Numerous Small Cells Research Articles

Nectar guides and floral nectary in Lamium album L. subsp. album: structure and histochemistry in light, fluorescence, and electron microscopy

Lamium album is a native common plant growing in Eurasia. It is used in medicine and cosmetics and is highly valued in apiculture. The aim of the study was to investigate the structure of the floral nectary in three stages of flower development. Additionally, histochemical studies of the nectary and nectar guides present on the lower corolla lobe were carried out. No detailed analyses of nectary tissues in this species have been conducted to date. The present analyses were performed with the use of light, fluorescence, and scanning electron microscopy. The nectary gland in the flowers of Lamium album subsp. album formed an incomplete ring at the ovary base. The nectarostomata were arranged in clusters only in the adaxial epidermis of the anterior part of the nectary. During the secretory activity of the nectary (1st day of flowering), numerous small vacuoles and cells with large lobulate nuclei with surrounding plastid clusters were observed in the epidermis and glandular parenchyma cells. The vascular bundles contained xylem and phloem elements. Corolla wilting (3rd day of flowering) was accompanied by destructive changes in the nectary parenchyma, leading to the formation of empty spaces and appearance of cell remnants on the nectary surface. The histochemical analyses revealed the presence of starch and phenolic compounds as well as acidic and neutral lipids, which are characteristic of essential oils, in the nectary tissues. The nectar guides were composed of large yellow papillae containing phenolic compounds and acidic and neutral lipids, which were also present in glandular trichomes and abaxial parenchyma cells. The present study has demonstrated that the scent of Lamium album subsp. album flowers is produced with the involvement of essential oils contained in adaxial and abaxial epidermis cells, glandular trichomes, and nectary tissues.

Ultrastructure of the Mycobacterium avium subsp. hominissuis Biofilm.

Mycobacterium avium subsp. hominissuis (MAH) is one of the most common nontuberculous mycobacterial pathogens responsible for chronic lung disease in humans. It is widely distributed in biofilms in natural and living environments. It is considered to be transmitted from the environment. Despite its importance in public health, the ultrastructure of the MAH biofilm remains largely unknown. The ultrastructure of a MAH-containing multispecies biofilm that formed naturally in a bathtub inlet was herein reported along with those of monoculture biofilms developed from microcolonies and pellicles formed in the laboratory. Scanning electron microscopy revealed an essentially multilayered bathtub biofilm that was packed with cocci and short and long rods connected by an extracellular matrix (ECM). Scattered mycobacterium-like rod-shaped cells were observed around biofilm chunks. The MAH monoculture biofilms that developed from microcolonies in vitro exhibited an assembly of flat layers covered with thin film-like ECM membranes. Numerous small bacterial cells (0.76±0.19‍ ‍μm in length) were observed, but not embedded in ECM. A glycopeptidolipid-deficient strain did not develop the layered ECM membrane architecture, suggesting its essential role in the development of biofilms. The pellicle biofilm also consisted of flat layered cells covered with an ECM membrane and small cells. MAH alone generated a flat layered biofilm covered with an ECM membrane. This unique structure may be suitable for resistance to water flow and disinfectants and the exclusion of fast-growing competitors, and small cells in biofilms may contribute to the formation and transmission of bioaerosols.

Effect of Male Diet on Accessory Gland Protein and Sperm Traits in D.melanogaster

The quality and quantity of nutrients present in the food consumed by organisms have a strong influence on reproductive fitness. The diet of individuals is apparently a key factor in reproduction with effects on their sexual performance and progeny production. Variation in reproductive success of individuals in a population depends on the quality and quantity of nutrients available and also consumed by the individuals. The investigations on the effects of diet on life events in insects include mate choice, mating incidence, activity levels, the quantity of seminal fluid and /or accessory gland proteins produced and sperm production. Here we investigate the effect of male nutrition on the accessory gland and quantity of sperms transferred to the mated female during copulation to understand its effect of male reproductive success in Drosophila melanogaster. We raised larvae on either the protein-rich diet or carbohydrate-rich diet. We found that flies consuming protein-rich diet had numerous small main cells in their accessory gland and formed a larger amount of accessory gland protein, whereas males fed on the carbohydrate-rich diet had fewer large main cells in their accessory gland and produced a significantly small amount of accessory gland proteins. Further males reared on the protein-rich diet had copulated longer and transferred a larger amount of accessory gland protein and sperms to mated females than those males which fed with wheat cream agar media or male fed on the carbohydrate-rich diet.

