Biomedical subjects

H Alexander

Publications and source records attributed to H Alexander.

At least 19 recordsLinked to original sources

PubMed1999

The prespore vesicles of Dictyostelium discoideum. Purification, characterization, and developmental regulation.

The coordinate fusion of the prespore vesicles (PSVs) with the plasma membrane at the terminal stage of spore differentiation in Dictyostelium discoideum is an important example of developmentally regulated protein secretion. However, little is known about the composition of the vesicles, the molecular signals regulating secretion, or the mechanics of the membrane fusion. Taking a biochemical approach, we purified PSVs from different developmental stages. These preparations are highly enriched for their specific cargo of spore coat proteins while devoid of markers for other cellular compartments. Electron microscopic observations show that the PSV preparations are homogenous, with the soluble spore coat protein PsB/SP85 distributed throughout the lumen and the acid mucopolysaccharide localized in the central core. During development the PSVs increase in size and density concomitant with an increase in their protein cargo. The PSVs contain approximately 80 proteins, and we have identified a PSV-specific GTP-binding protein that may be involved in regulating vesicle fusion. The PSVs are not clathrin-coated and do not contain the SpiA spore coat protein. The PSV preparations are ideal for a global proteome analysis to identify proteins involved in signal reception, vesicle movement, docking, and fusion in this developmentally regulated organelle.

Animals↗

PubMed1999

Heat shock proteins and heat shock protein-antibody complexes in placental tissues.

OBJECTIVE: The relationship between pregnancy outcome and expression of the heat shock proteins (hsps) or hsp-antibody complexes of 60kD (hsp60), 70kD (hsp70), and 90kD (hsp90) in placental tissue and circulating antibodies to hsps was evaluated. METHOD: Expression of hsp60, hsp70, and hsp90 in placentae from 12 women with preterm birth, eight with intrauterine growth restriction (IUGR), and 10 with term birth, as well as the presence of the corresponding antibodies, was investigated by a new carbocyanine double fluorescence technique. Results were compared with microbiological findings and circulating antibodies to hsps in sera. RESULTS: In each placental specimen examined, hsp60, hsp70, and hsp90 were identified. However, hsp70-antibody complexes were detected in only four of the preterm labor cases. Similarly, hsp60-antibody complexes were detected in only five preterm labor patients and in one patient with IUGR. None of the placentae contained hsp90-antibody complexes. In the preterm birth group, all patients with hsp60-antibody complexes were also positive for circulating antibodies to hsp60. The presence of hsp70-antibody complexes also correlated with hsp70 antibody in sera. CONCLUSIONS: Formation of hsp60- and hsp70-antibody complexes in the placenta may contribute to the induction of preterm birth. Women sensitized to these antibodies may be at increased risk for adverse pregnancy outcome.

Antigen-Antibody Complex↗

PubMed1999

The effect of surface roughness on the stress adaptation of trabecular architecture around a cylindrical implant.

The effect of implant-bone bonding and the effect of implant surface roughness on bone remodeling near the bone-implant interface were studied by using a surface remodeling theory and the boundary element method. The study has shown that implant attachment plays an important role in bone remodeling near the implant. It has been observed in animal experiments and in clinical situations that the remodeled trabecular bone architecture around a cylindrical implant could vary, on one hand, from a hub surrounding the implant with a set of external spokes to, on the other hand, a hubless situation in which a set of spokes attach directly to the implant. It is shown here that the difference in these structures may be attributed to differences in implant attachment. The results show that the bone with perfect bonding or roller boundary condition without a gap remodeled to a hubless spoke trabecular bone architecture. On the other hand, the roller boundary condition with a specified gap yielded a spoke trabecular architecture with a hub or ring surrounding the implant. These quantitative results mirror the experimental and clinical observations. It is concluded that the hub is a consequence of the gap and not a consequence of the lack of friction between the implant and the bone.

Humans↗

PubMed1999

Intra-aortic administration of epinephrine above aortic occlusion does not alter outcome of experimental cardiopulmonary resuscitation.

