Search PubMed⌕ Search

Biomedical subjects

C S Cooper

Publications and source records attributed to C S Cooper.

At least 73 records · Page 4Linked to original sources
PubMed1996

The synthesis and in vitro antibacterial activity of conformationally restricted quinolone antibacterial agents.

Two series of conformationally restricted quinolone antibacterials were synthesized. One series was restricted by formation of a tetrahydrofuran ring between the C-6 position and the C-7 position of the quinolone ring skeleton. The second series achieved conformational rigidity by formation of a tetrahydrofuran ring between the C-7 and the C-8 positions. These compounds were evaluated for their in vitro antibacterial activity. Compounds 19 and 20 were the most active compounds in either series and were about equipotent.

Anti-Infective Agents↗
PubMed1996

Azoospermia in a 46,XX/47,XXX phenotypic male.

We report the unique case of a 34-year-old 46,XX/47, XXX man with complete masculinization and azoospermia. Analysis of the patient's deoxyribonucleic acid failed to detect the azoospermia factor (AZF) region. Lack of germ cell elements on subsequent testicular biopsy illustrates the importance of the AZF region for spermatogenesis. Discussion concerning the genetics of testicular and germ cell formation is undertaken in the context of the patient presented.

Adult↗
PubMed1996

Management of prostate and bladder cancer in the elderly.

The management of prostate and bladder cancer in the elderly will increasingly require clinicians to judge the impact on comorbidity and toxicity of the proposed therapy in order to make sound management decisions. As PSA-based screening has rapidly increased, physicians are increasingly challenged to decide the upper age limits for such screening and therapy. Bladder cancer management in the elderly differs little from that offered to the younger patient and the new therapeutic developments may improve the risk-to-benefit ratio of treating advanced disease. It is clear that as the US population ages, management of prostate and bladder cancer will become an increasingly common dilemma for the urologic practitioner.

Age Factors↗
PubMed1996

Translocations in solid tumours.

Specific chromosomal translocations have now been identified in a variety of solid tumour types. Recent developments in this field include the identification of novel genes involved in the t(X;18) synovial sarcoma translocation and the discovery that the high-mobility group protein gene, HMGI-C, is involved in the chromosome 12 rearrangements found in lipomas and uterine leiomyomas. These discoveries may have important implications for the strategies used in tumour diagnosis and treatment.

Humans↗
PubMed1996

The t(X;1)(p11.2;q21.2) translocation in papillary renal cell carcinoma fuses a novel gene PRCC to the TFE3 transcription factor gene.

The specific chromosomal translocation t(X;1)(p11.2;q21.2) has been observed in human papillary renal cell carcinomas. In this study we demonstrated that this translocation results in the fusion of a novel gene designated PRCC at 1q21.2 to the TFE3 gene at Xp11.2. TFE3 encodes a member of the basic helix-loop-helix (bHLH) family of transcription factors originally identified by its ability to bind to microE3 elements in the immunoglobin heavy chain intronic enhancer. The translocation is predicted to result in the fusion of the N-terminal region of the PRCC protein, which includes a proline-rich domain, to the entire TFE3 protein. Notably the generation of the chimaeric PRCC-TFE3 gene appears to be accompanied by complete loss of normal TFE3 transcripts. This work establishes that the disruption of transcriptional control by chromosomal translocation is important in the development of kidney carcinoma in addition to its previously established role in the aetiology of sarcomas and leukaemias.

Adult↗
PubMed1996

The effect of exogenous testosterone on total and free prostate specific antigen levels in healthy young men.

PURPOSE: We evaluated the effect of exogenous testosterone administration on serum total and free prostate specific antigen (PSA) in healthy young men. MATERIALS AND METHODS: Nine volunteers received either 100, 250 or 500 mg. testosterone by intramuscular injection each week for 15 weeks. Blood was drawn every other week for 28 weeks and at week 40. Serum total and free PSA, and total and free testosterone were measured and compared to baseline values. RESULTS: Significant elevations in total and free testosterone occurred but no significant change in serum total and free PSA was detected. CONCLUSIONS: Serum PSA is not responsive to elevated serum testosterone levels in healthy young men. PSA metabolism in the normal prostate is unclear but our findings may have implications for differentiation of pathological conditions of the human prostate.

