Biomedical subjects
Publications and source records attributed to M Kitamura.
We herein report a case of surgically resected mediastinal extraadrenal myelolipoma. Myelolipoma is an uncommon tumor composed of adipose tissue and normal hematopoietic elements, and is most often found in the adrenal glands. We could find only five such cases of mediastinal myelolipoma in the English literature.
Successful gene transfer into specific renal structures allows for evaluation of in vivo effects of certain molecules on the structure and function of the kidney. It would also be useful for therapeutic intervention in renal diseases by introducing "beneficial" genes into the affected sites. Towards achieving these goals, several gene transfer approaches have been developed using retrovirus, adenovirus and liposome. By introducing these gene transfer vectors via particular access routes, it is feasible to selectively manipulate the function of certain renal structures. Through the renal circulation, exogenous genes can be targeted to the vasculature and glomerulus, and possibly to the proximal tubules. Using a retrograde approach via the urinary tract, access to the collecting ducts can be gained. Implantation of genetically modified cells under the capsule of the kidney allows for diffusion of transgene products into the interstitium. Transplantation of embryonic metanephric tissues also provides a biological window for genetic manipulation. Furthermore, utilisation of fertilised eggs or embryonic stem cells would enable the creation of "transgenic kidneys" or "gene knockout kidneys". This article summarises the current experience with gene transfer to the kidney and addresses the potential strategies in vivo.
Effects of the selective cyclooxygenase-2 (COX-2) inhibitors such as NS-398 and nimesulide on duodenal HCO3- secretory and ulcerogenic responses to mucosal acidification were examined in rats, in comparison with indomethacin, a nonselective COX inhibitor. Duodenal HCO3- secretion in anesthetized rats was increased in response to mucosal acidification. The increased HCO3- response to acid was significantly suppressed by pretreatment with indomethacin (10 mg kg(-1), s.c.), while both NS-398 and nimesulide (10 mg kg(-1), s.c.) had no effect on this response. The luminal release of prostaglandin E2 (PGE2) was increased during and after mucosal acidification, and this response was significantly inhibited by indomethacin but not NS-398 or nimesulide. Indomethacin provoked hemorrhagic lesions in the duodenum when acid hypersecretion was concomitantly induced by histamine (8 mg kg(-1) hr(-1), i.v.), while either NS-398 or nimesulide did not cause damage in the duodenum. Either of these drugs had no effect on histamine-induced acid secretion. On the other hand, both NS-398 and nimesulide showed a significant suppression against carrageenan-induced rat paw edema, similar to indomethacin. The present study supports a mediator role for endogenous PGs in duodenal HCO3- secretion in response to mucosal acidification and suggests that COX-1 but not COX-2 is a key enzyme in regulating this process and maintaining the mucosal integrity against acid in the duodenum.
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Three infertile patients fulfilling normal or subnormal criteria on routine semen analysis showed abnormal sperm CD46 (membrane cofactor protein of complement) by SDS-PAGE/immunoblotting analysis using a panel of monoclonal antibodies. The sperm CD46 isoform has been reported to be associated with sperm-egg interaction. These three patients expressed normal CD46 isoforms on their lymphocytes and granulocytes. Sperm-specific abnormalities in these proteins thus parallel male infertility, suggesting a new category of infertility, probably due to aberrations in the molecules related to sperm-egg interaction.
