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Biomedical subjects

M Beckman

Publications and source records attributed to M Beckman.

At least 19 recordsLinked to original sources
PubMed2006

Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months.

BACKGROUND: The influence of the duration of anticoagulant therapy after venous thromboembolism (VTE) on the long-term morbidity and mortality is unclear. AIM: To investigate the long-term sequelae of VTE in patients randomized to different duration of secondary prophylaxis. METHODS: In a multicenter trial comparing secondary prophylaxis with vitamin K antagonists for 6 weeks or 6 months, we extended the originally planned 2 years follow-up to 10 years. The patients had annual visits and at the last visit clinical assessment of the post-thrombotic syndrome (PTS) was performed. Recurrent thromboembolism was adjudicated by a radiologist, blinded to treatment allocation. Causes of death were obtained from the Swedish Death Registry. RESULTS: Of the 897 patients randomized, 545 could be evaluated at the 10 years follow-up. The probability of developing severe PTS was 6% and any sign of PTS was seen in 56.3% of the evaluated patients. In multivariate analysis, old age and signs of impaired circulation at discharge from the hospital were independent risk factors at baseline for development of PTS after 10 years. Recurrent thromboembolism occurred in 29.1% of the patients with a higher rate among males, older patients, those with permanent triggering risk factor - especially with venous insufficiency at baseline - signs of impaired venous circulation at discharge, proximal deep vein thrombosis, or pulmonary embolism. Death occurred in 28.5%, which was a higher mortality than expected with a standardized incidence ratio (SIR) of 1.43 (95% CI 1.28-1.58), mainly because of a higher mortality than expected from cancer (SIR 1.83; 95% CI 1.44-2.23) or from myocardial infarction or stroke (SIR 1.28; 95% CI 1.00-1.56). The duration of anticoagulation did not have a statistically significant effect on any of the long-term outcomes. CONCLUSION: The morbidity and mortality during 10 years after the first episode of VTE is high and not reduced by extension of secondary prophylaxis from 6 weeks to 6 months. A strategy to reduce recurrence of VTE as well as mortality from arterial disease is needed.

Aged↗
PubMed2004

Degradation of GFP-labelled POM121, a non-invasive sensor of nuclear apoptosis, precedes clustering of nuclear pores and externalisation of phosphatidylserine.

The nuclear pore membrane protein POM121 is specifically degraded during apoptosis by a caspase-3-dependent process enabling early detection of apoptosis in living cells expressing POM121-GFP. Here we further investigated temporal aspects of apoptotic degradation of POM121-GFP. We demonstrate that decreased POM121-GFP fluorescence precedes annexin V-labelling of apoptotic cells. This indicates that degradation of the nuclear pore complex starts prior to redistribution of plasma membrane phosphatidylserine, which serves as a signal for phagocytotic elimination of apoptotic cells. Furthermore, a caspase-resistant GFP-labelled mutant of POM121 resisted degradation even in late apoptosis and was detected in clustered nuclear pores. Thus, it can be concluded that loss of POM121-GFP is a specific sensor of the activation of caspase-3-dependent proteolysis at the nuclear pores.

Animals↗
PubMed2003

Epidemiology of liver injuries.

BACKGROUND AND AIMS: The aim of this study was to investigate the epidemiology of liver injuries and to grade injuries according to the Organ Injury Scale in a population-based study in Stockholm County comprising 1.75 million inhabitants. MATERIAL AND METHODS: Cases were retrieved from the National Board of Forensic Medicine and Public Health and Medical Services Committee Register. Autopsy reports and patients files were studied for liver injuries, associated injuries, age, sex, trauma mechanism, location of the injury, description of the injury, diagnostic and treatment modalities when available. RESULTS: The incidence of traumatic liver injury in 1996 and 1997 was 2.95/100 000 annually. Seventy seven autopsies with liver injuries revealed injury pattern of grade I in 6 cases (8%), grade II in 10 cases (13%), grade III in 21 cases (27%), grade IV in 15 cases (19%), grade V in 16 cases (21%) and grade VI in 9 cases (12%). Twenty four patients revealed injury pattern of grade II in 13 cases (46%), grade III in 4 cases (14%), grade IV in 5 cases (18%) and grade V in 2 cases (7%). CONCLUSIONS: The results demonstrate a low incidence of liver injuries in the studied population. Grade II and III injuries prevail. Surgical management of liver injuries is an infrequent treatment option in Stockholm County and simple operative measures were applied. No complex hepatic injuries were operated upon.

