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Object The fold plication method is a new operative procedure for lung volume reduction surgery whereby the target area is obliterated by plicating the folded tissue using a knifeless stapler, without the use of bovine pericardium. The effectiveness of this new method was evaluated in patients with advanced pulmonary emphysema. Patients and Methods Two weeks before and 6 months after surgery, pulmonary function, static lung compliance, maximal esophageal pressure, maximal inspiratory and expiratory mouth pressures, 6-min walking distance and the Borg scale were determined in twenty consecutive patients who underwent video-assisted thoracoscopic unilateral surgery. Results There was an increase in forced expiratory volume in one second (31%), forced vital capacity, peak expiratory flow rate and maximal voluntary ventilation, and a decrease in functional residual capacity (-16%) measured by plethysmograph. Static lung compliance decreased, and maximal esophageal pressure, and maximal inspiratory and expiratory mouth pressures increased. The 6-min walking distance increased (20%) and the Borg scale decreased (5.9 to 3.5). Conclusion The results compare favorably with those obtained with other methods. Thus, the fold plication method could be considered an alternative procedure for lung volume reduction surgery.(Internal Medicine 39: 381-384, 2000)

T cell migration into tumor masses is a critical process in the scenario of IL-12-induced tumor regression. Our previous study showed that this depends on the development of peritumoral stroma prior to IL-12 therapy. The present study investigated the regulation of the development of peritumoral stroma in comparison with tumor-parenchymal stroma. In the OV-HM and CSA1M tumor models, tumor regression associated with T cell migration was induced following IL-12 treatment. Both OV-HM and CSA1M tumor masses growing in syngeneic mice developed peritumoral stroma before IL-12 treatment. However, peritumoral stroma was not observed in these two types of tumor masses generated in nude mice, T cell-depleted syngeneic mice, anti-IFN-gamma mAb-treated mice or IFN-gamma-deficient mice. In contrast, parenchymal stroma formation did not appear to be affected because tumors generated in these groups of mice exhibited rather higher growth rates than those of tumors in normal syngeneic mice. Importantly, the lack of peritumoral stroma in tumor masses was associated with the failure of T cells to migrate to these tumor masses: splenic T cells prepared from IL-12-treated tumor-bearing mice migrated into the corresponding tumor mass growing in untreated syngeneic recipient mice, whereas portions of the same donor cells failed to migrate into the above stroma-negative tumor masses. These results indicate that the development of peritumoral and parenchymal stroma is differentially regulated; there exist functional differences in the two types of stroma; and the formation of peritumoral stroma requires components of the host's immune system such as IFN-gamma and T cells.

Treatment of 2-methylene-1,3-dithiane 1-oxide with aryl iodides under palladium catalysis in the presence of potassium carbonate and tetrabutylammonium bromide leads to the Mizoroki–Heck arylation ...

Mushroom bodies (MBs), which are higher centers in the insect brain, are implicated in associative memory and in the control of some behaviors. Intrinsic neurons of the MB, called Kenyon cells, receive synaptic inputs from axon terminals of input neurons in the calyx. Axons of Kenyon cells project into the pedunculus and to the alpha and beta lobes, where they make synaptic connections with dendrites of extrinsic (output) neurons. In this study, we examined the morphology of Kenyon cells in the cockroach by using Golgi stains and found that they can be classified into four classes (K1, K2, K3, and K4), according to the diameter, location, and morphology of the cell bodies, dendrites, and axons. The somata of Kenyon cells of different classes occupy different concentric zones; K1 cells occupy the most central zone, and K4 cells occupy the most peripheral zone. The main processes of Kenyon cells of different classes also occupy different concentric zones in the calyx. Dendrites of K2 and K3 cells are distributed throughout the calycal neuropil, whereas those of K1 and K4 cells cover the outer and inner halves of the depth of the neuropil, respectively. In the pedunculus and the alpha and beta lobes, axons of Kenyon cells of different classes occupy different zones, although the separation is not complete. A class of extrinsic neurons in the a lobe has dendrite-like arbors that cover the zones where either K1, K2, or K3 are located. These neurons probably transmit signals of each class of Kenyon cells. We conclude that, in the cockroach, four classes of Kenyon cells subdivide the cell body region, pedunculus, and lobes of the MBs, whereas subdivision is less prominent in the calycal neuropil.

