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Biomedical subjects

J S Rodman

Publications and source records attributed to J S Rodman.

At least 19 recordsLinked to original sources
PubMed1999

Struvite stones.

Struvite stones constitute only about 2-3% of the stones reaching the laboratory for analysis, but the clinical problems they create including sepsis and even renal demise are greater than with any other stone type. This article reviews the evidence that bacterial urease, usually from a Proteus species, is responsible for the chemical changes in urine which result in struvite formation. Available urease inhibitors and other forms of medical management of patients with these stones are discussed. A patient with struvite stones should be assumed to have a progressive disease which cannot be ignored. Even after seemingly successful elimination of stones with lithotripsy and/or percutaneous nephrolithotomy, careful medical follow-up is critical. The medical profession is probably underutilizing postprocedure hemiacidrin irrigation because of shortsighted financial considerations. Primary-care physicians need to be educated in the importance of aggressive management of Proteus and other urea-splitting infections.

Adult↗
PubMed1998

A two-year follow-up survey of antibody to Cryptosporidium in Jackson County, Oregon following an outbreak of waterborne disease.

To estimate the duration of Cryptosporidium-specific antibody, a Western blot assay measured antibody in paired sera from 124 residents of Jackson County, Oregon collected 0.5 and 2.5 years after the end of an outbreak in Talent, Jackson County. The outcome measure was the intensity of antibody responses, (which may approximate to a titre), to 27-kDa and 15/17-kDa antigens. Intensity of response to the 27-kDa antigen(s) declined to 54% of the 1992 value while responses to a 15/17-kDa antigen(s) remained close to the initial values. Increasing age of the donor predicted higher intensity of antibody to the 15/17-kDa antigen(s) in both the initial (P = 0.004) and follow-up (P = 0.038) surveys. No relationship was observed between age and antibody intensity for the 27-kDa antigen(s) during either survey (P > 0.10). Both the initial and follow-up surveys showed significant elevations in antibody intensity for Talent residents, possibly indicating a high endemic rate of infection/re-infection or high levels of chronic infection.

Animals↗
PubMed1998

Rate of accumulation of Luxol Fast Blue staining material and mitochondrial ATP synthase subunit 9 in motor neuron degeneration mice.

The rate of accumulation of Luxol Fast Blue staining material in the hippocampus of motor neuron degeneration (mnd/mnd) mice, a model of Batten Disease, was quantitated. Stained material increased linearly up to 8 months of age. A quantitative immunoassay was used to measure levels of mitochondrial ATP synthase subunit 9 in brain and liver of mnd/mnd mice. Levels of subunit 9 increased progressively throughout the lifespan of mnd/mnd mice reaching levels approximately 5-fold higher than in control animals. The rate of accumulation of subunit 9 is not consistent with any simple complete or partial degradation defect that is constant throughout the animal's life. Two more complicated models are discussed which are consistent with the observed accumulation rate of subunit 9.

Animals↗
PubMed1994

Two related proteolipids and dolichol-linked oligosaccharides accumulate in motor neuron degeneration mice (mnd/mnd), a model for neuronal ceroid lipofuscinosis.

In this study, we show that two biochemical markers of neuronal ceroid lipofuscinoses (NCLs) are present in a mutant mouse (mnd/mnd) that exhibits symptoms of the disease. Subunit c of the mitochondrial F1F0-ATP synthase, a proteolipid that accumulates in storage bodies of most forms of NCL and several animal models, is dramatically increased in mnd/mnd mouse brain, kidney, liver, heart, and pancreas. Interestingly, another related proteolipid, subunit c of the vacuolar H(+)-ATPase, also accumulates in several mnd/mnd tissues. The molar ratio of the vacuolar subunit c to the F1F0 subunit c is approximately one to two in enriched storage bodies from brain. The relative accumulation of the vacuolar subunit c correlates with its abundance in normal tissues. It appears in decreasing amounts in brain, kidney, and liver and is not detected in heart or pancreas. Aged mice and two mutant mouse lines, juvenile bare (jb) and mucopolysaccharidosis, type VII (gusmps), did not accumulate either of these proteolipids. Dolichol-linked oligosaccharides also accumulate in NCLs and are increased 17-fold in mnd/mnd mouse brain. Thus, mnd/mnd mice seem to be an excellent model for NCLs since they not only share clinical signs and histopathology, but also two biochemical markers. The accumulation of the vacuolar subunit c in this model may prove to be a marker for distinguishing different forms of NCLs.

