Search PubMed⌕ Search

Biomedical subjects

B E Johnson

Publications and source records attributed to B E Johnson.

At least 181 records · Page 10Linked to original sources
PubMed1987

Quinine induced photosensitivity: clinical and experimental studies.

Quinine induced photosensitivity, an infrequently described adverse effect, is reported in four patients. The clinical presentation and distribution was that of a light exposed site eruption characterized by oedema and erythema in three patients, and by lichen planus in the fourth. Monochromator phototesting demonstrated abnormal delayed erythema responses in the UVB, UVA and visible wavebands. The clinical features suggested a phototoxic effect but laboratory studies indicated that the molecular mechanisms involved are unusual. Clinical and phototest evidence of abnormal photosensitivity persisted for some months after stopping quinine. Broad spectrum sunscreens are advised for the management of such patients and, where possible, cessation of quinine administration.

Aged↗
PubMed1987

myc family oncogene amplification in tumor cell lines established from small cell lung cancer patients and its relationship to clinical status and course.

44 small cell lung cancer cell lines established from 227 patients were studied for myc family DNA amplification (c-myc, N-myc, and L-myc). Two of 19 lines (11%) established from untreated patients' tumors had DNA amplification (one N-myc and one L-myc), compared with 11 of 25 (5 c-myc, 3 N-myc, and 3 L-myc) cell lines (44%) established from relapsed patients' tumors (P = 0.04). The 19 patients who had tumor cell lines established before chemotherapy treatment survived a median of 14 wk compared with 48 wk for the 123 extensive stage patients who did not have cell lines established (P less than 0.001). Relapsed patients whose cell lines had c-myc DNA amplification survived a shorter period (median of 33 wk) than patients whose cell lines did not have c-myc amplification (median of 53 wk; P = 0.04). We conclude that myc family DNA amplification is more common in tumor cell lines established from treated than untreated patients' tumors, and c-myc amplification in treated patients' tumor cell lines is associated with shortened survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Non-small-cell lung cancer. Major cause of late mortality in patients with small cell lung cancer.

Among 360 patients with small cell lung cancer treated in National Cancer Institute therapeutic trials from 1973 to 1982, 40 were two-year cancer-free survivors. Of these 40 patients, six had later development of non-small-cell lung cancer at 3.5 to 8.0 years (median 5.1) after the diagnosis of small cell lung cancer. Three had the second malignant tumor in the contralateral lung, one in a different lobe, and two in the same lobe as the initial small cell lung cancer. Ten patients had relapses of small cell lung cancer at 2.1 to 6.2 years (median 3.2) from diagnosis. Three recurrences were in the same site or lobe as the initial lesion, four in the same lobe and in sites outside the thorax, and three solely in sites outside the thorax. It is concluded that these non-small-cell lung cancers usually represent second primary lung tumors and that most late small cell lung cancers represent relapses occurring up to 6.2 years from diagnosis. In this study, the risk of development of non-small-cell lung cancer after two years of disease-free survival following small cell lung cancer is 4.4 percent per person-year, approximately 10 times higher than the rate of 0.5 percent previously determined in screening studies of men at high risk for lung cancer. Non-small-cell lung cancer represents more than a third of lung cancer deaths in patients with small cell lung cancer surviving beyond two years from diagnosis and more than half of lung cancer deaths beyond three years. It is recommended that all patients treated for small cell lung cancer discontinue smoking.

Adult↗
PubMed1986

Molecular genetic analysis reveals chromosomal deletion, gene amplification, and autocrine growth factor production in the pathogenesis of human lung cancer.

