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G Kunz

Publications and source records attributed to G Kunz.

At least 37 records · Page 2Linked to original sources

Identification of 19 protein S gene mutations in patients with phenotypic protein S deficiency and thrombosis. Protein S Study Group.

Protein S is a protein C-dependent and independent inhibitor of the coagulation cascade. Deficiency of protein S is an established risk factor for venous thromboembolism. We have used a strategy of specific amplification of the coding regions and intron/exon boundaries of the active protein S gene (PROS1) and direct single-strand solid phase sequencing, to seek mutations in 35 individuals with phenotypic protein S deficiency. Nineteen point mutations (16 novel) in 19 probands (or relatives of probands) with venous thromboembolism are reported here. Fifteen of the 19 mutations were expected to be causal and included 10 missense mutations (Lys9Glu, Glu26Ala, Gly54Glu, Cys145Tyr, Cys200Ser, Ser283Pro, Gly340Asp, Cys408Ser, Ser460Pro, and Cys625Arg). Three of the 15 mutations resulted in premature stop codons (delete T 635 producing a stop codon at position 126, Lys368stop and Tyr595stop) and two were at intron/exon boundaries (+1 G to A in intron d and +3 A to C in intron j). Of the remaining four mutations, three were within intronic sequence and one was a silent mutation within the coding region and did not alter amino acid composition. In two of the 10 missense mutations, reduced plasma protein S activity compared with antigen level suggested the presence of variant (type II) protein S.

Alleles↗

Molecular genetics of antithrombin deficiency.

Antithrombin is the major proteinase inhibitor of thrombin and other blood coagulation proteinases. Antithrombin has two functional domains, a heparin binding site and a reactive centre (that complexes and inactivates the proteinase). Its deficiency results in an increased risk of venous thromboembolism. Appreciable progress has been made in recent years in understanding the structure and function of this protein, the genetic cause of inherited deficiency and its clinical consequence. The structure of antithrombin is now considered in terms of the models derived from X-ray crystallography, which have provided explanations for the function of its heparin interaction site and of its reactive loop. The structural organization of the antithrombin gene has been defined and numerous mutations have been identified that are responsible for antithrombin deficiency: these may reduce the level of the protein (Type I deficiency), alter the function of the protein (Type II deficiency, altering heparin binding or reactive sites), or even have multiple or 'pleiotropic effects' (Type II deficiency, altering both functional domains and the level of protein).

Antithrombin III↗

[Comparison of laparoscopically assisted vaginal hysterectomy with abdominal hysterectomy. Technique and results].

Technique and Results: The aim of this prospective randomised study was to compare laparoscopy-assisted vaginal hysterectomy (LAVH, group A) with abdominal hysterectomy (abd. HE, group B). Therefore, 35 hysterectomies due to non-malignant diseases such as uterine fibroma were performed in each group. A rather simple technique of LAVH was developed. In respect of the indication for hysterectomy, mean duration of operation and the size of the excised uteri there were no statistical differences between the two groups. One severe complication of haemorrhage was observed after LAVH in a patient suffering from a coagulopathy. The requirements for analgesics were significantly lower after LAVH compared to abd. HE during the postoperative period. A significantly lower serum concentration of the c-reactive protein on the first and third days after operation was found in group A. The patients of group A were discharged on the average 5 days after operation and 11 days in group B, respectively. Hence LAVH should replace abd. HE in most cases with the advantages of shorter hospitalisation, minimised requirements for analgesics and cost reduction.

Adult↗

The dynamics of rapid sperm transport through the female genital tract: evidence from vaginal sonography of uterine peristalsis and hysterosalpingoscintigraphy.

