PubMed Health⌕ Search

Biomedical subjects

J Pontén

Publications and source records attributed to J Pontén.

At least 19 recordsLinked to original sources
PubMed1996

Suppression of platelet-derived growth factor alpha- and beta-receptor mRNA levels in human fibroblasts by SV40 T/t antigen.

It is known that down-regulation of cell surface platelet-derived growth factor (PDGF) receptors accompanies transformation by SV40. In this work human embryonic lung fibroblasts were used as a model system to study the effects of SV 40 on PDGF receptor expression. It is shown that transformation by SV 40 early region leads to a total loss of PDGF alpha-receptor and partial loss of beta-receptor mRNA. Microinjection experiments revealed that receptor down-regulation was a primary effect, and not only secondary to transformation and clonal selection. Total loss of PDGF alpha-receptor expression requires both large T and small t, and down-regulation of the PDGF alpha-receptor occurs independently of p53 and Rb binding to large T.

Antigens, Polyomavirus Transforming↗
PubMed1995

The aetiology and pathogenesis of human breast cancer.

Whilst investigators have clearly shown that non-hereditary factors dominate the aetiology of human breast cancer, they have failed to identify quantitatively important causes, and prospects for prevention remain indeed limited. However, progress in epidemiological and basic research has taken place during the last few years. Current evidence suggests that breast cancer may be affected by the intra-uterine environment, that exposures during adolescence are particularly important, and that pregnancy has a dual effect on breast cancer risk: an early increase followed by long-term protection. Great variation exists in the structural development of the breast ductal system already in the newborn--and by inference in utero--and a pregnancy induces permanent structural changes in the mammary gland. We suggest that these observations fit into an aetiological model with the following key components: (1) breast cancer risk depends on the number of cells at risk, the susceptibility of individual cells to malignant transformation, and on the degree of cellular proliferation, notably cells which can act as founders of breast cancer; (2) the number of target cells is determined by the hormonal environment mainly early in life, perhaps already in utero; (3) in adult life, hormones which are non-genotoxic, increase breast cancer risk by increasing selective cell proliferation and thus number of target cells and the risk of retention of spontaneous somatic mutations; (4) while a pregnancy stimulates the growth of already malignant cells or cells close to malignant transformation (and thereby entails a short-term risk increase) the dominating long-term protection occurs due to permanent structural changes, terminal differentiation and perhaps decreased cell proliferation and carcinogen-binding in combination.

Adult↗
PubMed1995

Splanchnic and renal sympathetic activity in relation to hemodynamics during isoflurane administration in pigs.

The aim of the present study was to investigate the impact of isoflurane on regional neurogenic mechanisms in the control of vascular tone. Therefore, regional determinations of sympathetic activity and hemodynamics were made in chloralose-anesthetized swine before and during administration of 1.4% isoflurane. Sympathetic activity was examined from spillover of norepinephrine (NE) into the circulation using an isotope dilution technique. Administration of isoflurane caused a marked decrease in mesenteric (65 +/- 9 pmol.min-1.100 g-1; P < 0.05) NE spillover. Renal NE spillover was moderately decreased (25 +/- 6 pmol.min-1.100 g-1; P < 0.05), whereas liver NE spillover did not change significantly during isoflurane administration, suggesting that liver sympathetic activity is maintained at this level of isoflurane anesthesia. Total body NE spillover decreased (13 +/- 2 pmol.min-1.100 g-1, P < 0.05). Thus, isoflurane affected sympathetic outflow in a regionally differentiated pattern. Significant correlations were found between total body, mesenteric, and renal NE spillovers and vascular resistances, supporting the concept that the observed reductions in vascular resistances in these circulations during isoflurane administration were in part a consequence of reduced sympathetic outflow. In the liver circulation, no correlation was found between NE spillover and liver portal or liver arterial vascular resistances. Liver arterial resistance was significantly reduced during isoflurane administration while liver portal resistance was unchanged. Administration of isoflurane caused reductions in cardiac output, renal, portal, hepatic arterial, and total hepatic blood flows, whereas mesenteric blood flow was unchanged. To summarize, isoflurane decreased mesenteric and renal NE spillover with concomitant reductions in vascular resistances.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Ultraviolet light induces expression of p53 and p21 in human skin: effect of sunscreen and constitutive p21 expression in skin appendages.

