Castleman's disease--difficult diagnosis

A case of Mb. Castleman of the localized plasma cell type is reported. This disease expresses several symptoms from different organ systems and therefore an extensive investigation program is often performed. Diagnosis is possible through consideration of all clinical components at the same time: Refractory anaemia, high and refractory SR, weight loss, B-symptoms, but at the same time a relatively good health. CT-scan-demonstration of a localized tumour is an important clue. Histopathologically, the tumour shows vascular hyperproliferation and plasmacytosis of varying maturation. Immunophenotyping of the plasma cells and immunoblasts usually reveals a polyclonal population. Needle biopsies from several regions may be necessary to detect the polyclonality, because monoclonality is often widespread locally in the tumour. HHV8 is correlated to the multicentric PC-type of Mb. Castleman. However, no HHV8 was found in this case.     

Cellular responses to nitric oxide: role of protein S-thiolation/dethiolation

Nitrosothiols, the product of the reaction of nitric oxide-derived species (NOx) with thiols, participate in both cell signaling and cytotoxic events. Glutathione has recently been shown to modulate nitrosothiol-mediated signal transduction and to protect against NOx-mediated cytotoxicity. We have investigated the role of protein S-thiolation/dethiolation as a potential mechanism by which glutathione regulates nitrosothiol signaling and toxicity. Our data show that exogenous sources of NOx decreased both free protein thiol and total glutathione levels in endothelial cells. The decrease in glutathione levels could not be accounted for by formation of S-nitrosoglutathione (GSNO) since borohydride treatment of the nonprotein fraction of cell extracts did not restore glutathione levels, whereas borohydride treatment of protein-containing cell extracts led to recovery of glutathione levels. The NOx-mediated decrease in glutathione and protein thiol content was correlated with an increase in protein mixed disulfide formation, as measured by the incorporation of [35S]glutathione into cellular proteins. [35S]glutathione was incorporated into proteins via a covalent disulfide bond since dithiothreitol removed the radiolabel from cellular proteins. The withdrawal of the exogenous NOx source led to recovery of free protein thiol and cellular glutathione levels, which correlated with the dethiolation of proteins. Dethiolation required the action of the glutathione redox system since 1, 3-bis(2-chloroethyl)-1-nitrosourea, an inhibitor of glutathione reductase, blocked both the recovery of glutathione levels and the dethiolation of proteins. These results suggest that exposure of cells to NOx does not lead to accumulation of GSNO but rather stimulates protein S-thiolation, a mechanism which may have important implications with respect to nitrosothiol signaling and toxicity.     

EPR evidence for the involvement of free radicals in the iron-catalysed decomposition of qinghaosu (artemisinin) and some derivatives; antimalarial action of some polycyclic endoperoxides

The role of pharmacies that specialize in the treatment of specific chronic diseases in the alternate-site health care setting is discussed. The optimal use of medications through disease management programs can improve patient outcomes and lower overall health care costs. The increase in disease management programs has spawned the growth of disease-specific pharmacies in the home care and other alternate-site health care settings. These pharmacies usually operate from a single location or are regionalized operations that deliver pharmaceutical products to patients throughout the United States. The pharmacies employ clinicians who specialize in a particular disease. These clinicians conduct comprehensive patient education programs, drug-use review, and compliance monitoring. Disease management pharmacies focus on chronic, expensive diseases; costs related to inventory, equipment, and storage can be very high. Many disease management pharmacies are involved in preferred-distribution or closed-distribution arrangements with pharmaceutical manufacturers. Pharmacists involved in disease management programs routinely send compliance information about their patients to pharmaceutical companies, managed care organizations, or prescribing physicians. Disease management pharmacies act as advocates for patients with particular chronic diseases. Various foundations and patient advocacy and research groups have created their own disease management pharmacies. Disease management has also reached the community pharmacy practice setting. Pharmacies specializing in the treatment of specific chronic diseases in the alternate-site health care setting can improve health care and promote efficient use of health care dollars.     

Memory for emotional trait adjectives in clinically depressed youth

An experiment was conducted to examine memory for emotional trait adjectives in depressed children and adolescents. Two groups of children and adolescents, clinically depressed participants and non-clinical controls, were compared on computerized versions of recall and recognition memory tasks. Three groups of words (positive trait adjectives, negative trait adjectives, and categorized neutral words) were used in the experiment. Results showed that the depressed group recalled significantly more negative adjectives than positive adjectives, whereas the control group recalled the same number of positive and negative adjectives. This effect was predicted by the association between age and level of depression, with the depression-related bias becoming stronger with age. Signal detection analysis revealed that the depressed group did not show any bias in the recognition task. The findings are discussed with respect to cognitive theories of depression with consideration of the developmental implications.     

A novel human myo-inositol monophosphatase gene, IMP.18p, maps to a susceptibility region for bipolar disorder

Cerebral intraparenchymal cysts without communication with the ventricles are very rare. We report four such cases with no relevant past history or evidence of infection, haemorrhage, trauma, tumour or congenital neural tube defect. At operation smooth wailed cysts with an ependymal-type lining were found. To the best of our knowledge, we present the first correlation of their pathological and radiological features (including magnetic resonance imaging). We also review the literature on these cysts.     

Further evidence for the involvement of tachykinin receptor subtypes in formalin and capsaicin models of pain in mice

Affinity matured murine monoclonal antibody producing cell lines can now be rapidly generated using a novel repetitive, multiple site immunization strategy designated RIMMS. RIMMS capitalizes on rapid hypermutation and affinity maturation events which occur in B cell populations localized within secondary lymphatic tissue early in response to antigenic challenges. A murine myeloma cell line, P3XBcl-2-13, stably transfected with Bcl-2, enhances the outgrowth of hybridomas following somatic fusion with immune lymphocytes isolated from pooled peripheral lymph nodes (PLN) 8-14 days after the initial immunization. Immunizations somatic fusion, screening and isolation of affinity matured IgG secreting monoclonal antibody cell lines occur within a one month time period. By using RIMMS, we have been able to expedite the isolation of affinity matured monoclonal antibodies to numerous antigens, including a drug hapten.     

Influence of sampling on the reproducibility of ovarian follicle counts in mouse toxicity studies

Different ovarian follicle counting procedures were investigated to reduce labor while retaining statistical power. Intact ovaries of untreated CD-1 mice (20/group) from National Toxicology Program Reproductive Assessment by Continuous Breeding (RACB) studies were serially sectioned at 6 microm. Mean numbers of small and growing follicles were used to assess sampling efficiency. In 10 mice per group, comparisons were made between 10% nonrandom samples from every 10th section starting at either the first or sixth section having follicles (approximately 40 sections per ovary). These 10% counts were compared with 5% (20 sections) and 20% (80 sections) nonrandom samples and with 1% (4 sections), 5%, or 10% random samples from the same 10 animals. For two studies, a 10% nonrandom sample was analyzed from 20 mice per group. Follicle counts for each group were comparable regardless of the sampling paradigm. Four to 10 animals provided 90% confidence that a 20% difference in mean counts would be detected. The 1% sample had a larger error term and, thus, slightly reduced statistical power. These data suggest that follicle counts from 1% or 5% random samples may provide a suitable screen for ovarian toxicity.