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G Brodsky

Publications and source records attributed to G Brodsky.

At least 19 recordsLinked to original sources
PubMed1997

The human GARS-AIRS-GART gene encodes two proteins which are differentially expressed during human brain development and temporally overexpressed in cerebellum of individuals with Down syndrome.

Purines are critical for energy metabolism, cell signalling and cell reproduction. Nevertheless, little is known about the regulation of this essential biochemical pathway during mammalian development. In humans, the second, third and fifth steps of de novo purine biosynthesis are catalyzed by a trifunctional protein with glycinamide ribonucleotide synthetase (GARS), aminoimidazole ribonucleotide synthetase (AIRS) and glycinamide ribonucleotide formyltransferase (GART) enzymatic activities. The gene encoding this trifunctional protein is located on chromosome 21. The enzyme catalyzing the intervening fourth step of de novo purine biosynthesis, phosphoribosylformylglycineamide amidotransferase (FGARAT), is encoded by a separate gene on chromosome 17. To investigate the regulation of these proteins, we have generated monoclonal and/or polyclonal antibodies specific to each of these enzymatic domains. Using these antibodies on western blots of Chinese hamster ovary (CHO) cells transfected with the human GARS-AIRS-GART gene, we show that this gene encodes not only the trifunctional protein of 110 kDa, but also a monofunctional GARS protein of 50 kDa. This carboxy-truncated human GARS protein is produced by alternative splicing resulting in the use of a polyadenylation site in the intron between the terminal GARS and the first AIRS exons. The expression of both the GARS and GARS-AIRS-GART proteins are regulated during development of the human cerebellum, while the expression of FGARAT appears to be constitutive. All three proteins are expressed at high levels during normal prenatal cerebellum development while the GARS and GARS-AIRS-GART proteins become undetectable in this tissue shortly after birth. In contrast, the GARS and GARS-AIRS-GART proteins continue to be expressed during the postnatal development of the cerebellum in individuals with Down syndrome.

Animals↗
PubMed1996

Telepathology diagnosis by means of digital still images: an international validation study.

Telepathology affords the means to provide pathological diagnosis and consultation to remote sites. However, before telepathology can become an acceptable medical tool, it will be vital to determine the diagnostic accuracy of this technology. We report the results of a single-blind study of the accuracy of diagnosis performed using computerized still images obtained from a telepathology workstation used in a French telepathology network. Four pathologists, each working alone, reviewed a total of 200 cases of routine surgical pathology (50 cases each), and performed diagnosis based on both computer CD-ROM still images (CD) and conventional glass slides (GS). Concordance between GS and CD diagnosis, as well as accuracy, were determined. Other factors related to performance were also measured, including diagnostic certainty, reasons for uncertainty, and causes of diagnostic error. Overall, there was good agreement between CS and CD diagnosis. There was 87.5% concordance between CS and CD diagnosis, and comparison to consensus (correct) diagnosis showed accuracy of 95.5% and 88.5% for GS and CD diagnosis, respectively. Marked variability in accuracy of CD diagnosis was observed among the four pathologists, and issues related to image selection and/or quality appeared responsible for 60% of the diagnostic errors. The lack of sufficient images and clinical information were frequently cited as reasons for diagnostic uncertainty, as well as feelings of insufficient expertise. It is likely that the opportunity for interaction with the referring pathologist and the use of subspecialty consultants would likely improve the performance of telepathology.

CD-ROM↗
PubMed1995

Localized endometrial proliferations associated with pregnancy: clinical and histopathologic features of 11 cases.

