Alterations of peak distribution of auditory ERPs during transient global amnesia: a case report.
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Publications and source records attributed to T Ishida.
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A toxic coplanar polychlorinated biphenyl, 3,3',4,4',5-pentachlorobiphenyl (PenCB), significantly suppresses the expression of liver aldolase B in rats. Hepatic aldolase activity in PenCB-treated rats was significantly reduced to about 50% of that in free- and pair-fed control groups. The reduced aldolase activity following PenCB-treatment was due to the marked suppression of the expression of aldolase B shown by immunoblot analysis after SDS-polyacrylamide gel electrophoresis and two-dimensional gel electrophoresis. The suppression of rat liver aldolase B could be a key biochemical lesion caused by PenCB.
We employed in situ hybridization of chromosome-specific DNA probes ("chromosome painting") of all human chromosomes to establish homologies between the human and the silvered lead monkey karyotypes (Presbytis cristata 2n = 44). The 24 human paints gave 30 signals on the haploid female chromosome set and 34 signals on the haploid male chromosome set. This difference is due to a reciprocal translocation between the Y and an autosome homologous to human chromosome 5. This Y/autosome reciprocal translocation which is unique among catarrhine primates has produced a X1X2Y1Y2/X1X1X2X2 sex-chromosome system. Although most human syntenic groups have been maintained in the silvered leaf monkey chromosomes homologous to human chromosomes 14 and 15, 21 and 22 have experienced Robertsonian fusions. Further, the multiple FISH signals provided by libraries to human chromosomes 1/9, 6/16 indicate that these chromosomes have been split be reciprocal translocations. G-binding analysis shows three different forms of chromosome 1 (X2) which differ by a complex series of inversions in the 10 individuals karyotype. Comparisons with the hybridization patterns in hylobatids (gibbons and siamang) demonstrate that resemblances in chromosomal morphology and banding previously taken to indicate a special phylogenetic relationship between gibbons and colobines are due to convergence.
BACKGROUND: Plasminogen activators (PAs) and their inhibitors are thought to play an important role in tumor invasion and metastasis. However, there have been few reports in which histologic localization of PAs has been demonstrated in head and neck tumors. METHODS: We examined the patterns of expression of urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), and vitronectin in head and neck squamous cell carcinomas using immunohistochemical techniques. We also studied the correlation between the immunohistologic expression of these fibrinolytic proteins and the clinical staging of the tumor. RESULTS: Of 28 tumor specimens, 15 (54%) showed immunoreactivity for u-PA; 8 (36%), for t-PA; and 23 ( 82%), for PAI-1. There was a significant correlation between PAI-1 expression and the extent of the primary tumor. CONCLUSIONS: The present study demonstrates the existence and possible pathophysiologic significance of u-PA and PAI-1 in squamous cell carcinomas of the head and neck.
BACKGROUND AND HYPOTHESIS: Intrinsic vasoactive substances, such as serotonin and acetylcholine, are known to provoke coronary artery spasm in patients with vasospastic angina. It remains unclear, however, whether these different agents, which activate different receptors, produce spasms at the same sites in these patients. The present study was designed to clarify the disparity of receptor agonist-induced coronary artery spasms in the same patients. METHODS: We conducted sequential provocative tests of coronary artery spasm by acetylcholine, serotonin, and ergonovine in 20 patients with rest angina examined with quantitative coronary angiography. RESULTS: Coronary artery spasms were provoked in all patients at 27 spastic sites. In 13 patients, ergonovine provoked spasms and in 10 of 13 patients who were diagnosed with variant angina, both acetylcholine and serotonin provoked spasms at the same sites where ergonovine also did. In 4 of 13 patients, spasms were provoked by serotonin but not by acetylcholine. In the remaining seven patients, whose spasms were induced by ergonovine, spasms were produced by acetylcholine but not by serotonin. On coronary angiography, the spastic sites for both acetylcholine and serotonin, and those for serotonin alone, were located in the proximal segments of coronary arteries, whereas the spastic sites for acetylcholine alone were located in the distal segments. CONCLUSIONS: This study documented the disparity between serotonin- and acetylcholine-induced spasms. Provocative tests using agents that activate different receptors may produce coronary artery spasms at the same and/or different sites, and this disparity may reflect the clinical heterogeneity of vasospastic ischemic syndrome.