Intra-aortic balloon occlusion during experimental cardiopulmonary resuscitation (CPR) improves coronary perfusion pressure and resuscitability and provides unique access to the central circulation. It has been hypothesized that administration of epinephrine into the aortic arch in combination with aortic occlusion would further improve haemodynamics during CPR, resuscitability and 24 h survival. In 16 anaesthetised dogs intravascular catheters were placed for hemodynamic and blood gas monitoring. An aortic balloon catheter was placed by femoral artery insertion with its tip just distal to the left subclavian artery. Ventricular fibrillation for 7.5 min without CPR, 2.5 min of Basic Life Support with chest compressions and ventilation with 100% oxygen were followed by 30 min of Advanced Cardiac Life Support (ACLS) with systemic canine drug dosages. The intra-aortic balloon was inflated when ACLS started and gradually deflated shortly after restoration of spontaneous circulation (ROSC). Epinephrine, in 100 microg/kg boluses every 5 min until the heart was restarted or 30 min had elapsed was administered through the intra-aortic catheter in the experimental group (n = 8) and via a central venous catheter in the control group (n = 8). Coronary perfusion pressure increased during the ACLS period in both groups (P < 0.05) with no difference between the groups and there was no difference in the frequency of ROSC (experimental group 5/8, control group 4/8). Furthermore with respect to 24 h survival, there was no difference between the experimental group (2/8) and the control group (3/8). Severe macroscopic haemorrhagic necrosis of the myocardium in the dogs with ROSC was found in 4/5 in the experimental group compared to 1/4 in the control group. In conclusion, intra-aortic administration of 100 microg/kg epinephrine doses combined with aortic occlusion during experimental CPR did not alter outcome.

Analysis of Variance↗

PubMed1999

Changing patterns of coronary heart disease in the hunter region of New South Wales, Australia.

A population-based observational study of men and women aged 35-69 years in the Hunter Region of New South Wales, Australia, was conducted to assess the impact of risk-factor modification and increased drug therapy on the trends in major coronary events and case fatality. From 1985 to 1993, there were 3006 coronary deaths and 6450 nonfatal major coronary events. Rates of death and nonfatal myocardial infarction declined, but there was an increase in hospital admissions for prolonged chest pain. Reductions in cigarette smoking, diastolic blood pressure, total cholesterol, and increased use of aspirin can fully explain the 3.3% (95% confidence interval [CI] 2.4, 4.2) average annual reduction in rates of major coronary events for men and the 4.1% (95% CI 2.7, 5.5) reduction for women. In contrast, increased use of aspirin, beta-blockers, fibrinolytic therapy, and angiotensin-converting enzyme inhibitors explain less than half of the 8.9% (95% CI 5.9, 11.8) and 6.9% (95% CI 2.7, 10.9) average annual reduction in case fatality in hospital for men and women, respectively. These trends suggest a decline in severity of coronary heart disease consistent with reductions in risk-factor levels and improved acute medical treatment.

Adult↗

PubMed1999

Risk factors for cardiovascular disease and diabetes in two groups of Hispanic Americans with differing dietary habits.

OBJECTIVE: The purpose of this study was to determine if Hispanic Seventh-Day Adventists (SDAs), who typically eat a diet lower in fat, saturated fat and protein, and higher in complex carbohydrates and dietary fiber than the usual omnivorous diet, exhibit lower risk factors for cardiovascular disease (CVD) and Type 2 diabetes compared to Hispanic Catholic omnivores. METHODS: Anthropometric characteristics, dietary intake, blood pressure, serum lipids, glucose and insulin, as well as plasma ascorbic acid and vitamin E concentrations, were measured in two groups of Hispanic study participants residing in Denver, Colorado: 74 SDA study participants (x age: 42+/-1.5 y) and 45 Catholic participants (x age: 44+/-2.2 y). RESULTS: The SDAs reported lower dietary intakes of total fat, saturated fat and cholesterol and higher relative intakes of carbohydrate and dietary fiber compared to their Catholic counterparts. The SDAs exhibited significantly lower body mass index (BMI = 27.2+/-0.6) and waist-to-hip ratios (WHR = 0.84+/-0.01) compared to the Catholics (BMI = 31.4+/-1.1; WHR = 0.88+/-0.01). The SDAs, compared to the Catholics, had lower fasting insulin (11.4+/-0.6 vs. 18.9+/-3.1 microu/ml) and glucose concentrations (88.6+/-1.1 vs. 104.1+/-5.4 mg/dl). The SDA Hispanics, compared to the Catholic Hispanics, exhibited significantly lower values for systolic blood pressure (SBP = 1102 vs. 118+/-3 mm Hg), serum total cholesterol (STC = 198+/-5 vs. 214+/-6 mg/dl) and serum triglycerides (TG = 152+/-12 vs. 232+/-27) and higher serum concentrations of high-density lipoprotein cholesterol (HDL-C = 44.7+/-1.3 vs. 39.1+/-1.4 mg/dl) and ascorbic acid (1.14+/-0.08 vs. 0.87+/-0.07 mg/dl). Low-density lipoprotein cholesterol (LDL-C) and vitamin E concentrations were not significantly different between groups, but the SDAs exhibited lower ratios of STC/HDL-C and LDL-C/HDL-C. CONCLUSION: Hispanic American SDAs, who eat a plant-based diet, exhibit a more favorable blood lipid profile, lower blood pressure and lower risk for Type 2 diabetes compared to Hispanic American Catholics, who do not eat a plant-based diet.

