Biomedical subjects
J Walker
Publications and source records attributed to J Walker.
Adenocarcinoma of the cervix associated with human papillomavirus.
Eleven pure adenocarcinomas of the cervix were analyzed for human papillomavirus (HPV) types 6, 11, 16, 18 and 31 by Southern blot hybridizations. Seven tumors were positive for papillomavirus DNA. Five hybridized to the HPV 18 specific probe and two tumors hybridized to HPV 16. All tumors were negative for HPV 6/11 and 31, and no additional tumors became positive with hybridizations under nonstringent conditions to a mixture of HPV probes. No papillomavirus DNA was detected in 11 noncervical malignancies or in six hysterectomy specimens in which cancer was not present. The histopathologic and clinical features of the patients were correlated with the presence of HPV. The women with papillomavirus DNA in their adenocarcinomas tended to be younger (mean age, 37.3) than those that were negative for HPV (mean age, 49.0). The findings suggest that papillomaviruses may be an etiologic factor in the development of some adenocarcinomas of the cervix.
Photodynamic therapy of endobronchial malignancies.
Forty-nine tumor sites in 31 consecutive patients with tracheobronchial malignant neoplasms were treated with photodynamic therapy (PDT). After sensitization with the intravenous hematoporphyrin derivative (HpD) or its more purified form of dihematoporphyrin ether (DHE), 630 nm of light from a tunable sensitizer argon light system was delivered to the tumor site through the biopsy channel of a flexible bronchoscope. All patients had received, refused, or were ineligible for conventional surgery, ionizing radiation therapy, or chemotherapy. Before or at 1 month after each treatment, tumor response was evaluated according to the following categories: (1) complete response (CR) (no visible abnormality, and negative biopsy specimen and cytology); (2) partial response (PR) (degree of obstruction or size of tumor reduced more than 50%); (3) some response (SR) (degree of obstruction or size of tumor reduced 20% to 50%); and (4) progression (PROG) (degree of obstruction or size of tumor reduced by less than 20%). Results were as follows: (1) 37% of the tumors treated achieved CR; (2) 55% achieved PR; (3) 4% achieved SR; and (4) 4% were categorized as PROG. Complete follow-up was achieved in all patients. Clinical effect was evaluated 1 month after treatment by comparing the Karnofsky performance status (KPS), dyspnea level, oxygen requirement, and presence of symptoms. Sixty-eight percent had clinical improvement in at least one variable and 48% in two or more variables. The results of this study suggest that PDT can play a useful role in the treatment of endobronchial malignancies.
Daytime urinary frequency in children.
Explore the source record for details and available documents.
Effect of lumbar epidural anaesthesia on plasma cortisol levels in children.
The cortisol response to surgery was studied in two groups of children one to eight years old during the first 24 hours after lower abdominal or peripheral surgery. The children were randomly allocated to a control (C) group (n = 6) or an epidural (E) group (n = 7). In Group C, surgery was performed under general anaesthesia and postoperative pain relief was achieved by using non-narcotic analgesics only. In Group E, lumbar epidural anaesthesia was combined with light general anaesthesia and postoperative pain relief was achieved by intermittent doses of bupivacaine administered through an epidural catheter. Cortisol levels were assessed before surgery (C), at the end of surgery (H0), at the 3rd, 6th, 12th and 24th postoperative hours (H3, H6, H12, H24). In Group C, cortisol levels increased significantly at H0, H3 and H6, whereas in Group E, a significant decrease was observed at H0 and a significant increase at H12. Mean cortisol values at H0 and H24 were significantly lower in Group E, when compared with those measured in Group C. In Group E, all postoperative cortisol values remained within the normal range, despite the low level of sensory blockade achieved. This suggests that minimal doses of epidural bupivacaine are effective in decreasing the endocrine stress response to surgery in children. This could be of clinical relevance in high-risk children with poor nutritional status. In Group C, the cortisol response remained altered for a longer period of time.
