Merkel Cell Carcinoma In Situ: No More Serendipity?

A 50-year-old man, with a history of extensive sun exposure and multiple previous non-melanoma skin cancers, presented with an asymptomatic 8-× 10-millimeter scaly, skin-colored papule on his right shoulder. Subsequent biopsy and excision revealed epidermal hyperplasia containing large atypical basaloid cells with pagetoid spread. Immunoperoxidase staining for cytokeratin-20 demonstrated a focal perinuclear dot-like pattern, and after excluding other in situ entities, a diagnosis of Merkel cell carcinoma In Situ (MCCIS) was rendered.

Connexins: Intercellular Signal Transmitters in Lymphohematopoietic Tissues.

Life-long hematopoietic demands are met by a pool of hematopoietic stem cells (HSC) with self-renewal and multipotential differentiation ability. Humoral and paracrine signals from the bone marrow (BM) hematopoietic microenvironment control HSC activity. Cell-to-cell communication through connexin (Cx) containing gap junctions (GJs) allows pluricellular coordination and synchronization through transfer of small molecules with messenger activity.

Vasculopathy-associated hyperangiotensinemia mobilizes haematopoietic stem cells/progenitors through endothelial AT₂R and cytoskeletal dysregulation.

Patients with organ failure of vascular origin have increased circulating haematopoietic stem cells and progenitors (HSC/P). Plasma levels of angiotensin II (Ang-II), are commonly increased in vasculopathies. Hyperangiotensinemia results in activation of a very distinct Ang-II receptor set, Rho family GTPase members, and actin in bone marrow endothelial cells (BMEC) and HSC/P, which results in decreased membrane integrin activation in both BMEC and HSC/P, and in HSC/P de-adhesion and mobilization.

p62 is required for stem cell/progenitor retention through inhibition of IKK/NF-κB/Ccl4 signaling at the bone marrow macrophage-osteoblast niche.

In the bone marrow (BM), hematopoietic progenitors (HPs) reside in specific anatomical niches near osteoblasts (Obs), macrophages (MΦs), and other cells forming the BM microenvironment. A connection between immunosurveillance and traffic of HP has been demonstrated, but the regulatory signals that instruct the immune regulation of HP circulation are unknown. We discovered that the BM microenvironment deficiency of p62, an autophagy regulator and signal organizer, results in loss of autophagic repression of macrophage contact-dependent activation of Ob NF-κB signaling.

Rho GTPases control specific cytoskeleton-dependent functions of hematopoietic stem cells.

The Rho family of guanosine triphosphatases (GTPases) is composed of members of the Ras superfamily of proteins. They are GTP-bound molecules with a modest intrinsic GTPase activity that can be accelerated upon activation/localization of specialized guanine nucleotide exchange factors. Members of this family act as molecular switches and are required for coordinated cytoskeletal rearrangements that are crucial in a set of specialized functions of mammalian stem cells.

Morphea and its variants and the "floating sign"-an additional finding in morphea.

We report 2 patients with typical clinical findings of circumscribed morphea who on histopathologic examinations had histiocytes ("floating sign") surrounding individual collagen fibers in the dermis in addition to the key histologic findings of morphea. To our knowledge, there are no previous reports in the medical literature of such a phenomenon. Histopathological findings in idiopathic morphea and morphea-like conditions are reviewed.

Vav3 collaborates with p190-BCR-ABL in lymphoid progenitor leukemogenesis, proliferation, and survival.

Despite the introduction of tyrosine kinase inhibitor therapy, the prognosis for p190-BCR-ABL(+) acute lymphoblastic leukemia remains poor. In the present study, we present the cellular and molecular roles of the Rho GTPase guanine nucleotide exchange factor Vav in lymphoid leukemogenesis and explore the roles of Vav proteins in BCR-ABL-dependent signaling. We show that genetic deficiency of the guanine nucleotide exchange factor Vav3 delays leukemogenesis by p190-BCR-ABL and phenocopies the effect of Rac2 deficiency, a downstream effector of Vav3.

Treatment of squamous cell carcinoma in situ: a review.