It has been suggested that p53 plays an important role in skin carcinogenesis. The p21 molecule acts as a downstream effector of wild-type p53 by enacting cell cycle arrest. We studied p53 and p21 expression in sun-exposed skin. Healthy volunteers were exposed to ultraviolet irradiation (UVA + UVB) in normal, previously non-sun-exposed skin, and skin biopsies were taken. Immunohistochemically detectable p53 and p21 were quantified, and the pattern of distribution was recorded. p53 was induced in epidermal cells 4 h after irradiation and returned to nearly normal levels after 120 h. Suprabasal cells showed a peak at 4 h, whereas basal cells peaked later, at 48 h. In epidermis, the expression of p21 was induced with a pattern that mirrored that of p53. In addition, p21 was induced in mesenchymal cells of the upper dermis, where there was no p53, suggesting an alternative pathway for p21 induction. Topical sunscreen and pigmentation (skin type 5) nearly eliminated UV-induced expression of p53 and p21. In contrast to the complete absence of p53 in skin never exposed to UV radiation, p21 reactivity was found in sharply demarcated areas of anagen hair follicles and sebaceous glands, as well as in scattered epidermal cells. The prevalence and distribution suggest a physiologic role of p21 in stopping the cell cycle in terminally differentiating skin epithelium. Archival skin material from the vicinity of skin lesions with variable sun exposure were also stained for p53. There was an increased "disperse" reactive staining pattern in skin samples excised in the summer as compared with less sunny seasons. Intensely stained p53 foci were detected as "compact bands" in morphologically normal epidermis, predominantly in sun-exposed areas of the skin, suggesting the existence of clonal proliferation of p53 mutated keratinocytes. These data show that p53 and p21 play a role in the human skin response to UV exposure and that p21 is implicated in the homeostasis of differentiating skin appendages.

Adult↗
PubMed1995

Anesthetic modulation of the cardiovascular response to microlaryngoscopy. A comparison of propofol and methohexital with special reference to leg blood flow, catecholamines and recovery.

The modulating effects of propofol versus methohexital on the cardiovascular response to microlaryngoscopy were studied in 35 patients divided into four equal groups (one patient participated twice). Heart rate (HR), mean arterial blood pressure (MAP, cardiac output (CO; impedance cardiography), leg blood flow (LBF; occlusion plethysmography) and concentrations of arterial catecholamines were measured. After administration of atropine and fentanyl (2 micrograms.kg-1), anesthesia was induced by either an injection of propofol (2.0 mg.kg-1) followed by a low (6 mg.kg-1.h-1; n = 9) or a high (12 mg.kg-1.h-1; n = 9) dose propofol infusion or an injection of methohexital (1.5 mg.kg-1) followed by a low (5 mg.kg-1.h-1; n = 9) or a high (10 mg.kg-1.h-1; n = 9) dose methohexital infusion. The low methohexital infusion dose was insufficient to control MAP, which increased 41% during microlaryngoscopy compared to the awake state. The HR increased in all groups but the increase was most prominent in the low dose methohexital group. There were no statistically significant changes in CO in any group, whereas LBF increased consistently in all groups except in patients anesthetized with the low dose of methohexital. The increases of LBF in the propofol groups were intermediate and not dose dependent. The methohexital low dose group showed increases in norepinephrine levels compared to awake values and in epinephrine levels compared to the other groups. Propofol seems to differ from methohexital in modulation of peripheral vascular tone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Improved control of invasive cervical cancer in Sweden over six decades by earlier clinical detection and better treatment.

PURPOSE: Cancer of the cervix uteri can be controlled by cytologic screening for the detection of precursor lesions, but such intervention remains unrealistic in many countries in which this cancer is common. The possibility of reducing mortality by earlier clinical detection, followed by basic therapy, has never been properly assessed. PATIENTS AND METHODS: We compiled records of incident cases of invasive cancer of the cervix diagnosed in a defined area of Sweden from 1930 through 1990. In a cohort of 6,044 women, we analyzed temporal trends in incidence and survival by clinical stage and age at diagnosis. Generalized proportional hazards models were used to study several factors simultaneously and quantify the overall reduction in mortality. RESULTS: For each successive stage at diagnosis, the overall risk of dying increased 2.5-fold (95% confidence interval [CI], 2.4 to 2.7). From 1930, a marked improvement in stage distribution was accompanied by increasing survival rates in stages I and II disease. These changes largely took place before the introduction of screening and external-beam radiation. The 10-year relative survival rate increased from 33% in the 1930s to approximately 55% in the 1950s and thereafter. CONCLUSION: Improvements in public and professional awareness of cervical cancer resulted in diagnoses at earlier clinical stages. The rate of cure in early stages improved when basic local treatment was introduced, but only little of the progress was attributable to the introduction of more advanced treatment technologies. These findings offer considerable hope for a substantial reduction in the mortality of cervical cancer without cytologic screening, even in countries with limited resources.