The mushroom body (MB), a conspicuous neuropil structure in the insect brain, is implicated in associative memory and in some aspects of motor control. Intrinsic neurons of the MB (Kenyon cells) extend dendrites into the calyx, and their axons run through the pedunculus and then bifurcate to form the alpha and the beta lobes. At the pedunculus and the lobes, Kenyon cells make synaptic connections with dendrites of extrinsic (output) neurons. Previously, we reported that the alpha lobe of the cockroach MB consists of repetitive modular subunits (Mizunami et al. [1997] Neurosci. Lett. 229:153-156). Each subunit is composed of a dark layer and a light layer, and the layers are refereed to as slabs. Each slab is composed of axons of a specific subset of Kenyon cells. In the present study, we examined serial sections of reduced silver preparations and found that each dark and light slab continues throughout the length of the pedunculus and the alpha and beta lobes. We also found that Golgi-impregnated Kenyon cells often exhibit a characteristic grouping, forming a thin sheet interlaced by dozens or hundreds of axons. The sheet is much thinner than the slab, and each sheet remains within a particular slab throughout the length of the pedunculus and the lobes. Thus, the sheet is a component forming the slab. In the pedunculus and the beta lobe, a class of Golgi-impregnated extrinsic neurons exhibit segmented dendritelike arbors that interact with every other slab, i.e., either with only dark or light slabs. Because each neuron of this class interacts with each particular set of dark or light slabs, we conclude that the slabs are units for transmitting output signals from the MB.

Background. Continuing to refine minimally invasive thoracoscopic surgical procedures, we have established the two-windows method. Methods. Skin incisions required by this method consist of a 2- to 3-cm skin incision posteriorly, and a 2- to 3-cm skin incision anteriorly in the fourth intercostal space, with the inferior angle of the scapula as the midpoint. We used this method to perform pulmonary lobectomies in combination with thoracoscopy and mediastinal lymph node dissection in 100 consecutive patients with lung cancer (preoperative diagnosis, stage I, T1 N0 M0). Results. The mean operative time was 2 hours 46 minutes, the mean blood loss was 68.2 mL, and the mean number of mediastinal lymph nodes dissected was 24.3. In developing this minimally invasive thoracoscopic procedure, which facilitates mediastinal lymph node dissection, we realized that it is best performed through the fourth intercostal space. Because the tracheal bifurcation can be seen directly below this level, surgical manipulation in this area can be easily performed. This enables the same extent of mediastinal lymph node dissection as that performed during a standard thoracotomy. Another advantage of this method is that a standard posterolateral thoracotomy incision can be made whenever necessary by simply connecting the two incisions. Conclusions. We believe that the two-windows method is capable of serving as the standard method for the surgical treatment of stage I lung cancer.

