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Regional cerebral blood flow abnormalities in chronic solvent abusers.

This study aimed to reveal regional abnormalities of cerebral blood flow (CBF) and their relation to amotivational syndrome which causes poor social prognosis in solvent abusers Sixteen chronic solvent abusers (12 males and four females) along with five normal subjects underwent single photon emission computed tomography with N-isopropyl-p[123I]iodoamphetamine. The patients received a clinical evaluation with the Scale for the Assessment of Negative Symptoms. Using a semiquantitative method (normalized by the parietal cortex count), patients showed a statistically significant decrease in regional cerebral blood flow (rCBF) in the bilateral prefrontal cortices (P<0.01). In addition, the severity of hypoperfusion in the bilateral prefrontal cortices was related to the degree of severity of the avolition-apathy scale on SANS (left; P<0.05, right; P<0.01) even after excluding the effect of antipsychotics. These results suggest that rCBF abnormalities, especially in the prefrontal cortex, develop in chronic solvent abusers, and that this frontal hypoperfusion may be a biological basis of amotivational syndrome.

Adolescent↗

Crystallization and preliminary X-ray diffraction studies of cytochrome c6 from Porphyra yezoensis.

Cytochrome c(6) from the red alga Porphyra yezoensis has been purified and crystallized by the sitting-drop vapour-diffusion method. Two different crystal forms, tetragonal and orthorhombic, were obtained. The tetragonal crystals belong to space group P4(1)2(1)2 or P4(3)2(1)2, with unit-cell dimensions a = 49.33 (2), c = 83.70 (10) A. The orthorhombic crystals belong to space group P2(1)2(1)2(1), with unit-cell dimensions a = 46.74 (2), b = 49.42 (1), c = 37.11 (1) A. Absorption spectra of the crystals showed that the tetragonal form was oxidized and the orthorhombic form was reduced.

Crystallization↗

[Development of a fetoscope and its clinical application].

One of the major goals in modern obstetrics is to provide more detailed informations of prenatal fetal physiology. Since 1972, more than 200 amniocentesis were performed in our hospital and the importance of prenatal genetic diagnosis has been recognized. But amniocentesis has the limitations which are 1) the lack of expression of many single gene hereditary disorders in amniotic fluid and its cells, 2) the large percentage (90%) of nonviable fetal cells in any given sample, 3) the length of time required to culture fetal cells. Accordingly the necessity of development of other methods to obtain further direct data on the fetus from the uterine cavity has been indicated. Among gynecological endoscopies, fetoscopy which is direct visualization of the fetus by introduction of an endoscope into the amniotic cavity is expected to obtain direct information from the uterine environment in pregnant women. By our newly developed fetoscope, we investigated clinical indications and contraindications of fetoscopy as well as future possibilities of this endoscope. Our present study indicates that further developments and future benefits of fetoscopy entirely depend on the progress of laboratory techniques which can provide more accurate data through specimens obtained fetoscopy.

Adult↗

Association between the expression of inducible nitric oxide synthase by chondrocytes and its nitric oxide-generating activity in adjuvant arthritis in rats.

Inducible nitric oxide synthase (iNOS) is one of the clinical targets in rheumatoid arthritis. Synoviocytes, macrophages, and chondrocytes in the joints of patients with rheumatoid arthritis appear to express iNOS, but the contribution of iNOS molecules to rheumatoid arthritis is not yet clear. This study used adjuvant-induced arthritis in rats as a model to examine the association between the iNOS expression and its activity in rheumatoid arthritis. In adjuvant-injected rats, arthritic changes in the paw were first observed between days 10 and 12. NO-generation activity was precisely determined by combining an electron spin resonance/nitric oxide (NO)-trapping method with the method of standard addition using an NO generator, and we found that the activity in the joint samples was extremely high on day 10. The administration of S-(2-aminoethyl)isothiourea, a selective iNOS inhibitor, from day 0 to day 10, effectively reduced the paw swelling. Immunohistological studies showed that chondrocytes expressed iNOS on days 7-14 and that nitrotyrosine residues, a footprint of NO generation, were produced on day 10. This indicates that NO generation by iNOS induced in chondrocytes is a key event in the induction of adjuvant arthritis.

