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Biomedical subjects

M L Gross

Publications and source records attributed to M L Gross.

At least 91 records · Page 5Linked to original sources

Primary embryonal rhabdomyosarcoma of long bone. Case report and review of the literature.

We report a case of primary embryonal rhabdomyosarcoma of long bone, presenting as a lytic destructive bone tumor in the right femoral diaphysis of a 7-year-old girl. To our knowledge, this is only the third report of this entity. The neoplasm was a pure embryonal rhabdomyosarcoma with numerous rhabdomyoblasts. Immunohistochemistry confirmed the diagnosis: The cells were reactive with antibodies directed against desmin, muscle-specific actin, and myoglobin. No other neoplastic mesenchymal component was present within the tumor. Although rare, primary rhabdomyosarcoma, along with Ewing's tumor and osteosarcoma, should be considered in the differential diagnosis of malignant bone tumors in childhood.

Actins↗

N-acetylgalactosamine glycosylation of MUC1 tandem repeat peptides by pancreatic tumor cell extracts.

Synthetic peptides corresponding to the human mucin MUC1 tandem repeat domain (20 residues) were glycosylated in vitro by using UDP-N-[3H]acetyl-D-galactosamine (GalNAc) and lysates of pancreatic tumor cell lines. Results obtained with peptides of different lengths (from one to five repeats) suggest that increasing the number of tandem repeats has neither a positive nor a negative effect on the density of glycosylation along the MUC1 tandem repeat protein backbone. Purified glycopeptides were sequenced on a gas-phase sequencer, and glycosylated positions were determined by measuring the incorporated radioactivity in fractions collected following each round of Edman degradation. The results showed that two of three threonine residues on the MUC1 tandem repeat peptides were glycosylated by pancreatic tumor cell lysates at the following positons: GVTSAPDTRPAPGSTAPPAH (underlined T indicates position of GalNAc attachment). None of the serine residues were glycosylated. Determination of the mass of the glycopeptides by mass spectrometry confirmed that a maximum of two molecules of GalNAc were covalently linked to each 20-residue repeat unit in the peptides. The data presented here show that acceptor substrate specificity of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase detected in lysates of pancreatic and breast tumor cell lines is identical and is limited to some but not all threonines in the MUC1 tandem repeat peptide sequence. The influence of primary amino acid sequence on acceptor substrate activity was evaluated by using several peptides that contain single or double amino acid substitutions (relative to the native human MUC1 sequence). These included substitutions in the residues that were glycosylated and substitutions of the surrounding primary amino acid sequence. The results of these studies suggest that primary amino acid sequence, length, and relative position of the residue to be glycosylated dramatically affect the ability of peptides to serve as acceptor substrates for the UDP-GalNAc:polypeptide N-acetylgalatosaminyltransferase.

Acetylgalactosamine↗

Influence of acceptor substrate primary amino acid sequence on the activity of human UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase. Studies with the MUC1 tandem repeat.

Synthetic peptides (30 and 20 residues long) corresponding to the native MUC1 tandem repeat sequence (20 residues long) were glycosylated in vitro using UDP-[3H]GalNAc and lysates from the human breast tumor cell line MCF7. Purified glycopeptides were sequenced on a gas-phase sequenator, and glycosylated positions were determined by measuring the incorporated radioactivity in fractions collected following each round of Edman degradation. The results showed that 2 of 3 threonines on the MUC1 tandem repeat peptides were glycosylated at the following positions: GVTSAPDTRPAPGSTAPPAH (underlined Thr residues indicate positions of GalNAc attachment); no glycosylation of serine residues was detected. Determination of the mass of the glycopeptides by mass spectrometry showed that a maximum of two molecules of GalNAc were covalently linked to each 20-residue repeat unit in the peptides. The influence of substrate primary amino acid sequence in determining the substrate specificity of UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyl-transferase activity was evaluated using as acceptor substrates a series of overlapping 9-residue peptides that represent a moving set through the tandem repeat of the MUC1 mucin. In addition, the influence of primary amino acid sequence on acceptor substrate activity was evaluated using several peptides that contained single or double amino acid substitutions (relative to the native human MUC1 sequence). These included substitutions in the residues that were glycosylated and substitutions in the surrounding primary amino acid sequence. This study demonstrates that primary amino acid sequence, length, and relative position of the residue to be glycosylated dramatically affect the ability of peptides to serve as acceptor substrates for UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase.