Adolescent↗

PubMed1999

Stroke patients' informal caregivers. Patient, caregiver, and service factors that affect caregiver strain.

BACKGROUND AND PURPOSE: Research has revealed that caring for a stroke patient can result in caregiver strain and a myriad of other difficulties for caregivers. This study aims to identify the level of strain experienced by caregivers in the early months after stroke and to assess the relationship between caregiver strain and caregiver characteristics, patient characteristics, and service inputs. METHODS: Stroke patients were identified through a random stratified sample of general practices. Patients were asked to identify their principal informal caregiver. Strain was measured with the Caregiver Strain Index, and all data were collected from caregivers at 1, 3, and 6 months after the patient's stroke. Multiple regression analysis was used to examine the factors associated with caregiver strain. RESULTS: Six months after stroke, 37% of caregivers were experiencing considerable strain. The amount of time a caregiver spent helping a stroke patient, the amount of time the caregiver spent with the patient, and the caregiver's health were all significantly associated with the level of strain experienced. Although none of the services or patient factors tested in this study were consistently associated with strain, an indicator of stroke severity was significant at each time point. CONCLUSIONS: Caregivers are experiencing strain, which has implications for research and service provision. Service providers need to identify caregivers at risk of greater strain and to help caregivers work through situations that services cannot alter. Research is needed to identify services that are effective in strain alleviation. Future research should also aim to identify the interface between patient characteristics and strain, burden, and depression and particularly to assess the caregiver's perception of these relationships.

Adult↗

PubMed1998

A mutation in repB, the dictyostelium homolog of the human xeroderma pigmentosum B gene, has increased sensitivity to UV-light but normal morphogenesis.

Nucleotide excision repair (NER) is an important cellular defense mechanism which protects the integrity of the genome by removing DNA damage caused by UV-light or chemical agents. In humans, defects in the NER pathway result in the disease xeroderma pigmentosum (XP) which is characterized by increased UV-sensitivity, with increased propensity for skin cancer, and an array of developmental abnormalities. Some XP patients exhibit, in addition, symptoms of Cockayne's syndrome (CS) and trichothiodystrophy (TTD), which are characterized by increased UV-sensitivity, without increased cancer incidence, and an array of developmental abnormalities. Some NER genes, including the DNA helicases XPB and XPD, have been shown to function in transcription as well as repair, by virtue of being an integral part of the transcription initiation factor TFIIH. This dual function may account for the above-mentioned wide pleiotropy of phenotypes associated with defects in NER genes, and may explain why some XP patients exhibit developmental abnormalities in addition to XP symptoms. To date, only five XPB patients with three different mutations in the XPB gene have been reported. One of these mutations is a C to A transversion at the splice site at the beginning of the last exon, which resulted in a frameshift throughout the last exon. This patient shows combined clinical symptoms of XP and CS. The recent cloning of the repB gene, the Dictyostelium discoideum homolog of XPB, allowed us to generate a similar C-terminal mutation in the Dictyostelium, in order to test whether the defect in this NER gene has an effect on growth or development. To this end, we have constructed a C-terminal deletion repB mutant in Dictyostelium. To avoid the possibility that a null mutant would be lethal, we used direct homologous recombination to create a 46 amino acid C-terminal deletion mutant. Indeed, we were unable to obtain mutants with a longer 95 amino acid deletion. The repB delta C46 mutants showed an increased sensitivity to UV-light, but a normal pattern of UV-induced expression of repair genes, and no immediately obvious defect in either growth rate or development. The results suggest that the associated developmental defects in the human XPB patients may be due to mutations in another gene.

