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Biomedical subjects

F Peter

Publications and source records attributed to F Peter.

At least 19 recordsLinked to original sources

From bone biology to bone analysis.

Bone development is one of the key processes characterizing childhood and adolescence. Understanding this process is not only important for physicians treating pediatric bone disorders, but also for clinicians and researchers dealing with postmenopausal and senile osteoporosis. Bone densitometry has great potential to enhance our understanding of bone development. The usefulness of densitometry in children and adolescents would be increased if the physiological mechanisms and structural features of bone were given more consideration in the design and interpretation of densitometric studies. This review gives an overview on the most relevant techniques of quantitative noninvasive bone analysis. Furthermore it describes the relationship between bone biology, selected surrogates describing the biological processes and the possibilities of measuring these surrogates specifically and precisely by the different devices. The overall recommendation for researchers in this field is to describe firstly the biological process to be analyzed (bone growth in length, remodeling or modeling, or all together), secondly the bone parameter which describes this process, and thirdly the reason for selecting a special device.

Absorptiometry, Photon↗

Health equity and social justice.

There is consistent and strong empirical evidence for social inequalities in health, as a vast and growing literature shows. In recent years, these findings have helped to move health equity high on international research and policy agendas. This paper examines how the empirical identification of social inequalities in health relates to a normative judgment about health inequities and puts forward an approach which embeds the pursuit of health equity within the general pursuit of social justice. It defends an indirect approach to health equity, which views social inequalities in health as unjust in so far as they are the result of an unjust basic structure of society in Rawls' sense.

Health↗

Cardiopulmonary changes during laparoscopy and vessel injury: comparison of CO2 and helium in an animal model.

BACKGROUND: Injury of venous vessels during elevated intraperitoneal pressure is thought to cause possible fatal gas embolism, and helium may be dangerous because of its low solubility. METHODS: Twenty pigs underwent laparoscopy with either CO2 (n=10) or helium (n=10) with a pressure of 15 mm Hg and standardized laceration (1 cm) of the vena cava inferior. After 30 s, the vena cava was clamped, closed endoscopically by a running suture and unclamped again. During the procedure changes of cardiac output (CO), heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP), end tidal CO2 pressure (PETCO2), and arterial blood gas analyses (pH, pO2 and pCO2) were investigated. RESULTS: No animal died during the experimental course (mean blood loss during laceration: CO2, 157+/-50 ml; helium, 173+/-83 ml). MAP and CO values showed a decrease after laceration of the vena cava in both groups that had already been completely compensated for before suturing. PETCO2 increased significantly after CO2 insufflation (P<0.01), while helium showed no effect. Laceration of the vena cava caused no significant changes in PETCO2 values in either group. Significant acidosis and an increase of pCO2 were only found in the CO2 group. CONCLUSIONS: The incidence of gas embolism during laparoscopy and accidental vessel injury seems to be very low. With the exception of acidosis and an increase of PETCO2 in the CO2 group, there were no differences in cardiopulmonary function between insufflation of CO2 and helium.

Animals↗

Prognosis factors in carcinoma of the head of the pancreas.

BACKGROUND: Due to a low survival rate even after a R0 resection of cancer of the head of the pancreas, a strict indication for a pancreaticoduodenectomy seems to be sensible. We have therefore analyzed our patients for possible prognosis factors. METHODS: In a retrospective trial the courses of disease of all patients (1981-1996) with resected histologically proven carcinoma of the head of the pancreas were analyzed. The following patient-specific parameters were evaluated and examined in a single or multivariate analysis of prognosis factors: age, gender, tumor size (T status), lymph node involvement (N status), dimension of resection, operation method, time of operation, morbidity, clinic lethality and survival rate. RESULTS: Between 1981 and 1996, 500 patients with ductal adenocarcinoma of the head of the pancreas were treated surgically. The rate of resection increased from 32.1% (1981-1986) to 37.8% (1991-1996) whereas the mortality rate decreased from 13.3 to 7.3%. The 5-year survival rate after resection was 11.8% with a median survival time of 13.8 months. In a multivariate analysis, only small tumors (T1, p < 0.016), the R0 status (p < 0.017) and the resection had a significant influence on the survival rate. CONCLUSION: Prognosis factors in the treatment of pancreatic cancer were tumor size (T1), tumor resection and R0 status.

Adenocarcinoma↗

Laparoscopic aortofemoral bypass grafting: human cadaveric and initial clinical experiences.

