Volumes and numbers of intervillous pores and villous domains in placentas associated with intrauterine growth restriction and/or pre-eclampsia.

The intrauterine environment has an important influence on placental development. In pre-eclampsia (PE) and intrauterine growth restriction (IUGR), early remodelling of spiral arteries has repercussions for uteroplacental blood flow. The IUGR placenta exhibits compromised growth of villous trees, a smaller intervillous space and a lower diffusive conductance. Here, we test whether or not term placentas associated with PE or IUGR also exhibit changes in structural quantities (notably, sizes and numbers of intervillous pores and villous domains) pertinent to uteroplacental haemodynamics. Paraffin wax sections were sampled at random locations and orientations and structural quantities obtained by combining design-based stereological estimates of total and star volumes with model-based estimates of pore hydraulic diameters. Total volumes of intervillous pores and villi were estimated by point counting, total villous surface by intersection counting and star volumes by measuring point-sampled intercept lengths. Other quantities were derived secondarily and group estimates compared by two-way analysis of variance. We found significant main effects of IUGR but no main or interaction effects involving PE. In IUGR, there were fewer intervillous pores and these had larger hydraulic diameters. IUGR also produced fewer villous domains but these were constant in star volume and villi had a constant mean diameter and volume fraction. We concluded that IUGR compromises placental development by producing intervillous pores and villous trees different in size and shape from those in control and PE pregnancies. Calculations suggest that Darcian conductances in the intervillous space improve in IUGR but, in reality, placental performance is compromised by other physiological and structural constraints including the known decline in diffusive conductances.

Type IV hypersensitivity reactions to upper lid gold weight implants-is patch testing necessary?

AIMS: To report two cases of allergic reaction to upper lid gold weight implants in patients with facial nerve palsy and to identify the use of pre-implantation patch testing in predicting gold hypersensitivity. METHODS: One patient who had a positive family history of gold allergy and had undergone previous gold dental restoration underwent patch testing with gold sodium thiosulphate. The gold weight from the same patient was analysed using scanning electron microscopy and energy dispersive X-ray analysis, which can detect surface impurities. Tissue obtained during surgery to remove the gold weight from the second patient was examined histologically. RESULTS: Patch testing in the first patient gave a positive result. Analysis of the gold weight removed from the same patient confirmed 99.99% purity, and hence sensitivity to the gold itself was considered to be the cause of the inflammatory reaction. Histology of tissue taken from the eyelid of the second patient was consistent with type IV hypersensitivity. CONCLUSION: A personal and family history of gold allergy should be looked for before upper eyelid gold weight implantation. Patch testing should be performed for patients where there is doubt about whether gold has been the specific cause of previous allergic reactions, for patients who have undergone previous dental restoration involving gold, or if there is a positive family history of gold allergy.

Binding of anthrax toxin to its receptor is similar to alpha integrin-ligand interactions.

The secreted protein toxin produced by Bacillus anthracis contributes to virulence of this pathogen and can cause many of the symptoms seen during an anthrax infection, including shock and sudden death. The cell-binding component of anthrax toxin, protective antigen, mediates entry of the toxin into cells by first binding directly to the extracellular integrin-like inserted (I) domain of the cellular anthrax toxin receptor, ATR. Here we report that this interaction requires an intact metal ion-dependent adhesion site (MIDAS) in the receptor as well as the presence of specific divalent cations. Also, we demonstrate that the toxin-receptor interaction is critically dependent on the Asp-683 carboxylate group of protective antigen, which projects from the receptor binding surface. We propose that this carboxylate group completes the coordination of the MIDAS metal of ATR, mimicking integrin-ligand interactions.

Traumatic subluxation of the globe into the maxillary sinus.

We report a case of complete traumatic subluxation of the globe into the maxillary sinus as documented by CT. The cornea sustained a mild epithelial abrasion but the globe was otherwise intact without signs of trauma.

An immunocytochemical study of MHC class I expression on human Langerhans cells and melanocytes.

Classical MHC class I glycoproteins (HLA-A, B, and C) present endogenous cytosolic peptide antigen fragments to CD8-positive T-cells. CD8-positive T-cell recognition and destruction of virus-infected cells are dependent on adequate cellular MHC class I expression. Constitutive MHC class I expression is ubiquitous, but known to be deficient on specific differentiated cell types which include hepatocytes, neurones, chondrocytes and myocytes. Although enabling assessment of MHC class I expression on individual cells, limitations of immunocytochemistry were encountered with this assessment on Langerhans cells and melanocytes. These dispersed intraepidermal cells were obscured by adjacent keratinocytes in sections immunostained for MHC class I glycoproteins. Initiatives designed to resolve the issue have included immunoelectron microscopy, cell culture techniques, and animal bone marrow chimera models. Despite the elegance of these techniques, the issue of MHC class I expression on Langerhans cells and melanocytes remains unresolved. In this immunocytochemical study, an alternative strategy was based upon the recognized deficiency of epithelial MHC class I expression within pilosebaceous adnexal units. Langerhans cells and melanocytes were therefore studied within this microenvironment of deficient MHC class I expression, using monomorphic and polymorphic MHC markers. Langerhans cells and melanocytes were demonstrated within pilosebaceous units of scalp skin by immunocytochemistry. Differentiation markers OKT6 (CD1a) and TMH1 defined Langerhans cells and melanocytes, respectively. Monomorphic MHC markers W6/32 and TAL IB5 defined invariant epitopes of HLA class I and II, respectively. Polymorphic MHC class I markers defined the HLA-Bw4 and HLA-Bw6 supertypic determinants. Constitutive MHC class I expression was shown to be deficient on Langerhans cells and melanocytes.

