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Biomedical subjects

S A Martin

Publications and source records attributed to S A Martin.

At least 163 records · Page 9Linked to original sources

Proliferative activity of benign human prostate, prostatic adenocarcinoma and seminal vesicle evaluated by thymidine labeling.

The thymidine labeling index (TLI) was measured in vitro in the epithelium and stroma of benign prostate glands and seminal vesicles and in the epithelium of prostatic adenocarcinomas. The mean epithelial TLI of normal peripheral (posterior) prostatic zone was 0.12 per cent, and that of the normal central (deep) zone was 0.11 per cent. Mean normal stromal TLI's were 0.08 per cent and 0.06 per cent, respectively. The mean TLI of epithelium in nodular hyperplasia was 0.31 per cent, which differs significantly from normal epithelium (p less than 0.05), and the mean stromal TLI was also increased (0.16 per cent, p less than 0.1). The mean TLI of prostatic adenocarcinomas was 0.90 per cent (range 0.14 to 3.90 per cent) which was significantly higher than for either normal epithelium (p less than 0.001) or epithelium of nodular hyperplasia (p less than 0.05). Trends of increasing TLI with increasing histologic grades and increasing nuclear size and numbers of nucleoli were not significant. The data support participation of both epithelial and stromal proliferation in nodular hyperplasia, and indicate a low basal proliferative rate in normal prostatic glands. The low TLI's of prostatic adenocarcinomas relative to other malignancies are consistent with their frequently slowly progressive course. The very low proliferative rate of seminal vesicular epithelium (mean TLI 0.02 per cent) may account for the rarity of seminal vesicular carcinomas.

Adenocarcinoma↗

Adenomatoid metaplasia of prostatic urethra.

Adenomatoid metaplasia, or so-called nephrogenic metaplasia, is an uncommon alteration of urothelium associated with prior trauma and/or chronic infection. Although the majority of reported cases of adenomatoid metaplasia have involved the urinary bladder, two cases of patients in whom the metaplastic changes were present in tissue from prostatic resections are presented. The fact that both patients had undergone prior transurethral resections of the prostate further supports the association between adenomatoid metaplasia and trauma. Confusion of adenomatoid metaplasia with prostatic ductal carcinoma in one of the cases emphasizes the importance of the recognition of this lesion. The distinction of adenomatoid metaplasia from ductal carcinomas and from other benign proliferative lesions in the prostatic urethra is discussed.

Adenoma↗

Carcinoma of the pyriform sinus: predictors of TNM relapse and survival.

To determine predictors of TNM relapse and survival for 108 patients with epidermoid carcinoma of the pyriform sinus, the histopathologic features of tumor-related and host-related characteristics were correlated with primary and/or cervical nodal failure, distant metastases, and actuarial three-year survival. Patients in this study received preoperative irradiation and partial laryngopharyngectomy (PLP) or total laryngopharyngectomy (TLP) with en bloc radical neck dissection. Higher rates of local failure were observed in patients with keratinizing tumors (34 vs. 15%), with tumors having an "infiltrating" tumor-stromal interface (30 vs. 14%), with positive surgical margins in PLP or TLP specimens (30 vs. 16%), and with extranodal extension of tumor (39 vs. 22%). The development of distant metastases was significantly correlated with nonkeratinizing carcinomas (30 vs 11%, P = 0.02), and was observed more often in patients with positive lymph nodes (17 vs. 7%). Patients with negative surgical margins in PLP or TLP excision (50 vs. 21%, P = 0.01) survived significantly longer.

Adult↗

Wegener granulomatosis. Unusual cause of necrotizing urethritis.

We report a case of Wegener granulomatosis presenting as a destructive urethral mass. The initial clinical impression was carcinoma, and a urinary diverting procedure was considered before the correct diagnosis was established. The importance of recognizing this unusual disease and its dramatic response to appropriate therapy are emphasized.

Cyclophosphamide↗

Verruciform xanthoma of the vulva. Report of two cases.

Two cases of verruciform xanthoma of the vulva are described. This rare lesion, previously reported to occur only in the oral cavity, is characterized by a verrucous epithelial proliferation accompanied by xanthoma cells distributed exclusively in the papillary dermis. The histologic features of the lesion are diagnostic and include (1) regular acanthosis in which the rete pegs extend to a uniform level into the dermis; (2) hyperkeratosis with parakeratosis often extending deep into the rete pegs and manifesting a massive neutrophilic infiltrate; (3) hyalinization of the collagen and infiltrates of xanthoma cells that are restricted to the papillary dermis between the rete pegs. Additionally, a lichenoid inflammatory infiltrate is seen at the periphery of the verrucous lesions, and in one case this has the pattern of classic lichen sclerosus. Verruciform xanthoma must be differentiated from verruca vulgaris, condyloma acuminatum, granular cell tumor with pseudoepitheliomatous hyperplasia, and verrucous carcinoma.

