Extremely low frequency (ELF) electromagnetic fields and leukaemia in children.
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Biomedical subjects
Publications and source records attributed to J Bell.
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This study examined pharmacological factors contributing to persisting drug abuse by methadone maintenance clients. Three groups of clients, drawn from one treatment programme, were studied: persistent heroin users, persistent benzodiazepine users, and control subjects who were not using illicit drugs in addition to methadone. Persistent abusers mostly had high trough serum methadone levels, and their ongoing drug use appears to reflect a preference for a different drug effect rather than inadequate methadone dose. Several clients did have the expectation that methadone should prevent them from using other drugs; such expectations may diminish the effectiveness of treatment.
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In the sea urchin embryo, late histone genes are transcribed at low levels during cleavage and blastula formation and at substantially higher levels in later stages of embryogenesis. To investigate the molecular basis of the stage-specific expression of a late H2B histone gene, we injected mutant genes lacking portions of 5'- and 3'-flanking regions into Lytechinus pictus embryos and monitored their expression by RNase protection. A 200-bp region located 489 bp downstream of the mRNA 3' terminus was necessary for the increase in transcription of the late H2B gene at the mid-blastula stage of development. DNase I and methylation interference footprint analyses located only one factor-binding site in this region, and gel mobility shift experiments showed that the DNA-binding activity of this factor (designated H2B abp 1) paralleled the transcriptional activity of the L1 H2B gene. Additional mutagenesis and microinjection experiments located the activator element to a 32-bp DNA segment that includes the H2B abp 1-binding site. These experiments also showed that the 32-bp fragment functions independently of position and orientation and therefore has the hallmarks of an enhancer. That this fragment contains most or all of the L1 H2B gene transcription-stimulatory activity makes it unusual among enhancerlike elements, which generally consist of several clustered factor-binding sites that act additively or cooperatively to affect transcription. The nucleotide sequence of the L1 H2B enhancer element suggests that the trans-acting factor that interacts with it is a member of the antennapedia or engrailed class of homeodomain proteins.
The clinical, endoscopic, and radiological features of seven patients with an uncommon oesophageal injury characterised by long lacerations of the oesophageal mucosa with haematoma formation but without perforation are reported. The injuries were not related to forceful vomiting or any other definable cause but were similar to those previously described as intramural oesophageal rupture. Upper gastrointestinal endoscopy undertaken to identify the cause of haematemesis in six patients proved safe and useful. When dysphagia and odynophagia occurred early in the clinical course to alert the clinician to possible oesophageal injury, radiological contrast studies were used to exclude perforation. One patient in this study had oesophageal cavernocapillary haemangiomatosis which may have caused intramural oesophageal bleeding and submucosal dissection but in the remainder the aetiology of intramural oesophageal rupture remains uncertain. Conservative management was successful in all patients.
Our objective was to determine whether the fluorescence of skin collagen, which may reflect the accumulation of advanced glycosylation end products, is increased in young patients with type I (insulin-dependent) diabetes. Our study design was a cross-sectional case-control study in a referral-based diabetic clinic in an academic hospital. Study subjects comprised a convenience sample of 18 type I diabetic patients aged 17-30 yr and 8 age-matched healthy control subjects. The fluorescence of collagen was measured in skin biopsy material. Collagen-linked fluorescence (CLF) was increased in diabetic patients (mean 10.5 [range 5.8-15.8] U/mg) compared with control subjects (7.6 [5.6-10.1] U/mg, P less than 0.02). In diabetic patients, CLF was related to age (r = 0.581) and duration of diabetes (r = 0.697) but not concentration of glycosylated hemoglobin (r = 0.082). Partial correlation analysis demonstrated that duration of diabetes is the main factor determining the fluorescence of collagen in these patients. There was a relationship between CLF and presence of diabetic retinopathy after the data were adjusted for patient age and duration of diabetes (P = 0.023). Increased fluorescence of skin collagen can be detected in young type I diabetic patients and is primarily related to duration of diabetes.
