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Biomedical subjects

W L Clapp

Publications and source records attributed to W L Clapp.

16 recordsLinked to original sources
PubMed2000

Proteinuria: potential causes and approach to evaluation.

Proteinuria may be associated with a renal or systemic disease, or it may be isolated. The latter occurs in asymptomatic patients without evidence of any disease or abnormality of the urine sediment. Isolated proteinuria may be subdivided into two broad groups: (1) benign forms, with a favorable-to-excellent prognosis and (2) persistent forms, some of which have a worrisome prognosis. Functional proteinuria may occur in disorders with altered renal hemodynamics, usually resolves, and is not associated with progressive renal disease. Idiopathic transient proteinuria is typically discovered on routine screening and usually disappears on subsequent testing. In idiopathic intermittent proteinuria, a significant number (50%) of urine samples exhibit abnormal rates of protein excretion. Although structural abnormalities may be observed on renal biopsy, progressive renal insufficiency is unusual. In orthostatic proteinuria, the rate of protein excretion completely normalizes in the recumbent position. Long-term studies show this to be a benign condition. In persistent isolated proteinuria, at least 80% of random urine samples exhibit abnormal protein excretion. This represents a heterogeneous group, but a significant proportion of these patients have prominent renal pathologic findings and progress to serious renal disease. Proteinuria with significant renal disease may be non-nephrotic or nephrotic range. The former does not exclude glomerular disease, but tubulointerstitial or vascular disorders are also likely when proteinuria is less than 2 g/24 hours. Patients with nephrotic-range proteinuria generally have a glomerular disorder. Distinction between benign and more ominous forms of proteinuria requires careful evaluation.

Glomerulonephritis, Membranous↗
PubMed1999

Reduction in Ames Salmonella mutagenicity of mainstream cigarette smoke condensate by tobacco protein removal.

The mutagenic activity of cigarette smoke condensates (CSC) made from tobacco before and after removal of protein was assessed by the Ames Salmonella assay in bacterial strains TA98 and TA100. Removal of protein and peptides from flue-cured tobacco via water extraction followed by protease digestion reduced the mutagenicity of the resultant CSC by 80% in the TA98 strain and 50% in the TA100 strain. Similarly, reductions of 81% in TA98 and 54% in TA100 were seen following water extraction and protease digestion of burley tobacco. The significant reductions in Ames mutagenicity following protein removal suggest that protein pyrolysis products are a principal contributor to the genotoxicity of CSC as measured in this assay.

Endopeptidases↗
PubMed1996

Macrophages and chronic renal allograft nephropathy.

In a previous study we demonstrated that macrophage infiltrates stained for thromboxane A synthase (TxAS) correlated inversely with renal function six months after biopsy. We propose that macrophage based inflammation is a cofactor leading to chronic allograft nephropathy. For this study we compared four indices of renal allograft nephropathy with renal survival. The Banff Score of Inflammatory Changes (BSI) is an index of acute inflammation. The Banff Chronic Index (BCI) and Chronic Allograft Damage Index (CADI) are indexes of chronic disease. The Macrophage Index (MI) is the same as the BSI applied only to macrophages. These indices were determined on renal allograft biopsies obtained because of delayed graft function within the first week of transplantation, and for increasing plasma creatinine levels after stable function. All four indices predicted renal survival in the post-biopsy interval. MI predicted renal survival for the entire transplant period. In addition, the presence of TxAS transcripts in the renal allografts was determined using a reverse transcription-polymerase chain reaction-based assay. This confirms previous observations of TxAS in the grafts. This study supports the hypothesis that macrophage derived inflammation is a cofactor for chronic allograft nephropathy.

Biopsy↗
PubMed1995

Thromboxane synthase expression in renal transplant patients with rejection.

Thromboxane synthase (TS) catalyzes the formation of thromboxane (TxA2) in monocytes/macrophages, platelets, and various tissues. TxA2 is likely to play a role in graft dysfunction due to its vasoconstrictive and platelet aggregatory properties. We studied the expression of TS in 7 normal native kidneys, 29 consecutive renal allograft biopsies (performed for rising serum creatinine, n = 23, and delayed graft function, n = 6), and one transplant nephrectomy specimen with severe acute rejection. TS expression was determined by immunocytochemistry using a monoclonal antibody against human TS, Kon-7. Histologic grading of the transplant biopsy specimens was based on the Banff classification. The degree of TS staining was graded in the glomeruli, interstitium, tubules and vessels from 0 to 3+. Of 29 biopsies, 13 had chronic nephropathy (CN), 6 had acute rejection (AR) with chronic nephropathy (AR/CN), 4 had acute rejection (AR), and 6 had acute tubular necrosis (ATN). TS staining of native kidneys showed sporadic interstitial cells. The biopsy and transplant nephrectomy specimens showed significant staining, predominantly in the glomeruli and interstitium. Positively staining cells appeared to be of macrophage/monocyte lineage by morphology. The mean glomerular staining grade was significantly increased in specimens with AR (2.3 +/- 0.9) and the mean interstitial staining was increased in specimens with AR/CN (2.2 +/- 0.9). Follow-up renal function 6 months post-biopsy showed that patients with higher TS staining grades had a faster decline in graft function. In conclusion, TS expression is increased in patients with acute rejection with or without chronic nephropathy and is associated with more rapid deterioration in function.

