Radionuclide study of platelets and prosthetic interactions: external versus specimen quantitation

Twenty-nine New Zealand white rabbits were allocated to undergo insertion of either polytetrafluoroethylene (PTFE) (n = 22) or microporous silicone rubber (SR) (n = 7), 3-mm diameter, 10-mm long aortic grafts. Animals with PTFE grafts received aspirin (ASA) 10 mg/kg/d and dipyridamole (DPM) 10 mg/kg/d (n = 11) or placebo (n = 11). Autologous In-111-oxine-labeled platelets were reinfused on reestablishment of blood flow through the graft. Using gamma camera images, an external graft platelet accumulation index (E-GPAI) was calculated as the In-111 activity in the graft area to the reference aorta at 24, 48, and 72 hours post implantation. Mean E-GPAI +/- SEM values for the ASA/DPM (n = 4) and control groups (n = 7) were 1.13 +/- 0.16 and 1.34 +/- 0.05 (NS) at 24 hours, 1.20 +/- 0.16 and 1.33 +/- 0.07 (NS) at 48 hours, and 1.38 +/- 0.07 and 1.35 +/- 0.10 (NS) at 72 hours, respectively. A similar internal graft platelet accumulation index (I-GPAI) was constructed based on In-111 activity in excised grafts and reference aorta measured in a scintillation counter. Mean I-GPAI +/- SEM values for the PTFE ASA/DPM (n = 9) and control groups (n = 8) at 48 hours post implantation were 43.1 +/- 2.7 and 216.8 +/- 73.9 (P = 0.05), respectively. I-GPAI values for the SR grafts were 192.5 +/- 43.1. Conclusion: The E-GPAI was not sensitive enough to demonstrate the effect of antiplatelet medication on platelet accumulation on the PTFE grafts.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunosuppressant material in human seminal fluid. Inhibition of blast transformation and of NK activity by seminal fluid patients of a male infertility clinic

Human seminal plasma from normal or patients with abnormal parameters of the ejaculates contains an inhibitory material that expresses potent in vitro inhibitory activity on PHA-M-induced blast transformation and NK activity. Using the test of inhibition of NK activity, the semen samples from individuals with higher concentrations of fructose had higher inhibitory activity. The results described herein suggest that inhibitory activity for blast transformation may be present in the prostatic fluid while the NK inhibition aspects are correlated with the vesicle-marker (fructose). Inhibition of the immune responses by human seminal plasma of the effector functions indicates the interesting implication that soluble factors may indirectly protect against or promote human autoimmune infertility disease.     

Does an oral analgesic protocol improve pain control for patients with cancer? An intergroup study coordinated by the Eastern Cooperative Oncology Group

BACKGROUND: Cancer pain is highly prevalent and commonly undertreated. This study was designed to determine whether dissemination of a clinical protocol for pain management would improve outcomes in community oncology practices. PATIENTS AND METHODS: A pain management protocol was developed based on accepted guidelines. After baseline assessment, oncology practices were randomly assigned to 'analgesic protocol' (AP) sites, where oncologists implemented the guidelines in a group of lung or prostate cancer patients, or to 'physician discretion' (PD) sites, where customary treatment was continued. Patients treated on protocol and a comparison group of patients with pain due to breast cancer or myeloma were monitored for change in pain using the Brief Pain Inventory, and for change in other symptoms or mood. RESULTS: The protocol terminated early because of poor accrual. We compared groups using proportions of patients who had no or mild pain at follow-up. Although measures of protocol adherence did not suggest the occurrence of major practice change, the proportion of lung or prostate cancer patients with no or mild pain increased significantly from baseline for those treated at AP sites compared with those treated at PD sites. There was no significant difference between the breast and myeloma patients treated at AP sites versus those treated at PD sites. CONCLUSION: A protocol for cancer pain management can improve pain control. Diffusion of these benefits to other patients was not confirmed. Given the small sample size, these findings require confirmation in a larger trial.     

Missense mutations and evolutionary conserved amino acids at the human hypoxanthine phosphoribosyl-transferase locus.