Humans↗
PubMed2002

Modulation of nerve growth factor in peripheral organs by estrogen and progesterone.

Nerve growth factor (NGF) synthesized in peripheral organs plays a critical role in the development and maintenance of the nervous system and also participates in processing nociceptive stimuli. Previous studies suggest that reproductive hormones may regulate the expression of NGF. Ovariectomies were performed on female mice, and mice were killed 24 h after hormone replacement to evaluate the effects of estrogen and progesterone on NGF in peripheral organs, specifically the uterus, bladder, heart, and salivary gland. Sham-operated intact mice and untreated ovariectomized mice served as controls. Immunohistochemistry demonstrated the presence of NGF, estrogen receptor-alpha, estrogen receptor-beta, and progesterone receptors in these organs. Ovariectomy caused a significant decrease in NGF protein content in the uterus, and short term treatment of ovariectomized mice with estrogen and/or progesterone increased uterine NGF mRNA and restored NGF protein to concentrations similar to intact control mice. Ovariectomy did not affect NGF protein concentrations in the salivary gland, but treatment of ovariectomized mice with estrogen alone or in conjunction with progesterone stimulated concentrations of NGF protein that exceeded those observed in intact control or ovariectomized, untreated mice. NGF mRNA was increased in salivary glands from ovariectomized mice treated with progesterone alone or in combination with estrogen relative to other groups. NGF protein content of the hearts of ovariectomized mice treated with estrogen alone or in conjunction with progesterone was increased relative to intact controls and ovariectomized, untreated mice, but neither ovariectomy or hormone replacement affected NGF mRNA content in the heart. NGF protein content of the bladder was unaffected by ovariectomy or hormone treatment, and bladder NGF mRNA was unaffected by ovariectomy or hormone treatment. Collectively, these results indicate that reproductive hormones have the capacity to regulate NGF message and protein in a manner that varies among organs. Fluctuations in the expression of NGF, in conjunction with other factors, may help to explain gender differences in pain sensation and inflammatory response.

Animals↗
PubMed2001

Dieting dwarves live it up.

Two longevity pathways affect growth and metabolism in similar ways, and researchers have wondered for years whether the two routes coincide. A new study hints that these roads might not even lie on the same page of the atlas. Calorie restriction further extends the lives of mice already renowned for longevity due to a mutation in the Prop-1 gene. The results, reported in the 22 November issue of Nature, suggest that the two pathways don't overlap and indicate that researchers could travel a long way before they reach the maximum life-span of mice and perhaps humans.

Animals↗
PubMed2001

Intravesical Escherichia coli lipopolysaccharide stimulates an increase in bladder nerve growth factor.

OBJECTIVE: To investigate the effects of the intravesical instillation of Escherichia coli lipopolysaccharide (LPS) on nerve growth factor (NGF, which may mediate the pain associated with inflammation) protein and mRNA in the bladders of mice. MATERIALS AND METHODS: E. coli LPS was instilled into the bladders of female mice; the whole-bladder NGF content was then determined by an enzyme-linked immunosorbent assay and the NGF mRNA content of the bladder determined by semiquantitative reverse transcription-polymerase chain reaction. Bladder NGF was also evaluated by immunohistochemistry in some of the mice. RESULTS: LPS stimulated a significant increase in bladder NGF 90 min after instillation, but bladder NGF content was significantly less than that in bladders of control mice 3 and 7 h after LPS instillation. Twenty-four hours after the intravesical infusion of saline or LPS, there was no difference in NGF content in bladders from saline or LPS-infused mice. Immunohistochemistry confirmed the presence of increased NGF in the mucosa of detrusor from bladders 90 min after LPS instillation. Bladder NGF mRNA increased more slowly in response to LPS, and 7 and 24 h after LPS instillation the relative abundance of NGF mRNA was 1.5 and 2.0 times greater in LPS-infused bladders, respectively. CONCLUSIONS: E. coli LPS can stimulate increased NGF message and protein in the bladder. The increase in NGF protein preceded the increase in mRNA, suggesting that this increase was not the result of gene transcription. It is possible that NGF participates in the pathogenesis of pain associated with bacterial cystitis.