Adult↗
PubMed1994

Segmental localization of mRNAs encoding Na(+)-K(+)-ATPase alpha- and beta-subunit isoforms in rat kidney using RT-PCR.

To characterize the expression of genes encoding the alpha- and beta-subunit isoforms of the Na(+)-K(+)-ATPase in rat kidney, we used reverse transcription (RT)-PCR of microdissected renal structures combined with quantitation of subunit isoform mRNAs in the major renal parenchymal zones. Transcripts for alpha 1, alpha 2, alpha 3, beta 1, and beta 2 subunit isoforms were detected by RT-PCR in microdissected glomeruli, proximal convoluted tubules, medullary thick ascending limbs of Henle, cortical and inner medullary collecting ducts. The truncated alpha 1 (alpha 1-T) isoform was also amplified from cortex, outer and inner medulla and isolated glomeruli, but it was not detected in these nephron segments. The DNA sequence of the renal alpha 1-T PCR product was identical to that of the cDNA previously cloned from aortic smooth muscle cells. RNA dot-blot analysis indicated that the alpha 1, alpha 2, and alpha 3 isoforms contributed approximately 70%, approximately 20%, and approximately 10%, respectively, of the total alpha isoform mRNA in each parenchymal zone. RNase protection assays determined that the beta 1 and beta 2 isoforms accounted for approximately 95% and approximately 5%, respectively, of the beta isoform mRNA in each zone. These data provide definitive evidence for the differential expression of mRNAs encoding all the alpha and beta isoforms in the renal parenchyma, and for the coexpression of these isoforms in the nephron segments examined. The results suggest the potential expression of up to eight different Na(+)-K(+)-ATPase isoenzymes in the kidney, and for multiple molecular levels of regulation of renal Na(+)-K(+)-ATPase expression.

Animals↗
PubMed1994

Differential expression and induction of mRNAs encoding two inducible nitric oxide synthases in rat kidney.

We used quantitative PCR methods and renal microdissection to characterize the expression of inducible nitric oxide synthase (iNOS) mRNAs in rat kidney and cultured glomerular mesangial cells. A partial cDNA homologous to murine macrophage iNOS (macNOS), but distinct from rat vascular smooth muscle iNOS (vsmNOS), was cloned from normal rat kidney. macNOS was the principal iNOS isoform tonically expressed in microdissected glomeruli, proximal tubules, medullary thick ascending limbs (mTAL), cortical and inner medullary collecting ducts (IMCD), and cultured mesangial cells, whereas vsmNOS was the major isoform expressed in arcuate and interlobular arteries. Basal macNOS expression was greatest in mTALs and IMCDs. Restriction mapping of RT-PCR products indicated that basal expression of macNOS mRNA was comparable to that of vsmNOS in cortex, but greater than vsmNOS in outer and inner medulla. However, compared to controls, lipopolysaccharide (LPS)-treated rats exhibited a much greater proportion of vsmNOS mRNA and higher levels of total iNOS mRNA in each zone. Similarly, TNF alpha and IF-gamma preferentially induced expression of vsmNOS mRNA in cultured mesangial cells. We conclude that two iNOS isoforms are constitutively and heterogeneously expressed in the normal rat kidney, and that endotoxemia and cytokines differentially induce their expression.

Amino Acid Oxidoreductases↗
PubMed1993

Regulation of kidney organogenesis: homeobox genes, growth factors, and Wilms tumor.

Factors regulating the temporal and spatial expression of kidney developmental programs are beginning to be identified. Evidence accumulated in the past few years indicates that the Hox and Pax genes, in particular, are important for early kidney development. A number of soluble growth factors were also shown to be essential for nephrogenesis to proceed in vitro. Errors in kidney development include Wilms tumor, a common childhood malignancy, which in many cases seems to be caused by faulty transcriptional regulation.

Genes, Homeobox↗
PubMed1990

Potassium conductances in tracheal epithelium activated by secretion and cell swelling.

