Platinum levels in various tissues of a patient who died 181 days after cisplatin overdosing determined by electrospray ionization mass spectrometry

Platinum (Pt) levels were determined in various tissues and body fluids obtained from a patient who died 181 days after cisplatin overdosing. The symptoms of cisplatin overdose, however, might have almost disappeared by day 40, and the patient’s death was ascribed to the recurrence of malignant lymphoma. Determination of Pt derived from cisplatin was performed by electrospray ionization mass spectrometry (ESI-MS) using silver (Ag) as internal standard. Pt and Ag complexed with diethyldithiocarbamate (DDC) in wetashed blood, and tissue solutions were extracted into isoamyl alcohol, and then acidified with oxalic acid. By injecting an aliquot of the isoamyl alcohol layer into a mass spectrometer in the direct flow injection mode, the quantitation was performed using the signals of Pt(DDC)₃ ⁺ and Ag(DDC)₂ ⁺ at m/z 639 and 403, respectively. The Pt levels ranged from 25ng/ml in blood to 2050ng/g wet weight in the liver of the patient, indicating that Pt remained at high levels in tissues, even after a period as long as 181 days after cisplatin overdosing.     

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.     

Prevalence of non-alcoholic steatohepatitis (NASH) among biopsied cases of a urban hospital in Japan: significance of measurement of serum ferritin in the detection of NASH]

From April 1989 to December 2004, we performed liver biopsy on 475 patients and obtained biopsy proven 35 cases of non-alcoholic fatty liver. Among them, 18 cases were diagnosed as non-alcoholic steatohepatitis (NASH). During the last three years, we have tried to detect NASH using ultrasonography and elevated value of serum ferritin (> 300 ng/ml). All of the eligible 7 cases biopsied during the course were diagnosed as NASH. In these 7 cases, ALT levels improved after the body weight loss accompanied by the parallel decrease of serum ferritin levels. Measurement of serum ferritin is useful in the detection of NASH but the normal value of ferritin cannot rule out the possibility of NASH.     

利用口述史料研究中国近现代史的可能性——以山西省盂县日军性暴力研究为例

近年来,虽然遭遇阻力,但日本国内对于中日战争时期日军在华实施性暴力的调查、研究工作还是取得了重要进展。以石田米子为中心的调查小组经过长期不懈的努力,对当年日军在山西省盂县实施性暴力的事实进行了确证和揭露。本文在介绍石田小组的工作及其意义的同时,还对战时日军的性暴力活动进行了分类,并结合史学理论探讨了利用口述史料研究中国近现代史的意义与可能性。     

Induction of immunoreactive proliferating cell nuclear antigen (PCNA) in goldfish retina following intravitreal injection with tunicamycin.

Effects of a photoreceptor-specific biotoxin, tunicamycin (TM), injected intravitreally into the goldfish eye at one side, were explored on electroretinograms (ERGs) and proliferating cell nuclear antigen-immunoreactive (PCNA-ir) nuclei, representing the mitotic activity of rod precursors, in the retina at both sides. The eye-cup preparations were made for ERG recording, and the retinas were isolated and processed as cryosections or wholemounts by a routine immunohistochemical method for visinin (cones), opsin (rods), tyrosine hydroxylase (dopaminergic cells) and proliferating cell nuclear antigen (PCNA), at various intervals after intravitreal injection with TM (1.0 micrograms/eye). On some thin sections, autoradiographic study was combined following intravitreal injection with [3H]thymidine (TdR, 0.1 microCi/eye). The dose of TM used heavily destroyed cones and rods only in the treated retinas 2-15 days after injection, the photoreceptors being renewed for further 15-20 days. Approximately in parallel, ERGs were largely impaired 2-10 days after TM injection and recovered for 10-20 days. However, intravitreal TM altered the distribution and density of PCNA-ir nuclei in both treated and untreated retinas. The density of PCNA-ir nuclei reduced at first (on days 1 and 2), and then clustered and rapidly increased on days 3-5 and maintained at high levels with diffuse distribution over the whole area, particularly in the treated retinas, up to 60 days after TM injection; the maximum peak of 3.7 and 20 times the initial level was seen on day 20 in the outer nuclear layer (ONL) and inner nuclear layer (INL), respectively. PCNA-ir nuclei were found to be abundant in the ONL even after the photoreceptors and ERGs had been restored in the treated retinas on day 20, suggesting a kind of overproduction of retinal cells. The autoradiographic study provided comparable results to those obtained with PCNA immunohistochemistry. The mechanism by which damage to the treated retina causes rod precursor cells to proliferate in the untreated retina remains unresolved.