PURPOSE: Postoperative complications are mainly related to the surgical trauma derived from the extensive abdominal incision and dissection after a conventional aortofemoral bypass grafting procedure. In an attempt to reduce postoperative complications, a concept of video-endoscopic vascular surgery on the infrarenal aortoiliac artery has been developed. On the basis of our experience with the practicability of video-endoscopic vascular surgery in the pelvic region in an animal study and in a pilot study of human cadavers, the purpose of this report was to describe three different methods that we evaluated on human cadavers and that we partly applied to patients. METHODS: In this experimental study, three different approaches were used to perform video-endoscopic aortofemoral bypass grafting. We performed an observational trial on human corpses (n = 24) with the transabdominal-retroperitoneal approach (TARA), the extraperitoneal approach (EPA), and the transabdominal left paracolic approach (TAPA). The EPA also was applied to patients with aortoiliac occlusive diseases. RESULTS: The TARA on cadavers (n = 4) soon was abandoned because it caused a burdensome sliding of the intestine into the operative field adjacent to the renal vessels, particularly in cases with obese subjects. In comparison, the TAPA (n = 6) with right-sided positioning of the patient retained the intestine in the right upper abdomen throughout the procedure. Until a surgeon actually is acquainted with the anatomic landmarks and the laparoscopic preparation technique, the EPA (n = 14) is a challenging procedure that necessitates thorough training. As with the TAPA, the EPA represents a procedure that reveals constant exposure of the operating field, even in cases with obese subjects. In the clinical observational study (n = 7), aortobifemoral bypass grafting was achieved totally laparoscopically with the EPA. The mean operating time was 6.5 hours and ranged from 3 to 10 hours. Blood transfusions were necessary after surgery in three patients (range, 1 to 3 red packed blood cells). One patient, who had had occlusion of the inferior mesenteric artery, died of ischemic colitis at postoperative day 10. The other patients had uneventful postoperative courses with minor wound discomfort. CONCLUSION: Laparoscopic vascular surgery seems to be a promising procedure to minimize postoperative complications. On the basis of our experience, we do not favor the TARA. Because it necessitates steep Trendelenburg positioning to displace intra-abdominal organs, the TARA is not an appropriate approach, particularly in obese and cardiopulmonary frail cases. Contrarily, the TAPA and the EPA deliver potentially better results in terms of exposing the operative field and thus reducing operating time and perioperative morbidity rates. A prospective cadaveric and clinical trial may be justified to further evaluate the use of these surgical techniques.

Aged↗

Alpha-SNAP but not gamma-SNAP is required for ER-Golgi transport after vesicle budding and the Rab1-requiring step but before the EGTA-sensitive step.

N-ethylmaleimide-sensitive factor (NSF) and soluble NSF attachment proteins (SNAPs) have been implicated in diverse vesicular transport events; yet their exact role and site of action remain to be established. Using an established in vitro system, we show that antibodies against alpha-SNAP inhibit vesicle transport from the ER to the cis-Golgi and that recombinant alpha-SNAP enhances/stimulates the process. Cytosol immunodepleted of alpha-SNAP does not support normal transport unless supplemented with recombinant alpha-SNAP but not gamma-SNAP. In marked contrast, cytosol immunodepleted of gamma-SNAP supports ER-Golgi transport to the normal level. Neither antibodies against gamma-SNAP nor recombinant gamma-SNAP have any effect on ER-Golgi transport. These results clearly establish an essential role for alpha-SNAP but not gamma-SNAP in ER-Golgi transport. When the transport assay is performed with cytosol immunodepleted of alpha-SNAP, followed by incubation with cytosol immunodepleted of a COPII subunit, normal transport is achieved. In marked contrast, no transport is detected when the assay is first performed with cytosol depleted of the COPII subunit followed by alpha-SNAP-depleted cytosol, suggesting that alpha-SNAP is required after a step that requires COPII (the budding step). In combination with cytosol immunodepleted of Rab1, it is seen that alpha-SNAP is required after a Rab1-requiring step. It has been shown previously that EGTA blocks ER-Golgi transport at a step after vesicle docking but before fusion and we show here that alpha-SNAP acts before the step that is blocked by EGTA. Our results suggest that alpha-SNAP may be involved in the pre-docking or docking but not the fusion process.

Antibodies↗

The mammalian protein (rbet1) homologous to yeast Bet1p is primarily associated with the pre-Golgi intermediate compartment and is involved in vesicular transport from the endoplasmic reticulum to the Golgi apparatus.

