[Case of allergic granulomatous angiitis with kidney dysfunctions and heart failure].
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Biomedical subjects
Publications and source records attributed to S Hirano.
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Epithelial cadherin (E-cadherin) is a Ca(2+)-dependent cell-cell adhesion molecule that connects cells via homotypic interactions. Its function is critical in the induction and maintenance of cell polarity and differentiation, and its loss of downregulation is associated with an invasive and poorly differentiated phenotype in colon and other tumors. We have used an avidin-biotin immunoperoxidase technique to localize E-cadherin in microwave-treated, paraffin-embedded sections from 36 patients with pancreatic adenocarcinomas. E-cadherin was expressed by normal ductal and acinar cells with typical membranous staining at the intercellular junctions. Loss of normal surface E-cadherin expression was found in 19/36 (53 per cent) tumours compared to the adjacent normal ductal cells. Abnormal E-cadherin expression was found more frequently in poorly differentiated (grade III) (6/7, 86 per cent) than in well-differentiated tumors (grade I) (4/14, 28 per cent) (P = 0.012). Membranous E-cadherin expression was also lost more frequently in primary tumours with lymph node (stage III) (14/23, 61 per cent) and distant metastasis (stage IV) (2/2, 100 per cent) compared with 3/11 (27 per cent) lymph node-negative tumours (stage I) (P = 0.043). In conclusions, our data indicate that loss of membranous E-cadherin expression is associated with high grade and advanced stage in pancreatic cancer.
In preterm neonates, the risk for intracerebral haemorrhage is linked to immaturity of cerebral autoregulation. The preterm's 2-5/min cyclic variation pattern of cerebral blood flow velocity is thought to reflect the degree of immaturity of autoregulation--a speculation to be tested. In a cross-sectional study 15 infants (gestational age 26-40 weeks, postconceptional age (PCA) 26-42 weeks, age 1-99 days were investigated. We performed a 10 min pulsed Doppler tracing on an internal carotid artery by means of a computer controlled 5 MHz Duplex device. Systolic velocity (Vs) was recorded pulse by pulse. After appropriate data transformation, in all infants the Fast Fourier Transform of the time course of Vs revealed the presence of a 2-5/min cyclic variation pattern (one sample z-test, P < 0.0001). There was no significant correlation between proportionate spectral power of the 2-5/min frequency band and either PCA (r = 0.23, P = 0.42) or age (r = 0.41, P = 0.13). Between 26 and 42 weeks PCA, the cycling phenomenon is constant thus not reflecting cerebral maturation, and its presence does not mean immaturity of cerebral autoregulation.
In a preceding study, we reported that the numbers of macrophages and polymorphonuclear leukocytes (PMN) were increased in bronchoalveolar lavage fluid (BALF) following the intratracheal instillation of nickel sulfate (NiSO4) in rats. In the present study, BALF chemotactic activities for both macrophages and PMN were measured to investigate if the increases of these inflammatory cells in BALF depend on increases in chemotactic activities in epithelial lining fluid (ELF) of the lung. Both the number of PMN and the PMN chemotactic activity peaked at 2 days post-instillation and they were significantly correlated. However, the PMN chemotactic activity was inversely correlated with concentration of leukotriene B4 (LTB4), a well-known chemotaxin. Although PMN were not observed in control BALF, LTB4 concentration in the control ELF (ca. 5 x 10(-7) M) was estimated to have a potential to attract PMN chemotactically through a membrane in in vitro migration assay. These results suggest that the presence of LTB4 in ELF itself does not trigger transpulmonary PMN infiltration. The rat BALF were fractionated by high performance liquid chromatography (HPLC), and PMN chemotactic activity of each fraction was measured. The elution profiles of PMN chemotactic activity showed that there were at least two different chemotaxins in BALF obtained from the NiSO4-exposed rats. Macrophage chemotactic activity in BALF also peaked at 2 days post-instillation. However, the number of macrophages was not significantly correlated with the chemotactic activity for macrophage in BALF.(ABSTRACT TRUNCATED AT 250 WORDS)
Rats were exposed to nickel sulfate (NiSO4) either by intratracheal (IT) instillation or by acute aerosol inhalation, and pulmonary clearance of Ni and pulmonary inflammatory responses were studied. The half-time of Ni in the lung (initial lung burden = 50 micrograms Ni/rat) was about 32 h in both the IT instillation and inhalation groups. Ni retention in the lung tissue following IT instillation of NiSO4 was saturable with reference to dose, suggesting that clearance rate of Ni from the rat lung depends on lung burden of Ni. Lung inflammatory responses were evaluated by biochemical, elemental and cytological indicators in bronchoalveolar lavage fluid (BALF) following IT instillation of NiSO4. Activities of lactate dehydrogenase and beta-glucuronidase, contents of lysozyme, protein, sulfur and calcium, and the number of polymorphonuclear leukocytes were increased with a peak at 2-3 days post-instillation, while BALF alkaline phosphatase (ALP) activity was significantly decreased after IT instillation of NiSO4. Lung tissue ALP activity was also decreased by NiSO4. Because Ni does not inhibit ALP directly, the decrease in ALP activity is probably due to functional changes of type II cells (a major source of BALF ALP). Thiobarbituric acid reacting substances in the lung tissue were not changed by NiSO4, suggesting that lipid peroxidation plays a minimal, if any role, in the Ni-induced inflammation in the rat lung.
