An interview with ... Carol Jones. Interview by Dina Plowes.
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Biomedical subjects
Publications and source records attributed to C Jones.
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Rom-1 is a retinal integral membrane protein that, together with the product of the human retinal degeneration slow gene (RDS), defines a photoreceptor-specific protein family. The gene for rom-1 (HGM symbol: ROM1) has been assigned to human chromosome 11 and mouse chromosome 19 by Southern blot analysis of somatic cell hybrid DNAs. ROM1 was regionally sublocalized to human 11p13-11q13 by using three mouse-human somatic cell hybrids; in situ hybridization refined the sublocalization to human 11q13. Analysis of somatic cell hybrids suggested that the most likely localization of ROM1 is in the approximately 2-cM interval between human PGA (human pepsinogen A) and PYGM (muscle glycogen phosphorylase). ROM1 appears to be a new member of a conserved syntenic group whose members include such genes as CD5, CD20, and OSBP (oxysterol-binding protein), on human chromosome 11 and mouse chromosome 19. Localization of the ROM1 gene will permit the examination of its linkage to hereditary retinopathies in man and mouse.
BACKGROUND: Photodynamic therapy is an investigational method for the treatment of a variety of solid tumors. The purpose of this study was to determine the optimum factors and illustrate the effectiveness of photodynamic therapy in the treatment of basal cell carcinomas. This was a prospective study in which patients presenting with primary or recurrent basal cell tumors, particularly but not exclusively widespread tumors or large single tumors, were offered the option of photodynamic therapy in their treatment regimen. RESULTS: Patients were administered 1 mg/kg of a photosensitizer (Photofrin II). Light doses (630 nm) ranged from 72 to 288 J/cm2. A total of 37 patients with 151 sites were treated in this study. A complete response rate of 88% was achieved with one application. Morbidity was low; the most significant side effects were moderate pain and edema. CONCLUSIONS: Photodynamic therapy is a modality that offers localized treatment of primary or recurrent nonmelanoma skin cancer. By applying reciprocal doses of photosensitizer and light, the efficacy of photodynamic therapy in the treatment of skin lesions is demonstrated achieving significant light penetration into tissue with a high complete response rate of the lesions and acceptable normal tissue response.
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The 1H- and 13C-n.m.r. data on the capsular polysaccharide (1) produced by Streptococcus pneumoniae type 4, the depyruvated polysaccharide (2), and a tetrasaccharide (3a) derived by Smith degradation of 2 were used as constraints on a computer-generated model of the conformation of 1 and to assess the effects of the pyruvic acetal substituent on the conformation. The dynamics of the polysaccharide systems and the influence of the pyruvic acetal were investigated using 13C-n.m.r. relaxation measurements.
We have constructed a physical map of the region q12-13 on chromosome 11 by combining data generated from a panel of radiation-reduced somatic cell hybrids and pulsed-field gel electrophoresis (PFGE). Twenty different genetic markers have been sublocalized and ordered within this region and a total of 8.0 megabases has been mapped in detail using rare-cutting restriction endonucleases and PFGE. In two instances, the long-range restriction PFGE map spans the total distance between pairs of loci that have been previously mapped by genetic linkage in reference families. Comparison of this physical map with the available linkage map indicates a great variation in the recombination frequency over the region. The recombination rate is higher than expected, particularly for markers flanking the MEN1 region. Thus, for the closest pair of linked markers on the centromeric side, one centimorgan corresponds to approximately 300 kilobases, and for markers on the telomeric side, one centimorgan corresponds to approximately 350-600 kilobases.
The 1H-n.m.r. spectra of the Streptococcus pneumoniae type 9V (S68 in American nomenclature) capsular polysaccharide (PS) and its O-deacetylated derivative [which is structurally identical to the S. pneumoniae type 9A (S33) PS] were assigned using COSY, relayed-COSY, and 2D-NOESY experiments. The positions of the OAc groups in the alpha-GlcA, beta-ManNAc, and alpha-Glc residues of the native 9V PS were established using 2D-n.m.r. and chemical shift arguments, and the relative proportions of different O-acetylated species were estimated by integration of well-resolved 1H-n.m.r. signals. The locations of the OAc substituents differ from those previously reported. [formula: see text].
