The Role of Histological Examination of Nail Clipping in the Diagnosis of Onychomycosis.

BACKGROUND: Diagnosis of onychomycosis is based on potassium hydroxide (KOH), direct smear, culture, and polymerase chain reaction. Nail clippings are rarely used as a diagnostic tool. OBJECTIVES: To evaluate nail clippings for the diagnosis of onychomycosis and to compare it to KOH smears. METHODS: Nail clipping specimens of 39 patients were collected: 34 with onychomycosis proved by positive culture and 5 from normal nails. The specimens were submitted to histological processing and then stained with periodic acid-Schiff (PAS) and Grocott-Gomori's methenamine silver (GMS) stains. For each nail, KOH smear was also performed. Two pathologists who had no information on the KOH smear and the culture results evaluated the nail clipping histology for the presence of fungal element. Their assessment was compared to the KOH smear and culture results. RESULTS: Of the 34 specimens that had positive culture, 25 were dermatophytes, 5 were molds, and 4 were candida. Clipping specimens were positive in 30 cases (88%): 23/25 dermatophyte, 4/5 molds, and 3/4 candida. Pathologists were able to classify the pathogens into dermatophytes and non-dermatophytes based on the morphology. PAS stain results were the same as GMS in evaluation of the nail specimen. KOH smear was positive in 29 nails (85%): 20/25 dermatophytes, all 5 molds, and 4 candida. In all five nails where the culture was negative, both clipping and KOH smear did not show fungal elements. CONCLUSIONS: Nail clippings can serve as a rapid, inexpensive, and reliable method for evaluation of onychomycosis, comparable to KOH smear, with the advantage of pathogen group identification.

The impact of allergies and smoking status on nasal mucosa of hypertrophied turbinates - an immunohistologic analysis.

Background: Allergies and smoking are common reasons for nasal mucosa inflammations, which in turn, cause nasal obstructions. Nevertheless, the impact of coexisting allergies and smoking on nasal mucosa inflammation has not been studied.Objectives: To study the impact of smoking with relation to allergies on nasal mucosa histology and to characterize an immunologic profile using immunohistochemical (IHC) staining.Methods: A cross-sectional study. Nasal biopsies of inferior turbinates from smokers with different allergic statuses were compared. Demographics, comorbidities, histologic, and immunohistochemical (IHC) staining of CD3, CD68, CD 20, and CD138 receptors were compared and analyzed.Results: A total of 53 patients were included, of which 20 (37.7%) were smokers, and 20 (37.7%) had allergic backgrounds. Smokers, both allergic and non-allergic, demonstrated reduced edema compared to the control group (p Value = 0.034) and significantly lower eosinophil density in the stroma compared to the allergic nonsmokers' group (p Value = 0.04). Smokers had a significant negative correlation between the number of cigarettes per day and the expression of CD20 in the stroma (-0.452, p Value = 0.045) and the epithelium (-0.432, p Value = 0.057) in IHC staining. Allergic smokers had a negative correlation (-0.705, p Value = 0.023) between the number of cigarettes per day and the CD68 marked cell expression in the epithelium.Conclusion: The coexistence of an allergic background and smoking alters known immunologic responses within the nasal mucosa. Smoking may have an immunosuppressive role in the nasal mucosa in both innate and humoral immune systems.

Local inflammatory reaction to benign, pre-malignant and malignant glottic lesions: A matched case-control study.

