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Biomedical subjects

A J Howie

Publications and source records attributed to A J Howie.

At least 73 records · Page 4Linked to original sources

Distribution patterns of cytokeratins in epidermis and horny teeth of the adult sea lamprey, Petromyzon marinus.

An immunohistochemical characterization of cytokeratins in the skin tissues of the sea lamprey, Petromyzon Marinus was performed using a panel of monoclonal antibodies. Cytokeratins typical for simple epithelia have been detected in the epithelial cells, with a 8/18 pair expression. Granular cells and skein cells showed a labelling of cytokeratins 7, 8, 18 and 19, that is observed also in the non-keratinized layers of the horny teeth. Similar cytokeratins occur in the outermost cell layers of the epidermis; cytokeratin 19 shows a comparatively weaker reaction. These results suggest that the cytokeratin patterns in the above types of cells of adult epidermis are quite different from those in ammocoetes where the expression of cell specific cytokeratins may be correlated with specific programs of epidermal differentiation.

Age Factors↗

Asymmetrical atrophy of the renal medulla: a previously unreported abnormality.

Investigation of the smaller of a pair of unequal kidneys showed a band of atrophy in the inner medulla, sparing the papillary tip, which was viable and contained collecting ducts. The kidney had extensive cortical atrophy with glomerulocystic disease and multiple tiny renal cell neoplasms. These changes were considered secondary to the medullary lesion. Study of 85 other kidneys taken a autopsy and surgery showed 8 other cases with similar band-like atrophy in the medulla to various degrees. All 9 cases had severe vascular disease. This asymmetrical or band-like atrophy of the renal medulla seemed to be fairly common but previously unreported, could be differentiated from renal papillary necrosis, and was most likely due to an episode of severe ischaemia, possibly in kidneys with pre-existing vascular narrowing.

Adult↗

Morphometric studies of acute renal failure using anti-brush-border and other antisera.

Correlations have been shown between renal excretory function and the extent of immunohistological staining in the kidney of proximal tubular brush border and Tamm-Horsfall protein. These findings confirm the importance of the integrity of the proximal tubule in control of the glomerular filtration rate and also show that the thick limb of the loop of Henle is damaged, as well as the proximal tubule, in renal failure.

Acute Kidney Injury↗

Knowledge of renal histology alters patient management in over 40% of cases.

There is great debate as to whether the benefit gained from the knowledge of renal histology outweighs the risk to the patient from the biopsy procedure. We conducted a prospective study of 276 native renal biopsies performed on 266 patients from a single centre in 1991 to assess the effect of the knowledge of renal histology on patient management. Biopsies were performed under ultrasound guidance using the Trucut biopsy needle. The indications for biopsy were: non-nephrotic proteinuria alone (25), haematuria and proteinuria (28), nephrotic range proteinuria (28), acute renal failure (31), haematuria alone (36), and chronic renal failure (128). Two hundred and sixty-three biopsies were successful. The mean number of glomeruli obtained was 23, range 0-115. Eight patients developed macroscopic haematuria of which two required blood transfusion. The result of the biopsy altered management in 24/28 (86%) of cases of nephrotic range proteinuria, 22/31 (71%) of cases of acute renal failure, 58/128 (45%) of cases of chronic renal failure, 9/28 (32%) of cases with haematuria and proteinuria, 3/25 (12%) of cases with non-nephrotic proteinuria alone, and 1/36 (3%) of cases with haematuria alone. management was altered in 42% of cases overall. These data suggest that knowledge of renal histology is essential in the management of patients with renal disease.

Adolescent↗

Classical versus non-renal Wegener's granulomatosis.

