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Biomedical subjects

M Luther

Publications and source records attributed to M Luther.

At least 55 records · Page 3Linked to original sources
PubMed1997

Arterial reconstruction to the foot arteries--a viable option?

OBJECTIVE: To analyse the outcome of arterial reconstruction to the foot arteries for chronic critical leg ischaemia. DESIGN: Retrospective study. SETTING: Regional hospital and academic referral centre in Finland. SUBJECTS: 99 patients who underwent 109 reconstructions to the foot arteries. MAIN OUTCOME MEASURES: Patency, leg salvage and survival. RESULTS: Autogenous vein was used for the reconstruction in 91%. Two year patency of femoropedal and popliteopedal vein bypasses were 60% and 72% with similar rates of leg salvage. Prosthetic bypass had a low patency rate (20% at 2 years). Age, sex, diabetes and the condition of the outflow artery did not influence outcome. Survival of patients at 1, 2 and 3 years was 80%, 69% and 54%, respectively. CONCLUSIONS: Reconstructions to the foot arteries are demanding and have high immediate failure rates. If autogenous vein is used acceptable patency and leg salvage rates can be achieved. In old patients this may be enough to preserve mobility for the rest of their lives.

Aged↗
PubMed1996

A mechanism of adaptation to hypergravity in the statocyst of Aplysia californica.

The gravity-sensing organ of Aplysia californica consists of bilaterally paired statocysts containing statoconia, which are granules composed of calcium carbonate crystals in an organic matrix. In early embryonic development, Aplysia contain a single granule called a statolith, and as the animal matures, statoconia production takes place. The objective of this study was to determine the effect of hypergravity on statoconia production and homeostasis and explore a possible physiologic mechanism for regulating this process. Embryonic Aplysia were exposed to normogravity or 3 x g or 5.7 x g and each day samples were analyzed for changes in statocyst, statolith, and body dimensions until they hatched. In addition, early metamorphosed Aplysia (developmental stages 7-10) were exposed to hypergravity (2 x g) for 3 weeks, and statoconia number and statocyst and statoconia volumes were determined. We also determined the effects of hypergravity on statoconia production and homeostasis in statocysts isolated from developmental stage 10 Aplysia. Since prior studies demonstrated that urease was important in the regulation of statocyst pH and statoconia formation, we also evaluated the effect of hypergravity on urease activity. The results show that hypergravity decreased statolith and body diameter in embryonic Aplysia in a magnitude-dependent fashion. In early metamorphosed Aplysia, hypergravity decreased statoconia number and volume. Similarly, there was an inhibition of statoconia production and a decrease in statoconia volume in isolated statocysts exposed to hypergravity in culture. Urease activity in statocysts decreased after exposure to hypergravity and was correlated with the decrease in statoconia production observed. In short, there was a decrease in statoconia production with exposure to hypergravity both in vivo and in vitro and a decrease in urease activity. It is concluded that exposure to hypergravity downregulates urease activity, resulting in a significant decrease in the formation of statoconia.

Analysis of Variance↗
PubMed1996

Phosphorylation of a cAMP-specific phosphodiesterase (HSPDE4B2B) by mitogen-activated protein kinase.

A cAMP-specific phosphodiesterase, HSPDE4B2B, was found to be phosphorylated when expressed in Sf9 cells or yeast. Deletion of amino acids 81-151 and 529-564 had no effect on the phosphorylation of HSPDE4B2B. Mass spectrometric analysis of purified HSPDE4B2B(1-564). HSPDE4B2B(81-564) and HSPDE4B2B(152-528) showed that phosphorylation occurred predominantly on Ser487 and Ser489. The stoicheiometry of phosphorylation was 1.2:1 (Ser487:Ser487, 489). There was no evidence by MS for a non-phosphorylated form of HSPDE4B2B(81-564) or HSPDE4B2B(152-528) when expressed in Sf9 cells. There was no detectable phosphorylation of purified HSPDE4B2B(152-528) expressed in Escherichia coli. Radiolabelling experiments with 32P revealed that phosphorylation of HSPDE4B2B(152-528) expressed in Sf9 cells was abolished when Ser487 and Ser489 were mutated to alanines. Analysis of the amino acid sequence revealed that Ser487 and Ser489 of HSPDE4B2B conform to the consensus motifs for phosphorylation by mitogen-activated protein kinase (MAP kinase) and casein kinase II respectively. Kinetic experiments in vitro showed that MAP kinase-phosphorylated E.coli expressed and purified HSPDE4B2B(151-528) with a K(m) of 63 microM and a Vmax of 3.0 mumol/min per mg. In comparison, MAP kinase phosphorylated myelin basic protein with a Km of 26.0 microM and a Vmax of 5.5 mumol/min per mg under the same conditions. Using MS and mutational analysis we found that MAP kinase-phosphorylated E. coli expressed HSPDE4B2B(152-528) exclusively at Ser487. These results suggest that phosphodiesterases could contribute to the cross-talk between the cAMP and MAP kinase signalling pathways.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1996

Amputation rates as a measure of vascular surgical results.

