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Biomedical subjects

H Johansen

Publications and source records attributed to H Johansen.

At least 37 records · Page 2Linked to original sources
PubMed1990

Simple mastectomy with postoperative irradiation versus extended radical mastectomy in breast cancer. A twenty-five-year follow-up of a randomized trial.

From November 1951 to December 1957, all patients with untreated breast cancer admitted to the Radium Centre in Copenhagen were randomized before their operability was evaluated into two groups, if the patients were operable, viz. simple mastectomy with postoperative x-ray treatment or extended radical mastectomy. Twenty-five-year results are presented, showing no difference in survival or recurrence-free survival of the operable patients. Histological grading was performed in nearly all cases. Patients with grade 1 tumours had a better survival than grades 2 and 3, but there was no difference in survival between the two treatment groups, when histological grading was taken into account. Histological node positive patients had more grades 2 and 3, tumours, whereas node negative patients had more grade 1 than grades 2 and 3 tumours. Premenopausal women had a significantly better survival than postmenopausal in all stages.

Age Factors↗
PubMed1990

Canadian suicide mortality rates: first-generation immigrants versus Canadian-born.

This article examines suicide mortality rates and trends in Canada for first-generation immigrants and the Canadian-born population. Data are analyzed by age, sex and country of birth. Since 1950, suicide rates worldwide for both men and women have been increasing. In North America and most of Europe, suicide has been one of the major causes of death for many years. In Canada, suicide rates are also rising. However, this increase is due entirely to a rise in the rate for men; the rate for women has remained relatively stable. Several differences are apparent between the rates for the Canadian-born population and those for first-generation immigrants. For example, three times as many Canadian-born men as women commit suicide. For first-generation immigrants, the ratio is two to one. Suicide mortality rates for the Canadian-born are higher than those for first-generation immigrants in every age group except for the 65 and over groups. Canadian born males have higher ASMR than first generation immigrant males. The rates for women show that first-generation immigrant women have higher suicide mortality rates than their Canadian-born counterparts, and that the highest rate for all women is for immigrants born in Asia.

Adolescent↗
PubMed1990

Canadian cardiovascular disease mortality: first generation immigrants versus Canadian born.

Cardiovascular disease (CVD) is the major cause of death in Canada, as it is in most industrialized countries. Studies have shown that CVD mortality rates vary among ethnic groups. Since about one in six Canadian residents is a first generation immigrant, it is important to consider ethnic background when interpreting Canadian health statistics or planning health services. Overall, lower CVD mortality rates were found for first generation Canadians from Latin America, China and South Asia; higher rates are indicated for those from Scandinavia and Africa. The rates for North America are similar to those found for Eastern and Western Europe. Between two five-year time periods (1969-73 and 1984-88), CVD mortality rates generally were found to decrease, except for immigrants from Africa (age 35+). The rates were consistently higher for males than for females.

Adult↗
PubMed1990

Acute myocardial infarction. A feasibility study using record-linkage of routinely collected health information to create a two-year patient profile. Manitoba, 1984-85 and 1985-86.

Manitoba's hospital separations and physician medical files were linked for the fiscal years 1984-85 and 1985-86. The result was a study file consisting of records for 5,293 males and 3,143 females, who, during this period, suffered an Acute Myocardial Infarction (AMI), commonly called a heart attack. Merging the two types of files created a comprehensive data base for these AMI victims. The Manitoba age-sex standardized AMI rate was 38.0 per 10,000 population. Age-specific rates were higher for males than for females for all age groups. Hospitalized cases accounted for 7,201 individuals or 85.4% of AMI victims. Age-sex standardized rates of hospitalization per 10,000 population ranged from 27.1 in the Central region to 36.0 in the Westman region. The Manitoba age-specific rates of hospitalization for males in the 35-54 and 55-64 age groups were about three times the female rates for the same age groups. One quarter of AMI hospitalized victims died in hospital. The Manitoba age-specific death rates for males in the 35-54, 55-64 and 65-74 age groups were double the rates for females in the same age groups. Of the 8,436 AMI victims under study, 86.4% had at least one other concurrent medical condition such as angina, other forms of ischemic heart disease, diabetes, or hypertension. Of AMI victims, 93.8% underwent at least one of the following procedures: coronary artery bypass surgery, angiogram, electrocardiogram, cardiac catheterization, arteriography, or blood cholesterol testing. A higher percentage of procedures was performed on males than on females.