Vaginal ultrasonography of uterine peristalsis during the follicular phase of the menstrual cycle demonstrates an increasing frequency and intensity of subendometrial and myometrial peristaltic waves as the follicular phase progresses. During this time the numbers of contraction waves with a fundo-cervical direction decrease considerably in favour of waves of contraction with a cervico-fundal direction. There is evidence that rapid sperm transport through the female genital tract is passive and is provided by these uterine contractions. Using hysterosalpingoscintigraphy, rapid sperm transport was studied by placing technetium-labelled albumin macrospheres of sperm size at the external os of the uterine cervix and following their path through the female genital tract. Ascension of the macrospheres occurred immediately following deposition at the external os of the cervix. As early as 1 min thereafter, the macrospheres had reached the intramural and isthmical part of the tube. Quantitatively, the extent of ascension increased with progression of the follicular phase. While only a few macrospheres entered the uterine cavity and even fewer the tubes during the early follicular phase, the proportion of macrospheres that entered the uterine cavity increased dramatically during the mid-follicular phase despite continuing limited entry into the tube. During the late follicular phase there was considerable ascension of the macrospheres which was directed preferentially into the tube ipsilateral to the dominant follicle. These data indicate that rapid transport of the spermatozoa through the female genital tract is under the endocrine control of the dominant follicle, ensuring the preferential accumulation of spermatozoa at the site of fertilization.

Adult↗

Uterine hyperperistalsis and dysperistalsis as dysfunctions of the mechanism of rapid sperm transport in patients with endometriosis and infertility.

Women suffering from infertility in association with mostly mild endometriosis were subjected to vaginal sonography of uterine peristalsis during the menstrual period, the early, mid- and late follicular phases, and the mid-luteal phase of the menstrual cycle. The data obtained were compared with those of healthy controls. Women with endometriosis displayed a marked uterine hyperperistalsis that differed significantly from the peristalsis of the controls during the early and mid-follicular and mid-luteal phases. During the late follicular phase of the cycle, uterine peristalsis in women with endometriosis became dysperistaltic, arrhythmic and convulsive in character, while in controls peristalsis continued to show long and regular cervico-fundal contractions. Hysterosalpingoscintigraphy during the early, mid- and late follicular phases revealed that hyperperistalsis in the early and mid-follicular phases of patients with endometriosis resulted in a dramatic increase in the transport of inert particles from the vaginal depot, through the uterus into the tubes and also into the peritoneal cavity. During the late follicular phase of the cycle, the dysperistalsis observed in women with endometriosis resulted in a dramatic reduction of uterine transport capacity in comparison with the healthy controls. We consider uterine hyperperistalsis to be the mechanical cause of endometriosis rather than retrograde menstruation. Dysperistalsis in the late follicular phase of patients with endometriosis may compromise rapid sperm transport. Uterine hyperperistalsis and dysperistalsis are considered to be responsible for both reduced fertility and the development of endometriosis.

Adult↗

Directed search for thrombomodulin gene mutations.

Thrombomodulin is a principle thrombin receptor located on the vascular endothelium. Thrombomodulin alters the specificity of thrombin, redirecting its procoagulant function to an anticoagulant function by making it a more efficient activator of protein C. While mutation of the genes of other components of this anticoagulant mechanism, protein C, protein S and factor V, is known to predispose towards venous thromboembolism, there are only a few reports of the investigation of thrombomodulin gene mutation. We present the design and evaluation of a strategy to investigate thrombomodulin gene mutation in arterial and venous thrombosis.

Cerebrovascular Disorders↗

Involvement of oxygen in harvesting injury of the liver. An experimental study including substrate free organ persufflation to evaluate a specific therapeutic approach.

The present study was undertaken to assess the role of oxygen free radicals relating to cell damage upon reoxygenation of the ischemically altered isolated rat liver. Livers were excised and flushed via the portal vein with Ringer's solution and Euro-Collins solution, to which superoxide dismutase (SOD) was added in the experimental group. After warm ischemia at 37 degrees C and cold storage at 4 degrees C, the livers were reperfused via the portal vein with carbogen-saturated Krebs-Henseleit solution. Other livers were subjected to a retrograde persufflation via the infrahepatic caval vein with either oxygen or nitrogen and then rinsed with Ringer's solution. During reperfusion, SOD-treated livers showed markedly reduced vascular resistance, lower enzyme release and enhanced VO2 accordingly, energy charge at the end of reperfusion was significantly higher in the treated group. With reference to the tissue content of malondialdehyde, SOD-treated livers showed significantly less damage than the corroboration for these data. Enzyme activities in the eluate were significantly reduced under anoxic conditions as well as in the presence of SOD. We conclude from these data that oxygen free radicals do exert a detrimental impact on the reoxygenated liver, which could be specifically suppressed by application of exogenous SOD.

