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Biomedical subjects

A Herman

Publications and source records attributed to A Herman.

At least 55 records · Page 3Linked to original sources

Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium.

Conventional major histocompatibility complex (MHC) class I genes encode molecules that present intracellular peptide antigens to T cells. They are ubiquitously expressed and regulated by interferon gamma. Two highly divergent human MHC class I genes, MICA and MICB, are regulated by promoter heat shock elements similar to those of HSP70 genes. MICA encodes a cell surface glycoprotein, which is not associated with beta 2-microglobulin, is conformationally stable independent of conventional class I peptide ligands, and almost exclusively expressed in gastrointestinal epithelium. Thus, this MHC class I molecule may function as an indicator of cell stress and may be recognized by a subset of gut mucosal T cells in an unusual interaction.

Animals↗

Luminal foam cell accumulation is associated with smooth muscle cell death in the intimal thickening of human saphenous vein grafts.

BACKGROUND: Occlusion of saphenous vein grafts is a major problem after coronary artery bypass graft surgery. Diffuse intimal thickening develops in all implanted aortocoronary saphenous vein grafts within 6 months to 1 year. In some regions of the thickened intima, foam cells accumulate along the luminal margin. This particular morphology resembles the morphology of unstable atherosclerotic plaques as they occur in coronary arteries. In the present study, we focused on the possible topographic relation between luminal foam cell accumulation and cell death of smooth muscle cells (SMCs) within the adjacent thickened intima. METHODS AND RESULTS: Segments of occluded and suboccluded implanted human aortocoronary saphenous vein grafts were obtained during reintervention coronary artery bypass graft surgery in 30 patients. In the regions of the vein grafts with luminal foam cell accumulation, the percentage of SMC alpha-actin immunoreactive area of the superficial intimal thickening was 6 +/- 1.4%, which was different from the 17.6 +/- 2.3% of the deep intimal thickening. A strong negative correlation between the number of foam cell nuclei and the percentage of SMC alpha-actin immunoreactive area in the adjacent superficial intimal thickening was present (r = -.77, P < .001). Within the superficial intimal thickening, cytoplasmic and DNA fragmentation could be detected, which points to apoptotic cell death. A fraction of the cytoplasmic fragments fitted the ultrastructural characteristics of matrix vesicles and showed pronounced calcium and phosphorus accumulation as demonstrated with the use of x-ray microanalysis. CONCLUSIONS: The close spatial relation among foam cell accumulation, pronounced intimal SMC loss, and cell death suggests the presence of a foam cell-derived factor that can induce cell death in the SMC population of the intimal thickening. The depletion of the intimal SMC population could promote plaque rupture and thrombotic complications in the grafts.

Cell Death↗

Genetic separation of tumor growth and hemorrhagic phenotypes in an estrogen-induced tumor.

Chronic administration of estrogen to the Fischer 344 (F344) rat induces growth of large, hemorrhagic pituitary tumors. Ten weeks of diethylstilbestrol (DES) treatment caused female F344 rat pituitaries to grow to an average of 109.2 +/- 6.3 mg (mean +/- SE) versus 11.3 +/- 1.4 mg for untreated rats, and to become highly hemorrhagic. The same DES treatment produced no significant growth (8.9 +/- 0.5 mg for treated females versus 8.7 +/- 1.1 for untreated females) or morphological changes in Brown Norway (BN) rat pituitaries. An F1 hybrid of F344 and BN exhibited significant pituitary growth after 10 weeks of DES treatment with an average mass of 26.3 +/- 0.7 mg compared with 8.6 +/- 0.9 mg for untreated rats. Surprisingly, the F1 hybrid tumors were not hemorrhagic and had hemoglobin content and outward appearance identical to that of BN. Expression of both growth and morphological changes is due to multiple genes. However, while DES-induced pituitary growth exhibited quantitative, additive inheritance, the hemorrhagic phenotype exhibited recessive, epistatic inheritance. Only 5 of the 160 F2 pituitaries exhibited the hemorrhagic phenotype; 36 of the 160 F2 pituitaries were in the F344 range of mass, but 31 of these were not hemorrhagic, indicating that the hemorrhagic phenotype is not merely a consequence of extensive growth. The hemorrhagic F2 pituitaries were all among the most massive, indicating that some of the genes regulate both phenotypes.

Animals↗

Pregnancy outcome and intelligence at age five years.

