FOCAL INTRATUMORAL HETEROGENEITY FOR TELOMERASE ACTIVITY IN HUMAN PROSTATE CANCER

PURPOSE: The value of telomerase activity as a marker in clinical decision-making is closely related to how representative the analysis of a small tumor sample is for the whole tumor. We therefore evaluated the intratumoral distribution pattern of telomerase activity in prostatic carcinomas. MATERIALS AND METHODS: From 50 prostate cancer patients treated with radical prostatectomy, telomerase activity was determined using the telomeric repeat amplification protocol (TRAP assay). Comparative analysis of at least two separate cancer areas from a single tumor was performed in 42 cases. RESULTS: Telomerase activation has been demonstrated in 90% of the prostatic carcinomas. Focal intratumoral heterogeneity was found in 38.1% of the tumors with at least two different areas examined. Telomerase positivity of all samples from one given tumor was detected in 50%, telomerase negativity of all samples in 11.9%. A heterogeneous telomerase activity pattern was more frequently detected in tumors with a Gleason score < or = 7 than in those with a Gleason score > 7. Furthermore, there was an increase in the proportion of homogeneously telomerase-positive tumors with increase in severity of the Gleason score. The differences reached statistical significance. Telomerase activity was also detected in non-cancerous prostatic tissue samples. CONCLUSIONS: Telomerase activation is nearly ubiquitous in prostatic carcinomas, although a heterogeneous telomerase activity pattern within tumors might produce a false-negative result in the telomerase activity assay. This limits the value of telomerase activity assays for diagnostic means. There is evidence for a shift from telomerase-negative prostate cancer tissue toward telomerase positivity during the progression process of prostate cancer. The relatively high proportion of telomerase-positive nonmalignant prostatic tissue samples argues against cancer-specificity of telomerase activation.     

Reactive and neoplastic lymphocytes in human bone marrow: morphological, immunohistological, and molecular biological investigations on biopsy specimens

BACKGROUND: Slight, diffuse or focal lymphocyte proliferation is relatively common in bone marrow biopsy specimens. It may be impossible to determine whether this represents a reactive lymphocytosis or low grade non-Hodgkin lymphoma (NHL) on the basis of routine investigations alone. AIM: To investigate the supplementary use of molecular biological techniques in this situation. METHODS: 529 formalin fixed, paraffin embedded bone marrow biopsy specimens from the iliac crest were subjected to histological and immunohistochemical staining to determine the number and nature of the lymphocytes present. The cases were divided into three groups according to the lymphocyte count: normal (< 10% of nucleated bone marrow cells), slightly increased (10-30%), and markedly increased (> 30%). All of the last group could be diagnosed as NHL from the morphological findings alone. The clonality of rearrangements of the IgH and TCR gamma genes was investigated by polymerase chain reaction (PCR). RESULTS: Monoclonality was observed in 7.5% of the 372 cases with a normal lymphocyte count, in 50% of the cases with a modest increase in lymphocyte numbers (suggesting a diagnosis of low grade NHL not detected by immunostaining), and in 77% of the cases with markedly increased lymphocyte numbers. CONCLUSIONS: If PCR is used in addition to the immunohistochemical investigation of bone marrow biopsies, considerably more cases of NHL can be identified, making this of particular use in staging and detection of recurrences.     

Sleep and rest facilitate auditory learning

Sleep is superior to waking for promoting performance improvements between sessions of visual perceptual and motor learning tasks. Few studies have investigated possible effects of sleep on auditory learning. A key issue is whether sleep specifically promotes learning, or whether restful waking yields similar benefits. According to the "interference hypothesis," sleep facilitates learning because it prevents interference from ongoing sensory input, learning and other cognitive activities that normally occur during waking. We tested this hypothesis by comparing effects of sleep, busy waking (watching a film) and restful waking (lying in the dark) on auditory tone sequence learning. Consistent with recent findings for human language learning, we found that compared with busy waking, sleep between sessions of auditory tone sequence learning enhanced performance improvements. Restful waking provided similar benefits, as predicted based on the interference hypothesis. These findings indicate that physiological, behavioral and environmental conditions that accompany restful waking are sufficient to facilitate learning and may contribute to the facilitation of learning that occurs during sleep.     

