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M J Solomon

Publications and source records attributed to M J Solomon.

At least 91 records · Page 5Linked to original sources
PubMed1993

Clinical studies in surgical journals--have we improved?

A critical appraisal of all clinical studies published in 1980 and 1990 in three surgical journals--Diseases of the Colon and Rectum (DCR), Surgery (SURG), and the British Journal of Surgery (BJS)--was made to ascertain the frequency with which various research designs appeared, the standard of individual clinical studies, and a comparison of changes in the past decade. Clinical studies were classified into case studies or comparative studies. Comparative studies included randomized controlled trials (RCT), nonrandomized controlled trials, retrospective cohorts, and case-control studies. A 10-point index score (range, 0-10) was used to assess the comparative studies. A sample of articles was analyzed for interobserver and intraobserver variation, with strong agreement between reviewers for classification of trials (unweighted kappa, 0.87) and index scores (0.67). Of 1,481 articles reviewed, 1,060 were classified as clinical studies. Sixteen percent of all clinical studies were comparative studies in 1980, compared with 17 percent in 1990. Of these, 7 percent were RCT in both years. In 1980, 6 percent of clinical studies in DCR were comparative studies, 19 percent in BJS, and 18 percent in SURG. In 1990, 11 percent, 18 percent, and 18 percent, respectively, were comparative studies. In 1980, the proportion of RCT in DCR was 0 percent, in BJS 12 percent, and in SURG 4 percent, compared with 3 percent, 8 percent, and 8 percent, respectively, in 1990. Overall, 52 of 76 (68 percent) RCT were published in BJS. The standard of comparative studies increased overall from 5.49 to 6.04 (P = NS), and that of RCT increased from 7.06 to 7.70 (P = NS). The standard of comparative studies in DCR in 1980 was lower than those in BJS (P < 0.001) and SURG (P < 0.001). The standard of comparative studies in DCR improved from 1.67 in 1980 to 5.47 in 1990 (P < 0.001). There was no significant difference in the standard of comparative studies among the three journals in 1990. In conclusion, there has been no overall increase in the proportion of stronger clinical trial designs in the journals reviewed. A small increase seen in the overall standard of comparative studies was not statistically significant.

Case-Control Studies↗
PubMed1993

Endoluminal transrectal ultrasonography: accuracy, reliability, and validity.

The significant risk of local recurrence after curative resection and the relative inaccuracy of preoperative clinical assessment justify a more sophisticated assessment for carcinoma of the rectum. Endoluminal rectal ultrasonography (EU) can directly visualize the degree of rectal wall penetration by tumor and the immediate pararectal lymph nodes. Despite several reports reporting excellent accuracy of EU compared with pathology in detecting the degree of tumor penetration, EU remains restricted in terms of widespread availability. A review of the literature was performed to determine the accuracy, reliability, and current validity of EU. Raw data were collected from cross-sectional surveys assessing the degree of tumor penetration in 873 patients and lymph node involvement in 571 patients with primary rectal cancer. EU is very accurate at determining tumor penetration (kappa = 0.85) but is only moderately accurate at detecting lymph node involvement (kappa = 0.58). The reliability of EU has not been assessed, and a simple protocol is proposed. The validity of EU was assessed in only a few studies. EU is credible and feasible, makes intuitive biologic sense, and is, perhaps, sensitive to change. The ability to make clinical decisions based on EU (content validity) will decide whether widespread implementation is applicable.

Diffusion of Innovation↗
PubMed1993

Clinical assessment of biomedical technology.

The rapid expansion of new, unproven, and often expensive biomedical technology requires controlled clinical assessment before widespread diffusion into clinical practice. The accuracy, reliability, and validity all need to be assessed in an unbiased manner to determine whether implementation is of benefit to the clinician and patient. This article briefly describes the methodology available to determine whether new technologies such as diagnostic imaging techniques may be of benefit in clinical practice.

Bias↗
PubMed1993

Activation of the various cyclin/cdc2 protein kinases.

Recent research has led to the near culmination of the biochemical confirmation of the most basic genetic predictions about how p34cdc2 activity is controlled. The field is now moving from a biochemical dissection of the machinery to understanding how the system is regulated. The discovery of numerous, highly related protein kinase complexes that control other cell cycle events will test the generality of this paradigm.