OBJECTIVE: Our purpose was to determine the influence of being small for gestational age at term and being preterm < 34 weeks on cognitive functioning at age 5 years. STUDY DESIGN: Five hundred forty-six children of black low-income mothers, nearly all at risk for being small for gestational age, followed up prenatally with early ultrasonographic gestational age dating, were classified as either term appropriate for gestational age, term small for gestational age, or preterm at < 34 weeks. At a mean of 5.5 +/- 0.5 years, a Wechsler Preschool and Primary Scale of Intelligence-Revised intelligence quotient test was administered. An intelligence quotient < 70 was used to define mental retardation. Univariate and multivariate analyses adjusted for maternal age, smoking, education and language skills, home environment, and child gender and preschool attendance were performed. RESULTS: Term small-for-gestational-age and preterm infants at < 34 weeks had 4 and 6 point intelligence quotient reductions compared with term appropriate-for-gestational-age infants. In the regression analyses these differences in intelligence quotient remained significant after confounders were adjusted. High maternal receptive language level (8 points), a positive home environment (5 points), and attendance at preschool (5 points) were each significantly associated with an increase in intelligence quotient. CONCLUSION: Both term small-for-gestational-age infants and those born at < 34 weeks had a significantly lower mean intelligence quotient, and small-for-gestational-age infants had an increased risk of mental retardation at age 5 years. Higher maternal language skills, a positive home environment, and attendance at preschool each were associated with an increase in the mean intelligence quotient of 5 to 7 points.

Adult↗

Destruction of lacis cells of the juxtaglomerular apparatus in the hypercholesterolemic rabbit.

During a study of experimentally induced atheromatosis in hypercholesterolemic rabbits we found a heavy infiltration of the lacis cell field (G field) by lipids in the kidney. A systematic study was done in 12 rabbits receiving a dietary cholesterol supplement of 0.3% for 26 weeks and in 8 animals receiving a supplement of 2% for 8 weeks. Standard histology, immunohistochemistry for a-smooth muscle cell actin and with the macrophage specific antibody RAM 11, and transmission electron microscopy were performed. In the low cholesterol, long duration group, 90% of the G fields were involved. The lipid accumulation was mainly extracellular. The lacis cells contained moderate numbers of medium sized lipid vacuoles and showed signs of cytoplasmic damage leading to disintegration. The mesangial cells contained few dipid droplets and the matrix was normal. The arterioles were not involved. The lesion suggests an impairment of the clearance of lipids, leading to interstitial accumulation and cellular damage.

Animal Feed↗

Protein inheritance: lambda plasmid replication perpetuated by the heritable replication complex.

BACKGROUND: Replication of a plasmid derived from the Escherichia coli phage lambda initiates by binding of the lambda O protein initiator to the origin of lambda DNA replication, ori lambda. The lambda P protein participates in subsequent steps of assembly of the lambda replication complex. A function of lambda P required for replication complex assembly is inactivated at 43 degrees C by the ts1 mutation. RESULTS: We found that the lambda replication complex assembled at 30 degrees C survives the temperature upshift in lambda crotsPts1 plasmid-harbouring bacteria. We present several lines of evidence that in this system (in which the replication complex assembly does not occur), the replication complex assembled prior to the temperature upshift is inherited by one of two daughter plasmid copies at each replication round for more than 30 cell generations. The 'old' replication complex-driven replication is chloramphenicol-resistant and rifampicin-sensitive. This replication is dependent on lambda O and host dnaK, dnaJ and grpE chaperone gene functions. CONCLUSIONS: The lambda O-containing replication complex is inherited together with DNA and bears information how to initiate the next round of replication at ori lambda; thus, we consider that this phenomenon deserves to be called protein inheritance.

Bacterial Proteins↗

Three-dimensional saline contrast hysterosonography and surface rendering of uterine cavity pathology.

A new technique that combines saline contrast hysterosonography with three-dimensional surface rendering for the visualization of uterine intracavitary pathologies is described. A total of 32 patients suspected of having uterine cavity pathologies on the basis of previous ultrasonography, hysterosalpingography or hysteroscopy were involved in the study. They were examined by three-dimensional high-frequency endovaginal probes (Combison 530, Kretztechnik, Zipf, Austria), with normal saline used as an expander and contrast medium. Three perpendicular planes could be evaluated simultaneous, and surface renderings were readily available. Following the instillation of normal saline, the uterine cavity appears as an echo-free, well-defined structure, and the endometrium appears as an echogenic homogeneous lining around the cavity. Data acquisition time is short and images can be stored for later evaluation. Surface rendering of polypoid structures shows echogenic masses on a pedicle protruding into the uterine cavity. Submucous fibroids appear as mixed echogenic sites bulging into the cavity. Intrauterine synechiae appear as bands of varying thickness traversing the uterine cavity. Simultaneous display of the zone of interest in three perpendicular planes enhances imaging capabilities, while surface rendering provides a comprehensive overview of the surface area of the findings and their topographical orientation. Further research using this new technique is required to document its real contribution to ultrasonographic imaging.

