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Biomedical subjects

J R Wright

Publications and source records attributed to J R Wright.

At least 19 recordsLinked to original sources
PubMed1992

Specific binding of surfactant apoprotein SP-A to rat alveolar macrophages.

Surfactant protein A (SP-A) influences the function of alveolar macrophages in vitro. In this study the characteristics of the binding of 125I-labeled SP-A to rat alveolar macrophages has been investigated. The binding of SP-A to alveolar macrophages at 4 degrees C was saturable with half-maximal binding at a SP-A concentration of 4 micrograms/ml. Bound SP-A was rapidly displaced by an excess of unlabeled SP-A. The binding of labeled SP-A to the alveolar macrophages was blocked in a dose-dependent fashion by unlabeled SP-A, the collagen-like protein C1q and type V collagen but not by bovine serum albumin. These results suggest that a component of the interaction between SP-A and alveolar macrophages is mediated through the collagen-like domain of SP-A and that the characteristics of this interaction are consistent with there being a specific receptor for SP-A on the surface of alveolar macrophages.

Animals↗
PubMed1979

Synthesis and antibacterial activity of 1-N-(1,3-dihydroxy-2-propyl)kanamycin B (UK-31,214).

1-N-(1,3-Dihydroxy-2-propyl)kanamycin B was prepared and its in vitro activity against aminoglycoside-sensitive and aminoglycoside-resistant organisms was compared with that of kanamycin B and gentamicin. This kanamycin B derivative (code No. UK-31,214) demonstrated potent activity in all of these tests and gave good protection in experimental infections in mice.

Aminoglycosides↗
PubMed1979

1H-NMR effects in chloroquine-biopolymer binding interactions.

Chloroquine (CQ), an antimalarial and anti-inflammatory drug, is known to concentrate within lysosomes. 1H-NMR studies were conducted using the resonances of CQ itself during binding interactions with various polymers and proteins including lysosome fractions isolated from rodent livers by tritosome technique. Albumin, butyrylcholinesterase, and high molecular weight DNA interact with CQ, producing marked line-width changes that correlate with effective molecular weight. Triton WR-1339 and sucrose, probable contaminants of the lysosomal materials isolated, produced essentially no effect beyond a viscosity component. Lysosomal matrix and membrane fractions exhibited relatively weak interactions, membranes being the more tenacious toward CQ. Estimated binding constants are too small to permit explanation of CQ uptake in terms of protein affinity. The evidence is more consistent with a proton-pump trapping model proposed by de Duve et al.

Animals↗
PubMed1978

Influence of age and previous use of diazepam dosage required for endoscopy.

In 19 patients (10 men and 9 women) a 22-fold variation was observed in the intravenous dose of diazepam necessary as preparation for endoscopy (median dose, 20 mg; range, 5 to 110 mg). Analysis of plasma samples for diazepam and N-desmethyldiazepam revealed that the clinical response did not relate to the rate or character of initial drug distribution. There was a high correlation (r = 0.96) between the dose and the plasma concentration 10 minutes after administration. Users of diazepam displayed tolerance to its pharmacologic effects, requiring a significantly larger (P less than 0.05) dose than nonusers (median doses, 35.0 mg and 14.5 mg respectively). Older patients required less than younger patients (r = -0.54, P less than 0.05). The variation between individuals in the dose of diazepam required as preparation for endoscopy cannot be explained by variation in drug disposition but instead reflects previous diazepam use, age and probably differences in sensitivity at the site or sites of drug action.

Adult↗
PubMed1978

The 1H-nmr spectra of mixed valence complexes of copper with derivatives of 1-amino-2,2-dimethyl-2-mercaptoethane.

Paramagnetic cluster ions of the type Cu(II)6Cu(I)8L12ClZ, where Z Is charge and L a derivative of 1-amino-2,2-dimethyl-2-mercaptoethane, have been shown to produce detectable 1H-nmr absorptions. Linewidths are narrow enough to permit the use of high resolution instruments. Downfield shifting of all detectable resonances is indicative of S leads to Cu2+ charge transfer, which results in a positive spin density at sulfur. Exchange measurements with 67Cu indicate relatively static structures.

Chemical Phenomena↗
PubMed1978

Renal function in patients with multiple myeloma.

