A female patient with malarial nephropathy

Malaria remains one of the worlds major health problems, particularly in developing tropical countries. Imported malaria is reportedly increasing in Western countries. Acute renal failure (ARF) is the most common cause of death in severe malaria. We report the case of a 63-year-old female patient with a history of travel to a rural area in South Africa who was in coma and had a high fever on admission. Thirty percent of her erythrocytes were infected with Plasmodium falciparum. She had cerebral malaria, malarial nephropathy, anemia, hepatic dysfunction, and disseminated intravenous coagulation (DIC). Quinine and artesunate treatment decreased the number of parasites in the blood. To manage renal failure, hemodialysis was performed for 11 days. A relationship between ARF and hepatic dysfunction was suggested. This relationship is an indication of the clinical course of the disease. In this article, we discuss the mechanism underlying the development of malarial nephropathy and its management, particularly the usefulness of hemodialysis.     

Transient decrease in the CD45RA expression on T lymphocytes in neonates with fetal distress

To determine the expression of CD45 isoforms on T lymphocytes in neonates with fetal distress and to evaluate its diagnostic accuracy, peripheral blood samples were examined in 53 neonates who were classified into one of three groups: group I: 'control' group (n = 23), group II: 'mild distress' group (n = 15), and group III: 'moderate distress' group (n = 15). The expression of CD3 (mean +/- SD 24.2 +/- 10.1%), CD4 (23.0 +/- 5.7%), and CD45RA (27.3 +/- 9.6%) on total lymphocytes and the expression of CD45RA on CD4+ T lymphocytes (13.7 +/- 4.7%) in group III were significantly lower than in the other two groups 0-3 days after birth. Sensitivity and specificity of the CD45RA expression on CD4+ T lymphocytes for discrimination of group III were calculated as 0.79 and 1.0, respectively, when the cutoff value was 22.7%. The low CD3, CD4, and CD45RA expression returned to normal levels 10 days and more after birth. There were no differences in the CD8 and CD45RO expression between the groups. We conclude that CD4+ T lymphocytes from neonates with fetal distress show a transient decrease in the CD45RA expression without an increase in the CD45RO expression, and, therefore, analysis of the CD45 isoform expression is useful for laboratory evaluation of fetal distress.     

NO-release ability and DNA-damage activity of aromatic N-nitroso compounds

To develop a new nitric oxide-donor (NO-donor) that is useful for chemical and biochemical research, we synthesized several aromatic N-nitroso compounds including 1-[N-nitroso-N-(4-tolyl)carbamoyl] piperidine-4-carboxylic acid (1f) and phenyl(2-pyridyl)-N-nitrosamines, which spontaneously generate NO at ambient temperature. Thermal decomposition of these compounds was run under mild conditions. Gaseous NO released from them was quantified by means of the Griess reaction using a specially designed apparatus in which NO2- is generated from NO. The structure of products arose from the radical cleavage of N-NO bond was clarified by chemical and spectral studies. Generation of NO from the N-nitroso compounds was also confirmed by ESR spectroscopy. The action of these NO-releasing compounds against DNA was examined. When the pBR 322 DNA was treated with 1f at 37 degrees C for 3 h, the DNA single-strand breaks was 31% for 1 mM of 1f. The denitrosated compound and sodium nitrite did not show any effective DNA-cleaving activity. On the other hand, aromatic N-nitrosamines induced weak DNA-cleaving activity under the same condition.     

Risk factors for silent cerebral infarction in the elderly

BACKGROUND: A silent cerebral infarction (SCI) is often found in the elderly. However, studies on SCIs focusing on an elderly population are sparse. Our objective was to evaluate risk factors of SCIs in healthy elderly individuals. METHODS: One hundred seventy-five neurologically normal community-dwelling Japanese people aged >/=65 years (128 men and 47 women; 77.5 +/- 8.7 years) were studied. Among them we assessed the demographic data and detected SCIs on brain magnetic resonance imaging scans. RESULTS: Eighty four subjects had at least one SCI. Hypertension and low body mass index (BMI) were the significant risks for SCIs in multivariate analysis adjusted for age, sex and other risk factors. Mean BMI in subjects with SCIs was significantly lower than those without SCIs (20.8 +/- 3.2 kg/m(2) vs. 22.1 +/- 3.2 kg/m(2)). In the subgroup analysis by age stratum regarding hypertension and BMI, hypertension was a significant risk factor in subjects aged 65-75 years. Lower BMI had a significant risk in subjects aged >/=81 years. CONCLUSIONS: Hypertension and increasing age have been recognized as risk factors for SCIs, and low BMI might be a significant risk especially in superelderly subjects. Further data with a larger sample size is needed to confirm the relationship between BMI and SCIs among the elderly.     