There is a critical need for new agents with novel therapeutic targets and improved safety profiles in high-risk acute lymphoblastic leukemia (ALL), which is a significant cause of morbidity and mortality in pediatric and adult populations. Phenotypic high-throughput chemical screens allow for discovery of small molecules that modulate complex phenotypes and provide lead compounds for novel therapies; however, identification of their mechanistically relevant targets remains a major experimental challenge. We applied a chemical genetics approach involving sequential unbiased high-throughput chemical and ultra-complex, genome-scale shRNA screens to address this challenge and identify novel agents in ALL. A cell-based phenotypic high-throughput chemical screen of 115,000 compounds identified 640 compounds that inhibited growth of one or both ALL cell lines with high-risk Mixed Lineage Leukemia (MLL) genetic abnormalities, but did not inhibit the growth of a cell line lacking MLL rearrangement. The most potent and selective 64 were tested on an expanded panel of eight human B-ALL cell lines to identify lead compound STF-118804. STF-118804 inhibited the growth of most B-ALL cell lines with high potency demonstrating IC50 values in the low nanomolar range. Leukemic samples from five pediatric ALL patients were also sensitive to STF-118804 in the low nanomolar range. STF-118804 displayed 5–10 fold more potency against most leukemias in comparison to cycling human (lineage-negative cord blood) and murine (c-kit+ bone marrow) progenitor cells, demonstrating a therapeutic index. STF-118804 displays distinctive cytotoxicity by inducing apoptosis without causing a phase-specific cell cycle arrest. To discover the molecular target of STF-118804, a functional genomic screen was performed to identify shRNAs that conferred sensitivity or resistance to STF-118804, utilizing an ultra-complex (∼25 shRNAs per gene) library targeting in total ∼9300 human genes and 1000s of negative control shRNAs. NAMPT was the most statistically significant gene to confer sensitivity to STF-118804, suggesting that STF-118804 functioned as a NAMPT inhibitor. NAMPT encodes nicotinamide phosphoribosyl transferase, a rate-limiting enzyme in the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a crucial cofactor in many biochemical processes. STF-118804 was confirmed as a novel class of NAMPT inhibitor through metabolic rescue, enzymatic, and genetic studies. STF-118804 displayed strong inhibitory activity in in vitro NAMPT enzymatic assays. Over-expression of wild-type or mutant NAMPT in cells indicated that STF-118804 cytotoxicity is a result of its ability to inhibit NAMPT, and that STF-118804 does not have significant off-target effects on cell viability. The potential efficacy of STF-118804 in vivo was assessed in an orthotopic xenograft model of ALL. Sublethally irradiated immunodeficient mice were transplanted with human ALL cells engineered to constitutively express firefly luciferase. Dosing of STF-118804 was initiated two weeks post-transplant when ALL cells had engrafted and bioluminescent signal was detectable. Mice treated with STF-118804 showed regression of leukemia by bioimaging and significantly extended survival. The leukemia initiating cell (LIC) frequency in STF-118804 treated mice was significantly lower (∼8 fold) than vehicle treated mice, showing that STF-118804 was effective in reducing LICs. In summary, tandem high-throughput screening identified a highly-specific, potent, and structurally novel small molecule inhibitor of NAMPT that is active in ALL. Tandem high throughput screening using chemical and ultra-complex shRNA libraries provides a rapid chemical genetics approach for seamless progression from small molecule lead identification to target discovery and validation. Disclosures: No relevant conflicts of interest to declare.

Resection of a second primary lung carcinoma in a long-term survivor of small cell lung carcinoma is reported. The patient had adenocarcinoma as the second primary tumor and underwent lobectomy with mediastinal node dissection. He was alive 99 months after the initial diagnosis of small cell carcinoma and 54 months after curative pulmonary resection for his second primary carcinoma.

Intratracheal bleeding and intrapleural air leakage that are uncontrollable by conventional therapy are life-threatening in patients with blunt pulmonary trauma. Selective exclusion of the injured lung is the most effective treatment in such cases. Two hundred six consecutive patients over a 5-year period with blunt pulmonary trauma who survived 5 hours or more after arriving at the hospital were divided into three categories based on mode of treatment. In 190 (92%), intratracheal bleeding, intrapleural air leakage, and intrapleural bleeding were controllable by conventional treatment (class 1). In six (3%), intratracheal bleeding and intrapleural air leakage were controllable by selective pulmonary exclusion, and intrapleural bleeding was controllable by tube thoracostomy (class 2). In ten (5%), thoracotomy was required because of uncontrollable intratracheal bleeding or intrapleural air leakage, despite selective pulmonary exclusion, or intrapleural hemorrhage was not controllable by tube thoracostomy (class 3). Among the 16 patients with class 2 or 3 trauma, 14 survived.