Acantholysis↗

Carcinosarcoma of the prostate: report of a case with ultrastructural observations.

A carcinosarcoma of the prostate was examined by light and electron microscopy. The epithelial component was comprised of adenosquamous carcinoma. The stromal component demonstrated osseous and cartilaginous differentiation, and appeared mesenchymal by fine structure analysis. Despite aggressive therapy the patient died with disseminated disease 5 months after diagnosis.

Aged↗

Surgical considerations in treatment of intraductal carcinoma of the prostate.

Intraductal carcinomas of the prostate comprise about 3 per cent of all prostatic carcinomas and constitute a heterogeneous group of tumors that include 1) transitional or squamous cell carcinoma, 2) intraductal adenocarcinoma, 3) endometrioid carcinoma and 4) mixed ductal carcinoma. Generally, these tumors are poorly responsive to endocrine and radiation therapy, and complete surgical excision offers the best chance for long-term survival. A case of intraductal adenocarcinoma is presented that illustrates many of the features of these tumors.

Carcinoma, Intraductal, Noninfiltrating↗

Thymus related tumors and tumor-like lesions in childhood with rapid clinical progression and death.

Tumor and tumor-like lesions of the thymus, excluding Hodgkin and nonHodgkin lymphomas, are among the least frequent mediastinal tumors in childhood. For this reason the diagnosis is often overlooked. The clinical and pathologic features of four thymus related masses, three of which were thymomas and one a thymic cyst, are reported in children between the ages of five and 15 years. The thymic cyst occurred in a child with a five year history of aplastic anemia. A rapid clinical course to death occurred in all four cases. The behavior of these lesions is compared with that described in the literature. The impression exists that thymomas in the pediatric age group are much more aggressive than those in adults. There are also some signifant differences in their histopathologic appearance.

Adolescent↗

mRNA guanylyltransferase and mRNA (guanine-7-)-methyltransferase from vaccinia virions. Donor and acceptor substrate specificites.

Characterization of the donor and acceptor specificities of mRNA guanylyltransferase and mRNA (guanine-7-)-methyltransferase isolated from vaccinia virus cores has enabled us to discriminate between alternative reaction sequences leading to the formation of the 5'-terminal m7G(5')pppN-structure. The mRNA guanylyltransferase catalyzes the transfer of a residue of GMP from GTP to acceptors which possess a 5'-terminal diphosphate. A diphosphate-terminated polyribonucleotide is preferred to a mononucleoside diphosphate as an acceptor suggesting that the guanylyltransferase reaction occurs after initiation of RNA synthesis. Although all of the homopolyribonucleotides tested (pp(A)n, pp(G)n, pp(I)n, pp(U)n, and pp(C)n) are acceptors for the mRNA guanylyltransferase indicating lack of strict sequence specificity, those containing purines are preferred. Only GTP and dGTP are donors in the reaction; 7-methylguanosine (m7G) triphosphate specifically is not a donor indicating that guanylylation must precede guanine-7-methylation. The preferred acceptor of the mRNA (guanine-7-)-methyltransferase is the product of the guanylyltransferase reaction, a polyribonucleotide with the 5'-terminal sequence G(5')pppN-. The enzyme can also catalyze, but less efficiently methylation of the following: dinucleoside triphosphates with the structure G(5')pppN, GTP, dGTP, ITP, GDP, GMP, and guanosine. The enzyme will not catalyze the transfer of methyl groups to ATP, XTP, CTP, UTP, or to guanosine-containing compounds with phosphate groups in either positions 2' or 3' or in 3'-5' phosphodiester linkages. The latter specificity provides an explanation for the absence of internal 7-methylguanosine in mRNA. In the presence of PPi, the mRNA guanylyltransferase catalyzes the pyrophosphorolysis of the dinucleoside triphosphate G(5')pppA, but not of m7G(5')pppA. Since PPi is generated in the process of RNA chain elongation, stabilization of the 5'-terminal sequences of mRNA is afforded by guanine-7-methylation.

Guanosine Triphosphate↗

Purification of mRNA guanylyltransferase and mRNA (guanine-7-) methyltransferase from vaccinia virions.