A comparison of psychologically-induced cardiovascular reactivity in laboratory and natural environments.
This study focused on the possible role of heart rate reactivity in the development of essential hypertension in female subjects. Baseline heart rate, systolic and diastolic blood pressures, taken over a 6 week period, were used for comparison with the same measures taken during a laboratory session involving relaxation, cold pressor, mental arithmetic and exercise, and before and after an academic examination. Information about personality and lifestyle was included in subsequent univariate and multivariate analyses. Significant increases were produced in heart rate by the mental arithmetic task (p less than 0.00005), in systolic pressure by the exercise task (p less than 0.00005) and in systolic pressure prior to the examination (p less than 0.001). No significant diastolic effects were found. When subjects were divided into high and low reactors, on the basis of their heart rate reactivity to mental arithmetic, there was little difference in cardiovascular activity between the groups in any other condition. Significant effects on reactivity were found for diet, regular daily exercise and type A personality. The results are discussed in terms of Obrist's theory of the genesis of essential hypertension.
Identification of HPV 16 early genes retained in cervical carcinomas.
Fourteen cervical carcinomas containing HPV 16 DNA were analyzed by Southern blot hybridization with probes for HPV 16 E1, E2, E6, and E7 genes. All tumors hybridized with the E7 gene-specific probe while 2 tumors appear to be deleted in the E6 region. In 11 of the 14 tumors, deletions and/or rearrangements were detected in the E1 and E2 regions. Only one of the 14 tumors had a prototype HPV 16 restriction. Our findings that the E7 gene is the most conserved region of HPV 16 in cervical carcinomas suggest it may play a role in the maintenance of the malignant state.
Evaluation of memory and language function pre- and postthalamotomy with an attempt to define those patients at risk for postoperative dysfunction.
Memory and language dysfunction has been sporadically reported following stereotaxic thalamotomies. In order to determine which patients are at greatest risk and to better define the nature of this dysfunction, we have prospectively evaluated 18 patients undergoing stereotaxic thalamotomies for movement disorders (MDs). Patients were evaluated clinically, with computed tomography (CT) and with memory and language protocols (MLPs) pre- and postoperatively. Patients exhibiting postoperative deficits were again evaluated with the MLP on follow-up visits to the clinic. Significant changes in memory and language function occurred in 7 out of 18 patients. These 7 patients had diverse etiologies for their MDs. Five of the 18 patients had undergone previous thalamotomies on the contralateral side. Three of these 5 patients with bilateral thalamotomies experienced postoperative functional impairments in memory and language while only 4 of 13 patients with a unilateral thalamotomy experienced these problems. The postoperative functional impairments noted were primarily those requiring orientation and speech. All patients with postoperative memory and language impairments were again evaluated with MLPs months after the operation. In 3 of 7 patients, no improvement was noted, while the remaining 4 did recover to baseline. More severe deficits tended to occur in those patients with ventriculomegaly or evidence of other major cerebral tissue loss by preoperative CT scan and in those patients with lower MLP scores preoperatively. Postoperative memory and language dysfunction was not correlated with the number or size of the lesions made, the postoperative general neurologic examination or CT scans, or the clinical response of the MDs. From our data, it appears that patients with more profound neurologic compromise and/or bilateral involvement as evidenced by poor performance on the MLP, tissue loss on CT scanning, or previous thalamic lesion, are most at risk for memory and language dysfunction postoperatively. However, this dysfunction is not necessarily permanent. Preoperative evaluation with MLPs and CT scanning appear to be of value in predicting those patients at greatest risk for postoperative and language dysfunction.
Continuing professional education, continued learning or refreshment?
Explore the source record for details and available documents.
Human papillomaviruses and cervical cancer: analysis of histopathologic features associated with different viral types.