A specific and sensitive enzyme-linked immunosorbent assay (ELISA) and a single radial immunodiffusion (SRID) were developed for measurement of serum vitellogenin (Vg) levels in Sakhalin taimen (Hucho perryi). Regarding specificity for serum Vg, an antiserum raised against lipovitellin of taimen (a-Lv) was adequate for both assays. ELISA and SRID could detect Vg in serum at concentrations as low as 10 ng/ml and 25 micrograms/ml, respectively. In estrogen administration experiments, the level of serum Vg began clearly increasing within 12 to 24 hr after injection of immature females with estradiol-17 beta (E2). The appearance and levels of Vg in males treated with E2 were delayed and smaller, respectively, than for females. Vg levels varied throughout natural vitellogenesis from 0-4 micrograms/ml (3 years old) to approximately 30 mg/ml (5-6 years old). We observed an early transitory peak of serum Vg levels (primary reaction) at the time of early vitellogenesis and chronic high Vg levels (for 6-7 months) in winter period before ovulation. Changes of serum E2 levels were correlated with Vg levels. However, E2 levels decreased a month earlier than Vg levels near ovulation. It appears that the duration of vitellogenesis in taimen is considerably longer than that in other salmonids, lasting more than 2 years.
We measured serum concentrations of hapatocyte growth factor (HGF) in patients with gastric cancer and compared these with the histological findings and conventional tumour markers, including CEA, CA19-9 and CA125, for evaluation of the significance of serum HGF levels as a tumour marker. The HGF levels were measured by an enzyme-linked immunosorbent assay (ELISA) system. The average levels of serum HGF in 89 healthy control subjects, 104 patients with primary gastric cancer and 15 patients with recurrent gastric cancer were 0.31 +/- 0.11 ng ml(1), 0.42 +/- 0.50 ng ml(-1) and 0.92 +/- 0.39 ng ml(-1) respectively. The average level in patients with recurrent disease was significantly higher than in healthy control subjects and in primary cancer patients (P< 0.001 and P< 0.003 respectively). Of 104 patients with primary gastric cancer, 35 (33.7%) showed an aberrant increase in the circulating level of HGF. The increased HGF levels were significantly associated with the degrees of histological tumour invasion and venous invasion. Of 15 patients with recurrent gastric cancer, 14 (93.3%) showed an aberrant increase. No correlation was found between serum HGF levels and CEA levels, CA19-9 levels and CA125 levels. However, the rate of the aberrant increase in HGF levels was significantly higher than that of any other tumour markers, including CEA, CA19-9 and CA125, in primary gastric cancer patients. In conclusion, the circulating levels of HGF were elevated in approximately one-third of patients with primary gastric cancer, particularly in those with high grades of histological tumour invasion and venous invasion, and frequently in patients with distant metastases, suggesting that HGF might play important roles in the tumour progression of gastric cancer. Furthermore, serum HGF levels may be of value as a tumour marker in patients with gastric cancer.
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TGF-beta has been considered as the key regulator in the generation of glomerulosclerosis. Despite abundant descriptive data, it still remains undetermined whether sustained, local expression of TGF-beta leads to irreversible glomerulosclerosis. There is no doubt that TGF-beta stimulates ECM production in the glomerulus, but this molecule has several anti-inflammatory properties as well. Towards a better understanding of the pathogenesis of glomerulonephritis and for the development of novel and efficient therapeutic interventions, extensive efforts should be made to clarify the 'bright side' of TGF-beta as well as its 'dark side' in individual experimental and human diseases, focusing especially on the concentration and the time-point at which its anti-inflammatory properties spill over into its prosclerotic actions.
An uptake coefficient proportional to the glomerular filtration rate (GFR) can be estimated from dynamic renal images with 99Tcm-DTPA using Rutland's graphic method. We have developed a new method of extracting the input and retention functions by applying factor analysis to the renal dynamic images obtained with 99Tcm-DTPA, which we have called the 'factor uptake coefficient' (Factor UC). In the present study, we followed 13 living kidney donors (7 males, 6 females) by measuring the Factor UC in each kidney before nephrectomy and in the remaining kidney 3 weeks and 1 year after nephrectomy. The median Factor UC in the remaining kidney increased from a pre-nephrectomy value of 0.31 to 0.52 three weeks post-nephrectomy, which then remained unchanged for up to 1 year. These results indicate that functional compensation occurs following unilateral nephrectomy, and that this process is complete within 3 weeks after nephrectomy.