Adult↗
PubMed1994

Survival trend after invasive cervical cancer diagnosis in Sweden before and after cytologic screening. 1960-1984.

BACKGROUND: Cytologic screening can reduce mortality from cervical cancer by detection and removal of premalignant lesions. Conceivably, mortality is further reduced because more women with invasive disease are diagnosed at an earlier, curable stage. This hypothesis can be assessed in Sweden, where population-based screening programs were introduced successively over about a decade starting in 1964. METHODS: Record linkages permitted complete follow-up through 1986 of all 17,377 patients with invasive cervical cancer diagnosed in Sweden from 1960 through 1984. We analyzed relative survival rates that describe the survival of patients after elimination of the effects of causes of death other than cancer of the cervix. RESULTS: Prognosis improved substantially in patients younger than age 50 years at diagnosis; from 1960-1964 to 1980-1984, the 5-year relative survival rate increased from 69.8% to 88.8% at age 20-29 years, from 71.7% to 85.5% at age 30-39 years, and from 68.6% to 77.9% at age 40-49 years. The excess mortality was thus reduced by more than half in patients diagnosed when younger than 40 years. In contrast, only slight or no improvement was noted in those diagnosed at older ages when screening was less extensive. In all time periods, a strong association was found between older age at diagnosis and poorer prognosis. CONCLUSION: Although alternative explanations for our findings must be seriously considered, the most obvious interpretation is that cytologic screening reduces mortality from cervical cancer by earlier diagnosis of invasive disease.

Adult↗
PubMed1994

Epidemiologic correlates of breast cancer laterality (Sweden).

Breast cancer laterality was studied in relation to age in 80,784 cases of invasive and 3,835 cases of pre-invasive breast cancer in women and 548 cases of invasive breast cancer in men reported to the Swedish Cancer Registry, 1970-89. In a subset of 11,274 women with invasive disease, data on parity were available through the Swedish Fertility Registry. Laterality also was evaluated in relation to age and reproductive variables in 3,986 cases from an international study from the 1960s. The overall incidence of pre-invasive and invasive cancer was higher in the left than in the right breast among both women and men. The excess incidence of invasive cancer in the left breast was evident only after the age of 45 years in women; a similar phenomenon may exist with pre-invasive disease in women and in men. The age-dependent laterality pattern did not appear to be confounded by menopausal status. Among women younger than 45 years, nulliparity, right handedness, and late age at menarche was associated with a somewhat higher incidence of cancer in the right breast. The laterality findings are likely to be due to factors operating early in the carcinogenic process, perhaps at the pre-initiation stage.

Adult↗
PubMed1994

Sympathetic muscle nerve activity, peripheral blood flows, and baroreceptor reflexes in humans during propofol anesthesia and surgery.

BACKGROUND: With percutaneous recordings of muscle nerve sympathetic activity (MSA), it is possible to study interactions between the autonomic nervous system and anesthetics. This study describes the effects of propofol infusion both before and during microlaryngoscopy. METHODS: Nine patients participated. MSA was recorded, muscle and skin blood flows were measured. Sodium nitroprusside-induced decreases in blood pressure were used to quantitate baroreceptor reflex sensitivity. RESULTS: During steady state propofol anesthesia (0.1 mg.kg-1.min-1), "total MSA" (MSA burst area per minute) was 37% (P < 0.05) of awake control value; leg blood flow recorded by strain-gauge plethysmography was 227% (difference not significant); and skin blood flow recorded by laser Doppler flowmetry and finger pulse plethysmography was 300% (P < 0.05) and 376% (P < 0.05) of respective awake control values. During microlaryngoscopy, when mean arterial blood pressure was controlled as close as possible to mean arterial blood pressure in the awake state by individually adjusted propofol infusion rates (average 0.33 mg.kg-1.min-1) MSA was restored to 93% of the activity before anesthesia, and leg blood flow increased further. Both cardiac and muscle sympathetic baroreflex sensitivities were depressed by propofol. During surgery the cardiac baroreflex sensitivity decreased further, whereas the muscle sympathetic baroreflex sensitivity was unchanged. CONCLUSIONS: Propofol is a potent inhibitor of sympathetic neuronal activity and decreases the sensitivity of the baroreflex. When used to control the pressor response during surgery, the vasodilatating effect of propofol overrides the neural vasoconstriction induced by surgery, and a further inhibition of the cardiac baroreflex is observed.

