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N R Rose

Publications and source records attributed to N R Rose.

At least 163 records · Page 9Linked to original sources

Strain differences in mice in carbon tetrachloride-induced liver injury.

A study was made in inbred mice of genetic determinants of toxic liver cell injury, and the subsequent occurrence of autoantibodies to mouse liver-specific protein (M-LSP). Carbon tetrachloride was injected s.c. in sublethal doses to induce liver cell damage in 4 strains of mice, BALB/c, C3H, C57BL/6 and SJL/J. The degree of liver cell damage was assessed by blood cholylglycine levels and by semiquantitative histological analysis 1, 4, 7, 14, 21 and 45 days after dosing. Striking differences were observed among the 4 strains in degrees of liver necrosis, cellular infiltration and rate of removal of the necrotic tissue. BALB/c was the strain most susceptible to the necrotizing effects of CCl4. These mice showed confluent areas of hepatocellular necrosis from Day 1 and histological recovery was protracted up to 3 weeks, and was accompanied by pronounced macrophage activity and a cellular inflammatory response. Mice of the SJL/J strain were the least susceptible and showed minor hepatocellular necrosis, which resolved by Day 7, and a slight histiocytic response. C3H and C57BL/6 showed lesions which were intermediate between the other 2 strains. The autoantibody response to LSP was weak, transient and detected only in C57BL/6 mice. This study indicates the presence of genetic control, either H-2 or non-H-2 linked, over the degree of liver cell necrosis resulting from toxic liver injury, and the ensuing cellular infiltrate and rate of removal of the necrotic tissue.

Animals↗

Lymph node mast cells in athymic "nude" (Nu/Nu) and thymus containing (Nu/+ and +/+) Balb/c mice.

Total number of mast cells in popliteal lymph nodes of Balb/c mice is a function of time and Nu gene (complex?) content. The number of mast cells increases with age - in both wild +/+ and in Nu gene (complex?) carriers (Nu/+ and Nu/Nu). The increase in the number of mast cells is faster in the Nu gene carriers than in wild animals +/+ devoid of this gene. In "nude" mice having advanced hepatitis a dramatic increase in the number of lymphoid mast cells was observed. Results obtained deny the importance of thymus in the production of lymphatic mast cells in mice.

Age Factors↗

The use of hybridoma antibodies to probe the antigenic determinants of thyroglobulin.

Using monoclonal antibodies we have begun to define the epitopes of the murine thyroglobulin molecule that elicit autoimmune responses. Based on the principle of complementation, 18 monoclonal antibodies were classified into 8 groups, defined by their reactions with the same or neighboring determinants. Further distinctions between the monoclonals were drawn from comparisons of their cross-reactions with thyroglobulins of other species and their patterns in isoelectric focusing. One low molecular weight fragment of bovine thyroglobulin, which cross-reacts extensively with thyroglobulins of other species, has been isolated and partially characterized.

Animals↗

Monoclonal anti-human prostatic acid phosphatase antibodies.

Hybrid cell lines producing monoclonal antibodies against human prostatic acid phosphatase (E. C. 3.1.3.2) were prepared by the fusion of mouse myeloma cells with the spleen cells of BALB/c mice and Lewis rats immunized with prostatic acid phosphatase (PAP). Approximately 14% of the hybrid cell microcultures which produced specific antibodies were cloned, and 6 eventually yielded stable cell lines. The monoclonal antibodies produced by these 6 hybridomas were characterized for their isotypes, isoelectric points, concentrations and affinities. The specificity of these monoclonal antibodies was further investigated by radioimmunoassay and immunohistochemical methods. All of the 6 monoclonal antibodies exhibited strict specificity for prostatic acid phosphatase.

Acid Phosphatase↗

Monoclonal antibodies to human prostatic acid phosphatase: probes for antigenic study.

Hybrid cell lines producing monoclonal antibodies against human prostatic acid phosphatase [PAPase; orthophosphoric-monoester phosphohydrolase (acid optimum), EC 3.1.3.2) were prepared by the fusion of mouse myeloma cells with the spleen cells of PAPase-immunized BALB/c mice. Approximately 23% of the hybrid cells initially plated after cell fusion produced specific antibodies: 34 microcultures were cloned, and 8 eventually yielded stable cell lines. The monoclonal antibodies produced by these eight hybridomas were characterized for their isotypes, isoelectric points, concentrations, and affinities. All of the eight monoclonal antibodies exhibited strict specificity for PAPase as determined by radioimmunoassay and immunohistochemical methods. These antibodies were used as probes for the antigenic mapping of this enzyme, and three nonoverlapping determinants were recognized. Further binding studies with PAPase fragments, generated by cleavage with a submaxillaris protease, showed that those three determinants are clustered on one fragment of PAPase. These monoclonal antibodies may be useful in refinement of clinical immunoassays of PAPase or immunohistological study of PAPase-synthesizing cells.

Acid Phosphatase↗

A single domain of human prostatic acid phosphatase shows antibody-mediated restoration of catalytic activity.

By limited proteolysis with mouse submaxillaris protease, human prostatic acid phosphatase (EC 3.1.3.2) was cleaved into three fragments, Sp1, Sp2, and Sp3, which individually had no enzymatic activity. One of the fragments, Sp3, regained enzymatic activity after interaction with rabbit antibody to prostatic acid phosphatase. The Sp3 fragment was purified and characterized as to its molecular weight, amino acid composition, and carbohydrate content. The Sp3 fragment behaved like the parent molecule in L(+)-tartrate affinity and in trapping of a phosphoryl intermediate. The same Sp3 fragment also bears the most prominent antigenic determinants. This evidence suggest that Sp3 is the enzymatically active domain of prostatic acid phosphatase.