Simple chest X rays on film are the most common type of image in medical diagnosis. However, amongst the various types of medical X-ray images, they require the highest level of display quality due to the fact that the body structures they capture on film have varying degrees of permeability to X rays. Conventional high-definition digital display technology has not always been able to match the quality of such film images. This has been a major impediment against progress toward the complete digitization of simple chest X rays. The intent of this paper is to examine that, when applied to medical diagnosis of chest X rays, super-high-definition (SHD) images (digital images with resolution exceeding that of HDTV) are capable of producing a level of quality of diagnostic accuracy on a par with conventional film images. We will start out by seeking out the overall transmission characteristics of a system that uses digital radiography and a film digitizer to digitize images. We will then derive gray-scale transform characteristics based on the luminance linear method for approximating, as closely as possible on a CRT, film images on a light box that have wide dynamic range and high luminance. Finally, we will present the results of image evaluation experiments using high-definition CRT monitors. These results indicate that conventional film images and those on super-high-definition CRT monitors have nearly the same quality. They will also show that the contrast mapping selected by radiologists and theoretical luminance linear characteristics were almost the same except in low-luminance regions. We will also discuss radiologists' comments on CRT monitors after they participated in the evaluation experiment.
An 83-year-old female diagnosed with small cell carcinoma of the kidney is reported on. The clinical picture was similar to that seen with transitional cell carcinoma of the renal pelvis. A right nephroureterectomy was performed and a histological examination revealed similar morphological features to those of small cell carcinoma of the lung. Neuroendocrine differentiation was proven by a positive immunoreaction to neuron-specific enolase. A review of the literature indicated that in the urinary tract, most of the cases of small cell carcinoma occurred in the urinary bladder, with this case being the eleventh reported case of small cell carcinoma originating in the kidney. As with many of the other cases of small cell carcinoma of the urinary tract, this patient's tumor was associated with both adenomatous and squamous differentiation. The patient died 2 months after surgery, prior to any chemotherapy administration.
We examined a new technique of cross-circulation (CC) venoarterial bypass (VAB) with femoral arterial perfusion and superior vena cava drainage through a long femoral venous cannula. Six adult mongrel dogs weighing 15 to 20 kg underwent the CC-VAB with oxygenation after introduction of respiratory failure (RF). The flow of the CC-VAB was maintained at half the level of the control cardiac output, and the hemodynamic parameters were monitored. To evaluate hypoxia in the upper body, the arterial partial pressure of oxygen (PaO2 [mm Hg]) in the carotid artery and the venous saturation of oxygen (SvO2 [%]) in the pulmonary artery were measured during control, RF, standard VAB, and CC-VAB conditions. The PaO2 decreased significantly after the introduction of RF (41.7 +/- 12.4), and it returned to normal levels only after CC-VAB (151.2 +/- 24.5, p < 0.05). The SvO2 during CC-VAB (98.6 +/- 2.1) was significantly higher than that during VAB without CC (53.5 +/- 3.4, p < 0.05). These results suggest that this cross-circulation technique could be applied to patients with differential hypoxia during femoral VAB with oxygenation or percutaneous cardiopulmonary support (PCPS).