The sequences m7G(5')pppGm-and m7G(5')pppAm-are located at the 5' termini of vaccinia mRNAs. Two novel enzymatic activities have been purified from vaccinia virus cores which modify the 5' terminus of unmethylated mRNA. One activity transfers GMP from GTP to mRNA and is designated a GTP: mRNA guanylyltransferase. The second activity transfers a methyl group from S-adenosylmethionine to position 7 of the added guanosine and is designated a S-adenosylmethionine: mRNA (guanine-7-)methyltransferase. Advantage was taken of the selective binding of these activities to homopolyribonucleotides relative to DNA to achieve a 200-fold increase in specific activity. The guanylyl- and methyltransferase remained inseparable during chromatography on DNA-agarose, poly(U)-Sepharose, poly(A)-Sepharose, and Sephadex G-200 and during sedimentation through sucrose density gradients suggesting they were associated. A Stokes radius of 5.0 nm, an S20,w of 6.0 and a molecular weight of 127,000 were obtained by gel filtration on Sephadex G-200 and sedimentation in sucrose density gradients. Under denaturing conditions of sodium dodecyl sulfate-polyacrylamide gel electrophoresis two major polypeptides were detected in purified enzyme preparations. Their molecular weights of 95,000 and 31,400 suggested they were polypeptide components of the 127,000 molecular weight enzyme system.

Guanine Nucleotides↗

Modification of RNA by mRNA guanylyltransferase and mRNA (guanine-7-)methyltransferase from vaccinia virions.

A purified enzyme system isolated from vaccinia virus cores has been shown to modify the 5' termini of viral mRNA and synthetic poly(A) and poly(G) to form the structures m7G(5')pppA- and m7G(5')pppG-. The enzyme system has both guanylyltransferase and methyltransferase activities. The GTP:mRNA guanylyltransferase activity incorporates GMP into the 5' terminus via a 5'-5' triphosphate bond. The properties of this reaction are: (a) of the four nucleoside triphosphates only GTP is a donor, (b) mRNA with two phosphates at the 5' terminus is an acceptor while RNA with a single 5'-terminal phosphate is not, (c) Mg2+ is required, (d) the pH optimum is 7.8, (e) PP1 is a strong inhibitor, and (f) the reverse reaction, namely the formation of GTP from PP1 and RNA containing the 5'-terminal structure G(5')pppN-, readily occurs. The S-adenosylmethionine:mRNA(guanine-7-)methyltransferase activity catalyzes the methylation of the 5'-terminal guanosine. This reaction exhibits the following characteristics: (a) mRNA with the 5'-terminal sequences G(5')pppA- and G(5')pppG- are acceptors, (b) only position 7 of the terminal guanosine is methylated; internal or conventional 5'-terminal guanosine residues are not methylated, (c) the reaction is not dependent upon GTP or divalent cations, (d) optimal activity is observed in a broad pH range around neutrality, (e) the reaction is inhibited by S-adenosylhomocysteine. Both the guanylyltransferase and methyltransferase reactions exhibit bisubstrate kinetics and proceed via a sequential mechanism. The reactions may be summarized: (see article).

Cations, Divalent↗

Modification of the 5'-terminus of mRNA by soluble guanylyl and methyl transferases from vaccinia virus.

RNA guanylyl and methyl transferases have been solubilized from vaccinia virus cores. The guanylyl transferase specifically adds a GMP residue to the 5'-terminus of unmethylated vaccinia virus mRNA to form the structures G(5')ppp(5')Gp- and G(5')ppp(5')Ap-. Studies with [alpha-32P]GTP and [beta, gamma-32P]GTP indicated that only the alpha-phosphate is transferred. In the presence of S-adenosylmethionine, the methyl transferases convert the blocked 5'-termini to m7G(5')ppp(5')Gmp- and m7G(5')ppp(5')Amp-. Similarly, the enzymes can modify synthetic poly(A) to form the structure m7G(5')ppp(5')Amp-.

Calcium↗

Polypoid change of the glomerular basement membrane.

A peculiar and previously undescribed alteration in the glomerular basement membrane, which we designate as polypoid change, was found in a 4-year-old child with mongolism (trisomy 21). Light and electron microscopical studies were performed. Although the pathogenesis and significance of this lesion remain uncertain, we have compared the lesion with known processes that affect the glomerular basement membrane.

Basement Membrane↗

Studies on the topography of reovirus and bluetongue virus capsid proteins.

Protein labeling experiments confirm the surface location of proteins 2 and 5 in bluetongue virus, and proteins sigma3 and mu2 in reovirus. Lambda 2 is the major surface component of the reovirus core, and proteins 1, 3, and 4 appear to be the outer components of the bluetongue virus subviral particle.

Animals↗