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Biomedical subjects

Y Fukuda

Publications and source records attributed to Y Fukuda.

At least 919 records · Page 51Linked to original sources

Immunohistochemical detection of alpha-fetoprotein, carcinoembryonic antigen, and ferritin in formalin-paraffin sections from hepatocellular carcinoma.

Paraffin sections of livers from 20 patients with hepatocellular carcinoma were examined by a method using peroxidase antiperoxidase for the detection of alpha-fetoprotein, carcinoembryonic antigen, and ferritin. Ferritin was detected in 70% of the cases, alpha-fetoprotein was in 50% and carcinoembryonic antigen in 30%. The incidence of the detection of these antigens was in accordance with the incidence of these antigens in the sera of patients with hepatocellular carcinoma. Moreover, these antigens were mainly expressed in the well differentiated type of hepatocellular carcinoma by the Edmondson's criteria. Our results also revealed that different antigens were usually present in different tumor cells, although some cells displayed two or more antigens simultaneously. These findings suggest that hepatocellular carcinoma cells are functionally heterogeneous, even if they appear histologically monomorphic.

Aged↗

Modulation of the immunoreactivity of a T-lymphocyte subpopulation by neutrophil-released prostaglandin.

The effect of polymorphonuclear leukocytes (PMNs) on lymphocyte subpopulations and their reactivity was investigated by adding supernatants obtained by culturing PMNs with allogeneic or autologous lymphocytes which had been pre-treated with prostaglandin (PG) synthetase inhibitors. PMNs were obtained from 12 healthy individuals, 7 patients with systemic lupus erythematosus (SLE) and 6 patients with bacterial infections. Freshly prepared normal lymphocytes pretreated with PG synthetase inhibitors were incubated with the above supernatants, and the lymphocyte and T-lymphocyte subpopulations were then quantitated, the responses of lymphocytes to mitogens measured and the generation of helper and suppressor T-cell activities for PWM-stimulated cultures assessed. We also ascertained which T-cell population, i.e. OKT4+ or OKT8+ cells, which had been altered by incubation with supernatants, was responsible for the suppressor T-cell activity. A reduced per cent of OKT4+ cells; depressed responses to Con A, PHA, PWM and allogeneic lymphocytes, impaired helper T-cell activity; and increased suppressor T-cell activity were noted after incubation of lymphocytes with supernatants. The percentage of T lymphocytes and of OKT8+ cells was, however, not affected. Further, enhanced suppressor T-cell activity was obtained when supernatant-incubated OKT4+ cells were cultured with OKT8+ cells, regardless of whether the latter had previously been exposed to supernatants. Addition of PG inhibitors to PMN co-cultures nearly restored the original percentage and reactivity of the T-lymphocyte populations, indicating a role for PG released from PMNs in the effects observed. The amount of PG demonstrated in co-culture supernatants was 30 times more than obtained by sonification of fresh PMNs and 10 times more than found in the culture medium containing PMNs alone. These results suggest that, besides monocytes, other phagocytes, including PMNs, can modulate lymphocyte-mediated immune reactivity by the release of PG. Deceased number of OKT4+ cells, impaired helper T-cell activity and enhanced suppressor cell activity may, at least in part, result from the effect of PG released from PMNs as well as monocytes.

Adolescent↗

Immunocytochemical characterization of pulmonary histiocytosis X cells in lung biopsies.

Morphologic and immunohistochemical studies were made of open lung biopsies from 9 patients with pulmonary histiocytosis X (HX) and 12 patients with other conditions, and of skin biopsies from patients with cutaneous sarcoidosis, Chester-Erdheim disease, and eruptive histiocytoma. The monoclonal antibody OKT6 was detected with the use of goat anti-mouse IgG labeled with fluorescein (FITC) for light microscopy, and sheep antimouse Fab'2 fragment of IgG labeled with horseradish peroxidase (HRP) for immunoelectron microscopy. The presence of S-100 protein was revealed by an antibody prepared against bovine S-100 protein, using sheep anti-rabbit IgG labeled with FITC for light microscopy and with HRP for immunoelectron microscopy. OKT6 antibody and S-100 protein were detected simultaneously by double labeling with FITC and rhodamine. In all patients with pulmonary HX, the major cellular components (HX cells) of the granulomas showed labeling of the plasma membranes by OKT6 and of the cytoplasm by the anti S-100 protein antibody. The double-labeling technique demonstrated that the same cells carried both reactivities. Immunoelectron microscopy showed that the reactive cells had all the structural characteristics of Langerhans cells, including Langerhans cell granules. Cells reacting with OKT6 showed discrete internal labeling in some of the Langerhans granules, especially those in continuity with the plasma membranes. However, internal labeling of Langerhans granules was not demonstrated in preparations for the localization of S-100 protein. Control samples of sarcoid lesions and other pulmonary lesions unrelated to HX did not show any reactivity except in Langerhans cells; a skin lesion from a patient with eruptive histiocytoma contained OKT6-positive cells which did not have Langerhans granules.