Amino Acid Sequence↗

Tandem mass spectrometry for the determination of deoxyribonucleic acid damage by polycyclic aromatic hydrocarbons. Plenary lecture.

Tandem mass spectrometry (MS-MS) has proved to be a state-of-the-art technique for the structure of synthetic and biological compounds. One opportunity for MS-MS is the study of modified deoxyribonucleic acid (DNA) bases resulting from the attachment of carcinogens such as polycyclic aromatic hydrocarbons (PAHs). The determination of PAH-DNA adducts, formed in vivo via a one-electron oxidation or a diol-epoxide mechanism, requires high efficiency separation and very sensitive techniques. This is because the analyte will occur in complex biological mixtures and at low femtomole levels, considering that one modification occurs for 10(6) or 10(8) bases. This paper reviews various approaches to the separation and mass spectrometric structural determination of DNA adducts. The main emphasis of our research is the sub-picomolar detection and identification of DNA-PAH adducts, particularly those formed via a one-electron oxidation mechanism.

Animals↗

Deep fungal infections in the tropics.

Although tropical deep fungal infections are uncommonly identified in North America, these disorders are a diagnostic and therapeutic challenge to the clinician. Presented in this article is information on the management of patients suffering from mycetoma, chromomycosis, African histoplasmosis, or keloidal blastomycosis.

Africa↗

Regulation of expression of transgenes in developing fish.

The transcriptional regulatory elements of the beta-actin gene of carp (Cyprinus carpio) have been examined in zebrafish and goldfish harbouring transgenes. The high sequence conservation of the putative regulatory elements in the beta-actin genes of animals suggested that their function would be conserved, so that transgenic constructs with the same transcriptional control elements would promote similar levels of transgene expression in different species of transgenic animals. To test this assumption, we analysed the temporal expression of a reporter gene under the control of transcriptional control sequences from the carp beta-actin gene in zebrafish (Brachydanio rerio) and goldfish (Carrasius auratus). Our results indicated that, contrary to expectations, combinations of different transcriptional control elements affected the level, duration, and onset of gene expression differently in developing zebrafish and goldfish. The major differences in expression of beta-actin/CAT (chloramphenicol acetyltransferase) constructs in zebrafish and goldfish were: (1) overall expression was almost 100-fold higher in goldfish than in zebrafish embryos, (2) the first intron had an enhancing effect on gene expression in zebrafish but not in goldfish, and (3) the serum-responsive/CArG-containing regulatory element in the proximal promoter was not always required for maximal CAT activity in goldfish, but was required in zebrafish. These results suggest that in the zebrafish, but not in the goldfish, there may be interactions between motifs in the proximal promoter and the first intron which appear to be required for maximal enhancement of transcription.

Actins↗

Treatment of lower extremity injuries with orthotic shoe inserts. An overview.

Orthotic shoe inserts are very effective in providing symptomatic relief of lower extremity complaints in running athletes. Inserts adjust the biomechanical-variables associated with running injuries and reduce the effect of high stresses produced by running activities. Orthotic treatment is based on an understanding of complex coupling of rotation of the lower extremity with pronation and supination of the subtalar joint. Orthotic fabrication is initiated by determining the neutral position of the foot and obtaining an accurate cast of this position. Successful treatment with orthotic shoe inserts is dependent on careful evaluation of the runner and formulation of a properly fitted orthosis. When correctly utilised, orthotic shoe inserts are beneficial for a broad range of disorders experienced by runners. Since biomechanical deficits may be related to injuries along the entire lower extremity, specific diagnoses may be of lesser indication; however, accurate identification of the underlying biomechanical deficit is critical. Problems related to excessive or prolonged pronation are most amenable to orthotic treatment. While treatment of the cavus foot with orthotic shoe inserts is sometimes worthwhile, the clinician should be aware of limited success in this instance. Finally, orthotics are only one facet in the overall treatment plan for injured running athletes. Most overuse syndromes will respond to rest, training modification, and a change in the running surface or shoe. Equally important is the use of a proper conditioning and stretching programme both for injury prevention and for treatment of specific injuries. Treatment with orthotic shoe inserts should not be used as a substitute for any of these approaches.