Renal tubular and glomerular functions were evaluated in 35 consecutive patients with multiple myeloma and were correlated with changes in renal histopathology and myeloma protein patterns. All nine patients without Bence Jones proteinuria had CCr greater than 50 ml/min. In contrast 16/26 patients with Bence Jones proteinuria had CCr less than 50 ml/min and the magnitude of the Bence Jones proteinuria correlated well with the degree of renal insufficiency. Frequent abnormalities in renal tubular acidifying and concentrating ability were observed only in patients with Bence Jones proteinuria and occurred in the absence of significant reductions of glomerular filtration rate. Severely deranged renal histology was seen only in patients with Bence Jones proteinuria and consisted primarily of tubular atrophy and degeneration; glomeruli appeared normal. These data suggest that Bence Jones proteins exert a direct nephrotoxic effect at the tubular level with resultant tubular dysfunction and tubular atrophy. Glomerular filtration rate remains relatively preserved despite the significant abnormalities of tubular function. Although obstructing tubular casts were observed only in patients with severely impaired glomerular filtration rate, many patients with similarly impaired renal function had no evidence of such casts. Instead, tubular atrophy and degeneration correlated best with renal dysfunction.

Adult↗
PubMed1977

Histologic changes in preserved cadaveric renal transplants.

The histologic changes in human cadaveric kidneys preserved by either simple hypothermia or continuous pulsatile perfusion were studied by light and electron microscopy and by immunofluorescence in biopsies obtained immediately before (15 kidneys) and approximately 1 hour after (41 kidneys) transplantation. The changes observed in pretransplantation biopsies were largely similar in kidneys preserved by either method with the exception that foreign material was found in the vasculature of perfused kidneys only. Endothelial edema was more frequent and more severe in nonperfused kidneys only. Endothelial edema was more frequent and more severe in nonperfused kidneys. In the 1 hour posttransplantation biopsies, a lesion resembling intravascular coagulation (IVC) was noted in 18 of the 25 perfused kidneys but was absent from all 16 nonperfused kidneys. Transplants with severe IVC lesions failed to function and had extensive cortical necrosis when removed by the end of the first month. In follow-up biopsies, milder lesions appeared to heal fast and were compatible with transplant function. The IVC lesion is probably due to endothelial cell damage during perfusion of the kidneys.

Biopsy↗
PubMed1977

Potassium permanganate reaction in amyloidosis. A histologic method to assist in differentiating forms of this disease.

A simple and reproducible histochemical method for distinguishing different chemical types of amyloid is described. The method is based on the affinity of amyloid for Congo red dye after exposure to potassium permangenate and dilute sulfuric acid. The permanganate method represents a modification of the Romhanyi trypsin technique. It yields comparable results while obviating some of the technical difficulties associated with the latter method. The permanganate reaction was applied to a series of amyloid samples of known amino acid composition, to amyloid samples fixed in a variety of different preservatives, and to tissues obtained at autopsy from 67 amyloidosis patients whose disease had been previously subclassified on the basis of clinical presentation and autopsy observations. This method distinguished amyloid protein AA from other varieties of amyloid and proved effective when applied to amyloid samples preserved in any of several commonly used fixatives. This simple histochemical method proved useful in subclassifying amyloid type in the patient series particularly when used in conjunction with the available clinical history and the organ distribution of amyloid accumulation.

Amyloidosis↗
PubMed1977

Familial hemochromatosis: characteristics of the precirrhotic stage in a large kindred.

Ffty asymptomatic members of a kindred with familial hemochromatosis were studied in an effort to clarify some of the physiologic abnormalities present in the pre-cirrhotic or latent stage of the disease. Using excess hepatic iron as a marker for inheritance of hemochromatosis, results of liver biopsies on 31 family members suggest an auto-somal dominant mode of inheritance with incomplete expressivity. In addition to a relationship between alcohol intake and excess liver iron, there was a strong association between the level of alcohol intake and the presence of hepatic fibrosis in those subjects with excess iron stores. Both serum iron and transferrin saturation were significantly higher in family members with iron overload than in those who were not affected. Only transferrin saturation was significantly correlated with the severity of hepatic iron deposition. Studies of glucose tolerance (OGTT, IVITT, glucose clamp studies) demonstrated a defect in carbohydrate metabolism associated with deficient insulin secretion and insulin resistance, both of which were related to the degree of hepatic iron depostion. In this kindred we have found no evidence for a contribution of inheritance to the carbohydrate intolerance of hemochromatosis. Iron overload was not related to activity of hepatic collagen proline hydroxylase or urinary excretion of peptide-bound hydroxyproline. Serum ferritin, previously thought to be a reliable marker of reticuloendothelial iron stores, was normal in 19 of 20 family members with iron overload.