Interleukin-12 is produced in response to infection with bacteria or parasites or to bacterial constituents such as LPS in monocytes/macrophages and dendritic cells, and also generated by the interaction between activated T cells and antigen-presenting cells via CD40-CD40 ligand (CD40L). So far, transcriptional analyses of p40 have been carried out only using bacterial constituents such as LPS as stimuli. In the present study, we have characterized the transcriptional induction of p40 by CD40 ligation in a human B lymphoblastoid cell line, Daudi, and a human acute monocytic leukemia cell line, THP-1. These cells, stimulated by an agonistic monoclonal antibody against CD40 or by transfection with a CD40L expression vector, secreted p40 and showed enhanced p40 mRNA expression. Sequence analysis of the p40 promoter region identified two potential nuclear factor (NF)-kappaB binding sites conserved between mouse and human. Electrophoretic mobility shift assay revealed that the potential NF-kappaB binding sequence which is located around 120 bp upstream of the transcription initiation site in murine and human p40 genes formed an NF-kappaB complex with nuclear extract from Daudi cells stimulated by CD40 ligation. Moreover, transfection of Daudi cells with the polymerized NF-kappaB binding sequence ligated to a thymidine kinase/chloramphenicol acetyltransferase (CAT) reporter plasmid greatly induced CAT activity, but transfection with the polymerized mutated NF-kappaB binding sequence did not. These results suggest that the NF-kappaB binding site located around 120 bp upstream of the transcription initiation site in murine and human p40 promoter regions could be important for the p40 induction by CD40 ligation via activation of NF-kappaB.
We present herein the case of a 74-year-old woman found to have a pleomorphic adenoma, or so-called mixed tumor, of the breast. The patient presented with a hard mass, 3 cm in diameter, located just beneath the left areola. Physical examination suggested a diagnosis of breast carcinoma; however, the findings of both ultrasonography and mammography indicated a benign neoplasm. Aspiration biopsy cytology was evaluated as class III and the diagnosis of pleomorphic adenoma was finally confirmed by examination of an excisional biopsy specimen. As it is a rare benign tumor, pleomorphic adenoma of the breast has been mistaken for a malignant tumor clinically, mammographically, cytologically, and even by frozen section. Thus, an awareness of this disease in the breast will help to prevent misdiagnosis and overaggressive surgery.
We devised an automated classification scheme by using the rule-based method plus artificial neural networks (ANN) for distinction between normal and abnormal lungs with interstitial disease in digital chest radiographs. Four measures used in the classification scheme are determined from the texture and geometric-pattern feature analyses. The rms variation and the first moment of the power spectrum of lung patterns are determined as measures for the texture analysis. In addition, the total area of nodular opacities and the total length of linear opacities are determined as measures for the geometric-pattern feature analysis. In our classification scheme with these measures, we identify obviously normal and abnormal cases first by the rule-based method and then ANN is applied for the remaining difficult cases. The rule-based plus ANN method provided a sensitivity of 0.926 at the specificity of 0.900, which was considerably improved compared to performance of either the rule-based method alone or ANNs alone.
The purpose of this study was to evaluate, using MRI, the morphology of normal anterior cruciate ligament (ACL) and ACL grafts when the knee was extended compared with when the knee was flexed. Eighteen normal controls and 22 ACL graft patients were studied. Spin-echo (SE) T1-weighted images (TR 330 ms/TE 15 ms, NEX 1) were obtained with a slice thickness of 3 mm. Oblique sagittal images parallel to the ACL were obtained at various flexed angles of the knee joint. In 12 of the 18 normal controls the ACL appeared convex toward the posterior side when the knee was extended and gradually became straight when the knee was flexed. In 15 of the 22 ACL graft patients the grafts appeared straight when the knee was extended and became convex toward the anterior side when the knee was flexed. It is concluded that the morphological changes seen on MR images of ACL grafts from when the knee is extended to when the knee is flexed are different from those in the normal ACL.
A 64-year-old man in a severely immunocompromised state due to acute myelogenous leukemia died, respirator-unaided, about 10 h after the abrupt onset of coma. An earlier blood culture had yielded Bacillus cereus. The autopsy, performed 2 h after death, demonstrated diffuse subarachnoid hemorrhage without berry aneurysms, and the formalin-fixed brain was tinged with gray-brownish discoloration. The sections of the brain presented a whitish tint of the surface layer of all portion of the cerebral cortices, even those in the sulci. Histological examination of the brain revealed leptomeningeal B. cereus dissemination, and widespread necrosis of the leptomeninges and arachnoid vessels without inflammatory cell reaction. The grossly recognizable whitish surface layer of the cerebral cortex showed overt hyperchromatism, and contained neurons more degenerative than those located in the deeper cortical layer. The total absence of inflammatory reaction may be explained by a combination of the immunocompromised state of the patient and the character of B. cereus infection, which in itself induces little inflammatory reaction. The prominent lesions were confined to the cerebral surface layer and leptomeningeal tissue including the arachnoid vessels, which were all bathed in the cerebrospinal fluid, suggesting that some necrotizing toxins had been secreted into the fluid by the B. cereus. The necrosis of arachnoid vessels is thought to have in turn caused diffuse subarachnoid hemorrhage and marked disturbance of the cerebral blood flow, resulting in the terminal coma.
