Lignocaine–induced convulsion does not induce c–fos protein (c–Fos) in rat hippocampus

Recent studies have shown that proto–oncogene c–fos mRNA is induced in the central nervous system by a variety of stimuli including generalised convulsions. In this study, the expression of c–fos protein (c–Fos) following lignocaine–induced convulsions was examined and compared with that following convulsions induced by non–anesthetic convulsants, such as pentylenetetrazol, kainic acid and electroconvulsive shocks, in rat brain.
Administration of 120 mg kg^-1 lignocaine by the intraperitoneal route induced generalised convulsions in all rats examined within 10 min. C–Fos was markedly induced in the piriform cortex and amygdala, and slightly induced in the neocortex and thalamus, while no c–Fos expression was observed in the hippocampus. In contrast, c–Fos expression following generalised convulsions induced by non–anaesthetic convulsants was very marked in the hippocampal region, piriform cortex and amygdala, and extended to the thalamus and neocortex.
These results contradict those of previously reported local cerebral metabolic studies using 2–deoxyglucose as a metabolic marker, and suggest that lignocaine–induced convulsions, unlike those induced by non–anaesthetic convulsants, may not cause severe sequelae (plastic changes) in the hippocampus.     

Cerivastatin inhibits fetal calf serunvinduced DNA synthesis in cultured rat mesangial cells

SUMMARY: Inhibition of mevalonate synthesis by several statins has been shown to suppress DNA synthesis in glomerular mesangial cells. In the present study, we investigated the effect of a new statin, cerivastatin, on fetal calf serum (FCS)-induced DNA synthesis of cultured rat mesangial cells. Cultured rat mesangial cells were stimulated by 10% FCS in the presence or absence of cerivastatin and mevalonate. 5-bromo-2-deoxyuridine (BrdU) incorporation was used to assess DNA synthesis. the present study showed that 10% FCS caused marked stimulation of DNA synthesis in the mesangial cells. Cerivastatin inhibited FCS-stimulated BrdU incorporation in a dose-dependent manner. IC₅₀ was approximately 1 umol/L. Exogenous mevalonate, farnesyl pyrophosphate and geranylgeranyl pyrophosphate significantly prevented the inhibitory effect of cerivastatin on DNA replication. It appears that cerivastatin, by inhibiting the synthesis of mevalonate, may suppress DNA synthesis in the mesangial cells.     

Genetic susceptibility to type 2 diabetic nephropathy in human and animal models

SUMMARY:   Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) in Japan, Western Europe, and the United States. Mega studies such as Diabetes Control and Complication Trial (DCCT), Epidemiology of Diabetes Interventions and Complications (EDIC), and the United Kingdom Prospective Diabetes Study (UKPDS) clarified that poor glycemic and blood pressure control are undoubtedly involved in the development of nephropathy. However, these factors are not sufficient to predict which diabetic patients will develop renal disease, because not all patients with poor glycemic and blood pressure control develop renal disease. Since ethnic variations and familial clustering of diabetic nephropathy have been observed, genetic factors might contribute to susceptibility to this disease. Several methods such as (genome wide) association studies, sib-pair analysis, and quantitative trait loci (QTLs) analysis are available to examine polygenic diseases. However, no mutations that could explain the majority of nephropathy cases have been identified so far. The development of most diabetic nephropathy might be explained by the polygenic effect (i.e. many minor gene-gene interactions might be very important in the development of nephropathy). Identification of candidate genes of nephropathy enables targeting of therapy in patients at risk and development of novel therapeutic agents.     

Bifurcation properties of the two process model

Abstract Daan's two process model is known to be one of the most powerful models, covering various situations from free-running to sleep deprivation. In this study, bifurcation properties of the model dynamics as function of a gap, D , between the threshold processes are clarified using a circle map. As a function of D , we will show that the model has the different types of the mutual entrainment regions that are intervened by the tangent bifurcation. The variable behavior of human circadian rhythm is suggested to be systematically understood based on the bifurcation properties of the two process model.     

A vascular smooth muscle-specific CD4+ T cell line that induces pulmonary vasculitis in MRL-+/+ mice

We established a T cell line, MV1, specific for rat vascular smooth muscle antigen from the regional lymph nodes of immunized MRL/Mp-+/+ mice. Adoptive transfer of MV1 T cells induced vasculitis lesions in the lungs of the syngeneic recipient mice pre-treated with cyclophosphamide. Flow cytometric analysis showed that MV1 was a CD4⁺ T cell line. The T cells proliferated in the presence of the vascular smooth muscle antigen and mitomycin C-treated syngeneic spleen cells. The cross experiments using an ovalbumin-specific T cell line demonstrated that MV1 was specific for vascular smooth muscle antigen. The antigen-specific proliferation of MV1 was CD4-dependent, which was consistent with the flow cytometric analysis. In addition, MV1 T cells, upon activation with anti-CD3 antibody or antigen-specific activation, killed A20.2J mouse B lymphoma cells. MV1 T cells also killed a CD95 (Fas)-transfected T lymphoma line, but not its parental Fas-negative cell line. These findings indicate that MV1 T cells killed target cells via a Fas ligand (FasL)/Fas pathway. The cytotoxicity of MV1 T cells may play an important role in the development of vasculitis in this model. Although the antigenic epitopes of MV1 and the lung specificity of vasculitis remain to be clarified, MV1-induced vasculitis should serve as an experimental model of human pulmonary vasculitis.     