Background: Squamous cell carcinoma in situ (SCCIS) is thought to be a precursor to squamous cell carcinoma. It should be treated before invasive cancer develops, especially in transplant recipients, who may develop more aggressive skin cancers. Treatment can involve surgical and nonsurgical methods.

The operative management of melanoma: where does Mohs surgery fit in?

Background: Melanoma is a life-threatening malignancy. Surgery is the primary management for melanoma, and management guidelines have evolved gradually over a century from radical surgery with lymph node dissection to conservative margin surgery. There are specific rationales and problems with Mohs micrographic (MMS) surgery for managing melanoma.

Novel 16-minute technique for evaluating melanoma resection margins during Mohs surgery.

Background: Immunohistochemistry (IHC) applied to Mohs micrographic surgery (MMS) is time consuming and labor intensive, and the variability of staining quality has prevented its widespread use in clinical practice.

Objective: To investigate the readability of immunostains processed by a novel automated 16-minute technique used for evaluation of frozen sections prepared during MMS for melanoma.

Methods: A rapid automated instrument that performs MART-1 (melanoma antigen recognized by T cells) immunostains in 16 minutes was used to stain frozen sections and was compared with MART-1 stains of paraffin (permanent) sections, hematoxylin-eosin (H&E) stains of frozen and permanent sections from the positive or negative control specimens of the Mohs layers for melanoma.

Preoperative methicillin-resistant Staphylococcus aureus screening in Mohs surgery appears to decrease postoperative infections.

Background: Colonization with methicillin-resistant Staphylococcus aureus (MRSA) places patients at risk for postoperative MRSA wound infections.

Objective: To determine the effect of a decontamination and prophylaxis protocol on postoperative MRSA wound infections in patients with nasal MRSA.

Methods & Materials: Wound cultures over a 23-month period were reviewed before and 11 months after implementation of a screening and decontamination protocol.

Paracrine modulation of CXCR4 by IGF-1 and VEGF: implications for choroidal neovascularization.

Purpose: Modulators of angiogenesis typically work in an orchestrated manner. The authors examined the interaction between insulinlike growth factor (IGF)-1, vascular endothelial growth factor (VEGF), and stromal derived factor (SDF)-1 in vivo and in vitro using angiogenesis models.

Methods: The angiogenic effect of SDF-1, alone or in combination with IGF-1 and VEGF, was assessed in human lung microvascular endothelial cells using capillary tube formation and thymidine incorporation.

Treatment of severe alopecia areata with intralesional steroid injections.

Background: Treatment of alopecia areata with intralesional steroid injection is generally recommended for people who have less than 50% scalp involvement. In a specialized hair loss clinic, the authors successfully treated patients with extensive alopecia areata (over 50% but under 99%) with intralesional corticosteroid injections.

Observations: A review of patients with extensive alopecia areata was done.

Insulin-like growth factor binding protein-3 mediates vascular repair by enhancing nitric oxide generation.

Rationale: Insulin-like growth factor binding protein (IGFBP)-3 modulates vascular development by regulating endothelial progenitor cell (EPC) behavior, specifically stimulating EPC cell migration. This study was undertaken to investigate the mechanism of IGFBP-3 effects on EPC function and how IGFBP-3 mediates cytoprotection following vascular injury.

Objective: To examine the mechanism of IGFBP-3-mediated repair following vascular injury.

High-throughput identification of clinically important bacterial pathogens using DNA microarray.

Rapid and accurate detection of pathogenic bacteria is important for the treatment of patients with suitable antibiotics. Here we report the development of a diagnostic DNA microarray for the high-throughput identification of 39 pathogenic bacteria selected based on their high prevalence rate and/or difficulty of cultivation. The 23S ribosomal DNA and 16S-23S rDNA intergenic spacer region were used as target DNAs for pathogen detection.

Labeling of stem cells with monocrystalline iron oxide for tracking and localization by magnetic resonance imaging.

