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Biomedical subjects

B Held

Publications and source records attributed to B Held.

At least 19 recordsLinked to original sources

Electron beam transport in heterogeneous slab media from MeV down to eV.

An optimized Monte Carlo method based on the null collision technique and on the treatment of individual interactions is used for the simulation of the electron transport in multilayer materials from high energies (MeV or several hundred of keV) down to low cutoff energies (between 1 and 10 eV). In order to better understand the electron transport and the energy deposition at the interface in the composite application framework, two layer materials are considered (carbon and polystyrene with densities of 1.7 g cm(-3) and 1.06 g cm(-3), respectively) under two slab or three slab configurations as, e.g. a thin layer of carbon sandwiched between two polystyrene layers. The electron-matter cross-sections (electron-carbon and electron-polystyrene) used in the case of pure material (carbon and polystyrene) as well as our Monte-Carlo code have been first validated. The boundary interface layer is considered without any mean free path truncation and with a rigorous treatment of the backscattered and also the forward scattered electrons from one layer to another. The large effect of the choice of a low cutoff energy and the dissociation process consideration are also clearly shown in the heterogeneous multi-layer media more particularly on the secondary electron emission, inelastic collision number and energy spectra.

Carbon↗

Absence of the gamma subunit of the skeletal muscle dihydropyridine receptor increases L-type Ca2+ currents and alters channel inactivation properties.

In skeletal muscle the oligomeric alpha(1S), alpha(2)/delta-1 or alpha(2)/delta-2, beta1, and gamma1 L-type Ca(2+) channel or dihydropyridine receptor functions as a voltage sensor for excitation contraction coupling and is responsible for the L-type Ca(2+) current. The gamma1 subunit, which is tightly associated with this Ca(2+) channel, is a membrane-spanning protein exclusively expressed in skeletal muscle. Previously, heterologous expression studies revealed that gamma1 might modulate Ca(2+) currents expressed by the pore subunit found in heart, alpha(1C), shifting steady state inactivation, and increasing current amplitude. To determine the role of gamma1 assembled with the skeletal subunit composition in vivo, we used gene targeting to establish a mouse model, in which gamma1 expression is eliminated. Comparing litter-matched mice with control mice, we found that, in contrast to heterologous expression studies, the loss of gamma1 significantly increased the amplitude of peak dihydropyridine-sensitive I(Ca) in isolated myotubes. Whereas the activation kinetics of the current remained unchanged, inactivation of the current was slowed in gamma1-deficient myotubes and, correspondingly, steady state inactivation of I(Ca) was shifted to more positive membrane potentials. These results indicate that gamma1 decreases the amount of Ca(2+) entry during stimulation of skeletal muscle.

Animals↗

[Immunohistochemical study of the distribution of constitutive nitric oxide synthase in vascular endothelium of the nasal mucosa in the human].

BACKGROUND: Human nasal mucosa is a highly regulated tissue that performs a wide range of physiological functions. In addition to the classic and peptidergic neurotransmitters, the endogenously produced free radical gas nitric oxide (NO) has been found to be increasingly important for the vascular regulation of this tissue. NO-dependent control of vascular tone works in two ways, consisting of neurally produced NO acting as a neurotransmitter on the one hand and endothelially produced NO on the other hand. Neurons and endothelial cells contain various isoforms of the enzyme nitric oxide synthase, which forms NO out of L-arginine. The aim of this study was to examine the distribution of endothelial constitutive NO-synthase (ecNOS) in the human nasal mucosa of inferior turbinates. METHODS: Immunocytochemistry (avidin-biotin method) with polyclonal and monoclonal antibodies against eNOS and cluster of differentiation 31, a marker for endothelial and certain blood cells, was used in order to gain more detailed information on the physiological distribution and significance of NOS in vascular endothelium of different vessel types. RESULTS: Positive eNOS-immunoreactions were found in the endothelial cells of arterial blood vessels of different diameters as well as in capillaries and postcapillary venules. Venous sinuses with or without subendothelial cushions did not show any immunoreactions. CONCLUSIONS: There is strong evidence that vascular tone in human nasal mucosa is not only subject to nerval control, but also influenced directly by mediators released from the endothelium. The present results lead to the conclusion that in physiological conditions endothelially produced NO has an influence on the arterial component of the swelling mechanism in human nasal mucosa. Because eNOS could also be detected in capillaries and postcapillary venules, NO might also play an important role in plasma extravasation.