The apical cytoplasm of several absorbing epithelia contains well-developed apical tubules (AT) which contribute to membrane recycling from endocytic vacuoles to the apical cell membrane. In this study, we examined three-dimensional structures of the AT in rat kidney proximal tubule cells by transmission and scanning electron microscopy. In thin sections, the AT appeared as straight tubules with a rather constant diameter (70-90 nm), but others were curved and, occasionally, branching. No AT were labeled with the marker for the external cell surface (ruthenium red) or exhibited histochemical enzyme activity for lysosomal hydrolase (acid phosphatase). After intravenous injection of horseradish peroxidase, it was absorbed in the kidney proximal tubule cells and the AT were labeled with HRP reaction products. Stereo-viewing of the labeled AT in thick sections revealed that they formed an interconnected tubular network. Scanning electron microscopy allowed a three-dimensional view of the AT, in which a network of branching and anastomosing tubules was revealed. These observations indicate that the AT are intracellular endosomal compartments which form an extensive tubular network in the apical cytoplasm. The possibility that this apical tubular network serves as a large membrane store for membrane recycling is discussed.
OBJECTIVE: This retrospective study was designed to detect occult micrometastases in the lymph nodes with the use of monoclonal anti-cytokeratin reagent, which is specific for epithelial cells but not for lymphocytes or plasmacytes, as well as to assess the relationship between the presence of occult micrometastases in the lymph nodes and an early relapse in patients with stage I non-small-cell lung cancer. METHODS: The paraffin-embedded sections of 973 regional lymph nodes from 44 patients with stage I non-small-cell lung cancer were studied. We used CAM-5.2 as the primary monoclonal anti-cytokeratin reagent and an indirect staining technique with the streptavidin-biotin-peroxidase complex method. RESULTS: We identified cytokeratin-positive cells in 31 (70.5%) of 44 patients and in 91 (9.4%) of the 973 lymph nodes. Of these 31 patients with cytokeratin-positive cells, 19 and 12 were restaged as having N1 and N2 disease, respectively. Thirteen patients had recurrent disease at 17 sites during the follow-up. Two of these recurrences were in the mediastinal nodes and the other 15 occurred at distant organs. Twelve of the 13 patients had micrometastatic disease in the regional lymph nodes. Disease-free survival duration was significantly shorter in the patients with micrometastases in the mediastinal lymph nodes than in patients with node-negative disease (p = 0.004). The independence of this prognostic significance was demonstrated by a multivariate analysis. CONCLUSION: These findings indicate that the detection of occult micrometastases in the mediastinal lymph nodes with monoclonal antibodies to cytokeratin can thus be used to predict an early relapse in patients with stage I non-small-cell lung cancer.
Numerical analysis of the vestibular nerve in Méniè's disease was performed. Vestibular nerve specimens were obtained from three patients with classical clinical findings of Ménière's disease during retrosigmoid vestibular neurectomy. For each patient, an ultrathin section, including an entire cross-section of the nerve specimen, was examined. Fiber counts of nerve specimens with definite pathologic findings were compared with caloric testing results. A significant correlation was found between reduced vestibular response and the incidence of abnormal nerve fibers and also the density of the abnormal nerve fibers. However, the number of nerve fibers with pathologic findings was small. Results of the present study demonstrate no general degeneration of nerve fibers caused by the disease process of Ménière's disease.
A set of the title compounds having different substituents (R1, R2) on their phenyl groups was synthesized to find sigma receptor binding affinity. Among the compounds, 2b (R1 = R2 = Cl) has the most potent sigma 1-binding activity, while 2a (R1 = R2 = H, SA4503) was most selective to sigma 1 over sigma 2 receptor. The crystal structures of 2a and 2b were shown, by X-ray crystallography, to be similar except for the one torsional angle of their propylene parts. Quantitative structure-activity relationship study suggested the affinity of the compounds to the sigma 1 receptor was dependent on the electronic feature, Swain-Lupton's R or Sz that was derived by molecular orbital method, of R1 and R2.