We have generated somatic cell hybrids containing fragments of human chromosome arm 9q by an irradiation and fusion technique. No selection for human material was imposed, but of 23 clones analyzed most contained human DNA sequences and many contained multiple fragments of the human chromosome arm. A hybrid that appears to contain only two small fragments of human DNA from the regions of q33 and q34 has been used as a source from which to clone probes specific to those areas of the chromosome.
Human cytomegalovirus (HCMV) transforming region II (mtrII), a 980-bp sequence, can transform rodent fibroblasts. This region contains three small potential open reading frames (ORFs) of 79, 83, and 34 amino acid residues. To identify the specific role of mtrII sequences in transformation, we investigated (1) the presence of mtrII DNA and mtrII-specific RNA transcripts in NIH 3T3 transformants and their tumor derivatives, and (2) the ability of mtrII DNA and its subregions to cis-activate chloramphenicol acetyl transferase (CAT) gene expression. By hybridization analysis, mtrII-specific DNA and RNA were detected in both transformed and tumor cells. A 285-bp sequence upstream of the ORFs in mtrII exhibited weak promoter activity when linked to CAT gene in the sense orientation with respect to the ORFs. Promoter activity of this region was stronger than the enhancer activity in the sense orientation. No promoter or enhancer activity was detected in the antisense orientation. The mtrII 980-bp sequence did not exhibit any promoter activity in either orientation. These results suggested that HCMV mtrII may contain a small transforming gene that may be transcribed at low levels from its own promoter.
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BACKGROUND: Participants who had completed a multicomponent group smoking cessation program were interviewed to determine their smoking status and satisfaction with the program. METHODS: The follow-up interviews occurred an average of 20 months after entry to the program, with a response rate of 80% (89 out of 111 enrollees). Most individuals interviewed (82%) were able to quit for at least 24 hr; 25% were able to maintain nonsmoking status for 1 year or longer. RESULTS: Initial quit rates were comparable for both men and women, but women were more than twice as likely to have relapsed by the time of the follow-up interview. Participants rated self-monitoring as the most helpful of 10 program components, including nicotine fading, nicotine gum, group support, health information, and talks by ex-smokers. Ratings for the program overall were higher than the rating of any individual component. CONCLUSIONS: Since earlier studies have found that successful quitters use more coping strategies than relapsers, multicomponent programs offer participants an opportunity to learn a variety of techniques and choose the combination that works best for them.
NotI and EagI boundary libraries were constructed for human chromosome 21. One hundred forty-seven clones were isolated from the somatic cell hybrid 72532X-6 and localized using a hybrid mapping panel. After identification of those clones, which were isolated more than once, as well as those probes derived from a previously unrecognized integrated non-chromosome-21 fragment, 58 individual boundary clones (plus 2 additional NotI-EcoRI clones isolated from a flow-sorted library) were localized to 11 separate regions. The distribution of these probes is highly nonrandom, with 50% of the clones located in the distal band 21q22.3. Two probes, Not50 and Eag101, map to regions in the very proximal long arm which may contain the gene responsible for familial Alzheimer's disease (AD1), and Not50 would appear to be more proximal than D21S16 (E9). Twenty-eight probes map to the region between superoxide dismutase (SOD1) and the ETS2 oncogene, which appears to contain genes responsible for many of the phenotypic features of Down syndrome. Twenty clones contain (GT)n repeats, as determined by hybridization to a CA polymer, and should provide additional highly polymorphic probes. Closure of gaps in the physical linkage map of chromosome 21 should be facilitated by the isolation of these probes, as they identify many of the unmethylated CpG-rich islands that have hindered pulsed-field gel analysis. They will also be useful in identifying a set of genes in proximity to NotI and EagI restriction sites, as well as conserved DNA sequences for comparative mapping studies.
Analysis of polysaccharide components of meningococcal- and pneumococcal vaccines was carried out by proton n.m.r. spectroscopy and gas chromatography. The meningococcal polysaccharides were of high purity but showed differences in degree and position of O-acetylation between manufacturers. The level of contamination of the pneumococcal polysaccharides by C-substance was quantified. These methods provide an alternative to immunological methods for determining serotype and purity.
