Prospects for a parainfluenza virus vaccine.
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Animals↗
Biomedical subjects
M Klein
Publications and source records attributed to M Klein.
Pelvic ultrasound scanning of the ovaries in adolescent anorectic patients at low weight and after weight recovery.
In sixteen adolescent anorectic inpatients with secondary amenorrhea pelvic ultrasound examination of the ovaries was performed at lowest weight and after weight recovery. The outcome was assessed six months later at follow-up, assigning the patients to the categories of good, intermediate and poor outcome according to the modified Morgan and Russell criteria. At lowest weight all patients' ovaries were smaller than expected for age. After weight recovery the good outcome group had mature and fully developed ovaries whereas the ovarian morphology of patients with poor outcome remained prepubertal. The ovarian volume in the good outcome group was significantly higher than in the poor outcome group. From a threshold BMI of 17.8 upwards we observed a positive linear correlation between BMI and ovarian volume. At BMI 18 the probability for recovered ovaries was 53% rising to 82% at BMI 19.8, which was the highest noting in our study. Nevertheless, we could not find a clear cut-off BMI for definite prediction of recovered ovaries. Therefore, in patients with anorexia nervosa pelvic ultrasound is a very suitable method for determining the target weight required for recovery of ovarian function and resumption of menses. Normalized ovaries indicate favourable outcome and physical recovery.
Adolescent↗
Effect of body composition, feed intake, and ambient temperature on heat production of Vietnamese Sway-back pigs.
From theoretical considerations animals with a higher protein-fat ratio in the body should have a higher maintenance energy requirement (MEm). The literature on this problem shows a non-uniform picture with deviating results. From the results of a series of experiments it is possible to compare the heat production (HP) of male and female animals of the Vietnamese Sway-back breed pigs which vary quite widely in their body composition. The protein-fat ratio was 1.2 for the male and 0.2 for the female animals. In the experiments 4 male and 4 female animals in the live weight range of 20-33 kg and 33-42 kg, respectively, were involved. The HP measurements were carried out in climatized respiration chambers on two levels of energy intake at ambient temperatures of 6 degrees C, 12 degrees C, 18 degrees C, 24 degrees C, 30 degrees C, and 35 degrees C. The dependence of HP on the ambient temperature has been described by a cubic regression function. Thermoneutral temperatures are lower in the female animals caused by the better insulation effect of the backfat. The difference in HP which was expected by the large difference in body composition, was not found. The absolute protein mass determined the correlation to HP. Certainly the difference increased after lowering the ambient temperature. The influence of different factors on HP is discussed.
Animals↗
Influenza (H1N1)-ISCOMs enhance immune responses and protection in aged mice.
Aging is associated with a decline in immune function and the elderly are therefore more susceptible to infectious disease and less responsive to vaccination. Influenza antigens complexed as immunostimulatory complexes (ISCOMs) generate more potent protective immune responses compared with non-adjuvanted flu antigens in young adult mice. We report on the protective efficacy of flu-ISCOMs compared with the current split flu vaccine in an aged mouse model. DBA/2 mice aged 2 or 18 months were immunized with flu vaccine, ISCOMs or live virus, prior to challenge with the homologous virus. In aged mice, flu-ISCOMs induced significantly higher serum hemagglutination inhibition (HAI) titers compared to vaccine, similar to the levels obtained in young adult mice that received the split vaccine. Flu-ISCOMs but not vaccine induced cytotoxic T lymphocyte (CTL) responses in young and to a lesser degree in aged mice. In aged mice flu-ISCOMs significantly reduced illness and enhanced recovery from viral infection compared with vaccine. Our data suggests that flu-ISCOMs may offer an improved vaccine strategy for protection of elderly humans against the complications of influenza infection.
Aging↗
Additive beneficial effects of beta-blockers to angiotensin-converting enzyme inhibitors in the Survival and Ventricular Enlargement (SAVE) Study. SAVE Investigators.
