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Prognostic significance of plasma placental growth factor levels in renal cell cancer: an association with clinical characteristics and vascular endothelial growth factor levels.

BACKGROUND: Angiogenesis plays important roles in pathogenesis in human cancer. We assessed the relationship between clinical features of renal cell cancer (RCC) and PlGF levels in relation to VEGF. MATERIALS AND METHODS: Plasma PlGF and VEGF levels were measured in patients with renal cell cancer. The levels of these angiogenetic factors were analyzed in relation to clinical parameters. RESULTS: PlGF and VEGF levels in patients with RCC were significantly higher than those in non-cancer controls. PlGF levels were significantly associated with histological grade and total tumor vascularity (TTV), and VEGF levels were significantly associated with T, M stage, histological grade, venous invasion and TTV. Multivariate analysis showed plasma PlGF was an independent prognostic factor. CONCLUSION: These findings suggested that plasma PlGF levels were significantly associated with the clinical features of RCC, especially prognostic significance.

Carcinoma, Renal Cell↗

Inhibition by a new bisphosphonate (YM175) of bone resorption induced by the MBT-2 tumour of mice.

A new bisphosphonate, disodium dihydrogen (cycloheptylamino) methylene bisphosphonate monohydrate (YM175), was compared with 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate (AHPrBP) and 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) in terms of its effect on tumour induced osteolysis using a bladder tumour in mice (MBT-2). The method consisted of inoculating tumour cells subcutaneously (SC) over the calvaria in mice, resulting in a local tumour causing fragmentation of the bone. The compounds were active not only when administered preventively before establishment of bone resorption, but also in an inhibitory fashion once the variables were already under the influence of the tumour. This osteolysis was evaluated by measuring the increased area of bone resorption in reduced opacity to radiograph and histology. The results showed the following sequence of potency: YM175 > AHPrBP = HEBP. This inhibition was obtained with no apparent effect on the growth of the MBT-2 tumour. YM175 appears to be an interesting new bisphosphonate with possible clinical application.

Animals↗

[Evaluation of lesions of malignant lymphoma using histograms of regional SUV].

We designed new evaluation method using histogram of regional standardized uptake value (SUV) of every pixels of box shape volume of interest (VOI) on 18F-FDG PET. We evaluate lung and liver of normal volunteers and also the lesions of 4 cases of patients with non Hodgikin's malignant lymphoma using this method. SUV of pixels of pretreatment lesions shows log-normal distribution, whereas SUV of lung and liver show normal shape distribution. The next day of chemotherapy, 2 cases of them showed changes of distribution pattern from long-normal to normal with decrease of component of higher SUV values. No remarkable changes of distribution pattern were observed on other 2 cases, whereas decrease of regional mean values and max values of SUV were observed. And these findings were continued to 3 weeks later. These findings suggest that regional evaluation using histograms of SUV gives additional and predictive information for tumor therapies soon after the end of course.

Adult↗

[Factors affecting the occurrence of anastomotic leakage after graft replacement of type A aortic dissection].

Fifty-seven patients of type A aortic dissection were underwent operations from Jan. 1985 to Nov. 1994. The number of patients who underwent graft replacement of the aorta and received aortogram after the operation was twenty-nine. To investigate factors affecting the occurrence of anastomotic leakage after graft replacement of the aorta, the aortograms of the 29 patients were examined retrospectively. The aortograms revealed leakage at the distal anastomotic site on 11 of the 29 patients. Eight factors: the kind of graft, Marfan's syndrome, the use of felt at the anastomotic site, the clamping method, distal anastomotic site, acute or chronic, the state of the aortic wall at the anastomotic site and the blood pressure control after operation, were examined relating to the occurrence of anastomotic leakage. The results showed 3 factors; acute or chronic, the state of the aortic wall and the blood pressure control, affected the occurrence of anastomotic leakage. In short, the anastomotic leakage easily occurred in patients who underwent in the acute stage and whose blood pressure was uncontrolled after the operation. Therefore, strict control of the blood pressure after the operation is the most effective for preventing anastomotic leakage.

Anastomosis, Surgical↗

In vitro studies of leukocyte labeling with technetium-99m.