Eleven cases of an unusual endometrial glandular proliferation associated with early pregnancy are reported. All lesions were incidental discoveries in first-trimester gestational endometria (two elective abortions; five spontaneous abortions; three hydatidiform moles; one tubal ectopic pregnancy). Most patients (nine of 11; 82%) were older than 30 years of age; associated clinical features included oligoovulation (two), hypertension (one), and obesity (one). All lesions were small and localized, and displayed similar histological features of variable severity including glandular expansion with smooth external contours; epithelial stratification (4 to 15 layers); cribriforming (focal to extensive); mitotic activity; bland nuclear cytology; and prominent intraglandular calcifications (eight cases; 72%). Although the natural history of these distinctive pregnancy-associated endometrial lesions was unknown, nine lesions were initially classified as benign, and two were interpreted as atypical endometrial hyperplasia or focal adenocarcinoma. Follow-up for an average of 34 months (range, 18 to 56) in nine patients showed no residual endometrial lesion (seven endometrial curettages and two hysterectomies). Three patients followed by curettage have subsequently completed successful pregnancies. This unusual lesion may represent a localized, endometrial proliferation induced by pregnancy; although some endometrial lesions may display striking architectural complexity, follow-up to date suggests a benign behavior.

Adenocarcinoma↗
PubMed1994

A comparison of preservation techniques in a vascularized rat laryngeal transplant model.

In earlier laryngeal transplantation studies by Takenouchi, et al., the longest ischemic interval tolerated was 45 minutes. A new animal model and enhanced preservative solutions made reassessment timely. This study evaluated two determinants of graft viability: 1. the duration of ischemia and 2. the composition of the preservative media. Three groups of viable transplants were assessed. Groups I and II were preserved with iced heparinized saline with respective ischemic intervals of 3 and 6 hours. Group III was preserved with the Wisconsin solution during a 20-hour ischemic interval. All animals were sacrificed at 24 hours. Representative sections of group I confirmed viability whereas group II exhibited both clinical and histologic evidence of irreversible vascular change. In contrast, most representative sections in group III had little demonstrable change. These data suggest that laryngeal allografts can endure prolonged ischemic intervals if properly maintained.

Adenosine↗
PubMed1994

An assessment of corn oil as a vehicle for cyclosporin A (CsA) at varied injection sites in preventing rejection of rat laryngeal allografts.

This study was designed to determine the efficacy of corn oil as an alternative vehicle to olive oil for emulsifying cyclosporin (CsA) in preventing rejection of transplanted rat larynges. The issue of varied site absorption was also addressed. Thirty animals were transplanted to get 5 viable transplants at two weeks for three varied sites of administration; intramuscular (IM), subcutaneous (SQ) and intraperitoneal (IP). Five mg/kg of CsA in corn oil was the dose administered based on earlier data generated in our laboratory. Postulating selective absorption, the indirect measure of laryngeal histopathology, i.e. rejection, was chosen over blood levels for evaluation. In the IM group 2 grafts evidenced mild rejection whereas 3 showed marked cellular and vascular rejection. The SQ group had 1 mild, 1 moderate and 3 with severe rejections. The IP group had one moderate rejection and 4 severe rejections. Qualitatively the IM and SQ groups were similar. The IP group histologically evidenced far greater cellular rejection. CsA 5mg/kg emulsified in corn oil did not differ substantively in histologic scope or pattern of rejection from CsA in olive oil in experimental rat laryngeal transplantation. Further, the data did not support a change in the administration of CsA from an intramuscular site.

Animals↗
PubMed1993

The effects of cyclosporin A on transplanted rat allografts.

Since 1983, Cyclosporin A (CsA) has been the most successful primary drug in preventing rejection of organ transplants. This study was designed to determine the efficacy and dose response of CsA in preventing rejection of LBNF-1 rat allografts to Lewis recipients. Four groups of animals were studied. Group I served as the control, and groups II, III, and IV were given daily intramuscular doses of CsA for 1 month. The groups were given doses of 5 mg/kg, 7.5 mg/kg, and 10 mg/kg, respectively. Sixty-eight animals were transplanted to get eight viable transplanted animals at 1 month in each CsA group. Laryngeal viability was assessed with both clinical and histological parameters. Groups II, III, and IV had representative clinically viable larynges. The histology varied and had some correlation with CsA dosage. Group II evidenced changes ranging from mild to severe rejection. Group III was more homogeneous with the most severe change being characterized as mild-to-moderate rejection. Group IV was the most uniform with all representative specimens showing only limited infiltration of inflammatory cells with intact mucosa and submucosal glands (mild rejection). None of the CsA groups evidenced the squamous metaplasia characteristic of the control group. CsA can prevent rejection of laryngeal allografts from LBNF-1 donors to Lewis recipients.