Tail regeneration in a cephalochordate, the Bahamas lancelet, Asymmetron lucayanum.

Lancelets (Phylum Chordata, subphylum Cephalochordata) readily regenerate a lost tail. Here, we use light microscopy and serial blockface scanning electron microscopy (SBSEM) to describe tail replacement in the Bahamas lancelet, Asymmetron lucayanum. One day after amputation, the monolayered epidermis has migrated over the wound surface. At 4 days, the regenerate is about 3% as long as the tail length removed. The re-growing nerve cord is a tubular outgrowth of ependymal cells, and the new part of the notochord consists of several degenerating lamellar cells anterior to numerous small vacuolated cells. The cut edges of the mesothelium project into the regenerate as tubular extensions. These tubes anastomose with each other and with midline mesodermal canals beneath the regenerating edges of the dorsal and ventral fins. SBSEM did not reveal a blastema-like aggregation of undifferentiated cells anywhere in the regenerate. At 6 days, the regenerate (10% of the amputated tail length) includes a notochord in which the small vacuolated cells mentioned above are differentiating into lamellar cells. At 10 days, the regenerate is 22% of the amputated tail length: myocytes have appeared in the walls of the myomeres, and sclerocoels have formed. By 14 days, the regenerate is 35% the length of the amputated tail, and the new tissues resemble smaller versions of those originally lost. The present results for A. lucayanum, a species regenerating quickly and with little inter-specimen variability, provide the morphological background for future cell-tracer, molecular genetic, and genomic studies of cephalochordate regeneration.

Effects of extrusion conditions and nitrogen injection on physical, mechanical, and microstructural properties of red lentil puffed snacks

PurposeRed lentils are rich in proteins and fibres, and thus have great potential to be used as healthy ingredients in extruded snacks. However, at high protein and fibre concentrations, the level of expansion, microstructure uniformity and textural appeal are impaired. Using physical blowing agents during extrusion can overcome these quality issues. This study investigates the effects of moisture content (18%–22%), screw speed (150 rpm–200 rpm), and blowing agent (i.e., N2) injection pressure (0−500 kPa) on physical, mechanical and microstructural properties of puffed red lentil snacks. Principle resultsCompared to conventional extrusion, N2 injection at 300 kPa decreased extrudate density from 0.25 to 0.41 kg/m3 to 0.12 to 0.26 kg/m3 (across all feed moistures and screw speeds studied), and substantially altered the extrudate’s microstructure. Extrudates with N2 injection had numerous small cells that were more evenly distributed. Moreover, an increase in feed moisture from 18% to 22% increased extrudate hardness and decreased crispiness. Major conclusionsN2 injection during extrusion has a great potential in manipulating extrudate expansion, microstructure, texture, and colour of red lentil extrudates. Extrudates produced with 300 kPa N2 injection pressure had the maximum expansion compared to other N2 injection pressures studied.

On Developing Techniques for Sharing Satellite Spectrum with Indoor Small Cells in 5G

In this paper, we present two spectrum sharing techniques for a multisystem, incorporating an integrated satellite-mobile system and an autonomous terrestrial-mobile system (iSMS/aTMS), namely orthogonal spectrum sharing (OSS) and non-orthogonal spectrum sharing (nOSS) techniques. aTMS consists of numerous small cells deployed in several buildings, and iSMS consists of a satellite station integrated with complementary ground component (CGC) stations deployed within buildings. By exploiting the high external wall penetration loss of a building, the iSMS spectrum is shared with small cells per building in OSS, and small cells per 3-dimensional (3D) cluster per building in nOSS. An interference management scheme, to avoid interference in apartments with collocated CGC stations and small cells, was developed and an optimal number of almost blank subframes (ABSs) per ABS pattern period (APP) was defined. System-level capacity, spectral efficiency, and energy efficiency performance metrics were derived. Furthermore, we present an algorithm for both OSS and nOSS techniques. With extensive simulation and numerical analysis, it is shown that the proposed nOSS significantly outperforms OSS in terms of spectral efficiency and energy efficiency, and both techniques can meet the expected spectral efficiency and energy efficiency requirements for the fifth-generation (5G) mobile networks.

