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Biomedical subjects

A C Andersson

Publications and source records attributed to A C Andersson.

36 records · Page 2Linked to original sources

S-phase fraction and survival benefit from adjuvant chemotherapy or radiotherapy of breast cancer.

Cancer chemotherapy interacts with cell proliferation, but data on the relationship between cancer cell replication and the effect of adjuvant chemotherapy are scarce. We have investigated the S-phase fractions of the primary tumour from premenopausal breast cancer patients who participated in a randomised trial comparing 12 cycles of polychemotherapy (CMF) with post-operative radiotherapy. DNA flow cytometry was performed on frozen tissues from 208 primary breast carcinomas, of which the S-phase fraction was estimated in 176 cases. There was a significantly higher benefit from CMF among patients with a high S-phase fraction (P = 0.0033). The relative risk of distant recurrence or death in the chemotherapy group as compared with the radiotherapy group was 0.19 for patients whose tumours had an S-phase fraction of 10% or over (95% CI 0.07-0.51) and 1.55 (0.88-2.73) for patients whose tumours showed lower S-phase levels. The interaction was still significant in multivariate analysis (P = 0.0057), including lymph node metastases, tumour size and oestrogen receptor content. We conclude that the benefit from adjuvant chemotherapy compared with radiotherapy is largely confined to patients with highly proliferative tumours.

Breast Neoplasms↗

Expression of an endogenous retrovirus (ERV3 HERV-R) in human reproductive and embryonic tissues--evidence for a function for envelope gene products.

ERV3 (HERV-R) is a complete human endogenous retrovirus located on the long arm of chromosome 7. It is expressed in several human tissues as LTR env spliced transcripts (9 and 3.5 kb). The highest level of expression is to be found in placenta and virus expression is down-regulated in choriocarcinoma cell lines. By means of in situ hybridization, the expression of ERV3 env was studied in selected human reproductive and embryonic tissues. It is concluded that (a) ERV3 env is expressed in syncytiotrophoblasts not only in the placenta but also in hydatidiform moles and choriocarcinomas (irrespective of origin) (b) ERV3 expression in placenta correlates to cell fusion but probably not to the fertilization process itself (c) ERV3 env is highly expressed in certain cells in spermatogenesis but not in the Sertoli or Leydig cells, and finally (d) ERV3 env is expressed in certain embryonic tissues such as the adrenal gland and nervous tissues.

Choriocarcinoma↗

Knee laxity and function after conservative treatment of anterior cruciate ligament injuries. A prospective study.

Knee laxity and function were investigated in a prospective study including 40 patients with acute anterior cruciate ligament injury and 11 patients with minor knee injury not involving the cruciate ligaments (controls). None of the patients had primary ligament repair. Instrumental testing (OSI, Hayward, California) of the static laxity of both knees was performed at one, three, six, and 12 months after the injury. The initial laxity of the anterior cruciate-deficient knees was greater than that of the controls. At 12 months the laxity at 180N tibial load for the patients with anterior cruciate ligament injury exceeded the laxity found within one month of injury. At 12 months half of these patients complained of symptoms of instability and one out of four patients had had severe subluxations with accompanying haemarthrosis. Patients with combined anterior cruciate and medial collateral ligament injury had the greatest initial laxity and the worst outcome. In all, 20% of the patients were scheduled for reconstruction of the anterior cruciate ligament during the observation period.

Adolescent↗

S-erythropoietin levels decrease in patients with chronic hypoxia starting domiciliary oxygen therapy.

Consecutive determinations of erythropoietin in serum (s-Epo) were made in ten patients with chronic hypoxia starting domiciliary long-term oxygen therapy (LTO). After 24 h of supplementary oxygen treatment there was a fall in the median s-Epo level from 11.3 to 4.4 IU.l-1 (p less than 0.01). The initial decrease in s-Epo in conjunction with oxygen treatment was not sustained after one and three months of LTO. S-Epo levels above the reference range (3.3-13.5 IU.l-1) were found in three patients before and during LTO and in another two patients during LTO. Markedly elevated s-Epo levels were found in two patients with hypoxia and hypercapnia at the time of blood sampling. A significant negative relationship was found between the arterial oxygen tension and the log value for the s-Epo level (r = 0.40, p less than 0.005). The s-Epo levels were found to be normal in half of the measurements in patients using oxygen less than 15 h daily, a fact that indicates that s-Epo measurements are probably not suitable as indicators of compliance with LTO.

Aged↗

Changes in cadaverine and putrescine metabolism in the mouse kidney induced to growth by an anabolic steroid.