Acid Phosphatase↗

Fluorescent antibody technic used for identification and typing of Streptococcus pneumoniae.

A fluorescent antibody technic (FAT) has been developed for identification and typing of Streptococcus pneumoniae. The technic was first compared with the Neufeld test (NT) using polyvalent antiserum and isolates identified as S. pneumoniae. Of 197 isolates, 191 (97%) were positive by both technic, and six strains (3%) were negative by both methods. Both tests were also used for determination of pneumococcal types agreed in 23 of 25 tests (92%) but the Neufeld test gave false results in 2 of 25 determinations (8%). The polyvalent antiserum was used to examine by FAT direct films obtained from various specimens and the results were compared with Gram stain and cultures. Of 198 direct films in which gram-positive cocci resembling pneumococci were found, 154 were positive by FAT and 130 were positive by culture. FAT appears to be more reliable than Gram stain or culture. During a four-year period, isolated strains of pneumococci were typed by FAT and the results compared. A slight change in the incidence of the pneumococcal types was observed. Although the Neufeld test is simpler, FAT is easier to read and is a more reliable method if identifying pneumococci, especially in body fluids where the number of microorganisms might be limited. Also, FAT is a more reliable procedure in typing strains.

Antibody Specificity↗

Effects of nu gene on the numbers of mast cells in lymph nodes.

The total numbers of mast cells (MC) in popliteal lymph nodes of homozygous nude (nu/nu) and phenotypically normal, heterozygous (+/nu) BALB/c mice are greater than in normal (+/+) BALB/c mice at approximately 6 months of age. The values obtained from 4- to 7-month-old (nu/nu) and (+/nu) mice are twice as high as those from 2- to 3-month-old mice. It is concluded that the thymus does not directly determine the number of MC in lymph nodes, but the presence of the nu gene or another gene closely linked to the nu gene regulates the number of MC. 'Nude' mice infected with hepatitis virus accumulate many more MC than do healthy mice.

Aging↗

Regulation of experimental autoimmune thyroiditis: influence of non-H-2 genes.

Experiments were conducted to investigate the non-H-2 genetic effects on experimental autoimmune thyroiditis (EAT). Strains having C3H or BALB background in general produced higher autoimmune responses to mouse thyroglobulin (MTg) than the B10 or A strains. Comparisons of C3H and B10 congenic strains carrying similar H-2 haplotypes demonstrated that the C3H congenics had significantly higher MTg antibody titres and more severe thyroid damage, even when the strains carry the low responder H-2 haplotypes. These observations show that non-H-2 gene(s) influences EAT, in addition to genes in the MHC.

Animals↗

Characterization of antigenic sites of human prostatic acid phosphatase.

Human prostatic acid phosphatase [PAP] is antigenically uniquely different from acid phosphatases of other tissue origins. Nevertheless, a small degree of antigenic cross-reactivity between PAP and other lysosomal acid phosphatase(s) [LAP] has been suspected. In order to resolve this question, we have adopted two approaches: one involving structural studies by peptide mapping, and the other involving topological mapping through the use of uniquely defined antibodies. Purified PAP was dissociated into subunits and was further cleaved by chemical and enzymological methods. The limited digestion of PAP by submaxillary protease yielded three fragments [Sp-1, 2, and 3]. One of the fragments, Sp-3 [Mr = 11,000-12,000], was shown to regain catalytic activity after interaction with anti-PAP antibodies. This along with other data suggested that the active site is localized in the Sp-3 fragment. These submaxillary protease fragments were also used in the antigenic studies. For the detailed antigenic mapping studies, we prepared 12 monoclonal anti-PAP antibodies. These monoclonal anti-PAP antibodies exhibited a remarkably specific binding to PAP, particularly to the Sp-1 fragment, without binding to other acid phosphatase preparations. We also prepared lysosomal acid phosphatase [LAP] and raised anti-LAP antibodies in rabbits. The anti-LAP antibodies were fractionated into subpopulations by the preparative isoelectric focusing method. Three anti-LAP antibody subpopulations [pI 5.2, 6.9, and 7.5] exhibited specific binding to LAP. However, two anti-LAP subpopulations [pI 5.3 and and 6.8] showed binding to the Sp-3 fragment, an active site fragment of PAP. Thus, the PAP molecule seems to consist of three domains, namely, Sp-1, Sp-3, and Sp-2. Sp-3, which is the active site domain, is an antigenically cross-reactive region. The Sp-1 domain represents an antigenically unique region of PAP, whereas none of the antibodies studied thus far bind to the Sp-2 fragment.

Acid Phosphatase↗

Transient thyrotoxicosis in an infant delivered to a long-acting thyroid stimulator (LATS)- and LATS protector-negative, thyroid-stimulating antibody-positive woman with Hashimoto's thyroiditis.

A thyrotoxic infant was delivered to a woman with a long-standing history of Hashimoto's thyroiditis, but with no evidence of Graves' disease. Long-acting thyroid stimulator (LATS) and LATS protector were absent, but thyroid-stimulating antibody was transiently present in the infant and markedly and persistently elevated in the mother. It is concluded that the maternal level of thyroid-stimulating immunoglobulins determines the presence and duration of transient neonatal thyrotoxicosis, and that thyroid-stimulating antibody is distinct from LATS and LATS protector.

Adult↗

Autoimmunity in endocrine diseases.

The realization that autoimmunity underlies many endocrine disorders of previously unknown etiology has greatly broadened our understanding of the pathogenesis of these diseases. It has provided new explanations for their heredity and their association with particular HLA haplotypes. It has also offered new tools for diagnosing these diseases as well as monitoring their course or predicting their outcome. Finally, establishing the autoimmune basis of these diseases offers new potential for their treatment. The next quarter century of research into immunologic aspects of endocrine diseases promises to be as fruitful as the last.

Animals↗