Anastomosis, Surgical↗
PubMed1992

Histopathologic correlates of acute laryngeal allograft rejection in a rat model.

This study used both clinical and histopathologic criteria to define the sequence and time parameters of rejection in histoincompatible vascularized rat laryngeal allografts. Clinical onset of rejection was characterized at 1 week by graft edema. Pathologic examination at this time revealed arterial wall thickening and a diffuse lymphocytic and macrophage mucosal infiltrate. At 14 days, the graft was encased in an inflammatory exudate with no visible cartilaginous structure. This correlated microscopically with a lymphocytic infiltrate of the lamina propria, loss of minor salivary glands, and squamous metaplasia of the surface respiratory epithelium. Arterial thrombosis was always correlated with tissue necrosis, but venous occlusion, occurring more than 2 days after transplantation, was not an independent determinant of graft viability. Definition of the time sequence and histopathology of rejection will allow future determination of the efficacy of various immunosuppressive regimens.

Acute Disease↗
PubMed1989

A hyper-recombination mutation in S. cerevisiae identifies a novel eukaryotic topoisomerase.

A hyper-recombination mutation was isolated that causes an increase in recombination between short repeated delta sequences surrounding the SUP4-omicron gene in S. cerevisiae. The wild-type copy of this gene was cloned by complementation of one of its pleiotropic phenotypes, slow growth. DNA sequence of the clone revealed a 656 amino acid open reading frame capable of encoding a protein homologous to the bacterial type I topoisomerase. No homology was detected with previously identified eukaryotic topoisomerases. Construction of double mutants with either of the two known yeast topoisomerase genes revealed synergistic effects on growth suggesting overlapping functions. Expression of bacterial topoisomerase I in yeast can fully complement the slow growth defect of a null mutation. We have named this locus TOP3 and suggest that it defines a novel eukaryotic topoisomerase gene.

Amino Acid Sequence↗
PubMed1988

The effects of various indwelling ureteral catheter materials on the normal canine ureter.

In an attempt to objectively evaluate the biocompatibility of materials commonly used for ureteral stenting, stent-catheters made of four different materials were placed randomly in 31 ureters of 19 mongrel dogs. Animals underwent urography at four weeks and were sacrificed at six weeks. Mild hydronephrosis was noted in eight instances, essentially unrelated to specific material. Silicone, C-flex and polyurethane stents caused a similar, mild degree of ureteral edema, but ureters stented with Silitek demonstrated fairly marked edema. Epithelial ulceration and erosion, often severe, occurred with all polyurethane stents, and rarely with the three other materials. All materials differed statistically from controls, and C-flex caused less reaction overall than polyurethane, indicating differences in biocompatibility of the various materials which may be relevant to their use in patients undergoing long-term ureteral stenting. In practical terms, these suggest that certain materials, notably silicone and C-flex, are more suitable for ureteral stenting than others.

Animals↗
PubMed1986

Auditory brain-stem evoked potentials in patients undergoing dialysis.

Auditory brain-stem evoked potentials (ABEPs) and pure-tone audiograms were obtained for 38 patients with renal failure, undergoing dialysis, before and after a dialysis session, and for 40 healthy normal subjects. Blood chemistry was also evaluated for each patient before and after dialysis. ABEP abnormality (using 10/sec click rate) was observed for 24% of the patients, rising to 44% when 55/sec measures were included. Abnormalities included prolongations of peak latencies for both click rates, and prolongation of interpeak latency differences. Pre-dialysis calcium was significantly different between patients with or without ABEP abnormality. In addition to this chronic effect on ABEPs, an acute effect of the dialysis session was found. Blood chemistry data, ABEP latencies and I-III interpeak latency differences were significantly different before, as compared to after dialysis. The acute effect of dialysis on blood calcium levels correlated with its effect on latencies of peaks III and V at 10/sec click rate, and on peaks I and V latency at 55/sec. These results may indicate the types of dysfunction revealed by increased stimulus rate measures.

