Effect of chlorocresol vs caffeine on muscle contracture in malignant hyperthermia susceptible patients

The phenotype of susceptibility to malignant hyperthermia (MHS); can only be detected reliably by the in vitro caffeine-halothane contracture test (CHCT). Enhanced sensitivity of the calcium-induced calcium release mechanism is responsible for the exaggerated contracture response of skeletal muscle fibers from MHS patients to halothane and caffeine. Chlorocresol was demonstrated to be a potent activator of Ca++ release from skeletal muscle sarcoplasmic reticulum. This effect is probably mediated through action on a ryanodine sensitive Ca++ release channel known to be more sensitive in MH. We studied the effect of chlorocresol on the mechanical contracture response of skeletal muscle from patients presenting for the in vitro CHCT. Chlorocresol induces contracture response in a concentration 1/200 of that of caffeine in muscle strips from MH patients. By adding chlorocresol to the protocol of the CHCT, there is clearer discrimination between the responses of MH patients and normal subjects can be achieved.     

Expression of the opioid growth factor, [Met5]-enkephalin, and the zeta opioid receptor in head and neck squamous cell carcinoma

Heterogeneity of DNA content in multiple hepatocellular carcinomas (HCCs) was investigated by flow cytometry in 62 tumours from 26 patients who had undergone surgical treatment for multiple synchronous HCCs. Heterogeneity of DNA content was defined (a) when tumours had a different DNA ploidy pattern or (b) when the difference in the DNA index of the aneuploid clone was more than 0.1. A tumour with DNA aneuploidy was observed in 17 (66%) of the 26 patients. Heterogeneity of the DNA content was demonstrated in 12 (46%) out of 26 patients: in ten cases by definition (a) and in two cases by definition (b). Histological examination revealed that, of the 12 patients with a heterogeneous tumour DNA content, seven (58%) had a heterogeneous and the remaining five (42%) had a homogeneous type and grade of differentiation among the tumours, showing the absence of a relationship between histological heterogeneity and DNA content. The present results suggest the clinical relevance of DNA content analysis for identifying the clonal origin of multiple HCCs.     

Suppression of collagen-induced arthritis by continuous administration of IL-4

The onset of collagen-induced arthritis in DBA/1 mice is accompanied by a predominantly Th1 response, characterized by production of the proinflammatory cytokines IFN-gamma and TNF-alpha, and a predominance of IgG2a anti-collagen Abs. This study has primarily addressed the effects of continuous administration of exogenous IL-4, a Th2 cytokine, on collagen-induced arthritis in terms of time of onset, clinical symptoms, and histologic changes compared with those in untreated controls. The contributions of Th1 and Th2 cell responses were studied by examining anti-CII IgG subclasses, serum IgE levels, and cytokine production by synovial membrane and lymph node cell cultures. Continuous exposure to IL-4 for 28 days significantly delayed the onset of arthritis from 19 to 37 days and suppressed clinical symptoms. Arthritis occurred approximately 13 to 24 days after treatment ceased. Thereafter, the severity and duration of clinical symptoms were similar to those in control animals, although both joint damage and inflammation at the histologic and cellular levels were less severe than those in untreated controls. During IL-4 treatment, anti-collagen Ab levels were reduced (most significantly those of the IgG2a subclass), histology scores were lower, and the most striking effect was a 1000-fold decrease in TNF-alpha secretion by synovial cells. No significant differences in IgE levels were found between controls and IL-4-treated mice. These data suggest that the anti-inflammatory properties of IL-4 are mediated in part by down-regulation of Th1 responses rather than up-regulation of Th2 responses.     

Immunohistochemical demonstration of acid phosphatase isoenzyme 5 (tartrate-resistant) in paraffin sections of hairy cell leukemia and other hematologic disorders

The demonstration of tartrate-resistant acid phosphatase (TRAP) activity has long been a cornerstone in the diagnosis of hairy cell leukemia (HCL). Recently a monoclonal antibody to this enzyme has been developed that can be used in an immunoperoxidase method on paraffin-embedded tissues. By using a peroxidase-labeled streptavidin biotin method, paraffin sections of B5 and formalin-fixed tissue from 86 cases of HCL (41 bone marrow, 36 spleen, 9 liver) were stained with the antibody to TRAP and compared against staining for CD20 (L26) and DBA.44 (DAKO, Carpinteria, Calif). In addition, 193 specimens (127 bone marrow, 42 lymph node, 19 spleen, 5 other) from a variety of neoplastic and nonneoplastic hematologic conditions were stained using the monoclonal antibody to TRAP. For comparison, these cases were also stained with DBA.44. In the cases of HCL, 80 of 86 specimens were immunoreactive for TRAP. While the antibody to TRAP generally stained less than 50% of the hairy cells, CD20 and DBA.44 stained 90% and 50% to 60% of hairy cells, respectively. Two of three cases of marginal zone lymphoma showed weak immunoreactivity to the TRAP antibody. Two specimens from a patient with Gaucher's disease and 8 of 13 cases of mastocytosis also showed positivity to the TRAP antibody in the macrophages and mast cells, respectively. In contrast, staining for DBA.44 was positive in 3 of 9 cases of B-cell large cell lymphoma, 1 of 4 cases of mantle cell lymphoma, and in the paraimmunoblasts of 1 of 7 cases of small lymphocytic lymphoma. Only HCL was TRAP and DBA.44 positive. This antibody to TRAP is a useful addition to the diagnosis of HCL but should be used in conjunction with CD20 and DBA.44. The use of this antibody to determine minimal residual disease after chemotherapy was not addressed.     

