Transvaginal sonography in early pregnancy.
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Female↗
Biomedical subjects
M A Weiss
Publications and source records attributed to M A Weiss.
A symposium on the surgical pathology of the prostate.
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Humans↗
Diffuse proliferative lupus nephritis: long-term observations in patients treated with ancrod.
Twenty-two patients with histologically demonstrated diffuse proliferative lupus nephritis (DPLN) and glomerular thrombosis received a 14-day course of ancrod, followed in most by nitrogen mustard (mechlorethamine hydrochloride) 0.4 mg/kg. Many were referred when renal function was deteriorating despite large doses of prednisone. The patients had severe disease; there was a high degree of glomerular sclerosis; the median serum creatinine was 137 mumol/l, the diastolic blood pressure 101 mm Hg. Reported previously was a short-term improvement in renal function, blood pressure, and renal histology. Reported here is the long-term follow-up on all 22 patients for an average of 58 months. Three died of causes other than renal failure. Eleven developed end-stage renal disease an average of 27 months after ancrod treatment. The other 8 are alive with no deterioration of renal function after an average of 70 months. This outcome seems satisfactory when disease severity is taken into consideration. Factors present at treatment start that might be associated with subsequent renal function deterioration were: prior prolonged prednisone treatment, extensive glomerular sclerosis, high plasma alpha 2-antiplasmin and possibly triglycerides. During the follow-up period after completion of treatment, later relapses of SLE and DPLN appeared to be an important predictor of deterioration of renal function.
Adult↗
Two-dimensional NMR and photo-CIDNP studies of the insulin monomer: assignment of aromatic resonances with application to protein folding, structure, and dynamics.
The aromatic 1H NMR resonances of the insulin monomer are assigned at 500 MHz by comparative studies of chemically modified and genetically altered variants, including a mutant insulin (PheB25----Leu) associated with diabetes mellitus. The two histidines, three phenylalanines, and four tyrosines are observed to be in distinct local environments; their assignment provides sensitive markers for studies of tertiary structure, protein dynamics, and protein folding. The environments of the tyrosine residues have also been investigated by photochemically induced dynamic nuclear polarization (photo-CIDNP) and analyzed in relation to packing constraints in the crystal structures of insulin. Dimerization involving specific B-chain interactions is observed with increasing protein concentration and is shown to depend on temperature, pH, and solvent composition. In the monomer large variations are observed in the line widths of amide resonances, suggesting intermediate exchange among conformational substates; such substates may relate to conformational changes observed in different crystal states and proposed to occur in the hormone-receptor complex. Additional evidence for multiple conformations in solution is provided by comparative studies of an insulin analogue containing a peptide bond between residues B29 and A1 (mini-proinsulin). This analogue forms dimers and higher-order oligomers under conditions in which native insulin is monomeric, suggesting that the B29-A1 peptide bond stabilizes a conformational substate favorable for dimerization. Such stabilization is not observed in corresponding studies of native proinsulin, in which a 35-residue connecting peptide joins residues B30 and A1; this extended tether is presumably too flexible to constrain the conformation of the B-chain. The differences between proinsulin and mini-proinsulin suggest a structural mechanism for the observation that the fully reduced B29-A1 analogue folds more efficiently than proinsulin to form the correct pattern of disulfide bonds. These results are discussed in relation to molecular mechanics calculations of insulin based on the available crystal structures.
Circular Dichroism↗
Gleason grading of prostatic adenocarcinoma on fine-needle aspiration.
We attempted to use the Gleason grading scheme on fine-needle aspiration (FNA) of the prostate by examining 31 prostate aspirates that had concomitant surgical pathology tissue for correlation. A set of criteria is delineated in which it is proposed that Gleason grading is possible on FNA of the prostate by evaluating aspirated tissue fragments. Cell cytology, including qualitative nucleolar appearance, is not significantly helpful in this approach.
Adenocarcinoma↗
Pancreatic transplants: CT with clinical and pathologic correlation.