Adenosine Triphosphate↗

Influence of the duration of the oestradiol rise on the success rate in GnRH analogue/HMG-stimulated IVF cycles.

The influence of the duration of the serum oestradiol (E2) rise before human chorionic gonadotrophin (HCG) injection on the outcome of in-vitro fertilization (IVF) cycles was investigated. Two different stimulation protocols were compared. In 218 cycles, the Norfolk protocol for stimulation with human menopausal gonadotrophin (HMG) was used (protocol A). In 235 cycles, pituitary function was suppressed by a single injection of a long-acting GnRH analogue ('Decapeptyl microcapsules') before HMG stimulation was started (protocol B). The overall pregnancy rates were significantly higher with protocol B (22% per puncture, 21% per started cycle) than with protocol A (14% per puncture, 9% per started cycle). For each interval of E2 rise duration (5-11 days), the fertilization rates (per oocyte) and the pregnancy rates (per puncture) were evaluated. There was a clear-cut maximum of the pregnancy rates for 6 and 7 days of E2 rise (21 and 16% respectively) for protocol A. For protocol B, pregnancy rates were generally higher than for protocol A. There was also a maximum of the pregnancy rates for 6 (32%) and 7 (29%) days of E2 rise but this maximum was not as clear-cut as for protocol A. The fertilization rates showed no significant differences for each interval of E2 rise in both groups (between 63 and 89%). Therefore, it is concluded that endometrial maturity, and not the oocyte's ability for fertilization, is the most critical factor for success in IVF cycles.(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗

Frozen storage of Ham's F10 medium for human in-vitro fertilization.

A method of frozen storage of Ham's F10 medium was investigated that provides 'ready-to-use' culture medium for human in-vitro fertilization, without the necessity of readjusting and testing the medium after thawing. Ham's F10 medium, without bicarbonate, was adjusted to 245 mOsm/kg and stored in aliquots of 33 ml at -20 degrees C. Aliquots of 1 ml of a 7.5% (w/v) sodium bicarbonate solution were stored separately at the same temperature. The two components were mixed together after thawing. In the first test series, mouse embryos were cultured in media stored frozen for varying intervals between 2 weeks and 6 months and no difference in the rates of blastocyst formation was detected. Frozen-stored Ham's F10 medium was then used for human IVF in 256 cycles performed within a 16-month period in two different IVF centres. The pregnancy rates were evaluated and correlated with the duration of the frozen storage (between 1 week and 3 months) and compared to the outcome of 24 cases in which non-frozen medium was used. There was no significant difference in the pregnancy rates in the different groups (19% with non-frozen medium and between 21 and 33% with frozen-stored medium). Thus it was shown that there is no loss of quality of the frozen-stored media within the tested period of 3 months. The prolonged storage interval offers the possibility of extended quality tests and cross-tests between different IVF laboratories.

Animals↗

Activity of rat Mx proteins against a rhabdovirus.

Upon stimulation with alpha/beta interferon, rat cells synthesize three Mx proteins. Sequence analysis of corresponding cDNAs reveals that these three proteins are derived from three distinct genes. One of the rat cDNAs is termed Mx1 because it is most closely related to the mouse Mx1 cDNA and because it codes for a nuclear protein that, like the mouse Mx1 protein, inhibits influenza virus growth. However, this protein differs from mouse Mx1 protein, in that it also inhibits vesicular stomatitis virus (VSV), a rhabdovirus. A second rat cDNA is more closely related to the mouse Mx2 cDNA and directs the synthesis of a cytoplasmic protein that inhibits VSV but not influenza virus. The third rat cDNA codes for a cytoplasmic protein that differs from the second one in only eight positions and has no detectable activity against either virus. These results indicate that rat Mx proteins have antiviral specificities not anticipated from the analysis of the murine Mx1 protein.

Amino Acid Sequence↗

[Massive pulmonary brain tissue embolism].