Reconstructive surgery for critical leg ischaemia (CLI) increased in both hospital- and population-based patient samples over 12 years. In the referral centre amputation numbers were unchanged over this period, although amputation carried out for patients with CLI decreased from 58 to 35 per cent. In the population sample amputation numbers decreased by 25 per cent and amputations of patients with CLI decreased from 79 to 43 per cent. Patient characteristics and amputation patterns were different in the two settings. Amputation rates as a measure of the efficacy of an arterial reconstruction policy should be used only on a population basis. The analysis is skewed by selection bias in referral centres.

Aged↗
PubMed1996

Frequency of repeated vascular surgery. A survey of 7616 surgical and endovascular Finnvasc procedures. Finnvasc Study Group.

OBJECTIVE: To assess the incidence of repeated vascular surgical operations. DESIGN: A population-based cross-sectional survey established on the Finnvasc registry. SETTING: Multicentre, Finland. MATERIAL: 7616 vascular procedures consisted of 5201 open vascular operations and 2415 endovascular interventions done during the two years 1991-92. MAIN OUTCOME MEASURES: Mortality and number of reoperations and major amputations. RESULTS: A total of 5409 initial vascular procedures were done, 770 patients (10%) underwent a new procedure in the same anatomical segment as previously, and 1437 patients (19%) underwent a vascular or endovascular procedure on a new arterial segment excluding the coronary arteries; these patients had more risk factors than the two other groups, and were also treated more often for chronic leg ischaemia. Altogether 586 reoperations were needed in 487 patients (6%) during a 30-day postoperative period, more often after the initial surgical reconstruction than on other occasions. Altogether 126 postoperative below-knee and 170 above-knee amputations had to be done during the same period which corresponded to 14% of the total of 2128 surgical or endovascular revascularisations done for acute or chronic critical leg ischaemia. The risk of perioperative death was higher in patients with acute leg ischaemia undergoing their first vascular intervention than those having repeat operations. CONCLUSION: Although the present data are cross-sectional and might be affected by the recent increase in vascular surgery in Finland they show that almost a third of vascular operations done are repeat procedures.

Aged↗
PubMed1996

Femoropopliteal reconstructions--influence of risk factors on outcome.

The influence of risk factors on the outcome of femoro-popliteal reconstructions was analysed in a retrospective study of 207 patients undergoing 218 reconstructions to the popliteal artery in a regional hospital and in an academic referral centre. Increasing severity of preoperative ischaemia was associated with decreasing leg salvage and survival rates. The patients' sex, age and diabetes did not influence patency or leg salvage. Diabetes was associated with a decreased survival. An integrated outcome analysis combining patency, leg salvage and survival data was carried out. Although when separately analysed, patency, leg salvage and survival were similar in critical leg ischaemia (CLI) patients less than 70 and over 70 years of age, the combined analysis showed a difference in outcome with fewer patients alive with a functioning graft and leg in the older age group. However, the percentage achieving leg salvage up to three years or until death was similar. It is suggested that a combined analysis of patency, leg salvage and survival could be used to give useful additional information on the outcome after vascular reconstructions for CLI.

Aged↗
PubMed1995

Antifungal combination therapy with granulocyte colony-stimulating factor and fluconazole in experimental disseminated candidiasis.

The present studies were performed to determine whether any beneficial interaction results from combination therapy with recombinant human granulocyte colony-stimulating factor (GCSF) and fluconazole in disseminated candidiasis in mice. Fluconazole extended survival and reduced tissue counts. GCSF had no direct benefit, but GCSF combined with fluconazole extended survival beyond that for fluconazole alone and reduced renal tissue counts below those for fluconazole alone. Thus, GCSF and fluconazole may be a useful combined therapy for disseminated candidiasis.

Animals↗
PubMed1995

Acute leg ischaemia--a case for the junior surgeon?