Amino Acid Sequence↗

PubMed1998

Rapid changes of nucleotide excision repair gene expression following UV-irradiation and cisplatin treatment of Dictyostelium discoideum.

Organisms use different mechanisms to detect and repair different types of DNA damage, and different species vary in their sensitivity to DNA damaging agents. The cellular slime mold Dictyostelium discoideum has long been recognized for its unusual resistance to UV and ionizing radiation. We have recently cloned three nucleotide excision repair (NER) genes from Dictyostelium , the rep B, D and E genes (the homologs of the human xeroderma pigmentosum group B, D and E genes, respectively). Each of these genes has a unique pattern of expression during the multicellular development of this organism. We have now examined the response of these genes to DNA damage. The rep B and D DNA helicase genes are rapidly and transiently induced in a dose dependent manner following exposure to both UV-light and the widely used chemotherapeutic agent cisplatin. Interestingly, the rep E mRNA level is repressed by UV but not by cisplatin, implying unique signal transduction pathways for recognizing and repairing different types of damage. Cells from all stages of growth and development display the same pattern of NER gene expression following exposure to UV-light. These results suggest that the response to UV is independent of DNA replication, and that all the factors necessary for rapid transcription of these NER genes are either stable throughout development, or are continuously synthesized. It is significant that the up-regulation of the rep B and D genes in response to UV and chemical damage has not been observed to occur in cells from other species. We suggest that this rapid expression of NER genes is at least in part responsible for the unusual resistance of Dictyostelium to DNA damage.

Animals↗

PubMed1998

Development of a novel osteochondral graft for cartilage repair.

This study reports the development of a novel osteochondral graft for cartilage repair. A technique of proteoglycan extraction via timed enzymatic digestion with hyaluronidase and trypsin and subsequent processing with a chloroform-methanol solution to remove cellular debris from a fresh-frozen bovine osteochondral sample is a method described to prepare a stable biological carrier of low immunogenicity. Lyophilization of the carrier followed by rehydration in a suspension of lapine chondrocytes produced a chimeric xenograft that succeeded in vivo in enhancing cartilage repair. In a pilot study, full-thickness articular cartilage defects treated with these xenografts demonstrated improved healing compared to untreated defects or defects treated with unseeded grafts at 2, 6, and 12 weeks postimplantation. The xenograft provoked a mild inflammatory response; however this did not impede the repair process. Further investigation of this novel chimeric xenograft eventually may yield a method of cartilage repair superior to current methods of treatment.

Animals↗

PubMed1998

HCG secretion by peripheral mononuclear cells during pregnancy.

Peripheral mononuclear cells (MNC) in culture release a biologically active hCG. This effect is detectable during pregnancy with a maximum between the 9th and 16th wk. Peripheral MNC already secrete hCG between the 7th and 11th d after embryo transfer. The secretion of hCG is activated by the PKC-activator TPA. TPA induces hCG release into the medium, thus causing a decrease in intracellular hCG content. In contrast, db-cAMP inhibites hCG secretion into the medium. Protein synthesis inhibitors of transcription and translation suppress the production and secretion of hCG. Peripheral natural killer (NK) cells (CD56+/CD16+) and monocytes (CD14+) show the highest secretion rates. IL-1 beta, IL-4, IL-6, IL-10, TNF alpha, and GM-CSF stimulate, whereas IL-2 and INF gamma inhibit, the hCG secretion of mononuclear cells. Flow cytometric experiments with hCG antibody demonstrate a binding of hCG on the surface of monocytes more than lymphocytes. The binding capacity is improved during pregnancy. Different hCG bands are shown in the Western blot analysis. We could confirm the mRNA of beta hCG and alpha CG are in MNC as well in the placental control. Peripheral MNC, first and foremost NK cells and monocytes, produce and secrete hCG during pregnancy, which play an important role for the corpus luteum rescue during the early gestational age and possibly for the immunotolerance.

