Posttransplant primary cutaneous Ki-1 (CD30)+/CD56+ anaplastic large cell lymphoma

An anaplastic large cell lymphoma that was negative for Epstein-Barr virus and positive for Ki-1 (CD30) presented as a polypoid scalp mass in a 56-year-old man 16 years after renal transplantation. The lymphoma was of the CD4+ cytotoxic T-cell lineage, and the tumor cells also expressed CD56. Despite reduction in the dose of immunosuppression and localized radiotherapy, the tumor had rapidly progressed to involve the soft tissue of the right hand. Systemic chemotherapy induced complete regression of the soft tissue lesion. This case illustrates that posttransplant primary cutaneous CD30+ anaplastic large cell lymphomas may assume an aggressive clinical course but can still be controlled by systemic chemotherapy.     

Immunization with Combined HSV-2 Glycoproteins B2:D2 Gene DNAs: Protection against Lethal Intravaginal Challenges in Mice

The immunity of a combined DNA vaccine of HSV-2 glycoproteins B2 (gB2) and D2 (gD2) genes in comparison to individual vaccines was studied with regard to protecting against the HSV infection. Two recombinant DNA vaccines of the pHS2-gB2 or pHS2-gD2 were constructed and formulated. The neutralizing antibody titers appeared higher in the B2:D2 gene cocktail-vaccinated mice than that of the individual B2 or D2 gene-vaccinated group alone, and the positive KOS control induced higher titer of the neutralizing antibody than combined or individual gene vaccines. The mock-immunized mice failed to induce enough. The ranks for the CTL activity and the protection rates against the lethal intravaginal challenge were shown as KOS>B2:D2 cocktail>D2>B2 gene vaccines. The vaginal external diseases in the B2:D2 or D-vaccinated mice were significantly reduced against the challenging dosages. The virus titers in the vaginal secretions of the vaccinated mice significantly reduced with time, and the B2:D2 gene vaccine decreased more than each individual vaccine alone. It can be concluded that the cocktailed vaccines are more effective in the humoral and cellular immune responses in the mice, and in the protection of the mice against the intravaginal challenging dosages when compared with individual gene vaccines. All the DNA vaccines failed to block the latent infection in sensory nerves.     

p53 codon 72 polymorphism and risk of cervical carcinoma in Korean women

A common polymorphism of the wild type p53 is known at codon 72 of exon 4, with 2 alleles encoding either arginine (CGC, p53Arg) or proline (CCC, p53Pro). A recent study suggested that this polymorphism affects the susceptibility of p53 protein to human papillomavirus E6 oncoprotein mediated degradation and that individuals homozygous for p53Arg are seven times more susceptible to HPV-associated carcinogenesis of the cervix than heterozygotes. To examine whether the p53Arg genotype could be a risk factor for HPV-associated cervical carcinomas in the Korean population, we analyzed the p53 codon 72 polymorphism status of HPV-positive invasive cervical carcinomas from 52 Korean women and 103 healthy control samples. The proportion of individuals homozygous for p53Arg, homozygous for p53Pro, and heterozygous for the two alleles were 40%, 19%, and 41% in normal healthy controls; 42%, 17%, and 40% in women with HPV-positive invasive cervical carcinoma. There were no significant differences in the distribution of p53 genotypes between controls and cervical carcinomas. This finding indicates that the p53Arg genotype is not associated with an increased susceptibility to cervical carcinoma in Korean women.     

Monoacyl lipoteichoic acid from pneumococci stimulates human cells but not mouse cells

We have developed a method for obtaining pneumococcal lipoteichoic acid (LTA) with none, one, or two acyl chains. Anion-exchange chromatography at pH 9.5 yields pneumococcal LTA (labeled LTA-9.5) that has a mass spectrum identical to that of pre-ion-exchange LTA and loses 500 mass units after deacylation by alkali hydrolysis. Anion exchange at pH 10.5 produces LTA (labeled LTA-10.5) with mass peaks that are 264 mass units lower than those of pre-ion-exchange LTA, and deacylation of LTA-10.5 by alkali hydrolysis reduces the mass by only 239 mass units. This result indicates that LTA-10.5 has lost one of the two acyl chains, whereas LTA-9.5 has both acyl chains. When the biological properties of LTA-9.5 and LTA-10.5 are examined with mouse cells, only LTA-9.5 (and not LTA-10.5) is able to stimulate mouse cells to produce tumor necrosis factor alpha, interleukin-1beta, and nitric oxide. In contrast, both LTA-9.5 and LTA-10.5 can stimulate human cells. LTA became inactive when both acyl chains were removed. Thus, acyl chains are critical for LTA function, and small variations in acyl chains can alter biological properties of LTA.     

