The renal glomerulus is composed of three types of glomerular cells (mesangial cell (MC), endothelial cell and podocyte) and extracellular matrix (ECM) consisting of the glomerular basement membrane (GBM) and mesangial matrix. It constitutes a highly specialized microcirculation in which the permeability characteristics of the capillary wall allow its unique filtration function. The proliferation of MCs, an increase of mesangial ECM and detachment podocyte from GBM are key biological features of progressive glomerulonephritis (GN), leading to glomerular scarring and dysfunction. Thus, the study of the molecular and cellular mechanisms responsible for pathological glomerular alterations may help to elucidate the pathogenesis of progressive glomerular diseases. A growing body of evidence indicates that β1 integrin family (β1 integrins), that mainly mediates cell adhesion to ECM, controls cell behaviors such as cell migration, proliferation, apoptosis and ECM assembly. In addition, a correlation between glomerular expression of β1 integrins and their ligand ECM components is observed in various human and experimental GN, suggesting that altered β1 integrins-mediated cell behaviors may contribute to the progression of GN. It is now becoming apparent that the expression of glomerular β1 integrins is not only critical for maintaining the glomerular capillary permeability but it modulates cell signaling pathways regulating the cell phenotypes involved in the progression of glomerular diseases.
The aim of this article is to introduce the clinical utility of FDG PET as oncologic imaging. PET (positron emission tomography) is a newly developed imaging tool, and it has increased the accuracy of metabolic mapping of numerous malignancies, with significant impact on the management of cancer patients for initial staging, restaging and therapy monitoring. PET can provide functional information in addition to morphology from conventional imaging modalities. 18F-labeled 2-fluoro-2-deoxyglucose (FDG) is the most commonly used PET tracer and FDG PET can demonstrate the activity of glucose metabolism throughout the entire body in a single session. We describe the clinical utility of FDG in PET and display images of normal distribution and of patients with head and neck and lung cancer.
Brown adipose tissue (BAT) is believed to function by dissipating excess energy in mammals. It is very important to understand the energy metabolism held in BAT since disorder of its energy-dissipating function may cause obesity or lifestyle-related diseases such as hypertension and diabetes. This function in BAT is mainly attributable to uncoupling protein (UCP), specifically expressed in its mitochondria. This protein consumes excess energy as heat by dissipating the H+ gradient across the inner mitochondrial membrane that is utilized as a driving force for ATP synthesis. In this review article, in addition to providing a brief introduction to the functional properties of BAT and UCP, we also describe and discuss properties of cultured brown adipocytes and the results of our exploratory studies on protein components involved in the energy-dissipating function in BAT.
The effects of cardiotrophin-1 on hemodynamics, cardiac function, cardiomyocyte apoptosis, and expression of P53, Fas, Bax and Bcl-2 proteins in myocardium were determined in a rat model of acute myocardial infarction. Twenty-four male Sprague-Dawley rats weighing approximately 310 g were subjected to left coronary artery ligation. Seven days before surgery, the rats were randomized to receive cardiotrophin-1 (treated group) or phosphate-buffered saline (control group). Recombinant rat cardiotrophin-1 (2μg in 1 ml phosphate-buffered saline) or phosphate-buffered saline (1ml) was administered daily via the tail vein for 7 days (n=12 for each group). Hemodynamic parameters, apoptotic index, P53, Fas, Bax and Bcl-2 expression in myocardium were measured at 24 hours after coronary ligation. As compared with control animals, rats treated with cardiotrophin-1 had significantly higher mean arterial pressure, left ventricular systolic pressure and the maximum rate of left ventricular pressure rise or fall, and significantly lower left ventricular end-diastolic pressure. Cardiotrophin-1 pretreatment did not affect the heart rate, heart weight, body weight or the ratio of heart weight to body weight. The number of apoptotic cardiomyocytes in cardiotrophin-1 treated group was less than that in control group [(15.8±5.2) % vs (34.6±7.7) %, P<0.01]. Cardiotrophin-1 pretreatment significantly inhibited P53, Fas and Bax, and increased Bcl-2 expression in myocardium.
In the present study, we investigated the effects of hexamethonium, a ganglionic nicotinic receptor blocking agents and yohimbine, an α2-adrenergic antagonist, on reduction of ethanol absorption in presence of high acetaldehyde concentration. Hexamethonium had no effect, whereas yohimbine by itself reduced ethanol absorption, but no additional effects were observed with presence of high acetaldehyde. Propionaldehyde had an inhibitory action on intestinal 1-propanol absorption. As both yohimbine and propionaldehyde are associated with vagus nerve activation, these results indirectly support the hypothesis that a cholinergic mechanism through vagus nerve activation is responsible for the inhibition of intestinal ethanol absorption by acetaldehyde.
