Mechanism of action of Clostridium perfringens enterotoxin.
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Animals↗
Biomedical subjects
Y Horiguchi
Publications and source records attributed to Y Horiguchi.
Intraductal papillary adenocarcinoma with mucin hypersecretion and coexistent invasive ductal carcinoma of the pancreas with apparent topographic separation.
We report a 66-year-old man who had a cystic intraductal papillary adenocarcinoma containing a papillary adenoma, in the head of the pancreas and a coexistent invasive, well differentiated solid tubular adenocarcinoma in the tail of the pancreas. He was hospitalized with acute epigastralgia. Computed tomography demonstrated a multilocular cystic mass in the head of the pancreas and a solid tumor in the tail. Endoscopic retrograde pancreatography showed mucin secretion from an enlarged papilla of Vater, marked dilatation of the main pancreatic duct in the head and body, cystic dilatation of the uncinate branch, and irregular narrowing of the main pancreatic duct in the tail. Total pancreatectomy was performed. Between the cystic tumor and the solid tumor there was a distance of 4.8 cm of normal pancreatic parenchyma and duct, recognized both grossly and microscopically. The patient died 35 months after the operation. At autopsy, peritonitis carcinomatosa was found in the abdominal cavity. Microscopically, disseminated nodules were also well differentiated tubular adenocarcinoma. The apparent anatomic separation of these two tumors within the pancreas is extremely unusual.
Aged↗
Spontaneous autoimmune skin lesions of MRL/n mice: autoimmune disease-prone genetic background in relation to Fas-defect MRL/1pr mice.
The autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mouse is characterized by the lpr mutation, which is a defect in the Fas antigen. Since Fas mediates apoptosis, this defect results in CD4-CD8- double negative T-cell proliferation, lupus nephritis, and macroscopic lupus erythematosus-like skin lesions. The control counterpart of MRL/lpr mouse is the MRL/Mp-+/+ (MRL/n) mouse, which lacks the lpr mutation and is almost normal during the first 6 mo of life. The lpr mutation, however, accelerates autoimmune phenomena in MRL/lpr mice. Thus, it is important to investigate autoimmune diseases like systemic lupus erythematosis in relation to the autoimmune disease-prone genetic background of MRL/n mice. We found that skin lesions in aged MRL/n mice had unique characteristics. The first characteristic is spontaneous occurrence, and the second is epidermal cell nuclear immunostaining with IgGs by direct immunofluorescence. The skin lesions in aged MRL/n mice showed milder inflammation than in MRL/lpr mice. A homogeneous pattern of epidermal cell nuclear staining was always associated with nuclear staining in kidney cells and also correlated with the in vitro binding of sera to keratinocytes cultured from newborn MRL/n mice. These results suggest that the skin lesions of aged MRL/n mice are a good model for certain types of cutaneous lupus erythematosus and also can provide new insights into the long-standing controversy whether epidermal cell nuclear staining occurs in vivo.
Aging↗
Evaluation of sialyl Lewisx antigen in the skin and the sera of patients with psoriasis vulgaris.
The roles of sialyl-Lewisx antigen were evaluated in the pathogenesis of psoriasis. Sialyl-Lewisx expression was investigated immunohistochemically in the epidermis of normal human skin and erythematous lesional skin of psoriasis vulgaris by avidin-biotin-peroxidase complex procedures. A few sialyl-Lewisx positive dendritic cells were detected in the epidermis of normal human skin. In 7 out of 9 cases of psoriasis vulgaris, the number of sialyl-Lewisx-positive epidermal dendritic cells increased in the erythematous lesion over the adjacent normal skin; there were no marked changes in the numbers of CD1a-positive cells in the epidermis between the two skin types. In the double immunofluorescence studies, more than half of the sialyl-Lewisx-positive epidermal cells in psoriatic erythema were stained with a monoclonal Lag antibody that specifically reacts with Birbeck granules and related structures of human Langerhans cells. Furthermore, we determined the changes in serum levels of sialyl-Lewisx antigens in patients with psoriasis. Although levels in the sera were not significantly elevated over those of controls, the increases correlated with the degree of disease activity. These findings suggest that sialyl-Lewisx antigen is possibly involved in the development of psoriasis.
Biopsy, Needle↗
[Properties and action of Bordetella dermonecrotizing toxin].
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Acute-Phase Proteins↗
[Nodular-type carcinoma of extrahepatic bile ducts].
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Bile Duct Neoplasms↗
An acquired bullous dermatosis due to an autoimmune reaction against uncein.