OBJECTIVES: To study the inflammatory infiltrates associated with the different stages of laryngeal carcinogenesis. DESIGN: Observational, matched case-control study of histopathologic specimens. SETTING: An academic referral centre. PARTICIPANTS: A total of 45 patients who underwent removal of glottic lesions between 2008 and 2015. Patients were enrolled and categorised into three matched groups according to lesions' histopathologic diagnoses, 15 patients in each group: benign, pre-malignant and squamous cell carcinoma (SCC). Matching was based on age, gender and pack-years. MAIN OUTCOME MEASURES: Immunohistochemistry staining using monoclonal antibodies against CD4, CD8, CD68, CD20 and S100 representing T-helper cells, cytotoxic T cells, macrophages, B cells and dendritic cells, respectively. Cell counts and distributions were measured and compared between groups. Correlations between the different cells were examined. RESULTS: The predominant cell type was CD8+, followed by CD68+ and CD4+. All inflammatory cells increased significantly in number in SCC (P-value < 0.001), with no significant difference between benign and pre-malignant groups. Strong correlations between the different cells were demonstrated only in the malignant group. S100+ cells correlated with both T-cell subsets, CD4+ (rho = 0.769, P-value = 0.001) and CD8+ (rho = 0.697, P-value = 0.0004). Infiltrates exhibited more extensive distribution in SCC compared to pre-malignant and benign; CD8+ and CD68+ cells were demonstrated in both intraepithelial and stromal regions in 93% of SCC lesions (P-value = 0.0001). CONCLUSIONS: Laryngeal carcinoma demonstrates a unique pattern of inflammatory infiltrates, with significant changes in cell counts and distribution. Leucocyte infiltrates increased significantly in the transition from laryngeal pre-malignant lesion to malignancy while no significant differences were seen between benign and pre-malignant lesions.

Basal cell carcinoma induced by therapeutic radiation for tinea capitis-clinicopathological study.

AIMS: An increased prevalence of aggressive histological subtypes, such as micronodular and morpheaform, has been seen, irrespective of the clinical course, in basal cell carcinoma (BCC) following irradiation for tinea capitis. The aim of this study was to assess the histopathological features of BCCs among patients irradiated for tinea capitis and correlate them with the clinical course. METHODS AND RESULTS: The medical records and BCC biopsy specimens of individuals who were previously irradiated for tinea capitis were reviewed. Demographic data and clinical characteristics were retrieved. Biopsy specimens were evaluated for histological subtype classification and additional histopathological features. A telephone survey was conducted to assess the clinical behaviour of the tumours. Thirty-one patients (17 male; 14 female) were included. The average age at time of first biopsy was 56 years. The total number of lesions was 185, with 80% of subjects showing multiple lesions. The nodular subtype was the most prevalent, followed by superficial, micronodular and mixed tumours. One-third of the BCCs could be classified as aggressive histologically. Stromal fibroplasia and melanin deposits were common. There was no mortality related to BCC. None of the 17 patients who completed the survey had evidence of local invasiveness or metastases. CONCLUSIONS: BCCs following radiation therapy for tinea capitis show unique histological characteristics related to aggressive behaviour. These aggressive features did not reflect the clinical behaviour in the current cohort.

The role of IL-1ß in the early tumor cell-induced angiogenic response.

In this study, we assessed the involvement of IL-1ß in early angiogenic responses induced by malignant cells using Matrigel plugs supplemented with B16 melanoma cells. We found that during the angiogenic response, IL-1ß and vascular endothelial growth factor (VEGF) interact in a newly described autoinduction circuit, in which each of these cytokines induces the other. The IL-1ß and VEGF circuit acts through interactions between bone marrow-derived VEGF receptor 1(+)/IL-1R1(+) immature myeloid cells and tissue endothelial cells. Myeloid cells produce IL-1ß and additional proinflammatory cytokines, which subsequently activate endothelial cells to produce VEGF and other proangiogenic factors and provide the inflammatory microenvironment for angiogenesis and tumor progression. These mechanisms were also observed in a nontumor early angiogenic response elicited in Matrigel plugs by either rIL-1ß or recombinant VEGF. We have shown that IL-1ß inhibition stably reduces tumor growth by limiting inflammation and inducing the maturation of immature myeloid cells into M1 macrophages. In sharp contrast, only transient inhibition of tumor growth was observed after VEGF neutralization, followed by tumor recurrence mediated by rebound angiogenesis. This occurs via the reprogramming of VEGF receptor 1(+)/IL-1R1(+) cells to express hypoxia inducible factor-1α, VEGF, and other angiogenic factors, thereby directly supporting proliferation of endothelial cells and blood vessel formation in a paracrine manner. We suggest using IL-1ß inhibition as an effective antitumor therapy and are currently optimizing the conditions for its application in the clinic.