Adult↗

Histochemical and immunocytochemical study of nitrergic innervation in human nasal mucosa.

Nitric oxide (NO) is a free radical gas that has been found to be produced in neuronal cells by the action of the enzyme brain nitric oxide synthase (bNOS). The aim of this study was to identify NO-containing nerve structures in the human nasal mucosa by localizing bNOS and to find out whether NO production is attached to the parasympathetic system. For this purpose, immunocytochemistry with antibodies to bNOS and neurofilament was performed. Additionally, nicotinamide-adenine dinucleotide phosphate diaphorase (NADPH-d), an enzyme that correlates with the localization of NO synthase, and acetylcholinesterase were visualized in a histochemical double staining technique on frozen sections. The NADPH-d and bNOS reactions were found in axons of nerve bundles and in subepithelial, glandular, and vascular nerve fibers. Arteries showed a distinctly developed nitric innervation, whereas no activity was found in nerve fibers supplying veins. A high coexistence of NADPH-d in parasympathetic nerves could be detected. These findings suggest that NO takes part in the nerve control functions of the human nasal mucosa.

Acetylcholinesterase↗

Amyloid beta protein increases Ca2+ currents in rat cerebellar granule neurones.

The effects of amyloid beta protein on voltage-sensitive Ca2+ channels were measured in cultured rat cerebellar granule neurones using the whole-cell patch-clamp technique. Incubation of cells for 24 h with 1 microM amyloid beta protein resulted in a 40-60% increase in the Ca2+ channel current at potentials positive to 0 mV. The increase in current was accompanied by a 5 mV shift in channel activation in the positive direction and an increase in the rate of channel deactivation. Inhibition of L-type channels with 2 microM nifedipine did not prevent the rise in Ca2+ channel current or effects on current activation and deactivation. The N-type Ca2+ channel antagonist omega-conotoxin GVIA (1 microM) abolished the current increase and increase in the rate of channel deactivation but did not prevent the shift in the current activation curve. These data suggest that amyloid beta protein may exert its effects on cell survival by increasing Ca2+ influx through N-type Ca2+ channels in central neurones.

Amyloid beta-Peptides↗

Endothelin-1 inhibits voltage-sensitive Ca2+ channels in cultured rat cerebellar granule neurones via the ET-A receptor.

In this study, we have investigated the effect of the vasoconstrictor peptide endothelin-1 (ET-1) on voltage-sensitive Ca2+ channels in rat cerebellar granule neurones using the patch-clamp technique. Using amphotericin B perforated-patch recording of whole-cell currents, the Ca2+ channel current was inhibited by 28.4+/-6.4% by 400 nM ET-1, but was unaffected when experiments were repeated using the whole-cell, ruptured-patch configuration. In cell-attached patches, 400 nM ET-1 inhibited unitary L-type Ca2+ channel currents (IBa) by 85+/-5%. ET-1 decreased the open probability (NPo) and the frequency of channel opening and increased the mean closed time of channels. No effects on the mean open time or the time constants for channel opening or closure were observed. L-type Ca2+ channel inhibition was dose dependent with an IC50 of 19 nM. The effect of ET-1 was prevented by the combined endothelin-A and -B receptor antagonist PD145065 (10 microM), indicating a receptor-mediated effect. The ET-A receptor antagonist BQ-123 (10 microM) prevented Ca2+ channel inhibition by ET-1, while the ET-B receptor agonist sarafotoxin 6c (500 nM) had no effect. The inhibition by ET-1 was not due to a change in the voltage of channel activation. Fura-2 Ca2+ imaging showed that no substantial rise in intracellular Ca2+ levels occurred during ET-1 application excluding a Ca2+-dependent inhibition of the channels. Thus in cultured rat cerebellar granule neurones, ET-1 inhibits L-type Ca2+ channels via activation of the ET-A receptor. Inhibition may be mediated by an as yet unidentified cytoplasmic second messenger.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Biochemical and molecular characterization of the insecticidal fragment of CryV.