The interphotoreceptor matrix (IPM) in mammalian retinas is subdivided into rod and cone specific compartments: peanut agglutinin (PNA) binding glycoconjugates are associated with cones, whereas wheat germ agglutinin (WGA) binding glycoconjugates are associated with rods. To establish the identity of a photoreceptor cell type in the human retina with rod dimensions but with a matrix domain which stains with PNA, double label studies, using PNA-ferritin to decorate the extracellular domains and immunocytochemical techniques using a rod specific anti-opsin antibody were conducted. The PNA-binding domains were observed in the cone-associated IPM as well as in the IPM surrounding a small population of rod-shaped photoreceptors. The outer segments of these rod-shaped photoreceptors showed intense labeling with a rod specific anti-opsin antibody as did all other rods which were free of PNA-labeling. A quantitative analysis of all retinal quadrants indicates that this novel rod represents approximately 0.3% of the total rod population in the human retina. © 1992 Wiley-Liss, Inc.

The critical molecular determinants for leukemia stem cell (LSC) generation and maintenance are largely unknown. While the majority of studies focus on investigating key transcription factors and cytokines involved in hematological malignancies, very little is known about the roles of recently discovered microRNAs in leukemogenesis. Bioinformatic analysis of the Mouse Retroviral Tagged Cancer Gene Database (Neal Copeland et al.) revealed the 5′ regulatory region of the miR-142 gene as a recurrent target for retroviral integrations in a variety of mouse leukemia and lymphoma cancer models, including MLL-induced leukemia, thereby implicating miR-142 as a potential collaborating oncomir in hematologic malignancies. Subsequent expression analyses of differentially expressed microRNAs in LSC-enriched cell fractions (c-kit+) from MLL leukemias in comparison with various stages of normal hematopoietic progenitors indicated that the miR-17-5p family of microRNAs is highly expressed in LSC-enriched fractions and their possible normal counterparts, granulocyte-macrophage progenitors. Moreover, the expression of miR-142 and miR-17-5p family microRNAs was substantially reduced upon differentiation and loss of self-renewal in cells transformed by the conditional MLL-ENL-ER oncogene following withdrawal of tamoxifen. Forced expression of the miR-17-19b polycistron or miR-142 substantially shortened the latency for MLL leukemia development. In particular, leukemias expressing high levels of the miR-17-19b polycistron displayed a higher frequency of LSCs due to an efficient block of differentiation and enhanced proliferation associated with reduced expression of p21, a cyclin dependent kinase inhibitor previously implicated as a direct target of miR-17-19b microRNAs. Knock down of p21 in MLL oncogene transduced cells recapitulates the MLL-leukemic phenotype induced by over-expression of the miR-17-19b cluster including a significant decrease in MLL leukemia latency. This observation validates p21 as a biologically relevant in vivo target of the miR-17-19b polycistron in MLL leukemia. Thus, microRNAs are pathogenically important for quantitatively modulating the self-renewing LSC compartment in a murine model of MLL leukemia. Potential requirements of the miR-17-19b microRNA cluster for induction and/or maintenance of MLL leukemia are currently under study.

To investigate metabolic differences between the central and peripheral cornea the latter including the limbal area, corneas were dissected and examined using phosphorus-31 (31P) nuclear magnetic resonance spectroscopy. Since most 31P signals originate from the epithelium, 31P spectra of the cornea primarily represent the metabolic state of the epithelium. The spectra of the peripheral cornea showed all phosphorus resonances detected in the whole cornea; in contrast, the central cornea showed no phosphocreatine and glycerophosrylethanolamine, and only low levels of ATP. These results indicate that there is a higher metabolic activity in the peripheral epithelium, especially in the limbal area, than in the central epithelium. To evaluate the metabolic state of corneal epithelium during regeneration, we also examined corneas reepithelializing after 7 mm of central epithelial tissue had been removed by mechanical scraping. Rabbits were killed 24 and 48 h after scraping. The reepithelializing corneas clearly showed an increase in ATP, phosphocreatine, and sugar phosphates with time, although phosphorylcholine remained depressed. These findings suggest that the reepithelializing cornea has an elevated level of energy production and that it may have reached a higher steady state, thereby indicating accelerated metabolism of the epithelium during regeneration.

