Differential expression of hypoxia inducible factor-1 alpha and tumor cell proliferation between squamous cell carcinomas and adenocarcinomas among operable non-small cell lung carcinomas

This study aimed to evaluate whether the elevated level of hypoxia-inducible factor-1alpha (HIF-1alpha) correlated with histologic types, angiogenesis, tumor cell proliferation, and clinical parameters in common non-small cell lung carcinomas (NSCLCs). We performed immunohistochemical stains using paraffin-embedded tissue blocks from 84 cases of operable NSCLC [No. of squamous cell carcinoma (SCC), 45; No. of adenocarcinoma (AC), 39]. HIF-1alpha expression was related with histologic types (66.7% in SCCs vs 20.5% in ACs, p<0.001), but not with lymph node status, tumor stage, vascular endothelial growth factor expression, microvessel density (MVD), and proliferating cell nuclear antigen (PCNA) index (p>0.05, respectively). As for the histologic types, MVD and PCNA index were significantly higher in SCCs than in ACs (p=0.009 and p=0.016, respectively). Among HIF-1alpha positive carcinomas, MVD was significantly higher in HIF-1alpha positive SCCs than in HIF-1alpha positive ACs (p=0.023). The overall survival curves were not associated with HIF-1alpha expression or any other histologic parameters (p>0.05). These findings suggest that HIF-1alpha expression in NSCLCs may play a differential role according to histologic types, but its prognostic significance is indeterminate.     

Skin thickness of Korean adults

Skin thickness varies considerably between different races and age-groups, between men and women, and between different regions of the body surface. A few authors reported the skin thickness of different regions of the body, but no detailed study have been performed on Asian. We performed 452 biopsies on 28 different regions of the normal skin of Korean men and women. The specimens were stained with hematoxylin-eosin and measured microscopically. The thickness of the skin (epidermis plus dermis) ranged from 521 to 1977 microm; the eyelid, prepuce, and inguinal skin was thinnest (521-626 microm), and the back was thickest (1977 microm). The thickness of the epidermis varied from 31 to 637 microm; skin thickness in the prepuce, eyelid, supraclavicular region, postauricular region, and axilla ranged from 31 to 71 microm; the buttock, dorsum of the hand, and dorsum of the foot were relatively thick (138-189 microm); the palm and sole were thickest (601-637 microm). The thickness dermis varied from 469 to 1942 microm; skin thickness in the eyelid, prepuce, inguinal region, and postauricular region ranged from 469 to 645 microm; the buttock, chest, and anterior neck were relatively thick (1318-1586 microm); the back was thickest (1942 microm). The epidermis accounted for 3.7-16.8% of the entire skin in most regions, except in the palm and sole (40.6-44.6%). Thickness data may be useful in harvesting full- or split-thickness skin grafts.     

Immunogenicity and Safety of Two Different Haemophilus influenzae Type b Conjugate Vaccines in Korean Infants

The incidence of invasive diseases, including meningitis caused by Haemophilus influenzae type b (Hib) was markedly decreased after routine immunization of Hib vaccine through diverse schedules in many countries. The purpose of this study was to evaluate the immunogenicity and safety of Hib conjugate vaccines in Korean children before the implementation of a national immunization program against Hib in Korea. A multicenter controlled trial was performed on two different Hib vaccines in Korean children. A total of 319 infants were enrolled: 199 infants were immunized with the Hib polysaccharide conjugated to the tetanus toxoid (PRP-T) and 120 infants with the Hib polysaccharide conjugated to the outer-membrane protein of Neisseria meningitides (PRP-OMP). Immunogenicity was evaluated by enzyme-linked immunosorbent assay (ELISA) and serum bactericidal assay. Both vaccines showed good immunologic responses after primary immunization. After 2 doses of PRP-T or PRP-OMP, 78.9% and 91.7% of infants achieved an antibody level of ≥1.0 µg/mL, respectively. Both vaccines were safe and well-tolerated. No serious adverse events were observed. Thus, Hib conjugate vaccines appear to be safe and show good immunogenicity in Korean infants. These results will be important reference data for the implementation of Hib vaccine in the national immunization program of Korea.     