Antibodies, Monoclonal↗

Patterns of pulmonary structural remodeling after experimental paraquat toxicity. The morphogenesis of intraalveolar fibrosis.

For a study of the evolution of interstitial and intraalveolar fibrosis, ultrastructural and immunohistochemical observations were made of the lungs of 16 cynomolgous monkeys given 1 or 2 injections of 10 mg/kg of paraquat and sacrificed 2 days to 8 weeks later. At 2-3 days, alveolar epithelial cells were denuded in many areas, and fibronectin was conspicuous in alveolar spaces. At 1 week, fibroblasts and inflammatory cells were migrating through gaps in the denuded epithelial basement membranes; Type II cells were regenerating in some areas. At 3-4 weeks, alveoli developing intraalveolar fibrosis contained many myofibroblasts, collagen fibrils, and small elastic fibers; fibrotic alveolar walls were lined by metaplastic squamous cells and bronchiolar epithelial cells. Spiraling collagen fibrils were found in interstitium but not in alveolar spaces, which suggests that they were formed from breakdown of collagen. Newly formed intraalveolar collagen was mainly Type I. At 8 weeks, intraalveolar fibrosis had led to extensive remodeling, with new glandlike alveoli lined by Type II cells; alveoli without intraalveolar fibrosis had more normal architecture. Thus, intraalveolar fibrosis in paraquattreated lung is mediated by intraalveolar migration of interstitial cells, through gaps in the epithelial basement membranes, after epithelial injury. This is followed by connective tissue synthesis on the luminal side of the epithelial basement membrane, by differentiation of interstitial cells into myofibroblasts and smooth-muscle cells, by incorporation of areas of intraalveolar fibrosis into the interstitium, and by coalescence of alveolar walls. Intraalveolar fibrosis is more important than interstitial fibrosis in the structural remodeling that occurs in paraquattreated lung, because it results in obliteration of alveoli, coalescence of alveolar walls, and loss of functional alveolar-capillary units.

Animals↗

Serum levels of secretory immunoglobulin A in liver disease.

Secretory immunoglobulin A (sIgA) in serum was measured in patients with various liver diseases using enzyme immunoassay specific to sIgA. Marked elevation of the serum sIgA concentrations was found in liver diseases especially in intrahepatic or extrahepatic cholestasis. In chronic hepatitis and liver cirrhosis serum sIgA correlated significantly with leucine aminopeptidase (r = 0.69), GOT (r = 0.66), alkaline phosphatase (r = 0.55), and direct bilirubin (r = 0.42). In acute hepatitis their levels correlated significantly with total bilirubin (r = 0.59) and GPT (r = 0.55). In acute hepatitis and acute exacerbation of chronic hepatitis the major peaks of serum sIgA were observed later than those of liver enzymes. These results suggest two mechanisms working to elevate the serum sIgA levels in liver diseases. In chronic hepatitis, liver cirrhosis, and intrahepatic and extrahepatic cholestasis the raised serum sIgA probably reflects reflux of bile, a rich source of secretory component and sIgA, into circulation. In acute or chronic massive liver necrosis elevation of sIgA may be associated with liver regeneration. Serial measurement of serum sIgA with other conventional parameters will contribute much to the understanding of the pathophysiology of liver diseases.

Acute Disease↗

Immunological studies on the mechanism of halothane-induced hepatotoxicity: immunohistochemical evidence of trifluoroacetylated hepatocytes.