Athletic Injuries↗

Assessment and treatment of basketball injuries.

In this article, we have discussed acute musculoskeletal injuries, acute exacerbations of illness related to basketball, and preparation for these emergencies. Although the acute nature of the problems require constant diligence on the part of the health care provider, the rewards of good management to the player and to the treating physician make it all worthwhile.

Athletic Injuries↗

Impact of anesthetic agents on patients with sickle cell disease.

Fifty-two surgical procedures were performed on 45 patients with sickle cell anemia. All patients were managed perioperatively with hydration and were kept warm and well oxygenated. Patients were anesthetized with either halothane (n = 16), enflurane (n = 22), isoflurane (n = 6), or intravenous narcotics (n = 4). Four patients had epidural anesthesia. Perioperative morbidity was assessed using the criteria of atelectasis, urinary tract infection, wound infection, thrombophlebitis, drug reaction, hypotension, and vaso-occlusive crisis. The overall perioperative complication rate in this study was 45 per cent. Patients anesthetized with isoflurane and enflurane had postoperative morbidity rates of 83 and 59 per cent, respectively, while the patients anesthetized with halothane had a complication rate of 25 per cent. In all three groups, atelectasis was the main cause. No complications occurred in the epidural group. In the intravenous anesthesia group, one patient developed sickle cell crisis. It appears that the types of anesthetic agents used do not impact on postoperative morbidity in patients with sickle cell anemia more than any other type of patient.

Adult↗

Laparoscopic drainage of lymphocele after renal transplantation.

We describe the successful laparoscopic formation of a peritoneal window for the treatment of a symptomatic, recurrent lymphocele in a 25-year-old man after cadaveric renal transplantation. Because of minimal morbidity, relative ease and safety, this procedure should be strongly considered as a primary form of therapy for recurrent lymphoceles refractory to percutaneous drainage. However, thorough knowledge and experience with laparoscopic techniques are necessary.

Adult↗

Tubular ectasia within the mediastinum testis.

Eleven scrotal sonographic examinations showing a spectrum of findings within the mediastinum testis were collected over a 2 year period. Each case showed numerous small tubular or rounded anechoic structures within the mediastinum testis; often, the findings mimicked a hypoechoic mass. Findings were bilateral in eight of ten patients; one additional patient had only one testis because of orchiectomy. All patients had an associated extratesticular finding, in most cases a spermatocele. Tubular ectasia shares several features with testicular cysts and mechanisms of formation are postulated to be similar to those previously proposed for testicular cysts. Recognizing tubular ectasia is important to avoid unnecessary concern and potential surgery.

Aged↗

Monobromopolychlorodibenzo-p-dioxins and dibenzofurans in municipal waste incinerator flyash.

Capillary column gas chromatography/high-resolution mass spectrometry was used in two different selected-ion monitoring modes to analyze trace levels of monobromopolychlorodibenzo-p-dioxins and dibenzofurans (BPCDD/Fs) in municipal waste incinerator (MWI) flyash. The mass profile monitoring mode is well-suited for identification of unknown compounds in uncharacterized matrices because it has superior diagnostic capability. Owing to its high sensitivity, conventional peak top monitoring was used to quantify, on the basis of polychlorodibenzo-p-dioxin and dibenzofuran (PCDD/F) standards, the BPCDD/Fs in the sample. The results were compared with those obtained by using two commercial BPCDDs as standards, and the latter results are 4 times greater, indicating the need for appropriate standards. The high certainty and sensitivity obtained from these two mass spectrometric techniques combined with the resolving power of capillary gas chromatography enabled us to compare for the first time the isomer distribution patterns between BPCDD/Fs and their PCDD/F analogues at a high confidence level. The comparison indicates BPCDD/Fs and PCDD/Fs found in MWI flyash are closely related and that many BPCDD/Fs with a 2,3,7,8-substitution configuration may be present in MWI flyash.

Benzofurans↗

Mass profile monitoring in trace analysis by gas chromatography/mass spectrometry.