A 59-year-old male showed acquired, mechanically induced, scarring blisters on the fingers, toes, scalp and abdomen, as well as in the oral cavity. Ultrastructural and immunohistochemical examination of the bullae revealed junctional epidermal-dermal separation and IgG deposits in the lamina lucida of the basement membrane zone (BMZ), where the reactivity of the 19-DEJ-1 monoclonal antibody was decreased. Anti-BMZ autoantibodies detected in his serum were reactive to the lower lamina lucida region of normal human skin. SDS-PAGE of affinity purified antigens from human keratinocytes with IgG from the patient's serum revealed three polypeptide bands at 165, 135 and 100 kDa, in reduced condition. The indirect immunofluorescence test of his serum was negative on skin cryosections from patients with lethal junctional epidermolysis bullosa. Pretreatment of normal human skin sections with the patient's serum, blocked the binding of 19-DEJ-1 monoclonal antibody but not that of the GB3 monoclonal antibody. This case is considered to be an acquired autoimmune bullous dermatosis due to an autoantibody reaction against uncein (19-DEJ-1 antigen), a component of anchoring filaments.
Antigens↗
Obstruction of the proximal pulmonary artery branches after banding of the pulmonary trunk.
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Arterial Occlusive Diseases↗
The enterotoxin of Clostridium perfringens type A binds to the presynaptic nerve endings in neuromuscular junctions of mouse phrenic nerve-diaphragm.
The enterotoxin of Clostridium perfringens type A, a channel-pore forming protein toxin, inhibited neuromuscular transmission in isolated mouse phrenic nerve-diaphragm preparation at low concentrations of calcium. We investigated immunohistochemically the localization of the binding sites of the enterotoxin in the preparation under the conditions in which the enterotoxin reduced maximally the amplitudes of the twitch tension elicited by electrical stimulations to the phrenic nerve. Under the conditions, double immunohistochemical staining of the preparation with (1) rabbit anti-enterotoxin IgG-rhodamine-labeled goat anti-rabbit IgG and (2) mouse anti-synaptophysin (one of the synaptic vesicle-specific membrane proteins)-fluorescein isothiocyanate (FITC)-labeled goat anti-mouse IgG showed that the enterotoxin binds specifically to most of the sites which were stained with anti-synaptophysin exactly in the same configurations having the shapes of the nerve endings in the endplates. The thin section electron micrographs of the enterotoxin-intoxicated preparation showed no alterations in the ultrastructure of the neuromuscular junction and the nerve endings filled with numerous synaptic vesicles. The present results, together with our previous electrophysiological findings, indicate that the enterotoxin binds specifically to the presynaptic nerve endings and inhibits neurotransmitter release at the neuromuscular junction.
Animals↗
Coronary vasoconstriction is the most probable cause of death of rats intoxicated with botulinolysin, a hemolysin produced by Clostridium botulinum.
The pathophysiology of lethal intoxication by botulinolysin (Blyn) was studied using anesthetized rats and isolated rat organs. Intravenous injection of 10,000 and 1000 hemolytic units (HU) of Blyn killed rats rapidly while 100 HU of the toxin did not. Congestion and edema of lungs were observed at autopsies of the rats killed by intoxication. Hemoglobinemia was obvious in rats injected with 1000 HU of Blyn but not in rats with 10,000 HU. Electrocardiograms of the intoxicated rats showed depression of T waves but not changes characteristic of hyperpotassemia. All the rats injected with the above doses of Blyn showed a rapid fall in arterial blood pressure (BP) immediately after the toxin injection, and BP soon recovered in rats injected with 100 HU, partially and transiently in rats with 1000 HU, and not in rats with 10,000 HU of Blyn. Perfusion of Blyn (1 HU/ml) to isolated rat hearts caused a rapid and marked increase in perfusion pressure and cessation of spontaneous heart beat. Acetylsalicylic acid (10(-3) M) and quinacrine dihydrochloride (10(-5) M) did not essentially influence the effects of Blyn on the isolated hearts, but verapamil (10(-6) M) inhibited at least the initial increase in perfusion pressure elicited by Blyn. Spontaneous contractions of the isolated atria were little influenced by Blyn (60 HU/ml). Perfusion pressures of isolated kidneys, lungs and livers were also increased by Blyn (1 HU/ml). The results indicate that Blyn caused vasoconstriction but had little direct effect on myocardium. Based on the above findings, we conclude that coronary vasoconstriction elicited by direct action of Blyn causes acute cardiac dysfunction leading to systemic hypotension and death of the intoxicated animals.
Animals↗
A case of autoimmune bullous dermatosis with features of pemphigus vulgaris and bullous pemphigoid.