Animals↗

PubMed1998

Moderate hypothermia for 48 hours after temporary epidural brain compression injury in a canine outcome model.

In a previous study with this dog model, post-insult hypothermia of 31 degrees C for 5 h prevented secondary intraventricular pressure (IVP) rise, but during 35 degrees C or 38 degrees C, one-half of the dogs developed delayed IVP rise to brain death. We hypothesized that 31 degrees C extended to 48 h would prevent brain herniation. Using epidural balloon inflation, we increased contralateral IVP to 62 mm Hg for 90 min. Controlled ventilation was to 72 h and intensive care to 96 h. Group 1 dogs (n = 10) were normothermic controls (37.5 degrees C). Group 2 dogs (n = 10) were surface-cooled from 15 to 45 min of balloon inflation and maintained at moderate hypothermia (31 degrees C) to 48 h. Rewarming was from 48 to 72 h. Four additional dogs of hypothermia Group 2 had to be excluded from analysis for pneumonia and/or bleeding diathesis. After balloon deflation, IVP increased to 20 mm Hg or greater at 154 +/- 215 (range 15-720) min following the insult in Group 1 and at 1394 +/- 1191 (range 210-3420) min in Group 2 (p = 0.004), still during 31 degrees C but without further increase during hypothermia. Further IVP rise led to brain death in Group 1 in 6 of 10 dogs at 44 +/- 18 (range 21-72) h (all during controlled ventilation); and in Group 2, in 6 of 10 dogs at 87 +/- 11 (range 72-96) h (p = 0.001), all after rewarming, during spontaneous breathing. Survival to 96 h was achieved by 4 of 10 dogs in Group 1, and by 7 of 10 dogs in Group 2 (NS). Three of the six brain deaths in Group 2 occurred at 96 h. The macroscopically damaged brain volume was only numerically smaller in Group 2. The vermis downward shift was 6.8 +/- 3.5 mm in Group 1, versus 4.7 +/- 2.2 mm in Group 2 (p = 0.05). In an adjunctive study, in 4 additional normothermic dogs, hemispheric cerebral blood flow showed post-insult hypoperfusion bilaterally but no evidence of hyperemia preceding IVP rise to brain death. In conclusion, in this model, moderate hypothermia during and for 48 h after temporary epidural brain compression can maintain a low IVP during hypothermia but cannot prevent lethal brain swelling after rewarming and may cause coagulopathy and pulmonary complications.

Animals↗

PubMed1998

The presence of chorionic gonadotrophin beta subunit in normal cyclic human endometrium.

The aim of the present study was to determine whether human endometrial cells are able to secrete beta-chorionic gonadotrophin (betaCG). Immunohistochemical studies and in-situ hybridization were performed in order to provide evidence for the occurrence of betaCG in the normal endometrium in 15 patients in the proliferative phase, two patients in the periovulatory phase and 13 patients in the secretory phase. Neither immunohistochemical nor hybridization reactions could be recognized during the proliferative phase. In contrast, both protein and betaCG mRNA were observed in the glandular cells of the endometrium during the secretory phase. The results were supported by Western blotting of secretory phase endometrium extracts and the assessment of the functional secretory capacity of primary endometrium cultures. In comparison with cultured and separated cell fractions, tissue extracts showed a higher betaCG, indicating a regulatory interaction. In conclusion, betaCG can be demonstrated in normal human cyclic endometrium, suggesting a paracrine role in endometrial physiology.

Cells, Cultured↗

PubMed1998

[Hugo Sellheim (1871-1936): Leipzig acknowledgement of gynecology].