The timing of the appearance of leptomeningeal glioneuronal heterotopia (LGH) and its immunohistochemical development were examined on autopsied brains ranging from 12 to 43 weeks of postmenstrual age. LGH appeared at 20 weeks postmenstrual age and its incidence gradually increased until 28-31 weeks. All patients with trisomy 13 who were older than 34 weeks postmenstrual age had LGH. Glial fibrillary acidic protein-positive glial processes appeared earlier in the subpial layer of brainstems in patients with trisomy 13 than in the controls without LGH, and protruded along the perforating vessels into the leptomeninges; therefore, LGH may be formed from the midfetal period and develop with an increase of subpial glial processes along perforating vessels.
Two types of a shape memory alloy (SMA) catheter system with a mechanism for tip control and irrigation were evaluated in performing peroral pancreatoscopy (PPS) using an ultrathin-caliber endoscope. The selective cannulation of SMA catheters into the papilla was made possible in 18 of 19 patients with pancreatic diseases. Endoscopic sphincterotomy was necessary in six of seven patients with the two-directional catheter (2.6 mm) but in only one of 12 patients examined with the one-directional type (2.2 mm). In 17 of the 18 patients, the catheters were smoothly advanced to the desired positions in the main pancreatic duct, even to the distal pancreas, due to their controllable tip. PPS with adequate inspection of the ducts and lesions was successful in 16 of these 17 patients. Features of cancer (duct disruption, tumor infiltration) and chronic pancreatitis (smooth ductal surface, fine vascular network) could be distinguished. In this series, there were no obvious complications during or after the procedure. In our experience, the SMA catheter system is effective for PPS in patients with an intact papilla and without dilation of the main pancreatic duct. Further study will show the clinical benefits this technique may have in pancreatic diseases.
A 62-year-old man with a mucinous carcinoma of the skin on the left cheek is described. The excised specimen showed a characteristic histopathologic picture. The findings from histochemical, immuno-histochemical, and electron microscopic examinations suggested an eccrine differentiation of the tumor cells. The removed tumor was examined using DNA cytofluorometry in order to analyze the cell kinetics and to estimate its biological behavior and prognosis. The tumor cells showed a diploid mode with a small number of polyploid cells. Only a small number of cells in the S and G2/M phase ranges were detected. After four years, there has been no evidence of tumor recurrence nor metastasis. The results of DNA ploidy analysis were thus compatible with the nature of slow growth with a good prognosis in this case.
E-cadherin is transiently expressed in local regions of the embryonic mouse brain, which include several patchy areas on the mesencephalon and diencephalon and their roof plate and part of cerebellar rudiments. In the present study, we compared this E-cadherin expression with that of Wnt-1, which occurs in specific zones in the embryonic brain, and found certain spatiotemporal relations between them: Wnt-1 expression tended to run parallel or overlap with peripheries of the E-cadherin-positive areas. For example, in the dorsal midline, Wnt-1 was expressed at the middle of the roof plate, while E-cadherin was absent in the middle zone but detected in two arrays of marginal roof plate cells. Furthermore, alpha N-catenin, a cadherin-associated protein, was found to occur at the roof plate of the mesencephalon and diencephalon, coinciding with Wnt-1 expression. The expression of these molecules was then studied in two alleles of the Wnt-1 mutation, Wnt-1sw and Wnt-1neo. In mice homozygous for these mutant genes, E-cadherin expression in the roof plate was up-regulated; the middle E-cadherin-negative zone disappeared. Moreover, E-cadherin expression in the roof plate began earlier in the mutant mice than in wild-type mice. On the contrary, alpha N-catenin expression in the dorsal midline was suppressed in these mutants. These changes in cadherin and catenin expression occurred at the level of mRNA expression. These results suggest that the Wnt-1 signal is, either directly or indirectly, involved in the regulation of expression of E-cadherin and alpha N-catenin in restricted regions of the embryonic brain. This mechanism may contribute to the patterning of the expression of these adhesion-related proteins in the embryonic brain.