Interventional neurovascular techniques for treating patients with intracranial aneurysms are now being performed in selected cases. In certain anatomical locations that are difficult to reach surgically, such as the cavernous portion of the internal carotid artery (ICA), this technique may be especially useful. The procedure is performed from a transfemoral approach, using local anesthesia, thus permitting continuous neurological monitoring. Between 1981 and 1989, 87 patients diagnosed as having an intracavernous aneurysm were treated with endovascular detachable balloon embolization techniques. The patients ranged in age from 11 to 84 years. The presenting symptom was mass effect in 69 cases (79.3%), rupture of a preexisting aneurysm resulting in a carotid-cavernous sinus fistula in eight cases (9.2%), trauma resulting in a cavernous pseudoaneurysm in seven cases (8.0%), and hemorrhage in three cases (3.4%). Therapeutic occlusion of the ICA across or just proximal to the aneurysm neck was performed in 68 patients (78.2%). Since 1984, with the development of a permanent solidifying agent (2-hydroxyethyl methacrylate) to fill the balloon, it is now feasible in some cases to guide the balloon directly into the aneurysm and preserve the parent artery; this was achieved in 19 cases (22%). Follow-up examination has demonstrated complete thrombosis with partial or total alleviation of symptoms in all patients with therapeutic occlusion of the parent vessel. Of the 19 patients with preservation of the parent artery, follow-up studies have demonstrated total exclusion in 12 cases (63%) and subtotal occlusion of greater than 85% in seven cases (37%), with clinical improvement in all cases. Complications from therapy included transient cerebral ischemia during or after therapy requiring volume expansion in seven cases, embolic symptoms requiring antiplatelet medication in two cases, and stroke in four cases; there were no deaths. Detachable balloon embolization therapy, particularly for large and giant symptomatic aneurysms of the cavernous ICA, can be an effective mode of treatment.
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To assess the value of radioimmunoguided surgery in the intraoperative detection of ovarian cancer, we used monoclonal antibody B72.3, radiolabeled with 125I, and a hand-held gamma-detecting probe in 13 women with ovarian cancer undergoing exploratory laparotomy. B72.3, which recognizes a tumor-associated glycoprotein, TAG 72, was injected 12-29 days preoperatively (intraperitoneally in four cases, intravenously in nine, and by both routes in one). Intraoperatively, the abdomen was surveyed with the probe and probe counts were correlated with biopsies and excised specimens studied by routine histologic stains. Probe counts were positive in four of seven evaluable patients with histologically confirmed disease. In three of these four patients, the probe detected cancer in specimens interpreted as normal on frozen histologic sections. The probe also identified microscopic cancer in the one patient who had no gross disease. The specificity of the probe was 70%. Preoperative computed tomography was normal in all patients, including those with tumors as large as 3 cm. This pilot study shows the ability of radioimmunoguided surgery to detect occult ovarian cancer.
The putative involvement of reactive oxygen species in the etiology of lung damage in infants receiving mechanical ventilation has been examined by comparing the levels of peroxidation and expression of the antioxidant enzymes, CuZn and Mn superoxide dismutase, in lungs from control and affected infants as well as from fetuses and infants who died postnatally after term delivery. Mean levels (+/- SD) of lung peroxidation, determined with a thiobarbituric acid method, were similar in affected and control premature neonates and in fetal subjects (1.87 +/- 1.26, 1.92 +/- 2.07, and 1.19 +/- 1.36 nmol/mg protein, respectively). Expression of CuZn and Mn superoxide dismutases was also similar in these subjects and in the patients who died postnatally. Thus activity measurements and immunoblotting studies showed continuous expression of these enzymes throughout development with no apparent change in protein levels or size. Immunohistochemical examination of lung tissue showed expression of CuZn and Mn superoxide dismutases in epithelial, smooth muscle, endothelial, and some mesenchyme components. In patients with bronchopulmonary dysplasia, alveolar walls were thickened by an excess of fibrous tissue and terminal air spaces were lined mainly by type II pneumatocytes. All structures, including abnormal fibrous components, were positive for both CuZn and Mn superoxide dismutase. Our data show that, unlike some experimental animals, expression of at least these antioxidant enzymes in human infants born prematurely is similar to that in adults, and indicate that such infants are better adapted for life in an oxygen-containing environment than previously suspected.(ABSTRACT TRUNCATED AT 250 WORDS)
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Lymphocytic infiltration of breast cancer is often associated with a favourable prognosis. Seventy-seven women with operable breast cancer were followed for a minimum of 3 years. Tumours were frozen and sectioned by cryostat before staining with monoclonal antibodies using an immunoperoxide technique for total lymphocytes, helper/inducer, suppressor/cytotoxic, natural killer and B subsets. Lymphocyte density was assessed by light microscopy at x400 and divided at the 50th percentile to less than 30 and greater than or equal to 30 cells per high power field to give scanty and dense lymphocytic infiltration. The helper/suppressor lymphocyte ratio was greater than 1 in 45 patients but without improvement in survival or cancer recurrence. Natural killer and B lymphocytes were rarely seen in tumour sections. Poorly differentiated tumours excited a more marked lymphocytic infiltration (P less than 0.01). Neither the density of lymphocyte infiltration nor the ratio of helper to suppressor lymphocytes correlated with improved short-term survival or recurrence. These data suggest that the immune defence is ineffective in preventing spread from the primary tumour in breast cancer patients.
The developmental expression of the alpha, mu and pi class glutathione S-transferases has been defined in human liver using radioimmunoassay and immunohistochemistry. Expression of alpha and mu class isoenzymes increased significantly at birth, while that of the pi isoenzyme declined during the first trimester. Mu-class isoenzymes (GST1 1, GST1 2, GST1 2-1) were expressed in hepatocytes but not in other liver cell types.