OBJECTIVE: To evaluate the change in the type of acute leg ischaemia and the outcome of its treatment in relation to the experience of the surgeon responsible for the treatment. DESIGN: A 12-year (1980-1991) retrospective study based on hospital records and population vital statistics. SETTING: A defined population of 165,000 served by one central hospital (CH) and two district hospitals (DH). SUBJECTS: 282 interventions performed for acute leg ischaemia. MAIN OUTCOME MEASURES: Type of leg ischaemia, reintervention, amputation and survival rates in relation to the type of ischaemia, treatment and surgical expertise. RESULTS: Thrombotic acute ischaemia increased by 91% and graft occlusions by 130% while embolisation numbers remained unchanged during the period. With junior, general and vascular surgeons operating on acute ischaemia, the respective 30-day amputation rates were 25%, 18% and 9%. Postoperative mortality was 29%, 33% and 8% respectively. The reconstruction rate for the vascular surgeon was 67% with 33% thrombectomies, while the figures for junior surgeons were 2% and 98% and for senior surgeons 6% and 94%. CONCLUSION: Mortality and amputation rates in acute ischaemia are high. By judicious use of different treatment modalities, as judged by vascular surgical experience, better limb salvage rates may be achieved especially in patients with acute on chronic ischaemia.

Acute Disease↗
PubMed1994

Agouti protein is an antagonist of the melanocyte-stimulating-hormone receptor.

The genetic loci agouti and extension control the relative amounts of eumelanin (brown-black) and phaeomelanin (yellow-red) pigments in mammals: extension encodes the receptor for melanocyte-stimulating hormone (MSH) and agouti encodes a novel 131-amino-acid protein containing a signal sequence. Agouti, which is produced in the hair follicle, acts on follicular melanocytes to inhibit alpha-MSH-induced eumelanin production, resulting in the subterminal band of phaeomelanin often visible in mammalian fur. Here we use partially purified agouti protein to demonstrate that agouti is a high-affinity antagonist of the MSH receptor and blocks alpha-MSH stimulation of adenylyl cyclase, the effector through which alpha-MSH induces eumelanin synthesis. Agouti was also found to be an antagonist of the melanocortin-4 receptor, a related MSH-binding receptor. Consequently, the obesity caused by ectopic expression of agouti in the lethal yellow (Ay) mouse may be due to the inhibition of melanocortin receptor(s) outside the hair follicle.

Adenylyl Cyclases↗
PubMed1994

The chemokines IL-8, monocyte chemoattractant protein-1, and I-309 are monomers at physiologically relevant concentrations.

The chemokines are a family of immune mediators involved in a wide range of inflammatory processes, most importantly as chemoattractants of monocytes, neutrophils, lymphocytes, and fibroblasts to sites of inflammation. Nuclear magnetic resonance and x-ray crystallographic studies have shown that IL-8 and macrophage-inflammatory protein-1 beta (MIP-1 beta) form noncovalent dimers and that platelet factor-4 (PF-4) forms noncovalent dimers and tetramers, leading to the assumption that, as a family, the chemokines would form multimeric structures. In this study, we analyze the association states of the chemokines IL-8, monocyte chemoattractant protein-1 (MCP-1), and I-309, by using a combination of size exclusion HPLC, sedimentation equilibrium ultracentrifugation, and chemical cross-linking. We find that the association states of MCP-1 and IL-8 are characterized by an equilibrium between monomers and dimers: although dimers predominate at concentrations above 100 microM, these chemokines are almost exclusively monomeric at the nanomolar concentrations at which they display maximal chemotactic activity. I-309, by contrast, remains a monomer at all concentrations tested. I-309 contains two additional cysteine residues (C26 and C68) that are not found in any other members of the chemokine family. We used cyanogen bromide and trypsin digestion strategies to demonstrate that these two residues are linked in a unique intramolecular disulfide bond. Furthermore, by using site-directed mutagenesis, we show that the integrity of this bond is crucial for protein secretion.

Amino Acid Sequence↗
PubMed1994

Involvement of pp60c-src with two major signaling pathways in human breast cancer.

The phosphotyrosine residues of receptor tyrosine kinases serve as unique binding sites for proteins involved in intracellular signaling, which contain SRC homology 2 (SH2) domains. Since overexpression or activation of the pp60c-src kinase has been reported in a number of human tumors, including primary human breast carcinomas, we examined the interactions of the SH2 and SH3 domains of human SRC with target proteins in human carcinoma cell lines. Glutathione S-transferase fusion proteins containing either the SH2, SH3, or the entire SH3/SH2 region of human SRC were used to affinity purify tyrosine-phosphorylated proteins from human breast carcinoma cell lines. We show here that in human breast carcinoma cell lines, the SRC SH2 domain binds to activated epidermal growth factor receptor (EGFR) and p185HER2/neu. SRC SH2 binding to EGFR was also observed in a nontumorigenic cell line after hormone stimulation. Endogenous pp60c-src was found to tightly associate with tyrosine-phosphorylated EGFR. Association of the SRC SH2 with the EGFR was blocked by tyrosyl phosphopeptides containing the sequences surrounding tyrosine-530, the regulatory site in the SRC C terminus, or sequences surrounding the major sites of autophosphorylation in the EGFR. These results raise the possibility that association of pp60c-src with these receptor tyrosine kinases is an integral part of the signaling events mediated by these receptors and may contribute to malignant transformation.