Amino Acid Sequence↗
PubMed1994

Effect of calcium citrate supplementation on urinary calcium oxalate saturation in female stone formers: implications for prevention of osteoporosis.

In 14 women aged 37-68 y with a history of renal calcium calculi, bone densities were 12.0% below those of age-matched control subjects at the L2-4 lumbar spine (P = 0.007) and 6.4% less at the femoral neck (P = 0.095). A low-oxalate diet was supplemented with 1 g Ca/d as citrate. In 6 mo, plasma 1,25(OH)2D concentrations fell from 53.2 +/- 18.8 to 41.9 +/- 15.2 ng/L (P = 0.02) and parathyroid hormone from 39.1 +/- 17.0 to 30.8 +/- 12.5 ng/L (P = 0.02). Calcium oxalate saturation was 2.15 +/- 1.38 at baseline, 2.27 +/- 1.00 at 1 mo, and 2.06 +/- 1.57 at 6 mo. The increase in urinary calcium at 1 mo from 4.411 +/- 1.87 to 6.514 +/- 2.82 mmol/24 h (P = 0.01) was offset by a parallel increase in citrate excretion from 2.909 +/- 1.45 to 3.455 +/- 1.34 mmol/24 h (P = 0.03). Calcium citrate supplementation did not increase the lithogenicity of the women in this protocol.

Adult↗
PubMed1991

Distribution and structure of the vacuolar H+ ATPase in endosomes and lysosomes from LLC-PK1 cells.

Vacuolar proton pumps acidify several intracellular membrane compartments in the endocytic pathway. We have examined the distribution of the vacuolar H+ ATPase in LLC-PK1 cells and the structure of the biosynthetically labeled enzyme in membrane fractions enriched for endosomes or lysosomes. LLC-PK1 cells were allowed to internalize cytochrome c-coated colloidal gold as a marker for endocytic compartments. Proton pumps were identified in these cells by staining the cells with a monoclonal antibody against the vacuolar pump detected with either immunogold or immunoperoxidase techniques. H+ ATPase labeling was seen on structures resembling endosomes and lysosomes, but not on Golgi or plasma membrane. To examine the structure of the H+ ATPase in these compartments, we labeled LLC-PK1 cells for 24 h with [35S]methionine and used a Percoll gradient to obtain fractions enriched for endosomes or lysosomes. H+ ATPase immunoprecipitated from both fractions with monoclonal anti-H+ ATPase antibodies had labeled polypeptides of 70, 56, and 31 kDa. On two-dimensional gels, a comparison of the H+ ATPase from the endosomal and lysosomal fractions revealed that the 70-, 56-, and 31-kDa subunits were similar in both fractions. The results show that the vacuolar H+ ATPase in these cells is distributed primarily in endosomes and lysosomes and that the structure of the enzyme is similar in both compartments.

Animals↗
PubMed1991

Prophylaxis of uric acid stones with alternate day doses of alkaline potassium salts.

Uric acid stone formation ordinarily is prevented by increases in the urinary pH after meals. This postprandial alkaline tide is lost in patients who make such calculi. Single dose, alternate day administration of an alkaline potassium salt will increase urinary pH and simulate this normal physiological mechanism. An important part of the regimen is patient self-monitoring to verify that the urinary pH increases to greater than 6.8, 1 1/2 to 2 hours after the medication is taken. In contrast to multiple dose daily regimens, this mode of base administration is tolerated better and easier to follow. In 17 patients, 7 with the recurrent gravel/colic syndrome and 10 with prior stones, this regimen abolished calculus formation during an average followup of 2 1/2 years. However, further studies are needed before this regimen can be recommended as standard therapy for uric acid stone prophylaxis.

Adult↗
PubMed1990

Immunolocalization of endosomal cathepsin D in rabbit alveolar macrophages.

Intravacuolar proteolysis appears to be an important component of antigen presentation, the activation of peptide hormones, and the conversion of biologically important mediators from inactive precursors. Cathepsin D has been identified in the endosomes of rabbit alveolar macrophages by biochemical analyses [Diment and Stahl, J. Biol. Chem. 260,15311, 1985; Diment et al., J. Biol. Chem. 263,6901, 1988]. Using affinity-purified goat antirabbit cathepsin D IgG, we have localized cathepsin D to the endosomes of rabbit alveolar macrophages. Immunofluorescent staining of frozen sections showed labeling in lysosomes and small vesicles in the periphery of the cell. Label was not seen on the plasma membrane. With immunoperoxidase labeling at the electron microscopic level on cells containing endocytosed mannose-BSA gold, we saw labeling in endosomes and classical lysosomes. When the results were quantitated using immunogold labeling of thin cryosections, we found that the majority of cathepsin D (62.2%) was present in lysosomes, 4.0% in large clear vacuoles, a surprisingly high percentage (29.3%) in small vesicles, 4.9% in endosomes, and none on the plasma membrane. We conclude from this study that, in addition to being present in lysosomes, cathepsin D is present in endosomes and in small peripheral vesicles.

