Adiabatic mode coupling between SiGe photonic devices and SOI waveguides.

We describe the coupling between optical modes of silicon-on-insulator SOI waveguides and Ge/SiGe quantum well modulators using an eigenmode expansion method. Laterally tapered features in the epitaxial layers are investigated for adiabatic optical coupling, and we find that there is a critical width range of the Ge/SiGe structure of 200-300 nm, where the taper angle should be minimised. We identify optimised taper profiles, which, for 1-µm-wide waveguides, allow the length of an adiabatic taper to be reduced from 250 µm for a simple linear profile to 40 µm for the optimised structure.

Modulation of the absorption coefficient at 1.3 µm in Ge/SiGe multiple quantum well heterostructures on silicon.

We report modulation of the absorption coefficient at 1.3 µm in Ge/SiGe multiple quantum well heterostructures on silicon via the quantum-confined Stark effect. Strain engineering was exploited to increase the direct optical bandgap in the Ge quantum wells. We grew 9 nm-thick Ge quantum wells on a relaxed Si0.22Ge0.78 buffer and a contrast in the absorption coefficient of a factor of greater than 3.2 was achieved in the spectral range 1290-1315 nm.

Terahertz ambipolar dual-wavelength quantum cascade laser.

Terahertz frequency quantum cascade lasers (THz QCLs) are compact solid-state sources of terahertz radiation that were first demonstrated in 2002. They have a broad range of potential applications ranging from gas sensing and non-destructive testing, through to security and medical imaging, with many polycrystalline compounds having distinct fingerprint spectra in the terahertz frequency range. In this article, we demonstrate an electrically-switchable dual-wavelength THz QCL which will enable spectroscopic information to be obtained within a THz QCL-based imaging system. The device uses the same active region for both emission wavelengths: in forward bias, the laser emits at 2.3 THz; in reverse bias, it emits at 4 THz. The corresponding threshold current densities are 490 A/cm(2) and 330 A/cm(2), respectively, with maximum operating temperatures of 98K and 120 K.

Skin cancers or premalignant lesions occur in half of high-dose PUVA patients.

Although treatment of psoriasis with psoralen and ultraviolet A (PUVA) is associated with a long-term risk of development of cutaneous squamous cell carcinoma (SCC), the role of PUVA alone is not established, as many patients in reported series had also received treatment with other carcinogens, such as superficial X-rays or arsenic. We have recalled and examined 54 of the 63 patients still alive who have had PUVA treatment in our department, and who have been exposed to a cumulative UVA dose greater than 2000J/cm2. None of the patients had been treated with superficial X-rays or arsenicals. Ten patients (19%) had developed SCC, and 25 (46%) had histologically atypical squamous keratoses arising at body sites similar to the carcinomas. The patients with SCC were significantly older at the start of PUVA treatment than those with keratoses alone. None of the 13% of patients without PUVA lentigines had keratoses or SCCs. These results show that high-dose PUVA treatment in the U.K., even when given alone, can frequently result in the development of SCC. Further malignancies are to be expected with continued follow-up of the patients with squamous keratoses. Absence of PUVA lentigines may be a useful indicator of a lower risk of PUVA malignancy.

Nail features in Langerhans cell histiocytosis.

We report the case of an infant who presented with isolated cutaneous manifestations of Langerhans cell histiocytosis before the evolution of systemic features. In the transition period, at 9 months of age, nail unit changes became prominent, and persisted throughout the duration of systemic treatment. A change in clinical features coincided with a course of systemic gamma-interferon, which was given because immune paresis was suspected. Nail unit changes are rare in Langerhans cell histiocytosis, and this case illustrates the range of findings, including paronychia, nail fold destruction, onycholysis with subungual expansion, and nail plate loss. The significance of these changes as a prognostic indicator is controversial.

Mutations in the COL1A2 gene of type I collagen that result in nonlethal forms of osteogenesis imperfecta.

Although virtually all mutations that result in osteogenesis imperfecta (OI) affect the genes that encode the chains of type I procollagen, the effects of mutations in the COL1A2 gene have received less attention than those in the COL1A1 gene. We have characterized mutations in 4 families that give rise to different OI phenotypes. In three families substitutions of glycine residues by cysteine in the triple helical domain (a single example at position 259 and 2 families in which substitution of glycine at 646 by cysteine) have been identified, and in the fourth a G for A transition at position +4 in intron 33 led to use of an alternative splice site and inclusion of 6 amino acids (val-gly-arg-ile-leu-phe) between residues 585 and 586 of the normal triple helix. The relation between position of substitution of glycine by cysteine in the COL1A2 gene does not follow the pattern developed in the COL1A1 gene. To determine how COL1A2 mutations produce OI phenotypes, we have produced a full-length mouse cDNA into which we plan to place mutations and examine their effects in stably transfected osteogenic cells and in transgenic animals.

Sequence analysis of a full-length cDNA for the murine pro alpha 2(I) collagen chain: comparison of the derived primary structure with human pro alpha 2(I) collagen.

