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Biomedical subjects

D R Johnson

Publications and source records attributed to D R Johnson.

At least 235 records · Page 13Linked to original sources

Group B streptococcal Ibc protein antigen: distribution of two determinants in wild-type strains of common serotypes.

Studies were carried out on the distribution of the Ibc protein antigenic marker in wild-type strains of group B streptococci of diverse serotypes isolated from epidemiological studies. Rabbits were immunized with group B streptococcal strain H36B, a prototype Ib strain, to produce antibody to the Ibc protein antigens. One antiserum (no. 970) contained antibody only against the trypsin-sensitive (TS) portion of the Ibc antigen. A second antiserum (no. 973), however, contained antibody to both the TS and the trypsin-resistant (TR) determinants or components of the antigen. A total of 785 wild-type strains of group B streptococci were serotyped by using antiserum 973 as well as antisera to the polysaccharide types Ia, Ib, II, III, and IV. Remarkably, 59% of all the strains tested (462 of 785) reacted positively with the Ibc antiserum, although not all carried both components of the Ibc antigen. Of the 99 Ib strains examined, 84% carried both TS and TR components. In contrast, 96% of the 202 Ic strains carried only the TR component of the Ibc antigen. Antiserum 970 failed to identify these strains. Routine typing with an antiserum which contains antibodies to only one portion of the Ibc antigen could result in significant serotype misidentification. Differentiation of group B streptococcal strains by the presence or absence of individual TS or TR components of the Ibc antigen could prove to be a useful additional epidemiological and serological marker. It is noteworthy that wild-type Ic strains carry, ordinarily, only the TR component, in contrast to the prototype Ic strain, which possesses the complete Ibc protein antigen. The possible contribution of the Ibc antigen to group B streptococcal virulence is of interest and requires further study.

Antigens, Bacterial↗

Helper functions of antigen-induced specific and autoreactive T cell colonies.

Helper T cells have been distinguished on the basis of whether they provide carrier-specific or nonspecific helper functions. In previous experiments we determined that the predominant class of helper T cell in populations of primed lymph node cells is a nonspecific helper T cell unable to provide carrier-specific signals. Initial induction of nonspecific helper T cells in vitro requires restimulation with the immunogen. This suggested that such T cells may express antigen-specific receptors. In this case they would constitute a unique subpopulation distinct from T cells with identical antigen-specificity that are able to provide carrier-specific help. Alternatively, the requirement for antigen restimulation might reflect a role for antigen-specific T cells in the recruitment of T cells with unrelated specificity. To distinguish between these possibilities we have characterized the specificity and function of helper T cell colonies selected from primed lymph node cells. We report here isolation of autoreactive as well as antigen-specific helper T cells. All antigen-specific T cell colonies provide carrier-specific help in the presence of the homologous hapten-carrier conjugate. Only autoreactive T cells are limited to providing nonspecific helper function. Although selection of autoreactive T cells is initially dependent on antigen restimulation in vitro, activation of an established autoreactive T cell line requires restimulation with MHC-syngeneic spleen cells but does not require restimulation with either the immunogen or fetal calf serum. These results suggest that nonspecific helper T cells induced in the course of a normal immune response to randomly chosen foreign antigens are autoreactive. Such T cells may serve to enhance proliferation and maturation to immunoglobulin secretion of B cells activated by limiting numbers of carrier-specific helper T cells. The demonstration of large numbers of precursors to MHC-specific autoreactive T cells in antigen-primed populations raises important issues concerning regulation of the expansion of autoreactive T cells in vivo.

Animals↗

The ultrastructure of mandibular condylar and rib cartilage from mice carrying the spondylo-metaphyseal chondrodysplasia (smc) gene.

The ultrastructural appearance of cartilage from a new mutant spondylo-metaphyseal chondrodysplasia (smc) is described. The matrix is abnormally rich in collagen fibres which often form a sheath around the chondrocytes. Collagen balls - spherical inclusions of collagen fibres - are a unique and characteristic feature of the matrix, and the chondrocytes contain large amounts of lipid.

