Broadly tunable femtosecond pulses around 2.06 µm from a diode-pumped Tm3+-doped solid-state laser source.

We report on a broadly tunable diode-pumped femtosecond Tm:LuScO3 laser source around 2.06 µm. Tuning was obtained through the use of a steeply diving birefringent filter, maintaining sub-600 fs pulses over a tuning range of 2019-2110 nm. The minimum pulse duration of 240 fs was recorded at a central wavelength of 2080 nm with an average output power of 93 mW. Higher output coupling of 2% resulted in a narrower tuning range of 2070-2102 nm with generated pulses as short as 435 fs and an average output power of 119 mW at 2090 nm.

Diode-pumped femtosecond Tm3+-doped LuScO3 laser near 2.1 µm.

We report on the first demonstration, to the best of our knowledge, of a diode-pumped Tm:LuScO3 laser. Efficient and broadly tunable continuous wave operation in the 1973-2141 nm region and femtosecond mode-locking through the use of an ion-implanted InGaAsSb quantum-well-based semiconductor saturable absorber mirror are realized. When mode-locked, near-transform-limited pulses as short as 170 fs were generated at 2093 nm with an average output power of 113 mW and a pulse repetition frequency of 115.2 MHz. Tunable picosecond pulse generation was demonstrated in the 2074-2104 nm spectral range.

1.9 µm waveguide laser fabricated by ultrafast laser inscription in Tm:Lu2O3 ceramic.

The ultrafast laser inscription technique has been used to fabricate channel waveguides in Tm3+-doped Lu2O3 ceramic gain medium for the first time to our knowledge. Laser operation has been demonstrated using a monolithic microchip cavity with a continuous-wave Ti:sapphire pump source at 796 nm. The maximum output power achieved from the Tm:Lu2O3 waveguide laser was 81 mW at 1942 nm. A maximum slope efficiency of 9.5% was measured with the laser thresholds observed to be in the range of 50-200 mW of absorbed pump power. Propagation losses for this waveguide structure are calculated to be 0.7 dB⋅cm-1 ± 0.3 dB⋅cm-1 at the lasing wavelength.

Stable, continuous-wave, intracavity, optical parametric oscillator pumped by a semiconductor disk laser (VECSEL).

We report relaxation oscillation free, true continuous-wave operation of a singly-resonant, intracavity optical parametric oscillator (OPO) based upon periodically-poled, MgO-doped LiNbO3 and pumped internal to the cavity of a compact, optically-excited semiconductor disk laser (or VECSEL). The very short upper-laser-state lifetime of this laser gain medium, coupled with the enhancing effect of the high-finesse pump laser cavity in which the OPO is located, enables a low threshold, high efficiency intracavity device to be operated free of relaxation oscillations in continuous-wave mode. By optimizing for low-power operation, parametric threshold was achieved at a diode-laser power of only 1.4 W. At 8.5 W of diode-laser power, 205 mW of idler power was extracted, indicating a total down-converted power of 1.25 W, and hence a down-conversion efficiency of 83%.

High-power, (AlGaIn)(AsSb) semiconductor disk laser at 2.0 microm.

We report a high-power (AlGaIn)(AsSb) semiconductor disk laser emitting around 2 microm. With a diamond heat spreader used for thermal management, a maximum output power of just over 5 W and slope efficiencies of over 25% were demonstrated. The output wavelength was tunable over an 80 nm range centered at 1.98 microm. The beam propagation parameter (M2) was measured to be in the range of 1.1 to 1.4 for output powers up to 3 W.

Vesicle trafficking during sporozoite development in Plasmodium berghei: ultrastructural evidence for a novel trafficking mechanism.