The formation of cadaverine and putrescine was studied in the kidneys of gonadectomized male mice stimulated to growth by nandrolone, an anabolic steroid with low androgenic activity. Administration of nandrolone resulted in an increased kidney weight and elevated activities of lysine and ornithine decarboxylase (assayed by measurement of the formation of 14CO2 from the 1-14C-labelled amino acids). The responses were dose and time dependent. The elevated enzyme activities were reflected by an increased endogenous kidney content of cadaverine and putrescine as well as in an increased urinary excretion of the diamines. Further, the kidney content and the urinary excretion of the polyamines spermidine and spermine were elevated on nandrolone treatment. Fractionation of kidney extracts on pore gradient electrophoresis revealed an apparent molecular weight of about 95 000 Daltons of the lysine decarboxylase as well as of the ornithine decarboxylase. On electrofocusing it was evident that both enzymes were present as more than one isoelectric form. However, the main form in both cases focused at a pH of about 5.0.

Animals↗

Metabolism of putrescine in the pregnant rat.

The in vivo metabolism of 14C-putrescine injected to rats before, during and after pregnancy was studied. Within 30 min of the administration of the isotope 9-12% of the injected radioactivity was recorded as 14CO2 in the expired air and after 5 h 60% was expired. The radioactivity excreted in the urine during the first day following the 14C-putrescine administration consisted of unmetabolized putrescine, gamma-aminobutyric acid (GABA) and some unidentified compound(s). No radioactive polyamines were detected in the urine. After treatment of pregnant rats with the diamine oxidase inhibitor aminoguanidine the expiration of 14CO2 was almost completely inhibited. In the urine increased amounts of unmetabolized putrescine were excreted while the excretion of GABA and the unidentified compound(s) were decreased. In addition 14C-spermidine appeared in the urine. The in vitro metabolism of putrescine was determined by the incubation of different tissues of pregnant and non-pregnant rats with 14C-putrescine. The 14C-metabolites derived via the diamine oxidase pathway (delta 1-pyrroline, GABA, some unidentified compound(s) and carbon dioxide) varied in magnitude with the tissue investigated. GABA was found to be a main metabolite of putrescine in several tissues of the pregnant rat. The content of putrescine and spermidine was elevated in several tissues as well as the blood on the 19th day of pregnancy in rats treated with aminoguanidine, while the content of spermine was unchanged.

Animals↗

On the biogenesis of diamines and polyamines in the pregnant rat.

The urinary excretion of the diamines histamine, methylhistamine, putrescine and cadaverine and the polyamines spermidine and spermine was studied in rats which on the 19th day of pregnancy were subjected to various ectomizing operations. In sham-operated rats the urinary excretion of all the amines studied except spermine was highly elevated on the day preceding the sham-operation and on the 3 days studied post-operatively, i.e. sham-operation did not affect the elevated urinary amine excretion during pregnancy. Foetectomy resulted in an abolished increase in the urinary excretion of histamine and methylhistamine while the excretion of putrescine, cadaverine and spermidine was still significantly increased. Removal of both the foetuses and placentae reduced the excretion of putrescine, cadaverine and spermidine towards the level of non-pregnant rats. Combined hysterectomy and ovariectomy did not cause any additional effects to those after removal of the foetuses and the placentae except for cadaverine, the excretion of which was further reduced.

Animals↗

Diamine oxidase activity and gamma-aminobutyric acid formation in medullary carcinoma of the thyroid.

The formation of different metabolites from 14C-putrescine via oxidative deamination has been studied in patients with medullary carcinoma of the thyroid (MCT) and in control subjects. The neoplastic tissue from MCT patients produced in addition to delta 1-pyrroline, large quantities of GABA and some unidentified compound(s), whereas the formation of these metabolites in normal thyroid tissue was almost negligible. Plasma from patients with MCT contained higher diamine oxidase activity than plasma from control subjects, but there was a considerable overlap between the two groups. Determination of the as yet unidentified compound(s) could possibly become a sensitive tool in the diagnosis and follow-up of carcinomas associated with a high diamine oxidase activity.

Adult↗

In vitro metabolism of putrescine by diamine oxidase in tissues of the pregnant rat.

The metabolism of 14C-putrescine by diamine oxidase was tested on the 19th day of pregnancy in different organs of rats. The highest turnover was found in maternal placenta and uterus where 94% of the reaction product was identified as delta 1-pyrroline. Considerable deamination rates were also observed in ovary, liver and fetal placenta where, however, gamma-aminobutyric acid was the predominant product. In the kidney only a small diamine oxidase activity was measured. No formation of spermidine or spermine from 14C-putrescine was detected.

