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Biomedical subjects

J Bell

Publications and source records attributed to J Bell.

At least 19 recordsLinked to original sources
PubMed1992

Lung cancer following Hodgkin's disease: a case-control study.

It is recognized that survivors of Hodgkin's disease are at a substantially increased risk of lung cancer. A collaborative group of population-based cancer registries and major treatment centers carried out a case-control study, in which 98 cases of lung cancer were identified in patients who had survived at least 1 year following a diagnosis of Hodgkin's disease. A total of 259 matched controls were selected from patients with Hodgkin's disease who did not develop subsequent lung cancer, and for both cases and controls detailed information was abstracted from medical records concerning stage and treatment of Hodgkin's disease. Patients treated with chemotherapy alone had about twice the risk of developing lung cancer than those treated by radiotherapy alone or both modalities. There was no increase in risk with cumulative number of cycles of chemotherapy. Among patients treated with radiotherapy alone, there was an increase in risk related to estimated radiation dose to the lung. There was also a strong association between cigarette smoking and the risk of lung cancer. The finding of a higher risk following chemotherapy than following radiotherapy was unexpected, but could not be explained by any identified methodological flaws. A plausible inference from the study is that all forms of Hodgkin's disease therapy are carcinogenic to the lung and that, in particular, chemotherapy is associated with an increase in risk which is at least comparable to and perhaps higher than the risk produced by radiotherapy.

Antineoplastic Agents↗
PubMed1992

CD24, a signal-transducing molecule expressed on human B cells, is a major surface antigen on small cell lung carcinomas.

Cell lines derived from human small cell carcinoma of the lung express high levels of a surface polypeptide termed the cluster-w4 antigen, which was previously identified as a potential target for toxin-based immunotherapy of lung cancer. We have cloned a complementary DNA encoding the cluster-w4 antigen from COS-1 fibroblasts transfected with a SW2 small cell carcinoma library, by panning with a mixture of the cluster-w4-specific monoclonal antibodies SWA11, SWA21, and SWA22. The sequence of the cluster-w4 complementary DNA encodes an unusually short (80-amino acid) protein identical to that recently reported for the leukocyte activation molecule CD24 except for a single valine-alanine substitution due to a single-base polymorphism within the region of the gene coding for the extracellular domain. Biochemical analyses of the cloned cluster-w4 antigen confirmed both the presence of the phosphatidylinositol tail and the extensive glycosylation reported for the CD24 molecule. Furthermore, the cloned cluster-w4 antigen expressed on COS cells was shown to react with a comprehensive panel of CD24-specific monoclonal antibodies, as assessed by indirect immunofluorescence staining. Northern blot hybridization indicated the presence of several transcript sizes for the cluster-w4 antigen that were greatly overexpressed in small cell carcinoma cell lines, compared with normal hemopoietic cells and CD24-positive cell lines. Southern blot hybridization of restriction digests of genomic DNA identified a complex pattern of bands consistent with either a complex gene structure containing many exons or the presence of a family of closely related genes.

Alanine↗
PubMed1992

5-HT3 receptor-active drugs alter development of spinal serotonergic innervation: lack of effect of other serotonergic agents.