The histopathologic features of 41 cervical carcinomas were correlated with the presence of human papillomavirus (HPV). Southern blots of DNA extracted from the tumors were hybridized with 32P-labeled type specific probes for HPV 6, 11, 16, 18, and 31. HPV was found in 26/41 (63%) of the tumors. The HPV types were: HPV 16 in 17 tumors (41%), HPV 18 in six tumors (15%) and HPV 31 in two tumors (5%). No tumor hybridized to either HPV 6 or HPV 11. HPV was identified in all histologic subtypes of cervical carcinoma; however, different HPV types were associated with specific histologic features. HPV 18 was identified in four of eight adenocarcinomas, while HPV 16 was found in only one. HPV 16 was most strongly associated with the keratinizing tumors. It was found in 10/13 (77%) of the large cell keratinizing (LCK) and in only 4/16 (25%) of the large cell nonkeratinizing cervical carcinomas (LCNK). A mucoepidermoid with extensive keratinization and pearl formation also contained HPV 16. One of three additional adenosquamous carcinomas had HPV 31, as did one LCNK tumor. In one LCK tumor, a HPV was identified that hybridized to both HPV 16 and 18. The LCNK group contained the highest percentage of tumors in which no papillomavirus DNA was identified (9/16 lacked HPV DNA). No papillomavirus was detected in six tumors from other sites or in five cervical specimens with no histologic evidence of HPV infection. These data indicate that HPV is involved in all major histologic types of cervical carcinoma, and suggest that the different HPV types transform slightly different cell populations, or that transformation by HPV 18 tends to induce adeno-differentiation while HPV 16 leads to squamous maturation.
Fetal heart rate monitoring by telephone. II. Clinical experience in four centres with a commercially produced system.
A commercially produced domiciliary fetal monitoring (DFM) system was assessed in four centres in the UK (Bristol, Glasgow, London and Nottingham) chosen to allow for comprehensive assessment in various settings in many different women. Overall, 825 recordings were made from 368 women (2.24 per woman). There were 56 unsuccessful attempts at transmission (6.8%), most were due to problems with telephone equipment. The system worked most efficiently when a dedicated direct line was used. The data transmission time varied between 40 and 60 s. The median telephone time (including data transmission and conversation) with a dedicated direct line was 7 min. Mean acceptance times from the four centres were between 70 and 80%. All recordings with acceptance times of 40% or more were interpretable. Ten recordings were abnormal. The women and mid-wives were equally proficient at using the DFM system. The DFM system represents an important addition to current methods of fetal assessment. Specific guidelines are outlined.
Water-soluble contrast medium for intraoperative evaluation of anterior cervical discectomy. Technical note.
When anterior cervical discectomy is performed for either "hard" or "soft" cervical disc herniation using either the Cloward approach or simple discectomy, it is often difficult to confirm intraoperatively the adequacy of the lateral, superior, and inferior margins of the dissection. Placement of a nonionic contrast material, iohexol, into the disc space before obtaining anteroposterior and lateral x-ray spine films can indicate the adequacy of the margins of dissection of the soft disc or bone ridge to prevent a poor operative result.
Role of a SER immune suppressor in immune surveillance.
A potent immunosuppressor factor, known as SER (suppressive E-receptor factor) has been identified in the body fluids of cancer patients. SER has been proven to be immunochemically analogous to the fetal form of haptoglobin. In this paper, we examine the role of SER immune suppressor in the immune surveillance mechanism of the host, using an affinity-purified SER. As shown in this study, SER, at microgram/ml concentrations, inhibits the T-cell proliferation induced with either monoclonal or polyclonal T-cell activators in vitro in human, and also inhibits the primary antibody response to T-dependent antigens in vivo in mice. Likewise, SER also inhibits the immunoglobulin synthesis of human B lymphocytes induced by a B-cell mitogen, pokeweed mitogen, in the presence of a tumour promoter, phorbol myristate acetate (PMA). In contrast to the T-dependent antibody response in vivo in mice or T-dependent mitogen response in vitro in human, SER does not interfere with the T-independent antibody responses to DNP-Ficoll or TNP-LPS in mice. SER also interferes with the natural killer cell function of human peripheral blood mononuclear cells. Although SER inhibits the phagocytic functions of human peripheral neutrophils, it requires at least 10-20 times the concentration of SER present in normal human plasma. Since this concentration of SER is attainable in the sera of solid tumour-bearing patients, highly elevated levels of SER could predispose the patients to microbial infections as well. This study demonstrates that purified SER manifests multi-faceted down-regulatory effects on the defence mechanism of hosts, thereby it could compromise the patients' cell-mediated immunity in vivo.