Pleomorphic blisters, including tense bullae and annularly arranged vesicles around the erythema as well as erosive eruptions in the oral cavity, appeared on a 61-year-old woman 5 years after surgery for cholangiocellular carcinoma. A biopsy specimen from the oral cavity showed intraepidermal blisters, and those from skin lesions showed subepidermal blisters with infiltrates of eosinophils and neutrophils. The early-stage vesicles showed infiltrates along the epidermal-dermal junction, where electron microscopy disclosed disruption of the lamina densa, basal cells remaining on the dermis, and acantholytic keratinocytes among the infiltrates, but there was no cleavage of the epidermal-dermal junction at the lamina lucida. Direct immunofluorescence studies showed immune deposition at the intercellular space (ICS) and along the basement membrane zone (BMZ). Indirect immunofluorescence studies confirmed coexistence of IgG class anti-ICS and anti-BMZ antibodies. Although this case showed immunohistochemical features of bullous pemphigoid, the presence of suprabasal cleavage in the oral mucosa, acantholytic cells in the blister cavity, the deposition of IgG at the ICS of the perilesional epidermis, and circulating anti-ICS antibodies strongly suggested that this case was primarily pemphigus. The strong inflammation along the epidermal-dermal junction due to unknown factors may have modified the clinical appearance and the histopathology.
Autoantibodies↗
Nitric oxide synthase inhibition is detrimental to cardiac function and promotes bronchospasm in anaphylaxis in rabbits.
We studied the effects of a nitric oxide synthase (NOS) inhibitor, N omega-nitro-L-arginine-methyl ester (L-NAME), on cardiac depression and bronchospasm provoked by systemic anaphylaxis in vivo in rabbits. Animals pretreated with L-NAME showed lower survival rates than control animals pretreated with normal saline. The survival rate in L-NAME-pretreated animals was increased by the administration of L-arginine after initiation of anaphylaxis. Cardiac output fell significantly in animals pretreated with L-NAME compared with controls, although venous return was increased. In animals pretreated with L-NAME, pulmonary resistance was significantly increased, and administration of arginine attenuated the bronchospasm. In conclusion, these results, along with the low survival rates in the L-NAME-treated animals, suggest that NO production may be beneficial to cardiac depression and bronchospasm in anaphylaxis in vivo.
Analysis of Variance↗
Establishment of a human cell line secreting neuron-specific enolase from a primitive neuroectodermal tumor of the retroperitoneal cavity.
Primitive neuroectodermal tumor (PNET) is one of the small round cell malignancies of presumed neural crest origin for which an effective treatment has not yet been established. In the present study, a human cell line, designated KU-9, was established from a 27-year-old male patient with PNET of the retroperitoneal cavity and has been successfully maintained in nude mice and in culture. On histological examination, the primary tumor was composed of poorly differentiated small round cells arranged in clusters showing a variety of mitotic changes, and contained Homer-Wright rosettes. The histopathological appearance of the KU-9 xenografts was similar to that of the primary tumor. Electron microscopy revealed neurosecretory granules and cytoplasmic processes in the xenograft. No significant amplification of N-myc gene was observed in the KU-9 cells. The KU-9 cells showed chromosome numbers ranging from 56 to 61 with consistent structural abnormalities being add(2)(q31), +add(11)(p11.2), +add(13)(p11.1), and +del(22)(q12). Cultured KU-9 cells grew exponentially with a doubling time of about 50 h and a time-dependent increase in medium levels of neuron-specific enolase (NSE) was noted. Serum levels of NSE in KU-9 tumor-bearing nude mice were significantly elevated and a linear relationship between the serum NSE levels and the tumor NSE content or tumor volume was observed, suggesting that serum levels of NSE may reflect the PNET tumor burden and tumor extent. These results indicate that the KU-9 cell line provides a reproducible model system which could be useful in gaining some insight into the histogenesis and oncogenesis of PNET and in establishing an effective treatment for PNET.
Adult↗
Evaluation of left ventricular diastolic function in IgE-mediated anaphylaxis in dogs.
Depressed left ventricular (LV) systolic function remains controversial in patients with anaphylaxis and anaphylactic animal models. However, LV diastolic function has not yet been investigated in either patients or animal models. Therefore, we assessed LV diastolic and systolic function in IgE-mediated anaphylaxis in dogs. Seven dogs sensitized to Ascaris suum antigen were studied. An aqueous extract of Ascaris suum antigen was administered over 30 s into the systemic circulation to induce anaphylaxis. To assess LV function, the time constant of the fall of isovolumic LV pressure (T), as an index of LV diastolic function, and the maximum rate of rise of LV pressure (dP/dtmax), as an index of LV systolic function, were measured for a period of 120 min after antigen challenge. T was prolonged during the period of 5 to 15 min; however, changes in T were not significantly different from prechallenge values. LV d}/dtmax significantly decreased to 0.49 +/- 0.12 times the prechallenge value 5 min after antigen challenge, and significantly increased during the period from 30 to 120 min. However, these changes in dP/dtmax almost paralleled the changes in LV end-diastolic pressure, indicating that left ventricular systolic function was relatively well preserved. In conclusion, LV diastolic function, i.e., isovolumic relaxation, is little impaired in anaphylaxis, and LV systolic function is relatively well preserved during the early stage following the onset of anaphylaxis.
