Adsorption of Human Recombinant Erythropoietin on Dialysis Membranes In Vitro

Abstract: The adsorptive characteristics of 5 dialysis membranes for recombinant human erythropoietin (EPO) were studied in vitro in a closed circuit system. For 120 min, EPO added with bovine serum was significantly adsorbed by polymethylmetacrylate (PMMA) and polyacry–lonitrile (PAN) membranes but not by Cuprophan, ethylene vinyl alcohol (EVAL), or polysulfone (PS) membranes. In addition the EPO adsorptive rate, as well as that of β₂–microglobulin (β₂–MG), was greater with a PMMA membrane than with a PAN membrane. EPO was not detected in the ultrafiltrate at 15 min with 5 membranes. These results indicate that EPO was eliminated by membrane adsorption only with some dialysis membranes.     

Sex hormone-binding globulin in breast cancer

Serum level of sex hormone-binding globulin (SHBG) was measured by immunoradiometric assay in fifty two breast cancer patients and twenty nine healthy female volunteers. The results are as follows: 1) Although the serum SHBG concentration showed no significant difference between the breast cancer group and the healthy control group, the serum SHBG concentration in postmenopause was significantly higher in the breast cancer group (63.8 +/- 31.2nmol/ml/ml; mean +/- S.D.) than in the healthy control group (40.1 +/- 15.4nmol/ml). 2) Subsequently in the postmenopausal breast cancer group, the serum SHBG concentration was significantly higher in the estrogen receptor (ER)-negative cancer group (97.8 +/- 12.7nmol/ml) than in the ER-positive cancer group (55.8 +/- 32.1nol/ml). 3) No significant relationships were showed between the serum SHBG concentration and obesity or serum estradiol concentration in postmenopausal patients. 4) The serum SHBG concentration showed significant decrease 3 months after radical operation for breast cancer in postmenopausal patients. These results suggest the possibility of the SHBG synthesis in breast cancer tissue.     

Accumulation of cyanide and thiocyanate in haemodialysis patients.

BACKGROUND: Cyanide is a toxic agent, and its detoxification product, thiocyanate, may be a major pathogenetic substance in uraemia. Recent studies examining the myeloperoxidase(MPO)/thiocyanate system have suggested a link between thiocyanate and atherosclerosis. However, inaccuracies in conventional assays for cyanide and thiocyanate have limited the understanding of their metabolism in haemodialysis (HD) patients. METHODS: We used high-performance liquid chromatography to measure cyanide in erythrocytes and thiocyanate in plasma in 43 HD patients and in a group of 46 healthy controls that included 15 current smokers. To clarify the metabolic conversion of cyanide to thiocyanate in uraemic patients, we also measured cysteine and sulfate. We then used stepwise regression analysis to analyse factors that determine erythrocyte cyanide and plasma thiocyanate. RESULTS: Mean cyanide and thiocyanate were significantly greater in HD patients than in non-smoking controls. However, cyanide was far below lethal concentrations in dialysis patients. Thiocyanate was six to seven times greater in HD patients than in non-smoking controls, and decreases in thiocyanate following dialysis were only 19.3+/-3.5%. Multiple regression analysis showed a positive correlation between cyanide and thiocyanate in controls, but a negative correlation in HD patients. In patients, an inverse relationship between thiocyanate and BUN was also observed. CONCLUSIONS: The elevation of thiocyanate in patients undergoing dialysis probably is secondary to both limited efficiency of HD and deranged metabolism of cyanide and thiocyanate. Because thiocyanate is a preferred substrate for MPO, it may play a role in uraemic complications including cardiovascular events.     

Brain metastasis in patients with superior sulcus tumors

During a 20-year period, from 1963 to 1983, 68 patients were treated for carcinoma of the lung presenting in the superior sulcus. Their ages ranged from 41 to 79 years (median, 56 years). Thirty-six patients had squamous cell carcinoma, 13 had adenocarcinoma, 14 had large cell carcinoma, two had small cell carcinoma, and three had clinical diagnosis only. All tumors were considered to be inoperable or unresectable and were treated with external irradiation alone. The 3-year disease-free survival was 25%. Brain metastasis developed in 23 patients (34%); the brain was the first site of metastasis in 16 patients (24%), five of whom eventually developed other sites of metastasis. The cumulative probability of brain metastasis was 53% at 3 years. Brain metastases were seen in ten patients (28%) with squamous cell carcinoma, five patients (38%) with adenocarcinoma, seven patients (50%) with large cell carcinoma, and one patient without a histocytologic diagnosis. The proportion of patients younger than 60 years (19/41, 46%) who developed brain metastasis was significantly greater than that for patients 60 years or older (4/27, 15%) (P less than or equal to 0.01). Nine of 11 patients with metastasis only to the brain died as a consequence of the intracranial disease 1 to 13 months (median, 6 months) after the diagnosis of brain metastases. The other two patients received therapeutic irradiation to the entire brain and survived longer than 5 days after the whole-brain irradiation: one died at 62 months of intercurrent disease, and the other is alive and well 129 months after diagnosis. The high probability of brain metastasis from superior sulcus tumors, regardless of histopathologic type and the frequency with which the brain is the only site of clinical failure, suggest that systematic prophylactic cranial irradiation could reduce the morbidity and perhaps even contribute favorably to the survival of these patients.     

