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T Shirahama

Publications and source records attributed to T Shirahama.

At least 91 records · Page 5Linked to original sources
PubMed1983

Different regulatory mechanisms for serum amyloid A and serum amyloid P synthesis by cultured mouse hepatocytes.

Regulation of the in vitro synthesis of the serum amyloid proteins A and P has been studied with hepatocyte cultures from CBA/J and C3H/HeJ mice. Liver cells were isolated by the collagenase perfusion technique and established for 48 h in the presence of fetal calf serum. Viable cells could then be maintained in the absence of serum for at least 72 h and in the presence of serum for up to 2 weeks. Serum amyloid A synthesis differed from serum amyloid P synthesis in three significant ways. 1) Serum amyloid A production was stimulated in the presence of fetal calf serum, whereas serum amyloid P was not; 2) serum amyloid A synthesis was increased 200% by monokine-rich macrophage supernatants while serum amyloid P was increased only 10 to 20%; 3) serum amyloid A synthesis was strikingly resistant to cycloheximide inhibition as compared with serum amyloid P and other liver proteins. It is concluded that the in vivo asynchrony of the acute phase serum amyloid A and serum amyloid P responses results at least in part from differences in regulatory mechanisms for their synthesis by hepatocytes.

Amyloid↗
PubMed1982

The association of amyloid P-component (AP) with the amyloid fibril: an updated method for amyloid fibril protein isolation.

An amyloid fibril isolation procedure is proposed which uses citrate as well as saline washes to dissociate the calcium dependent linkage of amyloid P-component (AP) from the amyloid fibril. In two amyloid rich tissues, the amount of AP was quantitated in each saline and citrate wash and totalled 13.8% and 20.8% of the amyloid fibrils isolated. The amount of AP removed from these and 22 additional amyloid rich tissues was greater than had previously been recognized. AP protein was present in tissue only when amyloid fibrils were present. It could not be found in normal non-amyloidotic tissue, nor could it be found in tissue sediment after the fibrils were removed.

Amyloid↗
PubMed1982

Senile cerebral amyloid. Prealbumin as a common constituent in the neuritic plaque, in the neurofibrillary tangle, and in the microangiopathic lesion.

Three lesions that characterize the nosologic findings in the brain of Alzheimer's presenile dementia and senile dementia of Alzheimer type, ie, neuritic plaque, neurofibrillary tangle, and microangiopathy, all are frequently associated with amyloid deposition. There has been some question, however, as to whether these lesions share the same etiology. Moreover, the specific chemical nature of amyloid associated with these lesions has not yet been determined. In the present study, formalin-fixed paraffin sections of the affected brains were tested immunocytochemically for their reactivity against antiserum to prealbumin (recently disclosed as the major constituent of amyloid associated with familial amyloidotic polyneuropathy as well as senile cardiac amyloid) and known components of other types of amyloid (AA, AP, etc.). The results demonstrated that amyloid deposits in all three lesions reacted with anti-prealbumin, suggesting that it is a common constituent of these lesions. Indeed, it is likely that prealbumin is the major constituent of amyloid associated with neuritic plaque, neurofibrillary tangle, and microangiopathy.

Alzheimer Disease↗
PubMed1982

Immunohistochemical evidence for the lack of amyloid P component in some intracerebral amyloids.

Sections of brain tissue from patients with Alzheimer's disease with amyloid deposits in vessels, in plaques, and within nerve cells were studied by means of an immunoperoxidase method using a specific antiamyloid P component (AP) antiserum. Amyloid deposits in vessels were found to be strongly positive for protein AP, whereas the Alzheimer's plaques and the neurofibrillary tangles were negative or only weakly positive. The absence of protein AP in some intracerebral amyloid deposits might be due to an inability of the protein AP in some intracerebral amyloid deposits might be due to an inability of the protein to penetrate the blood-brain barrier. These findings support the theory that protein AP is absorbed to already formed amyloid fibrils, but the possibility that it may participate in the formation of vascular amyloid cannot be dismissed. The findings also indicate that protein AP is not necessary for the formation of amyloid fibrils at least in some forms of cerebral amyloidosis.

Alzheimer Disease↗
PubMed1981

Immunocytochemical identification of amyloid in formalin-fixed paraffin sections.

