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J Boddingius

Publications and source records attributed to J Boddingius.

14 recordsLinked to original sources
PubMed1993

Study of intracellular deposition of the anti-leprosy drug clofazimine in mouse spleen using laser microprobe mass analysis.

Laser microprobe mass analysis (LAMMA) was used to study the composition of the brick-red crystalline material which had accumulated in the spleen of mice that had received the anti-leprosy drug Clofazimine in their diet for several months. The crystalline deposits light-microscopically resembled pure Clofazimine crystals. The presence of the drug in the crystals was indicated by LAMMA by the appearance of the chloride mass peaks in the negative mass spectra. More specific information was obtained from the positive mass spectra. A mass signal for the protonated molecule was present.

Animals↗
PubMed1990

Subcellular localization of Mycobacterium leprae-specific phenolic glycolipid (PGL-I) antigen in human leprosy lesions and in M. leprae isolated from armadillo liver.

Phenolic glycolipid (PGL-I), an antigen specific to Mycobacterium leprae, was localized subcellularly in M. leprae residing in human skin, in M. leprae isolated from armadillo liver ('isolated M. leprae') and outside M. leprae in human lepromatous skin. For a quantitative localization of PGL-I sites, specimens, including skin segments stored for 6 years in glutaraldehyde, were embedded in hydrophilic Lowicryl (K4M) resin for ultrathin sectioning. Ultracryosections and Araldite sections of comparable specimens were used for comparison of localization results. A monoclonal antibody (F 47-21-3) directed to antigenic oligosaccharide of PGL-I was employed as primary antibody in immunogold labelling of ultrathin sections. K4M-immunogold methods gave very satisfactory quantitative gold-labelling of PGL-I. The localization of PGL-I by this method partially corresponded with sites detectable in both ultracryosections and the qualititatively superior Araldite sections, but new sites were also localized. Cell walls in human M. leprae and in isolated M. leprae possessed many PGL-I sites, particularly in dividing organisms. PGL-I or its antigenic oligosaccharide was also found, to a lesser extent, in the bacterial cytoplasm. Capsules discernible around part of isolated M. leprae cells displayed heavy PGL-I labelling, sometimes clearly confined to a zone distant from the cell wall. Extrabacterial PGL-I in M. leprae-infected human skin was encountered (1) in phagolysosomes and cytoplasm proper of dermal macrophages containing M. leprae, and (2) intra- and extracellularly in epidermal areas where basal cells harboured M. leprae in untreated multibacillary patients.

Animals↗
PubMed1989

Immunogold labeling method for Mycobacterium leprae-specific phenolic glycolipid in glutaraldehyde-osmium-fixed and Araldite-embedded leprosy lesions.

Phenolic glycolipid (PGL)-I, a Mycobacterium leprae-specific antigen currently used for serodiagnosis of preclinical leprosy, has thus far not been localized subcellularly in leprosy bacilli and their host cells. In this study, we developed an immunogold-labeling technique for qualitative identification of PGL-I sites in glutaraldehyde-osmium-fixed and Araldite-embedded M. leprae and host macrophages in human skin biopsies. Such "hard-fixed," plastic-embedded skin and nerve biopsies from patients with varying cell-mediated immunity to leprosy are amply available worldwide. Our method involves etching of plastic sections with H2O2, incubation with swine serum to eliminate nonspecific labeling, and long (22 hr) incubation at room temperature with monoclonal antibodies to PGL-I. Gold labeling was seen predominantly on cell walls of M. leprae, in vacuolar spaces of bacillated phagolysosomes, and occasionally on the cytoplasm and cell membrane of M. leprae. Host macrophage cytoplasm was labeled very infrequently. This technique allows studies on possibly persisting antigenic PGL-I in multibacillary leprosy patients during or after multidrug therapy. The method may also prove useful for subcellular localization of specific bacterial lipids in other mycobacterial diseases, including tuberculosis.

Antigens, Bacterial↗
PubMed1989

In situ locations of Mycobacterium leprae-specific antigens. Immunoelectronoptical studies.