The RUNX1/AML1 gene is essential for hematopoiesis and is most frequently involved in human leukemias. Loss-of-function of RUNX1 is the common underlying mechanism of RUNX leukemias: those carrying t(8;21), inv(16) and RUNX1 point mutations. As the weakest mode, haploinsufficiency of RUNX1/AML1 causes familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML). Mice heterozygous for Runx1 null mutation, Runx1+/−, appear genetically equivalent to human FPD/AML patients, but showed no apparent defects and did not develop spontaneous leukemia, implying that additional genetic alterations are required for leukemia. To identify such abnormalities, retroviral insertional mutagenesis was employed by using BXH2 mice that have spontaneously transmittable ecotropic retrovirus. BXH2-Runx1+/− mice showed a shorter disease latency and more myeloid-specific phenotype than wild-type littermates. Therefore, BXH2-Runx1+/− mice appear to serve as the mouse model for FPD/AML to investigate myeloid leukemia. The genes selectively affected in BXH2-Runx1+/− mice by retroviral integration are likely to cooperate with Runx1+/−. c-Kit locus was involved twice in 24 BXH2-Runx1+/− but neither in 17 wild-type littermates nor in 135 inbred BXH2 mice reported in the RTCGD database, suggesting that c-KIT mutation cooperates with RUNX alteration in human leukemia. In fact, constitutively active mutants of c-KIT or functionally equivalent FLT3, were found in 10 out of 25 (40%) of human RUNX leukemias. Together, BXH2-Runx1+/− system appears useful to identify the genes cooperating with RUNX1 abnormalities.

The chemokine receptor CXCR3 has been shown to play a key role in the recruitment of T cells to sites of inflammation such as allografts. Here, we investigated which signals and conditions areresponsible for CXCR3 induction. CXCR3 was induced on T cells that were stimulated with anti-CD3 plus anti-CD28 monoclonal antibodies and then recultured without any external stimuli. CXCR3 expression was inhibited when TCR stimulation was persistent in the reculture. CXCR3 induction also depended on the stimulation with IFN-gamma because CXCR3 expression was not induced in IFN-gamma-deficient T cells. The induction of another Th1 chemokine receptor CCR5 absolutely required IL-12 stimulation and STAT4 involvement. In contrast, CXCR3 was induced on STAT4-deficient T cells independently of IL-12 stimulation as long as IFN-gamma was produced as a result of potent TCR stimulation. These results show that CXCR3 induction on TCR-triggered T cells requires the release of these T cells from persistent TCR signaling and the stimulation with IFN-gamma and also indicate the differential regulatory mechanisms underlying the induction of two Th1 chemokine receptors.

We have studied the next-generation digital versatile disk (DVD) using a blue laser and investigated the application of a liquid crystal (LC) panel to the high-density disk. The LC panel can easily shift the optical path length of light beams making it possible to cancel out wavefront aberrations. First, the authors applied an LC panel to a tilt servo system. Compared with a mechanical tilt servo system, the LC tilt servo is expected to be more compact and reliable. We also developed a system for sensing the amount of disk tilt by comparing the signal levels of crosstalk from adjacent tracks. Consequently a tilt servo without any extra sensors was achieved. Another application of the LC panel is for the compensation of spherical aberrations. It was confirmed, by simulations and experiments, that the LC panel was practically useful for correcting disk thickness error which has been determined to become more serious when a blue laser was used.