Anaphylaxis↗
Effects of Bordetella bronchiseptica dermonecrotizing toxin on bone formation in calvaria of neonatal rats.
The effects of Bordetella bronchiseptica dermonecrotizing toxin on bone formation were investigated using a purified toxin preparation. Single injection of 4.3 ng of the toxin into the subcutaneous tissue overlying the calvariae of neonatal rats necrotized periosteum of parietal bone and degenerated osteoblasts within two days. Nine days after the injection, the lesion of the bone tissue became severe; the bone matrix became thin and fragmented. These observations indicate that dermonecrotizing toxin without other factors produced by the organisms impairs bone formation.
Animals↗
Hemodynamic adaptations at birth and neonates delivered vaginally and by Cesarean section.
In order to assess the possible influence of differences in delivery mode on cardiovascular adaptation at birth, we measured left ventricular output and its regional distribution in the major organs sequentially using an echographic technique during the first 96 h of life. We studied 27 normal newborns, of whom 15 were delivered vaginally and 12 by cesarean section. We also measured umbilical arterial and venous catecholamine concentrations. The umbilical arterial epinephrine and norepinephrine concentrations in the infants delivered vaginally were significantly greater than those in the infants delivered by cesarean section (epinephrine 1,195 +/- 208 vs. 565 +/- 81 pg/ml, p < 0.05; norepinephrine 11,832 +/- 3,819 vs. 5,153 +/- 1,400 pg/ml, p < 0.05). The left ventricular output and its regional distribution showed a similar pattern in the two groups, and there were no significant differences between them. These results indicate that the capacity of infants delivered by cesarean section to tolerate cardiovascular changes during the early neonatal period is comparable to that in infants delivered vaginally, even though there are significant differences in the catecholamine surge between these groups.
Adaptation, Physiological↗
Common mutations in the low-density-lipoprotein-receptor gene causing familial hypercholesterolemia in the Japanese population.
Familial hypercholesterolemia (FH) is a common genetic disorder caused by mutations of the LDL-receptor gene. In the present study, we investigated four Japanese FH homozygotes and identified five point mutations: a splice site mutation in intron 12 (the 1845 + 2 T-->C mutation), a missense mutation in exon 7 (the C317S mutation), a nonsense mutation in exon 17 (the K790X mutation), a missense mutation in exon 14 (the P664L mutation), and a missense mutation in exon 4 (the E119K mutation). We developed simple methods for detecting these mutations. When we examined the presence of these mutations in 24 unrelated FH homozygotes, the 1845 + 2 T-->C mutation was found in 7 of them, and the other four mutations were unique for each proband. We also screened 120 unrelated FH heterozygotes for these mutations and found that the frequencies of the 1845 + 2 T-->C, C317S, K790X, P664L, and E119K mutations were 13.3% (16/120), 6.7% (8/120), 6.7% (8/120), 3.3% (4/120), and 1.7% (2/120), respectively. These mutations were found in more than 30% of unrelated Japanese FH patients. By using the detection methods developed in this study, the diagnosis of more than 30% of the genetic bases of Japanese FH heterozygotes is expected.
Adult↗
Bordetella bronchiseptica dermonecrotizing toxin stimulates assembly of actin stress fibers and focal adhesions by modifying the small GTP-binding protein rho.
We studied the biochemical mechanism of morphological changes in cells treated with Bordetella dermonecrotizing toxin (DNT). DNT caused the morphological changes of serum-starved MC3T3-E1 cells from flat shapes to reflactile ones. These changes were accompanied by the assembly of actin stress fibers and focal adhesions, which is known to be regulated by the small GTP-binding protein rho. Clostridium botulinum C3 exoenzyme, which ADP-ribosylates and inactivates rho protein, 'rounded' the cells within 2 hours after addition to the extracellular fluid and their rounded shapes were maintained for at least 10 hours. However, when the cells were co-treated with C3 exoenzyme and DNT, they were rounded at 2 hours but recovered an apparently intact morphology after 3-8 hours of incubation. rho proteins in lysates from DNT-treated cells and untreated cells were radiolabeled by [32P]ADP-ribosylation with C3 exoenzyme and analyzed by SDS-polyacrylamide gel electrophoresis. Whereas the lysate from untreated cells showed a single band of [32P]ADP-ribosylated rho protein, the lysate from DNT-treated cells showed an additional two bands as well as the band identical to that of the lysate from untreated cells. Recombinant rhoA protein treated with DNT in vitro also showed a mobility shift in SDS-polyacrylamide gel electrophoresis. These results indicate that DNT causes the assembly of actin stress fibers and focal adhesions by directly modifying rho protein.
ADP Ribose Transferases↗