Search PubMed⌕ Search

Biomedical subjects

A J Howie

Publications and source records attributed to A J Howie.

126 records · Page 7Linked to original sources
PubMed1985

The glomerular ultrastructural distribution of immunoglobulin G in hyperalbuminaemic (protein-overload) proteinuria.

Female Munich-Wistar rats were given intraperitoneal injections either of bovine serum albumin to induce proteinuria or of water as a control. Their kidneys were fixed in situ. An ultrastructural technique was used to demonstrate IgG antiperoxidase antibodies either injected from a heterologous species or autologous, induced by immunization with horseradish peroxidase. Photometry of electron micrographic negative was used to determine the distribution of antiperoxidase antibodies. In glomeruli of control animals IgG was present in the basement membrane. There were three sites at which the passage of IgG across the basement membrane was hindered: between blood plasma and the lamina rara interna, between the lamina densa and the lamina rara externa, and between the lamina rara externa and the urinary space. Glomeruli of proteinuric animals were variable in appearance, some showing little structural damage and others showing marked changes with loss of epithelial foot processes and accumulation of vacuoles and protein droplets in epithelial cells. Both types of glomeruli contained IgG in the urinary space. The distribution of IgG in the basement membrane of both types was similar. Compared with control animals there was less IgG in the basement membrane and IgG was distributed uniformly across the basement membrane. The proteinuria in hyperalbuminaemia (protein-overload) is associated with a diffuse change in the barrier function of the glomerular basement membrane to IgG which is, at least in the initial stages, not related to structural changes in glomerular epithelial cells.

Albuminuria↗
PubMed1985

The distribution of cathepsin B in human tissues.

Cathepsin B is a lysosomal enzyme of importance in many physiological and pathological processes. Its distribution in human tissues was studied by an indirect immunoperoxidase method. Cathepsin B was demonstrated in macrophages, hepatocytes, renal tubules, gastrointestinal epithelium and fibroblasts, confirming previous studies. It was demonstrated for the first time by immunohistology in several other tissues, especially stratified squamous epithelium, transitional epithelium, salivary glands, pancreas, central and peripheral neuronal cell bodies, trophoblast and all endocrine organs. Widespread distribution of cathepsin B has been postulated several times but this is the fullest evidence that the enzyme indeed occurs in many organs. In pathology cathepsin B has so far been thought to be involved in demyelination, emphysema, rheumatoid arthritis and neoplastic infiltration.

Cardiovascular System↗
PubMed1985

Further studies on the glomerular tip lesion: early and late stages and life table analysis.

The glomerular tip lesion is a distinctive abnormality of the kidney associated with steroid-responsive proteinuria. It was first recognized at the stage at which there is a group of intracapillary foam cells adherent to Bowman's capsule next to the tubular origin. Late stages were investigated by studying changes to the lesion with time in seven patients known to have the foam cell stage in their first renal biopsy, and by identifying 13 patients whose biopsies had similar changes. Early stages were investigated by the study of biopsies from three patients who at some time had evidence of the tip lesion. The lesion appears to begin with leak of protein through glomeruli that are normal on light microscopy, with damage to proximal tubular epithelium. Adhesion of the glomerular tuft to Bowman's capsule and the development of foam cells then follows. The lesion is permanent but evolves either into a thin tip adhesion or into a larger area of hyalinosis and sclerosis, at first segmental and then global. The lesion can be specifically identified at all stages except the earliest. Actuarial analysis of 37 patients with the tip lesion indicated a 10-year survival of 55 per cent. The only factor identified that appeared to have an influence on survival was satisfactory control of proteinuria.

Actuarial Analysis↗
PubMed1985

Effect of neuraminidase on the expression of the 3-fucosyl-N-acetyllactosamine antigen in human tissues.

The monoclonal antibody AGF4.48 detects the 3-fucosyl-N-acetyllactosamine carbohydrate structure and reacts with a variety of human tissues, as shown by an immunoperoxidase method on paraffin sections of formalin fixed material. The intensity and distribution of the immunoperoxidase reactivity were affected by treatment of sections with neuraminidase. In some sites, such as bone marrow, brain, breast, and pituitary, the reaction was more intense after neuraminidase treatment. In several organs, including kidney, oesophagus, pancreas, submandibular gland, and uterus, the reaction was more widespread after neuraminidase treatment. Other organs, such as liver, lung, lymph node, skin, and uterine tube, showed an altered distribution of reactivity with AGF4.48 after sections were treated with neuraminidase. These results show that the 3-fucosyl-N-acetyllactosamine antigen is cryptic in many tissues. The antigen is masked to a variable extent in different tissues by neuraminic acid residues and can be revealed by the simple procedure of pretreating sections with neuraminidase. The value of using AGF4.48 antibody in combination with the enzyme neuraminidase to show accessible and cryptic antigen is that this reveals distinctive patterns of sialylation within various normal tissues. Whether similar patterns occur in disease will be of particular interest.

Antibodies, Monoclonal↗
PubMed1985

Further studies of the reasons for the lack of alveolar infection during influenza in ferrets.