Adolescent↗
PubMed1976

Normal serum ferritin concentrations in precirrhotic hemochromatosis.

We investigated 33 of 58 members of two families with latent or precirrhotic hemochromatosis to determine its pattern of inheritance and to evaluate the serum ferritin levels as an index of iron stores. In both families, the pattern of inheritance was as an autosomal dominant trait with incomplete expressivity. Mean serum ferritin values in the affected family members were 88.5 ng per milliliter (range, 28.0 to 201.9) for males and 65.2 ng per milliter (range 23.7 to 97.0) for females, which were no different from controls (P is less than 0.5). Furthermore, the serum ferritin values did not correlate with or reflect mobilizable iron stores, and there were no relations between the serum iron, iron-binding capacity and transferrin saturation (P is less than 0.2). Thus, serum ferritin concentrations in precirrhotic familial hemochromatosis appear to underestimate iron stores. Serum ferritin levels do not help to identify such patients with increased iron stores for therapeutic phlebotomy.

Adult↗
PubMed1976

Melanosis of the prostate gland: report of a case with neoplastic epithelium involvement.

Prostate gland melanosis is an uncommon lesion and the precise histogenesis is unclear. Melanin may be found within melanocytes in the prostatic stroma, within prostatic epithelium and, rarely, in both locations. The stromal dendritic cell has been shown to contain premelanosomes and melanosomes suggesting primary melanin production by this cell. The melanogenic potential of prostatic epithelial cells has not yet been conclusively established. An example of prostatic melanosis is presented in which stromal and epithelial components were found. This dual distribution of melanin has been regarded as an indication that melanin in the epithelial cells results from phagocytosis of melanin from stromal melanocytes as a secondary phenomenon. Melanin pigment was identified not only within hyperplastic prostatic epithelium but also was found in the epithelial component of a well differentiated prostatic adenocarcinoma.

Adenocarcinoma↗
PubMed1975

Properties of the red - violet complex of copper and penicillamine and further insight into its formation reaction.

A characteristic red-violet chromophore which forms in the reaction of cupric ion with beta-sulfhydryl- alpha-amino acids has been attributed by several authors to a mixed-valence Cu3L2 structure. We have isolated and examined the analogous chromophore of the chelating drug penicillamine (beta, beta-dimethyl-cysteine), finding instead a polymeric anion with a mixed valence Cu2L2 repeating unit. Direct evidence for a mixed valence polymer cooroborates earlier conclusions of Wilson and Martin (9). Under oxygen-free conditions the anionic complex forms in essentially quantitative yield according to the following reaction: (see article). It has been established that this reaction is halide ion-dependent. The chromophore may be isolated as a sodium salt. This form was found to be stable, and it possessed no measurable activity as an oxidation catalyst. It was also demonstrated through biological experiments with rabbits that a significant amount of the complex- (between 6 percent and 39 percent) is recovered in the urinary tract following intravenous infusions attaining between 1.8 and 10 ppm copper.

Binding Sites↗
PubMed1975

Acute renal failure in multiple myeloma.

1. The clinical manifestations, laboratory data and renal histologic features of acute renal failure occurring in 14 patients with multiple myeloma are reviewed and contrasted with the data from 29 previously reported cases. 2. Whereas other reports have stressed the role of intravenous pyelography and dehydration in the development of acute renal failure in multiple myeloma, the most common etiologic factor in our experience was hypercalcemia (7 patients). Other factors included potentially nephrotoxic antibiotics (3 patients) and volume depletion (2 patients). Intravenous pyelography could be clearly implicated in ony one patient. 3. The unusually high incidence of Bence Jones proteinuria in these patients is consistent with the possibility that Bence Jones protein excretion is associated with an increased susceptibility to renal injury. This could be due to an adverse effect of Bence Jones proteins on the renal tubules or their tendency to precipitate in tubular lumina during periods of reduced tubular flow. 4. The prognosis of patients with multiple myeloma who develop acute renal failure is poor; only 5 of our 14 patients survived the early period of acutely impaired renal function, and 4 of these subsequently died within 2 months. Preventive measures particularly the prompt correction of hypercalcemia and volume depletion, are the most important aspects of patient management.

Acute Kidney Injury↗