Formalin-fixed paraffin sections of livers, spleens and kidneys from patients with primary, secondary and familial amyloidosis as well as from a casein-induced murine amyloid model were analysed by an immunocytochemical (unlabeled antibody enzyme) method utilizing antisera to amyloid-related proteins. All amyloid deposits of all amyloid types showed positive reactions with anti-AP of the respective species. Positive reaction of anti-human AA to human secondary amyloid deposits and of anti-mouse AA to the deposits of casein-induced murine amyloid was also observed, but there was no species cross reactivity. No significant deposition of the reaction products was produced by anti-immunoglobulin light chains on deposits of any amyloid type, or by anti-AA in the tissues from primary or familial amyloidosis. The results indicate that amyloid proteins AA and AP can survive as antigens through routine histologic preparation, that anti-AP can be a universal marker for deposits of any amyloid type within the same species, and that AA-type amyloid can be identified by this method while there may as yet be no feasible universal marker for the AL-type at present.

Amyloid↗
PubMed1981

Arthritis in Whipple's disease.

Synovial fluid and membranes were studied in two patients with Whipple's disease. In the first, arthrocentesis revealed 28,350 white blood cells/mm3, 96% of which were polymorphonuclear leukocytes. A dense neutrophilic infiltrate, periodic acid-Schiff, positive macrophages and bacilliform structures were present in the synovial membrane. The synovial fluid and membrane findings in the second case, and during intercritical periods in the first case, showed mild to moderate nonspecific inflammation. Since polyarthritis and other systemic manifestations often precede the gastrointestinal features of Whipple's disease by many years, a closed synovial membrane biopsy should be obtained in the appropriate clinical setting.

Arthritis↗
PubMed1980

Redistribution of amyloid deposits.

After 21 daily subcutaneous injections of 0.5 ml 10% casein, CBA/J mice were left untreated and evaluated periodically for 6 months for the development of amyloid in spleens, livers, and kidneys. At the end of the amyloid-inducing regimen, the mice developed moderate to heavy splenic amyloid, trace to light hepatic amyloid, and virtually no renal amyloid. Renal amyloid appeared about 2 months after cessation of the casein and then increased steadily, while splenic and hepatic amyloid gradually diminished. Six months after the cessation of casein, moderate amyloid deposits were observed in the kidneys whereas no, or only traces of, amyloid remained in spleens and livers. This renal amyloid was localized predominantly in the peritubular area and differed from the renal amyloid seen in rapidly induced disease, when it localizes dominantly in glomeruli. This phenomenon is interpreted in the light of possible redistribution of amyloid deposits from organ to organ, and the clinical and investigative significances of this possibility and others are discussed.

Amyloid↗
PubMed1978

The identification of amyloid P-component (protein AP) in normal cultured human fibroblasts.

The amyloid protein, AP, has not previously been detected in normal or nonamyloidotic tissues. In this study, human fibroblasts were examined for the presence of AP by immunofluorescence technique. Normal human skin fibroblasts were cultured in Eagle's minimum essential medium for varying periods of time. Antiserum was prepared in rabbits using AP isolated from amyloid-rich tissues. Using indirect immunofluorescence and anti-AP, fluorescent material was found to be distributed in a punctate pattern throughout the cytoplasm with sparing of the nucleus. The fluorescent reaction was speicifically inhibited by absorption of anti-AP with AP-positive serum but not by addition of AP-negative human cord serum. Thus, AP may have a fibroblast origin and a relationship to normal connective tissue.

Amyloid↗
PubMed1977

Kinetics of serum amyloid protein A in casein-induced murine amyloidosis.

Serum amyloid protein A (SAA), the precursor of secondary amyloid protein, is elevated in chronic diseases which are associated with an increased incidence of amyloid. However, SAA is also elevated in acute bacterial and viral infections and somes forms of cancer. The murine model of casein-induced amyloidosis was studied to determine the relationship between SAA production and amyloid deposition. SAA levels measured by radioimmunoassay were found to be as high as 200 times the normal level in CBA/J mice receiving daily parenteral casein. After a single injection of casein the SAA level was elevated by 3h and peaked by 12-18 h. Similar levels were found in casein-treated A/J mice, a strain less susceptible to the induction of amyloid. Parenterally administered bovine serum albumin, which has low potential for amyloid induction, gave SAA levels in CBA/J and A/J mice comparable to casein treatment. These data show that, while SAA levels are elevated during chronic antigenic stimulation, there are other factors involved in amyloid formation. These factors may include alterations in the degradation of SAA by the reticuloendothelial system caused by substances such as casein. Nude (athymic) mice were shown to attain high levels of SAA after receiving casein parenterally. Therefore, thymus-derived lymphocytes are not necessary for the synthesis of SAA.

