Modified glutathione S-transferase fusion proteins for simplified analysis of protein-protein interactions.
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Amino Acid Sequence↗
Biomedical subjects
D B Smith
Publications and source records attributed to D B Smith.
Ocular dysfunction during the amytal suppression test.
We assessed the following parameters of visual function in 16 patients during amytal suppression test (AST): pupillary light response, consensual reflex, pupillary symmetry, monocular reading and monocular visual recognition. Significant visual impairment in the eye ipsilateral to injection (EII) occurred in 7 of 16 patients ranging from blurring to complete, transient loss of vision. We conclude that visual dysfunction of the EII during the AST is common and represents an important component of the test. Intracarotid amytal reaches the EII via ophthalmic artery and probably impairs vision in the EII due to cycloplegia, iridoplegia and retinal suppression.
Amobarbital↗
Efficacy and safety of zonisamide: results of a multicenter study.
The safety and efficacy of zonisamide (ZNS), a new antiepileptic drug, was tested in 167 adult participants who entered a historical-controlled 16-week open label, multicenter study. The median percent reduction from baseline of partial seizures was 51.8% in the fourth month of the study (baseline median = 11.5 sz/month; treatment weeks 13-16 = 5.5 sz/month). Persons completing the efficacy study successfully were eligible for a long-term safety study; 113 entered this study. Adverse effects involved principally the CNS and were similar to those seen with other antiepileptic drugs. Four persons (3.7%) developed kidney stones and were withdrawn from the study 250-477 days after starting ZNS. Because of the high percentage of kidney stones, development of ZNS was stopped in the United States but was continued in Japan.
Adolescent↗
Correlation between clinical staging (FIGO) and prognostic groups with gestational trophoblastic disease.
OBJECTIVE: To compare the Charing Cross Hospital scoring system with FIGO staging for gestational trophoblastic disease. DESIGN: A retrospective analysis of patients referred to Charing Cross during the period 1979-1989. SETTING: National referral centre. SUBJECTS: Two hundred and seven women with gestational trophoblastic disease presenting between 1979-1989. MAIN OUTCOME MEASURES: The women were classified according to the Charing Cross Hospital scoring system and FIGO clinical staging and the results of treatment compared. RESULTS: Of the 207 women studied, there were 102 low risk, 39 medium risk and 66 high risk according to the Charing Cross system and 26 stage 0, 83 stage 1, 23 stage 2, 51 stage 3 and 24 stage 4 according to the FIGO system. If the FIGO system had been used to determine therapy, 17 women would have been at risk of undertreatment and nine of overtreatment. The main prognostic factors contributing to a higher Charing Cross score and thus more intensive chemotherapy from the outset were: HCG > 10(5), interval from antecedent pregnancy > 12 months and term delivery. CONCLUSIONS: The Charing Cross scoring system incorporates factors predictive of the presence of drug resistant tumour and thus allows more appropriate use of chemotherapy from the start of treatment than is possible with the anatomically based FIGO staging. Moreover, the system is easy to apply relying only on history and clinical examination in addition to a reliable quantitative HCG assay.
Adult↗
The racial integration of health facilities.
No published measures of racial integration in health facilities in the United States exist. This article reviews the problems with possible sources of data. It then derives estimates of the degree of integration in nursing homes and hospitals from the 1985 National Nursing Home and National Hospital Discharge surveys. Nursing homes were less racially integrated than hospitals. Health facilities in the South were more integrated than in any other region of the country. There was little difference in the degree of racial segregation of publicly financed patients and those whose care was financed from private sources. Data on nursing homes in Pennsylvania illustrate in more detail some of the consequences of such patterns of segregation. The article discusses some of the reasons for the lack of easy access to such information and makes recommendations for addressing it.
Black or African American↗
Current approaches to diagnosis and treatment of gestational trophoblastic disease.
Diagnosis of molar pregnancy relies on serum and urine human chorionic gonadotropin estimations in addition to characteristic appearances on histology. Approximately 92% of hydatidiform moles resolve spontaneously after evacuation, and with careful human chorionic gonadotropin follow-up, the remainder can be successfully treated with a minimum of toxicity. Non-post-mole gestational choriocarcinoma is also highly curable with modern chemotherapy, and in the rare cases when drug resistance develops, surgery can be an effective salvage treatment. In cases when doubt exists as to whether a patient has a true gestational tumor or a human chorionic gonadotropin-producing carcinoma, the origin of the tumor can sometimes be determined by DNA analysis. This determination can help to avoid inappropriate chemotherapy for patients with nongestational tumors.
Antineoplastic Combined Chemotherapy Protocols↗
Computer system for assisting with clinical interpretation of tumour marker data.