Mu-Opioid Receptor Expression in Laryngeal Cancer.

OBJECTIVES: Expression of mu-opioid receptors (MORs) has not been investigated in head and neck cancer. In this study, we aimed to assess the expression of opioids receptors in laryngeal cancer, compared to adjacent non-malignant tissue. STUDY DESIGN: A retrospective case series in a single academic center. METHODS: Sixty-four specimens were taken from 32 matched patients, diagnosed with laryngeal-carcinoma (20 supraglottic and 12 glottic), and were analyzed using immunohistochemical stains for MOR. All sections were examined and evaluated with a semi-quantitative analysis for staining intensity and cell count for a percentage of the positively stained cells. Survival of patients was compared based on MOR expression. RESULTS: MOR staining intensity was significantly increased in laryngeal-carcinoma compared to the normal tissue adjacent to the carcinoma (P = 0.019). The percentage of stained cells in non-involved supraglottis was significantly higher compared to the non-involved glottis (P = 0.022), yet this difference was no longer found between supra- and glottic-carcinoma tissues. CONCLUSION: MOR may play a role in the laryngeal cancer environment, as the expression in tumor cells alters from adjacent non-cancerous tissue.

A second-generation microRNA-based assay for diagnosing tumor tissue origin.

BACKGROUND: Cancers of unknown primary origin (CUP) constitute 3%-5% (50,000 to 70,000 cases) of all newly diagnosed cancers per year in the United States. Including cancers of uncertain primary origin, the total number increases to 12%-15% (180,000 to 220,000 cases) of all newly diagnosed cancers per year in the United States. Cancers of unknown/uncertain primary origins present major diagnostic and clinical challenges because the tumor tissue of origin is crucial for selecting optimal treatment. MicroRNAs are a family of noncoding, regulatory RNA genes involved in carcinogenesis. MicroRNAs that are highly stable in clinical samples and tissue specific serve as ideal biomarkers for cancer diagnosis. Our first-generation assay identified the tumor of origin based on 48 microRNAs measured on a quantitative real-time polymerase chain reaction platform and differentiated 25 tumor types. METHODS: We present here the development and validation of a second-generation assay that identifies 42 tumor types using a custom microarray. A combination of a binary decision-tree and a k-nearest-neighbor classifier was developed to identify the tumor of origin based on the expression of 64 microRNAs. RESULTS: Overall assay sensitivity (positive agreement), measured blindly on a validation set of 509 independent samples, was 85%. The sensitivity reached 90% for cases in which the assay reported a single answer (>80% of cases). A clinical validation study on 52 true CUP patients showed 88% concordance with the clinicopathological evaluation of the patients. CONCLUSION: The abilities of the assay to identify 42 tumor types with high accuracy and to maintain the same performance in samples from patients clinically diagnosed with CUP promise improved utility in the diagnosis of cancers of unknown/uncertain primary origins.

Up-regulation of L1CAM is linked to loss of hormone receptors and E-cadherin in aggressive subtypes of endometrial carcinomas.