Solitary Plasmacytoma of Rib Origin in a Young Adult- A Rare CaseReport

Solitary plasmacytoma of bone, specially of a single rib, is a rare disease and is characterized by onlyone or two isolated bone lesions with no evidence of disease dissemination. Here we present a caseof 35-year-old male who was presented with a recurrent swelling in left lower lateral chest wall withsymptoms of localized pain. Radiological evaluation revealed a solitaryexpanding lesion in left lowerlateral chest wall. Fine needle aspiration showed numerous small round cells having hyperchromaticnuclei with scanty cytoplasm. en-bloc resection of the tumor, including involved part of left 9th rib,the intercostal muscle and the parietal pleura with primary closure of chest wall. Histopathology ofthe resected mass revealed plasma cell neoplasm, highly suggestive of solitary plasmacytoma. Thepatient referred to oncologist for further management.
 Journal of Surgical Sciences (2017) Vol. 21 (1) :39-41

Three Mutations in the Bilateral Frontoparietal Polymicrogyria Gene GPR56 in Pakistani Intellectual Disability Families

Bilateral frontoparietal polymicrogyria (BFPP, MIM 606854) is a heterogeneous autosomal recessive disorder of abnormal cortical lamination, leading to moderate-to-severe intellectual disability (ID), seizure disorder, and motor difficulties, and caused by mutations in the G protein-coupled receptor 56 ( GPR56 ) gene. Twenty-eight mutations in 40 different families have been reported in the literature. The clinical and neuroimaging phenotype is consistent in these cases. The BFPP cortex consists of numerous small gyral cells, with scalloping of the cortical-white matter junction. There are also associated white matter, brain stem, and cerebellar changes. GPR56 is a member of an adhesion G protein-coupled receptor family with a very long N-terminal stalk and seven transmembrane domains. In this study, we identified three families from Pakistan, ascertained primarily for ID, with overlapping approximately 1 Mb region (chr16:56,973,335-57,942,866) of homozygosity by descent, including 24 RefSeq genes. We found three GPR56 homozygous mutations, using next-generation sequencing. These mutations include a substitutional variant, c.1460T > C; p.L487P, (chr16:57693480 T > C), a 13-bp insertion causing the frameshift and truncating mutation, p.Leu269Hisfs*21 (NM_005682.6:c.803_804insCCATGGAGGTGCT; Chr16: 57689345_57689346insCCATGGAGGTGCT), and a truncating mutation c.1426C > T; p.Arg476* (Chr16:57693446C > T). These mutations fully segregated with ID in these families and were absent in the Exome Aggregation Consortium database that has approximately 8,000 control samples of South Asian origin. Two of these mutations have been reported in ClinVar database, and the third one has not been reported before. Three families from Pakistan with GPR56 mutations have been reported before. With the addition of our findings, the total number of mutations reported in Pakistani patients now is six. These results increase our knowledge regarding the mutational spectrum of the GPR56 gene causing BFPP/ID.

Efficient handover measurement technique for small‐cell networks using a virtual cell synchronization signal

AbstractA small‐cell network (SCN) constructed by splitting a macro‐cell into numerous small cells using an active antenna array system is studied. A synchronization signal appropriate for the SCN, virtually generated by an eNodeB with 3D beamforming, is proposed for efficient handover in SCNs. The virtual cell synchronization signal (VCSS) carries a macro‐cell ID (MCID) and virtual‐cell ID (VCID) in a hierarchical manner, allowing us to distinguish between an intra‐cell handover (virtual cell handover within a cell without changing the serving eNodeB) and inter‐cell handover (virtual cell handovers across cells while changing the serving eNodeB) in SCNs. Using the signal metrics obtained by the VCSS, an efficient handover measurement technique is proposed which can significantly reduce the processing time and overhead by distinguishing between the intra‐cell/inter‐cell handovers. The performance of the proposed technique is evaluated by simulating two different deployment scenarios of LTE‐based SCN with 3D beamforming. Copyright © 2017 John Wiley & Sons, Ltd.

Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset.

Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI) were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort), as well as during controlled and uncontrolled viremia (ANRS cohorts). We also addressed IP-10 expression levels with regards to lymphoid tissues (LT) and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker) gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10.

Lymphatic Markers in the Adult Human Choroid.