Amyloid↗
PubMed1977

Murine amyloid protein AA in casein-induced experimental amyloidosis.

Amyloidosis was induced in mice by 25 subcutaneous injections of casein. The splenic amyloid fibrils were identified by electron microscopy to be closely associated with reticular cells. After isolation of the fibrils by simple physical techniques, their ultrastructure revealed single filaments of 80 to 100 A width, which were rigid, nonbranching, and of indeterminate length. This is comparable to previous studies on human preparations. The amyloid fibrils were dissociated by solution in guanidine and chromatography. The resultant amyloid fibril protein was characterized as to its molecular weight, amino acid analysis, and amino-terminal sequence. It was thus definitely identified as protein AA, the major component of secondary amyloidosis. An antibody to this protein, murine AA, identified a cross-reacting mouse serum protein SAA and indicated a species specificity when tested against human preparations. A comparison is made with the AA protein in another murine model as well as AA proteins from human, guinea pig, monkey, and mink amyloidosis.

Amino Acid Sequence↗
PubMed1976

The SJL/J mouse: a new model for spontaneous age-associated amyloidosis. I. Morphologic and immunochemical aspects.

A high incidence of spontaneous amyloidosis is described in SJL/J mice. Amyloid was detected as early as 30 weeks of age and the incidence rose to 90 per cent by 60 weeks of age. Amyloid deposits were most prominent in the perifollicular zones of the spleen and the lobular areas of the liver. Ultrastructural analysis revealed rigid, nonbranching fibrils indistinguishable from those observed in casein-induced murine amyloidosis. On the other hand, immunochemical studies indicated that amyloid deposits in SJL/J mice differ from those found in casein-treated CBA mice with respect to size, amino acid content, and antigenic properties. Since the SJL/J mouse also develops spontaneous reticulum cell tumors and serum M components, it appears to be a useful model for study of the pathogenesis of amyloidosis and its relationship to aging, neoplasia, and certain B-cell dyscrasias.

Age Factors↗
PubMed1975

Suppression of in vitro antibody response by a serum factor (SAA) in experimentally induced amyloidosis.

Serum from CBA/J mice made amyloidotic by chronic casein injections has been shown to suppress in vitro antibody response to SRBC. Similar suppression was also found with normal mouse serum but to a much lesser degree. This suppressive activity of both amyloidotic serum and normal serum was removed by absorption of the sera with antiserum to protein AA, the major constituent of casein-induced (secondary) amyloid fibrils. This antiserum to the amyloid fibril protein AA (mol wt 8,400 daltons) detects an immunologically cross-reacting serum alpha globulin (SAA) (mol wt approx. 100,000). It is postulated that the serum factor (SAA) is a regulator of antibody response and may be present in elevated amounts as the result of chronic antigenic stimulation.

Alpha-Globulins↗
PubMed1975

Intralysosomal formation of amyloid fibrils.

Unusual inclusions, which occurred in the reticuloendothelial cells intimately associated with fresh amyloid deposits, were analyzed by electron microscopy. The inclusions were located in the areas rich in the primary lysosome type of dense bodies and the cytoplasmic invaginations containing well-oriented amyloid fibrils. They were single-membrane-bounded, measured 0.3 to 0.8 mu in width and 0.5 to several microns in length, and showed considerable variation in the electron density of their contents. The latter consisted of two different ultrastructural elements: fibrillar profiles and a homogeneous or finely granular electron-dense substance. The fibrillar profiles were virtually identical in ulstrastructure to the amyloid fibrils and were well-oriented parallel to the long axis of the inclusion. The homogeneous or finely granular electron-dense substance appeared to be comparable to that composing the dense body matrix. The inclusions were usually acid phosphatase positive, but did not take up intravenously injected Thorotrast particles. These data led us to conclude that these inclusions were transitional forms from the usual dense bodies to the deep cytoplasmic invaginations containing well-oriented amyloid fibrils (which are accepted by most investigators as the sites of amyloid formation) and thus constitute direct evidence for the involvement of lysosomes in amyloid fibril formation.

Acid Phosphatase↗