Administration, Intravesical↗
PubMed1998

Noninvasive monitoring of apoptosis versus necrosis in a neuroblastoma cell line expressing a nuclear pore protein tagged with the green fluorescent protein.

A fusion chimera between the integral nuclear pore membrane protein POM121 and GFP (green fluorescent protein) has been shown to correctly target to the nuclear pores when transiently expressed in a number of mammalian cell types. POM121-GFP is therefore an excellent marker for the noninvasive studies of the nuclear pores in living cells using fluorescence microscopy. We have established a line of neuroblastoma cells stably expressing the POM121-GFP fusion protein. We also monitored the nuclear envelope in living cells after induction of apoptosis or necrosis using 1 microM staurosporine or 100 microM p-benzoquinone, respectively. Interestingly, the POM121-GFP fluorescence was weaker or missing in the apoptotic cells. The disappearance of the nuclear pore marker accompanied apoptotic progression as judged by the degree of chromatin condensation and DNA fragmentation as analyzed by DNA staining and TUNEL assay, respectively. In contrast, the intensity of the nuclear rim fluorescence was unaffected in necrotic cells displaying an abnormal morphology with tilted nuclei. Thus, it was possible to distinguish between apoptotic and necrotic development in living cells using fluorescence microscopy. This cell line provides a fast and convenient model for screening suspected toxic xenobiotics.

Apoptosis↗
PubMed1997

Increased gene expression of beta-amyloid precursor protein and its homologues APLP1 and APLP2 in human neuroblastoma cells in response to retinoic acid.

beta-Amyloid precursor protein (APP) belongs to a family of homologous beta-amyloid precursor-like proteins (APLPs) including APLP1 and APLP2. Previously it has been shown that APP is subject to regulation by retinoic acid (RA). In this paper we show that APLP1 and APLP2 mRNA expression is upregulated during RA-induced differentiation of human SH-SY5Y neuroblastoma cells. The cells were treated with RA (10 microM) for 3 and 6 days and mRNA levels were analysed by a non-radioactive Northern blot assay. RA induced a 2- to 3-fold increase in the gene expression of both APLP2 and APP, whereas the increase in APLP1 mRNA expression was significantly higher. Our results support a role for APLPs during neuronal differentiation.

Amyloid beta-Protein Precursor↗
PubMed1995

Significant changes in neuropeptide concentrations in the brain of normotensive (WKY) and spontaneously hypertensive (SHR) rats following knee joint monoarthritis.

Changes induced by chronic monoarthritis in the nervous system was studied by measuring concentrations of substance P (SP)-, neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivities in the brain and in the knee joints of control and monoarthritic normotensive (WKY) and spontaneously hypertensive (SHR) rats on day 21 after the induction of monoarthritis. Knee joint monoarthritis was induced by intra-articular injection of Freund's adjuvant into the right knee joint. The severity of arthritis was examined by measuring knee volumes and scratching behaviour and by X-ray. The right knee of both WKY and SHR monoarthritic rats had an increased volume and osteoporosis. SHR rats had more severe arthritis and increased scratching behaviour compared to the WKY. Tachykinins were significantly decreased in the hypothalamus of arthritic rats. In the pituitary higher concentrations of tachykinins and CGRP were found in the arthritic and/or control SHR rats than in the WKY. In the occipital cortex, striatum and hippocampus NPY was increased in monoarthritic rats. No correlation was found between neuropeptide concentrations in the brain and knee joints. Decrease of tachykinins and increase of CGRP to different degree in the hypothalamus and/or pituitary of the arthritic WKY and SHR rats indicates that these changes were selectively associated with the basal level of sympathetic tone and possibly related to the greater severity seen in SHR rats. The increase of NPY in the brain, not influenced by sympathetic tone, may be part of a general defence reaction to inflammation.