Achondroplasia↗

Amelioration of mercuric chloride-induced acute renal failure by dithiothreitol.

Experiments were conducted to determine if administration of the sulfhydryl reducing agent and metal chelator dithiothreitol (31 mg/kg body wt) alters the development of renal dysfunction in the first 3 hr after injection of mercuric chloride (3 mg/kg). Mercuric chloride alone resulted in elevation of urine flow rate and fractional excretion of solutes within 30 min of injection. In animals injected with dithiothreitol 60 min after mercuric chloride, urine flow rate and fractional excretion of solutes were reduced within 30 min to values intermediate between control and mercuric chloride-treated rats. Neither the injection of mercuric chloride alone nor when followed by dithiothreitol resulted in changes in mean arterial blood pressure or glomerular filtration rate. In addition, dithiothreitol did not reduce urine flow rate or fractional excretion of solutes when these parameters were elevated during extracellular fluid volume expansion. Measurement of mercury in organs of those rats injected with mercuric chloride alone or prior to dithiothreitol revealed no alteration in organ distribution. The renal cortex contained the highest concentrations of mercury, and these concentrations were comparable in both groups of rats. These studies demonstrate that dithiothreitol can ameliorate the renal toxicity of mercury and suggest that this effect is mediated through an intrarenal site of action.

Acute Kidney Injury↗

Epstein-Barr virus (EBV)-induced lymphoproliferative disease in cotton-topped marmosets.

Six cotton-topped marmoset monkeys (Sangiunus oedipus) were inoculated with 10(5) transforming units of B95-8 virus, and two of them developed fatal lymphoproliferative disease. The EBV-carrying tumor cells from these marmosets had the following characteristics: (1) they were polyclonal by surface immunoglobulin and immunoglobulin production in vitro; (2) they had no specific chromosome abnormalities, and (3) they failed to form colonies in large percentages in agarose. It is proposed that a spectrum of phenotypes of EBV-induced lymphoproliferative diseases in the cotton-topped marmosets may be identified and are more akin to fatal infectious mononucleosis or X-linked lymphoproliferative syndrome than to Burkitt's lymphoma.

Animals↗

Type 49 Streptococcus pyogenes: phage subtypes as epidemiological markers in isolates from skin sepsis and acute glomerulonephritis.

Studies of group A, M type 49 streptococci from England, Trinidad and Alaska indicate that isolates of this serotype often differ with respect to phage subtype from one geographical area to another, but are generally homogeneous in one place at one time. The findings support the conclusion that acute glomerulonephritis can be associated with a variety of phage subtypes of M type 49 streptococci. In outbreaks of skin sepsis without nephritis in England, the phage subtypes of M type 49 streptococci isolated from skin lesions of meat handlers were the same as those recovered from skin lesions of non-meat handlers in the same community. The findings on the Trinidad isolates suggest that M type 49 streptococci of one phage subtype may persist in a population for 9 years and may result in a second outbreak of acute glomerulonephritis. In an Alaska Eskimo population in whom acute glomerulonephritis was occurring, most of the M type 49 isolates available for testing were of a single phage subtype. Equally prevalent in this population were group A streptococci that exhibited the same T antigen as the type 49 isolates but differed in their serum opacity reaction and phage subtype. This apparently related strain was not typable with available M antisera but showed functional evidence of M protein and is probably a new M type.

Alaska↗

Factors influencing antibody responses to streptococcal M proteins in humans.

In a defined population of 174 children followed at one- to two-week intervals for 23 months, the development of M type-specific antibodies to four different types of group. A streptococci was assayed in 408 serum samples from 68 children who acquired one or more of these types in the upper respiratory tract and/or skin lesions. M type 6, a classic pharyngitis strain, was isolated almost exclusively from the upper respiratory tract. Acquisition of this type resulted in the highest percentage of responders without antibody to M protein and in the greatest magnitude of type-specific bactericidal activity as compared with M types 31, 49, and 52, which were commonly associated with pyoderma lesions. Factors that appeared to influence the M type-specific antibody response included the streptococcal type, the age of the child, the number of culture-positive visits, and the stage of the outbreak. The site(s) of isolation by itself and the serum opacity reaction of the infecting strain did not appear to be important determinants of the M type-specific antibody response.

