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Biomedical subjects

M Schoenberg

Publications and source records attributed to M Schoenberg.

At least 37 records · Page 2Linked to original sources
PubMed1997

Graphical evaluation of alkylation of myosin's SH1 and SH2: the N-phenylmaleimide reaction.

Previous assertions about the effect of alkylation of SH1 and SH2 on the myosin high-salt calcium and EDTA ATPases have been summarized, and a simple procedure for obtaining the fractional labeling of SH1 and SH2 after treatment of myosin with alkylating agents has been derived. A simple graphical procedure for illustrating the degree of preference of a particular alkylating agent for SH1 over SH2 has also been developed. The procedures we developed were validated by applying them to two previously studied compounds, 4-(2-iodoacetamido)-TEMPO and 2,4-dinitrofluorobenzine, and then were used to determine a procedure for maximizing the extent of labeling of SH1 alone by N-phenylmaleimide, a compound not previously studied in this manner. It was found that approximately 80% of the SH1 sites could be alkylated without significant alkylation of SH2.

Alkylation↗
PubMed1997

Pseudotumor of the bladder: a late complication of inguinal herniorrhaphy.

Damage to the bladder during inguinal hernia repair is possible especially if the bladder or a bladder diverticulum is involved in the hernia sac. Unrecognized injury to the bladder can lead to late complications. We report a case of pseudotumor in a bladder diverticulum due to long-term retention of a misplaced suture. The literature on bladder injury after inguinal herniorrhaphy and on pseudotumor formation is briefly reviewed. It is important to be aware of a history of inguinal surgery and to obtain definitive histologic evidence of malignancy prior to making the diagnosis of bladder carcinoma. This will avoid unnecessary radical surgery, chemotherapy, or radiation therapy.

Diverticulum↗
PubMed1996

High-density mapping of chromosomal arm 1q in renal collecting duct carcinoma: region of minimal deletion at 1q32.1-32.2.

Collecting duct carcinoma (CDC) of the kidney is a rare malignant neoplasm of distal nephron origin. Previous studies of CDC have shown loss of heterozygosity on chromosomal arm 1q in 57% of the cases studied. To better characterize 1q loss in CDC, we performed high-density mapping of the entire long arm of chromosome 1 in 13 CDC tumor samples. We observed complete deletion of chromosomal arm 1q in 5 samples and partial deletion in 4 additional tumors. Our study further showed that the region of minimal deletion is located at 1q32.1-32.2. Sixty-nine percent (9 of 13) of the tumors showed loss of heterozygosity in this area. These data suggest that a gene or group of genes that contribute to the development of distal nephron tumors may be located within the 1q32.1-32.2 region.

Chromosome Deletion↗
PubMed1996

Distal nephron renal tumors: microsatellite allelotype.

Tumors of varying malignant potential arise from the complex epithelial lining of the nephron. Although the molecular characteristics of renal clear cell carcinomas, which arise from the proximal tubule, have been studied, little is known about tumors that develop from other parts of the renal tubular system. To elucidate common molecular lesions that may contribute to the development or progression of nonproximal tubule renal tumors, we performed a detailed microsatellite allelotype of lesions thought to arise from the renal collecting duct. Eighteen collecting duct carcinomas (CDCs) and 13 renal oncocytomas were studied using highly informative microsatellite markers on all autosomal arms. Loss of heterozygosity (LOH) was identified on multiple chromosomal arms in CDCs and renal oncocytomas. Microsatellite analysis revealed LOH of 1q in 57% of informative CDCs. LOH was also observed on arms 6p (45%), 8p (40%), and 21q (40%). In renal oncocytomas, LOH of 1q occurred in approximately 30% of tumors, but 1p LOH was observed in 57% of informative cases analyzed. High levels of LOH were also observed on arms 8p, 14q, 19q, and 21q in the oncocytomas studied. Loss of chromosomal arm 3p was infrequent in both tumor types. Our results suggest that the molecular events that contribute to the development of distal nephron tumors are distinct from those associated with the etiology of proximal tubule renal cancers.

Adenoma, Oxyphilic↗
PubMed1996

Familial transitional cell carcinoma.