Our work has focused on identifying the type of serotonin receptor through which serotonin acts as a developmental signal in the central nervous system. Previously, we have found that the regulation of development of ascending serotonergic neurons is through the balance of two serotonin receptors. One, the 5-HT1a receptor, releases a growth factor from astroglial cells. The other receptor is related to a release-regulating autoreceptor and can be stimulated indirectly by serotonin releasers such as fenfluramine. In the present study, we examined the receptors which regulate development of the descending neurons by treating pregnant rats with selective serotonergic drugs, from gestation day 12 until birth. Pups were subsequently tested for alterations in development by nociceptive testing (tail-flick latency) and by determining the binding of 3H-paroxetine, an indicator of serotonin terminal density, in spinal cord. Our results show that agents stimulating the 5-HT1a receptor (8-OH-DPAT) or the 5-HT1b receptor (TFMPP) or substances which release serotonin (fenfluramine) had no effect on the development of spinal serotonergic pathways. However, agents acting on the 5-HT3 receptor did--the agonist phenylbiguanide (PG) increased latency on tail-flick testing (postnatal days 10 and 30), while the antagonist, MDL 72222, decreased latency (postnatal days 10 and 18). Interestingly, both the agonist and the antagonist significantly increased 3H-paroxetine binding on postnatal day 18. Our results are discussed in terms of a possible mechanism by which 5-HT3 receptors may influence development.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Tumour oestrogen receptor content allows selection of elderly patients with breast cancer for conservative tamoxifen treatment.

Immunocytochemical analysis was used to determine tumour oestrogen receptor (ER) content in elderly patients with primary operable breast cancer. Only those ER positive were selected for conservative treatment with tamoxifen alone. Initial response was compared with that of historical controls not selected according to ER status. Early progressive disease was markedly reduced at 6 months, from 30 per cent in the unselected control group to 2 per cent in the study group (P < 0.001). Immunocytochemical analysis is useful for the initial selection of elderly patients with breast cancer who may be treated with tamoxifen alone.

Aged↗
PubMed1992

Intravascular balloon dilatation therapy for intracranial arterial vasospasm: patient selection, technique, and clinical results.

Patients presenting with symptomatic intracranial arterial vasospasm are now being treated by interventional neurovascular techniques in selected cases. From a percutaneous transfemoral approach, a custom-designed silicone microballoon can be guided through the intracranial vessels, and inflated to dilate the spastic vessel(s). This technique has been useful for both focal and diffuse areas of spasm. In clinical trials, 28 patients, ranging in age from 15-73 years have been treated. A total of 99 vascular territories have been successfully dilated in both the anterior and posterior circulations. Clinical improvement following treatment was observed in 17 cases (60.7%). Technical complications directly related to therapy included 2 cases (7.1%) of vessel rupture. In long term clinical follow-up 17 patients (60.7%) had good to excellent outcome, 2 patients (7.1%) remained in poor condition, and 9 patients (32.1%) died despite therapy. In patients presenting with symptomatic intracranial arterial vasospasm who are unresponsive to medical therapy, treatment by balloon angioplasty techniques may help to improve cerebral perfusion and clinical outcome of the patient.

Adolescent↗
PubMed1992

Cellular effects of tamoxifen in primary breast cancer.

We have investigated the effect of tamoxifen on the biological characteristics of the primary tumour in 33 patients with breast cancer. All patients had pre-treatment biopsy of the primary breast cancer and subsequent trucut biopsy of the primary tumour after 1-4 months on tamoxifen therapy. The staining patterns in the primary tumour of each of the tumour antigens 115D8, DF3, NCRC-11, and carcinoembryonic antigen (CEA) were unaffected by tamoxifen therapy: there was 16%-31% change before vs. during tamoxifen therapy, but this did not reach significance for any of the four antigens. Comparison of the pattern of staining between the four antigens showed 115D8, DF3, and NCRC-11 to be similar to each other both before and during tamoxifen therapy. All three antigens were significantly different from the staining pattern shown by CEA before and during therapy. Tumour antigen expression pre-treatment did not correlate with therapeutic response for any of the four antigens. However, NCRC-11 staining during tamoxifen therapy did correlate with response (p = 0.004). There was no significant difference in oestrogen receptor status before and during tamoxifen therapy, both of which correlated with response. DNA ploidy of the tumour before tamoxifen did not correlate with response to therapy, but there was a weak correlation between response and DNA ploidy measured during tamoxifen therapy. In only a minority of tumours (up to 30%) did tamoxifen exert an effect on the biological characteristics studied. Changes in these biological markers were mainly in tumours which responded to tamoxifen, and the changes seen were a tendency to greater expression of differentiation antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

An octamer element is required for the expression of the alpha H2B histone gene during the early development of the sea urchin.

