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Biomedical subjects

M A Weiss

Publications and source records attributed to M A Weiss.

At least 145 records · Page 8Linked to original sources
PubMed1987

Silicone-induced erosive arthritis: radiologic features in seven cases.

As silicone polymer implants are used more widely for arthroplasty of the wrist, hand, and foot, the complication of silicone-induced erosive arthritis in these areas is being recognized with increasing frequency. Pathologically, there is a chronic foreign-body type of inflammation with both intra- and extracellular silicone particulate debris. We report seven cases with this complication in various locations, showing distinctive radiographic findings. These include well-defined marginal articular erosions and subchondral cysts with marginal sclerosis; normal mineralization; and deformity, dislocation, or decrease in the size of the silicone implant. Prompt recognition of this complication is important, because surgical removal of the silicone implant terminates the progressive and destructive process.

Adult↗
PubMed1987

An immune complex glomerulopathy associated with glomerular capillary thrombosis in the laboratory mouse. A highly reproducible accelerated model utilizing cationized antigen.

An accelerated, highly reproducible model of an immune complex glomerulopathy in the laboratory mouse was developed by using cationized bovine gamma-globulin (cat-BGG) as the nephritogenic agent. Preimmunized Balb/c mice given three 250-micrograms doses of cat-BGG consistently develop a nonproliferative glomerular lesion which becomes manifested clinically by the nephrotic syndrome and results in death within 14 days. Significant proteinuria is evident by day 4 (24 hours after the third dose of cat-BGG) at which time extensive deposits of cat-BGG, IgG, and C3 are localized along the glomerular capillary walls. At the ultrastructural level, subepithelial deposits and foot process effacement are evident. By day 6, subendothelial and mesangial deposits are also present, and by day 10, extensive glomerular capillary thrombosis and early crescent formation develop. The reproducibility and rapidity of the induction of disease, and the spectrum of pathological changes occurring in the glomeruli make this murine model of an immune complex glomerulopathy potentially useful for the study of the mechanisms underlying the induction and progression of glomerular injury and the evaluation of potential therapy.

Animals↗
PubMed1987

Induction of mouse monocyte-macrophage replication by a mesangial cell-derived factor.

Conditioned media of cultured mouse mesangial cells (possessing microfilaments) were shown to contain a factor that stimulated splenic monocytes-macrophages and blood monocytes to replicate. Replicated cells were shown to express MAC-1 antigen as demonstrated by immunofluorescence with anti-MAC 1 and to possess Fc receptors as evidenced by their capacity to ingest sensitized erythrocytes. Preliminary characterization revealed the following characteristics: by Amicon ultrafiltration, fractions greater than 100,000 daltons were shown to have biologic activity; chromatofocusing of these active fractions revealed a peak of activity associated with fractions having pH 4; heating to 100 degrees C for 10 minutes abolished almost all activity, whereas trypsin treatment was without effect. The observations suggest a mechanism by which mesangial cells may modulate the proliferation of monocytes-macrophages that infiltrate the glomerulus in glomerulonephritis.

Animals↗
PubMed1987

Prostaglandin E2 in tylose gel for cervical ripening before induction of labor.

Two hundred seventeen women who received 3 mg of prostaglandin E2 (PGE2) gel applied to the cervix followed by adjunctive oxytocin were compared to 94 patients whose labor was induced with oxytocin alone (OA). Postdatism, pregnancy-induced hypertension and rupture of the membranes were the major indications for induction of labor, accounting for 70% of the PGE2 group and 88% of the OA group. Mean initial cervical scores were found to be significantly less favorable among PGE2 patients as compared with OA patients. Though PGE2 was associated with a significant improvement in mean cervical scores, responsiveness of the cervix to PGE2, as determined by clinical examination, was not necessary for a successful induction. Failed inductions were infrequent in both groups. Nulliparous PGE2 patients with unfavorable cervical scores had fewer cesarean sections (CSs) and shorter labors than did their OA counterparts. Complications were uncommon but largely due to the subsequent use of oxytocin. Patients with prior CSs were safely induced following PGE2 cervical ripening.

Cervix Uteri↗
PubMed1986

N-terminal domain of the bacteriophage lambda repressor: investigation of secondary structure and tyrosine hydrogen bonding in wild-type and mutant sequences by Raman spectroscopy.