Reports of lymphatics in the posterior human uvea are contradictory. We systematically analyzed the choroid by combining various lymphatic markers, following recently established guidelines for the immunohistochemical detection of ocular lymphatics. Human choroids were prepared for flat mount serial cryosectioning. Sections were processed for immunohistochemistry of the lymphatic markers LYVE-1, PDPN, PROX1, FOXC2, VEGFR3, CCL21, and combined with α-smooth muscle-actin and 4',6-diamidino-2-phenylendole (DAPI). Single, double, and triple marker combinations were documented using confocal microscopy. Messenger RNA analysis for CCL21, FOXC2, LYVE-1, PDPN, PROX, and VEGFR3 was performed in choroid and skin. In the choroid, CCL21 immunoreactivity was detected in choroidal blood vessels, intrinsic choroidal neurons, and numerous small cells of the choroidal stroma. These small cells were not colocalized with PROX1 and PDPN, while a subpopulation of cells showed immunoreactivity for CCL21 and LYVE-1, and very occasionally PDPN-only+ cells were detected. Nuclei positive for PROX1 were never detected in the choroid, and vessel-like structures immunoreactive for LYVE-1, PDPN, or CCL21 (other than blood vessels) were never observed. Immunoreactivity of VEGFR3 was absent in the majority of choroidal blood vessels, but present in choriocapillaris, while other structures positive for VEGFR3 were not detected. Nonvascular smooth muscle cells were lacking VEGFR3-immunoreactivity. Messenger RNA analysis detected all lymphatic markers investigated and confirmed immunohistochemical results. By combining several lymphatic markers, single cells expressed these markers, but classical lymphatic vessels were not detected in the human choroid. Therefore, the healthy adult human choroid must be considered alymphatic, at least with the markers applied here.

Fine structure of the male genital system of the predatory mite Rhagidia halophila (Rhagidiidae, Prostigmata, Actinotrichida).

The male genital system of the actinotrichid mite Rhagidia halophila is described and compared with other mites and arachnids. The large testes are composed of germinal and glandular parts and produce numerous small sperm cells. The glandular parts are connected via a testicular bridge. Spermiogenesis occurs in cysts containing spermatids in equal stages of development. Cysts of spermatids are embedded in huge somatic cells. The nuclei of the spermatids loose their envelope. Mature sperm cells are simple exhibiting a ring-shaped chromatin body and lacking an acrosomal complex. They are most similar to the sperm cells of the related mite Linopodes motatorius. The spermatopositor contains the ejaculatory duct divided into a dorsal channel and a ventral channel that are connected via a narrow passage. At its distal end, the spermatopositor is divided into three eugenital lips. The function of the spermatopositor during deposition of the peculiar thread-like spermatophores is discussed. Details of the sensilla of the spermatopositor and the progenital lips are reported. The genital papillae located on the inner side of the progenital lips exhibit characteristics of cells performing transport of ions and/or water. The results confirm the overall similarity of actinotrichid genital systems, which is profoundly different from that of anactinotrichid mites. With reference to other Arachnida it is corroborated that testes and sperm structure of Actinotrichida are most similar to that of Solifugae. However, synapomorphies between sperm cells of Rhagidia and Solifugae that could suggest a closer relationship between these two taxa as was suggested in earlier studies were not recognizable. On the contrary, the sperm cells of Rh. halophila being devoid of an acrosomal complex appeared to be more apomorphic than those of many other actinotrichid mites as well as Solifugae.

Theoretical study and performance evaluation of macro‐assisted data‐only carrier for next generation 5G system

SummaryWith the explosive growth of high‐data rate multimedia services and machine‐to‐machine (M2M) type communications, numerous small cells will be densely deployed in future fifth generation wireless network, resulting in serious interference, intolerable delay, and huge handover failure. Massive access M2M services, with low‐rate high‐frequency requests, will also generate much signaling overhead costs and cause enormous waste of system resources. In the Third Generation Partnership Project, the split of control and user (C/U) planes is perceived as one of the most promising methods for small cell enhancement to address these challenges. In this article, a new C/U split architecture of data‐only carrier (DoC) system is analyzed comprehensively from various aspects, such as overhead costs, coverage probability, spectral efficiency, and energy efficiency for the first time. Based on the model of stochastic geometry, the influences of density and power of small cell and cell range expansion factors are all taken into account to compare the DoC architecture with the baseline long‐term evolution (LTE) system. Numerical results show that the DoC system can greatly reduce the overhead costs and help to achieve higher throughput gain and better coverage performance over the conventional LTE system. Copyright © 2015 John Wiley & Sons, Ltd.

