphysis with new bone formation enclosing the medullary cavity. The lesion is eccentrically located involving the anterior aspect of the neck. Numerous vascular channels are apparent in the underlying bone. Sclerotic bone marks the limit of the lesion, and osseous lucency is visible in the radiograph. The individual displayed no other lytic lesions; vertebral osteophytic growth, compression fractures, and Schmorl's nodes were observed along with dental disease typical for older individuals. A traumatic etiology is eliminated due to the extensive osteolysis. Vascular, congenital, and developmental conditions are also not consistent with the observed changes. Expansive osteolytic lesions may have been caused by a cyst. Neoplastic tumors resulting in lytic lesions with a high risk of pathologic fracture are also consistent. There have been few reports of such extensive lytic lesions of the proximal femur in the paleopathological and clinical literature; this case adds an example of this underreported condition.

Two cases of skeletal dysplasia from New Kingdom (c. 1400-1050 BCE) Tombos, Sudan.

OBJECTIVE: This project investigates two cases of skeletal dysplasia from archaeological excavations of the New Kingdom Period (c. 1400-1050 BCE) portion of the Tombos cemetery in Sudan. MATERIALS: Fair to well-preserved skeletal remains of two individuals, one adult and one juvenile, are examined here. METHODS: All available skeletal elements were analyzed macroscopically. A differential diagnosis was conducted for each individual. RESULTS: The adult individual, U36.Sh2.B10, displays bilateral mesomelic dysplasia and Madelung's deformity. The juvenile individual, U36.Sh2.B5, also displays bilateral mesomelic dysplasia and characteristics associated with Madelung's deformity. CONCLUSIONS: A differential diagnosis of Léri-Weill dyschondrosteosis (LWD) is suggested for the adult female individual (U36.Sh2.B10). The second case (U36.Sh2.B5) is an approximately three to five-year-old individual and is difficult to diagnose given the young age; however, LWD remains the most likely diagnosis. SIGNIFICANCE: There are few cases of LWD in the paleopathological literature, and fewer still of juveniles. The cases described are useful examples in expanding research demonstrating the variability in the expression of skeletal dysplasias in juveniles and adults. LIMITATIONS: Taphonomic alterations and fragmentation of the crania and portions of the postcrania limited the observation of the full suite of characteristics associated with skeletal dysplasias. U36.Sh2.B5 is difficult to diagnose given the individual's young age and the possibility that this individual had not yet developed the more observable characteristics associated with these conditions. SUGGESTIONS FOR FURTHER RESEARCH: Researchers are encouraged to continue examining the range of expression of skeletal dysplasias in juveniles and adults.

Stable carbon and nitrogen isotope inter- and intra-individual dietary reconstruction from the late 14th to early 18th century site of Alytus, Lithuania.

OBJECTIVES: The Baltic region, particularly Lithuania, was a politically vibrant area of Eastern Europe during the medieval and early modern period. To better understand the diet of Lithuanians during the late 14th to early 18th century, we examine stable carbon and nitrogen isotope ratios from bone and dentin samples from the site of Alytus. We investigate possible dietary differences based on sex, age, and religious practice, as well as dietary changes throughout an individual's lifetime, within the broader European milieu. MATERIALS AND METHODS: Stable carbon and nitrogen isotope analysis was conducted on bone (n = 35) and dentin (n = 38) collagen samples from a total of 39 individuals buried in the cemetery at Alytus (late 14th to early 18th centuries). RESULTS: Results indicate individuals at Alytus consumed a C3 terrestrial based diet. The δ13 C and δ15 N values are not significantly different between bone and dentin, and did not vary by sex. DISCUSSION: The diet at Alytus was homogeneous between males and females and between tissue types. The lack of evidence indicating substantial consumption of fish is unexpected given widespread Catholic fasting practices and marine resource trade throughout Europe. Comparisons with other populations indicate that individuals from Alytus differ in diet from contemporaneous Polish-Lithuanian Commonwealth elites. Comparison of the diets of non-elite individuals in the Eastern Baltic region also reveals dietary variability.

Potential correlates of BCG induced protection against tuberculosis detected in a mouse aerosol model using gene expression profiling.

Tuberculosis (TB) is responsible for more than 2 million deaths per year with the incidence of new cases rising throughout the world. Mycobacterium bovis bacillus Calmette Guerin (BCG) is currently the only available licensed vaccine against M. tuberculosis. Despite the variable protective efficacy in different populations it affords some protection, particularly against childhood and disseminated forms of the disease. BCG remains the gold standard for assessing other prospective TB vaccines, yet there is a lack of information on the mechanisms of BCG protection and consequently there are no definitive correlates of protection for this vaccine. In order to further studies in this area we assessed lung RNA homogenates from naïve, BCG vaccinated and aerosol challenged mice. We found increased IFN-gamma levels in lungs of aerosol challenged mice previously vaccinated with BCG and a number of transcripts regulated by IFN-gamma were also increased in the lungs of these animals. These transcripts represent a cluster of IFN-gamma related transcripts that may assist in determining if BCG and maybe other potential vaccines will elicit protection against M. tuberculosis.

The effect of pertussis whole cell and acellular vaccines on pulmonary immunology in an aerosol challenge model.

Recent clinical trials have shown that the new generation of acellular pertussis vaccines (Pa) can confer protection against whooping cough with negligible adverse reactions. We have compared the effects of pertussis whole cell and acellular vaccines on pulmonary immune responses after aerosol challenge in a murine model of infection. Mice were vaccinated with PBS, Pw or Pa and challenged with Bordetella pertussis by the aerosol route. Cytokine gene expression was analysed from lung tissue and cells; lung lymphocytes were re-stimulated in vitro and cytokines produced measured. The results obtained are consistent with the proposal that a strong Th-1 response is associated with bacterial clearance in both the non-vaccinated and Pw vaccinated mice. The acellular vaccine treated mice cleared the bacterial challenge (with an intermediate efficacy) in the presence of low levels of any of the cytokines assessed. This suggests that Pa protects via a Th-2 independent mechanism.

The significance of carbohydrates on G-CSF: differential sensitivity of G-CSFs to human neutrophil elastase degradation.

It has been reported recently that granulocyte-colony stimulating factor (G-CSF) is degraded upon exposure to human neutrophil elastase (HNE), and this has a negative effect on the ability of the cytokine to promote the in vitro proliferation and maturation of CD34+ cells. This has important implications on the possible in vivo role of elastase in providing negative feedback to granulopoiesis by the direct antagonism of G-CSF. The cytokine used in that study was expressed in Escherichia coli [and was nonglycosylated (NG)], unlike the naturally occurring cytokine, which is an O-linked glycoprotein. As a Chinese hamster ovary-derived (glycosylated) cytokine is available, we compared the susceptibility of NG and glycosylated G-CSF to elastase degradation by incubating the cytokines with HNE and assessing its impact by sodium dodecyl sulfate gel electrophoresis and bioassay. We confirmed the ability of elastase to degrade NG G-CSF in a time- and concentration-dependent manner and found this was associated with a reduction in biological activity of the cytokine. Glycosylated G-CSF, however, was more resistant to elastase degradation, although prolonged exposure did lead to degradation and decreased biological activity. The significance of sugar residues on glycosylated G-CSF in providing protection against the effects of elastase was investigated using enzymatically deglycosylated G-CSF and a mutated form of the G-CSF molecule that was expressed in yeast but was NG. The possible role of HNE in serum-induced inactivation of NG G-CSF was also considered.