Laser Raman spectroscopy has been employed to investigate structures of the lambda repressor N-terminal fragment, which recognizes operator DNA. Examination of repressor fragments containing deuterated amide groups and specifically labeled deuteriotyrosines has enabled the assignment of many of the conformation-sensitive Raman bands. By use of Fourier deconvolution and signal averaging techniques, the spectra of both wild-type and mutant sequences have been obtained as a function of the total protein concentration in aqueous solution over the range 5-100 mg/mL. This analysis has permitted monitoring of the monomer-dimer association of the repressor fragment and determination of the effects of dimerization upon individual side-chain interactions and main-chain secondary structure. The spectra are interpreted to reveal the hydrogen-bonding environments of four tyrosines of the N-terminal fragment (Y22, Y60, Y85, and Y88). The fifth tyrosine (Y101) is known from NMR experiments to be exposed to solvent molecules. The results show that in the dimer Y22 and Y85 are each acceptors of a strong hydrogen bond from a positive donor group, while Y88 is the donor of a strong hydrogen bond to a negative acceptor and Y60, like Y101, is involved in both a donor role and an acceptor role. Y60, Y85, and Y88, which are all near the dimer interface, undergo a collective change in hydrogen-bonding environment with dissociation of the dimer. The net effect of this change is the conversion of one acceptor tyrosine, deduced to be Y88, to a combined donor and acceptor role. The Raman results also indicate a predominantly alpha-helical structure for the N-terminal fragment in aqueous solution, with 70 +/- 4% of the residues incorporated into helical domains. The amount of alpha-helix determined from the Raman spectrum is consistent with X-ray and prediction results and is altered neither by the mutations C85----Y85 and C88----Y88 nor by dissociation of the dimer.

Amino Acid Sequence↗
PubMed1986

An engineered intersubunit disulfide enhances the stability and DNA binding of the N-terminal domain of lambda repressor.

Site-directed mutagenesis has been used to replace Tyr-88 at the dimer interface of the N-terminal domain of lambda repressor with cysteine. Computer model building had suggested that this substitution would allow formation of an intersubunit disulfide without disruption of the dimer structure [Pabo, C. O., & Suchanek, E. G. (1986) Biochemistry (preceding paper in this issue)]. We find that the Cys-88 protein forms a disulfide-bonded dimer that is very stable to reduction by dithiothreitol and has increased operator DNA binding activity. The covalent Cys88-Cys88' dimer is also considerably more stable than the wild-type protein to thermal denaturation or urea denaturation. As a control, Tyr-85 was replaced with cysteine. A Cys85-Cys85' disulfide cannot form without disrupting the wild-type structure, and we find that this disulfide bond reduces the DNA binding activity and stability of the N-terminal domain.

Amino Acid Sequence↗
PubMed1986

Characterization of renal neoplasms with monoclonal antibodies to leukocyte differentiation antigens.

Several monoclonal antibodies against human leukocyte differentiation antigens have been shown to react with normal kidney. Four monoclonal antibodies with different patterns of reactivity on normal kidney were tested against 20 renal epithelial neoplasms and 5 Wilms' tumors. In general, the expression of these antigens on renal tumors was faithful to their presence on normal kidney; this finding suggested that most renal tumors may be derived from proximal tubule epithelium. There was, however, both intertumor and intratumor heterogeneity of expression of these antigens, but the different phenotypes encountered did not correlate in any simple way with histologic subclassification. In contrast, the five Wilms' tumors were phenotypically different from the epithelial neoplasms, consistent with an origin from a more primitive renal cell.

Antibodies, Monoclonal↗
PubMed1986

Squamous cell carcinoma of bladder: an increased incidence in blacks.

In a ten-year review of bladder cancer cases at the University Hospital, Cincinnati, Ohio, there was an apparent increased incidence of squamous cell histology in black patients. We report the findings of our local study as well as the results of our literature search on bladder cancer histology in racial subgroups. Squamous cell carcinoma represents 10 to 15 per cent of bladder cancer cases in blacks and approximately 5 per cent of bladder cancer cases in whites.

Adult↗
PubMed1986

Nephrotic syndrome, progressive irreversible renal failure, and glomerular "collapse": a new clinicopathologic entity?

