A case of aldosterone-producing adrenocortical adenoma associated with a probable post-operative adrenal crisis: histopathological analyses of the adrenal gland.

We describe a case of aldosterone-producing adrenocortical adenoma (APA) associated with a probable post-operative adrenal crisis possibly due to subtle autonomous cortisol secretion. The patient was a 46-year-old female who suffered from severe hypertension and hypokalemia. CT and MRI scans revealed a 2-cm diameter adrenal mass. The patient's plasma aldosterone level was increased, and her plasma renin activity was suppressed, both of which findings were consistent with APA. Cushingoid appearance was not observed. Morning and midnight serum cortisol and plasma adrenocorticotropic hormone (ACTH) levels were all within the normal range. Her serum cortisol level was suppressed to 1.9 microg/dl as measured by an overnight 1-mg dexamethasone suppression test, but was incompletely suppressed (2.7 microg/dl) by an overnight 8-mg dexamethasone suppression test. In addition, adrenocortical scintigraphy showed a strong uptake at the tumor region and a complete suppression of the contra-lateral adrenal uptake. After unilateral adrenalectomy, she had an episode of adrenal crisis, and a transient glucocorticoid replacement improved the symptoms. Histopathological studies demonstrated that the tumor was basically compatible with APA. The clear cells in the tumor were admixed with small numbers of compact cells that expressed 17alpha-hydroxylase, suggesting that the tumor was able to produce and secrete cortisol. In addition, the adjacent non-neoplastic adrenal cortex showed cortical atrophy, and dehydroepiandrosterone sulfotransferase immunoreactivity in the zonae fasciculata and reticularis was markedly diminished, suggesting that the hypothalamo-pituitary-adrenal (HPA) axis of the patient was suppressed due to neoplastic production and secretion of cortisol. Together, these findings suggested that autonomous secretion of cortisol from the tumor suppressed the HPA axis of the patient, thereby triggering the probable post-operative adrenal crisis. Post-operative adrenocortical insufficiency should be considered in clinical management of patients with relatively large APA, even when physical signs of autonomous cortisol overproduction are not apparent.     

Dissection of fission yeast microtubule associating protein p93Dis1: regions implicated in regulated localization and microtubule interaction

Background : Fission yeast microtubule associating protein (MAP) p93^Dis1 functions for sister chromatid separation: dis1 mutants fail to separate chromosomes, while the spindle elongates but without cyclin destruction. p93^Dis1 localizes along microtubules in interphase cytoplasm, but shifts to the spindle pole body (SPB) and spindle microtubules upon the entry into mitosis. In this study, regions of p93^Dis1 were dissected to examine their role.
Results : Nitrocellulose filter blotting shows that recombinant Dis1 binds to bovine brain microtubules in vitro . A basic central region rich in S, T and P is essential for this association. However, the whole p93^Dis1 with N- and C-termini containing a conserved repeat motif and heptad repeats, respectively, is necessary for normal microtubule association in vivo . The N-truncated region also binds to microtubules but only to the portions near the SPBs. Overproduction phenotypes indicate that p93^Dis1 greatly affects spindle formation and cell morphogenesis. The central region is essential but, by itself, not sufficient for generating such effects.
Conclusions : We propose that p93^Dis1 consists of three regions which carry distinct properties for localization: the N-region for cell cycle dependent localization, the central region for direct microtubule association, and the C-region for SPB and nuclear localization. The essential role of p93^Dis1 is carried out in the C-region, while the N-region acts as a regulator.     

Dotlike Hemosiderin Spots Are Associated With Past Hemorrhagic Strokes in Patients With Lacunar Infarcts

BACKGROUND AND PURPOSE: Dotlike hemosiderin spots ongradient-echo T2(*)-weighted magnetic resonance imaging of the brain have been histologically diagnosed as old microbleeds associated with small vessel disease (SVD). The authors hypothesize that the presence of many dotHSs may be correlated with the fragility of small vessels and the recurrence of SVD, including lacunar infarction and deep intracerebral hemorrhage (ICH). METHODS: To investigate how dotHSs are related to past history of SVD, the number of subcortical or deep dotHSs was investigated in 146 patients with lacunar infarctions (95 men, 51 women, age 38 to 90 [66.6+/-9.4] years). They were divided into 2 subgroups according to history of deep ICHs or lacunar infarctions. The odds ratio (OR) for past history was estimated from logistic regression analyses with the number of subcortical or deep dotHSs as well as other factors. RESULTS: Of 146 patients with lacunar infarctions, 11 had past symptomatic ICHs and 19 had past symptomatic lacunar infarctions. An elevated rate of history of ICH was found for lacunar infarction patients with many deep dotHSs (>or=3; OR, 9.1; 95% confidence interval, 1.6-51, P=.015). However, history of lacunar infarction was not significantly associated with the number of subcortical or deep dotHSs. CONCLUSIONS: Our findings suggest that many deep dotHSs on T2(*)-weighted magnetic resonance imaging may be correlated with deep ICH-lacunar infarction type of SVD recurrence but not lacunar infarction-lacunar infarction type.     