Sodium-independent phosphate transport in brush-border membrane vesicles prepared from the outer medulla of pig kidneys.
Explore the source record for details and available documents.
Photoexcited coherent tunneling in a double-barrier superlattice.
Explore the source record for details and available documents.
An analogy between fetal haptoglobin and a potent immunosuppressant in cancer.
In spite of the numerous reports indicating the presence of humoral immunosuppressive factors in cancer patients, only a few of these factors have been biochemically identified. Furthermore, their role as effective immunosuppressors in vivo remains to be established. Our laboratory has attempted to isolate and identify the major immunosuppressive factor in the malignant effusions derived from ovarian and lung cancer patients. We have previously demonstrated that the Mr 52,000 immunosuppressive factor isolated from the ascites fluid of an ovarian cancer patient inhibited T-dependent immune responses in vivo and in vitro including the inhibition of E-rosetting. Thus, this immunosuppressive factor was named "suppressive E-receptor" (SER). Our current study demonstrates that this SER factor purified from malignant effusions derived from ovarian, lung, or head and neck cancer patients had a common component which dissociated equally into Mr 38,000-42,000 and 17,000-19,000 moieties on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under vigorous reducing conditions. Electroelution of these two components followed by a limited amino acid sequence determination revealed these two components to have N-terminal amino acid sequences identical to the beta and alpha 2 subunits of normal adult haptoglobin. Immunoelectrophoresis of SER using a polyclonal antiserum to neonatal cord blood demonstrated that SER, unlike normal haptoglobin, has slower electrophoretic mobility than the normal adult haptoglobin. Western blotting analysis of SER separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis under denaturing conditions failed to recognize a monoclonal antibody directed specifically to SER. However, this monoclonal antibody exclusively reacted with the SER separated by an analytical polyacrylamide gel electrophoresis gel under nondenaturing conditions while normal adult haptoglobins or purified but denatured haptoglobin obtained from the same malignant fluid as SER all failed to react with this antibody. Thus, SER appears to bear an additional epitope(s) that is absent in normal adult haptoglobin. Since the SER as well as the neonatal haptoglobin have at least 100 to 1000-fold more potent immunosuppressive activity than the normal adult haptoglobin, this additional epitope(s) present in SER may be responsible for the potent immunosuppressive property of SER.
Genetically obese (ob/ob) mice are hypersensitive to glucocorticoid stimulation of feeding but dramatically resist glucocorticoid-induced weight loss.
The genetically obese (ob/ob) mouse is hyperphagic and hypercorticosteronemic; both hyperphagia and excessive weight gain are ameliorated by adrenalectomy. We report here that corticosterone or dexamethasone stimulate feeding in obese mice at one-fifth the dose needed to increase feeding in lean littermates. Metabolic weight loss, a measure of carbon dioxide and water lost due to respiration, is stimulated by glucocorticoids. Yet we find that obese mice are only one-seventh as sensitive as lean mice to the enhancement of metabolic weight loss following corticosterone. Therefore, hypersensitivity to glucocorticoid-induced feeding and hyposensitivity to glucocorticoid-stimulated weight loss may act in tandem to produce the ob/ob's exaggerated weight gain.