Six patients are reported with nephrotic syndrome and relatively rapid progression to irreversible renal failure. The renal histologic findings are unusual. The most striking changes are collapse of glomerular capillary loops, such as might occur with glomerular hypoperfusion; significant tubulointerstitial damage is also seen. These patients appear to have a clinicopathologic entity hitherto unreported. Its differentiation from other causes of progressive glomerular damage, and particularly from focal and segmental glomerulosclerosis, is discussed.

Adolescent↗
PubMed1986

Isotope-detected 1H NMR studies of proteins: a general strategy for editing interproton nuclear Overhauser effects by heteronuclear decoupling, with application to phage lambda repressor.

A strategy for editing interproton nuclear Overhauser effects (NOEs) in proteins is proposed and illustrated. Selective incorporation of 13C- (or 15N)-labeled amino acids into a protein permits NOEs involving the labeled residues to be identified by heteronuclear difference decoupling. Such heteronuclear editing simplifies the NOE difference spectrum and avoids ambiguities due to spin diffusion. Isotope-detected 1H NMR thus opens to study proteins too large for conventional one- and two-dimensional NMR methods (20-75 kDa). We have applied this strategy to the N-terminal domain of phage lambda repressor, a protein of dimer molecular mass 23 kDa. A tertiary NOE from an internal aromatic ring (Phe-51) to a beta-13C-labeled alanine residue (Ala-62) is demonstrated.

DNA-Binding Proteins↗
PubMed1986

Spindle-cell carcinoma of the upper aerodigestive tract mucosa. An immunohistologic and ultrastructural study of 18 biphasic tumors and comparison with seven monophasic spindle-cell tumors.

The histogenetic origin of the spindle-cell component of spindle-cell carcinoma of the head and neck mucosa remains controversial. The spindle cells have been considered a variant growth pattern of squamous-cell carcinoma, a non-neoplastic mesenchymal reaction, and a malignant admixture of epithelial and mesenchymal neoplasm. To evaluate the spindle-cell component, we studied 25 tumors (18 biphasic and seven monophasic) by utilizing the following: an avidin-biotin complex immunoperoxidase technique with a variety of antikeratin antibodies (AE1, AE3, CAM 5.2, 35BH11, and polyclonal Dako) and a monoclonal antivimentin antibody, and an avidin-biotin alkaline phosphatase double-labeling technique to detect coexpression of keratin and vimentin. The immunohistologic staining pattern was compared with electron-microscopic studies. Eight of 18 biphasic neoplasms contained immunoreactive keratin in the spindle-cell component that was distributed focally in a minority of cells in 3 tumors and diffusely throughout five of the neoplasms. Four of seven ulcerated monophasic spindle-cell tumors devoid of histologic squamous-cell carcinoma also were keratin positive, confirming epithelial differentiation. The majority of the spindle cells in all the tumors contained vimentin intermediate filaments. In three immunoperoxidase keratin positive biphasic tumors examined with alkaline phosphatase double labeling, occasional spindle cells were found that coexpressed keratin and vimentin and were interspersed with cells expressing either intermediate filament. Electron microscopy was performed on the spindle-cell component of 13 tumors, nine biphasic and four monophasic. Of the biphasic tumors, four were immunoperoxidase keratin positive; three of these showed epithelial differentiation by electron microscopy. Five biphasic tumors were keratin negative, and three tumors had epithelial differentiation by electron microscopy. Four monophasic spindle-cell tumors were immunoperoxidase keratin positive, and one of these had epithelial features by electron microscopy. Two monophasic tumors were keratin negative and without ultrastructural evidence of epithelial features. By using a combination of immunohistochemical and electron-microscopic observations, we identified evidence for epithelial differentiation in the spindled cells in 11 of 18 biphasic tumors and four of seven monophasic spindle-cell tumors.

Aged↗
PubMed1985

Segmental necrotizing glomerulonephritis: diagnostic, prognostic, and therapeutic significance.