Animals↗
PubMed1991

A simple nonisotopic in vitro bioassay for LT and TNF employing sodium fluoride-treated L-929 target cells that detects picogram quantities of LT and TNF and is as sensitive as TNF assays done with ELISA methodology.

We have developed a highly sensitive in vitro bioassay for lymphotoxin (LT) and tumor necrosis factor (TNF). This system employs a monolayer of 20,000 L-929 target cells in each well of 96-well microplates that are incubated in dilutions of LT and TNF at 37 degrees C for 20-24 h, after which the viability of the L-929 target cells is assessed by spectrophotometric techniques. We find that incorporation of 2 mM NaF increases the sensitivity of L-929 cells to lysis by 10(3)-10(4) x for LT and 10(4)-10(5) x for TNF. This method allows the regular detection of less than 1-5 pg of bioactive protein. ELISA assays did not detect synthetic TNF and TNF fragments that were not biologically active in this assay. The L-929 bioassay requires no isotopes, is very reproducible, is as sensitive as ELISA techniques, and detects only biologically active LT and TNF.

Animals↗
PubMed1991

Therapy of recurrent high-grade gliomas with surgery, autologous mitogen-activated IL-2-stimulated (MAK) killer lymphocytes, and rIL-2: II. Correlation of survival with MAK cell tumor necrosis factor production in vitro.

Seven patients with recurrent high-grade glioma were treated in a Phase I/II trial with surgical debulking, after which mitogen-activated IL-2-stimulated killer (MAK) lymphocytes and 10(5) units rIL-2 were implanted in the surgical defect. The therapy was well tolerated, and the mean survival of this group of patients was 29 weeks. Tumor necrosis factor (TNF) production by MAK lymphocytes stimulated with IL-2 in vitro was measured. A significant (r = .78, p = .04) correlation between survival of patients after therapy and the ability of the MAK lymphocytes to produce TNF in vitro was noted. A significant negative correlation (r = -.82, p = .02) was found when comparing TNF production and increasing tumor size measured on MRI. No correlation was found between TNF production in vitro and MAK lymphocytes lytic activity on K562 and U373 target cells. No correlation was found between survival and MAK cell lytic activity measured on K562 and U373 target cells. We conclude that TNF production in vitro and cytotoxic activity measured in vitro are measures of different antitumor activity in vivo and in vitro. TNF production during IL-2-stimulated proliferation may be an important in vitro assay in terms of predicting length of survival of recurrent high-grade gliomas.

Adult↗
PubMed1989

Rehabilitation of patellofemoral dysfunction in the athlete.

Patellofemoral dysfunction is a common but not yet well-managed condition affecting a large number of athletes. It is important to perform a thorough evaluation of these athletes including soft-tissue imbalances and faulty movement patterns. It is also important to develop a comprehensive treatment plan that addresses each abnormal component to return the athlete to his or her previous activity.

Athletic Injuries↗
PubMed1987

Brain metastases from ovarian cancer.

Brain metastasis from ovarian carcinoma is a relatively rare phenomenon. At NYU Medical Center five patients were treated for this entity from 1982 to 1985. The stage at presentation ranged from stage I to stage III, and all patients had received or were receiving chemotherapy. Two patients had active disease elsewhere at diagnosis of brain metastasis, but three patients were otherwise NED. Three patients had solitary cerebellar disease, and two patients had multiple lesions. All patients were treated with whole brain radiotherapy to 3,000 cGy, with neurological improvement in three of the five patients. The central nervous system may need special consideration for prophylactic treatment in those patients with ovarian cancer who receive adjuvant chemotherapy.

Adenocarcinoma↗
PubMed1987

Advanced ovarian cancer: three-year results of a 6-8 month, 2-drug cisplatin-containing regimen.