OBJECTIVES: This study assessed whether treatment with a beta-adrenergic blocking agent in addition to the use of the angiotensin-converting enzyme (ACE) inhibitor captopril decreases cardiovascular mortality and morbidity in patients with asymptomatic left ventricular dysfunction after myocardial infarction (MI) and whether the presence of neurohumoral activation at the time of hospital discharge predicts the effects of beta-blocker treatment in these patients. BACKGROUND: Both beta-blockers and ACE inhibitors have been shown to have beneficial effects in patients with left ventricular dysfunction but no overt heart failure after MI. These patients often have persistent neurohumoral activation at the time of hospital discharge, and one would expect that patients with activation of the sympathetic nervous system derive the most benefit from treatment with beta-blockers. However, beta-blockers are underutilized in this high risk group of patients, and it is unknown whether their beneficial effects are additive to those of ACE inhibitors. METHODS: We performed a retrospective analysis of data from the Survival and Ventricular Enlargement (SAVE) study and its neurohumoral substudy. The relations between beta-blocker use at the time of randomization and neurohumoral activation and the subsequent development of cardiovascular events were analyzed by use of Cox proportional hazards models controlling for covariates. RESULTS: After adjustment for baseline imbalances, beta-blocker use was associated with a significant reduction in risk of cardiovascular death (30%, 95% confidence interval [CI] 12% to 44%) and development of heart failure (21%, 95% CI 3% to 36%), but the reduction in recurrent MI (11%, 95% CI 13% to 31%) was not significant. These reductions were independent of the use of captopril. Beta-blockers were not found to have a greater effect in patients with neurohumoral activation at the time of hospital discharge. CONCLUSIONS: The beneficial effects of beta-blocker use at the time of hospital discharge in patients with asymptomatic left ventricular dysfunction after MI appear to be additive to those of captopril and other interventions known to improve prognosis. Neurohumoral activation at the time of hospital discharge fails to identify those patients who will derive the greatest benefit from treatment with beta-blockers.
Adrenergic beta-Antagonists↗
Otoplasty: a combined approach to different structures of the auricle.
A technique for otoplasty is presented, which combines the advantages of different methods. The procedure includes a dorsal skin excision, a cartilage incision at the border between the concha and scapha, scoring of the crus superior on the anterior side, and if necessary a reduction of the conchal height and modification of the position of the cauda helicis by cartilage excision. The results of the treatment of 526 ears in 312 patients are retrospectively analysed by a patient questionnaire and a chart review.
Adolescent↗
Computed tomographic study of bone availability for facial prosthesis-bearing endosteal implants.
In a computed tomographic study, 56 patients with facial defects were examined to assess the availability of bone for extraoral Brånemark implants (3 or 4 mm long, 3.75 mm diameter) to bear facial prostheses. Bone depths were determined in the auriculotemporal (2-8 mm), infraorbital (0-10 mm), lateroorbital (8-14 mm), supraorbital (1-14 mm) and medioorbital (1-6 mm) areas as well as at the base of the nasal skeleton (1-5 mm). The low values for the supraorbital and infraorbital areas were determined at the points closest to the frontal- and maxillary sinuses, respectively. Implantation in these areas would be permissible only under certain conditions. The very thin osseous structures of the nasal region also present problems for implants. In the auriculotemporal region, the bone width is always sufficient, but at the orbital margin it can vary from 3 to 8 mm. The three-year success rates for implant survival were found to be 100% and 85.8% respectively for auricular and orbital defects. No serious skin complications were seen. Six patients (10.7%) required secondary corrective surgery in a total of 13 implant areas.
Adult↗
Perception of pain in the persistent vegetative state?
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Letter↗
A TNF receptor antagonistic scFv, which is not secreted in mammalian cells, is expressed as a soluble mono- and bivalent scFv derivative in insect cells.
Single chain antibodies (scFv) are usually produced in E. coli, but generation of certain scFv derivatives, such as complex fusion proteins or glycosylated forms of scFv is restricted to eukaryotic expression systems. We investigated the production of soluble mono- and bivalent single chain antibodies (scFv) in eukaryotic cells and describe a cassette vector system for mammalian and baculovirus expression which is compatible with an established vector system for bacterial expression and phage display selection of scFvs. The applied model scFv was derived from a murine antibody (H398) against human tumor necrosis factor receptor 1 (TNFR60), known to be a potent antagonist of TNF action in its monomeric form and a potential therapeutic agent for treatment of TNF-mediated diseases. Surprisingly, the monomeric scFv form of H398 (scFv H398) is expressed but not secreted in different mammalian cells. In contrast, in insect cells using recombinant baculovirus, a monovalent scFv H398 and a bivalent scFv fusion protein with an human IgG1 Fc region were expressed and secreted with correctly processed signal sequence. Concerning the influence of valency of the model Ab and its derivatives on antigen binding affinity and neutralisation of TNF activity, we found that the mono- and bivalent form of scFv H398 possesses the same characteristics as proteolytically produced Fab H398 and original mAb H398, respectively. Furthermore, fusion of the Ig Fc protein to scFv H398 increase the in vitro half-life at 37 degrees C. We conclude that the described cassette vectors readily allow the eukaryotic expression of mono- and bivalent scFv derivatives to analyse the influence of valency of scFv molecules on antigen binding and biological activity.
Animals↗
Baculovirus expression of the respiratory syncytial virus fusion protein using Trichoplusia ni insect cells.