A retrospective evaluation of 68 CT scans in 17 patients with pancreatic allografts was performed with clinical and pathologic correlation to better define the nature of abnormalities detected with CT and the role of CT in patient treatment. Patients with clinical complications demonstrated variable degrees of pancreatic inhomogeneity and peripancreatic inflammation on CT scans. These findings were similar in appearance to pancreatitis in the native gland. Most patients proved to be undergoing acute rejection. However, these findings were not specific and were also seen with peripancreatic infection, hemorrhage, and exocrine anastomotic leaks. No CT changes were detected in two of three patients with late rejection. Thus, CT was not helpful in the diagnosis of pancreatic rejection. The most beneficial role of CT was in the detection of intraabdominal fluid collections, including abscesses, hematomas, and pseudocysts. Percutaneous aspiration was invaluable in the distinction between infected and sterile fluid collections; however, percutaneous drainage was of limited use in treatment.
Adult↗
Cyclosporine-associated glomerular and arteriolar thrombosis following renal transplantation.
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Antilymphocyte Serum↗
Glomerular eicosanoid production in acute serum sickness nephritis.
To determine if the induction of immune-mediated glomerular injury influences the formation of glomerular cyclooxygenase products, we measured thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and prostaglandin E2 (PGE2) production by isolated glomeruli of rabbits induced with acute serum sickness nephritis by the administration of bovine serum ablumin (BSA). Animals were randomly assigned to one of three experimental groups: animals injected with BSA (BSA group; n = 11); animals injected with normal saline (control group; n = 11); and animals injected with BSA which were treated with the thromboxane synthetase inhibitor, OKY-046 (BSA + OKY-046; n = 6). Animals in the BSA and BSA + OKY groups developed severe proteinuria and glomerular histologic lesions of nephritis. No differences in proteinuria, serum creatinine and severity of histologic nephritis were observed between the two groups. Examination of glomerular eicosanoid production at the end of the experiment showed a marked reduction of glomerular PGE2 and 6-keto-PGF1 alpha production with a smaller reduction of glomerular TXB2 production in the BSA group. In the BSA + OKY-046 group, the production of TXB2 was significantly less than that in the BSA group; despite this, no effect on proteinuria could be discerned.
Animals↗
Squamous papillary neoplasia of the adult upper aerodigestive tract.
Selected papillary squamous tumors of the upper aerodigestive tract (UADT) mucosa in adult patients do not have well-defined histologic criteria and the clinical behavior is poorly understood. To better characterize this spectrum of neoplasms, UADT papillary neoplasms were evaluated by routine histology, determination of cellular DNA content using Feulgen-stained tissue sections, and the typing of human papillomavirus (HPV) by in situ hybridization. Solitary papillomas were studied in two patients; there was no recurrence in either case, both had normal DNA content, and one was typed as HPV-6 while the other was typed as HPV-11. Seven adult patients with recurrent papillomatosis and at least one biopsy with dysplasia/atypia were identified (mean age at diagnosis, 13.3 years; mean age at last contact, 42.7 years). Six of seven patients had abnormal DNA cellular content in foci of epithelial atypia. In all biopsies evaluated, the papillomas of the seven patients were consistently typed as either HPV-6 or HPV-11. Six patients with malignant papillary neoplasms also had abnormal DNA cellular content, but none revealed evidence of HPV type 6, 11, 16, or 18 by in situ hybridization of tissue sections. In many of the recurrent papillomas, the degree of epithelial atypia encountered was pronounced and was commonly misdiagnosed as carcinoma in situ or papillary carcinoma. The aneuploid DNA content of these foci of atypia reflected the abnormal cellular appearance and partially explained the overdiagnosis of malignancy. However, none of the seven patients were treated for malignant disease and none progressed to invasive carcinoma, with an average follow-up period of almost 30 years. We conclude that histologic and cytologic atypia in HPV-containing papillomatosis may be appreciable. The aneuploid DNA content may represent premalignant conditions and the patient may be at an increased risk for the subsequent development of squamous cancer. However, none of the seven patients with recurrent papillomatosis developed any evidence of malignancy. In addition, none of the patients with papillary carcinomas had previous recurrent papillomatosis.