Transient expression of osteopontin mRNA and protein in amoeboid microglia in developing rat brain

To investigate a potential role of osteopontin (OPN) in developing rat brain, the expression of OPN mRNA and protein in the developing rat brain relative to the distribution of brain macrophages was investigated using in situ hybridization and immunohistochemistry, and the phagocytic capability of OPN-expressing cells was accessed using rhodamine isothiocyanate (RhIc) as a tracer. OPN-expressing cells appeared from embryonic day 16. During the first week of postnatal life, OPN-labeled cells increased markedly, and peaked around P7, then declined and had completely disappeared by the end of the second postnatal week. The spatiotemporal distribution pattern of OPN mRNA closely matched that of OPN protein. Their morphology and localization were compared with those of cells expressing the established microglial marker OX-42 in adjacent sections, and double-labeling studies demonstrated that OPN was localized to the amoeboid microglia which stain with the lectin GSI-B₄, another marker for microglia. Furthermore, OPN-labeled cells were confirmed to be active phagocytes emitting RhIc fluorescence indicating that the tracer into the brain tissues was engulfed by phagocytosis. Therefore, these results provide the first evidence that OPN is transiently expressed in active brain macrophages in the embryonic and early postnatal brain, and suggest that OPN may contribute to the migration and phagocytic function of brain macrophages in the developing brain.This work was supported by a Korea Research Foundation grant (KRF-2002-015-EP0106)     

Loss of heterozygosity on chromosomes 3p,8p,9p and 17p in the progression of squamous cell carcinoma of the larynx

Previous molecular genetic studies of laryngeal squamous cell carcinoma (SCC)have shown certain chromosomal regions with recurring alterations. But studies of sequential molecular alterations and genetic progression model of laryngeal SCC have not been clearly defined. To identify the chromosomal alterations associated with the carcinogenesis of laryngeal SCC, we analyzed genomic DNA from microdissected squamous metaplasia, squamous dysplasia, invasive SCC, and metastatic carcinoma samples from 22 laryngeal SCC patients for loss of heterozygosity (LOH) at microsatellite loci. Ten microsatellite markers on chromosome 3p, 8p, 9p, and 17p were used. LOH at 9p21 was observed in the all stages including squamous metaplasia, squamous dysplasia, invasive SCC and metastatic carcinoma. LOH at 17p13.1, 3p25 and 3p14.2 was observed from the squamous dysplasia, invasive SCC and metastatic carcinoma. LOH at 8p21.3-p22 was observed mainly from the invasive SCC and metastatic carcinoma. The results suggest that 9p21 in the early event, 17p13.1, 3p25 and 3p14.2 in the intermediate event and 8p21.3- p22 in the late event may be involved in the laryngeal carcinogenesis.     

Expression of E-cadherin and alpha-, beta-, gamma-catenin proteins in endometrial carcinoma

Loss of the cell adhesion molecule E-cadherin is suggested to promote tumor invasion and distant metastasis in tumor development. Recently, it has been proposed that E-cadherin function requires its linkage to the cytoskeleton through catenins. We evaluated the expression of E-cadherin and alpha-, beta-, gamma-catenins in tissues of human endometrial carcinoma, analyzed the patterns of cell adhesion molecules' expression in endometrial carcinoma and investigated the relationship between the statuses of cell adhesion molecules and various clinicopathological factors. This study investigated the immunohistochemical expression of E-cadherin and alpha-, beta-, gamma-catenins in 33 paraffin embedded formalin fixed tissues of endometrial carcinomas. Aberrant E-cadherin, and alpha-, beta-, gamma-catenin expression was observed in 33.3 (11 of 33), 27.3 (9 of 33), 18.2 (6 of 33), and 51.5 (17 of 33) % of the specimens, respectively. Statistically significant correlation was found between aberrant expression of E-cadherin and lymph node metastasis and cell types other than endometrioid adenocarcinoma. Aberrant pattern of gamma-catenin expression was also correlated with deep myometrial invasion. However, alpha-, and beta-catenin expression was not correlated with any clinicopathological parameters. Using the Kaplan-Meier method and log-rank comparison test, abnormal expression of E-cadherin was correlated closely with poor survival (p < 0.05), but cases with loss of both E-cadherin and catenin expression predicted even poorer survival than cases with only one or no aberrant expression in E-cadherin and catenins. We revealed aberrant expression of these cell adhesion molecules among patients with endometrial carcinoma. Aberrant expression of E-cadherin was correlated with lymph node metastasis and cell types other than endometrioid adenocarcinoma, while aberrant expression of gamma-catenin was related with deep myometrial invasion. The expression of E-cadherin might be a possible prognostic factor for endometrial cancer while the expression of catenins may help predict patient's survival.     