We investigated whether 'limited' or 'non-renal' Wegener's granulomatosis (WG) differs from classical or 'renal' WG. Renal WG is characterized by necrotizing granulomatosis of the upper and or lower respiratory tract, accompanied by systemic vasculitis and focal segmental necrotizing glomerulonephritis. This last feature is absent in non-renal WG. In a prospective follow-up study of all identified cases presenting to a single teaching hospital, we reviewed 22 patients with non-renal WG, and compared their presentation and outcome with that of 28 patients with renal WG. Clinical and laboratory assessment of disease activity, frequency of death, relapse and end-stage renal disease were assessed. The two groups differed in clinical presentation, laboratory features and outcome. The group with non-renal WG had less cutaneous and pulmonary disease; the haemoglobin, white cell count and platelet count tended to be normal. Residual mortality was confined to the renal group. However, the groups shared many features, particularly their requirement for immunosuppressive therapy, since WG causes major tissue destruction regardless of whether it is a localized or widespread process. At the immunopathological level, the two groups appear to be part of a single disease spectrum. Importantly, the non-renal WG group may change the pattern of their disease to involve the kidney. Long-term follow-up of such patients is therefore essential.

Adult↗

Distribution of immunoreactive Tamm-Horsfall protein in various species in the vertebrate classes.

A sheep antibody to human Tamm-Horsfall protein, the major protein in normal urine, was used in an immunohistological study of organs of 48 species of vertebrate animals, representing the classes Mammalia, Aves, Reptilia, Amphibia, Osteichthyes and Chondrichthyes. Immunoreactivity was shown in the thick limb of the loop of Henle in the kidney of mammals, but there was no reactivity with tissues of birds or reptiles. Superficial layers of the skin of several amphibians and fish, superficial layers of the oral mucosa and gills of fish, and the distal tubules of the kidney of some amphibians, reacted with the antibody. Immunoreactivity with mammalian kidney was removed by passage of the antibody down an immunoadsorption column coated with human Tamm-Horsfall protein, and amphibian immunoreactivity was removed by incubation of the antibody with material prepared from frogs in the same way as Tamm-Horsfall protein. These findings suggest that immunoreactive Tamm-Horsfall protein appeared early in vertebrate phylogeny, initially in skin and gills and later in kidney, and that although conserved in evolution, it shows antigenic differences between amphibians and mammals. Its distribution is consistent with the hypothesis that is acts as a waterproofing agent.

Amphibians↗

Segmental sclerosing glomerular lesions.

Segmental sclerosing glomerular lesions are usually all grouped together and called focal segmental glomerulosclerosis. This has meant that the term that was originally used for a defined clinical entity is now applied to a variety of conditions in man and experimental animals, with the assumption that the morphological changes are the same in all conditions. Studies of the position of segmental lesions within glomeruli, the size of glomeruli and the proportion of glomeruli affected have shown that this assumption is wrong. Such studies have identified a disease that corresponds to the original clinical concept of focal segmental glomerulosclerosis. This begins with the nephrotic syndrome in patients whose renal biopsies show large glomeruli with mesangial hypercellularity and segmental lesions at every tubular origin. Later the biopsies have segmental lesions throughout the glomerular tuft. This disease differs clinically and pathologically from other conditions that have segmental sclerosing lesions, such as in patients with reduced renal mass or patients with hypertension and proteinuria. The term focal segmental glomerulosclerosis is now too ambiguous and unsatisfactory to be used without qualification.

Adult↗

Distinctive patterns of renal neoplasms containing Tamm-Horsfall protein.

Sections of 114 renal neoplasms from adults, and 2 renal rhabdoid tumours from children, were examined by an indirect immunoperoxidase method using two antibodies to Tamm-Horsfall protein. Forty-five of the adult neoplasms were also examined with an antibody to proximal tubular brush border. Tamm-Horsfall protein is normally only found in the cells of the thick limb of the loop of Henle, and there are widely divergent reports on its occurrence in renal neoplasms. In the present series, Tamm-Horsfall protein was detected in parts of 31 neoplasms. Four distinctive patterns of cell contained the protein: cells with a paranuclear inclusion typical of rhabdoid tumours; 'plasma rich' cells, which were large cells with cytoplasm that was centrally dense and peripherally clear; eosinophilic cells forming one type of papillary structure; and giant cells. The areas containing Tamm-Horsfall protein did not express markers of proximal tubular brush border, and appeared white to the naked eye, rather than the yellow of typical clear cell carcinomas. Tamm-Horsfall protein can therefore be found in renal neoplasms. The four distinctive patterns of positive cells appear to represent neoplastic phenotypes of thick limb cells. This has implications for the classification of renal neoplasms and for theories of their origin.