Animals↗

Infrequent involvement of p53 mutations and loss of heterozygosity of 17p in the tumorigenesis of renal cell carcinoma.

Restriction fragment length polymorphism (RFLP) analysis and the polymerase chain reaction of the single-strand conformation polymorphism (PCR-SSCP) method were conducted to assess the loss of heterozygosity of chromosome 17p and mutations of the p53 gene in 30 surgical specimens of human renal cell carcinoma. Six of 29 tumors (20.6%) showed loss of heterozygosity on chromosome 17p in RFLP analysis, and in none of 21 tumors could a mutation be found on exons 5 to 8 of the p53 gene in PCR-SSCP analysis. We conclude that the p53 gene mutation does not play a role in the development of the majority of cases of renal cell carcinoma and that there may be another tumor suppressor gene on 17p.

Carcinoma, Renal Cell↗

Scanning of polypoid gallbladder lesions by ultrasonic microprobes using transpapillary catheterization.

BACKGROUND AND STUDY AIMS: Polypoid lesions of the gallbladder can be diagnosed by transabdominal ultrasonography and endoscopic ultrasonography. However, the image resolution is limited, and the histopathology of these lesions is difficult to determine. We report here on our preliminary results in four patients using a high-frequency (20 MHz) ultrasonic microprobe introduced into the gallbladder via the transpapillary approach. PATIENTS AND METHODS: Insertion of the microprobe into the gallbladder through the papilla of Vater was attempted in four patients with gallbladder diseases without preceding endoscopic sphincterotomy. RESULTS: The lesions in the gallbladder were clearly visualized in three of the four patients. We tried to correlate the characteristic ultrasound findings with the histopathology of the lesions, which were found to be early cancer, adenoma, and adenomyomatosis on histopathology of the specimens after cholecystectomy. No complications occurred. CONCLUSIONS: High-resolution endoscopic transpapillary ultrasonography of the gallbladder is feasible and safe, and may contribute to the diagnosis of gallbladder diseases, particularly of small polypoid lesions.

Adenoma↗

An affinity adsorbent, 5'-adenylate-aminohexyl-sepharose. I. Purification and properties of two forms of RNase U2.

An affinity adsorbent, 5'-adenylate-aminohexyl-Sepharose 4B, was prepared by the periodate oxidation of AMp followed by coupling and condensation with amino-hexyl-Sepharose 4B. RNase U2, a purine-specific RNase, was specifically bound to this adsorbent at pH 4.5 and eluted critically at pH 5.9 in the presence of 1 M NaCl, corresponding to the pH dependence of the binding of 2'-AMP to RNase U2. By using this affinity chromatography as a main tool, a simplified and effective purification method for RNase U2 was established with a high yield of 58%. Another form of RNase U2 with low specific activity, named RNase U2-B, was eluted at a slightly higher pH from this adsorbent. RNase U2-B was indistinguishable from the original enzyme (RNase U2-A) in base specificity, affinity for ApA, molecular weight and amino acid composition, but was clearly different in specific activity, molecular activity for ApA, isoelectric point and conformation of molecule. This affinity adsorbent is also effective for the detection or isolation of small amounts of base-specific RNases in crude cell extract.

Adenosine Monophosphate↗

Renal transplantation for the hemodialysis patient with axillofemoral bypass.

BACKGROUND: Axillofemoral bypass grafts are used in the treatment of aortoiliac occlusive disease caused by atherosclerosis. There have been no previous reports on renal transplantation used as treatment for chronic renal failure after an axillofemoral bypass graft being placed because of atypical coarctation of the aorta. METHODS: The patient was a 47-year-old woman who had received regular hemodialysis for 15 years. Axillofemoral bypass surgery was performed because of atypical coarctation of the aorta in October 1999. Three years after surgery, she underwent renal transplantation. RESULTS: Renal transplantation was successful, and helical computed tomography demonstrated patent graft bypass and good nephrographic effects of the renal artery. CONCLUSIONS: Even though dialysis patients with atypical coarctation of the aorta are treated with an axillofemoral bypass, it is possible for them to undergo regular renal transplantation, if part of the external or internal iliac artery is intact.

