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Biomedical subjects

E Johansen

Publications and source records attributed to E Johansen.

At least 37 records · Page 2Linked to original sources

Is there ever a role for salvage operations in limited small-cell lung cancer?

Combined modality treatment with chemotherapy and radiation produces tumor regression in most patients with small-cell lung cancer, but the impact on survival has been small, and less than 20% of patients with limited disease survive 2 years. Survival time is extremely short after failure to respond or relapse after treatment. Local control remains a problem, with one third of patients having recurrence only at the primary site. In an attempt to prolong survival and perhaps achieve cure, we undertook surgical resection in 28 patients with limited small-cell lung cancer who did not have complete remission with standard treatment or who had only local recurrence after treatment. There were 28 patients, 22 male and six female, median age 61 years (range 41 to 76). All patients had been treated with chemotherapy and 13 had received preoperative radiotherapy to the primary site and mediastinum. Eight patients underwent an operation for relapse after complete remission. Five patients had had no response to treatment, three had had a slight response followed by progression during chemotherapy, and 12 had achieved partial response but had greater than 3 cm residual masses. Twelve patients required pneumonectomy, 15 lobectomy, one patient had unresectable disease, and two had bulky residual masses after the operation. Three others had microscopic residual disease. Pathologic examination showed only small-cell lung cancer in 18 patients, mixed small-cell and non-small-cell in four, and only non-small-cell lung cancer in six. There were only four patients with stage I disease, 10 with stage II, and 14 with stage III. The median survival from the date of diagnosis for the entire group is 105 weeks and from the date of operation, 74 weeks. The projected 5-year survival rate is 23%. The two patients with residual masses died with local progression, and distant metastatic disease developed in 17 others. One patient died at 6 years without recurrent disease. Eight patients are alive 2 to 5 years after diagnosis. Seven of these patients required only a lobectomy, four had stage I disease, two had stage II, and two had stage III disease. Five had pure small-cell lung cancer and three had mixed small-cell and non-small-cell tumors. All of the patients with pathologic stage I disease remain alive compared with one of 10 with stage II disease and two of 14 with stage III. In summary, relapse or failure to respond to chemotherapy may be due to non-small-cell lung cancer or a mixed tumor.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Surgical treatment for limited small-cell lung cancer. The University of Toronto Lung Oncology Group experience.

Since 1977, 119 patients with limited small-cell lung cancer have undergone combined modality therapy including surgery at our institution. Seventy-nine patients (58 male, 21 female; median age 63 years) had surgery first, and 67 of these had adjuvant chemotherapy. Forty (27 male, 13 female; median age 59 years) had chemotherapy first, and 94% had a complete or partial response before the operation. Pretreatment staging revealed 69 stage I, 27 stage II, and 23 stage III tumors. Twenty-six patients required pneumonectomy, 88 lobectomy, and five had no resection. Four patients had gross and six had microscopic residual disease. Postoperative pathologic examination showed small-cell lung cancer only (n = 95), non-small-cell lung cancer (n = 3), mixed (n = 17), and no residual tumor (n = 4). Postoperative staging revealed 35 stage I, 36 stage II, and 48 stage IIIa tumors. The median survival of the entire group is 111 weeks and the projected 5-year survival rate is 39%. No survival difference was seen between patients treated with chemotherapy before the operation and those undergoing an initial operation followed by chemotherapy (p = 0.756). The median survival for patients with pathologic stage I disease has not been reached, and the projected 5-year survival rate is 51%. This is significantly better than for the patients with stage II (median 82 weeks, p = 0.001) or stage III (median 83 weeks, p = 0.001) disease, who have projected 5-year survival rates of 28% and 19%, respectively. Seven of the 12 patients who had no adjuvant chemotherapy remain alive at 6 to 48+ months. Sixty-seven patients have died (11 had no evidence of disease). Only 10 patients had a relapse in the primary site alone, seven at the primary and distant sites, and 39 only in distant sites. In summary, resection improves control at the primary site, and a significant proportion of patients with stage I (N0) disease achieve long-term survival and cure with combined modality therapy including surgery. Stage II and IIIa patients have survival predictions similar to stage IIIa non-small-cell lung carcinoma treated surgically.

Antineoplastic Combined Chemotherapy Protocols↗

Analysis of backscattered ultrasound from normal and diseased arterial wall.