Blood pressure response to erythropoietin injection in hemodialysis and predialysis patients.

Recombinant human erythropoietin (rHuEPO) has been reported to induce hypertension. We investigated the effect of a single injection of rHuEPO on blood pressure in patients receiving hemodialysis (HD) and in patients with predialysis chronic renal failure (CRF). Forty-one patients receiving HD and 36 patients with predialysis CRF received an intravenous injection of rHuEPO, and blood pressure and plasma endothelin-1 were measured before and 30 min after the injection. Mean blood pressure was increased significantly in HD patients, but not in CRF patients (HD: 103+/-5 to 105+/-6 mmHg, p<0.05; CRF: 103+/-4 to 103+/-6, NS). The percentage of patients with increased mean blood pressure of more than 10 mmHg after rHuEPO injection was significantly larger in the HD than in the CRF group (27.0% vs. 5.5%, p<0.01). A positive correlation was found between changes in endothelin-1 level and mean blood pressure in the HD (r=0.43, p<0.01) but not in predialysis chronic renal failure. In conclusion, a single injection of rHuEPO increased blood pressure with a positive correlation with endothelin-1 release in hemodialysis patients, but not in predialysis chronic renal failure patients.     

Ubiquitous Presence in Mammalian Cells of Enzymatic Activity Specifically Cleaving 8-Hydroxyguanine-containing DNA

Here we report the finding of enzymatic activity that specifically cleaves DNA containing 8-hydroxyguanine (oh⁸Gua) residues in various mammalian cells. To detect this activity, we used a synthetic double-stranded DNA containing a single oh⁸Gua at a defined position as the substrate, and analyzed the products of enzymatic digestion by polyacrylamide gel electrophoresis. Two cleavage sites near the oh⁸Gua residue were detected with partially purified fractions from cow brain and rat liver, and also with preparations from all mammalian tissues examined. These results suggest that enzymatic activity for the removal of oh⁸Gua from DNA is widely distributed in mammalian cells.     

In Vitro Evaluation of Platelet/Biomaterial Interactions in an Epifluorescent Video Microscopy Combined with a Parallel Plate Flow Cell

Abstract: Suitable evaluation systems are critical for ranking various biomaterials in order to develop a method to design and synthesize nonthrombogenic biomaterials. We have recently developed an in vitro test system to evaluate platelet/biomaterial interactions in whole blood. The system consists of a parallel plate flow cell and epifluorescent video microscopy (EVM). A glass coverslip coated with a polymer was incorporated into the flow cell, and blood was perfused using a syringe pump via a polymer–coated PVC tubing connected to the flow cell. Whole human blood was anticoagulated with heparin (2 U/ml), and the platelets were labeled with the fluorescent dye mepacrine (5 μM). This system permitted real–time and dynamic observations of platelet/biomaterial interactions in whole blood under a defined flow condition. In order to evaluate the feasibility of this system, two different segmented polyether–polyurethanes (SPEUs), PU–PTMG(650) and PU–PTMG(2000), were chosen as test polymers. Surface characteristics verified with electron spectroscopy for chemical analysis (ESCA) and contact angle measurements showed similar results in both SPEUs. Blood was perfused at a wall shear rate of 200 s^–1 for 20 min. Excitation light was applied for 2 s at 1 min intervals. The real–time image was then analyzed at each time point for the percentage of surface area of platelet coverage. Plasma β–thromboglobulin (β–TG) levels were also measured before and after each run. PU–PTMG(650) showed a significantly higher number of adhered platelets than PU–PTMG(2000) at each time point. β–TG levels of PU–PTMG(650) were also higher than those of PU–PTMG(2000), which is comparable to the results of EVM. Thus, this EVM system has been proven to be an excellent and highly sensitive in vitro analytical method for evaluating platelet/biomaterial interactions.     

Late Effects of Childhood Acute Leukemia and Its Treatment

Late effects of childhood acute leukemia and its treatment were studied in 766 patients (684 ALL, 73 ANLL, and 9 others) in Japan who had remained in remission for more than 1 year after their first complete remission. Delayed adverse sequelae involve a wide variety of organs and their functions. Short stature was present in 2.61%, obesity in 3.79%, abnormalities of growth hormone secretion in 1.5%, delayed secondary sex characteristics in 1.5% of males and 0.6% of females, motor disturbances in 1.17%, sensory disturbances in 0.91%, intellectual and learning disabilities in 2.48%, abnormal findings in routine neurologic examinations in 1.31%, EEG abnormalities in 4.30%, brain CT abnormalities in 5.09% and cardiac dysfunction in 1.07%. Various other disorders were seen in 20 patients. Many of these delayed adverse sequelae are caused by or related to central nervous system prophylaxis and systemic combination chemotherapy. The results suggest that it is needed to improve therapeutic methods through the stratification of patients by risk factors and detailed analysis of prognostic factors. Moreover it is important to render medical and psychosocial support to long-term survivors of childhood leukemia through interactions between the patient, parents and medical staff.