Aortic Coarctation↗

Induction of mononuclear cell infiltration into liver by Japanese herbal medicine.

Juzen-Taiho-To (JTT) is a Japanese herbal medicine that has been administered mainly to patients weakened by long illness. Currently, it has also been used for cancer patients and showed antitumor effects that have been reported as phagocytosis enhancement, cytokine induction and antibody production. In this study, we examined the effect of oral administration of JTT in mice on the immunological restoration of the liver, especially focused on natural killer (NK) T-cell induction. Mice were grouped to receive JTT or placebo orally for a period of 1, 3 and 7 days. After sacrifice, the liver tissue was fixed, embedded and stained with hematoxylineosin and some antibodies by common staining methods. Transmission electron microscope (TEM) observation was also carried out. Although the JTT-treated mice had the same appearance as the non-JTT-treated mice, their livers were infiltrated by massive mononuclear cells, some of which were aggregated in clusters. Immunohistochemical staining revealed that there was abundant cytokine expression of interleukin (IL)-12 and massive infiltration of mononuclear cells with large granules in the liver of JTT-treated mice. Oral administration of JTT may induce the expression of IL-12 and be followed by immunological restoration such as NK T-cell induction in liver

Animals↗

[Imaging diagnosis of head and neck cancer--diagnosis of laryngeal cancer, hypopharyngeal cancer and cancer of the cervical esophagus by CT x-ray].

Fifty-six patients with laryngeal cancer were examined. The rate of correct diagnosis of clinical staging was 64.3%. Whereas the rate of correct diagnosis of staging by CT was markedly improved, 89.3%. In particular, CT facilitated correct diagnosis of T4. Supraglottic T3 cancer is diagnosed on the basis of deep infiltration or fixation of the hemi-larynx. Disappearance of the pre-epiglottic space or ulcer formation was recognized as a CT finding of deep infiltration. Disappearance of the paraglottic space and dislocation of the arytenoid cartilage were used as the standard for CT findings of laryngeal T3 cancer. CT allowed diagnosis to be made in 84.4% of cases which were pathologically determined to be T4. It can be said that CT is a very effective method for staging diagnosis in patients with laryngeal cancer. Fifty-seven patients with hypopharyngeal cancer and cancer of the cervical esophagus were also examined. When 40 post-surgical patients were compared according to pathological classification of T, the rate of correct diagnosis of clinical staging was 77.5% while that of staging diagnosis by CT was 82.5%. The rate of correct diagnosis by postoperative CT was 80.0% compared with the pathological determination of depth of invasion. The diagnosis of depth of invasion by CT on initial examination is thus an effective means for the determination of prognosis.

Adult↗

Simple laparoscopic ultrasound technique for prevention of bile duct injuries.

BACKGROUND: Bile duct injuries are serious complications of laparoscopic cholecystectomy. Laparoscopic ultrasonography (LUS) has been utilized over the last several years to screen for bile duct calculi and to delineate biliary anatomy. We have found a simple LUS scanning technique that can be useful for preventing bile duct injuries. METHOD: After initial scanning for screening, laparoscopic dissection is continued, isolating the cystic duct. If necessary, scanning can be performed to assure the location of the cystic duct before clipping. After clips are applied to the cystic duct, prior to its incision or transection, LUS is repeated to examine the cystic and bile ducts. RESULTS: This postclipping study can confirm that the clips are applied to the cystic duct and that the hepatic and common bile ducts are intact without occlusion. CONCLUSION: This additional LUS scanning maneuver is simple and quick and may help prevent bile duct injuries.

Bile Ducts↗

Determinants of myelosuppression in the treatment of non-small cell lung cancer with cisplatin-containing chemotherapy.