Breast cancer detected by mass screening using physical examination alone

In Tokushima prefecture, mass screening for breast cancer has been conducted using physical examination alone since 1970. Breast cancer was detected in 116 of 111,571 screened women up until 1984. The detection rate was 0.08 per cent in total examinees, 0.13 per cent in initial examinees, and 0.04 per cent in subsequent examinees. The patients with breast cancer were divided into three groups, i.e., 62 cases detected at initial screening, 28 cases detected at subsequent screenings, and 26 interval cancer cases. 510 patients with breast cancer in the outpatient clinic were serving as controls. The stage classification and nodal involvement were significantly different between the mass screening group and the control group, but not significantly different among the three groups. The interval cases were detected at an early stage. The survival rates were not significantly different between the three groups and the control group. Efforts should be doubled to educate women about the proper method of breast self-examination in order to promote the early detection of breast cancer.     

Changes in Glucose Metabolism in Cerebral Cortex and Cerebellum Correlate With Tremor and Rigidity Control by Subthalamic Nucleus Stimulation in Parkinson's Disease: A Positron Emission Tomography Study

Objective. Employing [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET) to assess the correlation between the effect of deep brain stimulation (DBS) on the subthalamic nucleus (STN) and the regional cerebral metabolic rate of glucose (rCMRGlc) in advanced Parkinson's disease patients (N = 8). Materials and Methods. On the basis of patients’ diary records, we performed FDG‐PET during the off‐period of motor activity with on‐ or off‐stimulation by STN‐DBS on separate days and analyzed the correlation between changes in motor symptoms and alterations in the rCMRGlc. Result. When FDG‐PET was performed, the motor score on the unified Parkinson's disease rating scale (UPDRS) was 64% lower with on‐stimulation than with off‐stimulation (p < 0.001, Wilcoxon single‐rank test). STN‐DBS increased the rCMRGlc in the posterior part of the right middle frontal gyrus, which corresponded to the premotor area, and the right anterior lobe of the cerebellum (p < 0.005, paired t‐test). No region exhibited a decrease in rCMRGlc. Among the items of the UPDRS motor score, the changes in resting tremor and rigidity of the left extremities showed a significant correlation with the changes in rCMRGlc observed in the right premotor area (p < 0.02 and p < 0.05, respectively, Spearman's rank correlation). Conclusions. STN‐DBS either activates the premotor area or normalizes the deactivation of the premotor area. These FDG‐PET findings obtained are consistent with the idea that STN‐DBS modifies the activities of neural circuits involved in motor control.     

Abdominal vagotomy attenuates interleukin-1β-induced nitric oxide release in the paraventricular nucleus region in conscious rats

Nitric oxide (NO) has recently been shown to modulate the hypothalamic–pituitary–adrenal axis response to interleukin-1β (IL-1β). We measured levels of nitrite (NO₂⁻) and nitrate (NO₃⁻) in the hypothalamic paraventricular nucleus (PVN) region using an in vivo brain microdialysis technique in conscious rats. Intraperitoneally administered IL-1β produced a significant increase in both NO₂⁻ and NO₃⁻ levels in the PVN region. We also examined the possible involvement of the abdominal vagal afferent nerves in this effect. In abdominal-vagotomized rats, the increase was significantly attenuated compared to that in sham-operated rats. Our results suggest that the abdominal vagal afferent nerves are involved in intraperitoneally administered IL-1β-induced NO release in the PVN region.     

Overexpression of the Del1 gene causes dendritic branching in the mouse mesentery

In the present study, we established transgenic mice overexpressing Del1, a ligand of integrins, to examine the effect of overexpression of Del1 on vascular morphogenesis. In the wild-type mouse, mesenteric vessels are shaped like rakes consisting of a long stalk and short branches at the periphery. In contrast, those in transgenic mice showed typical dendritic architecture consisting of a few large primary branches with smaller spreading branches. The phenotype of mice overexpressing Del1 suggests the existence of a tissue-specific mechanism for branching morphogenesis in the mesentery.