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Biomedical subjects

H Rosen

Publications and source records attributed to H Rosen.

At least 19 recordsLinked to original sources

Prenatal stress selectively alters the reactivity of the hypothalamic-pituitary adrenal system in the female rat.

A study was made of the effects of prenatal stress on the reactivity of the hypothalamic-pituitary adrenal (HPA) axis in male and female offspring. Rat dams were subjected to noise and light stress on an unpredictable basis throughout pregnancy. At 28 days of age mRNA for POMC, proenkephalin and prodynorphin were measured in the hypothalamus of the offspring. A marked reduction was found in POMC mRNA in PS females (PSF) but not in males (PSM), but the other mRNA's did not differ from controls (C). At 60 days of age, PSF has 3 times higher resting levels of serum corticosterone (COR) and significantly lower dexamethasone (DEX)3H hippocampal binding sites than CF. Overnight adrenalectomy abolished the difference in DEX binding. After 10 min exposure to open field PS males and females voided more fecal pellets and made fewer center entries than C offspring, testifying to increased emotionality. Open field stress caused a 3-5-fold rise in circulating COR in all groups within 15 min, which returned to baseline by 90 min in all rats except PSF. These data show that prenatal stress can cause permanent alterations in the behavior of both sexes in stressful situations but appears to cause a selective effect on the HPA axis in the female rat.

Animals

Cytochrome b-245 is a flavocytochrome containing FAD and the NADPH-binding site of the microbicidal oxidase of phagocytes.

The NADPH oxidase of phagocytic cells is important for the efficient killing and digestion of ingested microbes. A very unusual low-potential cytochrome b (b-245) is the only redox molecule to have been identified in this system. The FAD-containing flavoprotein that binds NADPH and transfers electrons to the cytochrome has eluded identification for three decades. We show here that the haem/FAD ratio in the membranes does not change significantly on activation of this oxidase, indicating that the FAD is present in the membranes from the outset and not recruited from the cytosol. The FAD content of membranes from cells of patients with X-linked chronic granulomatous disease (CGD) lacking the cytochrome b was roughly one-quarter of that in normal subjects and in autosomal recessive CGD patients lacking the cytosolic protein p47-phox. Similar low amounts of FAD were present in uninduced promyelocytic (HL60) cells, suggesting that the low amount of FAD in cells from X-CGD patients was probably unrelated to this oxidase system. Cytochrome b-245 appears to bind both the haem and FAD, in a molar ratio of 2:1. The e.p.r. signal of the purified cytochrome was weak and had an asymmetric g(z) peak at g = 3.31. The purified cytochrome could be partially reflavinated (about 20%) in the presence of lipid. Amino acid sequence homology was detected between the beta-subunit of this cytochrome b and the ferredoxin-NADP+ reductase (FNR) family of reductases in the putative NADPH- and FAD-binding sites. 32P-labelled 2-azido-NADP was used as a photoaffinity label for the NADPH-binding site. Labelling that was competed off with NADP was observed in the region of the beta-subunit of the cytochrome. No labelling was seen in this region in X-CGD in three subjects in whom this cytochrome was missing and in a third in whom it was present but bore a Pro-His transposition in the putative NADPH-binding site. These studies indicate that cytochrome b-245 is a flavocytochrome, the first described in higher eukaryotic cells, bearing the complete electron-transporting apparatus of the NADPH oxidase.

Amino Acid Sequence

Antibody against the Leu-CAM beta-chain (CD18) promotes both LFA-1- and CR3-dependent adhesion events.

The Leukocytic cell-adhesion molecule (beta 2 integrin) family of adhesion molecules play a key role in the intercellular adhesive interactions necessary for normal immune cell function. In this study, we report an antibody that recognizes an epitope on the Leukocytic cell-adhesion molecule common beta-chain (CD18) and promotes both lymphocyte function-associated Ag-1- and CR3-dependent adhesion events. The antibody recognizes a temperature-sensitive epitope that is not dependent on the presence of divalent cations. It is proposed that antibody binding promotes a conformational change in both lymphocyte function-associated Ag-1 and CR3, which may mimic a natural activation mechanism, resulting in increased cellular adhesion.