A method for labeling leukocytes in vitro with 99mTc is described. Separated leukocytes are incubated with 99mTc, followed by reduction with stannous chloride and washing with acid citrate dextrose solution. Maximum labeling occurs after at least 5 min incubation with pertechnetate, followed by at least 10 min incubation with stannous chloride. Labeling is similar at room temperature and at 37 degrees C. The labeled leukocytes are viable, and reutilization of label does not occur in vitro. In acid conditions (pH 5.2), the elution of 99mTc from leukocytes is comparable with that of 32P-diisopropylfluorophosphate, but 99mTc elution is greater at pH 7.2--7.4. Neutrophils label more heavily with 99mTc than do monocytes, lymphocytes, erythrocytes, or platelets.

Blood Platelets↗

S-phase fraction of human prostate adenocarcinoma studied with in vivo bromodeoxyuridine labeling.

Forty-six patients with adenocarcinoma of the prostate were given an intravenous infusion of the thymidine analogue, bromodeoxyuridine (BrdU), 200 mg/m2, at the time of needle biopsy or transurethral resection to label tumor cells in the DNA synthesis phase. The tumor specimens were stained by an indirect immunoperoxidase method with anti-BrdU monoclonal antibody. The BrdU labeling index, S-phase fraction, was determined by counting the number of BrdU-labeled cells in the tissue sections. S-phase fraction correlates with the results of histologic tumor grade, Gleason score, and growth patterns. The higher S-phase fraction may indicate biologic malignancy. Moreover, the degree of heterogeneity concerning S-phase fraction distribution within prostate cancer tissue could be evaluated and the findings compared with the morphologic appearance. The authors results suggest that the measurement of BrdU labeling index in prostate cancer may prove to be a new objective and quantitative assay for biologic potential of individual tumors.

Adenocarcinoma↗

Immunohistochemical study of constituents other than beta-protein in canine senile plaques and cerebral amyloid angiopathy.

To clarify the significance of the constituents of canine senile plaques (SPs) or cerebrovascular amyloid deposits, paraffin and cryostat sections of canine brains were examined by immunohistochemistry using antibodies against cathepsin B (CB), cathepsin D (CD), cystatin C (CC), alpha-1-antichymotrypsin (ACT), heat shock protein 70 (HSP70), ubiquitin (Ubq), and apolipoprotein E (Apo E). On the cryostat sections, all types of canine SPs and cerebrovascular amyloid deposits in both arterioles and capillaries were positive for Apo E. On paraffin sections, the Apo E immunoreactivity of diffuse plaques was weak and varied according to the method of fixation or pretreatment before immunostaining. Moreover, amyloid plaques were found to contain several elements that were positive for CC, ACT, CD, and Ubq, and a subset of vascular amyloid deposits around cortical capillaries showed significant immunoreactivity for CD, CC, and ACT. In addition, vascular amyloid deposits in the arterioles showed moderate CD immunoreactivity and were intensely Apo E positive. No significant labeling of canine Sps or vascular amyloid deposits was detected when the antibodies against CB and HSP 70 were applied to the cryostat and paraffin sections. These results indicated that, of the constituents examined, Apo E might be most closely related to canine beta-amyloidosis in the early stage of this brain disorder.

Amyloid beta-Peptides↗

Immunohistochemical detection of proliferating cell nuclear antigen (PCNA)/cyclin in human prostate adenocarcinoma.

Tissue specimens from 12 patients with adenocarcinoma of the prostate and 7 patients with benign prostate hypertrophy were stained by an indirect immunoperoxidase method using antiproliferating cell nuclear antigen (PCNA) monoclonal antibody. The PCNA labeling index was determined by counting the number of PCNA-labeled cells in the tissue sections. Average PCNA labeling index of the benign prostate hypertrophy was 1.2 +/- 0.5%. Poorly differentiated tumors averaged 7.6 +/- 3.9% labeling versus 4.6 +/- 1.3% in moderately differentiated tumors, and well differentiated tumor in the series had a PCNA labeling index of 2.5 +/- 0.9%. The PCNA labeling indices for atypical hyperplasia were 1.9, and 4.1%, respectively. Our preliminary results suggest that the measurement of PCNA labeling index in prostate cancer may prove to be a new objective and quantitative assay of biological potential of individual tumor.