A 20 year old woman with a severe head injury and rapidly increasing brain edema died 46 hours after the accident. There was clinical evidence of protracted shock and disseminated intravascular coagulation. The autopsy revealed a macro-embolization of brain tissue of the lungs with many central and intermediate lung artery branches occluded by cerebral tissue. Preconditions of the brain tissue embolism were a severe fracture of the skull including a traumatic rupture of the right sigmoid sinus, together with a local brain laceration and an extremely elevated intracranial pressure. Fibrin precipitations were prominent at the surfaces of the brain tissue emboli as well as in peripheral blood vessels of the lung; in the systemic circulation, intravascular coagulation was much less pronounced.

Accidents, Traffic↗

Health lifestyles and self-direction in employment among American men: a test of the spillover effect.

This paper examines whether American males with a high degree of control over their work situation pursue healthy lifestyles and rate their physical health more positively than those who score low on occupational self-direction. That is, are persons who control their work more likely to also try to control their health through living in a particularly healthy manner? We found that there was no support for a spillover effect from high occupational self-direction to enhanced participation in health lifestyles or more positive self-rated health. The findings suggest health lifestyles have spread throughout occupational work groups in the U.S. and support research that maintains such lifestyles have spread across social strata in America.

Attitude to Health↗

Alcohol use and psychological distress: a comparison of Americans and West Germans.

This paper examines the relationship between alcohol use and tendencies toward depression and anxiety among Americans and West Germans. It was found that anxiety was not significant in promoting drinking, although depression was associated with alcohol use for Americans only. Nevertheless, the West Germans consumed more alcohol than Americans, and this study suggests that culture underlies the difference in alcohol consumption.

Adolescent↗

[The temporomandibular joint--structure and function during the course of development].

The temporomandibular joint is one of the most complicated articulations of our body. Its relative stability of function is in contrast to the apparent instability of some structures enclosed. The paper summarizes some thoughts about this joint and it should be stressed the especial difficulty in teaching the joint in the stomatological anatomy.

Humans↗

Psychological distress, perceived health status, and physician utilization in America and West Germany.

This paper reports on findings pertaining to levels of psychological distress, perceived health status, and physician utilization among a sample of Americans (N = 1204) and West Germans (N = 1266) living in Illinois and North-Rhine Westphalia, respectively. The conflicting perspectives of labeling theory and the clinical approach to cross-cultural variations in mental disorder are discussed. There were no significant differences between the two population groups with respect to anxiety tendencies or psychological distress generally, with the exception of Germans having significantly more tendency toward depression. In both countries, persons with the lowest expressions of anxiety were the most likely to perceive symptoms of physical problems as requiring a doctor's attention, thereby suggesting that anxiety operates to influence a denial of general readiness to deal with symptoms. Yet persons with the highest anxiety, depression, and overall psychological distress were most likely to report having experienced physical symptoms and visiting a doctor because of it. Persons with the highest anxiety, depression, and overall psychological distress also rated their health status the lowest.

Adolescent↗

[Effectiveness and tolerance of flumazenil in regional anesthesia with midazolam sedation].

In this double-blind placebo-controlled trial were studied the efficacy and safety of Flumazenil (Anexate) administered postoperatively for reversing the central effects of midazolam. Fifty-nine patients were sedated with midazolam for surgery under epidural or spinal anaesthesia. At the end of operations Flumazenil was i.v. injected in incremental doses up to the awakening of the patient or to a maximal dose of 1 mg. The parameters of efficacy (degree of sedation, amnesia, orientation and collaboration) and safety (vital signs, vital capacity), adverse reactions and the patient's subjective assessment were recorded up to 240 min after the injection of the trial drug. With efficacious doses of 0.2 mg-0.4 mg the Flumazenil group showed a significant improvement in collaboration and in reversing sedation and amnesia up to 30 min after the injection of the antagonist. The relatively short duration of action of Flumazenil can lead to secondary sleep and amnesia episodes. The vital signs remained stable after the administration of the trial drug. Patients assessed their subjective satisfaction on the awakening. There were no severe adverse reactions after Flumazenil.

Adult↗