OBJECTIVE: To design and evaluate a computer advisory system for the treatment of gestational trophoblastic tumour. DESIGN: A comparison of clinicians' treatment decisions with those of the computer system. Two datasets were used: one to calibrate the system and one to independently evaluate it. SETTING: Department of medical oncology. PATIENTS: Computerised records of 290 patients with low risk gestational trophoblastic tumour for whom the advisory system could predict the adequacy of treatment. The calibration set comprised patients admitted during 1979-86(227) and the test set patients during 1986-89(63). MAIN OUTCOME MEASURES: The system's accuracy in predicting need to change treatment compared with clinicians' actions. The mean time faster that the system was in predicting the need to change treatment. RESULTS: On the calibration dataset the system was 94% (164/174) accurate in predicting patients whose treatment was adequate, recommending change when none occurred in only 10 (6%) patients. In patients whose treatment was changed the system recommended change earlier than clinicians in 39/53 cases (74%), with a mean time advantage of 14.9 (SE 2.02) days. On the test dataset the system had an accuracy of 91% (31/34) in predicting treatment adequacy and a false positive rate of 9% (3/34). The system recommended change earlier than clinicians in 22/29 cases (76%), with a mean time advantage of 12.5 (2.22) days. CONCLUSIONS: The computer advisory system could improve patient management by reducing the time spent receiving ineffective treatment. This has implications for both patient time and clinical costs.
Biomarkers, Tumor↗
Immunological homology among azoreductases from Clostridium and Eubacterium strains isolated from human intestinal microflora.
Azoreductases from several anaerobic intestinal bacteria have been shown to reduce azo dyes to carcinogenic aromatic amines. To evaluate the structural similarities of azoreductases from four species of Clostridium and one species of Eubacterium, a polyclonal antibody against purified Clostridium perfringens azoreductase was generated in rabbits. This antibody inhibited the azoreductase activity of all five bacteria tested. ELISA showed different degrees of binding of the antibody to various species of bacteria. In a Western blot, the antibody reacted with the purified azoreductases from all four Clostridium species and the Eubacterium species. These results demonstrate that the azoreductases from the bacteria tested share similar antigenic domains, which are probably located in the active site of the enzyme. Azoreductases from these intestinal bacteria are similar enough to be considered as a single group of enzymes with respect to their functions and antigenicity.
Blotting, Western↗
Extreme heterogeneity of Ty1-copia group retrotransposons in plants.
We have used the polymerase chain reaction to analyse Ty1-copia group retrotransposons of flowering plants. All eight species studied contain reverse transcriptase fragments from Ty1-copia group retrotransposons. Sequence analysis of 31 subcloned fragments from potato reveals that each is different from the others, with predicted amino acid diversities between individual fragments varying between 5% and 75%. Such sequence heterogeneity within a single species contrasts strongly with the limited diversity seen in such retrotransposons in yeast and Drosophila. The fragments from the other seven plant species examined are also heterogeneous, both within and between species, showing that this is a general property of this transposon group in plants. Phylogenetic analysis of all these sequences reveals that many of them fall into subgroups which span species boundaries, such that the closest homologue of one sequence is often from a different species. We suggest that both vertical transmission of Ty1-copia group retrotransposons within plant lineages and horizontal transmission between different species have played roles in the evolution of Ty1-copia group retrotransposons in flowering plants.
Amino Acid Sequence↗
A Ty1-copia group retrotransposon sequence in a vertebrate.
We have used the polymerase chain reaction (PCR) to isolate a sequence characteristic of a Ty1-copia group retrotransposon from the genome of the herring (Clupea harengus). This is the first Ty1-copia group retrotransposon sequence described in a vertebrate. Phylogenetic comparison of this sequence with other members of this group of retrotransposons shows that it resembles more closely some Ty1-copia group members from Drosophila melanogaster than other group members in plants and fungi. These observations provide further evidence that the Ty1-copia group LTR retrotransposons span many of the major eukaryote species boundaries, suggesting that horizontal transmission between different species has played a role in the evolution of this retrotransposon group.
Amino Acid Sequence↗
Phase I trial of temozolomide (CCRG 81045: M&B 39831: NSC 362856).
Temozolomide (CCRG 81045: M&B 39831: NSC 362856) is an analogue of mitozolomide displaying similar broad spectrum activity in mouse tumours, but showing considerably less myelosuppression in the toxicology screen. Temozolomide was initially studied intravenously at doses between 50-200 mg m-2 and subsequently was given orally up to 1,200 mg m-2. A total of 51 patients were entered on the single dose schedule. Temozolomide exhibits linear pharmacokinetics with increasing dose. Myelotoxicity was dose limiting. Experimentally, temozolomide activity was schedule dependent and therefore oral administration was studied as a daily x 5 schedule between total doses of 750 and 1,200 mg m-2 in 42 patients. Myelosuppression was again dose limiting. The recommended dose for Phase II trials is 150 mg m-2 po for 5 days (total dose 750 mg m-2) for the first course, and if no major myelosuppression is detected on day 22 of the 4 week cycle, the subsequent courses can be given at 200 mg m-2 for 5 days (total dose 1 g m-2) on a 4 week cycle. Mild to moderate nausea and vomiting was dose related but readily controlled with antiemetics. Clinical activity was detected using the 5 day schedule in four (2CR, 2PR; 17%) out of 23 patients with melanoma and in one patient with mycosis fungoides (CR lasting 7 months). Two patients with recurrent high grade gliomas have also had partial responses. Temozolomide is easy to use clinically and generally well tolerated. In the extended Phase I trial temozolomide only occasionally exhibited the unpredictable myelosuppression seen with mitozolomide.