Animals↗
PubMed1989

Urothelial injury from ethylenediaminetetraacetic acid used as an irrigant in the urinary tract.

Although solutions containing disodium ethylenediaminetetraacetic acid (EDTA) will dissolve calcium oxalate stones in vitro, the safety of such solutions as urinary tract irrigants is questionable. These studies were designed to assess the degree of urothelial damage produced by the mildest EDTA formulation which has been reported to be effective. Rabbit bladders were irrigated antegrade via a ureterotomy for 20 hours and then removed for histological examination. A 0.03 M solution of disodium EDTA at pH 7.5 produced considerably more urothelial injury than did an otherwise identical solution of calcium EDTA (p = 0.006). The bladders from the latter group were undistinguishable from those irrigated with saline. As prior saturation of EDTA with calcium completely eliminated the tissue injury, these studies indicate that the same calcium chelating property which makes this chemical effective also makes it toxic. There was enough tissue damage from the relatively mild formulation used to suggest no EDTA solution yet formulated is safe for clinical use.

Animals↗
PubMed1989

The effect of ultraviolet B radiation treatments on calcium excretion and vitamin D metabolites in kidney stone formers.

Several factors could explain the effect of warm, sunny weather on kidney stone formation. To determine the role of sun exposure, we used a light box to administer artificial ultraviolet B radiation during the winter months in New York City. Eleven male stone formers and 7 age- and sex-matched controls received 10 UVB light exposures over a two-week period while maintaining a 400 mg calcium diet. 25-OH vitamin D levels increased significantly (p less than 0.001) in both patients (25.9 +/- 9.8 to 51.6 +/- 14.1 ng/ml) and controls (21.3 +/- 7.1 to 49.6 +/- 3.1 ng/ml). However, 1,25 dihydroxyvitamin D levels rose in the patients (50.8 +/- 14.8 to 55.9 +/- 13.1 pg/ml) but fell (60.1 +/- 6.5 to 49.4 +/- 3.1 pg/ml) in the controls. Only 2 of the 11 patients but all of the controls demonstrated this down regulation of 1,25 dihydroxyvitamin D levels (p less than 0.002). 24,25 dihydroxyvitamin D levels tended to rise in both groups but parathyroid hormone levels were unchanged. There was a trend, which did not reach statistical significance, for parameters of calcium excretion to increase after UVB radiation. 24-hour urinary calcium excretion rose 24% from 140 to 173 mg in the patients and 31% from 113 to 148 mg in the controls. The ratio of calcium/creatinine following a one gram calcium load showed a small increase after UVB radiation from 0.17 to 0.20 in patients and 0.118 to 0.124 in the controls. However, no correlation could be discerned between changes in vitamin D metabolite concentrations and changes in urinary calcium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Urothelial injury to the rabbit bladder from alkaline irrigants useful in the treatment of uric acid stones.

Irrigation of the urinary tract with alkaline solutions may be used appropriately in some clinical situations to dissolve uric acid stones. Since in vitro studies have suggested that tham-E (pH 10.6) is somewhat more effective than tham (pH 8.6) in promoting dissolution of uric acid, these studies were undertaken to assess the relative toxicities of these two irrigating solutions to the urothelium. Rabbit bladders were irrigated antegrade via a ureterotomy for twenty hours. Tham E produced considerably more mucosal injury than did tham (p = 0.0001). The minimal advantage in rapidity of stone dissolution offered by tham E over tham is more than offset by the considerably increased potential for toxic side effects. The results suggest tham and not tham E should be used for irrigation to dissolve uric acid stones.

Animals↗
PubMed1987

Hypercoagulability produced by treatment with acetohydroxamic acid.

Thrombosis has been observed with unusual frequency in patients receiving acetohydroxamic acid (AHA) for treatment of struvite nephrolithiasis. Because this clinical observation suggests a low-grade state of diffuse intravascular coagulation, standard clinical coagulation assays, platelet counts, and plasma fibrinopeptide A (FPA) levels were measured in patients before and during treatment with AHA. Coagulation assays, fibrinogen, and fibrin-split products were not significantly different when pretreatment and treatment values were compared. FPA levels were significantly elevated and platelet counts were significantly reduced in the treatment period, indicating augmented thrombin activity and consumption of platelets into thrombi or platelet microaggregates. FPA levels were elevated within 24 hours of the initiation of AHA therapy whereas platelet counts did not change significantly within the first 4 days of treatment. The data are consistent with low-grade intravascular coagulation with AHA treatment and suggest that patients treated with this agent should be observed cautiously for signs of thrombosis.