Increased basolateral membrane K conductance accompanies stimulation of Cl secretion across canine trachea. To assess the K conductance properties, we permeabilized the apical membranes with amphotericin B and monitored the current and conductance caused by K flow across the basolateral membranes. Under basal unstimulated conditions, two K conductances could be distinguished by blockers. One was inhibited only by barium; the other was sensitive also to quinidine and lidocaine. The permeabilities of the basal conductance pathways to K and Rb were similar (PK/PRb approximately equal to 1.5). The secretory agonist, epinephrine, selectively increased the quinidine-insensitive conductance, implicating it in the Cl secretory response. Cell swelling induced a third conductance with a low permeability to Rb (PK/PRb approximately equal to 10) that was quinidine sensitive. In tissues not treated with amphotericin, neither quinidine nor Rb-for-K replacement inhibited transepithelial Cl secretion. Thus neither of the quinidine-sensitive K conductances (basal or swelling induced) contribute to the increase in basolateral K conductance during Cl secretion. Cell shrinkage inhibited all three conductances and secretion, suggesting that the initial priority of the cell is volume regulation.

Amphotericin B↗
PubMed1989

Morphologic heterogeneity along the rat inner medullary collecting duct.

The qualitative and quantitative morphologic features of the cells lining the inner medullary collecting duct (IMCD) in the outer (IMCD1), middle (IMCD2) and inner (IMCD3) segments were investigated. Kidneys of male rats were fixed by in vivo vascular perfusion with glutaraldehyde and processed for light microscopy and scanning and transmission electron microscopy. The IMCD1 consisted of both principal cells and intercalated cells similar to those present in the outer medullary collecting duct. The principal cells were covered with small microvilli and a single cilium. Most of the IMCD2 and the entire IMCD3 contained one cell type (IMCD cell). When compared with the principal cells, the IMCD cells were taller, had fewer basal infoldings and a lighter staining cytoplasm containing numerous free ribosomes and small electron-dense cytoplasmic bodies in the basal region. The luminal surface was covered with prominent microvilli, but had no cilia. Morphometric analysis demonstrated that the surface density of apical and basal plasma membranes decreased from IMCD1 to IMCD3. However, because of an overall increase in tubule volume from IMCD1 to IMCD3, there were no significant differences in the absolute area of apical or basal membranes between the three segments. In contrast, the absolute area of lateral membranes increased significantly from IMCD1 to IMCD3. This study demonstrates that the IMCD1 consists of principal cells and intercalated cells similar to those in the outer medullary collecting duct, whereas the cells in most of the IMCD2 and the entire IMCD3 appear to represent a distinct and separate cell type which we choose to call the IMCD cell. Thus, both morphologic and functional heterogeneity appear to exist along the IMCD.

Animals↗
PubMed1988

Axial heterogeneity in the handling of albumin by the rabbit proximal tubule.

Morphologic and physiologic studies have established that filtered proteins are absorbed in the proximal tubule by endocytosis and transported to the lysosomes for degradation. The tubular absorption, hydrolysis and accumulation of albumin were examined in all three segments of the rabbit proximal tubule. S1, S2 and S3 segments were dissected and perfused in vitro with tritiated albumin at a physiologic concentration of 0.0364 mg/ml, and with [14C]inulin to determine fluid reabsorption. In addition, the three segments were fixed for ultrastructural examination after perfusion under conditions similar to those in the physiologic studies. The fluid reabsorption was similar in S1 and S2 but lower in S3. Albumin absorption was unexpectedly similar in the three segments. A lower percentage of absorbed albumin was hydrolyzed in the S3 segment compared with the earlier segments. The values were 70 +/- 15%, 61 +/- 11%, and 30 +/- 4% for S1, S2, and S3, respectively. The cellular accumulation of protein was highest in the S3 segment. The ultrastructure of the three segments was similar to that described in in vivo preserved kidneys, and no abnormalities were observed in the endocytic-lysosomal compartment. These results reveal axial heterogeneity in the hydrolysis of absorbed albumin by the rabbit proximal tubule and suggest that under normal physiologic conditions the S3 segment has a lower lysosomal proteolytic activity. Although the S3 segment maintains a high capacity for protein absorption, the earlier proximal segments likely have a greater role in protein degradation.

Absorption↗
PubMed1987

Intercalated cells of the rat inner medullary collecting duct.