The advantages of gas chromatography/mass spectrometry (GC/MS) selected-ion monitoring (SIM) in the mass profile (MP) mode at medium mass resolving power were investigated for analyses requiring detection of low-picogram quantities of analytes in complex mixtures. The mass profile monitoring provides a certainty at least 10 times greater than that achieved by conventional GC/MS-SIM in the peak-top monitoring mode, and it can be operated at lower mass resolving power to compensate for the loss of sensitivity in the MP mode. The examination of mass profile peak shape, central mass shift, and sequential changes during GC elution not only reveals the presence of interfering compounds but also results in accurate mass measurement for those interferences. The latter feature takes the MP mode beyond the target mass analysis that GC/MS-SIM was originally designed for. This additional dimension of information is particularly useful for those complex and incompletely characterized matrices that are frequently encountered in environmental and biological sample analyses.

Animals↗

Arthroscopic treatment of degenerative joint disease of the knee.

The role of arthroscopy in the management of degenerative conditions of the knee continues to evolve. This study was undertaken to: (1) assess the efficacy of arthroscopic treatment, (2) identify significant prognostic factors, and (3) further define the indications for treatment. A retrospective review of charts and operative videotapes along with follow-up evaluation was obtained for 43 knees in 40 patients. Average age was 54 years. Average follow up was 24 months; 72.1% of patients had good results at follow up, 16.3% had fair results, and 11.6% were treatment failures. Preoperative clinical status, severity of degenerative changes, and number of pathologic entities encountered at the time of surgery correlated with the results of treatment. We believe that arthroscopic debridement is an effective means of treatment for mild to moderate degenerative joint disease after failure of conservative measures. By using this treatment option, more extensive surgical procedures may be delayed or avoided.

Arthritis, Rheumatoid↗

Osteochondritis dissecans of the patella. MRI evaluation and a case report.

Osteochondritis dissecans of the patella is a rare cause of anterior knee pain. An illustrative case in a 22-year-old man demonstrates the current imaging modalities and surgical treatment. Specifically, magnetic resonance imaging (MRI) and arthroscopic knee surgery are discussed along with a review of the literature. Unlike standard roentgenograms, MRI can be helpful in determining the viability of the osteochondritic fragment and the amount of remaining attachment to the surrounding cancellous bone. This finding can have important bearing on choice of treatment. When surgery is indicated, arthroscopic treatment with excision of the fragment and curettage offers distinct advantages over open arthrotomy. Lateral release or other realignment procedures may be done in combination with the primary procedure. Prognosis for full recovery of knee function and relief of patellar pain is guarded in patients who require surgery.

Adult↗

Binding of benzo[a]pyrene to DNA by cytochrome P-450 catalyzed one-electron oxidation in rat liver microsomes and nuclei.

To investigate whether cytochrome P-450 catalyzes the covalent binding of substrates to DNA by one-electron oxidation, the ability of both uninduced and 3-methylcholanthrene (MC) induced rat liver microsomes and nuclei to catalyze covalent binding of benzo[a]pyrene (BP) to DNA and formation of the labile adduct 7-(benzo[a]pyren-6-yl)guanine (BP-N7Gua) was investigated. This adduct arises from the reaction of the BP radical cation at C-6 with the nucleophilic N-7 of the guanine moiety. In the various systems studied, 1-9 times more BP-N7Gua adduct was isolated than the total amount of stable BP adducts in the DNA. The specific cytochrome P-450 inhibitor 2-[(4,6-dichloro-o-biphenyl)oxy]ethylamine hydrobromide (DPEA) reduced or eliminated BP metabolism, binding of BP to DNA, and formation of BP-N7Gua by cytochrome P-450 in both microsomes and nuclei. The effects of the antioxidants cysteine, glutathione, and p-methoxythiophenol were also investigated. Although cysteine had no effect on the microsome-catalyzed processes, glutathione and p-methoxythiophenol inhibited BP metabolism, binding of BP to DNA, and formation of BP-N7Gua by cytochrome P-450 in both microsomes and nuclei. The decreased levels of binding of BP to DNA in the presence of glutathione or p-methoxythiophenol are matched by decreased amounts of BP-N7Gua adduct and of stable BP-DNA adducts detected by the 32P-postlabeling technique. This study represents the first demonstration of cytochrome P-450 mediating covalent binding of substrates to DNA via one-electron oxidation and suggests that this enzyme can catalyze peroxidase-type electron-transfer reactions.

Animals↗