Data on 16 potential risk factors for myelosuppression were assessed in 134 patients who received either vindesine and cisplatin (VP) or mitomycin C, vindesine and cisplatin (MVP) for inoperable stage III or IV non-small cell lung cancer in a randomized trial. Determinant factors for myelosuppression were evaluated by using univariate analysis and the logistic regression model. Recursive partitioning and amalgamation (RPA) was also used to define patient subgroups frequently suffering from severe bone marrow toxicity. Overall, 33 (25%) of 134 patients experienced at least one episode of grade 4 leukopenia. In univariate analysis, age, body surface area, serum creatinine, and pretreatment hemoglobin concentration were associated with severe leukopenia. A multivariate analysis using the logistic regression method showed that only raised creatinine level was an independent predictor for grade 4 leukopenia (P = 0.049). The RPA model generated three distinct subgroups based on age, body surface area and regimen. The three subgroups were distinguished by the frequency of severe (grade 4) leukopenia (50%, 25%, and 2.4%, respectively) (P < 0.001). Grade 4 leukopenia occurred more frequently in patients in class 3 (age > or = 65 years and treatment with MVP). The RPA model was useful in identifying the risk factors for myelosuppression induced by cisplatin-based chemotherapy, and in defining patient subgroups with elevated risk of toxicity.

Adult↗

[Clinical usefulness of three-D cerebral mensional MR imaging in the diagnosis of medullary venous malformation].

Medullary venous malformation (MVM) is one of the most common vascular malformations encountered pathologically. In fact, it is generally discovered incidentally during the workup of other disorders. In 18 cases (19 lesions) of MVM, we evaluated retrospectively the diagnostic value of CT and MRI. We set four evaluations, excellent, good, fair and poor, to assess the diagnostic value of each imaging method. Contrast enhanced CT and pre-contrast MRI could detect the abnormality in 80% of the cases, but it was difficult to demonstrate the umbrella like medullary vein. Contrast enhanced MRI showed the umbrella sign in 60%. Images reformated with three-dimensional (3-D) MR imaging were better able to demonstrate this structure. Medullary vein collection, drainage into a single central vein and termination into a superficial cortical vein or a dural sinus were clearly demonstrated in all cases. Thus, all cases were diagnosed correctly as MVM. Contrast enhanced 3-D MR imaging was superior to other imaging techniques except angiography.

Adolescent↗

Assay methods for prekallikrein and kininogens and their applications.

Prekallikrein activity in plasma was assayed using a synthetic peptidyl fluorogenic substrate (carbobenzoxy-L-phenylalanyl-L-arginine 4-methylcoumarinyl-7-amide), after activation of prekallikrein by acetone and kaolin. For total kininogen assay, the pretreatment of plasma at pH 2.0 was the best to eliminate bradykinin potentiators and kininase activity, before addition of trypsin to convert kininogen to bradykinin. Assay method of high molecular weight (HMW) kininogen was established by conversion of HMW-kininogen to bradykinin through activation of Hageman factor by glass powder and that of low molecular weight (LMW) kininogen was also by treatment of HMW-kininogen-depleted plasma in the same way as that for total kininogen. The marked reduction of prekallikrein and HMW-kininogen, not of LMW-kininogen, was found in pleural fluid of rat carrageenin pleurisy, and in plasma after i.v. injection of bromelain in rats. Members of the pedigree of hereditary angioneurotic edema patients also show low levels of prekallikrein and kininogens in plasma.

Animals↗

In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin decreases serotonin-immunoreactive neurons in raphe nuclei of male mouse offspring.

Female ddY mice were administered 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by gavage for 8 weeks prior to pregnancy. In the male breast-fed offspring born to the TCDD-exposed mice, serotonergic neurons in the brainstem were examined using an immunocytochemical method at 42 days of age. In all offspring, a marked decrease in the intensity of immunostaining occurred in all raphe nuclei compared with the control offspring. The number of serotonin-immunoreactive neurons in each raphe nucleus was measured by computer-assisted analysis. Approximately a quarter to half of immunoreactive neurons were detected in the TCDD-exposed offspring raphe nuclei compared with the control offspring. The present findings suggest that in utero and/or lactational TCDD exposure cause a long-lasting change in the serotonergic system in the raphe nuclei of offspring.

Aggression↗

Extracting 1/f fluctuation from the arterial blood pressure of an artificial heart.