The ocellar receptor and neuropil in the dorsal ocellar system of the cockroach and the lateral ocellar system of the swallowtail butterfly larva have been compared. In the dorsal ocellus of the cockroach more than 10,000 retinular cells each with a rhabdomere are piled up one upon another without a specific pattern in the ocellar capsule. Retinular axons synapse exclusively with branches of four thick second order neurons in the lower region of the capsule. Dark granule-containing neurons, originating in the brain, also synapse with the second order neurons in the ocellar neuropil. The ocellar nerve is comprised of four thick second order processes (ca. 6-16 micron) and 20-40 thin processes (ca. 1-5 micron), which include retinular axons, collaterals of thick processes, possible third order processes and unidentified processes. Synapses occur against these processes in the ocellar nerve and in the extreme proximal region of the ocellar neuropil. Six lateral ocelli occur on both sides of head in the butterfly larva. Each ocellus contains seven retinular cells, which are grouped into three distal cells and four proximal cells, or four distal cells, two peripheral cells and one central cell by the position of their rhabdomeres. Retinular axons extend to the brain, and enter the distal optic neuropil. There are six neuropils, each of which contains the seven axons from one ocellus and a dozen or so second order processes. Of seven retinular axons, four occur peripherally and the remaining three occur centrally in the neuropil. All axons synapse with fine branches of interneurons. Second order processes together with at least three central retinular axons extend to the second optic neuropil, but the peripheral axons could not be followed there. The highly organized receptors and the neuropil in the lateral ocellar system suggest a complexly integrated function. An ocellar nerve and proximal ocellar neuropil appear like an extension of the CNS, and direct connections of retinular axons with interneurons in the CNS appear characteristic of the dorsal ocellus. This difference may be related to the distribution of the two ocellar systems: the dorsal ocelli co-exist with the compound eyes of the adult, whereas the lateral ocelli are the only photoreceptor organs of the larval insect.

Retinal sheathed vessels from five patients with various vascular diseases were examined by light and electron microscopy. All of these vessels were characterized by a marked increase and disarrangement of collagen fibrils in the media and adventitia. Cytoplasmic processes of glial cells had invaded the adventitia in sheathed vessels and even in unsheathed ones. Thickening and multilamination of the basal laminae were observed in both the sheathed and unsheathed vessels. The lumens of most sheathed vessels were still patent, and the blood cells and endothelial cells of these vessels appeared to be intact. We found no essential differences in the ultrastructure of these vessels in the five patients with various vascular diseases. It is concluded that the increase and disarrangement of collagen fibrils may be mainly related to the ophthalmoscopic appearance of the sheathing and that other factors seem to be of lesser significance.

A multicolor projection display with a bright screen and high information content using nematic-cholesteric (NC) liquid crystals is discussed. Through investigation of light scattering in the focal-conic state of the NC liquid-crystal layer, it was found that the transmittance depends on the light wavelength due to diffraction scattering and that the color of light transmitted through the layer can be controlled by the birefringence and the thickness of the liquid-crystal layer. A 640*400 pixel multicolor projection display was fabricated using a two-layered liquid-crystal panel, each layer passing green and red light under the focal-conic state. The Munsell chroma value was six for both the projected colors. The projector provides excellent white and black because of the high transmittance of the nematic state and the subtractive mixture of complementary colors. >

The retinular axons from the lateral ocelli have been examined in the brain of the larva of the swallowtail butterfly, Papilio xuthus . The ocellar nerve, which joins the anteroventral part of the brain, is comprised of 42 axons originating from the six ocelli. In the brain these axons are divided into six bundles, each corresponding to one ocellus. The six bundles travel dorsally for 150–200 μ m along the surface of the brain, and then turn inward to enter their respective neuropils. Each neuropil is divided into a distal neuropil and a proximal neuropil, connected by a narrow intermediate region. Of seven retinular axons three occur centrally in the distal neuropil and extend to the proximal neuropil. The central retinular axons synapse with fine processes in both distal and proximal neuropils. Reciprocal synapses between axons are also observed. The remaining four axons occur peripherally in the distal neuropil, where they appear swollen and project many branches centrally. The branches synapse extensively with surrounding processes. These peripheral retinular axons could not be followed into the proximal neuropil. Several second-order processes (greater than 1 μ m in thickness) are observed together with three retinular axons in the intermediate region. Only the thickest process can be followed in the distal neuropil, where it branches extensively. These results are discussed in relation to the regular retinular pattern of the ocellus and in comparison with the optic neuropils of the insect compound eye.