PURPOSE: Bladder cancer is a common malignancy, and a frequent cause of urological consultation and surgical intervention. Except for smoking and certain occupational exposures, the etiology of bladder cancer is largely unknown. Although the majority of patients with bladder cancer do not have a family history of transitional cell carcinoma of the urinary tract, the study of familial transitional cell carcinoma may lead to knowledge of the pathogenesis of this disease. MATERIALS AND METHODS: To evaluate the current understanding of familial transitional cell carcinoma, we reviewed the contemporary literature for case reports and epidemiological studies about this disease. RESULTS: Numerous case reports document the clustering of transitional cell carcinoma in families, several of which demonstrate an extremely early age at onset of disease, which argues in favor of a genetic component to familial transitional cell carcinoma. The results of large epidemiological studies also suggest the existence of familial transitional cell carcinoma, and first degree relatives appear to have an increased risk for disease by a factor of 2. Familial clustering of smoking does not appear to be the cause of this increased risk. CONCLUSIONS: Familial transitional cell carcinoma may be the result of a genetically transmitted predisposition to disease, at least in some affected families. Further studies are required to identify candidate genes that may be responsible for this form of bladder cancer.

Carcinoma, Transitional Cell↗
PubMed1995

The site and stoichiometry of the N-phenylmaleimide reaction with myosin when weakly-binding crossbridges are formed in skinned rabbit psoas fibers.

Treatment of relaxed skinned rabbit psoas muscle fibers with 0.1 mM N-phenylmaleimide (NPM) for 1 h locks all of the crossbridges in a weakly-binding state resembling that of the myosin.ATP crossbridge. Under these conditions, NPM reacts mainly with myosin heavy chain (Barnett et al. (1992) Biophys. J. 61, 358-367). Here the specific sites for that reaction are explored. Small bundles of rabbit psoas muscle fibers were treated with Triton X-100 to make the fiber sarcolemmas permeable. The bundles were treated with 0.1 mM [14C]NPM for 1 h, and homogenized for SDS-PAGE. 43 +/- 2.2% of the muscle fiber protein ran in the myosin heavy chain band, the same as for untreated fibers. An alkylating stoichiometry of 2.2 +/- 0.33 moles NPM per mole myosin heavy chain was determined. Exhaustive trypsin digestion followed by two-dimensional thin-layer chromatography and reverse-phase HPLC revealed two major sites on myosin heavy chain for NPM binding. The sites contained about the same amount of linked NPM, suggesting that the reaction stoichiometry of each site under the conditions studied is approx. 1 mol NPM/mol myosin heavy chain. Comparison of the labeled tryptic peptides with NPM-reacted synthetic SH1 and SH2 tryptic peptides and analysis of the treated fiber bundles' ATPase activity suggested that the sites for NPM reaction on myosin heavy chain when it locks crossbridges in a weakly-binding state are Cys-697 (SH2) and Cys-707 (SH1).

Animals↗
PubMed1995

Frequent loss of chromosome arms 8p and 13q in collecting duct carcinoma (CDC) of the kidney.

Collecting duct carcinoma (CDC) is a malignant renal neoplasm that is believed to arise from the epithelium of the ducts of Bellini in the distal nephron. These tumors are clinically aggressive and more often occur in a younger population than is typical of the more common clear cell renal carcinoma (RCC). Using highly informative polymorphic microsatellite markers on chromosome arms 3p, 5q, 6q, 9p, 9q, 11p, 13q, 17p, and 18q, we analyzed DNA from nonmalignant and tumor tissue in 6 cases of CDC. We found no evidence of 3p loss of heterozygosity (LOH) in these renal tumors by using multiple markers, a finding that distinguishes CDC from RCC in which 3p LOH has frequently been observed. We found LOH of 8p in 50% of the tumors examined; in addition, we observed LOH of 13q in 50% of the tumors studied. Interestingly, 8p LOH may be associated with high stage and poor clinical prognosis. These data suggest that the molecular events responsible for the development of CDC differ from those associated with the origin of RCC, and that tumor suppressor genes on 8p and 13q may be involved in the pathogenesis of CDC.

Adolescent↗
PubMed1993

The strength of binding of the weakly-binding crossbridge created by sulfhydryl modification has very low calcium sensitivity.

The acto-subfragment-1.ATP state is an important intermediate in the Ca-activated acto-S1 ATPase reaction, suggesting that the myosin.ATP crossbridge seen in muscle fibers similarly may be an important intermediate in the contractile cycle. Treatment of muscle fibers with either para-phenylenedimaleimide (pPDM) or N-phenylmaleimide (NPM) alters the myosin crossbridges so that they bind to the actin filament with about the same affinity as the myosin.ATP crossbridge. Additionally, the treated crossbridges and the myosin.ATP crossbridge have virtually identical attachment and detachment rate constants. Thus the treated crossbridges appear to be reasonable analogues of the weakly-binding myosin.ATP crossbridges of relaxed fibers and studies of the treated fibers may shed some light on the behavior of the physiologically important myosin.ATP crossbridge. We have examined the influence of Ca2+ on the binding and rate constants of pPDM- and NPM-treated weakly-binding crossbridges. In agreement with earlier solution studies, we found almost no Ca-sensitivity of the binding of pPDM- or NPM-treated crossbridges.