Epstein-Barr virus-associated smooth muscle tumor in patients with acquired immunodeficiency syndrome.

Epstein-Barr virus (EBV)-associated smooth muscle tumor (SMT) is a recognized but uncommon disease that is found to occur in patients with immunocompromised conditions such as acquired immunodeficiency syndrome (AIDS). These tumors may be multifocal and located at unusual sites, such as the brain and liver. This report describes the case of 2 AIDS patients with EBV-associated SMT and highlights the features and outcome of this rare but potentially important tumor in human immunodeficiency virus management.     

High-level expression of EphA2 receptor tyrosine kinase in prostatic intraepithelial neoplasia

EphA2 is a transmembrane receptor tyrosine kinase that is overexpressed in many carcinomas. Specific targeting of EphA2 with monoclonal antibodies is sufficient to inhibit the growth, migration and invasiveness of aggressive cancers in animal models. Using immunohistochemical analyses, we measured the expression of EphA2 in prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia, and adjacent benign prostate tissue from ninety-three radical prostatectomy specimens. These results were related to multiple clinical and pathologicalcharacteristics. The fraction of cells staining positively with EphA2 in benign prostatic epithelium (mean, 12%) was significantly lower than that in high-grade prostatic intraepithelial neoplasia (mean, 67%, P < 0.001) and prostatic adenocarcinoma (mean, 85%, P < 0.001). Moreover, the intensity of EphA2 immunoreactivity in prostatic adenocarcinoma was significantly higher than in benign prostatic tissue (P < 0.001) or high-grade prostatic intraepithelial neoplasia (P < 0.001). Benign prostatic epithelium showed weak or no immunoreactivity for EphA2 in all cases examined. Whereas EphA2 immunoreactivity related to neoplastic transformation, it did not correlate with other clinical and pathological parameters examined. Our data suggest that EphA2 levels increase as prostatic epithelial cells progress toward a more aggressive phenotype. Progressively higher levels of EphA2 in high-grade prostatic intraepithelial neoplasia and prostatic carcinoma are consistent with recent evidence that EphA2 functions as a powerful oncogene. Moreover, the presence of high levels of EphA2 in these cells suggests opportunities for prostate cancer prevention and treatment.     

Effects of thyroxine on hyperkalemia and renal cortical Na+, K+ - ATPase activity induced by cyclosporin A

Cyclosporin A (CsA)-induced hyperkalemia is caused by alterations in transepithelial K+ secretion resulting from the inhibition of renal tubular Na+, K+ -ATPase activity. Thyroxine enhances renal cortical Na+, K+ -ATPase activity. This study investigated the effect of thyroxine on CsA-induced hyperkalemia. Sprague-Dawley rats were treated with either CsA, thyroxine, CsA and thyroxine, or olive-oil vehicle. CsA resulted in an increase in BUN and serum K+, along with a decrease in creatinine clearance, fractional excretion of potassium, and renal cortical Na+, K+ -ATPase activity, as compared with oil vehicle administration. Histochemical study showed reduced Na+, K+ -ATPase activity in the proximal tubular epithelial cells of the CsA-treated compared with the oil-treated rats. Histologically, isometric intracytoplasmic vacuolation, disruption of the arrangement and swelling of the mitochondria, and a large number of lysosomes in the tubular epithelium were characteristic of the CsA-treated rats. Co-administration of thyroxine prevented CsA-induced hyperkalemia and reduced creatinine clearance, Na+, K+ -ATPase activity, and severity of the histologic changes in the renal tubular cells when compared with the CsA-treated rats. Thyroxine increased the fractional excretion of potassium via the preservation of Na+, K+ -ATPase activity in the renal tubular cells. Thus, the beneficial effects of thyroxine may be suited to treatment modalities for CsA-induced hyperkalemia.     