Two C-terminal deletion constructs were made to study the effect of such deletions on the biological activity of the CryV protein of Bacillus thuringiensis subsp. kurstaki. The results of feeding on neonatal larvae of Ostrinia nubilalis (European corn borer [ECB]) indicated that the 50% lethal dose of the full-length CryV protein was 3.34 micrograms/g of diet (95% fiducial limits, 2.53 to 4.32 micrograms/g of diet). Removal of 71 amino acids (aa) from the C terminus had little effect on toxicity, whereas deletion of 184 aa abolished the insecticidal activity of the CryV protein completely. Truncations of the full-length CryV protein were also generated with trypsin and the midgut protease of ECB. The proteolytically treated products were characterized by determining their N-terminal amino acid sequences. The CryV protein was found to be cleaved by both proteases through a two-step process. Initially an intermediary form was generated which contained aa 45 of full-length CryV as its N-terminal end. The C-terminal end of this peptide was not experimentally determined. However, analysis of the deduced amino acid sequence of CryV indicated that the C-terminal end of the intermediary form is likely either aa 655 or 659. Further N-terminal processing of the intermediary form resulted in a protease-resistant core form. The core included aa 156 to aa 655 or 659. While the intermediary form retained 100% of the ECB larval toxicity, the core form exhibited only approximately 22% of the toxicity of the full-length protein.

Animals↗

[Otoacoustic emissions (TEOAE and DPOAE) after middle ear operation].

BACKGROUND: The behavior of transitory evoked otoacoustic emissions (TEOAE) and distortion products (DPOAE) in patients after middle ear surgery is unknown. METHODS: We examined TEOAEs and DPOAEs in 37 ears following stapes surgery, 16 ears following tympanoplasty type I, and nine ears after reconstruction of the ossicular chain. In all patients, the postoperative conductive hearing loss was less than 15 dB HL. In some cases, there was additional sensorineural hearing loss in the high frequencies. RESULTS: Surprisingly, TEOAEs were present only in 10 of 62 ears postoperatively compared to all 22 control subjects. TEOAEs were detected in four of 37 ears after stapes surgery, in six of 16 ears after tympanoplasty type I, and in none of the nine ears who had undergone reconstruction of the ossicular chain. DPOAEs were detected in only four of 31 ears postoperatively compared to all 22 control ears. CONCLUSIONS: These results and their relation to the retrograde OAE transmission in the middle ear are discussed. Changes enhancing the stiffness of the middle ear seem to have a greater effect than those enhancing the mass.

Adolescent↗

[Endogenously formed nitric oxide in nasal mucosa of the human: detection by nicotinamide-adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry].

BACKGROUND: Nitric oxide (NO) is an intercellular transmitter, both in the central and in the peripheral nervous system. In addition to nerve cells, NO is also produced in epithelial cells of various tissues and in the endothelium. NO is formed by the action of nitric oxide synthase (NOS). There is evidence that NOS can be marked by NADPH-diaphorase (NADPH-d) activity in many cell types. The aim of this study was to identify NOS-positive structures in human nasal mucosa by using NADPH-d-histochemistry. METHODS: Frozen sections from inferior turbinates were fixed with buffered formalin and then treated according to the description of Vincent and Kimura. Additionally, the same sections underwent a double staining procedure for acetylcholinesterase (Karnovski-Roots) to show a correlation with cholinergic nerve structures. RESULTS: Strong reactions were found in the epithelium and in nerve fibres, compared to less NADPH-d activity in seromucous glands and the endothelium of the different vessel types. Singular NADPH-d positive nerves were found within nerve bundles, periarterially, in the subepithelial layer and surrounding glands and their ducts. A frequent localisation of NADPH-d could be detected in parasympathetic nerve fibres. CONCLUSIONS: The occurrence of NADPH-d in epithelial, glandular and nerval structures suggests that NOS takes part in physiological functions and possible pathophysiological processes of the nose. Similar to findings in various other organs this investigation demonstrated that the neurotransmitter NO can also be associated with the parasympathetic nervous system in the human nasal mucosa.