Reproducibility of Bayesian belief network assessment of breast fine needle aspirates.

OBJECTIVE: To assess the consistency of diagnosis of fine needle aspiration biopsies of breast lesions by three experienced and five less experienced pathologists using conventional means and applying a Bayesian belief network (BBN) to 10 diagnostic features to support diagnostic decision making. STUDY DESIGN: Forty fine needle aspiration biopsies, previously assessed by one of the experienced pathologists both conventionally and using a BBN, were assessed by two further experienced pathologists and five less experienced pathologists. RESULTS: Using the BBN, the experienced pathologists arrived at diagnoses in agreement with an established consensus at a slightly lower rate than by conventional means. The less experienced pathologists arrived at the correct diagnoses no more frequently with the help of the BBN than conventionally. CONCLUSION: As used in this study, the BBN did not help less experienced pathologists to interpret their observations but did not enable less experienced pathologists to identify how their observations differed and affected their diagnoses. The prototype system used in this study has since been upgraded by providing computer graphic displays of the features to be observed so that a more uniform mental image can be held by the participating pathologists. This will be tested with the same study design.

Cortical blindness after a failed free tissue transfer: a case report and review of the literature.

Cortical blindness is an uncommon but well-documented entity that results from occipital ischemia or insult. We present a case of blindness following a failed free tissue transfer and review the pertinent literature. Careful history and physical examination can usually distinguish cortical blindness from other organic or psychogenic causes. The workup centers on the exclusion of treatable concurrent pathology. Despite the dramatic presentation of cortical blindness, its treatment is generally supportive and the prognosis for full recovery is excellent.

Joint and systemic distribution of dialysis amyloid.

Deposition of beta 2-microglobulin amyloid in the joints of dialysis patients is common and begins early in the course of treatment, but its pathogenic significance in the production of dialysis arthropathy is uncertain. The joints (hip, knee, shoulder, elbow, wrist, cervical and lumbar spine, sacroiliac joint) and systemic tissues of 19 autopsied patients who had undergone haemodialysis for between 6 and 231 months were examined histopathologically for the presence of beta 2-microglobulin amyloid; it was present in all joints examined, including those unassociated with radiological changes and those of patients who had been on haemodialysis alone for only 24 months. Osteoarticular beta 2-microglobulin amyloid deposits were also found in patients who had been treated mainly by continuous ambulatory peritoneal dialysis. Systemic amyloid deposition was only seen in patients who had been haemodialysed for more than 13 years and consisted of sparse tiny deposits in blood vessel walls.

Isolation of plasmid DNA sequences that complement Rhodobacter sphaeroides mutants deficient in the capacity for CO2-dependent growth.

Mutants deficient in the proper regulation and derepression of ribulose-1.5-bisphosphate carboxylase oxygenase (RuBPC/O) in Rhodobacter sphaeroides were isolated by ethyl methanesulphonate (EMS) and Tn5 mutagenesis of a recA parental strain. Mutants were identified by their ability to grow under conditions where the organism requires basal levels of RuBPC C/O for growth yet fail to grow under conditions which require derepression of the enzyme (Aut-). The newly isolated Aut- mutants exhibited phenotypes distinguishable from the previously isolated Aut- mutant, strain KW25/11. Rocket immunoelectrophoretic examination of RuBPC/O levels revealed marked variance in the ability of mutants to derepress form I and form II RuBPC/O in the absence of exogenous carbon. Evidence that some of the mutants possessed different mutations was substantiated by complementation of the EMS-generated mutants by entirely different genes isolated from a genomic library of R. sphaeroides constructed in the broad-host-range cosmid vector pVK102. Southern hybridization analysis of the complementing library isolates showed the complementing genes to be normally carried on the endogenous plasmids of R. sphaeroides. The gene complementing mutant strain KW25/11 was mapped by Tn5 insertional inactivation and the complementing region found to reside on a 1.5 kb PstJ. BamHI fragment. Complemented strains were unable to match wild-type levels of RuBPC/O under conditions requiring derepression of the enzyme, except for mutant strain EMS45. The Aut- phenotype, represented by the mutants isolated in this study, stems from a deficiency in some aspect of photoautotrophic growth.

Systemic amyloidosis of beta 2-microglobulin type: a complication of long-term haemodialysis.

A patient receiving long-term haemodialysis developed systemic amyloidosis, which was shown immunohistochemically to be of beta 2-microglobulin type, a previously unrecognised form of systemic amyloidosis. Histologically, the amyloid deposits were closely associated with foci of acute and granulomatous inflammation and vasculitis, although it was not clear if the amyloid deposits directly caused the inflammatory process, or if amyloid was deposited preferentially in areas of inflammation of uncertain aetiology.