Comparison of the nucleotide sequence and primary structure of murine and human pro alpha 2(I) collagen indicates a high degree of homology: 87% at the nucleotide level and 87% at the amino acid level, with the greatest degree of variability in the amino- and carboxy-pro-peptide domains. The homology is greatest in the triple helical domain, repeating [Gly-X-Y]338, exhibiting 90% homology at the amino acid level, with only X and Y position residue substitutions. The X and Y residues show 86% homology between murine and human pro alpha 2(I) collagen triple helices, with no truly nonconservative substitutions.

Distinct proliferative and differentiated stages of murine MC3T3-E1 cells in culture: an in vitro model of osteoblast development.

We examine clonal murine calvarial MC3T3-E1 cells to determine if they exhibit a developmental sequence similar to osteoblasts in bone tissue, namely, proliferation of undifferentiated osteoblast precursors followed by postmitotic expression of differentiated osteoblast phenotype. During the initial phase of developmental (days 1-9 of culture), MC3T3-E1 cells actively replicate, as evidenced by the high rates of DNA synthesis and progressive increase in cell number, but maintain a fusiform appearance, fail to express alkaline phosphatase, and do not accumulate mineralized extracellular collagenous matrix, consistent with immature osteoblasts. By day 9 the cultures display cuboidal morphology, attain confluence, and undergo growth arrest. Downregulation of replication is associated with expression of osteoblast functions, including production of alkaline phosphatase, processing of procollagens to collagens, and incremental deposition of a collagenous extracellular matrix. Mineralization of extracellular matrix, which begins approximately 16 days after culture, marks the final phase of osteoblast phenotypic development. Expression of alkaline phosphatase and mineralization is time but not density dependent. Type I collagen synthesis and collagen accumulation are uncoupled in the developing osteoblast. Although collagen synthesis and message expression peaks at day 3 in immature cells, extracellular matrix accumulation is minimal. Instead, matrix accumulates maximally after 7 days of culture as collagen biosynthesis is diminishing. Thus, extracellular matrix formation is a function of mature osteoblasts. Ascorbate and beta-glycerol phosphate are both essential for the expression of osteoblast phenotype as assessed by alkaline phosphatase and mineralization of extracellular matrix. Ascorbate does not stimulate type I collagen gene expression in MC3T3-E1 cells, but it is absolutely required for deposition of collagen in the extracellular matrix. Ascorbate also induces alkaline phosphatase activity in mature cells but not in immature cells. beta-glycerol phosphate displays synergistic actions with ascorbate to further stimulate collagen accumulation and alkaline phosphatase activity in postmitotic, differentiated osteoblast-like cells. Mineralization of mature cultures requires the presence of beta-glycerol phosphate. Thus, MC3T3-E1 cells display a time-dependent and sequential expression of osteoblast characteristics analogous to in vivo bone formation. The developmental sequence associated with MC3T3-E1 differentiation should provide a useful model to study the signals that mediate the switch between proliferation and differentiation in bone cells, as well as provide a renewable culture system to examine the molecular mechanism of osteoblast maturation and the formation of bone-like extracellular matrix.

Unilateral bullous pemphigoid in a hemiplegic patient.

A 78-year-old man with a long-standing left-sided hemiplegia presented with bullous pemphigoid which affected his paralysed side only. Although the rash was unilateral, direct immunofluorescence demonstrated IgG antibody at the dermo-epidermal junction on both sides of the body. Indirect immunofluorescence was also positive. A suction-blister test showed increased skin fragility on the affected side.

Effects of cetirizine, loratadine and terfenadine on histamine weal and flare reactions.

This randomised double-blind, placebo-controlled, cross-over study compared the effects of single oral doses of terfenadine 120 mg, cetirizine 10 mg, and loratadine 10 mg on experimentally induced weal and flare reactions. The areas of weal and flare induced by intracutaneous injections of histamine were measured using planimetry, weal thickness by A-scan pulsed ultrasound and erythema index by a device which measures the relative reflectance of red and green light. All three antihistamines suppressed the weal and flare area and weal thickness 3, 6, 12 and 24 h after dosing. At the usual currently recommended doses terfenadine and cetririzine were most effective after 6 h and were more potent than loratadine for the first 6 h of the study.

Multiple glomus cell tumours--treatment by infra-red coagulation.

This report describes the successful use of infra-red coagulation in the treatment of multiple glomus tumours. Glomus cell tumours are usually solitary and an excisional diagnostic biopsy therefore provides effective treatment. Such an approach is, however, impractical in the rarer condition of multiple glomus cell tumours where up to 400 lesions have been described in one patient. We describe a case of multiple glomus cell tumours in which more than 30 tumours were treated quickly and effectively by infra-red coagulation.

Construction of a full-length murine pro alpha 2(I) collagen cDNA by the polymerase chain reaction.