Adenocarcinoma↗

Surface modification of polyethylene balloon catheters for local drug delivery.

Local drug delivery is an attractive approach to the associated problems of percutaneous transluminal coronary angioplasty (PTCA), including arterial injury. The objective of the present research was to deliver a high concentration of a potent anti-thrombin agent, argatroban (ARG), to the vessel wall in order to reduce arterial injury. Local delivery was accomplished by the ionic attachment of drug particles to a modified balloon surface. Surface graft polymerization of ionic monomers to a high-density poly(ethylene) (PE) substrate was performed utilizing ultra-violet (UV) methods. Acrylic acid (AAc) and 2(dimethylamino) ethyl methacrylate (DMAEMA) were successfully grafted onto PE surfaces. Surface grafting was verified by contact angle, X-ray photoelectron spectroscopy, and zeta potential measurements. The amount of ARG adsorbed onto the modified PE surface was highly dependent on the pH of the drug media for both anionic and cationic grafted monomers. The efficacy of local drug delivery to the arterial wall was analyzed using drug-immobilized PE balloon catheters in the rabbit common carotid artery model. High concentrations of ARG (280 nmol/g tissue) were found within the ballooned arterial segment immediately after angioplasty, followed by a decrease after blood flow was restored.

Acrylates↗

In vitro activity of novel imidazole antifungal agent NND-502 against Malassezia species.

The in vitro activity of NND-502, a novel antifungal imidazole compound, was tested against the three major Malassezia species by an agar dilution method with modified Dixon medium and compared with the activities of three reference antifungal drugs of topical use, lanoconazole (LCZ), bifonazole (BFZ) and terbinafine (TBF). The geometric mean (GM)-MICs of NND-502 for 25 strains of M. furfur, 15 strains of M. sympodialis and ten strains of M. slooffiae were approximately 1.4, 0.1 and 1.0 mg/l, respectively, showing the greatest activity against M. sympodialis and the least against M. slooffiae. These values were similar to that of LCZ, but four to 69 times lower than that of BFZ and two to three times lower than that of TBF. The results suggest that NND-502 might be beneficial in the treatment of Malassezia-associated skin diseases.

Antifungal Agents↗

Aortic blood momentum--the more the better for the ejecting heart in vivo?

OBJECTIVES: The aim of the present study was to test two hypotheses: (1) the momentum of the blood flowing out of the left ventricle toward the aorta (inertia force) plays an important role in the initiation of decay and the maximum rate of decay (peak (-dP/dt)) of left ventricular pressure (P); (2) a normal heart itself generates the inertia force which enhances its function. METHODS: The contribution of the inertia force to (-dP/dt) was theoretically given as rho c alpha, where rho is the blood density, c the pulse wave velocity, and alpha the deceleration rate of aortic blood flow. The correlations of peak (-dP/dt) with rho c alpha and with the time constant (tau) of the pressure decay during isovolumic relaxation, which was considered to represent myocardial relaxation characteristics, were compared in seven dogs. We developed a method of grading the strength of the inertia force, using the phase loop of left ventricular pressure (dP/dt vs. P relation). The method was applied to the records of 25 patients with ischemic heart disease, from which high fidelity left ventricular pressure recordings were available. RESULTS: The correlation of peak (-dP/dt) with rho c alpha was much higher than with tau (0.75 vs. -0.46). 16 of the 25 patients showed evidence of the inertia force. However, other patients showed no inertia force. The strength of the inertia force showed a significant (P < 0.05) correlation with left ventricular end-diastolic pressure (r = -0.46), cardiac index (r = 0.62), stroke volume index (r = 0.69), ejection fraction (r = 0.46), and peak (-dP/dt) (r = 0.56). CONCLUSION: The inertia force of late systolic aortic flow contributed to ventricular relaxation in the normal heart.

Aged↗

Self-assembly of a silica-surfactant nanocomposite in a porous alumina membrane.