Molecular characterization of in vivo mutation at the human hypoxanthine phosphoribosyltransferase (hprt) locus has revealed a broad spectrum of mutation, both with regard to germ-line mutation in Lesch-Nyhan and gout patients, and somatic mutation in 6-thioguanine resistant T-lymphocytes from healthy individuals. The pattern of missense mutation shows a non-random distribution with a preferential location to codons for amino acids which are identical in human and the two parasites Schistosoma mansoni and Plasmodium falciparum. Although these 'evolutionary conserved' amino acids account for only 32% of the amino acids in the human hprt protein, they are involved in 76% of the missense mutations at the hprt locus in human T-lymphocytes, 67% in Lesch-Nyhan patients (with severe hprt-deficiency), but only 43% in gout patients (with partial hprt deficiency). This observation supports the notion that evolutionary conserved amino acids constitute functionally important sites in the hprt enzyme, and missense mutations affecting these amino acids will often lead to complete loss of enzyme activity. Substitutions of 'non-conserved' amino acids cause less severe hprt-deficiency (as seen in the gout patients), or may even escape clinical diagnosis. These considerations are important for the understanding of structure-activity relationships in the hprt protein, possible differences between hprt mutational spectra in germ-line and somatic cells, and the mutational spectra induced by specific exogeneous mutagens.     

A case-control study of breast cancer among Japanese women: with special reference to family history and reproductive and dietary factors

Summary To study the effects of family history and reproductive, anthropometric, and dietary factors on the risk of breast cancer among low risk populations, we conducted a hospital-based case-control study involving 908 patients with breast cancer and their matched controls, in Japan. A positive family history of breast cancer significantly increased the risk of breast cancer (odds ratio = 1.52, 95% confidence interval: 1.14–2.03). The risk further increased with increasing number of family members affected. Obesity, single marital status, fewer births, a late childbirth, and less consumption of green-yellow vegetables and dairy products were also associated with an increased risk of breast cancer. These associations were independent in multivariate analyses. There was no increase in risk associated with consumption of high fat foods. When analyzed by menopausal status, the association with family history of breast cancer, especially in the first degree of relatives, was more evident for premenopausal breast cancer. The associations with obesity and lower consumption of dairy products were more pronounced for postmenopausal breast cancer, while those with lower parity and single marital status were stronger for premenopausal breast cancer.     

CCR1 acts downstream of NFAT2 in osteoclastogenesis and enhances cell migration.

We found that a chemokine receptor gene, CCR1, acts downstream of NFAT2 in RANKL-stimulated RAW264 and bone marrow cells. The upstream regulatory region of CCR1 showed RANKL-dependent and CsA-suppressible promoter activity. Downregulation of the expression and function of CCR1 suppressed cell migration. INTRODUCTION: We previously reported that the expression of NFAT2 induced by RANKL is a key process for progression to multinucleated cells in an in vitro osteoclastogenesis system. Identifying the target genes of NFAT2 would thus be informative about the differentiation process. We focused here on chemokine and chemokine receptor genes that act downstream of NFAT2 in RAW264 cells as well as osteoclast precursors prepared from bone marrow cells. MATERIALS AND METHODS: RAW264 mouse monocyte/macrophage line cells were cultured with or without cyclosporin A (CsA) in the presence of RANKL or glutathione S-transferase (GST). Osteoclast precursors were prepared from bone marrow cells. RANKL-inducible and CsA-suppressible genes were searched for by microarray analysis, and expression was confirmed by quantitative RT-PCR. Promoter activity was measured by luciferase gene reporter assay. Short interfering (si)RNA for CCR1 was introduced in RAW264 cells. Cell migration activity was examined using a Boyden chamber assay. RESULTS AND CONCLUSIONS: We identified the chemokine receptor gene CCR1 as a gene showing significant differential expression profiles in osteoclastogenesis in the presence versus the absence of CsA, an inhibitor of NFAT. This property was unique to CCR1 among the chemokine and chemokine receptor genes examined in both RAW264 and bone marrow cells. The upstream regulatory region was isolated from CCR1, and its RANKL-dependent and CsA-suppressible promoter activity was confirmed. The functional significance of CCR1 was assessed by monitoring the migration of cells in a transwell migration assay, and this activity was abolished when either CsA- or CCR1 siRNA-treated cells were used. Moreover, treatment with a Galpha inhibitor pertussis toxin (PTX) or methiolynated-regulated on activation, normal T cells expressed and secreted (Met-RANTES), an antagonist of CCR1, suppressed multinucleated cell formation in the bone marrow cell system. Together, these results suggest that the CCR1 signaling cascade is under the control of NFAT2 and seems to enhance the migration of differentiating osteoclasts.