Adult↗
PubMed1994

Epithelial-stromal interactions in basal cell cancer: the PDGF system.

A proposed progenitor cell for basal cell carcinoma is a stem cell located in the bulge of the hair follicle. Previous investigations have shown that basal cell carcinoma has a specific stroma requirement for its growth. Likewise the development of a normal hair follicle requires the inductive force of a specialized structure with condensed mesenchyme that eventually forms the dermal hair papilla. Investigations in mouse embryos also strongly indicate that induction/growth of skin structures is dependent on platelet-derived growth factor (PDGF) alpha-receptor expression in the mesenchyme. We therefore investigated the expression of PDGF A and B chain and PDGF alpha and beta receptors in basal cell carcinoma and in normal skin by immunohistochemistry and in situ hybridization. alpha and beta receptors were found in the specific stroma components of basal cell carcinoma, dermal hair papilla, and sweat glands, but not in the epithelial structures. The A and B chains, on the other hand, were mainly found in basal cell carcinoma cells, in hair matrix, and in sweat gland epithelium. This "appositional" expression of PDGF/PDGF receptor closely resembles that found in epithelial/mesenchymal structures during normal development. The findings also suggest that PDGF receptor expression is one of the characteristics of the specific stroma that is necessary for basal cell carcinoma growth.

Capillaries↗
PubMed1994

Sequence-based analysis of the human p53 gene based on microdissection of tumor biopsy samples.

A procedure for direct sequencing of the human p53 gene based on micro-dissection of frozen tumor tissue stained with methylene blue without prior fixation is described. The approach, which is suitable for large-scale analysis, is based on solid-phase DNA sequencing of amplified genomic DNA and does not involve preparative electrophoresis, precipitations, extractions or centrifugations. Here we show that basal cell carcinoma tissue isolated from human skin can be analyzed in a semiautomated fashion using a robotic workstation and a laser fluorescent electrophoresis unit. The results of analyses of patient material displaying various immunohistochemical staining patterns using a p53-specific antibody are presented.

Base Sequence↗
PubMed1993

Detection of preinvasive cancer of the cervix and the subsequent reduction in invasive cancer.

BACKGROUND: Cytologic screening and follow-up can reduce the incidence of cervical cancer by detection and removal of precursor lesions. It is unknown, however, whether differences in histopathologic criteria for these precursor lesions affect the benefit of screening. These criteria may be difficult to study, but they are likely to be reflected in reported incidence of in situ cancer in small areas of Sweden. PURPOSE: Our purpose was to test the hypothesis that the benefit of screening can be predicted by histopathologic criteria as reflected in the reported incidence of cancer in situ. METHODS: Incidence data were from the Swedish National Cancer Registry. Regression models showing the relationship between in situ and invasive cancer were formulated and estimated. Each county (total, 24) was a unit of measurement, and adjustment was made for the incidence of invasive cancer before screening. RESULTS: During population-based screening in Sweden, the incidence of cancer in situ varied about fourfold among the 24 counties, which indicates that the criteria used to diagnose cancer in situ differed markedly. No statistically significant (P < .05) associations were found between the incidence of cancer in situ in 1965, 1970, or 1975 and the reduction in invasive cancer 5, 10, or 15 years later. According to the best-fitting model, detection of 100 extra cases of cancer in situ per 100,000 women per year in 1975 resulted in a reduction of 1.0 (95% confidence interval [CI] = -1.6-3.7) cases of invasive cancer 10 years later. The corresponding best model estimate implied a reduction of 4.6 cases (95% CI = 1.5-7.7) in a model restricted to cancer in situ in patients aged 20-50 years (when organized screening took place), invasive cancer in patients aged 30-60 years, and cancer in situ measured in 1970. CONCLUSIONS: The absent, or at most weak, association between detection of cancer in situ and subsequent reduction in invasive cancer indicates that relaxed histopathologic criteria for cancer in situ may result in extensive, unnecessary treatment of lesions that would regress spontaneously. IMPLICATION: Further studies are urgently needed to enable identification of neoplasms likely to progress to invasive, fatal disease.

Adult↗