Transplantation of marrow-derived mesenchymal stem cells and platelet-rich plasma during distraction osteogenesis--a preliminary result of three cases

Clinical results of distraction osteogenesis with transplantation of marrow-derived mesenchymal stem cells (MSCs) and platelet-rich plasma (PRP) were reviewed in three femora and two tibiae of the two patients with achondroplasia and one patient with congenital pseudarthrosis of the tibia. MSCs derived from the iliac crest were cultured with osteogenic supplements and differentiated into osteoblast-like cells. PRP, which is known to contain several growth factors and coagulate immediately by a minute introduction of thrombin and calcium, was prepared just before transplantation. Culture-expanded osteoblast-like cells and autologous PRP were injected into the distracted callus with the thrombin-calcium mixture so that the PRP gel might develop within the injected site. Transplantation of MSCs and PRP was done at the lengthening and consolidation period in each patient. The target lengths were obtained in every leg without major complications and the average healing index was 23.0 days/cm (18.8-26.9 days/cm). Although these results are still preliminary, transplantation of osteoblast-like cells and PRP, which seemed to be a safe and minimally invasive cell therapy, could shorten the treatment period by acceleration of bone regeneration during distraction osteogenesis.     

Role of lysophosphatidic acid as a mechanosensitizer

The mechanotransduction mechanisms play an important role in regulation of specific cellular response or maintenance of cellular homeostasis in a wide variety of cell types. Increase in intracellular free Ca(2+) concentration ([Ca(2+)](i)) is an important signal in the first step of mechanotransduction. Mechanosensitive (MS) cation channels are thought to be a putative pathway of Ca(2+) entry; however, the molecular mechanisms remain unclear. We have previously demonstrated that lysophosphatidic acid (LPA), a bioactive phospholipid present in human plasma, sensitizes the response of [Ca(2+)](i) to mechanical stress in cultured smooth muscle cells, cultured lung epithelial cells, and cultured lens epithelial cells. Using real-time confocal microscopy, local increases in [Ca(2+)](i) in several regions within the cell subjected to mechanical stress were clearly visualized in cultured bovine lens epithelial cells and cultured vascular endothelial cells in the presence of LPA. We called the phenomenon "Ca(2+) spots". Pharmacological studies revealed that the Ca(2+) spot is an elementary Ca(2+)-influx event through MS channels. In this review, possible physiological and pathophysiological roles of LPA as a mechanosensitizer are discussed.     

Chemical constituents of Millettia taiwaniana: structure elucidation of five new isoflavonoids and their cancer chemopreventive activity

We describe the isolation and identification of five new isoflavonoids, millewanins A (1), B (2), C (3), D (4), and E (5), together with six known isoflavonoids and three rotenoids, from the stems of Millettia taiwaniana collected in Japan. The major component, auriculasin (6), exhibited significant inhibitory effect on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. The results of the present investigation indicate that 6 might be a valuable antitumor promoter.     

Feasibility study of neoadjuvant chemotherapy followed by interval cytoreductive surgery for stage III/IV ovarian, tubal and peritoneal cancers: Japan Clinical Oncology Group Study JCOG0206

A feasibility study was started in January 2003 on neoadjuvant chemotherapy (NAC) followed by interval cytoreductive surgery (ICS) and postoperative chemotherapy for stage III/IV müllerian carcinomas such as ovarian, tubal and peritoneal carcinomas. The purpose is to assess the safety and efficacy of the treatment starting with NAC and also to know whether we can accurately diagnose these advanced carcinomas by imaging studies, cytologic findings and tumor markers without staging laparotomy or laparoscopy. Fifty-six patients with advanced müllerian carcinomas will be recruited to the study. After confirmation of diagnosis by laparoscopic inspection and biopsies, patients undergo four cycles of chemotherapy as NAC, followed by ICS and an additional four cycles of post-surgical chemotherapy. The primary endpoint is proportion of clinical complete remission after accomplishment of the protocol treatment, while the major secondary endpoint is positive predictive value of diagnosis before laparoscopy regarding tumor origin, histology and stage. Based on the results of this study, we will conduct a phase III study to compare the treatment starting with NAC and primary cytoreductive surgery followed by post-surgical chemotherapy.