Intra-arterial ultrasonic imaging has several features which affect the feasibility of clinical tissue characterization when compared with trans-thoracic ultrasound. The short distance from transducer to tissue, fluid path, high frequencies, and special characteristics of the tissues of interest all contribute to making practical tissue characterization by measurement of the backscattered signal more probable in intra-arterial imaging. The properties of backscattered ultrasound, and methods of characterizing such signals, are discussed with special reference to intra-arterial applications.

Acoustics↗

Cross sectional early mitral flow velocity profiles from colour Doppler.

Instantaneous cross sectional flow velocity profiles from early mitral flow in 10 healthy men were constructed by time interpolation of the velocity data from each point in sequentially delayed two dimensional digital Doppler ultrasound maps. This interpolation allows correction of the artificially produced skewness of velocities across the flow sector caused by the time taken to scan the flow sector for velocity recording of pulsatile blood flow. These results suggested that early mitral flow studied in an apical four chamber view is variably skewed both at the leaflet tips and at the annulus. The maximum flow velocity overestimated the cross sectional mean velocity at the same time by a factor of 1.2-2.2. Also the maximum time velocity integral overestimated the cross sectional mean time velocity integral to the same extent. This cross sectional skew must be taken into account when calculation of blood flow is based on recordings with pulsed wave Doppler ultrasound from a single sample volume.

Adolescent↗

Adjuvant chemotherapy following surgical resection for small-cell carcinoma of the lung.

Surgery alone is inadequate therapy for limited small-cell lung cancer (SCLC), resulting in less than 5% long-term survival. Since 1976, we treated patients undergoing surgery for SCLC with adjuvant chemotherapy in an attempt to prolong survival and increase cure. Seventy-seven patients who underwent surgery as their primary treatment were identified, and of these 63 (46 male and 17 female) received chemotherapy. Fifteen patients had a pneumonectomy, 46 a lobectomy, and two had wedge resections. Six patients had positive microscopic resection margins. Pathologic staging showed tumor, node, metastasis (TNM) involvement as follows: T1N0, eight; T2N0, ten; T1N1, six; T2N1, 18; T1N2, five; T2N2, nine; T3N0, three; T3N1, one; and T3N2, three. All patients received cyclophosphamide, Adriamycin (doxorubicion; Adria Laboratories, Mississauga, Ontario), and vincristine; four also received etoposide (VP-16) and cisplatin, one VP-16, and four methotrexate, procarbazine, and lomustine (CCNU). Forty-nine patients received prophylactic cranial irradiation, and 35 received radiotherapy to the mediastinum and primary site. The overall median survival of the 63 patients is 83 weeks, and the projected 5-year survival is 31%. Patients with T1 or T2 tumors without nodal involvement had a median survival of 191 weeks, and projected 5-year survival of 48%. Stage II (T1N1, T2N1) and stage III (any T3 or T1-2N2) patients had median survivals of 72 weeks and 65 weeks, and projected 5-year survivals of 24.5% and 24%, respectively. Thirty-three patients have relapsed and died of disease. Only two patients had an isolated relapse at the primary site. Seven other patients have died without recurrent disease. Adjuvant chemotherapy after surgery results in prolonged survival and cure for a significant number of patients with stage I SCLC, although nodal involvement at any level is associated with shorter survival.

Adult↗

Isolation of competition-defective mutants of Rhizobium fredii.

We coupled Tn5 mutagenesis with a competition assay to isolate mutants of Rhizobium fredii USDA 257 that are defective in competition for nodulation of soybeans. Two mutants with single Tn5 inserts in the chromosome showed reduced competitiveness in vermiculite but were identical to the wild-type strain in symbiotic properties when inoculated alone. Recombination of Tn5 and flanking genomic regions cloned from the mutants into the parent strain showed that Tn5 was responsible for the mutant phenotype.

Cloning, Molecular↗

Symbiotic mutants of Rhizobium meliloti that uncouple plant from bacterial differentiation.