These studies of lung cancer suggest that a number of molecular mechanisms may be important in the pathogenesis of lung cancer, especially SCLC. An inherited predisposition to develop SCLC may correlate with a nonfunctional, recessive allele for a gene (McKusick #18228, McKusick 1986) that maps to chromosome region 3p(14-23). Individuals at risk would be heterozygous for this allele in their germ line, carrying one copy of a normal functional gene and one mutant, recessive allele. Exposure to carcinogens, in particular cigarette smoke, can produce somatic genetic changes such as chromosomal deletion or gene mutation in the functional allele of this gene, unmasking the nonfunctional allele. Loss of this normal gene may alter the regulation of cell growth, perhaps by allowing the deregulated expression of proto-oncogenes of the myc family, or autocrine growth factors such as GRP and/or its receptor. Alternatively, loss of this gene may result in the cell returning to a less differentiated developmental state where growth regulation is less stringent. Persons with this mutant gene should be at increased risk to develop SCLC, and further RFLP analysis of the 3p region in SCLC may allow identification of specific haplotypes with increased risk of developing lung cancer. If this notion is correct, one might expect to find an increased frequency of second tumors in lung cancer patients and the presence of similar chromosomal deletions in second tumors arising in SCLC patients. In this regard, cured lung cancer patients, including those with SCLC, have a tenfold increased risk of developing a second lung cancer (Fontana 1977; Cortese et al. 1983; Johnson et al. 1986b). In fact, a chromosome 3p deletion along with other chromosomal abnormalities was identified in acute erythroleukemia cells arising in a long-term survivor of SCLC (Bradley et al. 1982), implicating this same region in the pathogenesis of both tumors. Other predictions include the correction of at least a portion of the defect by introducing a normal chromosome 3 into SCLC cells. While c-myc is expressed in many fetal and adult tissues, high-level expression of N- and L-myc is very restricted as to tissue and stage in the developing mouse, with N-myc expressed in the fetal but not adult lung, whereas the lung was the only adult tissue where L-myc expression was detected (Zimmerman et al. 1986). Could these patterns provide a clue to the differential expression of c-, N-, and L-myc found in different lung cancers (Nau et al. 1986)?(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Differentiation↗
PubMed1986

Photosensitivity due to retinoids: clinical and laboratory studies.

Six subjects taking isotretinoin were studied, none of whom had clinical or phototest evidence of photosensitivity. Of nine subjects taking etretinate, one had convincing clinical photosensitivity consisting of a burning erythema on sunlight exposure. His phototesting results showed a marked abnormality from 300 +/- 5 nm to 365 +/- 30 nm which returned close to normal limits within one month of stopping therapy. Although clinically normal, another subject taking etretinate had similar phototest evidence of abnormal photosensitivity. In vitro photohaemolysis studies demonstrated that tretinoin (all-trans-retinoic acid) and isotretinoin have a potential, while etretinate has none. However, the major metabolite of etretinate (Ro 10-1670) had a phototoxic potential greater than that of tretinoin. The apparently low incidence of photosensitivity suggests that an idiosyncrasy is responsible, perhaps due to a disorder of pharmacokinetics or metabolism. Clinical cases should use appropriate photoprotection against UVB and UVA wavebands.

Adult↗
PubMed1986

Changes in the phenotype of human small cell lung cancer cell lines after transfection and expression of the c-myc proto-oncogene.

Small cell lung cancer growing in cell culture possesses biologic properties that allow classification into two categories: classic and variant. Compared with classic small cell lung cancer cell lines, variant lines have altered large cell morphology, shorter doubling times, higher cloning efficiencies in soft agarose, and very low levels of L dopa decarboxylase production and bombesin-like immunoreactivity. C-myc is amplified and expressed in some small cell lung cancer cell lines and all c-myc amplified lines studied to date display the variant phenotype. To investigate if c-myc amplification and expression is responsible for the variant phenotype, a normal human c-myc gene was transfected into a cloned classic small cell lung cancer cell line not amplified for or expressing detectable c-myc messenger RNA (mRNA). Clones were isolated with one to six copies of c-myc stably integrated into DNA that expressed c-myc mRNA. In addition, one clone with an integrated neo gene but a deleted c-myc gene was isolated and in this case c-myc was not expressed. C-myc expression in transfected clones was associated with altered large cell morphology, a shorter doubling time, and increased cloning efficiency, but no difference in L dopa decarboxylase levels and bombesin-like immunoreactivity. We conclude increased c-myc expression observed here in transfected clones correlates with some of the phenotypic properties distinguishing c-myc amplified variants from unamplified classic small cell lung cancer lines.

Animals↗
PubMed1986

Chromosomal deletion, gene amplification, alternative processing, and autocrine growth factor production in the pathogenesis of human lung cancer.