Nonsteroidal anti-inflammatory drugs (NSAIDs) induced formation of intestinal ulcers as side effects, in which an unbalanced increase in the number of Gram-negative bacteria in the small intestine plays an important role. To clarify how intestinal microflora are influenced by NSAIDs, we examined the effects of 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl) thiophene (BFMeT), an NSAID, on intestinal motility and on the growth of Escherichia coli and Lactobacillus acidophilus. Transit index, a marker of peristalsis, was not different in BFMeT-treated and solvent-treated rats, indicating that BFMeT increased the number of Gram-negative bacteria without suppression of peristalsis. The factors that affect the growth of intestinal bacteria were not found in intestinal contents of BFMeT-treated rats, because the growth of E. coli and that of L. acidophilus in the supernatants of small intestinal contents of BFMeT-treated rats and solvent-treated rats were not different. The mechanism of the increase in the number of Gram-negative bacteria is still unclear, but heat-killed E. coli cells and their purified lipopolysaccharide (LPS) caused deterioration of BFMeT-induced ileal ulcers, while they could not cause the ulcers by themselves without the NSAID. Concentration of LPS and myeloperoxidase activity level were elevated correlatively in the intestinal mucosa of rats treated with LPS and BFMeT. These results suggest that an increase in the number of Gram-negative bacteria and their LPS in the mucosa induces activation of neutrophils together with the help of NSAID action and causes ulcer formation.
Fragile X syndrome is one of the most common causes of mental retardation in males, and patients with fragile X syndrome occasionally develop autism. It is usually caused by an expansion of the trinucleotide repeat in the 5’-untranslated region of the FMR1 gene, but in a small number of patients deletions and point mutations have been identified. We screened all 17 exons of the FMR1 gene for mutations in 90 autistic or mentally retarded children using polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) analysis. No mutations were found in 76 male patients. However, one female patient was heterozygous for a normal allele and a mutant allele with an A to C substitution at nucleotide 879 in exon 9. This mutation was not found in 50 controls. Reverse transcription-PCR revealed that a large proportion of the mutant transcripts were spliced aberrantly, causing premature termination of the protein synthesis. Although uncommon, point mutations in the FMR1 gene may be a cause of autism and mental retardation in Japanese patients.
[Objective] Cerebral function with a language task was evaluated by functional magnetic resonance imaging (fMRI), and the differences of activated pattern and signal changes were compared between autistic patients and normal controls. [Methods] Ten autistic and ten normal subjects were tested by fMRI with a language task requiring the attribution of complex mental states. Activation maps analyzed between two groups were generated and the asymmetry indexes calculated by the quotient of activated pixels of the right frontal lobe divided by those of the left frontal lobe were statistically compared by unpaired t-test. [Results] Both the autistic and the normal subjects showed activation at the bilateral prefrontal cortical areas and the ventral occipito-temporal regions. However, the autistic patients demonstrated more activation at the right frontal lobe than the normal controls. Thus it was considered that in the autistic patients the right-hemisphere was more dominant for the language task than that of the normal controls. The result is consist to the theory that autism is related to early left-hemisphere dysfunction. [Conclusions] We considered that fMRI may be a useful non-invasive method to evaluate the cerebral functional abnormality in autistic patients.
Background: The prognosis of liver transplantation for liver cancer is determined by recurrence in the liver graft. In this study, the effects of immunosuppressors, FK506 and cyclosporine A (CsA) on the migration of liver cancer cells were investigated. Methods: The effects of FK506 at concentrations of 1-100 ng/mL and CsA at 1-1000 ng/mL on the growth of poorly and well differentiated human hepatocellular carcinoma cell lines, HLE and HuH-7, respectively, were examined. After treatment of these cells with FK506 and CsA, the growth of these cells, their cytotoxicities and invasion assay on the Matrigel basement membrane invasion chamber were evaluated. In addition, the effects of FK506 and CsA on the changes in the production of a soluble intercellular adhesion molecule-1 (sICAM-1) of these cells were measured. Results: FK506 and CsA at concentrations of 1-10 ng/mL inhibited the growth of both HLE and HuH-7 and those immunosuppressors at concentrations over 100 ng/mL exhibited cytotoxicity on these cells. FK506 at concentration of 1ng/mL significantly inhibited the invasion of poorly differentiated HLE, but not well differentiated HuH-7, after treatment for 2-5 days in culture (p<0.05), but FK506 at 10 ng/mL showed less inhibitory efficient. CsA at concentrations of 1-10 ng/mL, however, did not inhibit or transiently inhibited the invasion of both cell lines. The production of ICAM-1 in HLE and HuH-7 was suppressed by FK506 at concentrations of 1-10 ng/mL after treatment for 3-5 days but the effect was not significant in the initial phase at days 1-2 and the last phase at days 5-6. Conclusions: FK506, but not CsA, at a clinical dose of 1ng/mL significantly inhibited the invasion of the poorly-differentiated HLE, but not HuH-7 and also inhibited the production of sICAM-1 in HLE.