Adult↗
PubMed1996

Splenectomy complicating left nephrectomy.

PURPOSE: We attempted to clarify the details of incidental splenectomy complicating left nephrectomy. MATERIALS AND METHODS: We reviewed the literature and operations involving splenectomy performed during left nephrectomy between 1984 and 1994 at our university. Factors reviewed included patient characteristics, renal pathology, mechanisms of injury, blood transfusions and postoperative complications. RESULTS: Of the 418 left nephrectomies 18 (4.3%) resulted in splenectomy via a transperitoneal approach. Patients with a large or upper pole renal lesion, malignancy or advanced age are increasingly likely to undergo unanticipated splenectomy. CONCLUSIONS: Our results, combined with recommendations from the Centers for Disease Control and Prevention, suggest that all patients older than 65 years undergoing left transperitoneal nephrectomy or those at increased risk for splenic injury should receive preoperative pneumococcal vaccination.

Age Factors↗
PubMed1995

Long-range organization of reiterated sequences, including the SSX1 cDNA at the OATL1 cluster in Xp11.23.

Analysis of four YACs at the OATL1 locus was undertaken to determine the organization of locally repeated sequences within the OATL1 cluster. A restriction map of ICRFy900C0874, a 600-kb YAC, was constructed using a range of rare-cutting enzymes. Several markers were isolated from the OATL1 cluster, and the YAC map was used for their localization. Markers are shown to be reiterated within the OATL1 cluster, and fine-scale mapping has identified the accurate map position and organization of these repeated sequences within a 275-kb interval. The SSX1 gene involved in synovial sarcoma tumorigenesis and localized at the OATL1 cluster is also shown to be present in a minimum of five copies, all of which map to the aforementioned region. Several markers generated in this study have homologous counterparts at OATL2; they have been utilized to delimit the duplicated region at the OATL clusters. Although instability of one of the OATL1 YACs, ICRFy900F0501, has precluded a precise sizing of this interval, it has been possible to place an upper limit of 520 kb on this region of duplication.

Base Sequence↗
PubMed1995

Fusion of SYT to two genes, SSX1 and SSX2, encoding proteins with homology to the Kruppel-associated box in human synovial sarcoma.

We demonstrate that the cytogenetically defined translocation t(X;18)(p11.2;q11.2) found in human synovial sarcoma results in the fusion of the chromosome 18 SYT gene to either of two distinct genes, SSX1 or SSX2, at Xp11.2. The SSX1 and SSX2 genes encode closely related proteins (81% identity) of 188 amino acids that are rich in charged amino acids. The N-terminal portion of each SSX protein exhibits homology to the Kruppel-associated box (KRAB), a transcriptional repressor domain previously found only in Kruppel-type zinc finger proteins. PCR analysis demonstrates the presence of SYT-SSX1 or SYT-SSX2 fusion transcripts in 29 of 32 of the synovial sarcomas examined, indicating that the detection of these hybrid transcripts by PCR may represent a very useful diagnostic method. Sequence analysis has demonstrated heterogeneity in the fusion transcripts with the formation of two distinct SYT-SSX1 fusion junctions and two distinct SYT-SSX2 fusion junctions.

Adolescent↗
PubMed1995

Fusion of the EWS gene to a DNA segment from 9q22-31 in a human myxoid chondrosarcoma.

Southern blot analyses revealed a rearrangement of the EWS gene in a skeletal human myxoid chondrosarcoma. Interphase fluorescence in situ hybridization (FISH) studies, using cosmid clones F7 and G9 that flank the EWS locus on 22q12, confirmed the presence of this EWS gene abnormality. Cloning the rearranged EWS DNA fragment and mapping by FISH demonstrated that the EWS gene is joined to DNA sequences localised in 9q22-31. These findings are consistent with previous cytogenetic reports of a recurrent t(9;22)(q22-31;q11-12) in the myxoid variant of chondrosarcoma and reveal involvement of the EWS gene in a fourth type of human sarcoma.

Adult↗
PubMed1995

Treating fluency disordered adolescents.