Animals↗
PubMed1993

Screening strategies for colorectal cancer.

The efficacy of screening for colorectal cancer has not been established. Policy-making organizations differ in recommendations for asymptomatic and high-risk groups because of the inadequacy of current evidence. A critical appraisal of the current evidence for screening for colorectal cancer and a discussion of the aims and pitfalls of screening programs are presented.

Colonoscopy↗
PubMed1993

Phosphorylation independent activation of human cyclin-dependent kinase 2 by cyclin A in vitro.

p33cdk2 is a serine-threonine protein kinase that associates with cyclins A, D, and E and has been implicated in the control of the G1/S transition in mammalian cells. Recent evidence indicates that cyclin-dependent kinase 2 (Cdk2), like its homolog Cdc2, requires cyclin binding and phosphorylation (of threonine-160) for activation in vivo. However, the extent to which mechanistic details of the activation process are conserved between Cdc2 and Cdk2 is unknown. We have developed bacterial expression and purification systems for Cdk2 and cyclin A that allow mechanistic studies of the activation process to be performed in the absence of cell extracts. Recombinant Cdk2 is essentially inactive as a histone H1 kinase (< 4 x 10(-5) pmol phosphate transferred.min-1 x microgram-1 Cdk2). However, in the presence of equimolar cyclin A, the specific activity is approximately 16 pmol.mon-1 x microgram-1, 4 x 10(5)-fold higher than Cdk2 alone. Mutation of T160 in Cdk2 to either alanine or glutamic acid had little impact on the specific activity of the Cdk2/cyclin A complex: the activity of Cdk2T160E was indistinguishable from Cdk2, whereas that of Cdk2T160A was reduced by five-fold. To determine if the Cdk2/cyclin A complex could be activated further by phosphorylation of T160, complexes were treated with Cdc2 activating kinase (CAK), purified approximately 12,000-fold from Xenopus eggs. This treatment resulted in an 80-fold increase in specific activity. This specific activity is comparable with that of the Cdc2/cyclin B complex after complete activation by CAK (approximately 1600 pmol.mon-1 x microgram-1). Neither Cdk2T160A/cyclin A nor Cdk2T160E/cyclin A complexes were activated further by treatment with CAK. In striking contrast with cyclin A, cyclin B did not directly activate Cdk2. However, both Cdk2/cyclin A and Cdk2/cyclin B complexes display similar activity after activation by CAK. For the Cdk2/cyclin A complex, both cyclin binding and phosphorylation contribute significantly to activation, although the energetic contribution of cyclin A binding is greater than that of T160 phosphorylation by approximately 5 kcal/mol. The potential significance of direct activation of Cdk2 by cyclins with respect to regulation of cell cycle progression is discussed.

Amino Acid Sequence↗
PubMed1993

Characterization of the Rickettsia prowazekii pepA gene encoding leucine aminopeptidase.

The pepA gene, encoding a protein with leucine aminopeptidase activity, was isolated from Rickettsia prowazekii, an obligate intracellular parasitic bacterium. Nucleotide sequence analysis revealed an open reading frame of 1,502 bp that would encode a protein of 499 amino acids with a calculated molecular weight of 53,892, a size comparable to that of the protein produced in Escherichia coli minicells containing the rickettsial gene. Also, heat-stable leucine aminopeptidase activity was demonstrable in an E. coli peptidase-deficient strain containing R. prowazekii pepA. Comparison of the amino acid sequence of the R. prowazekii PepA with the characterized leucine aminopeptidases from E. coli, Arabidopsis thaliana, and bovine eye lens revealed that 39.8, 34.9, and 34.0% of the residues were identical, respectively. Residues proposed to be part of the active site or involved in the binding of metal ions in the bovine metalloenzyme were all conserved in R. prowazekii PepA. However, despite the structural and enzymatic similarity to E. coli PepA, the R. prowazekii protein was unable to complement the cer site-specific, PepA-dependent recombination system found in E. coli that resolves ColE1-type plasmid multimers into their monomeric forms.

Amino Acid Sequence↗
PubMed1992

A new classification of hepatic territories using intraoperative ultrasound.