Implantation of bone marrow mononuclear cells using injectable fibrin matrix enhances neovascularization in infarcted myocardium

Neovascularization may improve cardiac function and prevent further scar tissue formation in infarcted myocardium. A number of studies have demonstrated that bone marrow-derived cells have the potential to induce neovascularization in ischemic tissues. In this study, we hypothesized that implantation of bone marrow mononuclear cells (BMMNCs) using injectable fibrin matrix further enhances neovascularization in infarcted myocardium compared to BMMNC implantation without matrix. To test this hypothesis, infarction was induced in rat myocardium by cryoinjury. Three weeks later, rat BMMNCs were mixed with fibrin matrix and injected into the infarcted myocardium. Injection of either BMMNCs or medium alone into infarcted myocardium served as controls. Eight weeks after the treatments, histological analyses indicated that implantation of BMMNCs using fibrin matrix resulted in more extensive tissue regeneration in the infarcted myocardium compared to BMMNC implantation without matrix. Examination with fluorescence microscopy revealed that cells labeled with a fluorescent dye prior to implantation survived in the infarcted myocardium at 8 weeks of implantation. Importantly, implantation of BMMNCs using fibrin matrix resulted in much more extensive neovascularization in infarcted myocardium than BMMNC implantation without matrix. The microvessel density in infarcted myocardium was significantly higher (p < 0.05) when BMMNCs were implanted using fibrin matrix (350 +/- 22 microvessels/mm2) compared to BMMNC implantation without matrix (262 +/- 13 microvessels/mm2) and medium injection (76 +/- 9 microvessels/mm2). In addition, average internal diameter of microvessels was significantly larger (p < 0.05) in BMMNC implantation with fibrin matrix group (14.6 +/- 1.2 microm) than BMMNC implantation without matrix group (10.2 +/- 0.7 microm) and medium injection group (7.3 +/- 0.5 microm). These results suggest that fibrin matrix could serve as a cell implantation matrix that enhances neovascularization efficacy for myocardial infarction treatment.     

Hypertrophic obstructive cardiomyopathy with infundibular stenosis treated by alcohol ablation therapy

This report describes an uncommon case of hypertrophic obstructive cardiomyopathy (HOCM) accompanying infundibular stenosis of the right ventricle treated by alcohol ablation therapy, in a 28-yr-old male patient presenting with dyspnea on exertion. HOCM with infundibular stenosis was detected by echocardiogram and cardiac catheterization and patient has dynamic obstructions of both ventricular outflow tracts. We performed alcohol ablation therapy to improve clinical symptoms and to relieve dynamic obstructions of both ventricular outflow tracts. This is the first case in which HOCM with infundibular stenosis of the right ventricle was treated by alcohol ablation therapy.     

Linear regression of eye velocity on eye position and head velocity suggests a common oculomotor neural integrator

The oculomotor system produces eye-position signals during fixations and head movements by integrating velocity-coded saccadic and vestibular inputs. A previous analysis of nucleus prepositus hypoglossi (nph) lesions in monkeys found that the integration time constant for maintaining fixations decreased, while that for the vestibulo-ocular reflex (VOR) did not. On this basis, it was concluded that saccadic inputs are integrated by the nph, but that the vestibular inputs are integrated elsewhere. We re-analyze the data from which this conclusion was drawn by performing a linear regression of eye velocity on eye position and head velocity to derive the time constant and velocity bias of an imperfect oculomotor neural integrator. The velocity-position regression procedure reveals that the integration time constants for both VOR and saccades decrease in tandem with consecutive nph lesions, consistent with the hypothesis of a single common integrator. The previous evaluation of the integrator time constant relied upon fitting methods that are prone to error in the presence of velocity bias and saccades. The algorithm used to evaluate imperfect fixations in the dark did not account for the nonzero null position of the eyes associated with velocity bias. The phase-shift analysis used in evaluating the response to sinusoidal vestibular input neglects the effect of saccadic resets of eye position on intersaccadic eye velocity, resulting in gross underestimates of the imperfections in integration during VOR. The linear regression method presented here is valid for both fixation and low head velocity VOR data and is easy to implement.