Indolent systemic mastocytosis with elevated serum tryptase, absence of skin lesions, and recurrent severe anaphylactoid episodes

BACKGROUND: In contrast to aggressive mastocytosis, patients with indolent systemic mastocytosis (ISM) usually present with urticaria pigmentosa-like skin lesions. In those who lack skin lesions, mastocytosis is often overlooked or confused with endocrinologic, allergic, or other internal disorders. CASE REPORT AND RESULTS: We report on a 33-year-old male patient in whom severe hypotensive episodes occurred after contact with ants or yellow jackets. Since no specific IgE was detected, the serum tryptase concentration was measured and found to be clearly elevated (70 ng/ml). Consecutive staging and examination of the bone marrow revealed ISM. The patient was advised to circumvent insect contact, to take antihistamines on demand, and to carry an epinephrine self-injector for emergency events. In a retrospective analysis of 40 patients seen between 1988 and 2003, only 2 had a life-threatening mediator-related episode before ISM was diagnosed. CONCLUSIONS: Our report confirms the diagnostic value of tryptase in patients with suspected mastocytosis. In addition, the report suggests that the lack of typical skin lesions does not exclude an indolent form of mastocytosis even if the serum tryptase is clearly elevated. Finally, our case further shows that mastocytosis can be an important differential diagnosis to be considered in patients with unexplained anaphylactoid or other mediator-related symptoms.     

Increase of bone marrow lymphocytes in systemic mastocytosis: reactive lymphocytosis or malignant lymphoma? Immunohistochemical and molecular findings on routinely processed bone marrow biopsy specimens

AIMS: To clarify the nature (reactive or neoplastic) of lesional, perifocally aggregated lymphocytes in bone marrow infiltrates of systemic mastocytosis (SM), the histopathology of which can resemble malignant lymphoma with focal bone marrow involvement, particularly low grade malignant B cell lymphoma of lymphoplasmacytic immunocytoma subtype, which frequently exhibits increased mast cell (MC) numbers. METHODS: Thirteen cases of SM and three of lymphoplasmacytic immunocytoma with predominant focal bone marrow infiltration were investigated. Immunostaining of formalin fixed, paraffin wax embedded bone marrow specimens was performed using antibodies against CD2, CD5, CD20, CD23, and CD25; kappa and lambda immunoglobulin light chains; and MC markers chymase, tryptase, and CD117 (KIT). Monoclonal rearrangements of IgH and TCRgamma were studied using seminested polymerase chain reaction (PCR). c-kit point mutation Asp816-Val was detected by PNA mediated PCR clamping and hybridisation probes. RESULTS: The lymphocytic clusters in SM contained nearly equal numbers of mature T and B cells, the latter with no coexpression of aberrant antigens, such as CD5 or CD23. Most MCs in SM cases constantly coexpressed tryptase, CD25, and CD117. No monoclonal rearrangements were seen for IgH or TCRgamma. In contrast, B cells from immunocytomas showed light chain restriction and monoclonal rearrangement for IgH, confirming their neoplastic nature. c-kit point mutation Asp816-Val was found in ten of 13 SM cases, but in none of the three immunocytomas. CONCLUSIONS: Focal accumulations of lymphocytes in the bone marrow of SM are reactive in nature and could be termed lymphocytosis. A diagnosis of SM-AHNMD/immunocytoma should not be made.     