This paper presents fluency disorders in three types of stuttering syndromes with etiological considerations. The syndromes consist of affective, behavioral and cognitive components useful for fluency assessment and establishment of therapy goals with adolescents who stutter. The ultimate goal of the treatment program is a feeling of fluency control rather than actual fluency. A therapy process for fluency disordered adolescents is suggested which outlines four stages with goals and objectives for each stage. Behavior techniques for eliciting a feeling of fluency control are also included. Finally, a case history illustrates the therapy process for an adolescent with a fluency disorder.

Adolescent↗
PubMed1995

Programmed cell death in response to chemotherapeutic agents in human germ cell tumour lines.

Testicular germ cell tumours are amongst the most chemosensitive neoplasms both in vivo and in vitro. In the present study we demonstrate that following exposure to drugs used in chemotherapeutic treatment of testicular germ cell cancer tumour cells undergo death by apoptosis. Thus, after exposure of the GCT27 embryonal carcinoma cell line to cisplatin, we observed the degradation of DNA into oligonucleosomal fragments, which is a hallmark of apoptosis. Furthermore, light, fluorescence and electron microscopy reveal the presence of condensed abnormal shaped nuclear chromatin which is characteristic of apoptosis. Changes diagnostic of apoptosis were also observed following (a) cisplatin treatment of the GCT48 and Susa embryonal carcinoma cell lines and the GCT44 yolk sac tumour cell line and (b) etoposide treatment of the GCT27 and Susa cell lines. When the GCT27 cell line was treated with 15 microns cisplatin, apoptosis was first observed at 6-9 h and greater than 90% of cells were dead within 24 h. Apoptosis was not blocked when cisplatin-treated cells were incubated in the presence of cycloheximide, although this agent did cause a 4-6 h delay in the onset of cell death. In addition, we demonstrated that the GCT27 cell line can be induced to undergo apoptosis by exposure to low concentrations of the calcium ionophore, ionomycin. These observations show that germ cell tumours are remarkably sensitive to a range of agents that act by different mechanisms. They are triggered to undergo apoptosis rapidly by a mechanism that is not blocked by inhibitors of protein synthesis.

Apoptosis↗
PubMed1995

Microsatellite instability in human testicular germ cell tumours.

DNA samples obtained from 29 testicular germ cell tumours have been screened for instability at nine different microsatellite sequences consisting of dinucleotide, trinucleotide and tetranucleotide loci. Overall, in tumours from six (21%) patients we found abnormalities in at least one of the loci examined. Mutation was most frequently found in tetranucleotide and trinucleotide repeats with only a low proportion of alterations in dinucleotide repeats. This pattern of instability is distinct from that reported in colorectal cancer and other cancers that have a high level of alterations in dinucleotide repeats.

Adult↗
PubMed1995

The human SB1.8 gene (DXS423E) encodes a putative chromosome segregation protein conserved in lower eukaryotes and prokaryotes.

We report that the human gene SB1.8 (DXS423E) encodes a protein of 1233 amino acids that is highly homologous (30% identity) to the essential yeast protein SMC1 which is required for the segregation of chromosomes at mitosis. Both SB1.8 and SMC1 contain an N-terminal NTP binding site, a central coiled-coil region and a C-terminal helix-loop-helix domain, and have structural features in common with the force generating proteins myosin and kinesin. SB1.8 also exhibits regions of homology and overall structural similarity to the prokaryote (Mycoplasma hyorhinis) protein 115p. Thus SB1.8 and SMC1 are members of a highly conserved and ubiquitous family of proteins that appear to have a fundamental role in cell division. In addition we show that SB1.8 (DXS423E) maps to a cosmid contig that lies centromeric to the OATL2 locus at chromosome Xp11.2.

Amino Acid Sequence↗
PubMed1995

Mapping the X chromosome breakpoint in two papillary renal cell carcinoma cell lines with a t(X;1)(p11.2;q21.2) and the first report of a female case.