Age Factors↗

Abnormal cartilage from the mandibular condyle of stumpy (stm) mutant mice.

The mammalian mandibular condyle is composed of secondary cartilage and may thus be susceptible to genes causing achondroplasia and which result in abnormal++ primary cartilage formation. This paper describes the secondary cartilage in the mandible of the stumpy achondroplastic mutation in the mouse: both primary and secondary cartilage are affected by the gene.

Achondroplasia↗

Cell kinetics of growth cartilage in stumpy: a new chondrodystrophic mutant in the mouse.

The proximal growth plates of the tibiae in normal and stumpy mice aged 10-41 days were studied. Autoradiographic studies using tritiated thymidine enabled the size of the proliferating cell population and the labelling indices of the growth plates to be determined. Hypertrophic cell heights were also measured. From these data the overall growth rates for the proximal growth plate of the tibia in normal and stumpy mice were calculated. It was found that the major factor responsible for the reduced growth rate in stumpy up to 21 days was the small hypertrophic cell height, while cell proliferation zone size and labelling indices were of minor importance. Histological observations also revealed a lack of organised endochondral ossification, which worsens with age.

Aging↗

Ultrastructurally abnormal bone and dentin produced by microphthalmic mice.

An ultrastructural study of the jaws of osteopetrotic microphthalmic mice (mi/mi) showed that both bone matrix and dentin were abnormal. In 5 days old mice, the number of osteoblasts was increased: in 15 days old mice, the number of osteocytes was decreased and many of the cells were dead or dying. Mutant osteocytes lacked osmiophilic laminae, calcospherites were irregular in size and density and collagen fibres were scarce and abnormally distributed. In mi/mi mice, the predentin layer of the incisor tooth was abnormally wide, the predentin-dentin junction irregular and patches of hypocalcified or uncalcified dentin were present.

Aging↗

Osteoclasts with ruffled borders from above the tip of the erupting incisors of osteopetrotic mice and rats.

Electron microscopy of the bone above the incisor of 10-day-old microphthalmic mice (mi) and incisors absent rats (ia) demonstrated that in both osteopetrotic mutants, osteoclasts indistinguishable from normal and with well-developed ruffled borders were present. Study of the same region in younger and older animals showed the type of abnormal osteoclast typical of the respective mutant strain.

Animals↗

Role of renal cortical sulfhydryl groups in development of mercury-induced renal toxicity.

The effect of lowering renal cortical sulfhydryl concentration on development of acute renal failure (ARF) was evaluated in rats receiving HgCl2 (15 mg/kg body weight, im). Within 90 min after HgCL2 injection urine flow rate and fractional excretion of sodium (FENa) were significantly elevated above control levels, and they remained elevated throughout the 3-h experimental period. Urine flow rate and FENa were not significantly elevated above control levels in animals injected with diethyl maleate (3 mmol/kg, ip) 30 min before and 90 min after HgCl2 (DEM/HgCl2). Administration of DEM alone did not alter renal function. Although lower than control levels, concentrations of protein-bound sulfhydryl groups (PBSH) were comparable in HgCl2- and DEM/HgCl2-treated animals. In contrast, concentrations of nonprotein sulfhydryl groups (NPSH) were 62% lower in DEM/HgCl2 animals than in those treated with HgCl2 alone. Similarly, Hg accumulation was 54% lower in DEM/hgCl2-treated animals than in animals treated with HgCl2 alone. These results suggest that NPSH play an important role in Hg uptake and subsequent development of Hg toxicity.

Acute Kidney Injury↗