Endometrial carcinomas (ECs) are classified into type 1 (less aggressive) and type 2 (aggressive) tumours that differ in genetic alterations. So far, reliable immunohistochemical markers that can identify patients with high risk for recurrence are rare. We have defined the expression of L1 cell adhesion molecule (L1CAM), a biomarker previously identified for EC, and compared its expression to oestrogen receptor (ER)/progesterone receptor (PR) and E-cadherin. We found that L1CAM was absent in normal endometrium and the vast majority of endometrioid ECs (type 1) but was strongly expressed in serous and clear-cell ECs, considered as type 2. 78/272 cases were identified as L1CAM-positive endometrioid ECs that were correlated with a poor prognosis. Strikingly, we observed an inverse relationship between L1CAM and ER/PR/E-cadherin expression in all ECs. In mixed ECs, composed of endometrioid (L1CAM(-) ER/PR(+) E-cadherin(+)) and clear-cell/serous (L1CAM(+) ER/PR(-) E-cadherin(-)), both phenotypes were co-expressed. In some of these cases L1CAM was up-regulated at the leading edge of the tumour, where ER/PR and E-cadherin expression were selectively lost. In EC cell lines treated with the epithelial-mesenchymal transition (EMT) inducer TGFbeta1, L1CAM and vimentin were strongly up-regulated, while E-cadherin expression was reduced. The treatment also resulted in an increased expression of the EMT transcription factor Slug and an enhanced cell invasion. Depletion of Slug by siRNA knockdown prevented both L1CAM up-regulation and enhanced cell invasion. According to our analysis, we suggest that L1CAM is a novel marker for EMT in ECs and that L1CAM-typing could identify endometrioid ECs that have type 2-like features and are at high risk for recurrence.

Organizing pneumonia and non-necrotizing granulomata on transbronchial biopsy: coexistence or bronchiolitis obliterans organizing pneumonia secondary to Mycobacterium kansasii disease.

Mycobacterium kansasii disease was diagnosed in an 85-year-old woman admitted to the hospital for cough and gradually worsening breathlessness. Transbronchial biopsy indicated either non-necrotizing granulomata or bronchiolitis obliterans organizing pneumonia (BOOP). She was cured with combined therapy of specific anti-mycobacterial medications and systemic steroids. To our knowledge, this is the first report of M. kansasii non-tuberculous mycobacterium disease with a BOOP-like pattern on lung biopsy.

Molecular mechanisms of enhanced wound healing by copper oxide-impregnated dressings.

ABSTRACT Copper plays a key role in angiogenesis and in the synthesis and stabilization of extracellular matrix skin proteins, which are critical processes of skin formation. We hypothesized that introducing copper into wound dressings would enhance wound repair. Application of wound dressings containing copper oxide to wounds inflicted in genetically engineered diabetic mice (C57BL/KsOlaHsd-Lepr(db)) resulted in increased gene and in situ up-regulation of proangiogenic factors (e.g., placental growth factor, hypoxia-inducible factor-1 alpha, and vascular endothelial growth factor), increased blood vessel formation (p<0.05), and enhanced wound closure (p<0.01) as compared with control dressings (without copper) or commercial wound dressings containing silver. This study proves the capacity of copper oxide-containing wound dressings to enhance wound healing and sheds light onto the molecular mechanisms by which copper oxide-impregnated dressings stimulate wound healing.

Down-Expression of Kinin Receptors in Allergic Nasal Polyps Epithelia: An Immunohistochemistry Study.

OBJECTIVES: To investigate the expression of B1 and B2 receptors in patients with nasal polyps (NPs) compared to controls. STUDY DESIGN: Retrospective case series. SETTINGS: Single academic center. SUBJECTS AND METHODS: Nasal biopsies of patients with NPs were compared to inferior turbinates of control patients. Comparisons included basic demographics and comorbidities, intensity of inflammation, and immunohistochemical staining of B1 and B2 receptors measured by immunohistochemistry staining scores (ISSs). RESULTS: A total of 41 patients were enrolled, with 21 patients (51.2%) in the NP group and 20 patients as controls. No differences were found in the prevalence of allergic comorbidities and smoking between the groups. The NP group demonstrated significantly higher prevalence of moderate and severe mononuclear infiltrates compared to the control group (57.1% vs 5.3%, P < .001). The NP group had significantly lower B1 expression in smooth muscle compared to the control group (mean ISS 0.22 vs 1.56, P < .001, respectively) and significantly more B2 expression in epithelial cells (mean ISS 1.81 vs 0, P < .001, respectively). CONCLUSION: Patients with NPs exhibit different expression patterns of B1 and B2 compared to control patients. This implies that bradykinin receptor regulation participates in the pathogenesis of NPs.

