Limit on the tau neutrino mass.
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Biomedical subjects
Publications and source records attributed to M Sung.
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We previously reported that circulating natural thymocytotoxic autoantibody (NTA) and IgG-anti-DNA antibodies were the major serological characteristics of a substrain of SAM, SAM-P/1. We present here a study of ageing in which we further measured and compared various kinds of circulating IgG antibodies including anti-collagen type II, rheumatoid factor (RF), and anti-2,4,-dinitrophenol (DNP), between SAM-P/1 and control SAM-R/1 mice. The results showed that age-associated increases in anti-collagen type II antibodies in SAM-P/1 were distinctively higher than those in SAM-R/1 when the mice were over 4 months of age, and the increases were significantly correlated with increases in NTA, anti-DNA antibodies, RF activities and anti-DNP antibodies. Anti-collagen type II antibody activity was not significantly inhibited by preincubating the antibodies with DNA, IgG-Fc and DNP-BSA samples. These findings suggest that antibodies specifically directed against collagen type II can be produced in a background of polyclonal B cell activation, and that these antibodies in association with NTA and anti-DNA antibodies may play a pathogenic role in the development of accelerated senescence in SAM-P/1 mice.
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Leader peptidase of Escherichia coli cleaves the leader sequence from the amino terminus of membrane and secreted proteins after these proteins insert across the membrane. Despite considerable research, the mechanism of catalysis of leader peptidase remains unknown. This peptidase cannot be classified using protease inhibitors to the serine, cysteine, aspartic acid, or metallo- classes of proteases (Zwizinski, C., Date, T., and Wickner, W. (1981) J. Biol. Chem. 256, 3593-3597). Using site-directed mutagenesis, we have attempted to place leader peptidase in one of these groups. We found that leader peptidase, lacking all of the cysteine residues, can cleave the leader peptide from procoat, the precursor to bacteriophage M13 coat protein. Replacement of each histidine residue with an alanyl residue was without effect on catalysis. Among all the serine and aspartic acid residues, serine 90 and serine 185 as well as aspartic acid 99, 153, 273, and 276 are necessary to cleave procoat in a detergent extract. However, only serine 90 and aspartic acid 153 were required for processing using a highly sensitive in vivo assay. In addition to the residues directly affecting catalysis, aspartic acid 99 plays a role in maintaining the structure of leader peptidase. Replacement of this residue with alanine results in a very unstable leader peptidase protein. This study thus defines two critical residues, serine 90 and aspartic acid 153, that may be directly involved in catalysis and provides evidence that leader peptidase belongs to a novel class of serine proteases.
We purified a new thiamine diphosphate-binding protein (ThDP-BP), produced an antiserum against it, and examined its immunohistochemical distribution in the rat gastrointestinal tract using the avidin-biotin complex method. Positive staining for ThDP-BP was found in the epithelial glands of the stomach, small intestine and large intestine, and in the nuclei of hepatocytes. Measurement of the content of thiamine and its phosphate esters in extracts from the gastric and intestinal mucosa also indicated the presence of ThDP-BP in the stomach and intestinal mucosa. ThDP-BP may be useful for investigating the absorption and metabolism of the thiamine in metabolic disorders.
A role for both the cellular and humoral components of the immune response has been established for chlamydial infection. The significance of helper (L3T4) T cells was evaluated by using a Chlamydia trachomatis murine salpingitis model for upper genital tract chlamydial infection. Mouse oviducts were inoculated with C. trachomatis by using the mouse pneumonitis agent (MoPn) or control medium. Mice depleted of L3T4-bearing lymphocytes had significantly higher (P less than 0.05) numbers of organisms recovered at day 7 postinoculation. The rate of hydrosalpinx formation was significantly higher in the mice depleted of L3T4-bearing lymphocytes (27 of 31 [87%] ) than in the infected undepleted group (8 of 16 [50%] ) (P less than 0.01). The geometric mean antichlamydial immunoglobulin G titers at day 54 postinoculation were significantly higher in the L3T4-depleted mice (mean titer, 2,030) than in the undepleted group (mean titer, 776; P less than 0.05). The rate of fertility was lower in the L3T4-depleted group (2 of 31 [6%]) than in the infected, undepleted mice (2 of 16 [13%]), but this difference did not reach statistical significance. In conclusion, the greater persistence of organisms in the oviduct and higher rates of hydrosalpinx formation in mice depleted of L3T4-bearing cells suggests that these cells play a role in the clearing of organisms following infection and thus in reducing the degree of oviduct obstruction and damage.