Adult↗
A thromboxane synthetase antagonist ameliorates progressive renal disease of Dahl-S rats.
Recent studies have suggested a role for thromboxane in the progression of renal disease. The current study evaluated the role of this arachidonic acid metabolite in a model of renal disease which bears many biologic similarities to that in the kidneys of patients with chronic progressive renal failure. The model is that induced by ferritin-anti-ferritin immune complex nephritis in Dahl-salt sensitive rats rendered hypertensive by a high salt intake. Rats with this model of renal disease were chronically given a thromboxane synthetase antagonist OKY-046 or a placebo treatment from 16 to 29 weeks of age. Sequential observations of serum creatinine and 24-hour urinary protein excretion showed an ameliorating effect of OKY-046 on these renal parameters. Histologic examination of the kidneys also showed significantly less glomerular sclerosis in OKY-046 treated animals. The efficacy of OKY-046 was monitored by measurements of serum TXB2 levels and of glomerular production of TXB2 (and other prostaglandins); amounts of TXB2 were significantly reduced in the OKY-046 group. It is concluded that blockade of thromboxane generation has been successful in ameliorating the functional and structural lesions in this model of renal disease, providing further support to the thesis that thromboxane is an important mediator in events leading to eventual chronic renal failure and sclerosis.
Acrylates↗
Alport's syndrome: risk of glomerulonephritis induced by anti-glomerular-basement-membrane antibody after renal transplantation.
Two patients with Alport's syndrome developed glomerulonephritis induced by anti-glomerular-basement-membrane (anti-GBM) antibody after renal transplantation. One patient presented at 5 months after transplantation the second patient 18 months after transplantation. Both grafts failed and the patients returned to dialysis. Our observations suggest that the patients with Alport's syndrome are at risk of developing anti-GBM antibody type glomerulonephritis in the transplanted kidney. This does not occur in the early period after transplantation, probably because of heavy immunosuppression.
Adult↗
C3 dependent, C5 independent immune complex glomerulopathy in the mouse.
This study examines the role of complement in a murine model of accelerated nonproliferative immune complex glomerulopathy. Two C5 deficient strains (DBA/2J and B10.D2oSnJ) as well as normocomplementemic mice consistently develop heavy proteinuria and glomeruli show loss of normal visceral epithelial cell architecture within 4 days of intravenous antigen administration. In contrast, animals depleted of C3 with cobra venom factor fail to develop proteinuria and retain discrete foot processes. Semiquantitative evaluation of antigen and antibody in glomeruli shows equivalent deposition in mice from all groups. The localization of these deposits, however, is different in C3-depleted mice. There is extensive accumulation of deposits along the subepithelial aspect of the glomerular basement membrane of normocomplementemic and C5 deficient mice while deposits in glomeruli of C3-depleted animals accumulate in the subendothelial region and do not cross the glomerular basement membrane. These data demonstrate that in this model, glomerular injury is dependent on complement components generated up thru C3 but not C5 or latter components. In addition, our data suggest that C3 is important in the movement of immune complexes across the glomerular basement membrane. Although the mechanism by which complement is mediating injury in this model is not known, it does not appear to involve an inflammatory cell infiltrate or the terminal complement components.
Animals↗
Fibrinolysis in glomerulonephritis treated with ancrod: renal functional, immunologic and histopathologic effects.