Construction of large collagen cDNA has been hindered by the relatively large size and high G-C content of processed mRNA. We describe here the development of a rapid and efficient method for obtaining large full-length collagen cDNA. A full-length (4.3 kb) murine pro alpha 2(I) collagen cDNA was constructed by synthesis of a first-strand cDNA library with use of poly-A RNA (MC3T3-E1) and the oligo-dT17-adapter primer described by Frohman et al (Proc Natl Acad Sci USA 85:8998, 1988). Pro alpha 2(I) collagen cDNA were specifically amplified by the polymerase chain reaction (PCR) with a pro alpha 2(I) specific primer as the 5' primer (20mer; corresponding to nucleotide positions 42-61 in the first exon of the murine pro alpha 2(I) collagen gene, COL1A2), and with the adapter sequence 5' to the dT17 as the 3' primer. The PCR conditions were optimized to allow amplification of the expected 4.0-5.0-kb product; a major 4.3-kb product was visualized by ethidium bromide, identified by in situ gel hybridization, and cloned. DNA sequencing determined that it contained the correct 5' sequence and the 3' end had a 68 basepair (bp) 3' untranslated region. The entire sequence that codes the amino-terminal propeptide domain has been determined and compared to the human sequence. The homology between human and mouse is less in the amino terminal propeptide than in the triple helical domain; exon 5 of murine COL1A2 codes for an additional six amino acids not found in human COL1A2.

Carcinoma erysipeloides.

We report an 83-year-old woman with carcinoma erysipeloides due to an occult carcinoma. Immunohistochemical study of skin biopsies showed reactivity to S-100 protein and human milk fat globule antigen indicating that the tumour originated in the breast.

The effects of different cysteine for glycine substitutions within alpha 2(I) chains. Evidence of distinct structural domains within the type I collagen triple helix.

Affected individuals from two apparently distinct, mild osteogenesis imperfecta families were heterozygous for a G to T transition in the COL1A2 gene that resulted in cysteine for glycine substitutions at position 646 in the alpha 2(I) chain of type I collagen. A child with a moderately severe form of osteogenesis imperfecta was heterozygous for a G to T transition that resulted in a substitution of cysteine for glycine at position 259 in the COL1A2 gene. Type I collagen molecules containing an alpha 2(I) chain with cysteine at position 259 denaturated at a lower temperature than molecules containing an alpha 2(I) chain with cysteine at position 646. In contrast to cysteine for glycine substitutions in the alpha 1(I) chain, the severity of the osteogenesis imperfecta phenotype is not directly proportional to the distance of the mutation from the amino-terminal end of the triple helix. These findings could be explained if the type I collagen triple helix contains discontinuous domains that differ in their contributions to maintaining helix stability.

Topical retinoid treatment for skin cancer: a review.

There is laboratory and clinical evidence to suggest that retinoids have a potentially important place in the management of neoplastic and preneoplastic disorders of the epidermis. Topical administration avoids the side-effects of orally administered retinoids, but doubts remain over their efficacy. Evidence from clinical studies suggests that although topical retinoids have some effect in treating established skin cancers, alternative treatments are more effective. Topical retinoids appear more effective in the treatment of solar keratoses and epidermal dysplasia in photodamaged skin.

Efficacy of topical dimetindene in experimentally induced pruritus and weal and flare reactions.

Double-blind, placebo-controlled studies were performed to assess the effect of 0.1% dimetindene gel on the itch threshold to intracutaneous histamine and on the weal and flare reaction after intracutaneous injection of histamine in normal volunteer subjects. Treatment of the forearm skin in 20 volunteers resulted in an increase in itch threshold with dimetindene gel compared to placebo. Treatment of the forearm skin with dimetindene gel in 32 volunteers had no significant effect on weal thickness in subjects treated for 10, 30 or 60 min, but there was a significant reduction in weal thickness in those subjects treated for 120 min. Topical dimetindene may be of value in treating conditions mediated through histamine release.

Investigations on the percutaneous absorption of the antidepressant rolipram in vitro and in vivo.

In vitro experiments using full-thickness human skin showed that it was feasible to deliver therapeutic amounts of the new antidepressant drug rolipram. Simple transdermal devices were constructed, and the presence of isopropyl myristate (IPM) in a silicone adhesive (Dow Corning X7-2920) enhanced the flux across excised human skin. The steady-state fluxes from adhesive mixtures containing 0, 5, and 10% IPM were 3, 5.2, and 6 micrograms/cm2/hr, respectively. The in vitro experiments were confirmed in a clinical study involving six healthy male volunteers. The formulations tested were an alcoholic solution and adhesive patches containing 5 and 10% IPM. The dose of drug administered was 0.5 mg/cm2 and the device size 25 cm2. Blood samples were withdrawn over a 24-hr period and analyzed using radioimmunoassay. The topical applications were well tolerated, with only mild or no side effects. A lag time of approximately 2 hr was found for the detection of rolipram in the plasma (detection limit, 50 pg/ml). Interindividual variations both for the peak drug levels and throughout the delivery were quite high but this magnitude of variation has been observed in many other transdermal studies. Plasma levels between 1 and 2 ng/ml were found for all formulations and the AUC0-30 hr was significantly higher for the patch containing 5% IPM.