Acute Disease↗
PubMed1989

Regulated expression at high copy number allows production of a growth-inhibitory oncogene product in Drosophila Schneider cells.

The Drosophila metallothionein promoter (Mtn) was used to obtain efficient, regulated expression of foreign gene products inserted in high copy numbers into Drosophila melanogaster Schneider 2 cells. An expression unit comprised of a reporter gene [Escherichia coli galactokinase (galK)] fused to the Mtn promoter was stably introduced into Schneider 2 cells in up to several hundred copies per cell in a single transfection-selection event. This system contrasts dramatically with other eukaryotic systems that permit only a few copies of a gene to be stably inserted in a single transfection-selection event. The transfected Drosophila S2 cell lines expressed high levels of both galK mRNA and protein in response to metal induction. Most important, and in contrast to mammalian cells, expression remained fully regulated even at high copy number, with low basal expression maintained in the absence of inducer. This regulated system was used to obtain efficient expression in Drosophila cells of an otherwise lethal or growth-inhibitory gene product, the human H-ras oncogene. The ability to obtain regulated high-level expression of potentially lethal foreign proteins is unique to the Drosophila cell system.

Animals↗
PubMed1989

The effect of thoracic irradiation for cancer of the breast on ventilation, perfusion and pulmonary permeability. A one-year follow-up.

Regional and overall lung function was studied in 14 women during a one-year follow-up after postmastectomy irradiation for cancer of the breast. The dose was 40 Gy in the chest wall and 20-40 Gy in the apex of the lung. Immediately after irradiation there was a slight increase in pulmonary clearance of 99TCm-DTPA compared to baseline values. This increase, however, was not restricted to the field of irradiation. Three months after irradiation there were regional defects in the ventilation and perfusion scintigrams in 11 of the patients. At the same time there was a greater decrease in total lung capacity, vital capacity and diffusion capacity for CO than in ventilation and perfusion. One year after irradiation the lung function impairment had only insignificantly regressed. It is concluded that local lung irradiation may cause persistent regional and generalized lung function impairment. The early increase in pulmonary clearance of 99Tcm-DTPA could not be used as a predictor of subsequent lung function impairment.

Adult↗
PubMed1988

Prognostic factors in osteosarcomas. A regression analysis.

A multivariate regression analysis of survival data, using the Cox proportional hazards model (PHM), was performed on the retrospective material of 184 osteosarcoma patients treated at the Aarhus and Copenhagen oncology centers, Denmark, from 1963 to 1984. All patients were previously untreated. Radical surgery, in general ablative when possible, was the primary treatment goal throughout this period. A number of clinical and pathologic variables were tested in the model to elucidate their prognostic importance. Tumors localized to the trunk, pelvis, or femur, and symptom duration of less than 6 months were poor prognostic signs. Tumors dominated by fibroblastic cells and a patient age of approximately 25 to 30 years were associated with an especially good prognosis. The prognosis worsened with advancing age. Children, adolescents, and adults ages 5 to 25 years had significantly poorer prognosis than young adults 25 to 30 years of age. Sex, radiologic appearance, and year of referral had no significant prognostic value in this series. Based on the regression model, a prognostic index is derived and survival is calculated for a good and a poor prognostic case. The overall 10-year survival with one standard deviation was 28.6 +/- 3.5%. Cancer deaths continue to occur 10 years after initial treatment, and the estimated hazard rate is still four times greater than that of a sex- and age-matched group of healthy individuals.

Adolescent↗
PubMed1988

Major risk factors for cardiovascular disease mortality in adults: results from the Nutrition Canada Survey cohort.