Micropapillary Carcinoma of the Urinary Tract: A Cytologic Study of Urine and Fine-Needle Aspirate Samples

Objective: Micropapillary carcinoma (MPC) is an aggressive variant of urothelial carcinoma that needs early and specific recognition. In order to determine whether this tumor variant can be recognized with cytology, we evaluated a large cytohistological series. Study Design: It was a retrospective cytohistological correlation study including 20 patients with MPC. Only those cases in which the tumor exhibited >50% of micropapillary growth were selected. Twenty exfoliative urine specimens and four needle aspirates from lymph node metastases were reviewed. Results: On histology, 14 cases were infiltrative, while 6 were exclusively superficial. Cytology was characterized by numerous small, cohesive groups and single neoplastic cells. Pseudopapillae were present in 17 cases and in 9 they were a relevant finding. Morules were present in 15 cases. Isolated microacini were seen in 14 cases. Infiltrative tumors showed more neoplastic groups. Cellular atypia was prominent in 17 cases. In 15 cases, a cytologic diagnosis of urothelial carcinoma was made. One case was diagnosed as adenocarcinoma. The remaining 4 cases were considered suspicious of malignancy. Conclusions: The peculiar morphology of MPC of the urinary tract is partially reflected on cytology, allowing in some cases a specific recognition. This is important since the aggressive behavior of this neoplasm needs rapid management and treatment.

Synchronous Primary Pulmonary Marginal Zone B-Cell Lymphoma and Large B-Cell Lymphoma

SESSION TYPE: Pleural Case Report Posters

Tumor-associated primo vascular system is derived from xenograft, not host

The primo vascular system (PVS), which is composed of very small primo-vessels (PV) and primo-nodes (PN), has recently emerged as a third component of circulatory system. Here, we report the presence of a tumor derived PVS in murine xenografts of human histiocytic lymphoma (U937) in close proximity to the tumor. Within this system, PNs are small (~500–600μM diameter) membranous sac-like structures which contain numerous small cells which can be demonstrated by DAPI staining. Hematoxylin and Eosin (H&E) staining of the peri-tumoral PVS shows the presence of loose structures lined by fibroblasts but filled with dense fibers, cells, lacunae and nerve-like structures. The origin and type of cells within the PVS was characterized by immunostaining with antibodies for CD68, CD45 and lysozyme. The results of these studies reveal that the PVS of the xenograft originates from the human U937 tumor cells. qRT-PCR analysis of mRNA isolated from PVS cells reveals a striking predominance of human, rather than mouse, sequences. Of particular interest, human stem cell specific transcription factors were overexpressed, most notably KLF4, an upstream regulator of NANOG which maintains the pluripotent and undifferentiated state of stem cells. These results suggest that the cells present within the PVS are derived from the human xenograft and suggests that the primo-vessels associated with the xenografted tumor may provide a safe haven for a select population of cancer stem cells. Further understanding of the biological properties of these cells may allow the development of new anti-cancer interventions.

Extrafloral Nectaries in Acacia mangium

Our microscopy studies describe the anatomy of extrafloral nectaries on the abaxial side of the basal part of every leaf stalks of Acacia mangium. The lens-like nectary expands with the development of the leafstalk, peaks at the stage at which the leafstalk itself has reached its mature size. The nectary is composed of numerous small parenchyma cells and a nectar cavity in which the nectar is pooled. Those small parenchyma cells are divided into nectariferous tissue and epithelial cells, which line the lumen of the nectar cavity, and secretes the nectar into the same. Each nectary is surrounded by several vascular bundles, which probably afford the nectar. In addition to the microscopic observation, the chemical constituents of the nectar are analyzed by NMR, and it mainly consists of sugars with 60 % sucrose, 25 % glucose and 15 % fructose.