Intratracheal inoculation of influenza virus in the ferret was followed by a more severe airway infection than that produced by nasal infection and was mainly bronchiolar rather than bronchial. Also, virus isolation from the alveolar zone of the lung together with immunofluorescence and immunoperoxidase techniques showed that some virus reached the alveoli. Nevertheless, there was no subsequent alveolitis suggesting the existence of a clearance phenomenon. Alveolar macrophages were shown to have phagocytosed virus in vivo and phagocytosis studies in vitro showed that two mechanisms could operate to eradicate the virus. First, a rapid destruction of virus and second an abortive cycle of replication which produced virus antigen but not infectious virus. Experiments with large doses of virus indicated that after intranasal inoculation little virus reached the alveoli so it would probably be quickly cleared by the macrophages.

Animals↗
PubMed1984

The glomerular tip lesion: a previously undescribed type of segmental glomerular abnormality.

We describe a distinctive and previously undescribed abnormality of the kidney. It consists of a combination of changes in the glomerulus and in the proximal convoluted tubule. The glomerular abnormality consists of a well-localized collection of intracapillary foam cells and marked vacuolation of the adjacent glomerular epithelial cells. The abnormality is always situated in the same position in the glomerular tuft namely adjacent to the origin of the proximal convoluted tubule, with adhesion to Bowman's capsule. The rest of the tuft appears normal by light microscopy but shows foot-process fusion by electron microscopy. The abnormality of the proximal convoluted tubular cells invariably affects the first part of the tubule adjacent to the glomerulus but in some cases involves the tubules more extensively in the cortex. Study of a series of 100 2-micron serial sections from one case indicated that probably every glomerulus had a lesion at the origin of the tubule. A study of 185 renal biopsies nearly all with segmental lesions revealed biopsies from 20 patients with this distinctive abnormality. There were 14 males, age 20-57, median 44 years, and six females age 19-65, median 22 years, all presenting with proteinuria, nearly all with the nephrotic syndrome. All except four were treated with steroids and in all those treated the proteinuria improved. Only one patient not treated with steroids had progressive renal impairment. Four patients died, none from renal failure. This lesion, the glomerular tip lesion, as we have called it, seems to be a well-defined and specific pathological entity. It has some similarities to minimal change nephropathy but there are clear and important differences. Previously it may have been included in series of cases of 'focal glomerulosclerosis' but that term is imprecise and is generally taken to have an unfavourable clinical course. For these reasons it is inappropriate to use 'focal glomerulosclerosis' as a name for the glomerular tip lesion.

Adult↗
PubMed1984

Widespread distribution in human tissues of an antigenic determinant of granulocytes.

The monoclonal antibodies AGF4 .48 and AGF4 .36 have previously been shown to distinguish human granulocyte lineage cells from other peripheral blood and bone marrow cells. The AGF4 .48 antigen, which is carbohydrate in nature, together with similar antigens described by numerous investigators have been considered specific differentiation antigens of myeloid cells. In immunohistological studies of a wide range of normal tissues, the AGF4 .48 antibody selectively stained cells in several apparently unrelated tissues. These included proximal tubules and descending thin limbs in the kidney, parietal cells in the stomach, a variety of other epithelial cells, astrocytes in the brain, and cells in the anterior pituitary containing adrenocorticotrophic hormone. The AGF4 .36 antibody gave similar results on kidney, stomach and pituitary. These findings emphasise the importance of assessing the binding of monoclonal antibodies, which appear unique in their reactivity with blood cells, to non-haemopoietic tissues before assigning specificity to reagents. The distribution of cells expressing the AGF4 .48 and AGF4 .36 antigen correlates with the occurrence of the 3-fucosyl-N-acetyllactosamine carbohydrate structure in various secreted glycoproteins.

Animals↗
PubMed1983

Extra-tubular deposits of Tamm-Horsfall protein in renal allografts.

Sections from 266 renal allografts that had been transplanted and removed were studied to determine the prevalence of deposits of Tamm-Horsfall protein outside tubules and resulting from tubular rupture, detected by the periodic acid-Schiff (PAS) reaction. The PAS-positive material was shown to be Tamm-Horsfall protein by an indirect immunoperoxidase method. Deposits were found in 152 kidneys (57.1 per cent.), and were commonest at the cortico-medullary junction and in arcuate veins. Deposits were rarely associated with thrombosis or an inflammatory response, and often contained tubules that were reforming. The lesions were rare in grafts totally infarcted from occlusion of the main vessels. Deposits were mostly found in kidneys that had tubular damage from acute rejection reactions, often with ureteric damage, but a few had ureteric obstruction alone. Old deposits were identified in kidneys showing chronic vascular rejection. No features of the deposits themselves could separate cases with ureteric obstruction alone from the other cases. Not every case with ureteric obstruction had the lesions. Extra-tubular deposits of Tamm-Horsfall protein are common in renal allografts and only rarely indicate a specific, surgically-correctable cause of graft dysfunction, namely ureteric obstruction.