The effects of a 14-day course of ancrod on fibrinolysis, renal function and structure, and immunologic findings are reported in 37 patients with glomerulonephritis. Patients were divided into two groups. In the first, the level of fibrin degradation products within 48 h was relatively low (less than 1 mg/ml). In these patients there was a linear relationship between changes in levels of fibrin degradation products and fibrinogen, suggesting that fibrin degradation products derived from ancrod-cleaved-fibrinogen in the circulating pool; in most, level of plasma alpha 2-antiplasmin before treatment was elevated. In the second, the level of fibrin degradation products within 48 h was high (greater than 1 mg/ml). Compared with the change in fibrinogen, a disproportionate increase in levels of fibrin degradation products suggested that a significant amount derived from sources other than plasmin digested ancrod-cleaved-fibrinogen, thus reflecting effective fibrinolysis, perhaps also in tissues; in most, the level of plasma alpha 2-antiplasmin was normal before treatment. In those with initial high levels of fibrin degradation products, higher levels persisted throughout treatment, changes in other fibrinolysis components were greater, and plasminogen activator inhibitor levels became normal. In patients with initial high but not with initial low response in fibrin degradation products renal function improved within 24 to 48 h and continued to improve thereafter; there was an immediate but temporary increase in proteinuria. Microvascular thrombosis decreased significantly, indicating effective removal of fibrin from glomeruli. The relation of early fibrinolysis to changes in immunologic and histopathologic findings was analyzed in patients with lupus nephritis. With ancrod, there was an increase toward normal of serum C3 and C4, a decrease in serum Igs, gamma globulin and anti-dsDNA antibody and in glomerular C3 and Ig deposits, suggesting that ancrod had favorable effects on immunologic factors. There were no clinical differences in patients with initial high and low responses, but the relationship of microvascular and inflammatory indexes before treatment differed. Initial renal biopsies and those after treatment were carried out on average 28 days apart. Inflammatory and microvascular indexes and glomerular thrombi decreased in patients with initial high levels of fibrin degradation products; fibrosclerosis index and glomerular sclerosis increased in patients with initial low levels of fibrin degradation products. Fibrinolysis expressed as the 48 h (fibrin degradation products/fibrinogen) ratio, correlated inversely with change in fibrosclerosis index and glomerular sclerosis in the whole group, and especially in those with initial high levels of fibrin degradation products.(ABSTRACT TRUNCATED AT 400 WORDS)
Ancrod↗
1H NMR aromatic spectrum of the operator binding domain of the lambda repressor: resonance assignment with application to structure and dynamics.
The aromatic 1H NMR resonances of the operator binding domain of lambda repressor are completely assigned. Since the resonances of this 23-kilodalton domain are too broad for the application of two-dimensional strategies for sequence-specific assignment, an alternative approach has been used. Assignments are obtained by a combination of one- and two-dimensional NMR methods, by the study of genetically altered domains, and by the biosynthetic incorporation of deuterium labels. The resulting assignments provide sensitive markers for tertiary and quaternary structure. Nuclear Overhauser enhancements demonstrate that the major features of the crystal structure, including the dimer contacts, are retained in solution. The rates of aromatic ring rotation indicate that the globular domain is not rigid; significant barriers to ring rotation are observed only in the dimer contact.
Bacteriophage lambda↗
Dimerization of the operator binding domain of phage lambda repressor.
Dimerization of lambda repressor is required for its binding to operator DNA. As part of a continuing study of the structural basis of the coupling between dimer formation and operator binding, we have undertaken 1H NMR and gel filtration studies of the dimerization of the N-terminal domain of lambda repressor. Five protein fragments have been studied: three are wild-type fragments of different length (1-102, 1-92, and 1-90), and two are fragments bearing single amino acid substitutions in residues involved in the dimer interface (1-102, Tyr-88----Cys; 1-92, Ile-84----Ser). The tertiary structure of each species is essentially the same, as monitored by the 1H NMR resonances of internal aromatic groups. However, significant differences are observed in their dimerization properties. 1H NMR resonances of aromatic residues that are involved in the dimer contact allow the monomer-dimer equilibrium to be monitored in solution. The structure of the wild-type dimer contact appears to be similar to that deduced from X-ray crystallography and involves the hydrophobic packing of symmetry-related helices (helix 5) from each monomer. Removal of two contact residues, Val-91 and Ser-92, by limited proteolysis disrupts this interaction and also prevents crystallization. The Ile-84----Ser substitution also disrupts this interaction, which accounts for the severely reduced operator affinity of this mutant protein.
