Human urotensin-II potentiates the mitogenic effect of mildly oxidized low-density lipoprotein on vascular smooth muscle cells: comparison with other vasoactive agents and hydrogen peroxide.

Human urotensin-II (U-II) is the most potent vasoactive peptide identified to date, and may be involved in hypertension and atherosclerosis. We investigated the effects of the interactions between U-II or other vasoactive agents and mildly oxidized low-density lipoprotein (mox-LDL) or hydrogen peroxide (H2O2) on the induction of vascular smooth muscle cell (VSMC) proliferation. Growth-arrested rabbit VSMCs were incubated with vasoactive agents (U-II, endothelin-1, angiotensin-II, serotonin, or thromboxane-A2) in the presence or absence of mox-LDL or H2O2. [3H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. On interaction with mox-LDL or H2O2, U-II induced the greatest increase in [3H]thymidine incorporation among these vasoactive agents. A low concentration of U-II (10 nmol/l) enhanced the potential mitogenic effect of low concentrations of mox-LDL (120 to 337%) and H2O2 (177 to 226%). U-II at 50 nmol/l showed the maximal mitogenic effect (161%), which was abolished by G protein inactivator (GDP-beta-S), c-Src tyrosine kinase inhibitor (radicicol), protein kinase C (PKC) inhibitor (Ro31-8220), extracellular signal-regulated kinase (ERK) kinase inhibitor (PD98059), or Rho kinase inhibitor (Y27632). Mox-LDL at 5 microg/ml showed the maximal mitogenic effect (211%), which was inhibited by free radical scavenger (catalase), intracellular and extracellular antioxidants (N-acetylcysteine and probucol), nicotinamide adenine dinucleotide phosphate oxidase inhibitor (diphenylene iodonium), or c-Jun N-terminal kinase (JNK) inhibitor (SP600125). These results suggested that U-II acts in synergy with mox-LDL in inducing VSMC DNA synthesis at the highest rate among these vasoactive agents. Activation of the G protein/c-Src/PKC/ERK and Rho kinase pathways by U-II together with the redox-sensitive JNK pathway by mox-LDL may explain the synergistic interaction between these agents.     

Classification of human liver transplant recipients by their preoperative CD8+ T cell subpopulation and its relation to outcome.

The primed status of T cells is markedly different among liver transplant recipients, due to a lifetime of antigen exposure and reduced thymopoiesis by aging, and diseases. This study aims to characterize the preoperative immunological status of CD8+ T cell subpopulations and relate it to the outcome for liver transplant recipients. We classified 112 liver transplant recipients into 5 groups, based on hierarchical clustering of the CD8+CD45 isoform proportion of T cells. In Groups I and II (pediatric), the naive T cell proportion was more than 50%. In adult recipients, Group III was characterized by a naive T cell proportion of 50%, Group IV had the greatest effector/memory T cells (EM), and Group V had the greatest proportion of effector T cells. In Groups IV and V, the effector T cell proportion was considerably higher, and was accompanied by marked downregulation of the CD27+CD28+ subsets and upregulation of interferon gamma (IFN)-gamma, tumor necrosis factor-alpha, and perforin expression. Group V recipients tended to be complicated postoperatively, with a significantly reduced survival rate (1 yr, 66.8%) and markedly reduced Eastern Cooperative Oncology Group performance status.     

Acute hemorrhagic colitis induced by the neuraminidase inhibitor oseltamivir]

A 23-year-old woman had lower abdominal pain, diarrhea and bloody stool was admitted and given a diagnosis of influenza B. Her home doctor had started treatment by neuraminidase inhibitor (oseltamivir) the previous day. Colonoscopic examination revealed an area of hemorrhage and erosion in the left transverse colon. After halting oseltamivir treatment these symptoms disappeared and her colonoscopic findings improved. A drug-induced lymphocyte stimulation test was positive for oseltamivir. This case is the first reported case of acute hemorrhagic colitis induced by oseltamivir.     

Effects of simultaneous increases in dietary phosphorus and magnesium concentrations on nephrocalcinosis and kidney function in female rats.

The effects of simultaneous increases in dietary phosphorus (P) and magnesium (Mg) concentrations while maintaining a constant P:Mg ratio on nephrocalcinosis and kidney function in female rats was investigated. Female Wistar rats were fed a control diet (3.12 g P, 0.51 g Mg per kg diet) or a diet having either 3 times the control P and Mg concentrations (3-fold diet; 9.25 g P and 1.42 g Mg per kg diet) or 5 times the control concentrations (5-fold diet; 14.97 g P and 2.37 g Mg per kg diet) for 21 d. The three experimental diets all had same P:Mg molar ratios (control diet; 4.81, 3-fold diet; 5.11, 5-fold diet; 4.96). The 3-fold diet had no significant influence on kidney calcium (Ca), Mg or P concentrations. However, kidney Ca, Mg and P concentrations were significantly higher in rats fed the 5-fold diet than in rats fed the control or 3-fold diets. No significant differences in creatinine clearance were observed among the three groups. Urinary albumin and beta 2-microglobulin excretion were higher in rats fed the 5-fold diet than in rats fed the control or 3-fold diets, while the 3-fold diet had no significant influence on the urinary albumin and beta 2-microglobulin excretion. These results suggest that absolute concentrations of dietary P and Mg are important factors with regard to the development of nephrocalcinosis and diminished kidney function.     