A t(X;1)(p11.2;q21.2) has been reported in cases of papillary renal cell tumors arising in males. In this study two cell lines derived from this tumor type have been used to indicate the breakpoint region on the X chromosome. Both cell lines have the translocation in addition to other rearrangements and one is derived from the first female case to be reported with the t(X;1)(p11.2;q21.2). Fluorescence in situ hybridization (FISH) has been used to position YACs belonging to contigs in the Xp11.2 region relative to the breakpoint. When considered together with detailed mapping information from the Xp11.2 region the position of the breakpoint in both cell lines was suggested as follows: Xpter-->Xp11.23-OATL1-GATA1-WAS-TFE3-SY P-t(X;1)-DXS255-CLCN5-DXS146-OATL2- Xp11.22-->Xcen. The breakpoint was determined to lie in an uncloned region between SYP and a YAC called FTDM/1 which extends 1 Mb distal to DXS255. These results are contrary to the conclusion from previous FISH studies that the breakpoint was near the OATL2 locus, but are consistent with, and considerably refine, the position that had been established by molecular analysis.

Carcinoma, Papillary↗
PubMed1994

Urological laparoscopic practice patterns 1 year after formal training.

The long-term impact of laparoscopic training on urological surgical practice patterns is unclear. We assessed urologist practice patterns 1 year subsequent to a formal training course in urological laparoscopic surgery. Results were compared to findings from an identical study performed 3 months following training. On 5 dates between January and October 1991, a total of 163 urologists participated in a 2-day, university sponsored, laparoscopic surgery training seminar. At 3 months and 1 year following the course, participants were mailed a 20-question survey inquiring as to the interval laparoscopic experience. Multiple questions were designed for later correlation with participant use of laparoscopic surgery. Totals of 105 and 128 course participants (64% and 78.5%) responded to the questionnaire at 3 and 12 months, respectively. No significant differences in 3-month and 12-month demographics were demonstrated with respect to practice setting, practice focus or percentage undergoing additional training. Significant increases were noted between 3 and 12 months in the number of candidates identified per month (1.5 versus 2.4), proportion of surgical case load taken by laparoscopy (2.6% versus 4.1%), number of laparoscopic patient inquiries per month (0.25 versus 1.0) and number of laparoscopies performed per month (0.55 versus 0.78). Additional post-course training was significantly correlated with clinical use at 3 and 12 months. Of the 105 and 108 respondents 64 (61%) and 83 (65%) had engaged in some form of additional training by 3 months and 1 year after the course, respectively. Additional training as well as performance of laparoscopy proved to be independent of practice setting or practice focus at 3 and 12 months. Those who attended the course with a partner were significantly more likely to have performed laparoscopy at 1 year than those who attended alone. At 12 months following course completion 66% of the respondents believed that the year of laparoscopic experience was sufficient to maintain skills. This survey suggests that laparoscopic techniques are being used consistently by urologists subsequent to formal laparoscopic training courses.

Education, Medical, Continuing↗
PubMed1994

Abnormalities of the p53 MDM2 and DCC genes in human leiomyosarcomas.

In this study we have screened a series of 29 primary leiomyosarcomas for abnormalities of both the p53 gene and the MDM2 gene, which encodes a p53-associated protein. SSCP (single-strand conformation polymorphism) analysis and direct sequencing of polymerase chain reaction (PCR)-amplified DNA were used to establish that 6/29 tumours possessed point mutations of the p53 gene. Using a monoclonal antibody that recognises the p53 protein in immunohistochemical staining experiments, we observed overexpression of the p53 protein in five of the six tumours containing point mutations in the p53 gene. Southern analysis of tumour DNA revealed that 2/29 tumours demonstrated amplification of the MDM2 gene. When considered together, these results indicate that alterations in both the p53 gene and MDM2 gene are important in the development of a significant minority of leiomyosarcomas. In addition, we have demonstrated a significant association between the presence of abnormalities of the p53 gene or MDM2 genes in leiomyosarcomas and a more advanced clinicopathological stage (P = 0.03). We have also examined the role of the DCC tumour-suppressor gene in the development of human soft-tissue tumours in a variety of histological types. Except for evidence of a rearrangement in a single leiomyosarcoma cell line, SK-UT-1, we have found no direct evidence to support a role for mutation of the gene in the development of human soft-tissue tumours.

Adult↗