Oocysts from Anopheles stephensi mosquitoes fed on murine blood infected with Plasmodium berghei berghei, were fixed for electron microscopy 6-12 days post-feeding. Ultrastructural analysis focused on Golgi-related trafficking pathways for rhoptry and microneme formation during sporogony. A small Golgi complex of 1-3 cisternae is formed close to the spindle pole body from coated vesicles budded from the nuclear envelope which is confluent with the endoplasmic reticulum. Rhoptries begin as small spheroidal bodies apparently formed by fusion of Golgi-derived vesicles, lengthening to 3-4 microm, and increasing in number to 4 per sporozoite. Ultrastructural data indicate the presence of a novel mechanism for vesicle transport between the Golgi complex and rhoptries along a longitudinal 30 nm - thick fibre (rootlet fibre or tigelle). Filamentous links between vesicles and rootlet indicate that this is a previously undescribed vesicle transport organelle. Genesis of micronemes occurs late in bud maturation and starts as spheroidal dense-cored vesicles (pro-micronemes), transforming to their mature bottle-like shape as they move apically. Filamentous links also occur between micronemes and subpellicular microtubules, indicating that as in merozoites, micronemes are trafficked actively along these structures.

Tunable, Single-frequency, Diode-pumped 2.3mum VECSEL.

We report high-performance single-frequency operation of a directly diode-pumped GaSb-based vertical-external-cavity surface-emitting laser (VECSEL) at 2.3mum. Tunability of 70nm and a maximum single frequency output of 0.68W is demonstrated.

Genetic control of serum IgE levels: a study of low molecular weight protein tyrosine phosphatase.

Protein tyrosine phosphatases (PTPases) have recently been recognized as important modulators of various signal transduction pathways in immune cells. Genetic polymorphisms have been described in genes codifying for members of this family of enzymes, and the genetics of PTPases is predicted to play an important role in the etiology of immune diseases and of their clinical variability. The low molecular weight protein tyrosine phosphatase (ACP1 or LMPTP) is one of the few PTPases with a known genetic polymorphism, and has been proposed to be associated with atopic dermatitis in a small sample from an Italian population. In this paper we describe the association of the ACP1 polymorphism with total IgE levels in two independent samples from English and Italian populations. In both the samples the mean value of serum IgE is lower among subjects carrying the BC genotype than in other ACP1 genotypes. The BC genotype is associated with the highest total ACP1 enzymatic activity. Our data suggest that one or both of the ACP1 isoforms exert an inhibitory role on some signal transduction pathway relevant for IgE hyperproduction.

Regression of multifocal, skin-restricted, CD30-positive large T-cell lymphoma with interferon alfa and bexarotene therapy.

We report the case of a 43-year-old male patient with persistent multifocal, skin-restricted, CD30-positive, large T-cell lymphoma. Combination therapy of systemic interferon alfa and oral bexarotene was initiated on an experimental basis in the hope of circumventing therapies such as methotrexate, radiotherapy, or multiple-agent chemotherapy that may be required in such cases. This treatment was associated with rapid and marked regression of the patient's cutaneous lesions.

Therapeutic advances in biological response modifiers in the treatment of cutaneous T-cell lymphoma.

Cutaneous T-cell lymphoma (CTCL) is most often a skin-infiltrating malignancy of clonal CD4+ T-cells. Therapy is based on staging and the likelihood of progression. Biological response modifiers and chemotherapeutic agents are used to preserve the integrity of the host antitumour response while selectively targeting the malignant cells. The biological response-modifying treatment options currently used to treat CTCL are bexarotene, denileukin diftitox, interferon-alpha, interferon-gamma and interleukin-12, as well as extracorporeal photopheresis and phototherapy. A combination therapy approach maximises response in patients with advanced CTCL. Biological response modifiers in combination with photopheresis are used for patients with the leukaemic phase of the disease. Among the majority of patients with advanced stage disease so treated, immune response augmentation appears to prolong survival. Future areas of research should assess not only survival and optimal treatment combinations, but also quality of life during the treatment period.

Generation of azines by the reaction of a nucleophilic carbene with diazoalkanes: a synthetic and crystallographic study.

Reactions of the nucleophilic carbene 1,3-dimesityl-imidazol-2-ylidene (1) with diazofluorene, diphenyldiazomethane, and azidotrimethylsilane were examined. Specifically, carbene 1 reacts with diazofluorene and diphenyldiazomethane to give addition products (azines: 3 and 4, respectively). Compounds 3 and 4 were further characterized in the solid-state by single-crystal X-ray crystallographic studies. [3 (a = 9.7936(6) A, b = 10.0529(7) A, c = 16.251(1) A, alpha = 75.765(1) degrees, beta = 79.711(1) degrees, gamma = 64.321(1) degrees, Z = 2, space group P1); 4 (a = 11.681(3) A, b = 11.861(4) A, c = 21.186(3) A, alpha = 90 degrees, beta = 97.05(2) degrees, gamma = 90 degrees, Z = 4, space group P2(1)/n)]. The structural parameters of 3 and 4 are discussed with reference to previously characterized symmetrical and unsymmetrical azines. Structural data suggest that charge separation is possible in 3.