Adenosine Triphosphate↗
PubMed1993

Equilibrium muscle crossbridge behavior: the interaction of myosin crossbridges with actin.

The interaction of myosin crossbridges with actin under equilibrium conditions is reviewed. Similarities and differences between the weakly- and strongly-binding interactions of myosin crossbridges with actin filaments are discussed. A precise, narrow definition of weakly-binding crossbridges is given. It is postulated that the fundamental difference between the weakly- and strongly-binding equilibrium interaction of crossbridges with actin is that the crossbridge heads are mobile after attachment in the first case but not in the second. It is argued that because the weakly-binding crossbridge heads are mobile after attachment, the heads appear to function independently of each other. The lack of head mobility in attached strongly-binding crossbridges makes the strongly-binding crossbridge heads appear to act cooperatively. This model of the strongly-binding crossbridge gives an explanation for two important and otherwise unexplained observations. It explains why the rate constant of force decay after a small stretch is a sigmoidal function of nucleotide analogue concentration, and why, in the presence of analogues or in rigor, the rate constant of force decay after a small stretch is often significantly slower than the rate constant for myosin subfragment-1 detachment from actin in solution. The model of the weakly-binding crossbridge accurately describes the behavior of the myosin-ATP crossbridge.

Actins↗
PubMed1992

Formation of ATP-insensitive weakly-binding crossbridges in single rabbit psoas fibers by treatment with phenylmaleimide or para-phenylenedimaleimide.

Chaen et al. (1986. J. Biol. Chem. 261:13632-13636) showed that treatment of relaxed single muscle fibers with para-phenylenedimaleimide (pPDM) results in inhibition of a fiber's ability to generate active force and a diminished ATPase activity. They postulated that the inhibition of force production was due to pPDM's ability to prevent crossbridges from participating in the normal ATP hydrolysis cycle. We find that the crossbridges produced by pPDM treatment of relaxed muscle cannot bind strongly to the actin filaments in rigor, but do bind weakly to the actin filaments in the presence and also absence of ATP. After pPDM treatment, fiber stiffness, as measured using ramp stretches of varying duration, is ATP-insensitive and identical to that of untreated relaxed fibers (both at high [165 mM] and low [40 mM] ionic strength). These results suggest that the pPDM-treated crossbridges, in both the presence and absence of ATP, are locked in a state that resembles the weakly-binding myosin ATP state of normal crossbridges. Their resemblance to the ATP-crossbridges of relaxed untreated fibers is quite strong; both bind to actin about equally tightly and have similar attachment and detachment rate constants. We also found that crossbridges are locked in a weakly-binding state after treatment with N-phenylmaleimide (NPM). In muscle fibers, this method of producing weakly-binding crossbridges appears preferable to pPDM treatment because, unlike treatment with pPDM, it does not increase the fiber's resting tension and stiffness and it does not disrupt the titin band seen on SDS-PAGE.

Actins↗
PubMed1992

Measurements of hepatic malondialdehyde and conjugated diene concentrations in 24-hour endotoxemic rats.

The aim of our study was to analyze if intraperitoneally administered E-coli endotoxin (1-7 mg.kg-1) causes an increase in liver malondialdehyde (MDA) and conjugated dienes, 24 h postinjection. Blood glucose, white blood cell counts, liver edema and mortality were also measured. The results of our study show that there were no signs of increased MDA or diene production in the liver. To our surprise, blood leukocyte counts of the experimental groups were not statistically different from controls. In the endotoxemic animals there was a slight liver edema which, however, did not influence the measurements of the lipid peroxidation metabolites. Blood glucose levels were decreased in the endotoxemic animals. There was no mortality in our study, perhaps due to the fact that the rats were fed and not starved. We conclude that, in our study, a bolus dose of endotoxin i.p. does not cause any signs of increased liver lipid peroxidation 24 h postinjection. The liver seems, however, to be affected with slight edema and low blood glucose levels.

Animals↗
PubMed1991

Orientational disorder and motion of weakly attached cross-bridges.