Respiratory syncytial virus (RSV) is a major viral pathogen responsible for severe respiratory tract infections in infants, young children, and the elderly. The RSV fusion (F) protein is highly conserved among RSV subgroups A and B and is the major protective immunogen. A genetically-engineered version of the RSV F protein was produced in insect cells using the baculovirus expression system. To express a secreted form of this protein, the transmembrane domain was eliminated by removing the region of the gene encoding 48 amino acids at the C-terminus. Production of the truncated RSV F protein (RSV-Fs) was compared in two different insect cell lines, Spodoptera frugiperda (Sf9) and Trichoplusia ni (High Five). The yield of RSV-Fs secreted from High Five insect cells was over 7-fold higher than that from Sf9 insect cells. Processing of the RSV-Fs protein was also different in the two insect cell lines. N-terminal sequencing demonstrated that while most of the RSV-Fs protein secreted by High Five cells was correctly processed at the F2-F1 proteolytic cleavage site, most of the RSV-Fs protein secreted by Sf9 cells was unprocessed or incorrectly processed. Antigenicity of the major RSV F neutralization epitopes was maintained in the RSV-Fs protein secreted from High Five cells. The RSV-specific neutralizing antibody titres in the sera of cotton rats immunized with the RSV-Fs protein were equivalent to those in the sera of animals intranasally inoculated with live RSV. Animals immunized with either live RSV or the immunoaffinity purified RSV-Fs protein from High Five cells were completely protected against live virus challenge.
Animals↗
Chemical synthesis of Haemophilus influenzae glycopeptide conjugates.
A simple procedure for conjugating synthetic fragments of the capsular polysaccharide of Haemophilus influenzae type b, poly-3-beta-D-ribose-(1,1)-D-ribitol-5-phosphate (sPRP) to linear peptides is described. The procedure consists of (i) reacting the amino group of amino-heptyl sPRP with m-maleimidobenzoyl-N-hydroxysuccinimide (MBS) in phosphate buffer, pH 7.5; (ii) selectively coupling the MBS-modified sPRP to the sulfhydryl group of the cysteine residue of peptides containing functional T-helper cell epitope(s). The glycopeptide conjugates were purified by gel filtration chromatography, biochemically characterized, and elicited protective level of anti-PRP antibody responses in rabbits.
Amino Acid Sequence↗
Effect of test duration on age-related differences in Stroop interference.
The effect of test duration on age-related differences in Stroop interference was assessed in a large cross-sectional study involving 429 healthy subjects in four age groups (25-35 years, 40-50 years, 55-65 years, 70-80 years). The results show a clear effect of test duration on Stroop interference. The Stroop Color Word Test was run in two parts. The young group performed the first part relatively rapidly but became slower in the second part, whereas the old group showed the reverse effect. The two middle-aged groups did not show differences between the first and second parts of the test. The results are interpreted in terms of a deficit in response inhibition by a controlled processing strategy. A psychological interpretation of the study findings in terms of increased cautiousness appears less probable. The first part of the test, that is, an abridged version of the test, may prove superior to the regular version for both clinical and research purposes.
Adult↗
A comparison of ICAGD (immediate complete anterior guidance development) to mock ICAGD for symptom reductions in chronic myofascial pain dysfunction patients.
The purpose of this study is to assess what impact shortening disclusion time to less than .5 seconds during right and left mandibular excursions has on myofascial pain(s) symptoms present in a dental student population. Twenty-five dental students, who exhibited symptomatology consistent with myofascial pains patient, were divided into a treatment, control, and an untreated group. They participated in an occlusal adjustment study which measured changes in disclusion time, as well as, myofascial pains muscular symptom remissions resultant from treatment. The treated group of ten subjects received ICAGD occlusal adjustments to shorten their disclusion time to less than .5 seconds per mandibular excursion. The goal of this therapy was to totally disclude the posterior teeth in a measurable time frame of .5 seconds or less. The control group of eight subjects received mock ICAGD with tooth polishing. The goal of this therapy was to simulate ICAGD adjustments for possible placebo effect on symptom remissions. The untreated group had their disclusion times measured but received no treatment to adjust, or to simulate adjustment to their occlusion. The goal of analyzing an untreated group was to attempt to show that mock treatment (performed on the control subjects), or no treatment (performed on the untreated subjects), resulted in no measurable change in the disclusion time in either of these two subject groups. Each subject was recalled for disclusion time measurement four to five times in a one-year period of observation, at which time, they were required to report their myofascial pains symptom status by answering an ordinal scale questionnaire. The results suggest that shortening disclusion time to less than .5 seconds per mandibular excursion can induce remissions of many muscular myofascial pains symptoms. Additionally, mock ICAGD occlusal adjustments did not appear to be a factor in the control subjects treatment response, as this group showed no statistically significant symptom remissions.