Intraoperative ultrasonography is now established as the most accurate technique for detecting and localizing hepatic tumors, be they primary or metastatic. A major problem is the accurate placement of any lesions found by intraoperative ultrasound and, hence, the correlation of the lesions found by ultrasound to the current classification of hepatic segments and to lesions seen by other imaging techniques. This paper outlines an objective and reproducible method of mapping hepatic lesions into territories defined solely by the major hepatic veins and their tributaries. It is a simple technique that can be readily used by any surgeon, which accurately determines the presence, number, size, and site of hepatic metastases.

Humans↗
PubMed1992

Role of phosphorylation in p34cdc2 activation: identification of an activating kinase.

Phosphorylation of p34cdc2 can both positively and negatively regulate its kinase activity. We have mapped two phosphorylation sites in Xenopus p34cdc2 to Thr-14 and Tyr-15 within the putative ATP-binding region of p34cdc2. Mutation of these sites to Ala-14 and Phe-15 has no effect on the final histone H1 kinase activity of the cyclin/p34cdc2 complex. Phosphopeptide analysis shows that there is at least one more site of phosphorylation on p34cdc2. When Thr-161 is changed to Ala, two phosphopeptide spots disappear and it is no longer possible to activate the H1 kinase activity of p34cdc2. We suggest that Thr-161 is a third site of phosphorylation, which is required for kinase activity. All three phosphorylations are induced by cyclin. None of the phosphorylations appears to be required for binding to cyclin, as indicated by the ability of the triple mutant, Ala-14, Phe-15, Ala-161, to bind cyclin. The activating phosphorylation that requires Thr- or Ser-161 occurs even in a catalytically inactive K33R mutant of p34cdc2 and hence does not appear to be the result of intramolecular autophosphorylation. We have detected an activity in Xenopus extracts required for activation of p34cdc2 and present evidence that this is a p34cdc2 activating kinase which, in a cyclin-dependent manner, probably directly phosphorylates Thr-161.

Adenosine Triphosphate↗
PubMed1991

cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2.

cdc25 controls the activity of the cyclin-p34cdc2 complex by regulating the state of tyrosine phosphorylation of p34cdc2. Drosophila cdc25 protein from two different expression systems activates inactive cyclin-p34cdc2 and induces M phase in Xenopus oocytes and egg extracts. We find that the cdc25 sequence shows weak but significant homology to a phylogenetically diverse group of protein tyrosine phosphatases. cdc25 itself is a very specific protein tyrosine phosphatase. Bacterially expressed cdc25 directly dephosphorylates bacterially expressed p34cdc2 on Tyr-15 in a minimal system devoid of eukaryotic cell components, but does not dephosphorylate other tyrosine-phosphorylated proteins at appreciable rates. In addition, mutations in the putative catalytic site abolish the in vivo activity of cdc25 and its phosphatase activity in vitro. Therefore, cdc25 is a specific protein phosphatase that dephosphorylates tyrosine and possibly threonine residues on p34cdc2 and regulates MPF activation.

Amino Acid Sequence↗
PubMed1991

INH, a negative regulator of MPF, is a form of protein phosphatase 2A.

MPF, a protein kinase complex consisting of cyclin and p34cdc2 subunits, promotes the G2 to M phase transition in eukaryotic cells. The pathway of activation and inactivation of MPF is not well understood, although there is strong evidence that removal of phosphate from a tyrosine residue on p34cdc2 is part of the activation process. INH was originally identified as an activity that could inhibit the posttranslational activation of a latent form of MPF, called pre-MPF, in immature (G2 phase-arrested) Xenopus oocytes. We have purified INH and demonstrated that it is a form of protein phosphatase 2A. Both INH and the catalytic subunit of protein phosphatase 2A can directly inactivate an isolated p34cdc2-cyclin complex. Both cyclin and p34cdc2 become dephosphorylated; the rate of inactivation closely parallels the removal of phosphate from a specific site on p34cdc2. We propose that INH opposes MPF activation by reversing this critical phosphorylation.

Animals↗
PubMed1991

Preliminary results of conservative treatment of early breast cancer with tumourectomy, axillary dissection and postoperative radiotherapy. A retrospective review of 107 patients.