To investigate the lymph network change in pancreatic duct obstruction in pigs as a model of pancreatic cancer invading pancreatic duct, six domestic pigs weighing 17-40 kg underwent surgery as protocol. Two of them were controls, and the others underwent ligation of the pancreatic duct as a model of ductal obstruction. A CH 40 and lipiodol mixture was injected in their pancreas at 7 or 21 Days after first operation. Radiographic examination had been also performed. Five or 14 days later, they were examined radiographically, and sacrificed for histological examination. Ligation of the pancreatic duct caused experimental pancreatitis. Dilatation of the pancreatic duct and dilatation of the lymph canal in the interlobular space of pancreas was demonstrated in the ligation group. CH 40 and lipiodol showed discrepancies in the distribution. There were not distinct differences between the two groups in a route of CH 40 traveling. Only fluoroscopic examination revealed an image of lipiodol enlargement to the caudal site in the ligated group. The congestive lymph system may have impaired flow like reflux.
The study investigated the possibility of pharmacologically modulating hepatic allograft function from non-heart-beating donors (NHBDs) using male Lewis rats. The donors were divided into 4 groups: Group 1 in which the vehicle was administered, Group 2 in which FK506 (tacrolimus; a powerful immunosuppressive agent) was administered, Group 3 in which OKY046 (a specific thromboxane synthetase inhibitor) was administered and Group 4 in which FK506 and OKY046 were administered. The recipients received orthotopic liver transplantation. The survival rates differed significantly between the recipients that had received liver transplantation from Groups 1 and 4. The serum liver enzyme and inflammatory cytokine concentrations of the recipients which had received liver transplantation from Groups 2, 3 and 4 were significantly lower than those of the recipients that had received liver transplantation from Group 1. Although there was no significant difference, all parameters were better in the recipients that had received transplantation from Group 4 than those that had received transplantation from Groups 2 and 3. The action mechanisms of FK506 and OKY046 are completely different. Therefore, concomitant use of FK506 and OKY046 might have additive effects on liver transplantation from NHBDs. In conclusion, we demonstrated that pretreatment of NHBDs using FK506 and OKY046 ameliorated graft viability.
Background. Hepatocellular carcinoma is likely to accompany liver cirrhosis in which the portal pressure increases with portasystemic shunt. When portal tumor thrombus is present in the primary bifurcation, blood flow differs between the thrombolic lobe and the non-thrombolic lobe. In those cases, it is difficult to evaluate exactly residual liver function by conventional test. Therefore, the following studies were performed. Materials and Methods. Adult mongrel dogs are divided into a control group (C group), group undergoing ligation of the left portal branch (PL group), group undergoing portacaval anastomosis (PCS group) and group undergoing both ligation of the left portal branch and portacaval anastomosis (PL+PCSgroup)(n=5). ICG-R15 and MEGX15 in peripheral venous blood and right hepatic venous blood were determined. Mitchondrial metabolic capacity (adenosine triphosphate level, energy charge) was measured by high-performance liquid chromatography using liver biopsied specimens. Results. The MEGX ratio (right hepatic venous blood MEGX 15/peripheral venous blood MEGX 15) positively correlated with energy charge in the right hepatic lobe. Conclusions. In evaluating liver function of the right hepatic lobe during portacaval shunt and the left portal branch ligation, the MEGX ratio may sensitively reflect the mitochondrial function.