MDM2 expression in EBV-infected nasopharyngeal carcinoma cells

To understand whether the p53-regulated mdm2 gene expression was altered by the Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC), the NPC-TW01 cell line was infected by EBV through IgA receptor-mediated endocytosis. The mdm2 gene was expressed only in a small fraction of the NPC cell population and could be enhanced in the EBV-infected (EBV+) cells. In the animals bearing EBV+ and EBV- NPC xenografts, the MDM2+ cells only appeared in clusters in both EBV+ and EBV- tumors with stronger expression in EBV+ cells. Cotransfection of pmdm2-Luc plus pSV40-p53 plus pCMV-LMP1 in the NPC-TW06 line that had p53 heterozygous point mutation showed stronger mdm2 promoter activity than cells cotransfected with pmdm2-Luc plus pSV40-p53, but no mdm2 promoter activity was seen in cells cotransfected with pmdm2-Luc plus pCMV-LMP1. Only the EBV-LMP1 but not the EBV-LMP2A gene could enhance p53 to upregulated mdm2 expression. Tumor cells in NPC biopsy specimens revealed similar mdm2 expression as in the animal model. It is concluded that although EBV can indirectly enhance mdm2 gene expression in tumor cells that express this gene, it cannot turn on or directly regulate mdm2 expression in cells that do not express this gene. In other words, EBV plays a role as an enhancer in NPC tumorigenesis.     

Hepatic and small bowel mucormycosis after chemotherapy in a patient with acute lymphocytic leukemia

Mucormycosis is a rare but invasive opportunistic fungal infection with increased frequency during chemotherapy-induced neutropenia. The clinical infections due to Mucor include rhinocerebral, pulmonary, cutaneous, gastrointestinal and disseminated diseases. The first two are the most common diseases and all entities are associated with a high mortality rate. Still hepatic involvement of Mucor is rarely reported. We experienced a case of hepatic and small bowel mucormycosis in a 56-year-old woman after induction chemotherapy for B-cell acute lymphocytic leukemia. Initial symptoms were a high fever unresponsive to broad spectrum antibiotics and pain in the left lower abdominal quadrant. It was followed by septic shock, deterioration of icterus and progressively elevated transaminase. An abdominal CT demonstrated multiple hypodense lesions with distinct margins in both lobes of liver and pericolic infiltration at small bowel and ascending colon. Diagnosis was confirmed by biopsy of the liver. The histopathology of the liver showed hyphae with the right-angle branching, typical of mucormycosis. The patient was managed with amphotericin B and operative correction of the perforated part of the small bowel was performed. However, the patient expired due to progressive hepatic failure despite corrective surgery and long-term amphotericin B therapy.     

Fatal pulmonary-renal syndrome manifested with immune complex crescentic glomerulonephritis in a patient with MPO-ANCA seropositivity

Recent reports have indicated that a significant number of immune complex glomerulonephritis (GN) cases are associated with antineutrophilic cytoplasmic antibody (ANCA). However, most of the reported cases were associated with underlying primary glomerular diseases. When primary glomerular diseases were not found, immune deposits tended to be non-specific and the level of ANCA is usually borderline. We report here upon a case of life-threatening pulmonary-renal syndrome manifested simultaneously with immune complex GN and myeloperoxidase (MPO)-ANCA seropositivity. A 29- year-old man was admitted with pulmonary hemorrhage and rapidly progressing renal dysfunction. On admission, ANCA revealed perinuclear staining with a titer of 1:160. The MPO-ANCA level was 59 IU by ELISA. Other serologic markers including ANA, anti-DS-DNA and anti-GBM Ab were negative. Renal biopsy showed cellular crescents in eight of 18 glomeruli. Immunofluorescence staining showed strong granular deposits of C3, C1q, IgG and IgM in the capillary loop and the mesangium. Electron microscopy showed multifocal electron dense deposits scattered in the mesangium, paramesangium, and the subendothelial and subepithelial areas. The patient initially responded to steroid and cyclophosphamide. MPO-ANCA decreased to less than 10 IU. Twenty three days after hospital discharge, the patient was re-admitted urgently with fever, generalized papulonodular skin lesions, and a recurrence of massive pulmonary hemorrhage and renal dysfunction. He died from uncontrolled pulmonary hemorrhage and respiratory insufficiency. P-ANCA titer and MPO-ANCA level at the second admission were 1:320 and 82 U/ml respectively. Interestingly, relapse was shown to be triggered by varicella zoster infection.