A consecutive series of 107 patients with early breast cancer treated by tumourectomy, axillary dissection and postoperative radiotherapy was retrospectively reviewed. The average age at presentation was 48, range 30-79. Only 23.4% of women were post-menopausal. Average follow-up time was 48 months, range 19-94 months. Eight-three per cent had palpable lesions, the remaining 16.8% had needle localization. Ninety-four patients (88.7%) had lesions less than 2 cm in diameter clinically. One patient had a lesion greater than 3 cm in diameter clinically. Seventy-two per cent had invasive duct carcinoma. Twenty (18.9%) had invasive disease at the margins and fifteen were re-excised. Of the 20 patients who had invasive disease at the margins, three developed local recurrence. True loco-regional recurrence rate (i.e., loco-regional recurrence rate without distant metastasis) was 2.8%. All had level I and II axillary dissections and 26.4% were up-staged from clinical stage 1 to pathological stage II. Five patients died, three with recurrences and two with unrelated disease. Tumourectomy, axillary dissection and postoperative radiotherapy is an acceptable regimen for early carcinoma of the breast.

Adult↗
PubMed1990

Cyclin activation of p34cdc2.

The gradual accumulation of cyclin in the frog egg induces an abrupt and concerted activation of p34cdc2 that initiates mitosis. Activation is delayed even after the accumulation of cyclin to a critical threshold concentration. We have reproduced these unusual kinetic properties of p34cdc2 activation in vitro using bacterially expressed cyclin proteins and extracts derived from Xenopus eggs. Abrupt activation follows a lag period, the length of which is independent of the concentration of cyclin. The threshold concentration of cyclin and the length of the lag period are regulated by INH, an inhibitor of MPF activation in oocytes recently identified as a type 2A protein phosphatase. Binding to cyclin induces both tyrosine and threonine phosphorylation of the previously unphosphorylated p34cdc2, rendering it inactivated. The concerted transition into mitosis involves both a reduction in the rate of p34cdc2 phosphorylation on tyrosine and an increase in its rate of dephosphorylation.

Animals↗
PubMed1990

The fate of the left kidney after end renosplenic shunt in experimentally induced extrahepatic portal hypertension.

Extrahepatic portal hypertension was induced in the rabbit by a one-stage complete ligation of the portal vein. End renal vein to side splenic vein shunts (renosplenic) were performed with haemorrhagic necrosis of the left kidney occurring after ligation of the left renal vein lateral to the adrenolumbar tributary. Thus the ureteric, lumbar, and pericapsular collaterals cannot adequately drain the left kidney. Ligation of the left renal vein on the medial side of the adrenolumbar tributary maintained a patent left renal vein in all cases with 60% of left kidney biopsies showing no histological evidence of changes to glomeruli or tubules, and the remainder showing early acute tubular necrosis.

Animals↗
PubMed1990

Oesophageal varices due to idiopathic portal vein thrombosis: a new surgical approach.

Life-threatening bleeding oesophageal varices due to idiopathic portal vein thrombosis occurred in a five-year-old male. Diagnosis was made by endoscopy and ultrasonography and decompression of the portal system performed by splenorenal shunt using the end renal vein to side splenic vein. This avoided the difficult mobilization of the splenic vein from the pancreatic bed in the conventional distal splenorenal shunt.

Budd-Chiari Syndrome↗
PubMed1988

Mapping protein-DNA interactions in vivo with formaldehyde: evidence that histone H4 is retained on a highly transcribed gene.

We have used formaldehyde-mediated protein-DNA crosslinking within intact cells to examine the in vivo chromatin structure of the D. melanogaster heat shock protein 70 (hsp70) genes. In agreement with previous in vitro studies, we find that the heat shock-mediated transcriptional induction of the hsp70 genes perturbs their chromatin structure, resulting in fewer protein-DNA contacts crosslinkable in vivo by formaldehyde. However, contrary to earlier in vitro evidence that histones may be absent from actively transcribed genes, we show directly, by immunoprecipitation of in vivo-crosslinked chromatin fragments, that at least histone H4 remains bound to hsp70 DNA in vivo, irrespective of its rate of transcription. The formaldehyde-based in vivo mapping techniques described in this work are generally applicable, and can be used both to probe protein-DNA interactions within specific genes and to determine the genomic location of specific chromosomal proteins.

Animals↗