小児のaganglionosisいわゆるHirschsprung病は有名であるが,成人においてはganglion cellの異常を問題とした報告は非常にまれである. 8年前から強い腹部膨満,頑固な便秘,便臭のある嘔吐を訴える55才の女性で全小腸の巨大な拡張を認めた.この原因追求のため大腸平滑筋々電図を施行しHirschsprung病に類似した筋電図を得,腸生検により回腸のganglion cell数はほぼ正常であるが,大腸では約1/4に減少している所見をえた.以上より本症例は大腸のganglion cellの減少が病因として一義的意味を有し, oligoganglionosisとでもいうべき疾患であると考えた.

SummaryLeukemia stem cells (LSCs) are thought to share several properties with hematopoietic stem cells (HSCs), including cell-cycle quiescence and a capacity for self-renewal. These features are hypothesized to underlie leukemic initiation, progression, and relapse, and they also complicate efforts to eradicate leukemia through therapeutic targeting of LSCs without adverse effects on HSCs. Here, we show that acute myeloid leukemias (AMLs) with genomic rearrangements of the MLL gene contain a non-quiescent LSC population. Although human CD34+CD38− LSCs are generally highly quiescent, the C-type lectin CD93 is expressed on a subset of actively cycling, non-quiescent AML cells enriched for LSC activity. CD93 expression is functionally required for engraftment of primary human AML LSCs and leukemogenesis, and it regulates LSC self-renewal predominantly by silencing CDKN2B, a major tumor suppressor in AML. Thus, CD93 expression identifies a predominantly cycling, non-quiescent leukemia-initiating cell population in MLL-rearranged AML, providing opportunities for selective targeting and eradication of LSCs.

We have experienced a rare and interesting case of Hemothorax occurring von Recklinghauen diease, in which emergency hemothorax operation was uccesfully performed, though the caue of bleeding is obscure. The patient is a housewife, 31 years old, who had been diagnosed as having von Recklinghausen disease while she was a high school student. She contracted abrupt back pain and dyspnea when she attempted to air the bedding, but without any contuion of the breast, and was hospitalized in our clinic. The patient was in shock on admission. An emergency operation wa conducted, because chest X-ray examination showed that the right thorax was totally filled up with blood and there was a massive outflow of blood through thoracic drainage. The riht thorax was opened by a standard thoracotomy. We found that the 10th intercostal artery and venous were ruptured, and at the same time the 10th and 11th intercostal spaces were expanded, here bleeding occurred froma venous engorged like a sinus or a hemangioma. We successfully achieved hemostasis by ligating the 10th intercostal arterya nd venous and by packing the expanded intercostal space with oxycel. At present, 5 months after surgery, no abnormality is observed.

The participation of T lymphocytes in the immunopathogenesis of corneal opacity in herpetic stromal keratitis was investigated. In BALB/c mice infected intracorneally with herpes simplex virus type 1, corneal opacity was manifested 10 days after infection, while in athymic mice corneas remained almost clear. Histologically, all opaque corneas revealed stromal edema accompanied by the diffuse presence of polymorphonuclear cells and lymphocytes. When complement (C')-treated immune spleen cells were adoptively transferred into athymic mice 6 or 72 h after corneal infection, stromal keratitis with mild opacity was observed 10 days after transfer. The athymic mice given anti-Thy 1.2+C'-treated immune spleen cells failed to develop corneal opacity. The difference, as revealed by light and electron microscopy, was the presence or absence of lymphocytic infiltration and edema in the posterior third layers of the stroma and endothelial lesions. The endothelium was infiltrated by lymphocytes or macrophages and showed various stages of destruction. The main cause of corneal opacity in the early stage of herpetic stromal keratitis is thought to be stromal edema due to an adverse effect on the endothelium by immune T lymphocytes.