Early (alpha) histone genes are one of several histone gene families in the sea urchin genome. They are expressed at high levels in blastula-stage embryos and are inactivated by the early gastrula stage. By microinjecting mutant early H2B genes into sea urchin zygotes and monitoring their transcriptional activity in blastula- and gastrula-stage embryos, we sought to identify the cis-regulatory elements responsible for this dramatic change in early H2B gene activity. We found that deletion of DNA 5' of -71 and 3' of +591 did not affect the timing or magnitude of early H2B gene expression. Neither was early H2B gene expression affected by the replacement of sequences downstream of -36 with the corresponding region of the L1 late H2B gene, expressed after the peak transcription of the early H2B gene. Further deletion of early H2B promoter sequences from -71 to -56, removing a conserved octamer element, resulted in near-complete inactivation of the early H2B gene in both blastula- and gastrula-stage embryos. Also inactivating early H2B gene expression were an internal deletion of the octamer element and a base substitution mutation that altered its sequence. This base substitution mutation also caused a parallel reduction in the ability of the octamer element to bind a factor present in nuclear extracts of sea urchin blastulae. These data strongly suggest that the proper expression of the early H2B gene in cleavage- and blastula-stage embryos depends on the octamer element and a factor with which it interacts.

Animals↗
PubMed1992

Model of the dynamics of receptor potential in a mechanoreceptor.

Mechanoreceptors are physiological units that convert mechanical stimuli to neural responses. An important one in the skin is the Pacinian corpuscle, which consists of a nerve ending surrounded by a capsule that is made up of alternating layers of fluid and elastic shells. In this paper a capsule model is coupled to a model for the dendrite via a variable representing the hoop strain imposed by the capsule on the receptor membrane of the dendrite. The transient behavior of the receptor potential due to step and periodic displacement-type stimuli imposed on the outer membrane of the capsule is investigated, and the results are compared to those of analogous experiments. The model is used to develop hypotheses concerning the role of the capsule as a filter for mechanical stimuli.

Animals↗
PubMed1992

Characteristics of patients with small-volume residual ovarian cancer unresponsive to cisplatin-based ip chemotherapy: lessons learned from a Gynecologic Oncology Group phase II trial of ip cisplatin and recombinant alpha-interferon.

The Gynecologic Oncology Group conducted a phase II trial of intraperitoneal (ip) cisplatin plus recombinant human alpha-interferon in patients with small-volume persistent/recurrent ovarian cancer. This study was based on the known single agent activity of the drugs administered by the ip route and experimental evidence of cytotoxic synergy between the agents. In 18 evaluable patients, only 1 partial response was observed (5.5% response rate). In an effort to explain these disappointing findings, patients were retrospectively divided into two groups; those with favorable disease (documented response to systemic platinum and absence of surgical findings of diffuse carcinomatosis at laparotomy prior to initiation of ip therapy) or unfavorable disease (no evidence of response to systemic platinum and/or laparotomy findings of diffuse carcinomatosis before ip treatment). The favorable patient population would be predicted to have a far greater chance of responding to local therapy, but only 3 of the evaluable patients fell into this category. In the 15 unfavorable patients, only 1 partial response was observed (7% response rate). We conclude that patients who have failed to demonstrate a response to systemic cisplatin or carboplatin or who have diffuse carcinomatosis at second-look laparotomy are poor candidates for second-line ip cisplatin-based therapy, even if they are considered to have small-volume residual disease (each individual tumor nodules less than 0.5-1 cm). Such patients should be considered for alternative therapeutic strategies.

Adult↗
PubMed1992

The effect of arginine vasopressin on the autologous mixed lymphocyte reaction.