Fifty-two patients with advanced (stage III and IV) ovarian cancer were treated with a regimen of cisplatin (100 mg/m2 over 5 days) and cyclophosphamide (600 mg/m2/day 4). Treatment was repeated every 3-4 weeks for 6-8 months and followed by second look surgery. The median follow up for this single institution study (1980-1984) is 36 months. The median progression-free survival (projected) is 24 months and the median overall survival (projected) is 37 months in this group of patients with unfavorable pretreatment characteristics: median age: 61, median performance status (ECOG) 2, poorly-differentiated tumors: 60%, extensive residual tumors (greater than 2 cm): 65%. Pretreatment performance status was the only independent predictor for prolonged survival. Pathologically documented complete responses were observed in 23% of all patients and 43% of the patients who underwent second-look surgery (28 patients). Neurotoxicity from this regimen was substantial: it occurred in 65% of cases, was severe in 17% and was often not entirely reversible. The results with this intensive 2-drug cisplatin-containing regimen compare favorably to other more complex regimens in the literature. It is possible that the 'dose intensity' of cis-platinum may be the most important element of current therapeutic regimens in ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

Spectral and perceptual evidence for CV coarticulation in devoiced /si/ and /syu/ in Japanese.

We examined the spectral and perceptual characteristics of devoiced /si/ and /syu/ syllables in Japanese. Measurements showed that the deleted vowel can color the spectrum of the [integral of] in these syllables, although the mean influence is small. Perception tests showed that Japanese listeners can use this spectral coloring as a cue to the identity of the underlying vowel, although identification was substantially worse than in syllables where the /i/ or /u/ is maintained. These results suggest that a supposedly lower-level coarticulation between the fricative and the vowel can occur before a higher-level process deletes the vowel, contradicting the order implied by traditional accounts of speech as a translation of discrete phonological units.

Cues↗
PubMed1983

Essential hypertension--implications for pathogenesis from repeated haemodynamic investigations in young men with elevated blood pressure.

Repeated invasive haemodynamic studies were performed in young men (18-21 years) with elevated blood pressures and age and sex-matched normotensive controls before military service and five years later as a follow-up study. Patients with high blood pressure initially showed increased cardiac output and increased vascular resistance during maximal vasodilatation. The latter observation suggests arteriolar wall hypertrophy but was restricted to the subgroup of patients with low/normal cardiac output (normokinetic subgroup). In the follow-up study the cardiac output in patients with high blood pressure was no longer increased in comparison with controls and this normalization was restricted to patients previously showing the highest cardiac output (hyperkinetic subgroup). Contrary to the hypothesis this subgroup of patients had not developed significant signs of arteriolar wall hypertrophy although a tendency was present.

Adult↗
PubMed1981

Blood pressure and heart rate recordings at home and at the clinic. Evidence for increased cardiovascular reactivity in young men with mild blood pressure elevation.

In 41 apparently healthy men, aged 22-25 years, with mild blood pressure elevation (MBPE) and 19 age- and sex-matched normotensive controls (MC), blood pressure (BP) and heart rate (HR) readings at the clinic were compared to self-determined morning and afternoon values at home. The criteria for inclusion in the MBPE group were auscultatory BP less than 150 mmHg systolic and/or less than 90 mmHg diastolic at the military enlistment center from which the subjects were recruited, and systolic BP less than 140 mmHg on two subsequent occasions at the clinic. The BPs of the controls, who were mainly recruited from the same center, did not exceed 130/80 mmHg either at the enlistment center or at the clinic. The magnitude of the difference in systolic BP between home and clinic readings in the MBPE group (+15.3 mmHg) differed significantly from that in the NC group (+1.8 mmHg) (p less than 0.001). In both groups the systolic BP increased slightly but significantly during the day and was higher at home in the afternoon than in the morning. HR showed the same type of variation as BP in both groups with higher values at the clinic. The rise tended to be more pronounced (p less than 0.1) in patients with MBPE. Surprisingly, resting HR at home in the morning was significantly lower in the MBPE than in the NC group. Normokinetic and hyperkinetic subgroups of patients with MBPE did not differ from each other with respect to the variations in HR and BP studied.

Adult↗