Spontaneous mutants at a new symbiotic locus in Rhizobium meliloti SU47 are resistant to several phages and are conditionally insensitive to a monoclonal antibody to the bacterial surface, apparently because they are deficient in a wild-type exopolysaccharide. On alfalfa, the mutants do not curl root hairs, but penetrate the epidermis directly, forming nodules that contain no visible infection threads or "bacteroids," have a few bacteria in superficial intercellular spaces only and not within the nodule cells, and fail to fix nitrogen (Fix-). Evidently, infection threads are not essential for cell proliferation and nodule formation, which are here induced by a bacterial signal at a distance and uncoupled from the bacterial differentiation that normally goes on as well.

Antibodies, Monoclonal↗

Monoclonal antibodies to Rhizobium meliloti and surface mutants insensitive to them.

Monoclonal antibodies were produced to the surface of the symbiotic nitrogen-fixing bacterium Rhizobium meliloti. Bacterial lysis in the presence of complement or cycles of agglutination and growth were used to select mutants no longer recognized by the antibodies. The mutants were used to produce new antibodies with different specificities. Several mutants had altered sensitivity to one or more bacteriophages. R. meliloti strains from different sources had distinct patterns of sensitivity to monoclonal antibodies and phages, which together can be used for discriminative typing.

Antibodies, Monoclonal↗

Fine structural studies of radiation-resistant human squamous cell carcinomas.

Squamous cell carcinomas of the oral cavity are relatively common lesions, and often can be controlled by radiation therapy. Recently, a series of these tumors has been encountered which did not respond positively to irradiation, necessitating subsequent extensive surgery. This report describes some fine structural changes which were observed in squamous cell carcinomas following exposure to x-irradiation. In addition to the common, keratin-forming differentiated cell, others which were observed were secretory-like, undifferentiated and phagocytic cells. Undifferentiated tumor cells occasionally became incorporated, at least temporarily, as a component of the blood vessel wall, perhaps reflecting metastatic potentiality. It is proposed that irradiation may either increase potential avenues of tumor cell differentiation or inactivate inhibitors thereof.

Aged↗

On the ABL1.

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Acid-Base Equilibrium↗

Reversion of the gal3 mutation of Escherichia coli: partial deletion of the insertion sequence.

The gal3 mutation of E. coli is an insertion of a DNA sequence, 1,100 base pairs in length, into the operator-promoter region of the galactose operon. This mutation reverts spontaneously to gal+ by excision of the insertion to produce stable, inducible revertants, or by tandem duplications of the gal operon to produce unstable, constitutive revertants. The nature of a third class of revertants, which are stable and constitutive, is the subject of the present study. The stable, constitutive class of revertants included approximately 30% of all gal+ revertants obtained from a gal3 (lambda) strain. Although the constitutive reversions could be transduced by lambda, the efficiency was found to be extremely poor and the rare transductants which did appear seemed to originate from abnormal transducing particles. It was concluded that these reversions were not normally packaged by lambda. In order to facilitate the packaging of these reversions, the chlD-pgl region was deleted from the parent gal3 (lambda) strain. Unexpectedly, the gal3 mutation in the majority of these deletions reverted to produce stable, constitutive reversions exclusively. The explanation proposed was that the chlL-pgl deletions had also removed part of the gal operator-promoter. These revertants were not considered to be true representatives of the stable, constitutive class. The specificity of deletion end-points at the insertion was found only in the gal3 (lambda) strain, and not in gal+, gal+(lambda), or gal3 strains. Moreover, the frequency of spontaneous chlD-pgl deletions increased 10- to 15-fold in presence of the gal3 insertions. A lambdagal phage bearing a true stable, constitutive reversion (galc200) was isolated from the revertant strain by subsequent deletion of the chlD-pgl segment (delta31). Electron micrographs of lambdagal+ and lambdac200 delta31(chlD pgl) DNA heteroduplexes were interpreted to indicate that the stable, constitutive reversion had arisen by a deletion of 3/4 of the gal3 insertion sequence. The main conclusions are: (i) the stable, constitutive reversions of gal3 can arise by partial deletions of the insertion sequence, apparently by elimination of the nucleotide sequence which causes polarity; (ii) the chlD-pgl deletions may exhibit preferential termination at the right extremity of the gal3 insertion in presence of prophage lambda; and (iii) the gal3 insertion appears to inhibit the production of lambdagal particles by providing a nucleotide sequence which is recognized and degraded by a specific endonuclease. It is suggested that inhibition of transducing particle formation by gal3 and the preferred termination of deletions at gal3 might represent related phenomena.

Base Sequence↗