An electrically writable bistable liquid crystal projection display has been developed. This projection display uses the bistable effect of nematic-cholesteric liquid crystal phase transition under an electric field. The nematic-cholesteric liquid crystal has some advantages in application for a projection display. These are a bright screen with no need for polarizers, a high information content, thanks to the bistable memory effect, a compact system written by only electric field, and a low cost projection system using a simple matrix panel. The newly developed liquid crystal projector has 640x400 pixels, and has good contrast under the bright ambient light of a normal office environment. It takes 1.6 seconds to write all the pixels and 100 milliseconds to type in a 16x16-dot letter. It operates satisfactorily between 5 to 45 T. Use of the nematic-cholesteric liquid crystal results in the total size of the projection system to that of a portable overhead projector. Writing by an electric field makes it quite easy to connect with floppy disk systems, key boards and communication equipment systems.

Newcastel disease (ND) occurred among flocks of racing pigeons in Japan from 1983 to 1984. Diseased pigeons exhibited nervous symptoms and diarrhea with a 13% of mortality rate. Thirty-three of the affected pigeons from 9 flocks were subjected to pathological examination. No characteristic gross changes were observed. In 15 of the 33 pigeons including 10 birds (group 1) from which ND viruses (NDV) were isolated and 5 affected birds (group 2) which had no hemagglutination-inhibition (HI) antibodies and in which no attempt was made to isolate NDV, the main histopathological changes consisted of necrosis or atrophy of the lymphoid tissue in the spleen as well as in the bursa of Fabricius and thymus, splenitis, nephritis, and hepatitis, in addition to non-purulent encephalomyelitis. In the others (18 of 33 pigeons; group 3) in which HI antibodies were detected but NDV was not isolated, the lesions consisted of hyperplasia of the lymphoid tissue in the spleen, follicular aggregation of lymphoid cells in the kidney and non-purulent encephalomyelitis. Based on the histopathological changes, it was considered that the viscerotropic and neurotropic strains of NDV had affected flocks of racing pigeons in Japan.

The balance between self-renewal and differentiation is crucial to ensure the homeostasis of the hematopoietic system, and is a hallmark of hematopoietic stem cells. However, the underlying molecular pathways, including the role of micro-RNA, are not completely understood. To assess the contribution of micro-RNA, we performed micro-RNA profiling of hematopoietic stem cells and their immediate downstream progeny multi-potent progenitors from wild-type control and Pbx1-conditional knockout mice, whose stem cells display a profound self-renewal defect. Unsupervised hierarchical cluster analysis separated stem cells from multi-potent progenitors, suggesting that micro-RNA might regulate the first transition step in the adult hematopoietic development. Notably, Pbx1-deficient and wild-type cells clustered separately, linking micro-RNAs to self-renewal impairment. Differential expression analysis of micro-RNA in the physiological stem cell-to-multi-potent progenitor transition and in Pbx1-deficient stem cells compared to control stem cells revealed miR-127-3p as the most differentially expressed. Furthermore, miR-127-3p was strongly stem cell-specific, being quickly down-regulated upon differentiation and not re-expressed further downstream in the bone marrow hematopoietic hierarchy. Inhibition of miR-127-3p function in Lineage-negative cells, achieved through a lentiviral-sponge vector, led to severe stem cell depletion, as assessed with serial transplantation assays. miR-127-3p-sponged stem cells displayed accelerated differentiation, which was uncoupled from proliferation, accounting for the observed stem cell reduction. miR-127-3p overexpression in Lineage-negative cells did not alter stem cell pool size, but gave rise to lymphopenia, likely due to lack of miR-127-3p physiological downregulation beyond the stem cell stage. Thus, tight regulation of miR-127-3p is crucial to preserve the self-renewing stem cell pool and homeostasis of the hematopoietic system.