LAPAROSCOPIC TREATMENT FOR PERFORATED APPENDICITIS WITH PELVIC ABSCESS

We performed laparoscopic appendectomy and drainage to treat panperitonitis due to perforated appendicitis that occurred in a 28‐year‐old woman. We believe this is an appropriate procedure to treat perforated appendicitis because it is safe and minimally invasive, and faster recovery can be expected than after conventional open appendectomy.     

Improved expression of gamma-aminobutyric acid receptor in mice with cerebral infarct and transplanted bone marrow stromal cells: an autoradiographic and histologic analysis.

Recent studies have indicated that bone marrow stromal cells (BMSC) have the potential to improve neurologic function when transplanted into animal models of central nervous system disorders. However, how the transplanted BMSC restore the lost neurologic function is not clear. In the present study, therefore, we aimed to elucidate whether BMSC express the neuron-specific gamma-aminobutyric acid (GABA) receptor when transplanted into brain that has been subjected to cerebral infarction. METHODS: The BMSC were harvested from green fluorescent protein-transgenic mice and were cultured. The mice were subjected to permanent middle cerebral artery occlusion. The BMSC or vehicle was transplanted into the ipsilateral striatum 7 d after the insult. Using autoradiography and fluorescence immunohistochemistry, we evaluated the binding of 125I-iomazenil and the expression of GABA receptor protein in and around the cerebral infarct 4 wk after transplantation. RESULTS: Binding of 125I-iomazenil was significantly higher in the periinfarct neocortex in the BMSC-transplanted animals than in the vehicle-transplanted animals. Likewise, the number of the GABAA receptor-positive cells was significantly higher in the periinfarct neocortex in the BMSC-transplanted animals than in the vehicle-transplanted animals. A certain subpopulation of the transplanted BMSC expressed a neuron-specific marker, microtubule-associated protein 2, and the marker protein specific for GABAA receptor in the periinfarct area. CONCLUSION: These findings suggest that BMSC may contribute to neural tissue regeneration through migrating toward the periinfarct area and acquiring the neuron-specific receptor function.     

Histological changes in the midbrain around the aqueduct in congenital hydrocephalic rat LEW/Jms

Primary aqueductal stenosis is one of the main causes of congenital hydrocephalus in humans and experimental models. The congenitally hydrocephalic rat strain LEW/Jms is one such model. In this report, we describe further detailed histological features of periaqueductal structure, including the posterior commissure, subcommissural organ (SCO), and ependyma, and discuss the changes in these structures in relation to the cause of hydrocephalus. Coronal sections of the aqueduct in normal rats showed that the usual ependyma was absent in the center of the base facing the dorsal side, which was replaced by tall columnar cells. On the other hand, in hydrocephalic rats the ependyma encircled the aqueductal cavity. In midline sagittal sections, normal and hydrocephalic rats showed the SCO, although the SCO in hydrocephalic rats was shorter than in normal rats. There was also a marked difference between normal and hydrocephalic rats in the dorsoventral dimension of the rostral midbrain. In hydrocephalus, this dimension was large in comparison with normal rats. The superior collicular commissure located caudal to the posterior commissure ran along the ventral side of the midbrain in rats with hydrocephalus, and there was a cell-depleted area just dorsal to the superior collicular commissure. The same findings were observed from the 17th day of gestation until the postnatal period. Although the role of the SCO has been widely discussed from the viewpoint of secretory function, the present study indicated that this organ might be involved in the formation of the shape of the aqueduct.     

The practice of breast self-examination results in the earlier detection and better clinical course of Japanese women with breast cancer

Using a questionnaire survey, we analyzed the relationship between the frequency of breast self-examination (BSE) and the clinical stage and course of breast cancer in Japanese patients. BSE had been performed monthly by only 5.4% of the patients (M group), occasionally by 35.4% (O group), and not at all by 59.2% (N group). There was a positive relationship between more frequent BSE and an earlier clinical stage, the percentages of Tis/stage 0 and I for the M, O, and N groups being 83%, 44%, and 36%, respectively (P<0.05). The mean maximum tumor diameters for the three groups were 1.7cm, 2.5cm, and 3.0cm, respectively. The tumor size in the M and O groups was significantly smaller than that in the N group atP<0.01 andP<0.05, respectively. The percentages of patients in the M, O, and N groups who underwent breast-conserving therapy were 42%, 11%, and 19%, respectively, with patients who had performed monthly, BSE more frequently undergoing breast-conserving therapy (P<0.05). At a median follow-up time of 34 months, 0%, 3.8%, and 7.6% of the patients from the M, O, and N groups, respectively, had died of breast cancer, the overall survival curve of the M group being significantly better than that of the N group (P<0.01). This retrospective study suggests the positive correlation of BSE frequency with earlier detection, and a more favorable clinical course in Japanese breast cancer patients.     

Serum and Cerebrospinal Fluid Vitamin B12 Levels in Demented Patients with CH3—B12 Treatment—Preliminary Study—

Abstract: The vitamin B12 (VB12) parameter was studied in the serum and cerebrospinal fluid (CSF) of 14 demented patients. Eleven of these patients were in a state of dementia of the degenerative type such as Alzheimer's disease, senile dementia and Pick's disease. The serum VB12 concentration in all the patients was within normal limits, I.e. 500–1,300 pg/ml. There was no significant difference between the CSF-VBl2 levels and the severity of dementia. The serum and CSF-VB12 levels of the demented patients did not show any significant elevation after the oral administration of CH3–Bl2, 2 mg per day. On the other hand, there was a marked elevation of both the serum and CSF-VB12 after an oral medication (2 mg per day) plus intramuscular administrations (500 μg per day). These results confirm that the intramuscular administration of CH3–B12 is an effective way to get a higher value of the serum and CSF-VB12 levels.