A mesoporous membrane composed of nanochannels with a uniform diameter has a potential use for precise size-exclusive separation of molecules. Here, we report a novel method to form a hybrid membrane composed of silica-surfactant nanocomposite and a porous alumina membrane, by which size-selective transport of molecules across the membrane becomes possible. The nanocomposite formed inside each columnar alumina pore was an assembly of surfactant-templated silica-nanochannels with a channel diameter of 3.4 nm; the channel direction being predominantly oriented along the wall of the columnar alumina pore. Molecules could be transported across the membrane including the silica-surfactant nanocomposite with a capability of nanometre-order size-exclusive separation. Our proposed membrane system has a potential use not only for separation science, but also catalysis and chip technologies.

Aluminum Oxide↗

New characterization method for pore and packing structure in powder compacts using confocal laser scanning microscope.

The internal structure of powder assemble was observed by a confocal laser scanning microscope and the results were compared with those of other conventional methods. Two kinds of specimens were examined in this paper: powder compacts from alumina granules and set plaster of gypsum. The structure was sensitive to humidity during pressing of the granule compact of alumina containing polyvinyl alcohol as a binder. Narrow interstices were noted along the boundaries of granules in low humidity. However, uniform internal structure was noted in high humidity. The origin of the difference of packing structure was attributed to the change of binder characteristics with humidity. Interstices were formed in low humidity due to poor adhesion of binder and spring back after pressure removal. The superior capability of the present characterization technique can distinguish a minor difference of internal structure successfully.

Journal Article↗

Increased expression of tumor necrosis factor-alpha messenger RNA in the intestinal mucosa of inflammatory bowel disease, particularly in patients with disease in the inactive phase.

BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha), may be involved in the pathogenesis of inflammatory bowel diseases (IBDs). The aim of this study was to evaluate the effect of TNF-alpha on the inflammatory activity of IBD. METHODS: TNF-alpha mRNA expression in intestinal mucosal biopsy specimens from IBD patients [ulcerative colitis (UC), n = 54; and Crohn's disease (CD), n = 11] was analyzed using a competitive polymerase chain reaction. The degree of macrophage infiltration was analyzed by immunohistochemistry, using an antihuman CD68 antibody. RESULTS: TNF-alpha mRNA expression was increased in UC patients, corresponding to the inflammatory activity. However, in CD, TNF-alpha mRNA expression was not correlated with the endoscopic findings. CONCLUSIONS: We clarified that TNF-alpha mRNA expression was responsible for the inflammatory activity in UC. However, TNF-alpha mRNA expression was not correlated with the mucosal injury in CD.

Adolescent↗

Clonality analysis by methylation-specific PCR for the human androgen-receptor gene (HUMARA-MSP).

The human androgen-receptor gene (HUMARA) has been used for analysis of X chromosome inactivation (XCI) pattern because of a polymorphic short tandem repeat (STR) near the 5'-promoter region correlated with XCI. We introduce a novel method to analyze XCI pattern, named HUMARA methylation-specific PCR (HUMARA-MSP) assay, which analyzes methylation status of the HUMARA gene by bisulfite modification instead of a methylation-sensitive restriction enzyme. Although the original MSP method shows whether there is a methylated band or not, our HUMARA-MSP method identifies the patterns of methylated and unmethylated bands. Because this method identifies either unmethylated or methylated alleles in each PCR tube and shows opposite band patterns dependent on methylation status, we can assess the XCI pattern independently twice. This method can avoid false results by incomplete enzyme digestion and incomplete bisulfite modification will not affect the results. Extremely small quantities of samples, such as hematopoietic colonies, were also available for HUMARA-MSP assay. Because DNA modified by sodium bisulfite is also available for assessment of methylation status of other genes by setting specific primers for them, we performed the simultaneous assessment of clonality and aberrant hypermethylation of p15INK4B gene in myelodysplastic syndromes. These simultaneous assessments were easily possible and provided much information despite requiring only a small volume of DNA. The HUMARA-MSP assay may facilitate the analyses for pathogenesis of hematological disorders because of its simplicity, sensitivity and wide applicability. Leukemia (2000) 14, 207-212.