Adult↗

Glomerulonephritis in rheumatoid arthritis.

We present data on 10 patients with RA who developed glomerulonephritis which was not related to gold or penicillamine therapy. Although two of these patients had received gold this had been discontinued 13 and 18 yr before the diagnosis of glomerulonephritis. Seven patients presented with nephrotic syndrome and three with proteinuria and microscopic haematuria. Renal histology showed a membranous nephropathy (five patients), mesangial IgA nephropathy (two patients), focal segmental necrotizing glomerulonephritis (two patients) and focal segmental glomerulosclerosis (one patient).

Adult↗

Reconsideration of the development of the distal tubule of the human kidney.

The human kidney develops from 2 embryonic tissues, the ureteric bud and the metanephric blastema. The site in the adult renal distal tubule corresponding to the junction between these tissues has never been established unequivocally and is usually said to be the union between the collecting duct and the connecting piece, based on microdissection evidence. We have examined kidneys from 21 human fetuses of various ages using an immunohistological method for substances related to the ABO blood group system, various cytokeratins including those detected by the monoclonal antibody PKK2, and Tamm-Horsfall protein. The ureteric bud and connecting piece expressed the type 1 precursor chain of ABO antigens mostly early in gestation, the H antigen of the ABO system mostly later in gestation, and cytokeratins detected by PKK2. The induced nephrons after the S-shaped body stage expressed Tamm-Horsfall protein. In the adult renal tubule, distal from the macula densa, it was already known that there is a sharp junction between the segment expressing Tamm-Horsfall protein and the more distal segment that expresses the H antigen and cytokeratins detected by PKK2. The finding that the ureteric bud and connecting piece express the same antigens as this segment while the S-shaped body eventually expresses Tamm-Horsfall protein is consistent with the concept that (1) the connecting piece arises from the ureteric bud, not the S-shaped body, and (2) the junction of ureteric bud derivatives and metanephric blastema derivatives is on the distal side of the macula densa at the distal end of Tamm-Horsfall staining.

ABO Blood-Group System↗

Relapses in patients with a systemic vasculitis.

Treatment with cyclophosphamide and steroids has greatly improved survival in patients with systemic necrotizing vasculitis but does not always provide a complete cure. There are as yet few data on the incidence, pattern and outcome of relapses in these diseases. We studied relapses in 150 consecutive patients with an idiopathic necrotizing vasculitis: 12 with classical polyarteritis (CPAN); 95 with microscopic polyarteritis (MPA); 28 with Wegener's granulomatosis (WG); and 15 with limited Wegener's granulomatosis (LWG). The relapse rates and median time to relapse in months were: CPAN, 41.7%/33; MPA, 25.4%/24; WG, 44%/42; LWG, 52%/18. The clinical features of relapse were similar to or more aggressive than those of the original presentation in CPAN and LWG and included renal disease for the first time, but in MPA and WG, relapse involved less renal involvement in the majority of cases. Laboratory tests, although often positive at relapse, were unhelpful in its prediction. The considerable accumulative non-fatal relapse rate contrasts with the very good long-term survival rates, and confirms the importance of long-term follow-up in systemic vasculitis.

Adult↗

Hypertension and end-stage renal failure in tropical Africa.

We report clinical data and autopsy renal histology in 78 patients who died from chronic renal failure in Ghana. There were 78 patients, 54 male and 24 female, and the majority were aged between 20 and 50 years. The major causes of chronic renal failure were hypertensive renal damage (38 patients) and chronic glomerulonephritis (33 patients). The most common glomerular lesion leading to end-stage renal failure was a focal segmental sclerosing glomerulonephritis. It is possible that some of these segmental sclerosing glomerular lesions were secondary to glomerular hyperfiltration caused by reduced renal mass from hypertension-induced glomerular ischaemia. A public health programme leading to better awareness of the importance of detecting hypertension and having this treated could be a major contribution to reducing by at least half the number of deaths from renal failure reported here.