Antibodies, Monoclonal

Influence of valve surgery on female fertility.

Pregnancies following cardiac valve surgery represent a considerable maternal and fetal risk. The present paper is a report of 163 women in child-bearing age who underwent cardiac valve surgery. Congenital (14.7%) and acquired (85.3%) cardiac defects required a total of 72 alloplastic and 16 bioprosthetic valve implantations. In 69 patients, purely instrumental correction was performed, in 6 patients conduits were placed. Thirty-four pregnancies were observed and led to the delivery of 18 healthy infants. The birth weight was always in the 2-sigma normal range or slightly above. Three cesarean sections were performed due to the cardiac defect, in 6 patients vacuum extraction or forceps delivery was done, and in 9 patients delivery was spontaneous. We observed 4 cases of spontaneous abortion, and in 12 cases interruption of pregnancy. 75.1% women never became pregnant. Potential risks in terms of endocarditis, repeated valve implantation and anticoagulation are emphasized, methods to decrease the physical strain during delivery are discussed.

Bioprosthesis

On enactment.

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Family

Expression and regulation of a proenkephalin beta-galactosidase fusion gene in the reproductive system of transgenic mice.

A fusion gene containing 3 kilobases of human proenkephalin 5'-flanking sequences and 1 kilobase of human proenkephalin 3'-flanking sequence and the easily visualized histochemical marker, Escherichia coli beta-galactosidase, was used to study the function of cis-regulatory elements within the human proenkephalin gene in transgenic mice. Here data are presented on expression and regulation of this fusion gene in the reproductive system of three independent lines of transgenic mice. Within the male reproductive system, the fusion gene is expressed in the proximal epididymis and in developing germinal cells but not in mature or elongating spermatids. In the female reproductive system, the transgene was expressed at low basal levels, but expression was dramatically stimulated in the ovary and oviduct by hormonal stimulation and pregnancy; additionally, expression was induced at the uteroplacental junction in pregnant mice. Taken together these observations suggest that critical sequences for expression and regulation of the proenkephalin gene within the reproductive system are contained within sequences of the construct.

Animals

Bactericidal activity of a superoxide anion-generating system. A model for the polymorphonuclear leukocyte.

The acetaldehyde-xanthine oxidase system in the presence and absence of myeloperoxidase (MPO) and chloride has been employed as a model of the oxygen-dependent antimicrobial systems of the PMN. The unsupplemented xanthine oxidase system was bactericidal at relatively high acetaldehyde concentrations. The bactericidal activity was inhibited by superoxide dismutase (SOD), catalase, the hydroxyl radical (OH.) scavengers, mannitol and benzoate, the singlet oxygen (1O2) quenchers, azide, histidine, and 1,4-diazabicyclo[2,2,2]octane (DABCO) and by the purines, xanthine, hypoxanthine, and uric acid. The latter effect may account for the relatively weak bactericidal activity of the xanthine oxidase system when purines are employed as substrate. A white, carotenoid-negative mutant strain of Sarcina lutea was more susceptible to the acetaldehyde-xanthine oxidase system than was the yellow, carotenoid-positive parent strain. Carotenoid pigments are potent 1O2 quenchers. The xanthine oxidase system catalyzes the conversion of 2,5-diphenylfuran to cis-dibenzoylethylene, a reaction which can occur by a 1O2 mechanism. This conversion is inhibited by SOD, catalase, azide, histidine, DABCO, xanthine, hypoxanthine, and uric acid but is only slightly inhibited by mannitol and benzoate. The addition of MPO and chloride to the acetaldehyde-xanthine oxidase system greatly increases bactericidal activity; the minimal effective acetaldehyde concentration is decreased 100-fold and the rate and extent of bacterial killing is increased. The bactericidal activity of the MPO-supplemented system is inhibited by catalase, benzoate, azide, DABCO, and histidine but not by SOD or mannitol. Thus, the acetaldehyde-xanthine oxidase system which like phagocytosing PMNs generates superoxide (O.2-) and hydrogen peroxide, is bactericidal both in the presence and absence of MPO and chloride. The MPO-supplemented system is considerably more potent; however, when MPO is absent, bactericidal activity is observed which may be mediated by the interaction of H2O2 and O.2- to form OH. and 1O2.