Amine Oxidase (Copper-Containing)↗

Formation of GABA via oxidative deamination of putrescine in ovaries of immature rats after gonadotrophin stimulation.

The diamine oxidase catalyzed metabolism of 14C-putrescine was studied in the ovaries of immature rats with and without stimulation by gonadotrophin. This stimulation resulted in a statistically significant increase in the deamination rate of putrescine with a very predominant production of gamma-aminobutyric acid. No formation of polyamines was observed which indicated an importance of putrescine or of products of its oxidative deamination during this cellular activity.

Amine Oxidase (Copper-Containing)↗

Biosynthesis and accumulation of cadaverine and putrescine in rat ovary after administration of human chorionic gonadotrophin.

In the ovaries of pre-pubertal rats stimulated by human chorionic gonadotrophin (hCG) the temporal changes in cadaverine and putrescine formation were investigated. In addition, the dose-response relationship of hCG and its effect on the diamine formation and the effect of hCG on the content of diamines and polyamines in the ovaries and the urine were studied. The results show that the ovary stimulated by hCG, in addition to putrescine, forms cadaverine at a highly increased rate. The elevated diamine formation was parallelled by an increased content of cadaverine and putrescine in the ovary. Treatment with aminoguanidine elevated the content of cadaverine in the ovary, suggesting that diamine oxidase has a role as a regulator of the intra-ovary level of cadaverine. These results confirm that cadaverine can be synthesized in an inducible manner in mammalian tissues. This is, virtually, the first report of elevated formation of cadaverine in response to an exogenous gonadotrophin.

Animals↗

Formation of cadaverine in the pregnant rat.

The formation as well as the content of cadaverine were determined in different tissues of pregnant and non-pregnant rats. The placenta and ovary were most potent in the ability to form cadaverine. To our knowledge this is the first report of an in vitro formation of cadaverine linked to a normal physiological process, i.e. pregnancy. The highest concentration of cadaverine was found in the placenta and ovary of the pregnant rat. Treatment with aminoguanidine generally elevated the content of cadaverine, indicating a role of diamine oxidase as a regulator of diamine content.

Amine Oxidase (Copper-Containing)↗

Aspects on diamine oxidase activity and its determination.

Homogenate of guinea-pig liver and human placenta, tissues known to be rich in diamine oxidase, were incubated with 14C-putrescine and the metabolites formed were determined. In the incubate of guinea-pig liver, the major metabolites were GABA and some unidentified compound(s); delta1-pyrroline and 14CO2 were also obtained. In both the maternal and fetal parts of human placenta, radioactive GABA and the unidentified compound(s) as well as delta1-pyrroline were found. The results indicate that GABA is an important intermediate in putrescine metabolism. Determination of the amount of delta1-pyrroline is thus not well suited as a measure of the diamine oxidase activity in tissues.

Amine Oxidase (Copper-Containing)↗

Increased formation of diamines and polyamines in the pregnant rat.

1. The urinary excretion of histamine, methylhistamine, putrescine, cadaverine, spermidine and spermine was examined before, during and after pregnancy in rats. 2. During the last third of undisturbed pregnancy a distinct and steep rise occurred in the excretion of all amines studied except spermine. The peak values were found a few days before the birth of the young. In spermidine excretion a second peak was observed one or two days after delivery. 3. Before and during the first 2 weeks of gestation on a molar basis putrescine excretion was the greatest one. During the last trimester histamine was excreted in the largest amount. 4. Under the influence of the diamine oxidase inhibitor aminoguanidine the general pattern of excretion of diamines and polyamines in pregnant rats remained essentially unchanged but the total amount excreted increased. Most conspicuous was the great elevation of urinary contents of putrescine and cadaverine.

Animals↗

Diamines and polyamines in DMBA-induced breast carcinoma containing mast cells resistant to compound 48/80.

In female rats, mammary carcinoma were induced by DMBA (7,12-dimethylbenz(alpha)anthracene) administration. The activities of histidine and ornithine decarboxylases and the concentrations of histamine, putrescine and polyamines were determined in tumour extracts and urine. In the tumour tissue, formation of histamine and putrescine took place at much higher rates than in normal mammary tissue. Administration of compound 48/80 in doses that mobilized about 70% of histamine contained in the ear failed to release histamine contained in the tumour; 48/80 also failed to produce histological signs of degranulation of the tumour mast cells. It thus appears that these cells are different from mast cells in most normal tissues, a distinction that calls for further study.

Animals↗