Lethal outcome in xanthogranulomatous endometritis

Xanthogranulomatous inflammation is rare, mainly involving the kidneys, while primary xanthogranulomatous endometritis (XE) is a very unusual finding, histologically characterized by partial or complete replacement of the mucosa by granulation tissue with an abundance of foamy histiocytes, siderophages and multinucleated giant cells. We present the case of a 69-year-old woman with a short history of abdominal pain and a palpable mass in the pouch of Douglas. Dilatation of the cervix drained a pyometra. Histological examination of the curettage rendered the diagnosis of XE. Microbiological studies revealed enterococcus spp. and Peptostreptococcus magnus. Despite antibiotic treatment the patient died of heart failure due to systemic inflammation. Autopsy confirmed the diagnosis of XE with transmural extension into the peritoneal cavity. Such a lethal course of XE is extraordinary. Proposed causes of XE include obstruction, infection and hemorrhage. Demonstration of enterococcus spp. and P. magnus supports the probable significance of bacteria in the development of XE. Because this condition may mimic malignant disease macroscopically and histologically, knowledge of XE is of major importance for both pathologists and gynecologists.     

Analysis of the ST-segment in terms of principal components: application on multichannel magnetocardiographic recordings

Parameterization of the ST-segment is used as a tool for risk stratification for patients to suffer from ventricular tachycardia. This parameterization is performed in terms of Principal Component Analysis (PCA) applied on multichannel magnetocardiographic (MCG) recordings. 55-channel MCG was recorded from 14 normal persons, 10 patients with CHD, 14 patients with MI, and six patients with VT. We found a significantly (p < 0.05) lower PCA-score in patients with MI compared to normals. The lowest PCA-score was found in VT patients. Significant differences can be found between VT patients and normals and also between VT patients and CHD patients.     

Optimal degradation rate for collagen chambers used for regeneration of peripheral nerves over long gaps

The experimental study of peripheral nerve regeneration has depended heavily on the use of a nerve chamber in which the stumps of the transected nerve are inserted. A large variety of chamber fillings and chamber types have been used in an effort to induce a higher quality of regeneration across the gap initially separating the two stumps. In this study we studied the morphology of nerves regenerated across a 15 mm gap following implantation of a series of five chambers. The chambers were fabricated from type I collagen and possessed identical pore volume fractions as well as average pore diameters, but differed in cross-link density continuously along the series. The residual mass of the implanted chambers at 9 weeks was observed to increase continuously with increasing cross-link density along the series, indicating a continuous decrease in degradation rate. The quality of regenerated nerves, determined by the number of large diameter fibers (A-fibers) per nerve, the average diameter of all axons and the ratio of area occupied by axons (N-Ratio), was superior at an intermediate level of chamber degradation rate. The maximal quality of peripheral nerve regeneration corresponded to an optimal degradation rate with an estimated chamber half-life of approximately 2-3 weeks following implantation. A speculative mechanistic explanation of the observed optimum focuses on the hypothetical role of cell and cytokine traffic that may take place through holes in the chamber generated by the degradation process. The data show the presence of a hitherto unreported optimal chamber degradation rate that leads to regenerated nerves of maximum quality.     

Primary lymph node plasmacytomas (plasmacytic lymphomas)

To determine whether primary lymph node plasmacytoma (PLNP) is a distinct entity among other types of plasma cell neoplasia, we analyzed a large series of PLNPs from 2 large lymphoma registries to compare histologic, immunophenotypic, and clinical features of PLNPs, nonnodal extramedullary plasmacytomas, and multiple myeloma. Twenty-five PLNPs (clinical data on 15 cases) were compared with 10 non-lymph node plasmacytomas and 51 cases of multiple myeloma; 36 cases of reactive plasmacytoses were used as controls. The histologic features of PLNP and other extramedullary plasmacytomas were similar. The histologic features of PLNPs were more immature than those of reactive plasmacytoses and less immature than in multiple myeloma. The immunophenotype of PLNPs significantly differed from that of reactive plasmacytoses, other extramedullary plasmacytomas, and multiple myeloma. PLNPs did not progress to multiple myeloma, unlike other extramedullary plasmacytomas, even though survival in PLNPs and other extramedullary plasmacytomas was similar. Our findings suggest that PLNPs may be distinct from other plasma cell dyscrasias.