Auditory Perception↗
PubMed1985

Focal acantholytic dyskeratosis and epidermolytic hyperkeratosis of the oral mucosa adjacent to squamous cell carcinoma.

A 74-year-old woman presented with an ulcerating squamous cell carcinoma of the posterior mandibular gingiva. Biopsy of the mucosa directly anterior to the tumor revealed areas of both focal acantholytic dyskeratosis (FAD) and epidermolytic hyperkeratosis (EH). Rare solitary lesions of FAD have been described in the oral mucosa; this is the first report of FAD as an incidental finding. EH has only recently been reported in the mouth, and the concept is unknown in the oral pathology literature. Both FAD and EH may represent nonspecific reaction patterns of skin and oral mucosa to numerous stimuli, including carcinogens or adjacent neoplasms.

Acantholysis↗
PubMed1984

Tumor-cell heterogeneity in soft tissue sarcomas as defined by chemoradiotherapy.

This report documents heterogeneous cell populations within high-grade soft tissue sarcomas in seven patients. The authors observed that, following chemoradiotherapy (five patients) or chemotherapy alone (two patients), surgically resected residual or recurrent sarcoma was found to be of low-grade histology. All chemotherapy was of Adriamycin (doxorubicin)-containing combinations. Seven other patients with regional recurrence after resection of high-grade sarcomas had high-grade recurrent tumors. Five of these patients had received no adjuvant therapy; two with extensive retroperitoneal liposarcomas and gross tumor-involved margins had received chemoradiotherapy. Follow-up ranged from 3 to 60 months (median, 12 months). These findings suggest that high-grade populations of sarcoma cells are more susceptible to chemoradiotherapy, as long as there is minimal residual disease. Low-grade clones of tumor cells may survive such therapy and present as clinical recurrence after initial treatment of low-grade or high-grade soft tissue sarcomas. Surgical resection is warranted for these recurrent lesions.

Adult↗
PubMed1984

Metastasis to the submandibular gland as the initial presentation of small cell ("oat cell") lung carcinoma.

A 45-year-old man had a submandibular mass, which was resected. Histopathologic evaluation and the subsequent course revealed it to be a metastasis from a small cell carcinoma of the lung. This is the first case in which a metastatic lesion in the submandibular gland was the presenting manifestation of an extrasalivary neoplasm, predating discovery of the primary tumor. Metastases to the salivary glands in general and to the submandibular gland in particular are discussed, as is the differential diagnosis with primary salivary gland carcinoma.

Carcinoma, Small Cell↗
PubMed1983

Nuclear magnetic resonance for the differentiation of benign and malignant breast tissues and axillary lymph nodes.

We have utilized proton T1 (spin-lattice relaxation time) values of Nuclear Magnetic Resonance to study 110 tissue samples obtained from 11 mastectomy specimens. Samples of 1 cm3 from primary tumor sites, nipples, and other breast quadrants, as well as intact lymph nodes were studied and then histologically scored for the presence or absence of carcinoma and, if present, whether it was an isolated microscopic focus (micro). Of 54 samples of breast tissue, 12 contained carcinoma, 5 micro: of 45 lymph nodes, 15 contained metastatic carcinoma, 2 micro; of the 11 nipples, 2 had carcinoma, both micro. For the malignant samples (excluding micro) mean T1 value was 0.47 +/- 0.07 sec, (range 0.39-0.79 sec). For the 72 benign samples (excluding nipple) mean T1 value was 0.26 +/- 0.03 sec (range 0.14-0.36 sec). The 13 tumor-bearing nodes had a mean T1 value of 0.47 +/- 0.03 sec (range 0.40-0.63 sec); mean for the benign nodes was 0.26 +/- 0.007 sec (range 0.19-0.35 sec). The differences were highly significant in each case (p less than 0.001). For micro examples, T1 values were at malignancy threshold levels or just below, except for nipple tissues, where discrimination was poor. For the 20 other malignant samples, there was no correlation between T1 value and the per cent of sample containing malignancy.

Axilla↗