In 1928 Hugo Sellheim, Professor and Chairman of gynaecology and obstetrics at the University of Leipzig (1926-1936), inaugurated the new Clinic of Gynaecology and Obstetrics. The opening ceremony found a critical public response. Although the new building had been drawn up by his predecessor Walter Stoeckel, Sellheim developed own ideas concerning the equipment of the institution. In Leipzig Sellheim is continued his scientific efforts with a story focus on female reproduction and its sociocultural impact during the period of the Weimar Republic.

Female↗

PubMed1998

Heterogeneity of noninvasive arrhythmic risk indicators in patients with ischemic cardiomyopathy.

Noninvasive electrocardiographic variables for arrhythmic risk stratification in chronic heart failure are of great clinical interest but remain highly controversial. This study analyzed repolarization dispersion, heart rate variability, ventricular ectopic activity, and hemodynamic parameters in 30 patients with ischemic heart failure and in 20 normal control subjects. The values for all parameters were distinctly separated between the failure and control group. Left ventricular ejection fraction had a strong relation to ventricular ectopic activity (r = .54), a weak association with repolarization dispersion (r = .29), and seemingly no parallels with heart rate variability (r = .12). However, no linear association could be detected between any of the arrhythmic risk indicators (r = .10-.22), whereas a number of linearly related angiographic-hemodynamic variables readily defined the mechanical risk profile. Thus, alterations of noninvasive arrhythmic risk indicators in heart failure are not uniform, which confounds approaches for a composite ECG risk score in individual patients.

Arrhythmias, Cardiac↗

PubMed1998

[Some aspects of the life work of Ludwig Fraenkel (1870-1951) with special reference to his social gynecology and sexology studies].

The gynaecologist Ludwig Fraenkel is known because of his works concerning the endocrine function of the corpus luteum. Moreover he was an important representative of the social gynaecology and sexology during the first decades of this century. His studies in these fields identify Fraenkel as an independent scientist considering for example social living conditions as a cause of gynaecological illnesses. On the other hand he took over problematic positions in eugenics hoping to improve public health. During the Hitler era the Jew Ludwig Fraenkel was dismissed from the directorate of the Women's clinic of the University of Breslau. He left Germany forever.

Germany↗

PubMed1997

Synthetic strategies for the preparation of precursor polymers and of microcapsules suitable for cellular entrapment by polyelectrolyte complexation of those polymers.

The production of microcapsules suitable for the entrapment of mammalian cell by means of polyelectrolyte complexation has, of a necessity, led to the development of novel strategies for the preparation of relatively bioinert polymers which complex efficiently under unique conditions to produce a mechanically resilient membrane with efficient transport properties. In this communication we relate a brief overview of capsule-membrane forming systems for the immunoisolation (or potential immunoisolation) of mammalian cells, which are based upon the complexation of polyelectrolyte (PE) polymers; with emphasis on precursor synthesis and relationships between precursor polymer structure and capsule membrane stability.

Animals↗

PubMed1997

The Dictyostelium discoideum beta-1,4-mannosyltransferase gene, mntA, has two periods of developmental expression.

The precise roles of protein glycosylation in multicellular development are poorly understood. We have characterized the mntA gene from Dictyostelium discoideum which encodes the beta-1,4-mannosyltransferase enzyme that catalyzes the reaction: GDP-Man + dolichol-PP-GlcNAc2 --> dolichol-PP-GlcNAc2-Man + GDP. This gene has a central role in the synthesis of the lipid-linked oligosaccharide precursor which becomes the core of all asparagine-linked (N-linked) glycans. The mntA gene contains a single small intron and encodes a 493 aa protein with a predicted molecular size of 56 kDa. It is located 5' to the repE gene on chromosome IV and is transcribed in the opposite orientation to repE with which it shares a 585 bp of upstream intergenic region. The predicted mntA gene product shares 38% homology with the S. cerevisiae ALG1 gene product. The MntA protein has a region homologous to the putative dolichol-binding region in the yeast ALG1 protein, but it is located in a different part of the molecule. Northern analysis revealed that the expression of the mntA gene is regulated during multicellular development with two periods of mRNA accumulation. The mntA gene product has a classical endoplasmic reticulum retention motif, and is the first Dictyostelium gene encoding a protein that is active in this organelle. The identification of this gene will allow expanded studies of the role of N-linked glycans in multicellular development.

Amino Acid Sequence↗