The cardiovascular mortality experience of over 7000 Canadians ages 35-79 years free of self-reported heart disease or stroke who participated in the Nutrition Canada survey is presented. The effects of various risk factors on cardiovascular disease mortality were assessed using multivariate Poisson regression analyses. Factors associated with a significantly increased risk of dying included cigarette smoking, hypertension, diabetes and, for women, serum cholesterol. Relative risks were similar for those ages 35-64 years compared to those 65-79 years for diabetes but were higher among those 35-64 years for cigarette smoking, diastolic hypertension, obesity and serum cholesterol (females only). Individuals drinking three or more drinks daily had a relative risk of 3.18 for stroke. Population attributable risks for smoking, hypertension, elevated serum cholesterol and diabetes, respectively, were 47%, 21%, 7% and 8% for men and 10%, 21% 18% and 16% for women.

Adult↗
PubMed1988

Postmastectomy irradiation in high-risk breast cancer patients. Present status of the Danish Breast Cancer Cooperative Group trials.

All pre- and postmenopausal high-risk breast cancer patients in the protocols DBCG 77 of the Danish Breast Cancer Cooperative Group received postmastectomy irradiation before randomization to either adjuvant systemic therapy or no such treatment. The actuarial loco-regional recurrence rate at 9 years was 6-17%, with the lowest rate in patients who also received additional adjuvant chemotherapy or tamoxifen. In a subsequent study (DBCG 82) the role of postmastectomy irradiation together with systemic treatment was evaluated in high-risk patients. Pre- and menopausal patients were randomized to postmastectomy irradiation + CMF (cyclophosphamide, methotrexate, 5-fluorouracil), CMF alone or CMF + TAM (tamoxifen). Postmenopausal patients were randomized to postmastectomy irradiation + TAM, TAM or CMF + TAM. At 4 years the loco-regional recurrence rate was significantly lower in the irradiated patients (5-7% vs. 23-33%). Further, disease-free survival was significantly improved in both pre- and postmenopausal irradiated patients compared with those who had only systemic treatment. At present, there are no significant differences between survival in the treatment groups. Thus, adjuvant systemic treatment alone (chemotherapy and/or tamoxifen) did not prevent loco-regional recurrences in high-risk patients after mastectomy and axillary lymph node sampling. However, a longer observation time is necessary to evaluate the consequence of primary optimal loco-regional tumour control in high-risk breast cancer patients with respect to survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Important risk factors for death in adults: a 10-year follow-up of the Nutrition Canada survey cohort.

Data on mortality among over 8000 Canadians aged 35 to 79 years who participated in the Nutrition Canada survey are presented. The effects of various risk factors on mortality were assessed with a multivariate Poisson regression analysis. Factors associated with a significantly increased risk of death over a 10-year follow-up period ending in 1981 included cigarette smoking, hypertension and diabetes mellitus. A shallow U-shaped mortality pattern was observed for body mass index and for serum cholesterol level. No statistically significant increases in risk were associated with alcohol consumption. The population attributable risks for smoking, hypertension and diabetes were 39%, 8% and 6% respectively for men and 21%, 12% and 7% respectively for women.

Adult↗
PubMed1987

High-level production of fully active human alpha 1-antitrypsin in Escherichia coli.

The human alpha-1-antitrypsin (A1AT) gene expressed in Escherichia coli as a full-length, non-fusion gene product accumulates to a relatively low level approaching less than or equal to 0.1% of total cellular protein. In contrast, deletion of the first 5, 10 or 15 codons leads to production of truncated A1AT derivatives at levels between 10 and 30% of total cellular protein. The protein with the largest truncation was insoluble and inactive following solubilization by chaotropic agents. In contrast, the two derivatives with the smaller truncations were found to be soluble, and exhibit identical specific activities in both trypsin and elastase inhibition assays to authentic human A1AT. The expression of the full-length A1AT was also optimized by making silent third position mutations within its first 15 codons. These mutations were chosen to optimize codon usage and minimize the possibility of RNA secondary structure formation in this region. Via this approach, expression of full-length, authentic, fully active A1AT was increased at least 20-fold to 2% of total cellular protein. Optimal expression was obtained using as few as three silent mutations in the first five codons, confirming the importance of this 5'-terminal region as had been defined by our deletion mutants. Both the full-length derivatives as well as the small N-terminal deletion derivative can be readily purified from bacterial extracts in fully active form suitable for the examination of their potential therapeutic application.