Ultrastructure of rhoptry development in Plasmodium falciparum erythrocytic schizonts.

Prior to the separation of merozoites from the Plasmodium falciparum schizont, various stage-specific organelles are synthesized and assembled within each merozoite bud. The apical ends of the merozoites are initiated close to the ends of endomitotic spindles. At each of these sites, the nuclear membrane forms coated vesicles, and a single discoidal or cup-like Golgi cisterna appears. Reconstruction from serial sections indicates that this structure receives vesicles from the nuclear envelope and in turn gives off coated vesicles to generate the apical secretory organelles. Rhoptries first form as spheroidal structures and grow by progressive fusion of small vesicles around their margins. As each rhoptry develops, 2 distinctive regions separate within it, an apical reticular zone with electron-lucent areas separated by cords of granular material, and a more homogenously granular basal region. The apical part elongates into the duct, with evidence for further vesicular fusion at the duct apex. The rounded rhoptry base becomes progressively more densely packed to form a spheroidal mass, and compaction also occurs in the duct. Typically, one rhoptry matures before the other. Cryofractured rhoptry membranes show asymmetry in the sizes and numbers of intramembranous particles at the internally- and externally-directed fracture faces.

Neutrophilic dermatosis of the dorsal hands: pustular vasculitis revisited.

An entity termed "pustular vasculitis of the hands" was recently described. Patients with this condition presented with low-grade fevers and erythematous plaques, pustules, and bullae limited to the dorsal hands and fingers, which were characterized histologically by a dense neutrophilic infiltrate and leukocytoclastic vasculitis. We describe patients with a similar clinical presentation, but who lacked vasculitis on biopsy findings. We describe 3 otherwise asymptomatic patients with hemorrhagic bullae, plaques, and pustules solely on the dorsal hands. Biopsy specimens showed a neutrophilic infiltrate and leukocytoclasis, but no necrotizing vasculitis, and were reminiscent of Sweet's neutrophilic dermatoses. In our patients, corticosteroids or dapsone led to clearing of the lesions, and small maintenance doses of dapsone prevented their recurrence. Our 3 patients had clinical lesions similar to those termed pustular vasculitis of the hands, but which lacked leukocytoclastic vasculitis on biopsy findings. Because of histologic findings and a therapeutic response more characteristic of Sweet's syndrome, we propose the term neutrophilic dermatosis of the dorsal hands. In addition, low-dose dapsone is proposed as a possible first-line therapy in this condition, especially in those with recurrent disease.

A brief illustrated guide to the ultrastructure of Plasmodium falciparum asexual blood stages.

Interpretation of the new information arising from the Plasmodium falciparum Genome Project requires a good working knowledge of the ultrastructure of the parasite; however many aspects of the morphology of this species remain obscure. Lawrence Bannister, John Hopkins and colleagues here give an illustrated overview of the three-dimensional (3-D) organization of the merozoite, ring, trophozoite and schizont stages of the parasite, based on available data that include 3-D reconstruc-tion from serial electron microscope sections. The review describes the chief organelles present in these stages, emphasizing the continuity of structure in addition to specialized, stage-specific features developed during the asexual erythrocytic cycle.

Photopheresis: clinical applications and mechanism of action.