Yeast Bet1p participates in vesicular transport from the endoplasmic reticulum to the Golgi apparatus and functions as a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) associated with ER-derived vesicles. A mammalian protein (rbet1) homologous to Bet1p was recently identified, and it was concluded that rbet1 is associated with the Golgi apparatus based on the subcellular localization of transiently expressed epitope-tagged rbet1. In the present study using rabbit antibodies raised against the cytoplasmic domain of rbet1, we found that the majority of rbet1 is not associated with the Golgi apparatus as marked by the Golgi mannosidase II in normal rat kidney cells. Rather, rbet1 is predominantly associated with vesicular spotty structures that concentrate in the peri-Golgi region but are also present throughout the cytoplasm. These structures colocalize with the KDEL receptor and ERGIC-53, which are known to be enriched in the intermediate compartment. When the Golgi apparatus is fragmented by nocodazole treatment, a significant portion of rbet1 is not colocalized with structures marked by Golgi mannosidase II or the KDEL receptor. Association of rbet1 in cytoplasmic spotty structures is apparently not altered by preincubation of cells at 15 degrees C. However, upon warming up from 15 to 37 degrees C, rbet1 concentrates into the peri-Golgi region. Furthermore, rbet1 colocalizes with vesicular stomatitis virus G-protein en route from the ER to the Golgi. Antibodies against rbet1 inhibit in vitro transport of G-protein from the ER to the Golgi apparatus in a dose-dependent manner. This inhibition can be neutralized by preincubation of antibodies with recombinant rbet1. EGTA is known to inhibit ER-Golgi transport at a stage after vesicle docking but before the actual fusion event. Antibodies against rbet1 inhibit ER-Golgi transport only when they are added before the EGTA-sensitive stage. These results suggest that rbet1 may be involved in the docking process of ER-derived vesicles with the cis-Golgi membrane.

Amino Acid Sequence↗

A SNARE involved in protein transport through the Golgi apparatus.

In eukaryotic cells, the Golgi apparatus receives newly synthesized proteins from the endoplasmic reticulum (ER) and delivers them after covalent modification to their destination in the cell. These proteins move from the inside (cis) face to the plasma-membrane side (trans) of the Golgi, through a stack of cisternae, towards the trans-Golgi network (TGN), but very little is known about how proteins are moved through the Golgi compartments. In a model known as the maturation model, no special transport process was considered necessary, with protein movement along the Golgi being achieved by maturation of the cisternae. Alternatively, proteins could be transported by vesicles or membrane tubules. Although little is known about membrane-tubule-mediated transport, the molecular mechanism for vesicle-mediated transport is quite well understood, occurring through docking of SNAREs on the vesicle with those on the target membrane. We have now identified a protein of relative molecular mass 27K which is associated with the Golgi apparatus. The cytoplasmic domain of this protein or antibodies raised against it quantitatively inhibit transport in vitro from the ER to the trans-Golgi/TGN, acting at a stage between the cis/medial- and the trans-Golgi/TGN. This protein, which behaves like a SNARE and has been named GS27 (for Golgi SNARE of 27K), is identical to membrin, a protein implicated earlier in ER-to-Golgi transport. Our results suggest that protein movement from medial- to the trans-Golgi/TGN depends on SNARE-mediated vesicular transport.

Animals↗

[Reconstructive plastic surgery of thoracic wall defects].

Full-thickness defects of the thoracic wall following tumor resection, irradiation damage or secondary wound healing in thoracic surgery require early interdisciplinary cooperation to achieve patient-specific treatment modalities. Plastic surgical differential therapy allowing for sufficient soft tissue coverage, stabilisation of the thoracic wall and space filling in intrathoracic cavities, is presented and critically discussed.

Adult↗

The mammalian homolog of yeast Sec13p is enriched in the intermediate compartment and is essential for protein transport from the endoplasmic reticulum to the Golgi apparatus.

The role of COPII components in endoplasmic reticulum (ER)-Golgi transport, first identified in the yeast Saccharomyces cerevisiae, has yet to be fully characterized in higher eukaryotes. A human cDNA whose predicted amino acid sequence showed 70% similarity to the yeast Sec13p has previously been cloned. Antibodies raised against the human SEC13 protein (mSEC13) recognized a cellular protein of 35 kDa in both the soluble and membrane fractions. Like the yeast Sec13p, mSEC13 exist in the cytosol in both monomeric and higher-molecular-weight forms. Immunofluorescence microscopy localized mSEC13 to the characteristic spotty ER-Golgi intermediate compartment (ERGIC) in cells of all species examined, where it colocalized well with the KDEL receptor, an ERGIC marker, at 15 degrees C. Immunoelectron microscopy also localized mSEC13 to membrane structures close to the Golgi apparatus. mSEC13 is essential for ER-to-Golgi transport, since both the His6-tagged mSEC13 recombinant protein and the affinity-purified mSEC13 antibody inhibited the transport of restrictive temperature-arrested vesicular stomatitis virus G protein from the ER to the Golgi apparatus in a semi-intact cell assay. Moreover, cytosol immunodepleted of mSEC13 could no longer support ER-Golgi transport. Transport could be restored in a dose-dependent manner by a cytosol fraction enriched in the high-molecular-weight mSEC13 complex but not by a fraction enriched in either monomeric mSEC13 or recombinant mSEC13. As a putative component of the mammalian COPII complex, mSEC13 showed partially overlapping but mostly different properties in terms of localization, membrane recruitment, and dynamics compared to that of beta-COP, a component of the COPI complex.