Lipid or protein antigen sites in Mycobacterium leprae proper and in M. leprae -infected human or armadillo tissues were investigated by immunogold-electron microscopy. Simultaneous preservation of immunogenicity of antigens and conservation of ultrastructural details of M. leprae and host cells was aimed at by subjecting organisms and tissues, prior to immunolabelling, to differing fixation, embedding and ultramicrotomy techniques. The M. leprae-specificity of monoclonal antibodies (MoAbs) utilized in the study was tested first. Hereto, ultracryosections of M. leprae, M. tuberculosis and M. nonchromogenicum suspended in gelatin were employed. MoAb anti-phenolic glycolipid I (PGL I) and MoAb anti-36 kD were found to be specific for M. leprae. MoAb anti-65 kD also labelled the cytoplasm of M. tuberculosis. After incubation with MoAb anti-lipid MAIS, employed as control MoAb, no gold labelling of leprosy bacilli or host cells was seen. PGL-I immunogenicity was still present after "hard" fixation of M. leprae and host cells in glutaraldehyde-OsO4 and after Araldite embedding. This enabled the qualitative demonstration of PGL-I inside the cell wall and capsular area of M. leprae and in vacuoles of bacillated phagolysosomes of macrophages in Araldite-embedded human skin biopsies and armadillo liver parenchymal cells. Sites of 65 kD and, to a lesser extent, of 36 kD protein antigens in M. leprae were demonstrable only in ultracryosections of non-fixed organisms and not in Araldite sections. Results are discussed and recommendations for future investigations on M. leprae antigen sites are presented.

Animals↗
PubMed1987

Replication characteristics and core size of intranuclear herpes simplex virus (HSV-1) in genital skin lesions: electronmicroscopy studies of a biopsy from a female patient.

Herpes simplex virus (HSV) type 1 genital infection, leading to ulcerating lesions in a female patient, was studied by electronmicroscopy. Infection had probably been recent, through oro-genital contact with a cold sore on the husband's lip. Cell-culture typing and serological tests indicated that the patient currently had an HSV-1 secondary infection. Aspects studied in a skin biopsy from an ulcerating labium majus were epidermal cell types infected, stages in virus genesis, virus core diameter in intranuclear capsids and extracellular appearance of virus. Different stages in virus genesis, in virus envelope formation and in nuclear and cytoplasmic degeneration were observed in the few remaining, rounded and swollen, epidermal (?) spinosum cells. Their nuclei, some with marginated chromatin, harboured besides dense-cored or empty capsids, electron-dense blobs possibly representing clones of immature virus and falling apart into aggregates of small granules. In other nuclei, large clusters of dense-cored capsids, some distinctly hexagonal in shape, had accumulated in wide gaps in the nuclear membrane whereas remaining nuclear membrane portions were quadruple and often engaged in viral envelope formation. Partially enveloped capsids and naked dense-cored capsids were seen extracellularly indicating their survival outside cells. An occasional virion was present in dermal blood vessel lumina. Measurements of the electron-dense core (nucleoid) of intranuclear capsids in electronmicrographs showed that the HSV-1 core diameter differs very significantly from the core of intranuclear HSV-2 capsids, thus allowing a clear distinction by electronmicroscopy between the two HSV subtypes in plastic-embedded biopsies.

Adult↗
PubMed1987

HSV-2 replication sites, monocyte and lymphocytic cell infection and virion phagocytosis by neutrophils, in vesicular lesions on penile skin. Electronoptical studies of a biopsy.

From a heterosexual male with recurrent genital herpes simplex virus (HSV-2) infection, a fresh intraepidermal vesicle on the penile skin was excised by punch biopsy, fixed and processed for electron microscopy. Differing locations and appearances of capsids and virions were studied to elucidate true host or destroyer cells. HSV-2 propagation and virion formation occurred predominantly in multi- or mononucleate spinosum cells situated at the base of the vesicle. However, some of the monocytes, young histiocytes and lymphocytic cells floating in the vesicle fluid were also involved. They harbored a small number of intranuclear capsids, designating the cells as viral (capsid) carriers. Infrequently encountered free virions in the vesicle fluid were invariably seen near neutrophils. All neutrophil granulocytes examined lacked intranuclear capsids. In contrast, distinct evidence of phagocytosis of virions and some capsids by neutrophils was found in the vesicle fluid near apical portions of spinosum cells packed with virions, or in neutrophils located between virion-loaded spinosum cells in the base lining of the vesicle. In the cytoplasm of neutrophils, single and lysosome-enclosed clusters of virions were noted. Myelin figures and vacuolation of lysosomes in free-floating neutrophils were suggestive of virion distintegration. Viral propagation and abundant virion formation, beside neutrophil and lymphocyte attack, eventually lead to spinosum cell destruction. The minimal cytopathic effects (CPE) observed in involved monocytes and lymphocytic cells floating in the vesicle fluid suggest that these cells might function as vehicles for HSV-2 (capsid) transport to the exterior or interior.

Adult↗
PubMed1984

Ultrastructural and histophysiological studies on the blood-nerve barrier and perineurial barrier in leprosy neuropathy.