Adult↗
Proliferative cell activity in correlation to human chorionic gonadotrophin release of trophoblast tissue of tubal pregnancy.
The degree to which the relative rise of serum human chorionic gonadotrophin (HCG) concentration was related to proliferative cell activity and the biological vitality of tubal pregnancy was investigated. Salpingectomy was performed in 15 patients diagnosed as having non-ruptured tubal pregnancy. Serum HCG was evaluated twice preoperatively, with a 48-h time interval. Proliferative cell activity was measured through the use of the cell proliferation marker 'Ki-67'. A significant correlation between the relative increase in HCG over a 48-h period, independent of the initial serum HCG value, and the biological cell activity of the trophoblast was shown. Furthermore, it became evident that cell activity was also correlated to the intracellular HCG of the trophoblast. The relative increase in serum HCG over a period of 48 h can serve as a parameter for the biological activity of the trophoblast in tubal pregnancies.
Cell Division↗
The implantable fuzzy controlled Helmholtz-left ventricular assist device: first in vitro testing.
To perform first experimental tests for validation of a new left ventricular assist device (LVAD) with a high efficiency energy converter, a new pump design and a novel type of perfusion control, a functional labtype, were manufactured. With a stroke volume of 65 ml, a total pump housing volume of 450 ml (including valves and connectors), and a weight of 430 g, it is one of the smallest and lightest implantable pulsatile electromechanical LVADs. Pulsatile operation is generated by a special reduction and displacement gear which transforms a uniform rotational movement of a sensorless, electronically commutated DC motor into a translatory pusher plate movement. A prolonged duration for filling (60% of the cycle time) supports full-empty pumping and consequently a high overall pump efficiency. Active adaptation of output flow to organ perfusion demand is achieved by changing the rotational speed of the motor by means of a sensorless fuzzy controller, which detects preload and afterload induced effects at the motor current input. First in vitro test results obtained within a circulatory mock loop that simulates physiological preloads and afterloads are presented. They comprise preload sensitivity and the function of the novel perfusion controller as well as preload and afterload related flow data. The results prove the feasability of the energy conversion with the novel gear and control concept for an implantable electromechanical pulsatile LVAD.
Animals↗
Fas ligand expression in glioblastoma cell lines and primary astrocytic brain tumors.
Fas/APO-1 (CD95) is a cell surface receptor that mediates apoptosis when it reacts with Fas ligand (FasL) or Fas antibody. We previously reported that Fas expression is predominantly induced in perinecrotic glioma cells, suggesting that Fas induction is associated with apoptosis and necrosis formation, a histological hallmark of glioblastomas. In this study, we assessed the expression of FasL in 10 glioblastoma cell lines and in 14 astrocytic brain tumors (three low-grade astrocytomas and 11 glioblastomas). Reverse transcriptase (RT)-PCR revealed that all glioblastoma cell lines and primary astrocytic brain tumors express FasL. Immunohistochemically, FasL was predominantly expressed on the plasma membrane of glioma cells. These results suggest that FasL expression is common in human astrocytic brain tumors and may cause apoptosis of glioma cells if Fas expression is induced.
Adult↗
Use of the pre-pro part of Staphylococcus hyicus lipase as a carrier for secretion of Escherichia coli outer membrane protein A (OmpA) prevents proteolytic degradation of OmpA by cell-associated protease(s) in two different gram-positive bacteria.
Heterologous protein secretion was studied in the gram-positive bacteria Bacillus subtilis and Staphylococcus carnosus by using the Escherichia coli outer membrane protein OmpA as a model protein. The OmpA protein was found to be translocated across the plasma membrane of both microorganisms. However, the majority of the translocated OmpA was similarly degraded in B. subtilis and S. carnosus despite the fact that the latter organism does not secrete soluble exoproteases into the culture medium. The finding that purified OmpA, which was added externally to the culture medium of growing S. carnosus cells, remained intact indicates that newly synthesized and exported OmpA is degraded by one or more cell-associated proteases rather than by a soluble exoprotease. Fusion of the mature part of OmpA to the pre-pro part of a lipase from Staphylococcus hyicus allowed the efficient release of the corresponding propeptide-OmpA hybrid protein into the supernatant and completely prevented the cell-associated proteolytic degradation of the mature OmpA, most likely reflecting an important function of the propeptide during secretion of its natural mature lipase moiety. The relevance of our findings for the biotechnological use of gram-positive bacteria as host organisms for the secretory production of heterologous proteins is discussed.
Bacillus subtilis↗