Animals↗

Thyroid volume and urinary iodine in European schoolchildren: standardization of values for assessment of iodine deficiency.

Up to 1992, most European countries used to be moderately to severely iodine deficient. The present study aimed at evaluating possible changes in the status of iodine nutrition in 12 European countries during the past few years. Thyroid volume was measured by ultrasonography in 7599 schoolchildren aged 7-15 years in one to fifteen sites in The Netherlands. Belgium, Luxemburg, France, Germany, Austria, Italy, Poland, the Czech and Slovak Republics, Hungary and Romania. The concentrations of urinary iodine were measured in 5709 of them. A mobile unit (ThyroMobil van) equipped with a sonographic device and facilities for the collection of urine samples visited all sites in the 12 countries. All ultrasounds and all urinary iodine assays were performed by the same investigators. The status of iodine nutrition in schoolchildren has markedly improved in many European countries and is presently normal in The Netherlands, France and Slovakia. It remains unchanged in other countries such as Belgium. There is an inverse relationship between urinary iodine and thyroid volume in schoolchildren in Europe. Goiter occurs as soon as the urinary iodine is below a critical threshold of 10 micrograms/dl. Its prevalence is up to 10 to 40% in some remote European areas. This work produced updated recommendations for the normal volume of the thyroid measured by ultrasonography as a function of age, sex and body surface area in iodine-replete schoolchildren in Europe. This study proposes a method for a standardized evaluation of iodine nutrition on a continental basis, which could be used in other continents.

Adolescent↗

GS28, a 28-kilodalton Golgi SNARE that participates in ER-Golgi transport.

Little is known about the integral membrane proteins that participate in the early secretory pathway of mammalian cells. The complementary DNA encoding a 28-kilodalton protein (p28) of the cis-Golgi was cloned and sequenced. The protein was predicted to contain a central coiled-coil domain with a carboxyl-terminal membrane anchor. An in vitro assay for endoplasmic reticulum-Golgi transport was used to show that p28 participates in the docking and fusion stage of this transport event. Biochemical studies established that p28 is a core component of the Golgi SNAP receptor (SNARE) complex.

Amino Acid Sequence↗

Guanine nucleotide dissociation inhibitor is essential for Rab1 function in budding from the endoplasmic reticulum and transport through the Golgi stack.

The small GTPase Rab1 is required for vesicular traffic from the ER to the cis-Golgi compartment, and for transport between the cis and medial compartments of the Golgi stack. In the present study, we examine the role of guanine nucleotide dissociation inhibitor (GDI) in regulating the function of Rab1 in the transport of vesicular stomatitis virus glycoprotein (VSV-G) in vitro. Incubation in the presence of excess GDI rapidly (t1/2 < 30 s) extracted Rab1 from membranes, inhibiting vesicle budding from the ER and sequential transport between the cis-, medial-, and trans-Golgi cisternae. These results demonstrate a direct role for GDI in the recycling of Rab proteins. Analysis of rat liver cytosol by gel filtration revealed that a major pool of Rab1 fractionates with a molecular mass of approximately 80 kD in the form of a GDI-Rab1 complex. When the GDI-Rab1 complex was depleted from cytosol by use of a Rab1-specific antibody, VSV-G failed to exit the ER. However, supplementation of depleted cytosol with a GDI-Rab1 complex prepared in vitro from recombinant forms of Rab1 and GDI efficiently restored export from the ER, and transport through the Golgi stack. These results provide evidence that a cytosolic GDI-Rab1 complex is required for the formation of non-clathrin-coated vesicles mediating transport through the secretory pathway.

Animals↗

Beta-COP is essential for transport of protein from the endoplasmic reticulum to the Golgi in vitro.

Using a novel in vitro assay which allows us to distinguish vesicle budding from subsequent targeting and fusion steps, we provide the first biological evidence that beta-COP, a component of non-clathrin-coated vesicles believed to mediate intraGolgi transport, is essential for transport of protein from the ER to the cis-Golgi compartment. Incubation in the presence of beta-COP specific antibodies and F(ab) fragments prevents the exit of vesicular stomatitis virus glycoprotein (VSV-G) from the ER. These results demonstrate that beta-COP is required for the assembly of coat complexes mediating vesicle budding. Fractionation of rat liver cytosol revealed that a major biologically active form of beta-COP was found in a high molecular pool (> 1,000 kD) distinct from coatomer and which promoted efficient vesicle budding from the ER. Surprisingly, rab1B could be quantitatively coprecipitated with this beta-COP containing complex and was also essential for function. We suggest that beta-COP functions in an early step during vesicle formation and that rab1B may be recruited as a component of a precoat complex which participates in the export of protein from the ER via vesicular carriers.

Animals↗