Renal biopsies from 50 patients with segmental necrotizing glomerulonephritis (SNGN) were divided into three groups on the basis of initial clinical information: (group A) Wegener's granulomatosis (WG)--14 patients; (group B) SNGN without renal vasculitis (RV)--21 patients; and (group C) SNGN with RV--15 patients. Renal biopsy findings did not distinguish the SNGN in WG from non-WG patients. However, focal endocapillary proliferation was more common in non-WG groups B (48%) and C (33%) than in WG (7%). In addition, GBM deposits of both IgG and C3 were present in 35% of biopsies in group B and 33% in group C in comparison to only 7% in WG. Glomerular fibrin deposition was common in all groups (54% group A, 70% group B, and 100% group C), suggesting that coagulation plays a role in the development of SNGN. Histologic parameters of severity and chronicity of the SNGN were inconsistent predictors of outcome, although an increased percentage of crescents in the non-WG groups correlated with a poorer prognosis. Chronic renal failure developed in 46% of group A patients, 65% group B, and 73% group C. After clinical follow-up, 15 patients had WG, 15 patients had documented or suspected systemic vasculitis (SV), and idiopathic SNGN was present in 20 patients. Sixty-six percent of patients with SV had RV, and 62% of biopsies with RV were from patients with SV. Chronic renal failure developed in 78% of patients with idiopathic SNGN and 57% patients with SV. These findings confirm that SNGN carries a poor prognosis, independent of its association with WG or SV. Fourteen of the 15 WG patients were treated with alkylating agents, and the development of chronic renal failure appeared to be related to delays in diagnosis and therapy. In the non-WG groups, presentation in acute renal failure with high serum creatinine and long duration of symptoms was predictive of development of chronic renal failure. Therapy in the non-WG patients consisted of alkylating agents (seven patients), steroids (20 patients), and dialysis only (seven patients). The seven non-WG patients treated with alkylating agents had clinical responses similar to WG patients, and cyclophosphamide therapy appeared to be most beneficial to patient outcome. Results of this retrospective study stress the importance of early diagnosis and, although based on small numbers of patients, suggest that aggressive chemotherapy should be recommended for SNGN, independent of its association with biopsy-proven WG or documented SV.

Adult↗
PubMed1985

Transplant glomerulopathy: evolution of morphologically distinct changes.

The study was undertaken to redefine morphological appearance and clinical implications of the diagnosis of transplant glomerulopathy (TGP). Fifty-seven renal transplant biopsy specimens from thirty patients with the diagnosis of TGP were evaluated. Multiple repeat biopsies in several cases enabled us to follow the pattern of the evolution of the changes. Transplant dysfunction manifested itself 8 days to 13 years post-transplantation by proteinuria and/or elevated creatinine level. The earliest recognizable morphological change was the swelling of endothelial and mesangial cells. This stage was called evolving TGP. The intermediate stage was characterized by enlarged glomeruli with lobular simplification, spongy matrix, and glomerular basement membrane (GBM) deformities. The advanced stage of TGP showed pronounced GBM changes (reduplication, interposition). These light microscopic changes were associated with vascular rejection. Immunofluorescence showed significant glomerular deposition of IgM (83% of biopsies) and fibrinogen (66%). Electron microscopy at an early stage showed subendothelial widening with cellular debris and focal endothelial damage with fibrin deposition. In the advanced stage, complex GBM changes developed as a reparative response to the capillary wall injury. Effacement of foot processes was a constant finding at all stages. In follow-up, twenty-three allografts failed (77%), five patients are stable, and two died due to other causes. TGP has specific morphology with an attendant poor long-term prognosis for the allograft.

Basement Membrane↗
PubMed1985

NH2-terminal arm of phage lambda repressor contributes energy and specificity to repressor binding and determines the effects of operator mutations.

Several lines of evidence indicate that the phage lambda repressor recognizes its operator by using, in part, an alpha helix (the "recognition helix"), which it inserts into the major groove of DNA. In addition to its recognition helix, lambda repressor has an "arm," consisting of the first six amino acids, that wraps around the DNA helix. We constructed plasmids that, in Escherichia coli, direct the expression of derivatives of lambda repressor that lack the NH2-terminal one, three, six, or seven amino acids. We studied these modified proteins in vivo and in vitro, and from our results we argue that the arm: contributes a large portion of the binding energy; helps to determine sequence specificity of binding and, in particular, the relative affinities for two wild-type binding sites; determines entirely repressor's response to one operator mutation (a "back-side" mutation); magnifies repressor's response to other operator mutations ("front-side" mutations); and increases the sensitivity of repressor binding to salt concentration and temperature.

Amino Acid Sequence↗