There is increasing evidence of acidification along the entire mammalian collecting duct including the inner medullary collecting duct (IMCD). Recent studies have provided morphologic evidence that the intercalated cells are involved in hydrogen ion secretion in the cortical and outer medullary collecting duct of the rat. In the present study we performed a quantitative and qualitative morphologic examination of the intercalated cells in the IMCD of the rat and compared the results to observations obtained from intercalated cells in the collecting duct in the inner stripe of the outer medulla (OMCDi). Kidneys of male rats were preserved by in vivo perfusion with glutaraldehyde and processed for morphologic evaluation. With light microscopy and scanning electron microscopy intercalated cells were found in the outer third of the IMCD (IMCD1) and accounted for 10% of the total cell population. They were absent in the terminal two-thirds of the IMCD. Examination of the intercalated cells using transmission electron microscopy revealed striking similarities between the cells of the IMCD1 and those in the OMCDi. In addition, no differences were found in the surface densities of the apical or basolateral plasma membranes or the volume densities of the mitochondria of the intercalated cells in the two regions. In light of the morphologic similarity with the intercalated cells of the OMCDi that are believed to be involved in hydrogen ion secretion, it is likely that the intercalated cells of the IMCD1 are also involved in the acidification of tubular fluid.

Animals↗
PubMed1987

Ultrastructural localization of acidic compartments in cells of isolated rabbit PCT.

Acidic intracellular compartments were identified in cells of isolated perfused rabbit proximal convoluted tubules (PCT) with the weak base, N-(3-[(2,4-dinitrophenyl)amino]propyl)-N-(3-aminopropyl)methylamine, dihydrochloride (DAMP), a congener of dinitrophenol (DNP) and immunogold staining at the ultrastructural level in Lowicryl-embedded tissue. DAMP is protonated upon entrance into an acidic compartment and binds to protein. Glutaraldehyde fixation cross-links the DAMP-protein complex to maintain the complex in its original environment. Monoclonal antibodies directed against DNP cross-react with DAMP to identify its location in tissue sections. Accumulation of colloidal gold-conjugated antibodies to the monoclonal anti-DNP antibodies, indicating the presence of an acidic environment, was found in large endocytic vacuoles (diam greater than 0.5 micron) and lysosomes, and to a lesser extent in endocytic vesicles. Qualitatively, activity greater than background was not found in other organelles, including the Golgi apparatus and the cell nuclei. The specificity of the technique was tested by treating tubules with the ionophore, monensin, to collapse the intracellular pH gradient. This treatment resulted in the complete disappearance of the specific localization of colloidal gold particles. Quantitative analysis of the number of colloidal gold particles per area of cross-sectioned cell organelle demonstrated that monensin especially affected those counts obtained over large endocytic vacuoles and lysosomes. The present ultrastructural observations, therefore, identify endocytic vesicles, endocytic vacuoles, and lysosomes as acidic intracellular compartments in isolated rabbit PCT. This technique affords the opportunity to identify the location of acidic compartments along the entire nephron at the ultrastructural level.

Acids↗
PubMed1980

Acute lymphoblastic leukemia: hand mirror variant.

The presence of numerous hand mirror cells in the bone marrow of patients with acute leukemia may be related to a good prognosis. To further evaluate this relationship, the bone marrows of 21 consecutive patients with a diagnosis of acute lymphoblastic leukemia were reviewed for the presence of greater than 40% hand mirror cells. Four of these 21 patients (19%) demonstrated this finding during the course of their illness. These patients were characterized by ease of remission and/or prolonged survival. Three (75%) patients are alive and well at the time of this writing. At the present time, of the 17 patients without hand mirror cells, seven (41%) are alive and ten (59%) are dead. Although not statistically significant, our findings suggest a positive relationship between the presence of greater than 40% hand mirror cells in the bone marrow ans a favorable prognosis. Future larger prospective studies are indicated to further understand the importance of this complex, apparently immunologically stimulated cell.

Adult↗
PubMedDate not supplied

Renomedullary deficiency in partial nephrectomy-salt hypertension.

Partial nephrectomy-salt hypertension (PN-SH) of the rat is associated with Na volume loading. As the hypertensive state evolves, the renomedullary interstitial cells (RIC) of the renal nubbin undergo major changes, decreasing significantly in number while the remaining ones exhibit degenerative changes. The antihypertensive action of the RIC in the renal nubbin, as measured by transplants of fragmented papillae into hypertensive recipients, virtually disappears as the hypertension develops. The changes in the RIC occur whether vascular disease of the kidney is or is not overtly present. It is suggested that deficiency of the antihypertensive action of the RIC allows the prohypertensive effects of Na volume loading to operate without proper control. Thus, the sustained hypertensive state of this model does not appear to be due solely to volume expansion. Rather, it appears due to a combination of the effects of Na and volume and a renomedullary deficiency of hormonal type. The specific cause(s) of the changes in the RIC was not determined. It seems evident that it is related to the high salt intake since the partial nephrectomy procedure without the added salt load did not alter the appearance of the RIC.

Animals↗