The compressive creep and the recovery of commercially available composites, 2 kinds for posterior and 2 kinds for anterior use, in water were examined. In posterior composites, creep strain after 500h at a stress level of 8.3 kgf/mm2 was significantly small (within 1%). The results of the compressive creep test showed that posterior composites would be resistant to occlusal stress. Creep strain was higher in anterior composites than that in posterior composites because of their lower inorganic filler content. The rate of recovery of composites was rapid immediately after the creep test. The water sorption of composites after 500h test was almost constant at some reduced stress levels, especially in posterior composites.
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Graft-versus-host disease (GVHD) is one of the major complications which should be resolved to improve the survival rates in allogeneic bone marrow transplantation (BMT). Recently, several cytokines have been identified, suggesting that they form a cytokine network and play an important role in immune system and hematopoiesis. Among several cytokines, it has been reported that tumor necrosis factor alpha (TNF alpha) and interleukin-6 (IL-6) are mainly involved in GVHD. In the present report, we analyzed the role of cytokines in GVHD. When we measured serum cytokine levels, IL-6, interferon gamma (IFN gamma), and TNF alpha levels were increased prior to the onset of acute GVHD. For chronic GVHD, a similar pattern of cytokine increment was observed. Interestingly, these cytokines appeared to interact synergistically to induce clinical GVHD, suggesting that none of those cytokines does not function solely. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed that increased IL-1 beta mRNA expression was also observed in acute GVHD in addition to increased IL-6 and TNF alpha mRNA expressions. Unexpectedly, no increased IL-2 levels were observed in both assays. In hyperacute GVHD, only IL-6 level was increased. However, in vivo administration of IL-6 into allogeneic bone marrow chimeras did not induce severe GVHD. Therefore, some other factors also appeared to be involved in inducing hyperacute GVHD. Furthermore, it is important to consider the role of inhibitory cytokines such as transforming growth factor beta (TGF beta) or IL-10.
The anti-arthritic effects of cytogenin (8-hydroxy-3-hydroxymethyl-6- methoxyisocoumarin) on type II collagen-induced arthritis in DBA/1J mice and adjuvant arthritis in Lewis rats were examined. Prophylactic treatment with cytogenin (30, 100 mg/kg) had a potent inhibitory effect on type II collagen-induced arthritis. Prophylactic or therapeutic treatment with cytogenin (10, 30 and 100 mg/kg) also had a potent inhibitory effect on adjuvant arthritis. In contrast to nonsteroidal anti-inflammatory drugs (NSAIDs), cytogenin (10, 30 and 100 mg/kg) had neither an anti-inflammatory effect on carrageenan-induced paw oedema in rats nor an analgesic effect on acetic acid-induced writhing in mice. These results suggest that the mode of the anti-arthritic action of cytogenin is different from that of NSAIDs and that cytogenin may become a useful drug for the treatment of rheumatoid arthritis.
The authors have examined the cardiotoxic actions of pirarubicin (THP), compared with epirubicin (EPI) and doxorubicin (DXR), on the electrocardiogram (ECG) and myocardial structure in rats. The rats were treated once a week for four weeks with DXR (total dose 10 mg/kg), and then further treated (post-treated) once a week for four weeks with THP, EPI or DXR (total dose 5 and 10 mg/kg). In the ECG study, a prolongation of QaT interval (interval from the upstroke of R wave to the apex of T wave) and a flattening of T wave were observed more severely in the rats post-treated with EPI and DXR than in those treated with THP. Also, a prolongation of QRS duration was observed more prominently in those treated with DXR than with THP and EPI. Histopathologically, a vacuolization and swelling of myocardial cells and an infiltration of mononuclear cells were observed more severely in the rats post-treated with EPI and DXR than in those treated with THP. Furthermore, a meandering of myofibril was observed in those treated with EPI and DXR, but not with THP. These results suggest that the cardiotoxic actions of THP are weaker than those of EPI and DXR and that the replacement of DXR with THP leads to more successful cancer chemotherapy with less cardiotoxicity.