Identification of potential human corneal endothelial stem‐like cell niches

Abstract Purpose to study the localization of potential stem‐(like) cells in human adult corneal endothelium Methods Fresh (6‐12h post mortem) and organ cultured (OC) corneas were studied after flat mount. The whole endothelium and posterior limbus (PL) was observed after triple staining with Trypan blue, Alizarin red and Hoechst 33342, in order to determine cells shape, localization and viability. The level of endothelial cell (EC) differenciation was determined after immunostaining (fluorescence) for ZO‐1, Na+/K+ ATPase and COX IV; the cell proliferation status was assessed using Ki67; four markers for stem cells were used: Oct‐4, BCRP, Nestin and Telomerase; ability for cell migration was evaluated from Myosin IIA expression Results In several corneas, the nuclei of peripheral EC were centripetally aligned suggesting continuous slow central migration. Numerous small cells with a reduced expression of differenciation markers were accumulated near peripheral Hassall Henle bodies. In these potential niches, cells were distributed in 3‐5 layers. A high expression of Myosin II was found in peripheral cells. Ki67+ cells were found in PL and peripheral EC only after OC. None of the 4 stem cell markers was found in EC, and their expression in PL was poorly reliable because of high background noise. Numerous trypan blue positive cells were located at the PL and in the extreme periphery of endothelium Conclusion several strong arguments suggest the location of corneal endothelial stem‐like cell niches in endothelial periphery or in the PL, and the capacity of EC to migrate from these niches toward the centre. Trypan blue staining pattern suggests that they could rapidly die in ex vivo corneas, and be therefore hard to indentify

Combination treatment of db/db mice with exendin-4 and gastrin preserves β-cell mass by stimulating β-cell growth and differentiation.

Aim/Introduction: Preservation of β-cell mass is crucial for maintaining long-term glucose homeostasis. Therapies based on incretin and its mimetics are expected to achieve this goal through various biological functions, particularly the restoration of β-cell mass. Here we tested the effects of gastrin and exendin-4 in type 2 diabetic animals. The effects of exendin-4 and gastrin on β-cell function and mass were examined in 8-week-old db/db mice. INS-1 beta cells and AR42J cells were used to determine the molecular mechanism underlying the effects of the two agents. Immunohistochemistry, western blotting and RT-PCR assays were used to assess the biological effects of the two agents. Two weeks of combination administration of exendin-4 plus gastrin resulted in a significant improvement of glucose tolerance associated with a marked preservation of β-cell mass in db/db mice. Immunohistochemical analysis showed that such treatment resulted in the appearance of numerous irregularly-shaped small islets and single insulin-positive cells. While gastrin had little biological effect on INS-1 β-cells consistent with low expression of its intrinsic receptor on these cells, it caused differentiation of AR42J cells into insulin-producing cells. Co-stimulation with exendin-4 significantly enhanced gastrin-induced endocrine differentiation of AR42J precursor cells. These findings were further supported by enhanced expression of key genes involved in β-cell differentiation and maturation, such as neurogenin3 (Ngn3) and MafA. These results suggest that combination treatment of db/db mice with exendin-4 and gastrin preserves β-cell mass by stimulating β-cell growth and differentiation. (J Diabetes Invest, doi: 10.1111/j.2040-1124.00044.x, 2010).

Carcinomatous infiltration of cerebrospinal fluid with reactive lymphocytosis and granulocytosis

Hematologists are frequently involved with morphological analysis of centrifuged cerebrospinal fluid (CSF) for the diagnosis of malignant infiltration of the central nervous system (CNS). Although malignant cells in the CSF are most often due to underlying hematological cancers, leptomeningeal carcinomatous infiltration from a solid tumor is not uncommon. A 46-year-old lady presented with focal neurological signs suggestive of cauda equina compression. She was on adjuvant therapy for invasive ductal carcinoma of breast with expression of human epidermal growth factor receptor-2 (HER-2). MRI scan confirmed a metastatic deposit in the conus medullaris with tumor nodules in the cauda equina and diffuse meningeal enhancement. Clear CSF was obtained from a diagnostic lumbar puncture and microscopy showed the presence of 50/mm3 white cells and 10/mm3 red cells, with no evidence of infection. A centrifuged cytospin preparation of CSF stained with May-Grunwald-Giemsa (MGG) showed numerous small lymphocytes, neutrophils, metamyelocytes, and metastatic breast carcinoma cells (Image 1). The latter cells were much larger than the hematological cells, with homogeneous nuclei containing open chromatin and abundant cytoplasm with prominent blebs from the cell surface (Image 1). Six large metastatic carcinoma cells on a background of hematological cells including two neutrophils (bottom left), a metamyelocyte (top right), and numerous small lymphocytes (MGG stained CSF cytospin; ×40). HER-2 positive breast cancers are known to carry a higher risk for CNS metastasis [1]. The presence of lymphocytosis and granulocytosis in this nonhemorrhagic CSF is a likely localized inflammatory response to metastasis from the breast carcinoma.