Effects of triazolam and ethanol on proactive interference: evidence for an impairment in retrieval inhibition

The effects of two memory-impairing drugs, ethanol and triazolam, on proactive interference (PI) in memory were studied. Following ingestion of either one of these drugs or a placebo, subjects studied an A-B list (e.g., BEE-WASP) of paired associates, followed by an A-C list (e.g., BEE-HONEY) on the interference trial, and a D-E list (e.g., KING-QUEEN) followed by an A-C list on the control trial. A PI effect was found in the data, such that subjects produced fewer correct second list targets on the interference trial than on the control trial. Neither ethanol nor triazolam was found to influence the size of the PI effect. However, both drugs were found to increase B intrusions on the test of the A-C list, to impair subjects' ability to produce more than one studied response for each cue word, and to impair the subjective experience of retrieved memory information. These data suggest that ethanol and triazolam impair an inhibitory process that normally operates as one component of intentional retrieval, playing an important role in the suppression of unwanted information during a memory task.     

Quantitative assessment of respiratory function following contusion injury of the cervical spinal cord

A prerequisite for higher-level visual tasks such as object recognition is a segmentation of the image into distinct two-dimensional regions. While it has long been assumed that the human visual system jointly exploits region and boundary cues for image segmentation, we report the results of psychophysical experiments which suggest that the visual system relies on geometric properties of bounding contours such as closure and not on the texture of the two-dimensional regions they partition. These findings suggest that the visual system may code and links contours into coherent shapes before surface properties are conjoined.     

Malignant mucosal melanoma of the head and neck: review of the literature and report of 14 patients

BACKGROUND: Fortunately, primary malignant mucosal melanoma of the head and neck is a rare entity. A paucity of data elucidating the predictive factors as well as the unpredictable and aggressive biologic behavior of mucosal melanoma compound the vexing clinical situation. This review summarizes what the literature reveals about the epidemiology, patient survival, patterns of local recurrence, and local and distant metastasis of the disease. Over 1000 patients with this disease have been reported. Survivals at 5 and 10 years is 17% and 5%, respectively. Approximately 19% of patients present with lymph node metastasis and another 16% develop lymph node metastases after treatment, whereas 10% present with distant metastasis. Local metastasis does not affect survival; this is in sharp contrast with skin melanoma. Over 50% of patients experience local treatment failure, and salvage treatment is effective in only 25% of these cases. Local failure is the harbinger of distant metastases. Patients with nasal mucosal melanoma have a 31% 5-year survival rate, whereas sinus melanoma patients fare poorly, with a 0% rate of 5-year survival. METHODS: The authors conducted a retrospective review of 14 patients with characteristics similar to those in the literature in terms of outcome. RESULTS: The 5-year survival rate for these patients was 14%. Whole-body positron emission tomography was performed on 3 patients to detect metastatic disease. The patterns of local recurrence, distant metastasis, and survival for these patients were compared with the same data for patients described in the literature. CONCLUSIONS: Surgery appears to have the greatest efficacy in the management of mucosal melanoma, although radiation therapy may play an increasingly important role in the future.     

Estimation of Koc values for deuterated benzene, toluene, and ethylbenzene, and application to ground water contamination studies

Sorption partition coefficients between water and organic carbon (Koc) for deuterated benzene, toluene, and ethylbenzene have been estimated by measuring values of the octanol-water partition coefficient (Kow) and HPLC retention factors (k1), which correlate closely to values of Koc. Measured values of log Kow for non-deuterated and deuterated toluene are 2.77 (+/- 0.02) and 2.78 (+/- 0.04), respectively, indicating that within experimental error, log Koc for deuterated and non-deuterated toluene are the same. The HPLC method provides greater precision, and yields values of delta log Koc (= log Koc [deuterated]-log Koc [non-deuterated]) of -0.021 (+/- 0.001) for benzene, -0.028 (+/- 0.002) for toluene, and -0.035 (+/- 0.003) for ethylbenzene. The small values of delta log Koc demonstrates that deuterated compounds are excellent tracers for the hydrologic behavior of ground water contaminants.     

Capsular polysaccharide synthesis in Streptococcus pneumoniae serotype 14: molecular analysis of the complete cps locus and identification of genes encoding glycosyltransferases required for the biosynthesis of the tetrasaccharide subunit

We suggested that sexual differentiation of the reproductive system in gonochoric species of invertebrates can be characterized by common molecular mechanisms in spite of high morphological divergences of reproductive tract organs in different animal groups. The present study focused on this problem and report our observations on biochemical characteristics of male-associated polypeptide (MAP) identified in the gonad tissue of bivalve molluscs, Mytilus galloprovincialis, in comparison to those of male-specific carboxylesterase (esterase S) of Drosophila virilis ejaculatory bulbs. We provide evidences for the immunochemical similarity of Mytilus MAP and Drosophila esterase S. We also show that MAP is characterized by esterase activity toward both, alpha- and beta-naphthyl acetates. Using immunofluorescence, we found MAP in the gonad (mantle) connective tissue, membranes of follicles and around gonad ducts but not in sperm cells. Nevertheless, the levels of MAP expression depend on presence or absence of ripe spermatozoa in the gonad follicles. In mature gonads before spawning, MAP is expressed at high level, while in the spent gonads only traces of this polypeptide could be detected. Using Western immunoblot, MAP was not observed in spermatozoa obtained by biopsy of gonad follicles. In contrast, we found this protein in spawned sperm cells. Thus, we suggest that spawning may be required to establish the trafficking mechanisms that control whether MAP is retained or excreted by the gonad. Taken together, the results indicate that MAP of M. galloprovincialis is structurally and functionally related to esterase S of D. virilis ejaculatory bulbs.