Base Sequence↗
PubMed1987

Selection of mutations that increase alpha 1-antitrypsin gene expression in Escherichia coli.

The gene encoding human alpha-1-antitrypsin (A1AT), when cloned and expressed as a full-length, non-fusion gene product in Escherichia coli, accumulates to levels up to 0.1% of total cellular protein. Truncation of the gene at its 5' end or synthesis as a fusion protein increases expression up to 200-fold. Extensive mutagenesis in vitro within this same 5'-terminal region aimed at improving codon usage and disrupting potential secondary structure increased expression only 10 to 20-fold. We have developed a translational fusion system for selecting mutations and applied it to the study of A1AT expression in E. coli. With this methodology, we have obtained single base-pair mutations having up to a 20-fold effect on A1AT expression. When we combined these multiple single base-pair mutations, we achieve up to a 200-fold increase in A1AT expression. The resulting gene product is of authentic size (394 amino acid residues) and contains two amino acid substitutions (Asn in place of Asp) in codons 2 and 6. This protein is primarily in the soluble fraction of the E. coli lysate and has identical activity to A1AT purified from human sera. The methodology used to generate these mutations may be generally applicable to the study of genes that do not express well in E. coli initially, and provides an alternative to secondary structure analysis in the redesign of such genes.

Amino Acid Sequence↗
PubMed1987

Overview of randomized trials comparing radical mastectomy without radiotherapy against simple mastectomy with radiotherapy in breast cancer.

An overview of mortality in the mature randomized trials comparing radical mastectomy without radiotherapy against simple mastectomy with radiotherapy has been conducted. These trials mark a transitional period between radical mastectomy and simple mastectomy as the generally preferred surgical treatment and as such are not strictly trials assessing the value of postoperative adjuvant radiotherapy. All known mature trials have been included and these four trials have entered a total of 3236 patients, in whom 1678 deaths have been recorded. Overall, no significant difference in survival was seen, but there was a nonsignificant trend for patients given radiotherapy to do worse after 15 years of follow-up.

Breast Neoplasms↗
PubMed1984

Affecting gene expression by altering the length and sequence of the 5' leader.

We have utilized a recombinant vector system designed to study gene control elements by fusing them to the Escherichia coli galactokinase gene (galK) to examine the effects of gene expression that result from introducing changes into the 5' noncoding leader region of the galK transcription unit. We varied the length of the 5' leader region and found no effect on galK expression, provided that the galK initiation codon remained the first AUG in the transcription unit. Using synthetic linkers, we then inserted specific sequences, each containing a single AUG codon at a defined position within the leader region. We found that the AUG inserts had widely different effects on galK expression and that the sequences surrounding the inserted AUG codons determined the magnitude of these effects. In addition, we placed these upstream inserted AUG codons into each of the three possible translation reading frames so that translation occurring in these frames terminates prior to, within, or downstream of the galK initiation codon, respectively. Single-nucleotide frameshift mutations were also introduced into one of these constructs to shift upstream translation into the other two possible reading frames. Depending upon where upstream translation stopped relative to the galK initiation codon, we observed consistently different effects on galK expression. Our results show that an upstream AUG that interferes with downstream translation initiation exerts its greatest effect when it translates out-of-frame through the downstream initiator into the gene. If translation is stopped upstream of or within the initiator, an unexpectedly high level of expression from the downstream AUG is maintained.

Codon↗
PubMed1984

Soft tissue sarcomas in adults. Surgical, radiologic and cytotoxic treatment.

Soft tissue sarcomas are a heterogeneous group of malignant tumours of mesenchymal and neuroectodermal origin, comprising about one per cent of all malignant diseases. The prognosis of soft tissue sarcomas is generally poor with 5 and 10 year survival rates of about 50 and 40 per cent, respectively. The modern guidelines for the different treatment modalities in soft tissue sarcomas, including local therapy (surgery, radiation therapy) and systemic therapy (cytotoxic chemotherapy) are described. The multidisciplinary approach to the treatment, optionally organised in national or international cooperative groups is emphasized .

Antineoplastic Combined Chemotherapy Protocols↗