Blood Coagulation↗
PubMed1986

Urothelial injury to the rabbit bladder from various alkaline and acidic solutions used to dissolve kidney stones.

Different irrigating solutions are used clinically to dissolve uric acid, cystine and struvite stones. These studies were undertaken to assess the toxicity to the rabbit bladder epithelium of several commonly used formulations. Test solutions were infused antegrade through a left ureterotomy overnight. Bladders were removed and routine histological sections made. A pH 7.6 solution of NaHCO3 appeared harmless. The same solution with two per cent acetylcysteine produced slight injury. All pH 4 solutions caused significant damage to the urothelium. Hemiacidrin, which contains magnesium, produced less damage than did other pH 4 solutions without that cation. Our data tend to support Suby's conclusions that addition of magnesium reduces urothelial injury even though the presence of magnesium will slow dissolution of struvite.

Acetylcysteine↗
PubMed1986

The membrane composition of coated pits, microvilli, endosomes, and lysosomes is distinctive in the rat kidney proximal tubule cell.

The distribution of a number of membrane proteins on plasmalemmal microdomains (microvilli, coated pits) and in endosomes and lysosomes of the proximal tubule epithelial cell was determined in normal rat kidneys by immunofluorescence and immunoelectron microscopy. Two major brush border proteins, 130 and 94 kD, and gamma-glutamyl transpeptidase were detected on the membranes of the microvilli but were not found on membranes of coated pits. Gp330, the Heymann nephritis antigen, and clathrin were localized in coated pits. The lysosomal membrane glycoprotein, lgp120 (Lewis, V., S. A. Green, M. Marsh, P. Vihko, A. Helenius, and I. Mellman, 1985, J. Cell Biol., 100: 1839-1847) was restricted to lysosomes where it co-localized with beta-glucuronidase. Endosomes, identified by preloading with HRP injected 5-15 min before rats were killed, did not contain detectable amounts of any antigen tested. The distribution of the same proteins was also determined in rats given sodium maleate, which is known to slow or reduce protein absorption by the proximal tubule and to cause vacuolation of the endocytic apparatus. After maleate treatment the distribution of microvillar and lysosomal markers was unchanged, but the coated pit markers were redistributed--gp330 was concentrated in newly formed apical vacuoles, and clathrin was diffusely distributed in the apical cytoplasm or on apical coated vesicles. These findings indicate that the membrane composition of microvilli, coated pits, endosomes, and lysosomes is distinctive in the proximal tubule cell; and that gp330, unlike other known coated pit membrane components, is not transferred to endosomes during endocytosis. After maleate treatment, the coated pits lose their clathrin coats, and the corresponding membrane is internalized.

Animals↗
PubMed1986

Cytoskeletal proteins of the rat kidney proximal tubule brush border.

Cytoskeletal components backing the brush border of the rat kidney proximal tubule cell were identified and compared with those of the well characterized intestinal brush border by immuneoverlay and immunocytochemistry. Antibodies reactive against the intestinal microvillus core components, villin and fimbrin, as well as against the terminal web components, spectrin (fodrin) and myosin, were used. Proteins of similar molecular weight to these intestinal brush border cytoskeletal components were identified in isolated kidney brush borders by immuneoverlay. Spectrin, a major component of the terminal web region of both cell types, was more concentrated in the kidney brush border relative to both actin and myosin. By immunofluorescence, villin and fimbrin were localized in the microvilli, and spectrin and myosin were localized to the terminal web region of the brush border. In addition, spectrin was found along the basolateral membranes of the proximal tubule cell, and myosin was detected in a punctate staining pattern throughout its cytoplasm. By immunoelectron microscopy using immunogold labeling procedures, fimbrin and villin were localized in the terminal web as well as in microvilli, and spectrin and myosin were localized to fibrils in the terminal web. A key difference between the epithelia of the two organs is the extensive network of clathrin coated pits found in the terminal web region of the kidney but not the intestinal brush border. The clathrin-rich terminal web region of the kidney, like the intestinal brush border, proved to be quite stable and resistant to disruption by non-ionic detergents and harsh mechanical treatment.

Animals↗