Amino Acids↗
Quaternary structure and function in phage lambda repressor: 1H-NMR studies of genetically altered proteins.
The quaternary structure and dynamics of phage lambda repressor are investigated in solution by 1H-NMR methods. lambda repressor contains two domains separable by proteolysis: an N-terminal domain that mediates sequence-specific DNA-A binding, and a C-terminal domain that contains strong dimer and higher-order contacts. The active species in operator recognition is a dimer. Although the crystal structure of an N-terminal fragment has been determined, the intact protein has not been crystallized, and there is little evidence concerning its structure. 1H-NMR data indicate that the N-terminal domain is only loosely tethered to the C-terminal domain, and that its tertiary structure is unperturbed by proteolysis of the "linker" polypeptide. It is further shown that in the intact repressor structure a quaternary interaction occurs between N-terminal domains. This domain-domain interaction is similar to the dimer contact observed in the crystal structure of the N-terminal fragment and involves the hydrophobic packing of symmetry-related helices (helix 5). In the intact structure this interaction is disrupted by the single amino-acid substitution, Ile84----Ser, which reduces operator affinity at least 100-fold. We conclude that quaternary interactions between N-terminal domains function to appropriately orient the DNA-binding surface with respect to successive major grooves of B-DNA.
Bacteriophage lambda↗
Basal cells of prostate in fine-needle aspiration.
Fine-needle aspiration in conjunction with a transrectal core biopsy was performed on a 58-year-old man who presented with a prostate nodule. The aspirate contained many cell clusters that were negative for prostatic acid phosphatase and cytologically appeared to be basal cells. The entity of basal cell hyperplasia of the prostate is discussed with reference to its appearance in aspiration cytologic examination. Emphasis is placed upon the possibility that these cells may be mistaken for cancer cells.
Adenocarcinoma↗
Small cell undifferentiated carcinoma of the urinary bladder. A light-microscopic, immunocytochemical, and ultrastructural study of 12 cases.
The clinicopathologic, immunocytochemical, and ultrastructural features of 12 small cell undifferentiated carcinomas (SCUCs) of the urinary bladder are herein reported. The patients ranged in age from 50 to 82 years (median, 76 years). Ten patients were male and two were female. Gross hematuria was the most frequent complaint (67%). Five patients died of disease (median survival, 4 months), three patients are still living with unresectable disease after 6, 10, and 12 months, and four patients were only recently diagnosed. Grossly, most of the tumors were large polypoid masses. On light-microscopic examination, they resembled the intermediate and oat cell variants of pulmonary SCUC. Eight SCUC were associated with other forms of in situ or invasive carcinoma, including transitional cell carcinoma (seven cases), adenocarcinoma (three cases), squamous cell carcinoma (three cases), spindle cell carcinoma (one case), and atypical carcinoid tumor (one case). Immunocytochemically, 11 of the 12 tumors expressed one or more epithelial cell markers (epithelial membrane antigen, human milk fat globule protein-2, cytokeratin). Eleven of the 12 SCUCs were also positive for one or more neuroendocrine markers (neuron specific enolase, chromogranin, Leu-7, vasoactive intestinal polypeptide, serotonin). Electron microscopy performed on seven tumors demonstrated dense-core granules (150-250 nm) in all cases, with tonofilaments in four cases, dendrite-like processes in two cases, and intercellular lumina in one case. The clinicopathologic features of 18 previously reported SCUC of the urinary bladder are also reviewed. SCUC arising in this location is an aggressive neoplasm that often demonstrates multidirectional differentiation, including the frequent but not invariable expression of neuroendocrine features.
Aged↗