Contrast Media↗

Intravenous immunoglobulin treatment of pregnant patients with unexplained recurrent abortions.

Intravenous immunoglobulins, first given to recurrent aborters with anti-phospholipid syndrome, have been administered to unexplained aborters since 1986. They probably have immunomodulatory properties beyond supplying blocking antibodies. When pregnancy was confirmed, women were started with a loading dose which was repeated every 3-4 weeks until the second trimester. Dosages were empirical. Pregnancy rates ranged between 50 and 82%. The main maternal complications, i.e. allergic reactions and infections, were rare.

Abortion, Habitual↗

The benefits of mid-luteal addition of human chorionic gonadotrophin in in-vitro fertilization using a down-regulation protocol and luteal support with progesterone.

Luteal support is essential in in-vitro fertilization (IVF) when long-acting gonadotrophin-releasing hormone agonist (GnRHa) is used. Because progesterone lacks luteotrophic stimulation, it seems to be the drug of choice in cases with an increased risk of ovarian hyperstimulation syndrome (OHSS). The aim of this study was to assess the beneficial effect of the mid-luteal addition of human chorionic gonadotrophin (HCG) in IVF, using a down-regulation protocol and luteal support with progesterone, in a prospective randomized study. The study included 170 IVF cycles down-regulated with long-acting GnRHa which were supported with 50 mg/day progesterone i.m. during the luteal phase. Patients were evaluated in the mid-luteal period. Those without clinical signs of OHSS, oestradiol concentrations <1000 pg.ml and progesterone concentrations <50 ng/ml were randomly allocated to either the addition of 2500 IU HCG (HCG+ group) or no HCG (HCG- group). End luteal phase progesterone concentrations among non-pregnant patients were used to assess the contribution of exogenous progesterone and to categorize pregnancies according to their corpus luteum function. Similar low OHSS (2.7 and 1.8%) and pregnancy (30 and 29%) rates were observed in the HCG+ and HCG-groups respectively. Of the 26 pregnancies in the HCG+ cases, there was only one case with reduced corpus luteum function, compared with 12 or the 25 pregnancies among HCG-patients. Cases with reduced corpus luteum function required continuous progesterone support and presented lower betaHCG concentrations and a higher rate of adverse pregnancy outcome. We conclude that mid-luteal HCG addition does not affect pregnancy rate, but in fact helps to preserve corpus luteum function and avoids the need for further supplementation during early pregnancy.

Adult↗

Sequential measurements of human decidua-associated protein (hDP) 200 in the uterine fluid during the menstrual cycle.

PROBLEM: To examine the relationship between the concentration of uterine fluid human decidua-associated protein (hDP) 200, identified as a monoclonal rheumatoid factor, and different phases of the menstrual cycle. METHODS: Sequential measurements of hDP 200 concentration in uterine fluid were performed in 11 normal ovulatory women, aged 22-36 years. The samples were collected in early proliferative phase, late proliferative phase, periovulatory period, early secretory phase, and late secretory phase. RESULTS: Consistent fluctuations of hDP 200 levels in uterine fluid were found throughout the menstrual cycle. High levels were found during early proliferative phase and periovulatory period related to significantly lower levels during late proliferative and early luteal phases. CONCLUSION: There is menstrual phase dependent variation in the uterine fluid levels of hDP 200.

Adult↗

Hysteroscopy is superior to hysterosalpingography in infertility investigation.