Designing ageing conditions in tumour microenvironment-a new possible modality for cancer treatment.

While tumour incidence is known to augment with age, paradoxically tumour growth and metastasis were often found to proceed at a slower rate at late ages. This age-related biological behaviour of tumours actually imposes a differential therapeutic approach to the old cancer patient. Several mechanisms of the age-related reduced tumour progression have been demonstrated: decreased tumour cell proliferation, increased apoptotic cell death, decreased angiogenesis and anti-tumoural immune response changes. We postulated that it might be possible to design age-adjusted treatment modalities based on the mechanisms responsible for the reduced tumour progression rate in the aged. Based on these mechanisms, we compared the effect of different treatments (apoptosis-inducing agents, Hydrocortisone and Adriamycin, anti-angiogenic agent, TNP-470, and immunomodulators-Levamisole and BCG) on two experimental tumours (B16 melanoma and AKR lymphoma) growing in young and old mice. Most treatments showed, in both tumours, a higher inhibitory effect on tumours growing in old mice than on those developing in young ones, to our knowledge, a feature not described before for anti-tumoural agents. We suggest that designing ageing conditions in tumours of young patients might possibly alleviate neoplastic aggressiveness in these patients as well.

Decreased DNA ploidy may constitute a mechanism of the reduced malignant behavior of B16 melanoma in aged mice.

Numerous data demonstrate a lower aggressiveness of tumors in aged as compared to young patients. The mechanisms underlying this phenomenon have not yet been completely elucidated. Several mechanisms have been shown, such as reduced tumor cell proliferation, increased apoptosis, immune response modifications and reduced angiogenesis in aged organism tumors. In the present study we report an incidentally found, not yet described mechanism, of the age-related reduced tumor progression, namely a decreased ploidy in B16 melanoma growing in old (near diploidy) as compared to young mice (tetraploidy). We surprisingly observed that tumor cells from aged mice were of smaller cell and nuclear size than those of young animals. Flow cytometry forward scatter data also showed a smaller cell size of melanoma cells from old mice. DNA flow cytometry profile comparison demonstrated that while B16 melanoma cells from young animals contained a high percentage of tetraploid cells, those derived from old animals were mostly close to diploid. A high importance has recently been attributed to aneuploidy as being at the origin of the genetic instability of neoplasia. Our results may support this notion. The transit from tetraploidy to near euploidy in melanoma cells growing in aged mice might avoid the genetic instability inherent to tumor progression.

Efficacy of anti-angiogenic treatment of tumors in old versus young mice.

Cancer treatment in the older population, the most afflicted by the disease, is as yet, inefficient. A reduced aggressiveness of tumors is often observed in the elderly, implying the necessity for therapeutic modalities adjusted to age. A rational design of age-related cancer therapy could be based on the mechanisms of this phenomenon. It is suggested that, in addition to the patient's old age-specific health problems (which prohibit the use of the aggressive cancer treatments now in use), the age-related differential tumor biology (apparently beneficial to the old) should also be considered for the design of treatment modalities suitable for the aged. Based on one mechanism of the reduced aggressiveness of tumors in the old (age-dependent decreased angiogenesis), we compared the effect of an anti-angiogenic treatment in young and old mice. TNP-470 treatment resulted in an inhibitory effect on B16 melanoma in both young and old mice but the effect was more pronounced in old animals. Moreover, a high percentage of long-term surviving animals was observed only in the old-treated mice. Treatment with TNP-470 of the AKR lymphoma produced similar results. We thus found a differential age-dependent therapeutic efficiency of an anti-angiogenic agent on two tumors. Importantly, the anti-angiogenic drug was more efficient against tumors of old animals.

Expression profile analysis in multiple human tumors identifies L1 (CD171) as a molecular marker for differential diagnosis and targeted therapy.