Anti-neutrophil cytoplasmic antibodies (ANCA) in ulcerative colitis: anti-cathepsin G and a novel antibody correlate with a refractory type

We analysed the clinical significance of ANCA in patients with ulcerative colitis. On either an indirect immunofluorescence assay or an ELISA with fixed neutrophils, 71% (25/35) of the patients were positive for ANCA. However, only half of them reacted with either cathepsin G or lactoferrin. Western blot assays revealed positive bands in 40% (10/25) of the antibody-positive patients. The sizes of the bands detected were ≈58, 47, 44, 40, and 28 kD. No significant correlation was found between the ANCA positivity and various variables, i.e. disease activity, extent of lesion, or treatment of the disease. The anti-cathepsin G and 28-kD positivity, however, significantly correlated with a refractory type of ulcerative colitis.     

Influence of left ventricular filling proffle during preceding control beats on pulse pressure during ventricular premature contractions

We investigated whether the left ventricular filling profile,defined as the early to late diastolic left ventricular fillingvolume ratio, during the preceding control beats actually affectsthe pulse pressure during a ventricular premature contraction(PVC). Twenty patients underwent invasive electrophysiologicalstudy for sinus bradycardia. VPCs with various coupling intervalswere induced by right ventricular electrical stimulation, andthe mitral filling flow velocity pulsed Doppler echocardiography,the femoral arterial pressure curve and the electrocardiogramwere simultaneously recorded The early to late diastolic velocity-rimeintegral ratio (E₁/A₁ ratio) of the mitral filling flow velocityduring the control beats which preceded the VPC was measuredas an index characterizing left ventricular filling profile.The coupling interval of each VPC and the extrasystolic beatpulse pressure were measured The ratio of the extrasystolicbeat pulse pressure to the control beat pulse pressure was expressedin % (% extrasystolic beat pulse pressure). The correlationbetween the coupling interval and the % extrasystolic beat pulsepressure was investigated. Coupling intervals of 0·80,0·70, 0·60, 0·50, and 0·45 s wereused At a coupling interval of 0·80 or 0·45 s,the % extrasystolic beat pulse pressure showed no significantcorrelation with the E₁/A₁ ratio. In contrast, the % extrasystolicbeat pulse pressure with coupling intervals of 0·70,0·60, and 0·50 s showed a significant positivecorrelation with the E₁/A₁ ratio (r=0·67, 0·74,and 0·66 P<0·01, respectively). In additionto the prematurity and the site of origin of the VPCs, the leftventricular filling profile during the preceding control beatsmay significantly affect the height of the pulse pressure duringextrasystoles with medium length coupling intervals.     

RELATIONSHIP BETWEEN GENETIC POLYMORPHISM OF CYP2E1 AND ALDH2, AND POSSIBLE SUSCEPTIBILITY TO ALCOHOLISM

In 45 healthy Japanese volunteers, it was found that personsheterozygous for ALDH2 (ALDH2^*1/ALDH2^*2), and also either heterozygousor mutant homozygous for CYP2E1 (C₂/C₂ or C₁/C₂ can drink muchmore alcohol, even with (slight) flushing, than persons heterozygousfor ALDH2 (ALDH2^*1/ALDH2^*2) and normal homozygous for CYP2E1(C₁/C₁)     

Metastatic tumor extending through the inferior vena cava into the right atrium: a case report of carcinoma of the uterine cervix with para-aortic lymph node metastases

Carcinoma of the uterine cervix with cardiac metastasis is not uncommon in autopsy cases. However, an intraatrial tumor extending through the inferior vena cava (IVC) from the site of para-aortic lymph node metastasis has never been reported. A 57-year-old Japanese woman was admitted to an emergency care unit complaining of mild chest pain and shortness of breath. She had progressive multiple lymphatic metastases of stage IIIB squamous cell carcinoma of the uterine cervix that had initially been treated with concurrent chemoradiation. Echocardiogram showed pedunculated tumor in the right atrium (RA), and computed tomography demonstrated multiple pulmonary tumor embolism. Surgical specimen from the RA showed squamous cell carcinoma resembling the primary cervical tumor, and the peduncle appeared to originate from within the IVC. Postoperative ultrasonography showed severe stenosis of the abdominal IVC due to the invasive growth of para-aortic lymph node metastases. The stalk of the tumor originated from this lesion. We present an extremely unusual case of intraatrial metastatic tumor originating from the para-aortic lymph nodes of cervical cancer.