BACKGROUND: The development of advanced endoscopic instrumentation in recent years has demonstrated the superiority of direct visual examination over radiographic demonstration of various body cavities. Just as laparoscopy has gradually taken a primary role in the surgical investigation of the ovulatory infertile patient, the role of intrauterine endoscopy in comparison to hysterosalpingography (HSG) needs to be reevaluated. METHODS: Four hundred and sixty-four infertile women had undergone both hysterosalpingography and a diagnostic hysteroscopy and the findings were analysed. RESULTS: Compared to hysteroscopy the sensitivity of HSG was 98%, but its specificity only 15%, the positive predictive value 45%, and negative predictive value 95%. On hysteroscopy a normal uterine cavity was found in 53% of the cases with a filling defect and in 56% of those with uterine wall irregularity on HSG. CONCLUSIONS: Hysteroscopy, a safe and rapid direct visualisation of the uterine cavity, is superior to HSG in the identification of intrauterine pathology. In view of the low positive predictive value and the low specificity of the HSG, we believe it should be replaced by the diagnostic hysteroscopy as a first line infertility investigation.

Female↗

Effect of increased ppGpp concentration on DNA replication of different replicons in Escherichia coli.

The plasmids harbouring the relA gene under an inducible promoter allowed us to increase the guanosine 5'-diphosphate-3'-diphosphate (ppGpp) concentration in Escherichia coli cells without any starvation and thus, to directly investigate the effect of ppGpp on DNA replication. We studied all types of replicons which were investigated previously in amino acid-starved bacteria and found that ColE1, oriC, lambda plasmid and pSC101 but not RK2 replicons are sensitive to high ppGpp level. To our knowledge, this paper presents the first direct evidence that replication of most, but not all, replicons is dependent on ppGpp concentration and thus, is under stringent control.

DNA Replication↗

Ovarian function following abdominal hysterectomy with and without unilateral oophorectomy.

There is no consensus concerning optimal adnexal surgery during abdominal hysterectomy, when continued hormonal function is desired, associated with reduced sequelae in the future. The aim of the study was to compare residual ovarian function following abdominal hysterectomy with preservation of one or both ovaries, in a prospective randomized study. Forty patients were allocated randomly and sequentially into two groups: those undergoing abdominal hysterectomy with unilateral oophorectomy, and those undergoing abdominal hysterectomy only. Ovarian function was evaluated by measuring FSH, TLH and E2 before, and 1 week, 1 month, 3 months and 6 months after the operation. Thirty-five percent of the patients undergoing abdominal hysterectomy with unilateral oophorectomy demonstrated impaired ovarian function 6 months after the operation. None of the patients with both preserved ovaries showed impaired ovarian function 6 months later. Therefore, when continued ovarian function following abdominal hysterectomy is desired, preservation of both ovaries seems to be more beneficial.

Adult↗

Sephadex induced granulomatous reaction in rats.

Granuloma formation in the rat lung after single or repeated i.v. injections, intratracheal instillation and intradermal implantation of Sephadex beads was studied over a time period from 3 h to 3 mo. Macrophages were identified with the mAB ED1, vascular smooth muscle cells with an mAB against alpha SMC-actin, endothelial cells with a polyclonal AB against factor VIII and cyclic activity with an mAB against PCNA. The morphology and the time course of the development of the granulomas is identical in the different experimental conditions. The macrophages form the bulk of the cellular infiltrates, giant cells appear after 24 h. Cyclic activity is early and marked in the interstitially located macrophages, it is delayed and slight around the beads, suggesting a biphasic pattern. The macrophage reaction is markedly enhanced after a second i.v. injection, indicating the development of a hypersensitivity state. Numerous eosinophils are located in the interstitium, but only few are in direct contact with the beads. Their number doesn't increase after a second i.v. injection. Intradermal implantations show only macrophages and lymphocytes. A special feature is the disappearance of the arterial wall around the beads resulting in extrusion without haemorrhages or thromboses.

Animals↗

First trimester embryo reduction: a medical solution to an iatrogenic problem.

The incidence of multiple pregnancies is increasing, mainly as a consequence of the widespread use of various infertility protocols. Since such gestations present a high risk of feto-maternal morbidity and mortality, selective first trimester fetocide remains one of the few reasonable options. We reviewed the literature dealing with the outcome of 804 multiple pregnancies following the use of transcervical, transvaginal or transabdominal approaches. Questions relating to dealing with technical failure, method of fetocide and procedural improvements are examined. In a comparison of the variables: miscarriage, preterm delivery, perinatal and neonatal loss rates, the transvaginal approach fares better, but statistical significance (P < 0.001) is achieved only for preterm delivery. We speculated that this might be attributable to the very early gestational age at which the procedure is usually performed. However, the transabdominal approach offers better results when post-manipulation maternal morbidity is considered, i.e. infection and vaginal bleeding. Since each option offers different advantages and disadvantages, additional experience and larger population samples are required to further clarify this important issue.

Female↗