OBJECTIVE: To compare percutaneous tracheostomy with conventional operative tracheostomy. DESIGN: Randomized clinical trial. SETTING: The medical and surgical critical care units of a large, tertiary-care, private hospital. PATIENTS: Twenty-five male and 21 female translaryngeally intubated patients with respiratory failure, in whom tracheostomy was indicated on clinical grounds, were randomly assigned to one of two groups. INTERVENTIONS: The 24 patients in group 1 underwent conventional operative tracheostomy, and the 22 patients in group 2 underwent percutaneous tracheostomy. One patient in group 2 required tracheostomy on three separate occasions during a prolonged hospital stay. MEASUREMENTS AND MAIN RESULTS: Patients were examined daily throughout their hospital stays for adverse events related to the tracheostomy. In all patients who survived until decannulation, plain tomography of the trachea was performed within 3 days of decannulation. Repeat physical and tomographic examinations were performed 6 and 12 wks later. Fifty-eight percent (14/24) of the operative tracheostomies were associated with at least one complication, compared with 25% (6/24) of the percutaneous tracheostomies (p less than .05, 95% confidence interval 7% to 59%). Predecannulation problems were more frequent in group 1 patients than in group 2 (46% vs. 13%, respectively; p less than .01, 95% confidence interval 9% to 57%), as were later sequelae (88% vs. 27%; p less than .05, confidence interval 26% to 96%) in survivors. Group 1 patients were more likely to have multiple complications, and their complications tended to be more serious. CONCLUSION: In this study, percutaneous tracheostomy appeared to be superior to the conventional operation.
Microvascular thrombosis in free flap and replantation surgery may be amenable to thrombolytic therapy. A blinded, controlled, preliminary study in rats compared urokinase (UK) and tissue plasminogen activator (t-PA) on thrombolytic efficacy, systemic fibrinolytic effect, and reocclusion. Bilateral femoral vein clots were induced in 38 rats. Local infusion of UK, t-PA, or saline was performed. Fibrinogen levels were drawn from one group. A second group was evaluated for reocclusion up to one month. Ipsilateral lysis occurred for reocclusion up to one month. Ipsilateral lysis occurred in 10/12, 13/13, and 0/13 of the UK, t-PA, and saline groups, respectively, with no significant difference detected between the UK and t-PA groups. Contralateral clot lysis occurred in both the UK and t-PA groups. No significant differences in the fibrinogen levels was detected among the three groups. Reocclusion occurred only in the UK group.
The host range of retroviruses is determined primarily by the presence of specific receptors on target cells which are recognized by the retroviral envelope glycoprotein. Somatic cell hybrids have been used to determine the chromosomal locations of several retroviral receptors in mice prior to their molecular cloning. Here we report that by using human-Chinese hamster somatic cell hybrids and a retroviral vector, we have mapped the receptor for the amphotropic murine leukemia virus to the pericentromeric region of human chromosome 8.
We reported previously that the herpes simplex virus type 1 (HSV-1) thymidine kinase reporter gene (tk) was expressed in the testes of transgenic mice when coupled to the promoter of a liver-specific mouse major urinary protein (MUP) gene. Here we show that HSV-1 tk is also expressed in the testis when coupled to a MUP pseudogene promoter, to a truncated MUP promoter that is not active in the liver, and to the promoter of the bovine thyroglobulin gene. Furthermore, HSV-1 tk itself was expressed in the testis, although its normal expression had been disabled by removing an upstream regulator of transcription. In every case, the same multiple transcripts were observed, with their 5' ends located downstream of the normal HSV-1 tk translation initiation codon. We conclude that the transcription of HSV-1 tk in the testis is directed by a cryptic TATA box-independent promoter located in the coding region of the gene. The longest HSV-1 thymidine kinase (TK) polypeptides synthesized in the testis were shorter than full-length TK and probably result from translational initiation at Met46 and Met60, the second and third ATG codons of the tk reading frame. Male mice of most transgenic lines were sterile, and the severity of the lesion in spermatogenesis was directly related to the level of TK expression. In the most highly expressing lines, sperm counts were low and morphologically defective sperm were common. In other sterile lines, TK was expressed at a lower level and sperm counts were normal but sperm motility was greatly reduced. Lines with the lowest levels of HSV-1 TK expression were fertile. HSV-1 TK was expressed in germ line cells, mainly in the haploid spermatids. However, low-level HSV-1 TK activity was found in the testis before the first germ cells entered meiosis, showing that if expression is confined to the germ cells, it also occurs in spermatogonia.