Amino Acid Sequence↗
PubMed1994

Introduction of a population-based vascular registry: validity of data and limitations of registration. The Finnvasc Study Group.

A study was performed to assess the validity of the data in a nationwide vascular registry, Finnvasc, initiated in 1991. Data recorded during the first year were of 3507 procedures (immediate reoperations were excluded); 2436 (69 per cent) were surgical and 1071 (31 per cent) endovascular in nature. The Finnvasc data were compared with 2325 hospital records and re-registration of a random sample of 233 patients treated during October 1991 in nine centres was also carried out. In all, 21 per cent of patients from hospitals participating in Finnvasc were not registered and so it was calculated that about 4500 vascular procedures, 3125 surgical and 1375 endovascular, were performed in Finland in 1991. This represents an average of 900,625 and 275 procedures per million population per year respectively. The non-registration rate in October was 17 per cent. Apart from operation classification, and function and patency at 1 month, all simple binary and code data at re-registration were in agreement in at least 92 per cent of cases; checklist and numerical data did not show such good conformity. During the first year of the registry many data were either missing or inadequately recorded, emphasizing the need for cross-validation and re-registration of a random sample of cases. Furthermore, the non-uniformity of coding between hospital records and the Finnvasc registry illustrated deficiencies in the current coding system.

Finland↗
PubMed1994

Intraoperative cardiac output monitoring: comparison of impedance cardiography and thermodilution.

Impedance cardiography (IC) is a noninvasive, simple to use method of cardiac output (CO) determination. A prospective evaluation of IC monitoring was performed in 50 patients undergoing noncardiac surgery. IC CO measurements (NC-COM3-Revision 7, BoMed Manufacturing) were compared to simultaneous measurements of thermodilution (TD) CO to assess the validity of this technique for intraoperative cardiac monitoring. Adequate impedance signals could not be obtained in 7 of the 50 patients. IC CO measurements were highly correlated to TD CO (P < .005), with a correlation coefficient r = 0.84. Bias analysis, however, indicated clinically significant disagreement between the two techniques. IC CO tended to underestimate TD CO (mean bias = -0.41 L/min) and the SD of the bias was 1.0 L/min (95% level of agreement 1.6 to -2.4 L/min). Trending data showed IC to accurately track the direction of TD CO changes but to underestimate their magnitude (r = 0.60, intercept -0.7 L/min, slope 0.47). Factors that may have impaired the performance of IC in this study include the high prevalence of cardiac disease in the study population and electrical noise in the operative setting. Further development of IC appears warranted if it is to prove useful as an intraoperative cardiac monitor.

Aged↗
PubMed1994

The influence of arterial reconstructive surgery on the outcome of critical leg ischaemia.

OBJECTIVES: To analyse the effect of an aggressive vascular reconstruction policy on the outcome of critical leg ischaemia in a defined population. DESIGN: A retrospective survey of surgical in-hospital patient data related to population data in the study region over 22 years (1970-1991). SETTING: Vasa Central Hospital district in Western Finland. The area is served by one Central Hospital and two District Hospitals. MATERIALS: The population of 165,000 at the beginning of the study and 178,000 at the end of the study needing 977 interventions for chronic critical leg ischemia (CLI), 397 for acute ischaemia and 313 for noncritical leg ischemia. CHIEF OUTCOME MEASURES: Total and age-group related major amputation rates, mortality, rates of arterial interventions, limb salvage rate. MAIN RESULTS: The population > 65 years of age increased by 50% from 1970 to 1991. Major amputation rates increased 2.5 times from 1970 to 1981. The mean age at amputation increased from 71 to 78 years and at reconstruction from 68 to 74 years. The increase in numbers of reconstructions for CLI by 100% from 1980 onwards was associated with a reduction in amputation rate by 60% from 1983 to 1991. The 1- and 5-year survival rate after amputation was 55 and 20% and after reconstruction 83 and 45%. After reconstruction 1-, 3- and 5-year limb salvage rates were 83, 78 and 77% and limb salvage until death was 74%. CONCLUSIONS: With an aggressive reconstruction policy in CLI it is possible to reduce amputation rates with a reasonable mortality and morbidity even in patients in the 8th and 9th decade of life.

