Genetic and morphometric variances in three human populations

Data from three human populations were used to investigate the putative relationship between genetic and morphological variances. There was no evidence to support the hypothesis that individuals heterozygous at a small number of marker loci are more often near the mean for anthropometric characters than are homozygotes. In one population (Otmoor), apparent support for the hypothesis was due to the confounding factors of correlations between anthropometric traits and population subdivision. It is unlikely that such relationships can be detected by intrapopulation comparisons because of the low association between measured and total heterozygosity.     

The structure of human skin collagen as studied with the electron microscope

1. The structure of the collagen fibrils of normal human skin corium has been investigated with the electron microscope. 2. Under the conditions of observation the fibrils ranged in width from about 700 to 1,400 A with 1,000 A as the value occurring most frequently. They showed little tendency to fray longitudinally as is characteristic of tendon fibrils; when fracture of fibrils occurred it was usually in planes transverse to the axis. 3. The axial repeating periods observed in fibrils stained with phosphotungstic acid or shadowed with chromium or platinum range from about 500 to 800 A, the maximum occurring between 620 and 660 A. The average period in fibrils from infant skin does not differ significantly from that of adult and aged skin. 4. Depending on conditions of preparation, intraperiod fine structure, in the form of cross-bands, was observed in varying detail. The most detailed pattern commonly observed contains six bands of characteristic density and position. 5. Shadowed plastic replicas of dried collagen fibrils reproduce much of the structure commonly seen in shadowed fibrils. Replicas of moist fibrils show considerably less surface contouring than do dried fibrils. Replicas from smears of connective tissue fragments on glass show detailed structure, indicating the feasibility of applying this technique to biopsy material. 6. Infant skin differs from adult skin in having considerably greater amounts of amorphous material, little of which is strongly adherent to the collagen fibrils.     

Characterization of the antisecretory action of prostaglandin D2 in the rat colon

Previous studies have shown that prostaglandin D₂ (PGD₂) inhibits neuronally mediated secretion in the rat colon. This antisecretory action of PGD₂ was further characterized by the use of a prostaglandin D receptor blocker. Prostaglandin D₂ inhibited the neuronally mediated short-circuit current evoked by prostaglandin I₂, which represents Cl^- secretion. The concentration-response curve for the inhibition by PGD₂ was shifted to the right in the presence of the prostaglandin D receptor blocker, AH 6809. AH 6809 had no effect on the short-circuit current response induced by prostaglandin E₂ or iloprost, a stable prostaglandin I₂ analogue, suggesting an interaction of the blocker with receptors specific for PGD₂. A direct interaction of PGD₂ with enteric neurones was studied by determining its effect on acetylcholine release from enteric neurones preloaded with [³H]choline. Prostaglandin D₂ suppressed ³H release induced by electric field stimulation. It had, however, no effect on the release induced by depolarization with potassium. The results suggest that the inhibitory action of PGD₂ on enteric cholinergic neurones is mediated by prostaglandin D receptors.     

Human Epidermal Cell-Induced Generation of Alloreactive Cytotoxic T-Lymphocyte Responses against Epidermal Cells

Human epidermal cells act as stimulators in the mixed-skin cell lymphocyte culture reaction (MSLR). To analyse the generation in MSLR of alloreactive cytotoxic T lymphocytes (CTL) in cell-mediated cytolysis of human epidermal cells. a phenomenon suggested by various observations of skin inflammatory processes in vivo, 18-h 51Cr-release assays against epidermal cells cultivated on collagen-coated plates (epidermal cells autologous to the stimulator cells in MSLR) were conducted after allogenic human MSLR. To analyse the role of human Langerhans cells and related epidermal dendritic cells, which are the only cells expressing the DR-Ia-like (class II) antigens in normal epidermis and in suspensions of normal epidermal cells, MSLR and CTL assays were conducted with, as stimulator cells, suspensions of normal human epidermal cells as controls, and, in parallel, suspensions of epidermal cells after preincubation with anti-class II monoclonal antibody and complement. The generation of alloreactive CTL to epidermal cells occurred only after allogenic MSLR and when targets and stimulator cells were from the same donor; it was abolished when epidermal cell suspensions used in MSLR were depleted in HLA-DR-expressing cells. These findings demonstrate that an epidermal cell-induced generation of cell-mediated cytotoxicity to human epidermal cells may occur in vitro. Langerhans cells and other class II antigen-expressing epidermal cells (dendritic indeterminate cells) are necessary for an optimal in vitro sensitization in MSLR and the subsequent generation of alloreactive CTL towards epidermal cells in man.     