Molecular and cell biologic studies of a large number of lung cancer cell lines of all histologic types have revealed several mechanisms active in the pathogenesis of these cells. Small cell lung cancer (also called "oat cell" lung cancer) has a deletion involving chromosome region 3p(14-23) that is confirmed by DNA restriction fragment length polymorphisms analysis (studies done in collaboration with Dr. Susan Naylor). Several lung cancers of both small cell and non-small cell type (including adeno- and squamous cell lung cancer) express the proto-oncogenes c-, N-, or L-myc, and in some cases more than one of these family members. N-myc appears restricted in its expression to the small cell lung cancer type while c-myc and L-myc can be expressed in both small cell and non-small cell lung cancers. Many lung cancers of all histologic types also express large amounts of p53, which are not correlated with the amount or type of myc gene product expressed. In small cell lung cancer, high levels of myc gene expression are usually associated with gene amplification, and not uncommonly there is rearrangement of some of the amplified copies. In non-small cell lung cancer, expression without amplification or rearrangement of myc genes is seen. In contrast, high level expression of p53 is not associated with gene amplification in any lung cancer type. In addition, to these proto-oncogenes acting at a presumed nuclear locus, there is increased expression of various ras family members and the c-raf-1 proto-oncogene (in collaboration with Dr. Ulf Rapp). Lung cancer cells in tissue culture can grow in medium without serum and few or no other growth factors added. Thus, it appears that lung cancer cells can produce their own growth factors which can act in an "autocrine" fashion. The best characterized example of this is gastrin releasing peptide (GRP, also called bombesin) produced by small cell lung cancer. In at least some small cell lung cancers, interference with GRP action by specific monoclonal antibodies results in inhibition of tumor cell growth in culture and in nude mouse xenografts. Thus, constitutively expressed GRP gene may function as a cellular oncogene under certain circumstances in small cell lung cancer. Based on these observations we are proposing to test monoclonal anti-GRP antibodies in patients.

Chromosome Deletion↗
PubMed1985

Comparative mutagenicity tests in the Salmonella/microsome assay with rat and woodchuck S9 preparations.

The Salmonella mutagenicity assay was utilized to compare the hepatic S9 fractions from untreated and 3-methylcholanthrene (MC) induced woodchucks with Aroclor 1254 induced rats. Three known promutagens, benzo[a]pyrene (BP), 7,12-dimethylbenz[a]anthracene (DMBA), and 2-aminofluorene (AF) were tested at 5 concentrations with the strain TA100 against 3 levels of S9 fraction. Both woodchuck S9 fractions were as effective as the rat S9 in activating BP and both were more effective than the rat S9 in activating DMBA. Untreated woodchuck S9 was also as effective as rat S9 in activating AF. The protein content of the S9 fraction did not differ significantly between rats and woodchucks, but the P-450 content of the rat S9 was approximately 3.5 times that of woodchuck.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

A study of cutaneous photosensitivity induced by amiodarone.

Amiodarone-induced cutaneous photosensitivity was studied in 12 subjects treated with the drug. The action spectrum for the abnormal response to sunlight was shown to be within the range of 335-460 (+/- 30) nm. The clinical features of the photosensitivity response suggested that it was most probably a phototoxic reaction, a conclusion supported by the results of in vitro studies which indicated activity mainly against cell membranes. Of the five in vitro models used, three--namely photohaemolysis, the inhibition of DNA synthesis in PHA stimulated lymphocytes and the killing of mouse peritoneal macrophages--provided unequivocal evidence of the phototoxic potential of both amiodarone and its major metabolite, desethylamiodarone. In each model desethylamiodarone produced a greater effect by a factor of between 2 and 10. In vitro, UV-B wavelengths produced a greater effect than UVA but the difference between the effective wavelengths in vivo and in vitro might be explained by the greater absorption of the shorter wavelength UV-B in the epidermis. Zinc oxide-containing preparations appeared to be the most effective in reducing the cutaneous photosensitivity. It is suggested that the long-term cutaneous pigmentation resulting from oral amiodarone has a significant photosensitivity component.

Adult↗
PubMed1985

Neurologic, neuropsychologic, and computed cranial tomography scan abnormalities in 2- to 10-year survivors of small-cell lung cancer.