We studied the effects of unilateral sciatic neurectomy (USN) on the development of the femoral shaft in the 30 growing Wistar-derived rats aged 5 weeks. Rats were allocated to three groups. One of these was immediately used for measurements, and the remaining 2 groups underwent USN of internal control. Specimens obtained from each group were divided into 2 subgroups : left femurs of each group served as the control subgroup (CONT) and right femurs from each group as the USN-operated subgroup (USN-OP). The bone mineral density (BMD), bone mineral content (BMC), bone area, periosteal circumference and endosteal circumference were measured by peripheral quantitative computed tomography (pQCT) and the mineral/matrix ratio was evaluated by Fourier transform infrared spectroscopy (FTIR). A three-point bending test was performed to analyze the biomechanical effects of sciatic neurectomy. USN-OP showed a significant decrease in cortical BMC, bone area, and periosteal circumference compared with CONT. The mineral/matrix ratio of cortical bone did not differ significantly between USN-OP and CONT. Strength and stiffness were significantly decreased in USN-OP compared with CONT. The results showed that USN inhibited periosteal bone formation, but has no significant effects on the mineral/matrix ratio of cortical bone in femurs.
Heavy-ion beams have the feature to administer a large radiation dose in the vicinity of the endpoint in the beam range, its irradiation system and biophysical characteristics are different from ordinary irradiation instruments like X-rays or gamma-rays. In order to get clarify characteristic effects of heavy-ion beams on the brain, we have developed an experimental system for irradiating a restricted region of the rat brain using heavy-ion beams. The left cerebral hemispheres of the adult rat brain were irradiated at dose of 50 Gy charged carbon particles (290 MeV/nucleon ; 5mm spread-out Bragg peak). After irradiation, the characteristics of the heavy-ion beams and the animal model were studied. Histological examination and measurement showed that extensive necrosis was observed between 2.5 mm and 7.5 mm depth from the surface of the rat head, suggesting a relatively high dose and uniform dose was delivered among designed depths and the spread-out bragg peak used here successfully and satisfactorily retained its high-dose localization in the defined region. We believe that our experimental model for irradiating a restricted region of the rat brain using heavy-ion beams is a good model for analyzing regional radiation susceptibility of the brain.
Patients with Parkinson’s disease develop gait disturbances. Although the use of walkers is very effective for maintaining locomotive ability, patients who have symptoms such as frozen gait (FG) and festinating gait may fall even with a walker equipped with a brake as they cannot use the brake well in an emergency and fail to follow the accelerating walker. None of the studies on walking aids to date have addressed real-time detection of FG or the use of this information for the control of the walking aid, monitoring of the state of improvement in the ambulatory function, or evaluation of the effect of the use of a walker. In this study, we evaluated whether the state called FG, a characteristic symptom of Parkinson’s disease, can be detected by the use of a sensor-controlled walker with heel-to-toe pressure sensors. The following two measurements were carried out in one male healthy and a one male patient with stage 3 Parkinson’s disease by the Hoehn-Yahr scale showing mild muscle rigidity, hypokinesia, and FG. In the healthy subject, the heel-to-toe pressure showed smooth heel-to-toe shifts during the standing phase. In the patient with Parkinson’s disease, the heel-to-toe response time was about 2.4 times longer than in the healthy subject at the beginning of walking, and FG could be recorded as the difficulty in lifting the foot by the toes. Also, when FG was observed during walking, the pressure waves recorded by the same sensors showed two peaks occurring at a short interval, indicating double landings.
Various walk supporting systems have been devised and developed. However, they have not been designed for supporting or evaluating the gait of parkinsonian patients, and not much consideration has been given to gait disturbances of parkinsonian patients. In this study : (a) We prepared a tentative model of walk supporting and monitoring system in consideration of typical symptoms of parkinsonism. (b) We conducted gait rehabilitation in a parkinsonian patient using the walk supporting and monitoring system and confirmed (i) the occurrence of frozen gait during walking, (ii) brachybasia, (iii) the absence of anterior tilting of the posture, pulsion symptom, and festination, and (iv) occurrence of hesitation to start walking. Therefore, typical symptoms of parkinsonism can be detected by the use of this system. (c) The medical staff can evaluate the state of recovery of patients on the basis of the data obtained from this system and use them for purposes such as guidance of rehabilitation.
This study was designed to investigate the quality of life (QOL) of cancer patients being cared for in a hospice, in the expectation that the results would serve as useful basic materials for improving the care of such patients. The subjects were 24 patients who had been diagnosed as having cancer and were hospitalized in the hospice wing of a hospital. The study was carried out as a crossing investigation using the Japanese version of the EORTC-QLQ-C30 Ver. 3 questionnaire prepared by the European Organization for Research and Treatment of Cancer. The results of the survey showed that it was important to be prepared to prevent or treat diarrhea at the time of bowel movement and confirmed the need for care aimed at reducing fatigue. In addition, the emotional functioning and financial problems of the patients showed strong correlations with the QOL, revealing the need for psychological and financial support of cancer patients in hospices.