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Biomedical subjects

D B Smith

Publications and source records attributed to D B Smith.

At least 19 recordsLinked to original sources

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

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

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 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

Myoclonus with electrocerebral silence in a patient receiving penicillin.

Multifocal myoclonus is a well-recognized complication of high doses of penicillin. In man, the site of origin of penicillin-induced myoclonus has not been clearly established, but there is evidence from animal studies that it may originate at a cortical, subcoritcal, or spinal level. We report a case of multifocal myoclonus occurring in a patient receiving large doses of penicillin. The myoclonus appeared when there was no clinical or EEG evidence of upper brain stem or cerebral function. The observations reported suggest that penicillin-induced myoclonus may occur in man and may originate at a caudal brain stem or spinal level.

Adult

EEG and autonomic responding to verbal, spatial and emotionally arousing tasks: differences among adults, adolescents and inhalant abusers.

The present study investigated the physiological responses of an adolescent inhalant abuse group, an adolescent non-abuse group, and an adult non-abuse group elicited by three types of tasks: verbal, spatial, and emotionally arousing. Each group consisted of 10 male Mexican-American subjects. Bilateral EEG and electrodermal activity, as well as heart rate, were monitored. While exploring for possible heart rate and hemispheric alpha wave differences in response to predominantly verbal and spatial tasks, an attempt was also made to discover if electrodermal responses could be bilaterally differentiated. Another purpose of the study was to explore possible psychophysiological differences between a younger and older group, and between an inhalant abusing group and a non-abuse group, in response to the three types of tasks. Results indicated that attempts to produce task-related EEG hemispheric asymmetry were largely nonsuccessful. Bilateral electrodermal responses were also not greatly differentiated. It was suggested that stronger task manipulations were needed. Significant group differences were found for initial physiological response levels (adults demonstrated higher levels than the two adolescent groups) and for heart rate response to the emotionally arousing task (non-abusing subjects demonstrated greater heart rate acceleration than inhalant abusing subjects). It was suggested that group differences in initial levels occurred due to the adult groups's greater involvement in the experimental situation. Heart rate differences to the emotionally arousing situation were discussed in terms of Zuckerman's sensation seeking hypothesis.

Adolescent

Stability of microtubule protein over the pH range: 6.9--9.5.

The pH stability range of a microtubule protein preparation has been investigated between 6.9 and 9.5. Microtubule protein was exposed to various pH values in this range and then returned to pH 6.9. The appearance of microtubules as verified by electron microscopy and sedimentation analysis under polymerizing conditions was taken as an indication of a conformationally stable protein. Between pH 6.9 and pH 8.0 the loss in the ability to form microtubules was found to be reversible, at pH 8.2 it was partially reversible, above pH 8.2 it was irreversible. Tubulin and the microtubule-associated protein fraction were separately exposed to high pH. It was observed that tubulin exposed to high pH can still form microtubules in the presence of untreated microtubule-associated protein. On the other hand, microtubule-associated protein exposed to high pH could not initiate microtubule assembly with untreated tubulin. It was concluded from these observations that the loss in the ability of a microtubule protein preparation to assemble at high pH is due to a change in the microtubule-associated protein fraction and that tubulin is conformationally stable even after exposure to pH 9.5.

Animals

Mouthwash and oral cancer: carcinogen or coincidence?

Among 200 patients with squamous cell cancer of the head and neck, 11 persons abstained from all alcoholic beverages and tobacco. All but one of these 11 patients had used mouthwash many times daily for more than 20 years. Most of them used a brand of mouthwash that contained 25% alcohol. This evidence, along with information from other patients, may be used to confirm or refute the theory that mouthwash may be carcinogenic for susceptible persons.

Aged

Evaluation and control of a respiratory exposure to 3-(dimethylamino) propylamine.

In 1974 a study was undertaken to assess the symptoms and pulmonary function of a group of 25 workers who were exposed to an epoxy resin system in the mold room of a ski manufacturing plant. The amine 3-dimethylamino propylamine (3-DMAPA) was the only volatilized substance. Assemblers, the sub-group with the highest breathing zone exposure to 3-DMAPA (0.9 ppm), had the highest prevalence of symptoms and a significant decrease in lung function over the workshift. Extensive improvements in local ventilation reduced the average breathing zone exposure to nearly one-seventh of the 1974 concentration. A 1977 cross-sectional study showed that at this level there was a marked reduction in symptoms and the expiratory function of assemblers no longer decreased over the workshift. Longitudianl comparison of the lung function of workers exposed more than two years showed evidence of a decrease from 1975 to 1977, but none from 1977 to 1978.

Cross-Sectional Studies