Neuroimaging in childhood arterial ischaemic stroke: evaluation of imaging modalities and aetiologies

Aim The aim of this study was to describe neuroimaging patterns associated with arterial ischaemic stroke (AIS) in childhood and to differentiate them according to stroke aetiology. Method Clinical and neuroimaging (acute and follow‐up) findings were analysed prospectively in 79 children (48 males, 31 females) aged 2 months to 15 years 8 months (median 5y 3mo) at the time of stroke by the Swiss Neuropaediatric Stroke Registry from 2000 to 2006. Results Stroke was confirmed in the acute period in 36 out of 41 children who underwent computed tomography, in 53 of 57 who underwent T2‐weighted magnetic resonance imaging (MRI) and in all 48 children who underwent diffusion‐weighted MRI. AIS occurred in the anterior cerebral artery (ACA) in 63 participants and in all cases was associated with lesions of the middle cerebral artery (MCA). The lesion was cortical–subcortical in 30 out of 63 children, cortical in 25 out of 63, and subcortical in 8 of 63 children. Among participants with AIS in the posterior circulation territory, the stroke was cortical–subcortical in 8 out of 16, cortical in 5 of 16, and thalamic in 3 out of 16 children. Interpretation AIS mainly involves the anterior circulation territory, with both the ACA and the MCA being affected. The classification of Ganesan is an appropriate population‐based classification for our Swiss cohort, but the neuroimaging pattern alone is insufficient to determine the aetiology of stroke in a paediatric population. The results show a poor correlation between lesion pattern and aetiology.     

Insulin Infusion Normalizes Cardiovascular Responses and Plasma Noradrenaline after Oral Glucose in Type 1 (Insulin-dependent) Diabetes

ABSTRACT. We examined whether the abnormal regulation of the cardiovascular system and plasma noradrenaline observed after oral glucose in insulin-dependent diabetic patients could be normalized by intravenous infusion of insulin. Eight patients with type 1 (insulin-dependent) diabetes were examined after an oral glucose load with and without simultaneous infusion of insulin. Insulin infusion increased plasma insulin from 0.07 to 0.31 nmol/1. In the control experiment (glucose only), mean heart rate and mean arterial systolic blood pressure remained unchanged and plasma noradrenaline (NA) decreased (p < 0.05). After oral glucose plus intravenous insulin, mean heart rate increased by 11 % and mean systolic blood pressure by 5 % (p < 0.05, p < 0.01), whereas plasma NA did not change significantly. The present study indicates that physiologic increments in plasma insulin concentration are of importance in the regulation of the cardiovascular system and plasma NA following an oral glucose load.     

Methotrexate specifically modulates cytokine production by T cells and macrophages in murine collagen-induced arthritis (CIA): a mechanism for methotrexate-mediated immunosuppression

Immunosuppressive therapy with methotrexate (MTX) has been established as effective treatment for patients with rheumatoid arthritis. To analyse the therapeutic potential and mechanisms of action of MTX, we determined serum cytokine levels and cytokine production by splenic T cells and macrophages in untreated and MTX-treated mice. Furthermore, we assessed the role of MTX in a murine model of experimental arthritis induced by collagen type II (CIA). MTX reduced spontaneous and IL-15-induced tumour necrosis factor (TNF) production by splenic T cells but not by macrophages from healthy mice in vitro in a dose-dependent manner. In contrast, interferon-gamma (IFN-γ) production was less strikingly reduced and IL-4 production was virtually unaffected. In addition, treatment of healthy mice with MTX in vivo led to reduced TNF serum levels and diminished TNF production by splenic T cells and macrophages. Intraperitoneal administration of MTX prior to the onset of arthritis completely prevented clinical and pathological signs of CIA. This was associated with a striking reduction of TNF production by spleen cells from MTX-treated mice. The role of TNF in MTX-mediated effects on cytokine production was further underlined by the finding that MTX effects on IFN-γ production were augmented in TNF-transgenic mice but abrogated in mice in which the TNF-α gene had been inactivated by homologous recombination. Thus, MTX specifically modulates spontaneous and IL-15-induced TNF-α production in mice and prevents experimental murine CIA. These data suggest that TNF production by T cells is an important target of MTX and may serve as a basis to understand and further analyse MTX-mediated mechanisms of immunosuppression in patients with RA.