Photopheresis is a leukapheresis-based therapy that utilizes 8-methoxypsoralen and ultraviolet A irradiation. Photopheresis is currently available at approximately 150 medical centers worldwide. Recent evidence suggests that this therapy used as a single agent may significantly prolong life, as well as induce a 50%-75% response rate among individuals with advanced cutaneous T cell lymphoma (CTCL). Furthermore, a 20%-25% complete response rate with photopheresis alone, or in combination with other biologic response modifiers, has been obtained at our institution among patients with Sezary syndrome. These complete responses have been characterized by the complete disappearance of morphologically atypical cells from the skin and blood. The use of sensitive molecular techniques has also confirmed the sustained disappearance of the malignant T cell clone from the blood of patients with complete responses. In addition to the treatment of CTCL, numerous reports indicate that photopheresis is a potent agent in the therapy of acute allograft rejection among cardiac, lung, and renal transplant recipients. Chronic graft versus host disease also appears to be quite responsive to photopheresis therapy. Likewise, there may also be a potential role for photopheresis in the therapy of certain autoimmune diseases that are poorly responsive to conventional therapy. The immunologic basis for the responses of patients with these conditions is likely due to the induction of anticlonotypic immunity directed against pathogenic clones of T lymphocytes. Treatment-induced apoptotic death of pathogenic T cells and activation of antigen presenting cells are postulated to have important effects in this therapeutic process.

Desmoplastic fibroblastoma.

Previous reports of a distinctive, fibrous, soft-tissue tumor include eight patients with subcutaneous lesions and six patients with intramuscular lesions. We report a 48-year-old woman with a 2-cm cutaneous and subcutaneous nodule on the left arm with the same histologic features. An excisional biopsy showed a large, well circumscribed tumor replacing the reticular dermis and subcutaneous tissue. The tumor was relatively hypocellular and composed primarily of large, spindled, plump or stellate fibroblasts haphazardly dissecting between thickened fibrotic collagen bundles. The stroma contained a large amount of mucin which was positive with alcian blue at pH 2.5, and relatively numerous mast cells were present. The fibroblastic-like cells were positive with Vimentin and Factor XIIIA and negative with S-100, desmin, actin and keratin.

The cone synapses of cone bipolar cells of primate retina.

One each of bipolar cell types DB2 and DB4, together with a flat and an invaginating midget bipolar cell, were taken from a Golgi-stained rhesus macaque retina; then serially sectioned for EM examination of their synapses with cone pedicles. The cone input to the dendrites of the DB2 cell was exclusively at basal junctions; it had a characteristic distribution. Fifty per cent of the basal synapses were with cone pedicle membrane immediately adjacent to the dendrite of a bipolar cell invaginating to end opposite the ribbon of a cone triad (this, therefore, is called triad-associated). The remainder were one or more synapses distant from the triad-associated position (and, therefore, non-triad associated). The DB4 cell had both basal (predominantly in the triad-associated position) and ribbon-related synaptic input. But the basal to invaginating ratio differed from that of our previously published cell; 56% basal, 43% invaginating, as compared with 31% basal and 69% invaginating. Like foveal IMB cells the synapses of the mid-peripheral invaginating midget bipolar cell were exclusively invaginating; but were about 25% more numerous. The flat midget bipolar cell made exclusively basal synapses. These were 2.5 times more numerous than those of foveal flat midget bipolar cells, and 3.5 times the number of invaginating midget bipolar synapses at equivalent eccentricity. The synapses between cones and diffuse and midget bipolar cells are characteristic for each particular bipolar cell type, but the details depend on a cell's distance from the fovea (eccentricity). A rather constant number of cone pedicle synaptic ribbons 38.6 +/- 2.5 (n = 60) was found across mid-peripheral macaque and vervet monkey retinae. The smaller mean number for vervet monkey, 27.4 +/- 3.5 (n = 23), suggests there can also be generic differences in synaptic detail at cone bipolar cell synapses.

Ultralow-pump-threshold, femtosecond Cr(3+):LiSrAlF(6)laser pumped by a single narrow-stripe AlGaInP laser diode.

We report what we believe to be the first demonstration of a Kerr-lens mode-locked Cr(3+):LiSrAlF(6)laser that is pumped by a single narrow-stripe AlGaInP laser diode with a diffraction-limited output beam. A novel low-loss three-mirror laser cavity design is described in which strong, localized Kerr lensing was exploited such that 75-fs-duration pulses were obtained for only 36mW of incident pump power. This pump power was maintained for 18h by just three AA batteries as the electrical power source. We have shown that mode locking can be sustained for pump powers as low as 22mW.