Arginine vasopressin (AVP) is a nonapeptide that has been shown to be released from the supraoptic and paraventricular nuclei of the hypothalamus during stress. Although noted primarily for its hemodynamic as well as homeostatic properties, AVP also appears to have an effect on the immune system. It may modulate cellular immunity via its enhancement of the autologous mixed lymphocyte response (AMLR), an effect which we have demonstrated to occur over a wide dose range with a maximum at 10(-7) M. The increase in proliferation following a single addition of AVP in a 6-day culture appears to be augmented when the peptide is added daily throughout the same culture period. Enhanced proliferation appears to be a specific response that is influenced by arginine residues in position 8 of this nonapeptide. Having provided evidence for the existence of receptors with moderate affinity for AVP, we suggest a potential modulatory role for AVP in support of the concept of a communication between the neuroendocrine and immune systems. Since various autoimmune conditions may be aggravated by stress, stress-induced release of neuropeptides such as AVP may play an important role in modulating immune regulation of these disease states.

Amino Acid Sequence↗
PubMed1992

Groin dissection versus groin radiation in carcinoma of the vulva: a Gynecologic Oncology Group study.

PURPOSE: The objective of this study was to determine if groin radiation was superior to and less morbid than groin dissection. METHODS AND MATERIALS: Members of the Gynecologic Oncology Group randomized 58 patients with squamous carcinoma of the vulva and nonsuspicious (N0-1) inguinal nodes to receive either groin dissection or groin radiation, each in conjunction with radical vulvectomy. Radiation therapy consisted of a dose of 50 Gray given in daily 200 centiGray fractions to a depth of 3 cm below the anterior skin surface. RESULTS: The study was closed prematurely when interim monitoring revealed an excessive number of groin relapses on the groin radiation regimen. Metastatic involvement of the groin nodes was projected to occur in 24% of patients based on this Group's previous experience. On the groin dissection regimen, there were 5/25 (20.0%) patients with positive groin nodes. These patients received post-operative radiation. There were five groin relapses among the 27 (18.5%) patients on the groin radiation regimen and none on the groin dissection regimen. The groin dissection regimen had significantly better progression-free interval (p = 0.03) and survival (p = 0.04). CONCLUSION: Radiation of the intact groins as given in this study is significantly inferior to groin dissection in patients with squamous carcinoma of the vulva and N0-1 nodes.

Adult↗
PubMed1992

Myocardial infarction associated with inappropriate use of topical cocaine as treatment for epistaxis.

A case of a 57-year-old man with hypertension and stable angina, on aspirin therapy, who was treated for epistaxis with intranasal cocaine, and who subsequently suffered a non-Q wave myocardial infarction is reported. Of note, the cocaine was administered in a manner which differs from that advocated in standard references. Specifically, intranasal packing soaked with 4% cocaine was left in place with continuous nasal mucous membrane contact over 5 to 6 hours. The authors speculate that myocardial infarction occurred on the basis of coronary artery spasm. This case should alert practitioners to myocardial ischemia occurring as a complication of the therapeutic use of intranasal cocaine for the treatment of epistaxis.

Administration, Intranasal↗
PubMed1992

Identification of a CA repeat at the TCRA locus using yeast artificial chromosomes: a general method for generating highly polymorphic markers at chosen loci.

The creation of a comprehensive genetic map in human has been limited by the lack of highly polymorphic markers spaced evenly throughout the human genome. We have utilized yeast artificial chromosomes (YAC) containing large human DNA inserts to help identify highly polymorphic (CA)n repeats at a chosen locus. The DNA of a YAC containing the locus was subcloned in M13 vectors, and the recombinants were screened at high stringency to detect preferentially long (CA)n repeats (n greater than 20). These repeats, which are the most likely to be highly polymorphic, were then studied to confirm both the level of polymorphism and their precise genetic location. This strategy has permitted the identification of a new, highly polymorphic CA repeat (77% heterozygosity) at the T cell receptor alpha chain (TCRA) locus on chromosome 14q. It provides a powerful marker for assessing the role of this locus in the susceptibility to autoimmune and infectious diseases. This approach should permit the development of highly polymorphic markers at any targeted locus and rapidly improve the current human genetic map.