Adult↗
Single agent activity of carboplatin in patients with previously untreated non-seminomatous germ cell tumours.
The response to a single course of carboplatin has been investigated in 12 patients with previously untreated non-seminomatous testicular germ cell tumours. Patients received one course of carboplatin at a dose calculated to achieve a target area under the free carboplatin plasma concentration versus time curve (AUC) of 7 mg/ml x mins using the formula: dose (mgs) = target AUC x (GFR + 25). Response to carboplatin was assessed after a single course and treatment was then continued on the POMB/ACE schedule. Ten of 12 patients had either a greater than 50% decrease in serum HCG and/or AFP levels or a greater than 50% decrease in tumour volume after a single course of carboplatin. No patient had evidence of disease progression after carboplatin. This study demonstrates that single agent carboplatin is highly active in patients with non-seminomatous testicular germ cell tumours and thus provides evidence to justify its inclusion in chemotherapy combinations.
Carboplatin↗
The future of research at the Department of Veterans Affairs.
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Research↗
Experimental tests of the cortical imaging technique--applications to the response to median nerve stimulation and the localization of epileptiform discharges.
In a previous paper a method for simulating the electric potentials on the surface of the brain was introduced. This method consisted of the construction of a layer of radially oriented current dipoles in a conducting sphere that simulated the head so that the voltages generated by the layer would take the values measured on the surface of the medium (the scalp). The harmonic potential function for this layer was then evaluated in the interior of the medium in an attempt to approximate the potentials that would be generated by the actual neural sources but which could not be observed without recourse to invasive recording techniques. This method, the cortical imaging technique (CIT), has been previously tested by applying it to artificially generated data where the "cortical surface" potentials were known and could be compared with CIT-generated potentials. In this paper the method is tested by applying it to the scalp-recorded potentials evoked by right median nerve stimulation, where direct cortical recordings are available for comparison, and to the scalp-recorded epileptiform discharges from two patients where the spike foci were well defined. The effects of varying the "noise ratio," an input parameter in CIT which allows one to account for noise in scalp-recorded data, is discussed.
Cerebral Cortex↗
Activation of simian virus 40 transcription in vitro by T antigen.
Simian virus 40 is repressed when the viral early gene product large tumor antigen (TAg) binds to specific sites within the viral origin and DNA replication ensues. Late transcription is activated by TAg, even in the absence of viral DNA replication. We show here that TAg produced in human 293 cells can selectively activate Simian virus 40 transcription in a cell-free system. In the absence of DNA binding by TAg, early and late transcription are both activated, as they are in vivo, suggesting that the effect might be mediated by a cellular component(s) utilized by both the early and late promoters. When TAg binds to the viral origin of replication, early transcription is repressed but the late promoter activation is unaffected. Various preparations of TAg differed in their activities, with some able both to bind DNA and to activate transcription and others able to do only one or the other. Since these variations might be explained by variable amounts of associated factors that copurified with TAg, we asked whether a bacterially derived protein could regulate transcription. An NH2-terminal 272-amino-acid fragment of TAg, produced in Escherichia coli as a glutathione S-transferase fusion protein, retains the ability to activate transcription in vitro, similar to that of the full-length protein. Structural features of this region that might be important are discussed.
Amino Acid Sequence↗
The racial integration of medical and nursing associations in the United States.
Nursing associations and hospital nursing staffs integrated well before most racial integration took place in American society. In contrast, hospital medical staff integration lagged behind, and separate medical associations representing the distinctive concerns of two groups of practitioners have continued to exist. This article describes the divergent histories of these two fields and explores some reasons for these differences from a population ecology perspective. Nursing associations, unlike their medical counterparts, faced environmental constraints that made them ineffective as advocates for the economic interests of nurses. Yet, the American Nurses' Association served a more constructive role in the efforts to achieve racial integration than did the American Medical Association. More recent increases in market competition are now moving the more broadly based hospital and medical associations into a niche similar to the American Nurses' Association and giving rise to new organizations that are addressing more narrowly defined interests.
Black or African American↗
The effects of treatment for cancer on male fertility and sexuality.
The sequelae of some treatments for cancer, by virtue of their systemic action, adversely affect three aspects of male sexuality: desire, physical function, and cytokinetic gonadal processes. Other more localized therapies, such as surgery and radiation therapy, may affect only one aspect. Frequently, the effects of cancer therapy are interrelated, thus making it difficult to identify any single problem. This article discusses the impact of medical therapy, including chemotherapy, surgery, radiation therapy, and hormonal manipulation, as they relate to male sexuality. Interventions to promote sexual rehabilitation, either by intensive therapy or nursing actions, are discussed.
Antineoplastic Agents↗
Pneumocystis carinii pneumonia and high-dose dexamethasone to prevent emesis of chemotherapy.
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Adult↗