Acetaldehyde

The validity of temporomandibular joint radiographs using the head positioner.

1. TMJ radiographs made using the head positioner provide a valuable adjunct to diagnosis and treatment planning for patients with MPD syndrome. 2. Where extensive restorative procedures are anticipated, TMJ radiographs can be useful before embarking on a treatment plan and in documenting the postoperative results. 3. Bilateral condylar symmetry is a reasonable objective of extensive restorative dentistry. 4. Radiographic retrusion is more frequently accompanied by signs and symptoms than bilateral condylar symmetry and protrusion.

Dental Equipment

Hydroxyl radical generation by polymorphonuclear leukocytes measured by electron spin resonance spectroscopy.

Electron spin resonance spectroscopy using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) was employed to detect the formation of hydroxyl radicals (OH.) by phagocytosing polymorphonuclear leukocytes (PMN). An electron spin resonance signal with the identical g value and splitting characteristics of the DMPO/OH). adduct was detected on incubation of normal PMN with opsonized zymosan. Adduct formation was strongly inhibited by superoxide dismutase and by the OH. scavenger mannitol, but catalase had little or no effect. (DMPO/OH). was not formed by PMN from a patient with chronic granulomatous disease; in contrast, adduct formation by PMN which lack myeloperoxidase was greater than normal. These findings are discussed in relation to the formation of OH. by PMN.

Catalase

Response of patients to participation in psychiatry board examinations.

The patient who volunteers to be a subject for Part II of the certifying examination in psychiatry and neurology is an indispensable but surprisingly invisible participant in a highly controversial process. A survey of the attitudes of 78 patients toward this experience revealed that although they experienced a significant degree of stress, the overwhelming majority viewed their participation in strongly positive terms. The patient's loyalty to the host institution and the manner in which the patient is prepared for the experience appear to be the major factors in determining a positive outcome.

Adult

A study of patient falls from bed.

An analysis of patient falls from bed can help identify high risk patients and can lead to staffing, inservice education, equipment, and environmental adjustments. The method used to investigate falls in this community hospital can be adapted to any other hospital.

Accident Prevention

Ethylene formation by polymorphonuclear leukocytes. Role of myeloperoxidase.

Ethylene formation from the thioethers, beta-methylthiopropionaldehyde (methional) and 2-keto-4-thiomethylbutyric acid by phagocytosing polymorphonuclear leukocytes (PMNs) was found to be largely dependent on myeloperoxidase (MPO). Conversion was less than 10% of normal when MPO-deficient PMNs were employed; formation by normal PMNs was inhibited by the peroxidase inhibitors, azide, and cyanide, and a model system consisting of MPO, H2O2, chloride (or bromide) and EDTA was found which shared many of the properties of the predominant PMN system. MPO-independent mechanisms of ethylene formation were also identified. Ethylene formation from methional by phagocytosing eosinophils and by H2O2 in the presence or absence of catalase was stimulated by azide. The presence of MPO-independent, azide-stimulable systems in the PMN preparations was suggested by the azide stimulation of ethylene formation from methional when MPO-deficient leukocytes were employed. Ethylene formation by dye-sensitized photooxidation was also demonstrated and evidence obtained for the involvement of singlet oxygen (1O2). These findings are discussed in relation to the participation of H2O2, hydroxyl radicals, the superoxide anion and 1O2 in the formation of ethylene by PMNs and by the MPO model system.

Azides