We have examined the therapeutic effects of combination therapy of pirarubicin ((2"R)-4'-O-tetrahydropyranyladriamycin, THP) with various antitumor agents against P388 murine leukemia. THP showed a high antitumor activity in combination with various antitumor drugs, especially with cyclophosphamide (CPM), cisplatin (CDDP), mitomycin C (MMC), enocitabine (BHAC), vindesine (VDS) or methotrexate (MTX). The effects of combination therapy depended on the order of administration of THP and combined drugs. THP-preceding treatment gave more synergistic effects in combination with 5-fluorouracil (5-FU) or MTX. THP-preceding or simultaneous treatment with etoposide (ETP) indicated the higher synergistic activity than ETP-preceding one. Moreover, THP showed much higher synergistic effects in any order of the combination with CPM, CDDP, MMC, BHAC, VDS or MTX. These results suggest that THP possesses a therapeutic usefulness clinically in combination with various antitumor drugs, if the selection of drugs combined with THP and the order of administration are suitable.
Between January, 1980 and December, 1992, 256 patients underwent resection of pancreatobiliary carcinoma. Sixty eight of these patients were more than 70 years old and are the subject of this review. The morbidity rate for pancreatic cancer patients undergoing pancreaticoduodenectomy was 50%. The five years survival rate was 15%. The morbidity rate for biliary cancer patients undergoing major resection was 40%. The five year survival rate was 40%. The data presented demonstrate that extended operation for pancreatic cancer should not be performed in the elderly patients but major resection for biliary cancer can be performed, even in elderly patients, with a low but somewhat increased mortality risk. Methods of estimating risk factor for elderly patients are required.
Mismatch negativity (MMN) of the event related potential (ERP) is generated when patients can discriminate two different kinds of stimuli even if he or she is not conscious of their differences. The authors examined auditory ERPs of passive paradigm in 16 patients with severe multiple handicaps. All patients showed no or scarce clinical response to human voices or environmental sounds. This study investigated whether they showed MMN, since it is hard to evaluate their auditory perception clinically. Auditory stimuli were the tone bursts of 700 and 1,000 Hz in frequency offered at a 4:1 occurrence. Nine of 16 patients showed a definite N2 wave followed by an N 1 wave. The latency of the N 2 wave ranged from 150 to 596 milliseconds after the onset of the target stimuli. This N 2 was considered compatible with mismatch negativity (MMN) in healthy patients. These results suggest that the patients could discriminate subtle difference in two kinds of tones, although their responses to auditory stimuli were very poor.
In patients with acute graft-versus-host disease (GVHD), IL-6 gradually increased > 14 days before clinical onset of acute GVHD and decreased when acute GVHD disappeared. Interferon-gamma (IFN gamma) levels increased < 14 days before clinical acute GVHD and decreased at the disappearance of acute GVHD. Tumor necrosis factor-alpha (TNF alpha) levels increased almost simultaneously with the onset of acute GVHD and also decreased when it disappeared. However, these results do not necessarily mean that the increased levels of IL-6, IFN gamma and TNF alpha induced acute GVHD; they merely show that acute GVHD is observed more frequently in patients with increased IL-6, IFN gamma and TNF alpha levels than in those with normal levels. Although increased IL-6 levels were also observed in patients without acute GVHD, concomitant increase of IFN gamma and TNF alpha was not detected in such cases, showing that IL-6 can be increased by even graft-versus-host reaction (GVHR) which may not develop into clinical acute GVHD. Taken together, acute GVHD appeared to be induced by synergistic interaction of IL-6, IFN gamma and TNF alpha, consistent with a cytokine cascade. A similar interaction of IL-6 and TNF alpha was also observed in chronic GVHD. Although IFN gamma levels were slightly increased in chronic GVHD and sometimes aggravated the disease status, IL-6 and TNF alpha appeared to be more closely involved in the induction of chronic GVHD. In autologous BMT, increased cytokine levels were not observed unless IL-2 was administered.(ABSTRACT TRUNCATED AT 250 WORDS)