The fulminant hepatotoxicity caused by halothane has been thought to have an immunological basis because this toxicity occurs most often after repeated administration of halothane and because sera from patients recovering from severe halothane hepatotoxicity contain antibodies that bind to the surface membranes of hepatocytes of rabbits treated with halothane. In order to determine whether the major reactive metabolite of halothane, trifluoroacetyl halide, covalently binds to hepatocytes, we have developed specific and sensitive peroxidase enzyme-linked immunosorbent assays and an indirect immunofluorescence staining method for identifying trifluoroacetylated (TFA)-hepatocytes. Liver sections prepared from rats at 4 hr after halothane administration were stained preferentially in the centrilobular region with anti-TFA serum whereas livers of control rats showed no staining. The specificity of the assay for the TFA group was confirmed by the complete inhibition of the staining with 200 microM N-epsilon-TFA-L-lysine in the diluted antiserum. On the other hand, 2 mM halothane or L-lysine did not inhibit this staining. Moreover, treatment of rats with deuterated halothane resulted in significantly less staining than did halothane. At 24 hr after halothane administration, hepatocytes isolated and stained by indirect immunofluorescence showed a linear and granular pattern on their surface membranes. These results indicate that trifluoroacetyl halide either reacts directly with constituents of the plasma membranes or with other cellular components which become incorporated into the plasma membranes.

Animals↗

[Clinical evaluation of CEA in colorectal carcinoma].

Carcinoembryonic antigen (CEA) titer (Dinabot-Kit) were determined in proven 177 patients with colorectal carcinoma preoperatively, and at routine intervals following operation. The assay was positive in 39.1% with stage I, II, 65.9% with III, 65.9% with IV and 85.7% with V. Elevated CEA levels were noted in those who had infiltration of cancer cells extending through the proper muscle layer. In 79.2% of curative resections CEA levels returned to normal within one month, but the titers remained elevated in 73.3% of palliative resections. Among 26 patients with recurrent disease, 16 had a hepatic metastasis showing a previous or simultaneous CEA rise, whereas 10 had a local recurrence with a slow rise or normal. In addition, a quantitative study of CEA in extracts of 87 tumors was made in order to examine the factors affecting the level of circulating CEA. There was no significant difference between the CEA contents of the tumor and its level of circulating CEA. The level of circulating CEA might be influenced by the spread cancer cells, rather than the tumor contained CEA.

Carcinoembryonic Antigen↗

[The concomitant effect of a newly developed gamma-globulin preparation (SM-4300) with some antibiotics on severe bacterial infections].

Twenty-six patients with bacterial infections, mainly respiratory infections, were treated with newly developed gamma-globulin preparation (SM-4300), as a combination therapy with some antibiotics. The result was as follows. Clinical effects of 18 cases evaluated were excellent in 1 case (5.6%), good in 10 (55.6%), fair in 4 (22.2%) and poor in 3 (16.7%). No remarkable adverse reactions and abnormal value in laboratory data due to administration of SM-4300 were observed. Significant changes of complement system before and after administration of SM-4300 were not observed. It was considered that SM-4300 was effective as a combination therapy with some antibiotics for the treatment of severe or refractory bacterial infections.

Adult↗

Retinotopic organizations of the expanded ipsilateral projection to the rat's superior colliculus; variations along its rostrocaudal axis.

The retinotopic organization of the expanded projection to the ipsilateral colliculus was studied electrophysiologically in 12 adult albino rats with one eye removed at birth. For comparison, the contralateral projection was rather variable in the representation of the nasotemporal axis of the retina along the rostrocaudal dimension of the colliculus; on the other hand, the representation of dorsal-to-ventral retinal axis onto the mediolateral dimension of the colliculus was relatively stable.

Animals↗

The relation between axon diameter and axonal conduction velocity of Y, X and W cells in the cat retina.

Axon diameters of ganglion cells were measured electronmicroscopically from the cross-sections of the optic nerve fiber layer in the cat retina. The diameter distribution revealed 3 well-separated groups which correspond to axons of Y, X and W cells. Mean intraretinal axonal conduction velocities were estimated physiologically for the 3 classes. Between the means of axon diameter (D, micron) and conduction velocity (V, m/s) the following positive correlations were obtained: V = 3.85 square root D-2.3 when short axes of cross-sections were measured, and V = 3.33 square root D-2.3 when long axes were measured.

Animals↗

Plastic changes in the distribution and soma size of retinal ganglion cells after neonatal monocular enucleation in rats.