Onset and nature of ultrastructural changes in endoneurial vasa nervorum during the pathogenesis of leprosy neuropathy and possibly associated alterations in the "blood-nerve barrier" were investigated, together with perineurial barrier functioning, in mice infected 20-28 months previously with Mycobacterium leprae and in (ageing) non-infected mice. Barriers were tested by i.v. administration of markers (Trypan blue and ferritin) 1-4 days before killing the mice. Twenty-eight months after infection, histopathology of sciatic nerves was comparable to that seen in sensory nerves in clinically early human (borderline-) lepromatous leprosy. Schwann cells and endoneurial macrophages were bacillated, endothelia of endoneurial vessels not, and the perineurium rarely. Many infected mice and all (ageing) controls possessed ultrastructurally and functionally normal endoneurial vessels. Their continuous endothelium with close junctions had prevented marker passage, even when surrounding endoneurial tissue cells were quite heavily bacillated. The perineurium was also normal. By contrast, in infected mice showing hind limb paralysis serious histopathologic involvement and large globi of bacilli intrafascicularly in sciatic nerves, endoneurial blood vessels were abnormal. Open endothelial junctions, extreme attenuation, fenestrations, and luminal protrusions were all features comparable to neural microangiopathy encountered in leprosy patients (Boddingius 1977a, b). The "blood-nerve barrier" clearly had become defective allowing excessive exudation of Trypan blue and ferritin, via four pathways from the vessel lumen, deep into surrounding endoneurial tissues but halted by a normal perineurial barrier. Markers in such "blue" nerves were not found in bacillated or non-bacillated Schwann cells, thus denying significant phagocytotic and lysosomal activities of Schwann cells at this stage of neuropathy. Possible implications of barrier performances for anti-leprosy drug treatment of patients are discussed.

Age Factors↗
PubMed1976

The influence of social rank on adenohypophysial cell activity in Salmo irideus. With special reference to basophil ACTH-cells of the proximal pars distalis.

In nine cell types of the adenohypophysis in untreated adult rainbow trout, histologically different activity phases, seasonal changes in activity, and the relation between certain cell types and the interrenal gland, thyroid or gonads were investigated by light and, occasionally, by electron microscopy. Special attention was given to the effect of social rank on the synthetic activity in adenohypophysial cells of trout kept in small groups in which a social hierarchy with one (light) dominant and several (dark) submissives is established. Cell types in the rostral pars distalis were azocarminophil (I) or amphiphil (II). Proximal pars distalis cell types were slightly basophil (IV), orangeophil (V), strongly basophil (VI) or chromophobe (VII). In the pars intermedia, cell types were amphiphil (VIII) or very slightly basophil (IX). Type III was a non-secretory supporting (?) cell. Histologically different activity phases abounded in type IV cells, which mainly occurred in the proximal pars distalis but were also found dispersed in the rostral pars distalis, the pars intermedia and the neurohypophysis. Influences of social rank were pronounced in type IV cells. Phases with a high synthetic activity were exclusively found in submissive animals, phases with a low synthetic activity occurred in dominants. As a positive relation existed between type IV cell activity and the social rank dependent activity of the interrenal gland, it was suggested that type IV cells produce ACTH. In (dominant) male trout treated with DOCG or ACTH, colloid-containing type IV cell phases, reflecting accumulation of the secretory product, were found. This supported the earlier suggestion that ACTH in the trout is produced in the basophil type IV cells and not, as reported in the literature, in cells comparable to type II.

Adrenocorticotropic Hormone↗
PubMed1976

Ultrastructural changes in blood vessels of peripheral nerves in leprosy neuropathy. I. Tuberculoid and borderline-tuberculoid leprosy patients.

Radial or superficial peroneal nerve biopsies of 6 patients with tuberculoid or borderline-tuberculoid leprosy and 6 control nerve biopsies were examined by electron microscopy. Endoneurial blood vessels showed histopathology in all the leprosy patients. Changes, in particular, involved the basement membrane in postcapillary venules and venules. Multilayered parellel basement membranes, with collagen and ground substance, formed a thick coat ("hyaline zone") around the vessels. It is suggested that the zone inhibits passage of nutrients and metabolites and, thus, contributes to or is the main cause of the local destruction of (unmyelinated) nerve fibres and the lack of nerve fibre regeneration observed in this type of leprosy. The perivascular zone, presumably, is produced by pericytes in response to defects in the "blood-nerve barrier" of endoneurial vessels. In granulomata of leprosy skin lesions, a perivascular zone was not present. The endothelium of endoneurial vessels, in affected nerves, generally was normal. Occasionally, however, gaps and fenestrations were seen and there were histological indications that leakage of blood plasma had occurred through the gaps and through the basement membrane of the endothelium. Occlusion of endoneurial vessels was found only in the oldest patient and the degeneration of nerve fibres generally observed thus is considered not to be caused by ischaemia. Histopathology in epi-and perineurial vessels was definitely less pronounced than in endoneurial vessels.

Adolescent↗