Acetylcholinesterase↗

Exocytosis and selective neurite calcium responses in rat cerebellar granule cells during field stimulation.

The free calcium concentration, [Ca2+]c, in fura-2-loaded rat cerebellar granule cells was investigated by digital imaging during trains of uniform field stimuli in order to compare the ability of calcium channels in somata and neurites to respond to brief, physiologically relevant depolarizations. Very few somata responded to 20 Hz trains of 1 ms pulses, while virtually all neurites showed an extensive increase which was rapidly reversed when stimulation was terminated. In contrast, both somata and neurites responded when cells were depolarized with 50 mM KCI. The field stimuli evoked a tetrodotoxin-sensitive increase in Na+ concentration in both somata and neurites. When 4-aminopyridine, which inhibits delayed K+ currents in these cells, was present during the field stimulus both somata and neurites increased their [Ca2+]c, suggesting that prolongation of the duration of depolarization is required for somatic Ca2+ channel activation. The neurite response did not depend on the orientation of the neurite relative to the applied field. The neurite response was insensitive to nifedipine (1 microM) and omega-agatoxin-IVA (30 nM) but was uniformly inhibited by omega-conotoxin-GVIA (30% inhibition at 1 microM) and omega-conotoxin-MVIIC (44% inhibition at 5 microM). The two inhibitors were not additive. The neurite [Ca2+]c response was insensitive to the combination of ionotropic glutamate receptor antagonists. Field stimulation caused the exocytosis of the fluorescent probe FM1-43 previously loaded during KCI depolarization, suggesting that presynaptic Ca2+ channels contribute to the field-evoked neurite response.

Animals↗

Low-dose tretinoin does not improve striae distensae: a double-blind, placebo-controlled study.

Striae distensae occur on the abdomen and/or breast in 90 percent of all pregnant women and are the result of extrinsic and intrinsic factors. This study investigated the response of pregnancy-related abdominal striae to treatment with tretinoin cream (0.025 percent) applied daily for seven months. In this study, eleven subjects were randomly assigned to tretinoin or placebo treatment groups. Before and after photographs were evaluated by a standardized system. There was no difference or improvement in the treated group compared with control subjects. Tretinoin 0.025 percent cream was ineffective in improving striae distensae in these subjects.

Abdomen↗

Retrospective maternal mortality case ascertainment in West Virginia, 1985 to 1989.

OBJECTIVE: The death of women from pregnancy-related causes remains a threat to national maternal and child health. Maternal deaths as persistent, albeit rare occurrences are overlooked if vital registration systems are relied on to report such deaths. STUDY DESIGN: Live birth records were matched with death records for women of reproductive age to detect if a woman died within 1 year of delivery. The data for potential cases were reviewed by committee and classified as maternal and nonmaternal deaths. RESULTS: Of all linked birth-death records, 32% were related to pregnancy: 81% were directly related to pregnancy and 19% were indirectly related to pregnancy. The most frequent causes of death were hemorrhage and embolism. Thirty-eight percent of the women were transferred to tertiary hospitals before death. The case ascertainment through this study improved maternal death detection by 100% over official vital statistics. CONCLUSION: Enhanced maternal mortality surveillance increased the detection of maternal death in West Virginia. Case review of these deaths yielded important information useful in shaping the state's perinatal system.

Adult↗

Luteal-phase support in stimulated cycles in an in vitro fertilization/embryo transfer program: progesterone versus human chorionic gonadotropin.