Base Sequence↗

[Experimental study of glistening in silicone intraocular lenses].

PURPOSE: To assess the whether glistening(GP) occurs on silicon lenses. METHODS: ALLERGAN, SI-40NB and CANON STAAR, AQ110NV lenses(Alcon MA60BM control). The lenses were immersed in 50 degrees C physiological saline solution for 2 hours, and then immersed in 35 degrees C physiological saline solution. Changes in the lens were observed regularly with a slit lamp microscope until the 90th day. RESULTS: Numerous microvacuoles of 10 microns diameter occurred in the MA60BM and of several microns in the SI40NB. Some clouding was seen in the AQ110 NV. CONCLUSION: The presence of numerous microvacuoles in the SI40NB means there may be GP. The light clouding in the AQ110NV that was resolved with drying is thought to be due to particles in the material which cause discoloration.

Biocompatible Materials↗

[Viral diseases of the outer eye--rapid diagnosis by immunohistochemistry].

Rapid diagnosis of viral diseases of the outer eye was attempted by means of immunohistochemical methods. Specimens were obtained with a nitrocellulose membrane, used as a blotter of immunoblotting test. An impression of the corneal or conjunctival surface was obtained by anesthetizing the eye and lightly pressing the membrane against the tissues. In some cases, scraping materials were taken on a slide glass. Viral antigens in the specimens were detected by peroxidase-antiperoxidase (PAP) method, ABC system (Vectastain), or immunofluorescence. Four common diseases were studied. Dendritic corneal lesions caused by herpes simplex virus (HSV) were impressed on the membrane, and exhibited exact duplicates of lesions which were composed of PAP-positive epithelial cells. Under a high magnification, pathologic changes such as margination of chromatin, intranuclear inclusion bodies, and multinucleated giant cells were observed. Of 27 cases of epithelial herpetic keratitis, 25 showed positive results. The impression can permit examination of a minute lesion, therefore, is superior to scraping. Dendritic lesions caused by varicella-zoster virus (VZV) have a characteristic morphology different from those of HSV. Impressions showed the virus antigen, when treated with fluorescein-labeled anti-VZV monoclonal antibody. Appearance of such a dendrite in disorders of unknown cause indicates the etiology. Conjunctival impressions of adenovirus (Adv) conjunctivitis examined by the PAP method revealed Adv-antigen containing cells. Of 64 cases analyzed, 24 PAP-positive cases were compared with the 35 culture-proven cases. The sensitivity of PAP method was 69%, and the specificity was 97%. The detection rate varied according to serotype, and was especially low (33%) in type 3. Guinea pig antisera with high titers against enterovirus type 70 (EV70) and a variant of coxsackievirus A type 24 (CA24v), the causative viruses of acute hemorrhagic conjunctivitis (AHC), were obtained. Using these sera as the primary antibody, the antigen of each virus was localized in the cytoplasm of infected HeLa cells by either ABC, or immunofluorescence. Conjunctival cells from patients with EV70 AHC were antigen-positive for 3 days after the onset of disease. Though epidemics of CA24v AHC have only been experienced in Okinawa, sporadic cases have been observed in other districts of Japan.

Adenovirus Infections, Human↗

[Imaging diagnosis of ruptured site in hepatocellular carcinoma].

Rupture causes frequently the patients with HCC to death. Then it is important to investigate ruptured site of HCC in order to stop bleeding effectively and safely by emergent TAE without causing liver failure. We evaluate the usefulness of 3 major imaging method, such as US, CT and angiography in our 18 cases of HCC. In ultrasonography, ruptured site was shown as the high echoic area localized around the tumor in 4/15 cases (26.7%). In computed tomography of rapid scanning, it was shown as the intraperitoneal high density area around the tumor in 3/18 cases (16.7%). And lipiodol CT showed the characteristic leakage in the abdominal cavity. In angiography, it was shown as the extravasation of contrast material only in 2/13 cases (15.4%). In the results, it was possible to diagnose the ruptured site in 8/18 cases (44.4%) by using these procedures. Diagnosis of ruptured site will make it possible to reduce the frequency of hepatic failure caused by emergent TAE.

Adult↗