The amino acid sequence of rubber elongation factor, a recently discovered protein tightly bound to rubber particles isolated from the commercial rubber tree Hevea brasiliensis, is presented. The role of this protein in rubber elongation and its interaction with prenyltransferase and rubber particles have been discussed in the preceding paper in this series (Dennis, M. S., and Light, D. R. (1989) J. Biol. Chem. 264, 18608-18617). Trypsin, Staphylococcus protease, chymotrypsin, acetic acid, and hydroxylamine cleavage were used to generate peptide fragments that were isolated by reverse phase high pressure liquid chromatography and analyzed by amino acid composition and automated Edman degradation. Each digest contained one blocked peptide identified as the amino terminus. The blocked amino-terminal peptide from the tryptic digest was analyzed by amino acid composition, fast atom bombardment mass spectrometry (molecular ion 1659.9), subdigested with Staphylococcus protease for partial sequence analysis, and finally deblocked with bovine liver acyl-peptide hydrolase removing an acetylalanine to allow analysis by Edman degradation. Rubber elongation factor is 137 amino acids long, has a molecular mass of 14,600 daltons, and lacks four amino acids: cysteine, methionine, histidine, and tryptophan. The NH2 terminus is highly charged and contains only acidic residues (5 of the first 12 amino acids). The first four amino acids are highly represented in other known NH2-terminally acetylated proteins. Comparison of the sequence of rubber elongation factor with other known sequences does not reveal significant sequence similarities that would suggest an evolutionary relationship.
We studied the immunoreactivity by immunohistology of two carcinoembryonic antigens (CEA) with specific and two CEA antibodies with nonspecific cross-reacting antigen (NCA) cross reactivity (CEA/NCA) in 180 primary breast carcinomas. Positive tissue staining was found in more than 90% of the specimens with CEA/NCA antibodies, compared with less than 30% for both CEA-specific antibodies. There was no correlation between the positivity of CEA immunocytochemistry for any of the four antibodies and histologic grade, lymph node stage, locoregional recurrence, disease-free interval (DFI), or patient survival. This large study with a long follow-up period for patients has shown that CEA and CEA/NCA immunocytochemistry have no relation to prognosis in breast cancer. An extensive review of the literature that confirms these findings should end the controversy over the place of CEA and CEA/NCA immunocytochemistry in breast cancer.
Eukaryotic tRNA expression initiates with transcription by RNA polymerase III and requires two additional protein factors and two regions within the tRNA gene (the 5'-internal control region (ICR) or A-box and the 3'-ICR or B-box). Using a reconstituted Saccharomyces cerevisiae RNA polymerase III system, the transcription of various 5'-ICR, 3'-ICR, and double mutation alleles of the Schizosaccharomyces pombe sup3-e dimeric tRNA gene were studied. The sup3-e tRNA locus consists of an upstream serine tRNA gene and a downstream initiator methionine tRNA gene which are transcribed as a dimeric precursor and processed to give two tRNAs. Only the ICRs of the tRNA(Ser) gene are active in directing dimeric gene transcription. Mutations in the 3'-ICR of the tRNA(Ser) gene reduce transcription of the dimer more than those in the 5'-ICR. Mutations in the 5'-ICR were found which greatly increased or decreased transcription of the dimer, while base changes in the 3'-ICR were only found to decrease transcription. This suggests a modulatory role for the 5'-ICR in transcription regulation. Mutation of the methionine tRNA gene ICR has little effect on sup3-e transcription, and no detectable transcripts initiate from the methionine tRNA gene when the tRNA(Ser) gene promoter is inactivated by mutation. Comparison with transcription studies of other mutant tRNA genes suggests that nucleotides sites within the ICRs, such as nucleotides 8, 10, 13, 18, and 19 in the 5'-ICR and 48, 53, 56, 57, and 58 in the 3'-ICR, appear to have evolved universal importance for RNA polymerase III transcription in eukaryotes. Thus these ICR sequences may play a critical role in regulation of tRNA expression.
50 previously untreated patients with multiple myeloma received two-phase treatment: repeated cycles of 4 day infusion with vincristine, doxorubicin, and methylprednisolone (VAMP) followed by high-dose melphalan (HDM), with autologous bone marrow transplantation where possible. The overall response rate was 74% (37/50), with 25 patients (50%) achieving complete haematological and biochemical remission. These remissions were associated with a good quality of life as measured by performance status, pain grade, and the reversal of humoral immunosuppression. 6 patients died during the VAMP phase and there was 1 death related to HDM. The achievement of complete remission, as defined here, in such a high proportion of patients is exceptional and may represent a useful advance in the management of myeloma.
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