The development and testing of candidate vaccines for trachoma are constrained because only humans and nonhuman primates are susceptible to conjunctival infection with Chlamydia trachomatis. Guinea pig inclusion conjunctivitis (GPIC), an analogous disease of guinea pigs, provides a useful, less expensive model to study ocular chlamydial infections. GPIC is caused by a Chlamydia psittaci strain whose external constituents are very similar to those of C. trachomatis. To develop a better model for studying GPIC immunity, conjunctival pockets were established under the abdominal skin of guinea pigs by subcutaneous implantation. Up to six implants could be produced in each animal. The success rate of implantation was 79.0% (n = 148). These pockets were then infected with GPIC. The organism was recovered from the autografts indicating local replication, and tests for serum antibody by microimmunofluorescence showed production of GPIC-specific antibody of IgG and IgM classes after infection. There was minimal antibody response after moderate inoculating doses to the implants, and the titers increased more slowly than after eye infection with GPIC; with higher concentration of the inoculum, however, the antibody response increased to the same levels as with the ocular challenge but more slowly. Inoculation of pockets with GPIC also produced acute inflammatory changes in infected autografts (n = 101). Histologic examination of infected grafts showed chlamydial inclusions in epithelial cells and significant infiltration with lymphocytes and polymorphonuclear cells. Subcutaneous autografts may provide a useful model for chronologic studies of chlamydial infection. The delayed immunologic response, however, suggests that these pockets of implanted epithelium do not have full access to the immune system.
In order to study the lysozyme activity in the cystic mucosal and submucosal glands in the stomal area of the gastric remnant, which is one of the components of gastritis cystica polyposa, we carried out a pathological and immunohistochemical examination of 55 patients with gastric remnants, including 19 with stomal carcinoma, after partial gastrectomy for benign gastro-duodenal diseases. These stomach specimens were examined immunohistochemically for lysozyme. The cytoplasm of some epithelial cells of cystic mucosal and submucosal glands, which showed characteristic changes in the gastro-intestinal stoma as well as background changes in the stomal carcinoma, showed a strongly positive reaction for lysozyme. These strongly lysozyme-positive cells in the cystic mucosal glands appeared more frequently in the cases of stomal carcinoma than in the non-cancerous controls.
Acute self-limited salpingitis developed when guinea pigs' fallopian tubes were infected with the guinea pig inclusion conjunctivitis agent (Chlamydia psittaci). The disease peaked at approximately 8 days post infection and had diminished markedly by day 14. The inflammatory reaction was concentrated at the luminal surface. Chlamydial replication was demonstrated and inclusions were found in epithelial cells.
During a one-year period, 101 parakeets and parrots were submitted for laboratory examination. The birds were sick, dead, or from premises where morbidity had been observed. Tissue specimens from these birds were tested for the presence of Chlamydiapsittaci by two methods. A tissue culture system using McCoy cells treated with 5-iodo-2-deoxyuridine was found to be more sensitive than intraperitoneal inoculation of mice for isolation of the chlamydiae. Chlamydiae were recovered from 21 (34%) of 61 parakeets and 16 (40%) of 40 parrots tested. This high rate of infection persists despite the availability of effective chemotherapeutic regimens for control of chlamydial infection in psittacines. The origins of some of the infected birds were traced to aviaries where subsequent treatment with chlortetracycline was successful in eradication of the chlamydial infection. Other infected birds had been imported recently and could be traced back to quarantine centers where (by law) the birds received chemoprophylaxis for chlamydial infection. Our results suggest that this program is an administrative failure.
A case of adenoid squamous cell carcinoma arising in the tongue is presented. This histologic variety of squamous cell carcinoma originates almost exclusively in the skin, and the few examples of oral mucosal lesions have heretofore been restricted to the lip. In the oral mucosa, the neoplasm should be differentiated from several types of adenocarcinoma of salivary origin. Surgical excision in our case was followed by rapid local recurrence and death. This behavior is in contrast to the generally favorable prognosis of analogous cutaneous and lip neoplasms, and may indicate a more aggressive course in lesions of lingual origin.
Chlamydial isolates of bovine origin were serotyped by a plaque reduction method. Of the two major serotypes observed, type 1 included isolates from bovine abortion and enteric infections, whereas type 2 isolates were associated with polyarthritis or encephalomyelitis. These two serotypes were identical to those with a similar disease distribution previously observed in isolates of ovine origin. The two groups did not cross-react and they were serologically unrelated to chlamydiae of avian origin. Thus, it appears that many chlamydial isolates causing intestinal infections or abortion in sheep or cattle are closely related antigenically, as are those producing polyarthritis, encephalomyelitis, and conjunctivitis, and that the two groups are distinct.
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Eight chlamydial isolates of ovine origin were tested in a plaque reduction system using homologous and heterologous rooster antisera. The eight isolates could be separated into two separate immunotypes. Type 1 included isolates associated with ovine abortion and one agent recovered from the feces of an apparently normal sheep. Type 2 isolates were associated with polyarthritis and conjunctivitis. These two serotypes were not cross-reactive with several chlamydiae of avian origin. Further application of the plaque reduction test may provide a useful means of typing chlamydiae.
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Some members of the genus Chlamydia (Bedsonia or psittacosis-lymphogranuloma venereum-trachoma-inclusion conjunctivitis group of microorganisms) produce plaques in monolayers of mouse fibroblast (L-929) cells. Hyperimmune chicken antisera may be capable of specifically reducing plaque counts. When the test was applied to chlamydiae isolated from avian species, the results indicated that different isolates with a common source had similar antigenic reactivity. The plaque reduction test is a potentially useful method for serotyping chlamydiae. The difficult aspect of the method appears to be a readily reproducible means of producing neutralizing antiserum.