In a relaxed muscle fiber at low ionic strength, the cross-bridges may well be in states comparable to the one that precedes the cross-bridge power stroke (Schoenberg, M. 1988. Adv. Exp. Med. Biol. 226:189-202). Using electron paramagnetic resonance (EPR) and (saturation transfer) electron paramagnetic resonance (ST-EPR) techniques on fibers labeled with maleimide spin label, under low ionic strength conditions designed to produce a majority of weakly-attached heads, we have established that (a) relaxed labeled fibers show a speed dependence of chord stiffness identical to that of unlabeled, relaxed fibers, suggesting similar rapid dissociation and reassociation of cross-bridges; (b) the attached relaxed heads at low ionic strength are nearly as disordered as in relaxation at physiological ionic strength where most of the heads are detached from actin; and (c) the microsecond rotational mobility of the relaxed heads was only slightly restricted compared to normal ionic strength, implying great motional freedom despite attachment. The differences in head mobility between low and normal ionic strength scale with filament overlap and are thus due to acto-myosin interactions. The spectra can be modeled in terms of two populations: one identical to relaxed heads at normal ionic strength (83%), the other representing a more oriented population of heads (17%). The spectrum of the latter is centered at approximately the same angle as the spectrum in rigor but exhibits larger (40 degrees) axial probe disorder with respect to the fiber axis. Alternatively, assuming that the chord stiffness is proportional to the fraction of attached crossbridges, the attached fraction must be even more disordered than 400, with rotational mobility nearly as great as for detached cross-bridges.

Adenosine Triphosphatases↗
PubMed1991

Equilibrium muscle cross-bridge behavior. Theoretical considerations. II. Model describing the behavior of strongly-binding cross-bridges when both heads of myosin bind to the actin filament.

A model has been developed for characterizing the interaction between strongly-binding myosin cross-bridges and actin in muscle fibers under equilibrium conditions where both heads of the myosin cross-bridge bind to actin. The model, that of Anderson and Schoenberg (1987. Biophys. J. 52:1077-1082) is quite similar to that of Schoenberg (1985. Biophys. J. 48:467-475), except that explicit account is taken of the fact that each crossbridge has two heads which can bind to actin. The key assumption that allows this model to explain a large body of data unexplained by the Schoenberg (1985) model is that the two crossbridge heads are not totally independent of one another after attachment. After the first head attaches, the second head is then free to attach only to an actin site distal to the first head. This means that when the more distally attached head subsequently detaches and reattaches (as the heads continually do), it will not reattach in a position of lesser strain and reduce the force it supports, but instead will remain attached in its strained position until the proximally attached head also detaches. This model gives an explanation for two important and otherwise unexplained observations made previously: it explains why at ionic strengths in the range of 50-120 mM, (a) the rate constant of force decay after a small stretch is a sigmoidal function of nucleotide analogue concentration, and (b) why in the presence of analogues or in rigor the rate constant of force decay after a small stretch is significantly slower than the rate constant for myosin subfragment-1 detachment from actin in solution.

Actins↗
PubMed1991

Effect of ionic strength on skinned rabbit psoas fibers in the presence of magnesium pyrophosphate.

The effect of ionic strength on the kinetics of myosin cross-bridges in the presence of the ATP analogue PP, has been examined. It was found that increasing ionic strength from moderate values (mu approximately 100 mM) to high values (mu approximately 200 mM) has three effects. It causes a big decrease in the half time for the force decay after a small stretch, it causes a significant decrease in the sigmoidicity of the nucleotide analogue concentration dependence of the "apparent rate constant" of force decay after a small stretch, and it causes a big decrease in the range of rate constants necessary to describe the multiexponential force decay. It causes the last of these by causing a much larger increase in the slowest rate constants of the decay than in the fastest rate constants. The results suggest that whereas the behavior of cross-bridges in the presence of ATP is well-described by the simple independent-head equilibrium cross-bridge model of Schoenberg (1985. Biophys. J. 48:467-475), cross-bridges in the presence of the ATP analogue PPi require the more complicated double-headed equilibrium cross-bridge model of Anderson and Schoenberg (1987. Biophys. J. 52: 1077-1082) to describe their behavior.

Animals↗
PubMed1990

Long-term followup of subclinical human papillomavirus infection treated with the carbon dioxide laser and intraurethral 5-fluorouracil: a treatment protocol.

We evaluated 162 high risk male patients for the presence of subclinical anogenital human papillomavirus infection with magnified penile surface scanning. Infected patients were treated as outpatients with the carbon dioxide laser under local anesthesia. Of the patients 43 were followed for a mean of 8.7 months or 2.1 treatments after the initial treatment (range 3 to 30 months). A subset of 10 patients was followed for more than 20 months or 6.2 treatments. To date a 51% recurrence rate has been observed in the over-all population and a 50% recurrence rate was noted in the 20-month followup population. In a separate arm of this study a small number of patients (15) with deoxyribonucleic acid typed subclinical intraurethral disease plus subclinical skin lesions were treated with topical carbon dioxide laser therapy for the penile lesions and adjuvant intraurethral 5% 5-fluorouracil. Mean followup in the group was approximately 4 months. The addition of intraurethral therapy in this positive human papillomavirus reservoir group had no significant effect on the high rate of human papillomavirus recurrence.

Combined Modality Therapy↗