Spinal antinociceptive effects of adenosine compounds in mice

The effects of injecting ATP, ADP, AMP, adenosine and adenine intrathecally on the pain response induced by the injection of substance P (10 ng/mouse) intrathecally were studied. All the compounds except adenine inhibited the pain response in a dose-related manner. The ED50 values of ATP, ADP, AMP and adenosine were 2.10, 0.93, 0.88 and 0.48 micrograms/mouse, respectively. Pretreatment with theophylline at a dose of 100 mg/kg p.o. markedly diminished all the antinociceptive effects. The effect of adenosine was not affected by s.c. injection of naloxone. These results suggest the existence of adenosine receptors which modulate spinal nociceptive sensory processing, independently of the endogenous opiate system.     

PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells

PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM.     

School-refusal and social-withdrawal in the clinical setting at a psychiatric medical institution]

Fifty two outpatients, who showed signs of school-refusal-withdrawal at the Shiga Prefectural Psychiatric Institution have been analyzed according to their age, gender, ICD-10 diagnosis, medical evolution, and total number of consultations. A total of 61.5% of the population were male, and they showed a higher average and a wider range of age than female patients. According to the ICD-10 diagnosis, 67.3% were in the group of F40-48 neurotic, stress-related and somatoform disorders, and 11.5% were in the group of F30-39 mood [affective] disorders. Twenty five % of the patients were assumed to have show medical improvement, and 42.3% of the patients continued to have further consultations. This article discusses the possible role of psychiatric medical institutions in supporting cases of school-refusal and social-withdrawal.     

Scintigraphic detection of recurrence of medullary thyroid cancer

A case of recurrent medullary thyroid cancer (MTC) was evaluated with¹²³I-MIBG,^99mTc(V)-dimercaptosuccinic acid (DMSA), and²⁰¹Tl scintigraphy. This patient had been operated on for MTC in the right thyroid. Recently a left neck mass was noticed, and was suspected of being a. recurrence of MTC based on increased plasma calcitonin (CT) and carcinoembryonic antigen (CEA). He was operated on for the neck mass which revealed MTC, and papillary thyroid cancer was incidentally found in the left thyroid, but the CT and CEA levels remained high, and remaining MTC tumor was suspected. But the location of the tumor was unknown. Although^99mTc(V)-DMSA scintigraphy is generally believed to be superior in sensitivity to¹²³I-MIBG scintigraphy, it did not demonstrate the tumor site but²⁰¹Tl and¹²³I-MIBG did. Furthermore,¹²³I-MEBG scintigraphy has greater specificity for tumors which arise in the neural crest. Judging from the results of this case and cases reported in the literatures, both¹²³I-MIBG and^99mTc(V)-DMSA should be performed in the detection of recurrent MTC.     

Relation between toxicity and carcinogenesis in the kidney: an heuristic hypothesis

Cellular toxicity and cellular carcinogenesis are closely linked. In the kidney, this relationship has been emphasized by the recent discovery of a number of putatively non-mutagenic chemicals that result in acute and chronic toxicity and ultimately in carcinogenesis, especially in the male rat. Many, but not all such compounds, result in renal PTE phagolysosomal overload. At the same time, known metabolites of other carcinogens, e.g., HCBD and FBPA, result in acute renal injury and/or necrosis, followed by chronic tubular disease, interstitial nephritis, and ultimately carcinogenesis. A series of cell mechanisms have been suggested that lead from acute cell injury to altered control of cell division. These mechanisms appear to involve ion deregulation, (especially [Ca2+]i) resulting from a variety of continued injuries, (e.g., oxidative stress from inflammatory cells) and ultimately leading to altered gene expression.     

Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

Performance standards for toric soft contact lenses.

PURPOSE: To simplify the clinical assessment of toric soft contact lens (TSCL) on-eye behavior by establishing a set of standard clinical evaluation techniques. The likely performance range expected among the TSCL wearing population was determined for a series of lens designs and acceptable performance standards indicated for each variable. METHODS: Four prism-ballast, two peri-ballast and one dynamic stabilization TSCL designs were each worn by groups of 20 subjects in a nondispensing study. After 20 min of lens wear, lenses were assessed, in right eyes only, for subjective comfort (100-point scale), lens mislocation (degrees deviation from vertical) and rotational recovery after deliberate 30 degrees mislocation (degrees/10 blinks). The percentage of lenses orienting within +/-10 degrees of target orientation (zero rotation) and the variability of orientation (standard deviation of mislocation) were also calculated for each lens group. RESULTS: Based on partitioning of the data distributions for each variable, performance was designated as excellent, acceptable or poor. Corresponding performance cut-offs were determined at > or =90, 89 to 80, and <80 for subjective comfort, < or =+/-6 degrees , +/-7 degrees to 10 degrees , and >+/-10 degrees for mislocation, >10 degrees /10 blinks, 10 degrees to 6 degrees /10 blinks, and <6 degrees /10 blinks for rotational recovery. For groups of wearers the appropriate cut-offs were > or =90%, 89 to 70%, and <70% of lenses orienting within +/-10 degrees of target orientation and <+/-6 degrees , +/-6 degrees to 10 degrees , and >+/-10 degrees for variability of orientation. CONCLUSION: Techniques suitable for the evaluation of TSCL clinical performance have been described and guidelines for the assessment of such lenses established. In the process, we have identified potential performance differences that may relate to variations in TSCL design.