Adolescent↗

Glomerular tip lesion in the 1962-66 Medical Research Council trial of prednisone in the nephrotic syndrome.

A multi-centre controlled trial of prednisone in the nephrotic syndrome in adults was run by the Medical Research Council between 1962 and 1966. Sections of renal biopsies and necropsy kidneys from the trial had been kept. These were restained 25 years later with periodic acid-methenamine silver and examined for the glomerular tip lesion, an abnormality of the kidney described after the trial in patients with the nephrotic syndrome. The glomerular tip lesion was found in material from 10 patients, representing 7% of 150 patients with the nephrotic syndrome and glomerulonephritis. In the trial, seven had been classified as minimal-change nephropathy and three as proliferative glomerulonephritis. Detailed follow-up was limited but it was known that two patients died shortly after presentation, not, apparently, from progression of the glomerular disorder; that none of the others had progressed to renal failure, at least for the duration of follow-up of the trial, 2-4 years; and that those classified as minimal-change nephropathy appeared to have behaved clinically as though they had minimal-change nephropathy. These findings show that at least one adult series of minimal-change nephropathy has contained cases of the glomerular tip lesion but that clinically this may not be an important error as the conditions behave similarly. A more important error may be to call the glomerular tip lesion a proliferative glomerulonephritis, which may lead the clinician to withhold steroids.

Adolescent↗

The mammalian glomerulotubular junction studied by scanning and transmission electron microscopy.

The structure of the junction of glomerulus and tubule was investigated in man and 5 other mammalian species (rat, mouse, ferret, rabbit and pig) by scanning and transmission electron microscopy. The junction between parietal epithelium and proximal tubular epithelium was usually abrupt but varied in position: inside Bowman's capsule, especially in the male mouse; at the anatomical tubular origin, in the rat, ferret and man; and down the tubule, in the rabbit. All animals but especially the pig had cells intermediate in appearance between parietal and tubular cells at the junction. Serial sections of 3 rat junctions studied by transmission electron microscopy showed a variety of appearances of the arrangement of parietal and tubular cells, but the glomerular aspect of the first tubular cell up to its microvillous border was always covered by parietal epithelium, even though this was reduced to a thin sheet in places. This arrangement appeared to be the rule in all species studied.

Adult↗

Different clinicopathological types of segmental sclerosing glomerular lesions in adults.

Renal biopsies and kidneys from 111 adult patients with segmental sclerosing glomerular lesions were put into different morphological groups by pathologists unaware of clinical findings. 'Overload changes' (n = 11) were large glomeruli with hilar lesions. Ten of these patients had reduced renal mass. In the 'glomerular tip lesion' (n = 10) there were changes at the tubular origin in otherwise normal glomeruli. All patients in this group had the nephrotic syndrome, completely responsive to steroids. 'Mesangial hypercellularity with diffuse segmental changes at the glomerular tip', corresponding to 'early classical focal segmental glomerulosclerosis' (n = 18), differed from the glomerular tip lesion in that glomeruli were larger and hypercellular. Most patients with this classification had the nephrotic syndrome, several were given additional immunosuppression, and less than half had complete remission. 'Diffuse multiple segmental lesions', corresponding to 'late classical focal segmental glomerulosclerosis' (n = 16), presented usually with the nephrotic syndrome, and most of these patients had no response to immunosuppression. Unlike most other groups, in 'focal segmental sclerosing lesions' (n = 56) there were genuinely focal lesions, not in every glomerulus. Most patients had asymptomatic proteinuria. Pathological study is able to classify segmental lesions that would often be grouped as 'focal segmental glomerulosclerosis' into types with different pathogenesis, clinical findings, appropriate treatment, response to treatment, and prognosis.

Adolescent↗