In order to evaluate the relationship between neurologic function and cranial irradiation, 20 patients treated on National Cancer Institute (NCI) small-cell lung cancer (SCLC) trials who were alive and free of cancer 2.4 to 10.6 years (median, 6.2) from the start of therapy were studied. All were tested with a neurologic history and examination, mental status examination, neuropsychologic testing, and review of serial computed cranial tomography (CCT) scans. Fifteen patients had been treated with prophylactic cranial irradiation (PCI), two patients with therapeutic cranial irradiation, and three received no cranial irradiation. All patients but one were ambulatory and none were institutionalized. Fifteen patients (75%) had neurologic complaints, 13 (65%) had abnormal neurologic examinations, 12 (60%) had abnormal mental status examinations, 13 (65%) had abnormal neuropsychologic testing, and 15 (75%) had abnormal CCT scans. Compared with those given low-dose maintenance chemotherapy during PCI using 200 to 300 rad per fraction, patients who were given high-dose induction chemotherapy during the time of cranial irradiation or large radiotherapy fractions (400 rad) were more likely to have abnormal mental status examinations (6/6 v 4/9) and abnormal neuropsychologic tests (6/6 v 4/9), but no major difference in CCT findings was present. CCT scans in the majority of cases (11/18) showed progressive ventricular dilatation or cerebral atrophy up to 8 years after stopping therapy. We conclude neurologic abnormalities are common in long-term survivors of SCLC, and may be more prominent in patients given high-dose chemotherapy during cranial irradiation or treated with large radiotherapy fractions. The CCT scan abnormalities are common and progressive years after prophylactic cranial irradiation and chemotherapy are stopped.

Adult↗
PubMed1985

Patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation. Data on potential cures, chronic toxicities, and late relapses after a five- to eleven-year follow-up.

We assessed the outcome in 252 patients with small-cell lung cancer 5 to 11 years after treatment with combination chemotherapy, with or without chest and cranial irradiation, in National Cancer Institute therapeutic trials from 1973 through 1978. Twenty-eight patients (11%) survived free of cancer for 30 months or more. Fourteen patients remain alive without evidence of cancer beyond 5 years (range, 6.4 to 11.3 years), and 7 patients have returned to a lifestyle similar to that before diagnosis. The other 14 patients who were cancer-free at 30 months have developed cancer or died; 6 patients had a relapse, 4 developed or died from non-small-cell lung cancer, and 4 died of unrelated causes. A few patients with small-cell lung cancer (5.6%) may be cured. Thirty-month, cancer-free survival is insufficient to show a cure. Although late toxicities are troublesome, they do not outweigh the benefits of prolonged survival and potential for cure with modern aggressive therapy in small-cell lung cancer.

Adult↗
PubMed1985

A study of compositae plant extract reactions in photosensitivity dermatitis.

In subjects with chronic photosensitivity of the photosensitivity dermatitis/actinic reticuloid type the persistent reaction of the skin appears to be due to a number of factors, including those of contact allergic sensitivity and of photosensitivity (i.e., phototoxicity and/or photoallergy). The assessment of the relevant importance of these factors can be complicated by the reactivity of the skin resulting in false positive responses from skin patch and photopatch testing. Moreover, difficulties may also arise in the assessment of the results using commercially available patch test materials. However, the study described here indicated that, provided the reactivity of the skin is suppressed prior to investigation, reliable results are obtained from photopatch testing and that these results are similar whether the extract is from a commercial source or has been obtained from locally grown Compositae plants. Also, that although there may be a photoallergic component in the cutaneous photosensitivity, the results of the in vivo and in vitro studies reported here indicate the likely involvement of phototoxicity as well.

Adult↗
PubMed1985

The action spectrum for benzanthrone photosensitization of mouse macrophages.

An in vitro method for determination of the phototoxic action spectrum of benzanthrone was established using a cover slip-test tube culture system with mouse peritoneal macrophages. The action spectrum peaked between 380 and 400 nm with abrupt fall-off to either side. These findings correlate closely with both the absorption spectrum of benzanthrone and the clinical action spectrum of phototoxicity in humans.

Animals↗