A study was undertaken to compare the hormonal parameters [serum concentrations of estradiol (E2), and progesterone (P) and P/E2 ratios] of patients undergoing in vitro fertilization/embryo transfer to whom either progesterone in oil or human chorionic gonadotropin (hCG) was administered as luteal support. Seventeen patients were studied in 20 cycles. In 10 randomly assigned cycles 25 mg of intramuscular progesterone in oil was administered daily from the day of embryo transfer (day +4) until day +18. In the other 10 cycles, 1500 IU of hCG was given intramuscularly on days +4, +7, +10, and +13. Even when accounting for the differences in recruitment in the two groups, the hCG-treated group had significantly higher concentrations of serum P (P less than 0.01) and E2 (P less than 0.05) during the luteal phase. The luteal P/E2 ratios were higher in the progesterone-treated group because of the lower E2 levels in that group, although the difference was not statistically significant. The ratio of the mean luteal P to the preovulatory serum E2 was significantly higher in the hCG-treated group (P less than 0.01). There were three clinical pregnancies in the hCG-treated group. We conclude that (1) higher P concentrations are achieved with hCG treatment than with progesterone treatment during the luteal phase; (2) high luteal P/E2 ratios per se may not be an important determinant of implantation; (3) progesterone production by the corpus luteum is not maximal in progesterone-treated cycles; and (4) the usefulness of hCG as a luteal support agent should be further evaluated.

Chorionic Gonadotropin↗

Histologic response to microsuture materials.

Long- and short-term reactions of reproductive tract tissue to microsurgical suture materials were compared. The five materials were: polyglactin 910 (Vicryl), polyglycolic acid (Dexon-S), polypropylene (Prolene), nylon (Ethilon and Dermalon) and chromic catgut; the calibers ranged from 6-0 to 10-0. Sixteen days after suture placement the smallest tissue reaction was seen with 9-0 and 10-0 suture materials; Dexon-S caused a slightly greater reaction than did Vicryl. Prolene, 8-0 and 9-0, produced the smallest tissue response when compared to other sutures of similar size. Larger sutures incited greater tissue reactions. Forty-two days after placement, each suture was associated with similar or lower reaction scores than those observed at 16 days. At 90 days all the Dexon-S sutures had been absorbed. Vicryl had less of a late reaction as compared to the other sutures. Reactions persisted longer with nonabsorbable suture, and the tissue response depended on both the suture material and caliber. Vicryl, 8-0 to 10-0, incited the smallest short- and long-term tissue reaction; at those sizes it seems optimal for reconstructive tubal surgery.

Animals↗

Patterns of increase in serum estradiol in response to ovarian stimulation and their relationship to oocyte fertilization and cleavage in vitro.

The in vitro fertilization and cleavage rates of oocytes obtained from patients exhibiting two different patterns of increase in serial serum concentrations of estradiol (E2) in response to ovarian stimulation were compared. Forty-two cycles (from 38 stimulated patients) were evaluated because they fulfilled requirements from two pre-defined patterns of E2 response to ovarian stimulation. In 16 cycles, serial serum E2 concentrations followed a "plateau" pattern (group A), viz., the rate of increase in the serum concentration of E2 decreased prior to the administration of human chorionic gonadotropin (hCG). In 26 cycles, serial serum E2 concentrations followed a "leap" pattern (group B), in which the rate of increase in serum concentrations of E2 increased progressively up to and including the day of hCG administration. There was no significant difference in the fertilization rate of oocytes obtained from patients exhibiting either pattern A or pattern B (78 versus 74%) but the cleavage rate was significantly higher in ova obtained from patients who exhibited pattern A rather than pattern B (72 vs 50%; P less than or equal to 0.01). In addition, embryos resulting from fertilized ova obtained from women in group A were of better quality morphologically than those obtained from women in group B (mean embryo grades, 3.9 vs 3.2; P less than or equal to 0.005). We conclude that cycles in which serial serum concentrations of E2 follow pattern A in response to stimulation give rise to oocytes that, when fertilized, yield higher cleavage rates and better-quality embryos than oocytes obtained from women in whom serial serum E2 concentrations follow pattern B.(ABSTRACT TRUNCATED AT 250 WORDS)

Chorionic Gonadotropin↗

Subclavian vein stenosis as a complication of subclavian catheterization for hemodialysis.

Thirteen patients had placement of a subclavian vein catheter for temporary vascular access for hemodialysis. Peripheral venography was performed within two to six weeks of catheter placement. Forty-six percent (six of 13 patients) developed subclavian vein narrowing, which resolved in two patients. The duration of catheter placement had no impact on the incidence of this complication. Subclavian vein catheterization can frequently lead to subclavian vein stenosis, which often will resolve spontaneously. Consideration should be given to placement of subclavian lines on the contralateral side of a planned permanent vascular access.

Catheterization↗