Basement Membrane↗
PubMed1982

The cells in tonsillar crypts.

The material lying within the crypts of 11 human palatine tonsils was studied by scanning and transmission electron microscopy. There was a mixture of desquamated epithelial cells and various non-epithelial cells, mainly lymphocytes, with some mononuclear phagocytes and plasma cells, and a few erythrocytes, neutrophil leucocytes and mast cells. Many of the cells were degenerating and there was a great deal of cellular debris. The non-epithelial cells seemed to have entered the crypts from the lining epithelium, probably by being caught up between superficial squamous epithelial cells as they sloughed into the lumen. The widespread cellular degeneration in the crypts suggested that the cells were being lost from the body and that they had no further immunological or phagocytic function. This also suggested that the first level of defence mechanisms of the tonsil was in the epithelium, not in the crypt lumen.

Adolescent↗
PubMed1982

The definition of branchial cysts, sinuses and fistulae.

In a study of 57 lateral cervical lesions, 46 cysts were found to form a homogeneous group and four sinuses and fistulae formed another homogeneous group. The cysts lay behind the angle of the mandible, and were lined by stratified squamous epithelium resting on lymphoid tissue, with part of the wall resembling a lymph node. The sinuses and fistulae had life-long external openings and were muscular tubes lined by respiratory-type epithelium. The other seven lesions had some other structure. Such uniformity of clinico-pathological features of supposed branchial lesions has not been demonstrated before and no explicit definition of them has ever been published. We suggest that our empirical findings in the two groups of lesions can be used as clinico-pathological definitions of "branchial cysts' and "brachial sinuses and fistula' respectively. Lesions with other features should be given other names.

Adolescent↗
PubMed1981

The lining of branchial cysts studied by electron microscopy and enzyme histochemistry.

The lining of five branchial cysts from patients aged from 17 to 51 was studied by histochemical methods for non-specific acid esterase and acid phosphatase and by scanning and transmission electron microscopy. The stratified squamous epithelium was shown to be a specialised structure, with a few microvillous cells on the surface and an intra-epithelial network of channels containing lymphocytes, notable T cells, and mononuclear phagocytic cells. The appearance of the cyst lining was similar to that of the epithelium lining the crypts of palatine tonsils. The demonstration of a complex lympho-epithelial lining of the cysts does not settle the controversial question of their origin, but it must be taken into account by hypotheses explaining the development of branchial cysts.

Adult↗
PubMed1980

Scanning and transmission electron microscopy on the epithelium of human palatine tonsils.

Twelve human palatine tonsils were studied by scanning and transmission electron microscopy. The epithelium lining the tonsillar crypts was shown to be stratified squamous in type, with an extensive system of channels occupying nearly the full thickness of the epithelium. The channels were infiltrated by lymphocytes, plasma cells and mononuclear phagocytic cells. Specialised surface cells, or M cells, were also seen. These had microvilli and surrounded lymphocytes which were brought very close to the crypt lumen. The presence of numerous holes in the crypt epithelium was thought to be an artefact resulting from the delicate nature of the M cells. These showed the organisation of the epithelium related to the function of the tonsil as part of the gut-associated lymphoid tissues. The tonsil has similarities to other gut-associated lymphoid organs but also has its own particular features.

Adolescent↗
PubMedDate not supplied

Treatment of vasculitic IgA nephropathy.

BACKGROUND: Patients with IgA nephropathy and histological vasculitic/crescentic lesions have a poor prognosis. We performed a retrospective study to assess whether treatment with steroids and immunosuppressants would preserve renal function by healing these lesions and thereby prevent progression to glomerular sclerosis and renal failure. METHODS: Sixteen patients with IgA nephropathy and a vasculitic/crescentic glomerulonephritis diagnosed by renal histology were treated with a reducing course of prednisolone (initial dose 60 mg/day). Six patients also received cyclophosphamide (2 mg/kg/day) for three months followed by azathioprine (100 mg/day) in five patients. Ten patients received azathioprine (100 mg/day) in addition to prednisolone. The median duration of treatment was 12 months (range 5-30 months). At the end of treatment each patient had a second renal biopsy. RESULTS: Following treatment there was a significant reduction in the proportion of glomeruli with acute vasculitic lesions from a median of 17.4% (range 4.8-57.5%) to 0 (range 0-15.8%) (p=0.001). There was an increase in the proportion of globally sclerosed glomeruli from a median of 13.4% (range 0-44.4%) to 21.5% (range 0-90%) after treatment but this did not significantly differ from baseline (p=0.24). The proportion of renal cortex with chronic tubular atrophy increased from 2.55% (0.4-57.7%) to 11.3% (0.3-61%) (p=0.09). The median duration of follow-up was 30 months (inter-quartile range 6-30 months). At both 12 and 24 months there was no significant increase in serum creatinine. Four patients, however, developed end-stage renal failure between 24 and 81 months. CONCLUSION: In this retrospective study we show that treatment with steroids and immunosuppressants leads to healing of vasculitic lesions and may thus arrest progression of glomerular scarring.

Adolescent↗