Precise localization of exogenously delivered stem cells is critical to our understanding of their reparative response. Our current inability to determine the exact location of small numbers of cells may hinder optimal development of these cells for clinical use. We describe a method using magnetic resonance imaging to track and localize small numbers of stem cells following transplantation.

Carbon monoxide and nitric oxide mediate cytoskeletal reorganization in microvascular cells via vasodilator-stimulated phosphoprotein phosphorylation: evidence for blunted responsiveness in diabetes.

Objective: We examined the effect of the vasoactive agents carbon monoxide (CO) and nitric oxide (NO) : n the phosphorylation and intracellular redistribution of vasodilator-stimulated phosphoprotein (VASP), a critical actin motor protein required for cell migration that also controls vasodilation and platelet aggregation.

Research Design And Methods: We examined the effect of donor-released CO and NO in endothelial progenitor cells (EPCs) and platelets from nondiabetic and diabetic subjects and in human microvascular endothelial cells (HMECs) cultured under low (5.5 mmol/l) or high (25 mmol/l) glucose conditions.

IGF binding protein-3 regulates hematopoietic stem cell and endothelial precursor cell function during vascular development.

We asked whether the hypoxia-regulated factor, insulin-like growth factor binding protein-3 (IGFBP3), could modulate stem cell factor receptor (c-kit+), stem cell antigen-1 (sca-1+), hematopoietic stem cell (HSC), or CD34+ endothelial precursor cell (EPC) function. Exposure of CD34+ EPCs to IGFBP3 resulted in rapid differentiation into endothelial cells and dose-dependent increases in cell migration and capillary tube formation. IGFBP3-expressing plasmid was injected into the vitreous of neonatal mice undergoing the oxygen-induced retinopathy (OIR) model.

Ischemic vascular damage can be repaired by healthy, but not diabetic, endothelial progenitor cells.

Endothelial precursor cells (EPCs) play a key role in vascular repair and maintenance, and their function is impeded in diabetes. We previously demonstrated that EPCs isolated from diabetic patients have a profound inability to migrate in vitro. We asked whether EPCs from normal individuals are better able to repopulate degenerate (acellular) retinal capillaries in chronic (diabetes) and acute (ischemia/reperfusion [I/R] injury and neonatal oxygen-induced retinopathy [OIR]) animal models of ocular vascular damage.

Usefulness of 23S rRNA amplification by PCR in the detection of bacteria in CAPD peritonitis.

Background: Peritonitis is the most common complication of continuous ambulatory peritoneal dialysis (CAPD), and the spectrum of organisms causing CAPD peritonitis is broad. Polymerase chain reaction (PCR) has recently broadened its diagnostic capabilities in infectious diseases. PCR can provide a sensitive method for identifying causative infectious organisms.

DNA microarray-based detection of nosocomial pathogenic Pseudomonas aeruginosa and Acinetobacter baumannii.

Infection by nosocomial pathogenic bacteria is increasingly becoming a major threat to the patients in the hospital. We have developed a diagnostic DNA microarray for the detection of two important nosocomial pathogens, Pseudomonas aeruginosa and Acinetobacter baumannii. The diagnostic DNA microarray contains the species-specific probes of 15mer oligonucleotides designed based on the sequences of 23S ribosomal DNA.

Clinical outcomes of tuberculosis in renal transplant recipients.

Tuberculosis (TB) is an important cause of morbidity and mortality in renal transplant recipients. Rifampin has a potent sterilizing activity, but it reduces the serum concentrations of the immunosuppressive agents. Moreover, the possible contribution made by mycobacterial infection to the incidence of graft rejection or renal dysfunction remains unclear.

Clinical manifestations and diagnosis of extrapulmonary tuberculosis.

Since the diagnosis of extrapulmonary tuberculosis (EPT) is largely depended on the physician's suspicion in respect of the disease, we believed that it would be worthwhile to scrutinize the clinical characteristics of EPT. Thus, here we present retrospectively evaluated clinical manifestations of patients who were diagnosed as EPT cases in a tertiary referral care hospital. Medical records of 312 patients, diagnosed as having EPT at Yongdong Severance hospital from January 1997 to December 1999, were reviewed retrospectively.