Aged↗
PubMed1994

Effects of hydrocortisone on pulsatile pituitary glycoprotein secretion.

During states of stress, hypothalamic-pituitary-thyroid and hypothalamic-pituitary-gonadal function can be suppressed. One putative mediator of this stress response may be glucocorticoids, which have widespread effects on thyroid and gonadal function. To characterize dynamic pituitary glycoprotein secretion during glucocorticoid administration, 24-h TSH, LH, FSH, and alpha-subunit pulses were measured in 10 healthy young subjects on 3 occasions: 1) at baseline, 2) during infusions of 100 mg hydrocortisone (HC) over 24 h, and 3) during infusions of 300 mg HC over 24 h. These HC infusions led to serum cortisol levels similar to the endogenous cortisol levels seen in moderate and severe stress. Both HC infusions had profound rapid effects on TSH levels, decreasing TSH pulse amplitude by 60% and abolishing the nocturnal TSH surge. However, TSH pulse frequency was unaltered. In contrast, HC infusions did not change mean or pulsatile LH, FSH, or alpha-subunit secretion. These results suggest that stress levels of cortisol acutely suppress TSH secretion at the pituitary level, with little effect on the TSH pulse generator. On the other hand, the effects of stress and/or hypercortisolism on the gonadal axis may require higher cortisol levels, more prolonged exposure, or other mediators of the stress response.

Adult↗
PubMed1994

Transtracheal Doppler cardiac output monitoring: comparison to thermodilution during noncardiac surgery.

The validity of transtracheal Doppler (TTD) cardiac output (CO) monitoring during noncardiac surgery has not been established. A prospective evaluation was undertaken in 30 patients undergoing noncardiac surgery to assess the agreement between TTD and thermodilution measurements of CO. Linear regression, Bland-Altman analysis, and receiver operator characteristic (ROC) techniques were employed to evaluate the accuracy, reliability, and trending capability of TTD monitoring. A total of 250 simultaneous TTD and thermodilution CO values were compared. TTD and thermodilution CO measurements were highly correlated (P < 0.005, r = 0.84) and Bland-Altman analysis revealed a small systematic underestimation of thermodilution CO (mean bias = -0.25 L/min) with a SD of the bias of 0.88 L/min and a mean percent error of 12.4%. TTD performed particularly well in patients in whom the Doppler signal was stable throughout surgery and required minimal manipulation. In these patients, linear regression yielded the relation TTD CO = 0.96 thermodilution CO + 0.15 with a correlation coefficient r = 0.92. Mean percent error was 10.0% with a mean bias of -0.02 L/min and a SD of the bias of 0.58 L/min. The ability of TTD to track directional changes in thermodilution CO was evaluated by regression analysis and a ROC plot. Changes in TTD CO were highly correlated to changes in thermodilution CO (r = 0.81). ROC plots showed that changes in TTD CO reliably identified large (greater than 15%) changes in thermodilution CO with a sensitivity of 92% and a specificity of 87%. Clinical experience with the TTD device is needed to obtain accurate measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Pulsatile TSH secretion during 48-hour continuous TRH infusions.

Thyroid-stimulating hormone (TSH), like other anterior pituitary hormones, is normally secreted in a series of pulses over 24 h. However, the factors that control TSH pulse generation are unknown. We investigated the potential role of thyrotropin-releasing hormone (TRH) in TSH pulse generation by measuring TSH pulses during constant TRH infusions. Two groups of subjects were studied: five healthy subjects and five subjects with treated primary hypothyroidism and normal TSH levels. Each subject underwent four separate studies: (1) TSH levels were measured every 15 min over 24 h (baseline study). (2) TSH levels were measured every 15 min over 48 h during TRH infusions at 0.1 microgram/min (low dose TRH study). (3) TSH levels were measured every 15 min over 48 h during TRH infusion at 0.5 microgram/min (medium dose TRH study). (4) TSH levels were measured every 15 min over 48 h during TRH infusions at 1.0 microgram/min (high dose TRH study). TSH pulses were located by cluster analysis. We found that constant TRH infusions at any of the doses utilized did not alter TSH pulse frequency in normal or treated hypothyroid subjects, although pulse amplitude increased. Normal subjects had lower TSH pulse amplitude than treated hypothyroid subjects at all TRH doses, perhaps due to slightly higher serum T3 levels. This suggests that, at least acutely, pulsatile input of TRH to the pituitary gland does not determine pulsatile TSH release. However, TRH may modulate TSH pulse amplitude.

Adult↗