Using the method of retrograde labeling of ganglion cells with HRP, we studied in adult rats the plastic changes in the retinogeniculate projections due to monocular enucleations shortly after birth. Four normal and 6 neonatally enucleated rats were used. In two of the normal and 4 of the enucleated rats a small amount of HRP was injected into the dorsal lateral geniculate nucleus (LGd) and in 4 other rats massive injections were made into the optic tract near the LGd. Neonatally unilaterally eye-enucleated rats were characterized by an expanded distribution of ipsilaterally projecting ganglion cells all over the retina of the remaining eye and by a densely packed distribution of these cells in the lower temporal retina in which area these cells have only a moderate density in normal rats. On the contrary, in the lower temporal retina of monocularly enucleated rats the incidence of contralaterally projecting ganglion cells was decreased. Soma areas of ipsi- and contralaterally projecting ganglion cells were measured for the peripheral crescent in lower temporal and lower nasal retinas. As compared with normal rats, neonatally enucleated rats had a larger mean soma area of ipsilaterally projecting cells and a smaller mean soma area of contralaterally projecting cells. This result was interpreted as suggesting that after neonatal monocular enucleation medium to large cells had changed their side of axonal projection from the contralateral to ipsilateral LGd.

Animals↗

Bilateral changes in soma size of geniculate relay cells and corticogeniculate cells after neonatal monocular enucleation in rats.

Soma areas of relay cells of the lateral geniculate nucleus and of corticogeniculate cells of normal rats (n = 4) were compared with those of neonatally unilaterally eye-enucleated adult rats (n = 13). These cells were labeled by retrogradely transported HRP. Monocular enucleation was performed on postnatal days 1 (PND 1) (n = 4), 3 (PND 3) (n = 5) and 6 (PND 6) (n = 4). The results are summarized as follows. In PND 1 rats soma areas of relay cells were 12-16% smaller than those of normal rats, but only for the geniculate nucleus ipsilateral to the remaining eye. In PND 3 and 6 rats the areal shrinkage of relay cells was 27-39% of the normal control for both hemispheres, though it was less marked in the hemisphere contralateral to the remaining eye. The corticogeniculate cells were distributed in layers V and VI in eye-enucleated rats as well as in normal rats. Soma areas of both layer V and VI cells increased in PND 1 rats for both hemispheres by about 15-47% of the normal control. In PND 3 rats increase in soma size tended to occur for layer VI cells, although the data varied from animal to animal. In summary, it was established that unilateral eye-enucleation in rats at birth induced soma size changes of the geniculate relay cells and of the corticogeniculate cells in the non-deafferented as well as in the deafferented hemisphere. Possible mechanisms for the bilateral changes in soma area of central visual cells after neonatal monocular enucleation are discussed.

Animals↗

Development of elastic fibers of nuchal ligament, aorta, and lung of fetal and postnatal sheep: an ultrastructural and electron microscopic immunohistochemical study.

The morphogenesis of elastic fibers of the nuchal ligament, aorta, and lung of sheep was studied by light microscopy, transmission electron microscopy, and immunohistochemical methods for the detection of elastin. The degree of maturation of the amorphous materials of elastic fibers was assessed morphologically in preparations stained by the tannic acid and periodic acid methenamine-silver methods. With both of these methods, the amorphous components of mature fibers stained less intensely than did those of immature fibers. Elastic fibers in early stages of development consisted of many microfibrils and few, small, branching masses of immature amorphous material. Thicker fibers were formed by the coalescence of growing masses of amorphous materials. In late stages of formation of elastic fibers, the mature amorphous materials were associated with few microfibrils; and they were partially surrounded by immature amorphous materials associated with many microfibrils. Antielastin antibody reacted evenly with amorphous materials in very early stages of elastic-fiber development, but reacted only with the other zones of amorphous materials in later stages; it also reacted with the microfibrils in all stages. These findings were interpreted as indicating that the microfibrils were associated with small amounts of elastin on their surfaces. This conclusion is in agreement with ultrastructural observations showing 1) that development of microfibrils precedes that of the amorphous material and 2) that the microfibrils adjacent to the immature amorphous materials are covered with small amounts of tannic acid-positive amorphous materials. These observations suggest that microfibrils serve as sites for elastin deposition, both in early elastogenesis and in subsequent growth of elastic fibers. However, the nature of the interaction between elastin and microfibrils remains unknown.

Animals↗