Base Sequence↗
PubMed1992

P-glycoprotein expression in locally advanced breast cancer treated by neoadjuvant chemotherapy.

Using immunohistochemistry and the monoclonal antibody C219 we have investigated P-glycoprotein expression in 26 locally advanced breast cancers. Twenty four patients had received four cycles of chemotherapy (mitozantrone, mitomycin-C and methotrexate) prior to mastectomy; two received tamoxifen. Twelve tumours exhibited an objective response to the chemotherapy. A background pattern of isolated weakly positive (1+) stromal staining (myofibroblast) was observed in seven tumours, two of which had been treated by tamoxifen alone. Two of the tumours treated by induction chemotherapy showed positive staining (1+) within a very small number of isolated tumour cells (maximum of three) and macrophages. The significance of this staining is not clear although C219 may simply be cross reacting with myosin. We have failed to demonstrate a clear clinical utility for C219 in breast cancer, particularly regarding the identification of patients in whom MDR chemotherapy be avoided once metastases develop.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

In search of a discourse on aging: the elderly on television.

This article analyzes the images of aging presented in five of the prime-time television programs of 1989 most watched by the elderly: Murder, She Wrote, The Golden Girls, Matlock, Jake and the Fatman, and In the Heat of the Night, all of which have central elderly characters. An examination of the title sequences reveals that earlier television stereotypes of the elderly "as more comical, stubborn, eccentric, and foolish than other characters" have been replaced by more positive stereotypes of them as powerful, affluent, healthy, active, admired, and sexy.

Aged↗
PubMed1992

T-cell receptors and rheumatic disease: approaches to repertoire analysis.

T-lymphocytes are thought to play a major role in the pathogenesis of a number of autoimmune rheumatic diseases. Techniques have recently been developed to study the T-cell receptor (TCR) usage of individual T-cells, and are likely to give major insight into the pathogenesis of rheumatic diseases. We describe the development of the TCR repertoire and the techniques available to study it. There is evidence that germline TCR complex polymorphisms may contribute to genetic susceptibility to rheumatoid arthritis. A number of studies have looked at rheumatoid synovial T-lymphocytes, some of which have found restricted TCR usage.

Animals↗
PubMed1992

Routine diagnosis of mammary Paget's disease. A modern approach.

This study compares the diagnostic reliability of conventional mucin histochemistry and immunocytochemical techniques in distinguishing mammary Paget's disease from superficial spreading malignant melanoma and primary intraepidermal carcinoma. Formalin-fixed, paraffin-embedded archival tissue was used and comprised 13 cases of mammary Paget's disease, five cases of superficial spreading melanoma, and six cases of intraepidermal carcinoma. Sections from each case were stained for the presence of mucin using diastase periodic-acid-Schiff (d-PAS) with and without an alcian blue counterstain as well as immunocytochemistry for cytokeratin (CAM 5.2), epithelial membrane antigen (NCRC-11) and c-erb B-2 (21N). Mucin staining in intraepidermal carcinoma and malignant melanoma was consistently negative. Diastase-resistant PAS positivity was seen in six of 13 cases of mammary Paget's disease and eight of 13 cases using an alcian blue counterstain. NCRC-11 showed positive immunoreactivity in four of six cases of intraepidermal carcinoma, one in five cases of melanoma, and five of 13 cases of mammary Paget's disease. Positive immunoreactivity using CAM 5.2 and 21N was seen in all cases of mammary Paget's disease, with consistent negative immunoreactivity in the other tumor types. We conclude that CAM 5.2 and 21N should be used in the investigation of mammary Paget's disease in preference to conventional mucin stains.

Antibodies, Monoclonal↗