L1 cell adhesion molecule (CD171) represents a strongly unfavorable prognostic biomarker for ovarian and endometrial carcinomas. Here we carried out an immunohistochemical survey of L1 expression in normal adults and in a broad range of benign and malignant tumors using monoclonal antibody L1-11A and the novel monoclonal antibody L1-14.10. In normal tissues, L1 was expressed in the collecting tubules of adult tissues and pediatric kidney and in peripheral nerve bundles. In tumors of the female genital tract, L1 was detected in adenocarcinomas of the cervix and fallopian tubes, in addition to ovarian and endometrial carcinomas. Nongynecological tumors expressing L1 comprised malignant melanoma, colon adenocarcinoma positive to chromogranin, clear-cell adenocarcinoma of the urinary bladder, pheochromocytoma, small cell lung carcinoma, and tumors of the nervous system. L1 was absent in breast carcinoma, gastrointestinal tract carcinomas, gastrointestinal carcinoids, renal clear-cell carcinomas, prostate adenocarcinomas, and mesotheliomas. Surprisingly, L1 expression in established breast and renal carcinoma cell lines was not a predictor for its presence in these human tumors in vivo. Our results suggest that L1 expression in tumors is not ubiquitous but restricted to certain subtypes and may be a helpful molecular marker for differential diagnosis and target for antibody-based therapy.

Lens epithelial cell growth on the anterior optic of 2 hydrophobic intraocular lens models.

PURPOSE: To evaluate lens epithelial cell (LEC) proliferation on the anterior optic of 2 types of hydrophobic intraocular lenses (IOLs). SETTING: Harlan Biotech Israel and Kaplan Medical Center, Rehovot, Israel. DESIGN: Experimental study. METHODS: Ten New Zealand white rabbits had crystalline lens removal and implantation of an Acrysof IOL in 1 eye (Group 1) and a Tecnis IOL in the fellow eye (Group 2). A weekly biomicroscopy examination was performed during the 2-week study duration, after which the rabbits were humanely killed. The eyes were enucleated, and the complexes containing the IOL and the capsular bag were evaluated for the presence of LECs and large cells (macrophages and giant cells) on the IOL anterior optic and for proteinaceous matrix deposits along the capsulorhexis margin. RESULTS: Lens epithelial cell were detected on all of the IOLs in Group 1 and on none in Group 2 (P < .001). Areas of proteinaceous matrix deposits adjacent to the edge of the capsulorhexis were detected on 8 IOLs in Group 1 and on none in Group 2 (P < .001). Large cells were identified on all IOLs in Group 1 and on 9 IOLs in Group 2 (P = 1.0). No difference in the general inflammation markers was found between the 2 IOL types (P = .234). CONCLUSIONS: Lens epithelial cell with corresponding proteinaceous matrix deposits were significantly more abundant on the IOLs in Group 1 than on the IOLs in Group 2. There was no difference in the presence of large cells or in general inflammation markers between the 2 IOL types. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Age-adjusted antitumoral therapy based on the demonstration of increased apoptosis as a mechanism underlying the reduced malignancy of tumors in the aged.

In view of the constant increase in the aged population, age-adjusted cancer therapy becomes an urgent target. Although cancer incidence rises with age, paradoxically, growth rate and metastasis often proceed at a slower rate in the aged. Determining the mechanism(s) underlying this reduced tumor progression in the old might have implications for a rational design of age-adjusted therapy. Thus far, decreased cell proliferation or immune response modifications were suggested as possible mechanisms. We show here that an increased tendency to apoptotic tumor cell death in the aged could constitute an additional mechanism. Based on this mechanism, we compared the therapeutic efficacy of two apoptosis inducers, hydrocortisone and adriamycin, on AKR lymphoma and B16 melanoma growth in young and old mice. Treatment with hydrocortisone acetate inhibited tumor growth practically only in old mice in the two tumor systems. Similar effects were obtained with adriamycin treatment of AKR lymphoma but opposite results were seen with B16 melanoma. We thus demonstrated, in three of the four tumor-therapeutic modality systems examined, an age-related antitumoral efficacy of two apoptosis-inducing agents, with tendency for a remarkably more pronounced effect in aged mice.

