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Biomedical subjects

A J Howie

Publications and source records attributed to A J Howie.

At least 19 recordsLinked to original sources
PubMed1995

Detection of human 11 beta-hydroxysteroid dehydrogenase isoforms using reverse-transcriptase-polymerase chain reaction and localization of the type 2 isoform to renal collecting ducts.

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD), responsible for the interconversion of hormonally active cortisol to inactive cortisone, dictates specificity for the mineralocorticoid receptor (MR) in the distal nephron and colon. Two isoforms of human 11 beta-HSD have been cloned, an NADP(H)-dependent (type 1) dehydrogenase/oxo-reductase enzyme, and a high-affinity NAD-dependent (type 2) unidirectional dehydrogenase. Using the reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of RNA extracted from human adult tissues, type 1 11 beta-HSD mRNA was found in decidua, placenta, liver, lung, spleen, kidney medulla, cerebellum and pituitary, but was absent in kidney cortex, sigmoid and rectal colon, salivary gland and thyroid. In contrast, type 2 11 beta-HSD mRNA was found only in placenta and in the classical mineralocorticoid target tissues, kidney cortex, kidney medulla, sigmoid and rectal colon, salivary gland, and colonic epithelial cell lines (AAC1 and RGC28). In situ hybridization studies of renal cortex, cortico-medullary junction and medulla using a 35S-labeled antisense cRNA probe for type 2 human 11 beta-HSD, revealed specific localization of type 2 11 beta-HSD mRNA expression exclusively to renal cortical and medullary collecting ducts. Type 1 and type 2 isoforms of human 11 beta-HSD are expressed in a distinct tissue-specific fashion, in keeping with the proposed differences in their physiological roles. Type 2 11 beta-HSD is found predominantly in mineralocorticoid target tissues where it serves to protect the MR in an autocrine fashion.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1995

Pathogenesis of segmental glomerular changes at the tubular origin, as in the glomerular tip lesion.

Segmental abnormalities at the glomerulo-tubular junction, or tip changes, are a common and early feature in several experimental and human renal disorders. Scanning and transmission electron microscopic study of an experimental model, Lewis rats given anti-glomerular basement membrane antibodies, showed that at 5 days there were monocytes/macrophages in glomerular capillary loops next to the tubular origin, with abnormalities of visceral epithelium, including prolapse of groups of these cells into the tubular origin. At 12 days, there was contact and adhesion between glomerular capillary loops and Bowman's capsule. Transmission electron microscopic study of human renal biopsies showed that the human tip changes resembled the later lesions seen in rats, with intracapillary foam cells confirmed by immunohistological study to be monocytes/macrophages. These findings show that abnormalities of the glomerular tuft precede adhesion to Bowman's capsule and that the earliest changes recognized by light microscopy in human renal biopsies are relatively late in their natural history, meaning at least several days old. Prolapse of visceral epithelial cells into the tubular origin may explain the characteristic site of tip changes.

Animals↗
PubMed1995

An optical practice based diabetic eye screening programme.

In many cases, blindness due to diabetic retinopathy can be prevented provided treatment with laser photocoagulation is used at the correct time. A screening programme is required to identify cases of sight threatening retinopathy. An optical practice based diabetic eye screening programme has been established in Dorset. The optometrist undertaking the examination is paid a fee. The findings are recorded on a coded form and sent to the hospital diabetologist who recalls positive cases. Seventy-six optical practices have joined the scheme and 3224 patients have been screened in the first 6 months (Dorset population 655,000). In the Poole area (population 230,000), 1922 patients were screened and 129 (6.7%) were recalled in 6 months. Outcome of 3 months screening, identified 59 recalls. Referral to the opthalmologist was made in 15 cases for potentially sight threatening retinopathy, 14 cases were followed in the diabetic clinic for significant background retinopathy, and 24 cases were returned to the annual screening in the optical practices. Six cases where the patients either failed or were unable to attend were reviewed by the GP. An optical practice based diabetic eye screening programme has been successful in screening a large number of patients.

Diabetic Retinopathy↗
PubMed1995

Tamm-Horsfall protein in reflux nephropathy.

The distribution of Tamm-Horsfall protein, the main protein in normal urine, was studied immunohistologically in the kidneys of 70 pigs with unilateral vesico-ureteric reflux but without outflow obstruction. Strains of Escherichia coli were inoculated in the bladder. Inflammatory changes of reflux nephropathy (chronic pyelonephritis) were found in 52 pigs. There were extra-tubular deposits of Tamm-Horsfall protein in the kidneys of only 26 pigs. These deposits were small, increased in prevalence as the size of inflamed areas increased, and were not associated with deposits of the protein in glomeruli. These findings suggest that escape of Tamm-Horsfall protein from tubules and backwash into glomeruli are not major features of low pressure reflux nephropathy, unlike the findings in outflow obstruction of the lower urinary tract. There was no evidence that a reaction to Tamm-Horsfall protein was important in the pathogenesis of reflux nephropathy.

Animals↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