Insufficient unloading of the left ventricle with blood stagnation is a main cause of unsuccessful left ventricular (LV) recovery during percutaneous cardiopulmonary support (PCPS). The purpose of this investigation was to evaluate the effectiveness of transaortic catheter venting (TACV) for LV unloading. Six adult mongrel dogs (mean weight 16.3 kg, range 14-20 kg) underwent venoarterial bypass (VAB) with TACV. Bypass flow ranged from 0.8-1.2 L/min, and TACV flow ranged from 160-240 ml/min. In addition to monitoring the standard hemodynamic parameters, the slope of the LV end-systolic pressure-volume relation (Emax) during transient occlusion of the inferior vena cava, the slope of the LV end-systolic pressure-stroke-volume relation (Ea), the stroke work (SW), the LV pressure-volume area (PVA), and the slope of the SW end-diastolic volume relation, the preload recruitable stroke work (PRSW) were assessed by means of a microtip manometer and a conductance catheter. The LV contractility (Emax) and aortic elastance (Ea) were equivalent in the 2 groups with or without TACV (7.7 +/- 1.1 versus 8.4 +/- 1.5 mm Hg/ml and 8.2 +/- 1.4 versus 7.6 +/- 1.3 mm Hg/ml). Comparing the measurements for the baseline to those for VAB with TACV, the SW was significantly reduced, and the PVA/SW was increased by TACV (1,685 +/- 309 versus 867 +/- 188 x 10(-4) J, p < 0.05 and 1.32 +/- 0.03 versus 1.58 +/- 0.11, p < 0.05, respectively). Furthermore, the PRSW was gradually decreased from the baseline value to the value resulting from VAB with TACV (75 +/- 8 versus 44 +/- 3 x 10(-4) J/ml, p < 0.01). In comparison, the percent reduction of SW between VAB and VAB with TACV tended to be increased by TACV (23.2 +/- 7.2% versus 46.9 +/- 7.7%, p = 0.05). These results suggest that TACV might reduce LV work (SW and PRSW) and might increase the LV energetic charge. In conclusion, TACV would be an adjunctive technique to VAB or PCPS for patients with LV failure.
Thrombosis of the innominate vein and SVC is a serious complication in patients with pacemakers, inducing pulmonary embolism or SVC syndrome. Venography is the definitive method for its diagnosis; however, it is too invasive for related studies. The purpose of this study was to validate sonography, pulse Doppler, and color flow in detecting noninvasively innominate vein or SVC thrombosis in patients with pacemakers. In 53 patients with pacemakers, the 1 severe SVC stenosis and 18 severe innominate vein stenoses due to thrombosis were diagnosed by digital subtraction angiography. Sonography accurately showed the severe SVC stenosis due to thrombosis, but had limitations on the innominate vein thrombosis. Color flow demonstrated mosaic flow, indicating poststenotic turbulence due to stenosis of the innominate vein and SVC caused by thrombosis in 15 of 16 patients, and pulse Doppler disclosed absence of flow due to complete occlusion of the innominate vein in 2 of 2 patients. Sensitivity and specificity for detecting severe innominate vein stenosis due to thrombosis using combined color flow and pulse Doppler was 94% and 100%, respectively. In conclusion, sonography, pulse Doppler, and color flow allow accurate detection of severe innominate vein or SVC stenosis due to thrombosis, and are therefore useful for the follow-up of patients with a pacemaker.
Two barriers prevent adenovirus-based vectors from having wide application. One is the difficulty of making new adenoviruses, and the second is the strong immunological reaction to viral proteins. Here we describe uses of Cre-lox recombination to overcome these problems. First, we demonstrate a simple method for constructing E1-substituted adenoviruses. Second, we demonstrate a method to construct adenovirus vectors carrying recombinant genes in place of all of the viral genes, so-called gutless adenovirus vectors. The pivotal feature in each method is the use of a negatively selected adenovirus named psi5. We engineered a cis-acting selection into psi5 by flanking its packaging site with loxP sites. When psi5 was grown in cells making a high level of Cre recombinase, the packaging site was deleted by recombination and the yield of psi5 was reduced to 5% of the wild-type level. To make a new E1-substituted virus, we used psi5 as a donor virus and recombined it with a shuttle vector via a loxP site. The resulting recombinant virus has a single loxP site next to the packaging site and therefore outgrows psi5 in the presence of Cre recombinase. To make a gutless virus, we used psi5 as a helper virus. The only viral sequences included in the gutless vector are those needed in cis for its replication and packaging. We found that a loxP site next to the packaging site of the gutless virus was necessary to neutralize homologous recombination between psi5 and the gutless viruses within their packaging domains.