L1 expression as a predictor of progression and survival in patients with uterine and ovarian carcinomas.

BACKGROUND: Ovarian and uterine carcinomas are the most common cause of cancer-related deaths in gynecological malignant diseases. We aimed to assess whether the L1 adhesion molecule, an important mediator for cell migration for neural and tumour cells, is expressed in these carcinomas. METHODS: We investigated L1 expression by immunohistochemistry, RT-PCR, and Western blot analysis of tumour samples. Soluble L1 in the serum was detected by ELISA and immunoprecipitation. FINDINGS: We detected the L1 adhesion molecule in ovarian and uterine tumours in a stage-dependent manner. In a retrospective study L1 was found in 46 of 58 ovarian carcinomas and 20 of 72 uterine adenocarcinomas. L1 expression was an excellent predictor of poor outlook (p<0.00001). Patients with L1 positive uterine tumours were at high risk for progression even in the endometrioid-type tumours, which usually have a favourable prognosis. In uterine tumours, expression of L1 in curettage samples enabled us to identify aggressive tumours before the operation. Soluble L1 was specifically detected in serum samples from patients with ovarian and uterine tumours. ADAM10, which was implicated in previous studies as L1 sheddase, was expressed in tumours in which soluble L1 was present in the serum. INTERPRETATION: L1 is overexpressed in ovarian and uterine carcinomas and is associated with short survival. L1 can serve as a new marker for prediction of clinical outcome and could be helpful to identify patients with uterine tumours who are at high risk for recurrent disease. L1 expression and cleavage could promote dissemination of tumours by facilitating cell migration.

Ageing-apoptosis relation in murine spleen.

Relatively few studies have been published with regard to modification of apoptosis in normal tissues as a function of ageing. The majority of these studies demonstrated an increase in programmed cell death (PCD) with age. However, opposite results, namely loss of apoptotic control with age, have also been reported. In the present study, we examined proliferation and apoptotic cell death in spleens of C57/BL mice of different ages. A tendency towards decrease in cell proliferative capacity was seen with age. By contrast, apoptosis was increased in spleens from aged animals. Moreover, the proliferative cell/apoptotic cell ratio decreased in function of age. Ladder type DNA degradation was much more pronounced in DNA derived from splenocytes of old mice. These results were supported by a decrease of Bcl-2 and an increase in Fas receptor expression as well as by increased activation of caspases 8, 3 and 9 in splenocytes from aged animals. In addition, cell surface molecular markers recognizable by macrophages in apoptotic cells, namely decreased sialic acid concomitant with increased unmasking of galactose residues, were more pronounced on splenocytes from old mice than on those from young animals. In addition to the experimental evidence which supports a role of apoptotic cell death in ageing, a series of theoretical reasoning, which could also favor this possibility, are discussed.

L1 adhesion molecule (CD 171) in development and progression of human malignant melanoma.

The L1 adhesion molecule (CD171) plays an important role in axon guidance and cell migration in the nervous system. In the human, L1 is expressed on tumors derived from neurocrest and on certain carcinomas. We have analyzed immunohistochemically L1 expression on paraffin embedded specimens of acquired melanocytic nevi, primary cutaneous melanomas, and cutaneous and lymph node metastases of malignant melanomas. We found an increase in L1 immunoreactivity in malignant melanomas and metastases of malignant melanomas as compared to acquired melanocytic nevi that was statistically significant (P<0.05). Additionally, a correlation of L1 immunoreactivity with histological data of prognostic value such as Clark level and the expression of alphav-integrins was found. We detected soluble L1 in the conditioned medium of cultivated melanoma cells but only in 1/40 serum samples from a panel of melanoma patients representing various stages of disease. Our findings suggest that the presence of L1 might contribute to tumor progression by promoting cell adhesion and migration.