We have studied the fluctuations of an artificial circulation for the analysis of the physiological aspects; however, the conventionally used fast Fourier transform (FFT) method cannot separate harmonic oscillations, such as respiratory and Mayer waves, from the 1/f fluctuation, which has been though to represent underlying fractal dynamics. Fractal structure was shown in the strange attractor with chaotic dynamics, which is thought to be a flexible and intelligent system. In this study, the coarse-graining spectral analyzing (CGSA) method was utilized to quantitatively evaluate the proportion of the 1/f fluctuation in the total power in the frequency domain and to analyze artificial circulation in the whole system. We implanted two pneumatically actuated ventricular assist devices as biventricular bypasses (BVBs) in chronic animal experiments using 4 healthy adult goats. To compare the natural and prosthetic circulation of each experimental animal, the BVB-type complete prosthetic circulation model with electrically induced ventricular fibrillation was adopted. All hemodynamic parameters of natural and prosthetic circulation were recorded under awake conditions and calculated with the use of a personal computer. With the use of the CGSA method, time-series data of the hemodynamics were analyzed and fractal percentages, extracting the 1/f fluctuation from a given time series, were calculated. Fractal percentages of the arterial blood pressure were 85.8 +/- 10.7% and 82.0 +/- 7.3% with natural and artificial circulation, respectively (not significant [NS]). 1/f fluctuation showed the characteristics of being fractal in a time series. The fractal structure showed robustness and error resistance in nonlinear dynamics. Therefore, our results suggest that the circulatory regulatory system of the artificial heart may have desirable characteristics such as error resistance.

Animals↗

Proliferative capability of hepatocytes and expression of G1-related cell cycle molecules in the development of liver cirrhosis in rats.

Liver cirrhosis is the end stage of various chronic liver diseases and its prognosis is very poor. One of the most important causes of liver cirrhosis appears to be impaired proliferative capability of hepatocytes caused by continuous hepatic damage. Cell cycle-related molecules have been shown to play essential roles in cell proliferation. Specifically, G1-related cell cycle molecules are important, because they are requisite for the entry into the cell cycle from the quiescent state. However, the role of these cell cycle molecules during the development of liver cirrhosis remains to be examined. In the present study, liver cirrhosis was produced in rats by intraperitoneally administering dimethylnitrosamine (DMN). Proliferative capability of hepatocytes estimated immunohistochemically by proliferating cell nuclear antigen staining was markedly increased at an early stage of cirrhosis development. However, it was gradually decreased thereafter and suppressed substantially at the time of cirrhosis manifestation. Cyclin D1 expression estimated by a real-time reverse transcription-polymerase chain reaction (RT-PCR) method was also increased markedly at an early stage of cirrhosis development but decreased substantially thereafter. mRNA levels of catalytic subunits of cyclin D1, cyclin-dependent kinase 4 (Cdk4) and Cdk6, did not show significant changes during the development of liver cirrhosis. Among G1-specific Cdk inhibitors, expression of p15INK4b and p16INK4a estimated by an RT-PCR method was increased according to the progression of cirrhosis and reached a peak at the time of cirrhosis manifestation. Conversely, p18INK4c expression did not change significantly during the development of liver cirrhosis. These results suggest that cyclin D1 plays an essential role in hepatocyte proliferation in response to hepatic damage. However, with the decrease of cyclin D1 expression and increase of p15INK4b and p16INK4a expression, proliferative capability of hepatocytes is severely impaired and extracellular matrix components are deposited to retrieve space lost by the destruction of hepatic parenchyma, resulting in establishment of liver cirrhosis.

Animals↗

[In vitro antifungal activity of omoconazole nitrate, a new imidazole antimycotic].

In vitro antifungal activities of omoconazole nitrate (OMZ), a new topical imidazole antifungal agent, were studied against 364 strains of 22 genera and 47 species of stock cultures of a wide range of medically important fungi. The test was carried out using the agar dilution method with bifonazole (BFZ) as the reference drug. OMZ exhibited a broad spectrum of antifungal activities. Most of yeasts including Malassezia, dimorphic fungi, non-pigmented hyphomycetes and dermatophytes were almost equally or more greatly susceptible to OMZ than to BFZ, although the MIC values of these drugs against Candida and probably some other fungi were influenced differently by testing media. Comparable susceptibility to OMZ were observed for fresh clinical isolates of dermatophytes and Candida albicans. OMZ was also active against Malassezia. These results have encouraged us to proceed in vivo studies using animal models of cutaneous mycoses.

Antifungal Agents↗