We examined 159 consecutive cases of non-small-cell lung cancer (NSCLC) for a mutation at codon 12 of the K-ras gene and for a mutation of the p53 gene occurring in exons 5-8. Eleven (6.9%) had mutations of the K-ras (ras+) and 57 (35.8%) had mutations of the p53 (p53+). There were 95 cases (59.7%) with ras- p53-, seven cases (4.4%) with ras+/p53-, 53 cases (33.3%) with ras-/p53+ and four cases (2.5%) with ras+/p53+. The ras+ group had a worse prognosis than the ras group in all cases and in 107 early-stage cases (stage I-II, P<0.05). The p53+ group had a worse prognosis in 107 early-stage cases (P<0.01), but there was no statistically significant difference when 52 advanced-stage cases (stage III-IV) or all patients were considered. Both ras and p53 mutations were unfavourable prognostic factors in 94 cases with adenocarcinoma, but there was no statistical significance in 57 cases with squamous cell carcinoma. According to Cox's model, the pathological stage, ras mutation and p53 mutation were found to be independent prognostic factors. Our results suggest that ras and p53 mutations were independent unfavourable prognostic markers especially in the early stage of NSCLC or in adenocarcinoma.
Drug resistance is one of the problems severely limiting chemotherapy in cancer patients. Thus, it is very important to develop new drugs that are effective against drug-resistant tumour cells. The novel anti-tumour agent NK109 has been developed from benzo[c]phenanthridine derivatives by Nippon Kayaku (Tokyo, Japan). We have confirmed that NK109 shows anti-tumour effects against a number of human tumour cell lines by inhibiting DNA topoisomerase II activity through the stabilization of the cleavable complex. Further, its efficacy against several drug-resistant tumour cell lines was also shown. NK109 showed potent anti-tumour activity against doxorubicin-resistant human tumour cell lines that have a typical multidrug resistance phenotype caused by P-glycoprotein. NK109 was not pumped extracellularly by P-glycoprotein and, consequently, NK109 accumulated in resistant cells. Cisplatin-resistant human tumour cell lines, which demonstrated decreased cisplatin accumulation, were sensitive to NK109. NK109 non-cross-resistance was confirmed using xenografts of tumour cells that were resistant to cisplatin in SCID mice. Furthermore, etoposide-resistant cells, with decreased topoisomerase II activity, were markedly sensitive to NK109 when compared with their parent cells, suggesting the possibility that the cytotoxic mechanism of NK109 differs from that of etoposide. In conclusion, NK109 is a very promising new anti-tumour drug for clinical use, because the efficacy of NK109 is not susceptible to several known molecular alterations that are associated with drug resistance. A clinical study of this compound is now in progress in Japan.
PURPOSE: We reviewed CT and MR findings in crush injuries in muscles and compared them with findings at muscle biopsy. MATERIAL AND METHODS: CT and MR examinations were made of the lower extremities in 6 adult patients whose muscles were crushed in the big earthquake in Kobe, Japan, on 17 January 1995. All CT examinations were performed twice and within 60 days of the earthquake. In 5 of the 6 patients, biopsies were taken of the injured muscle after the CT and MR examinations. RESULTS: At CT investigation, the images in 5 patients showed calcification in the muscles, and the crushed muscle appeared atrophic. In 3 of these 5, the degree of calcification decreased with time. At MR investigation, T1-weighted images of the crushed muscle showed isointensity in 4 of the 6 patients and high intensity in the remaining 2. T2-weighted images of the crushed muscle showed inhomogeneous high intensity in all patients. After Gd injection, all the crushed muscles were enhanced, either slightly or markedly. At muscle biopsy, in 5 of the 6 cases, the findings showed calcification in the muscle cells and the total destruction of the normal muscle structure. CONCLUSION: CT and MR findings in crush injury correlated well with the findings at histopathology.
The binding mode of CA074 [N-(L-3-trans-propylcarbamoyl-oxirane-2-carbonyl)-L-isoleucyl-L-pr oline], a specific irreversible inhibitor, to bovine spleen cathepsin B was elucidated by X-ray crystal structure analysis of the complex at 2.2 A resolution (conventional R=0.185). Inconsistently with our model used for the development of CA074, the L-isoleucyl-L-proline and propylcarbamoyl moieties are located at the S' and S subsites, respectively. This unexpected binding is primarily due to (i) similar extended chain conformations (due to the same S configurations) at the oxirane C2 and C3 atoms of CA074 and (ii) the just fit formation of double hydrogen bonds between the carboxyl oxygens of L-proline and the imidazole nitrogens of His-110 and His-111 residues (these residues are missing in papain, the tertiary structure of which was used for the design of CA074). The oxirane C3 atom possessing the P' substituent is covalently bound to the Cys-29 Sgamma atom (C3-Sgamma=1.79 A) and the S configuration is maintained. The present result will provide useful information for characterizing the substrate-specificity of cathepsin B.