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Biomedical subjects

D Singer

Publications and source records attributed to D Singer.

At least 55 records · Page 3Linked to original sources
PubMed1994

Gastric intramural pH as indicator of early allograft viability in orthotopic liver transplantation.

The determination of the viability of OLT grafts has relied upon metabolic tests of the liver, which take several hours to evaluate and therefore are only conclusive in most patients well into the postoperative period. Earlier diagnosis of graft failure or nonfunction would allow intraoperative reassessment of surgical technique and, in the case of graft failure, earlier planning for retransplantation. Since gastrointestinal mucosal ischemia is one of the earliest manifestations of impaired core tissue in the critically ill, a tonometric nasogastric tube (Tonomitor) was used in our patients to measure intramucosal gastric pH (pHi) during the preanhepatic (stage I), anhepatic (stage II), and neohepatic (stage III) phases of OLT in 35 patients as an indicator of graft liver function and viability. Based on the results of the pHi measurement 30 min after reperfusion during stage III, patients were divided into 2 groups using a pHi of 7.30 as the dividing point. Patients with a pHi equal or higher than 7.30 were assigned to group 1 (n = 24) and patients with a pHi lower than 7.30 were assigned to group 2 (n = 11). The pHi in group 1 patients averaged 7.37 +/- 0.5 30 min after reperfusion and throughout surgery. The pHi in group 2 patients was lower than that of the group 1 patients 30 min after reperfusion, 7.23 +/- 0.04 (P < 0.001). The pHi in 10 group 2 patients returned to normal within 3 hr after reperfusion and the pHi values for these patients were not significantly different from those of group 1 at 3 hr after reperfusion. The pHi in 1 group 2 patient remained lower than 7.30 and never returned to normal; this patient underwent retransplantation the following day. Utilizing the tonometric nasogastric tube to sample intramucosal pH allowed early detection of graft function and intermittent trending of pHi in patients with questionable graft function during the operative period. It also provided a means of assessing graft function independent of enzymatic criteria, which provide little information in the early phase of transplantation.

Adult↗
PubMed1994

Polygalacturonase-inhibiting protein accumulates in Phaseolus vulgaris L. in response to wounding, elicitors and fungal infection.

Polygalacturonase-inhibiting protein (PGIP) is a cell wall-associated protein that specifically binds to and inhibits the activity of fungal endopolygalacturonases. The Phaseolus vulgaris gene encoding PGIP has been cloned and characterized. Using a fragment of the cloned pgip gene as a probe in Northern blot experiments, it is demonstrated that the pgip mRNA accumulates in suspension-cultured bean cells following addition of elicitor-active oligogalacturonides or fungal glucan to the medium. Rabbit polyclonal antibodies specific for PGIP were generated against a synthetic peptide designed from the N-terminal region of PGIP; the antigenicity of the peptide was enhanced by coupling to KLH. Using the antibodies and the cloned pgip gene fragment as probes in Western and Northern blot experiments, respectively, it is shown that the levels of PGIP and its mRNA are increased in P. vulgaris hypocotyls in response to wounding or treatment with salicylic acid. Using gold-labeled goat-anti-rabbit secondary antibodies in EM studies, it has also been demonstrated that, in bean hypocotyls infected with Colletotrichum lindemuthianum, the level of PGIP preferentially increases in those cells immediately surrounding the infection site. The data support the hypothesis that synthesis of PGIP constitutes an active defense mechanism of plants that is elicited by signal molecules known to induce plant defense genes.

Amino Acid Sequence↗
PubMed1994

Toothbrushes: manual and electric.

Newer designs of manual and electric toothbrushes are briefly described. It is difficult to conduct meaningful clinical studies to detect the apparently small differences between these devices. Recommendations that dentists make to their patients should therefore be based on individual patient considerations.

Humans↗
PubMed1994

The effects of spiramycin and/or scaling on advanced periodontitis in humans.

It has long been questioned whether antibiotics, used as a supplement to traditional therapy, provide any lasting benefit in the treatment of chronic periodontitis. This study was designed to evaluate Spiramycin as an adjunct to scaling and root planing in the treatment of advanced chronic periodontitis. In total, 193 patients with advanced periodontitis were recruited in seven centres using selection criteria previously described. After undergoing thorough scaling and root planing, all patients randomly received either Spiramycin, 1,500,000 international units, twice per day (IU, bid) for 14 days (96 patients), or a visually-identical placebo capsule (97 patients). The clinical parameters measured were plaque index, crevicular fluid level, probing depths, bleeding on probing and attachment level changes. Data was recorded at baseline, two-, eight-, 12- and 24-weeks visits. A total of 189 patients completed the study (96 placebo, 93 Spiramycin). Statistically significant differences in probing depth, favoring Spiramycin, were seen at two weeks (p < 0.0125), eight weeks (p < 0.0020), 12 weeks (p < 0.0032) and 24 weeks (p < 0.0075). Spiramycin also produced a significant improvement in attachment level at 12 weeks (p < 0.0146). All other clinical parameters showed no difference between drug and placebo. This study shows that Spiramycin, as an adjunct to thorough scaling and root planing, provides a statistically significant improvement in probing depths for up to 24 weeks when compared with scaling and root planing alone. Both longer studies and microbiologic evaluations are necessary to determine whether a more lasting benefit is possible.

Adult↗
PubMed1993

Ventricular expression and circulating levels of immunoreactive dynorphin in heart transplant recipients.

1. Dynorphin, an endogenous opioid peptide, acts on specific kappa-opioid receptors in the rat heart for the local regulation of atrial natriuretic peptide release. No known study has examined the expression of dynorphin in the human heart. 2. In the present study a specific radioimmunoassay technique was used to determine ventricular expression of dynorphin at the peptide level in endomyocardial biopsy specimens and in plasma obtained from 13 heart transplant recipients. Ventricular biopsy specimens collected from 10 patients without cardiac complications during necropsy (less than 24 h from time of death) and plasma samples from 10 normal healthy subjects were used as controls. 3. The immunoreactive level of ventricular dynorphin was higher in heart transplant recipients (mean +/- SEM 141 +/- 32 pg/mg of soluble protein, range 7-573 pg/mg of soluble protein, P < 0.001) than in control subjects (16 +/- 3 pg/mg of soluble protein, 2-34 pg/mg of soluble protein). The plasma concentration of immunoreactive dynorphin was also higher (P < 0.001) in heart transplant recipients (mean +/- SEM 14 +/- 1 pg/ml, range 5-39 pg/ml) than in normal healthy subjects (7 +/- 0.4 pg/ml, 5-10 pg/ml). No relationship was observed between ventricular and plasma levels of dynorphin. 4. These results show that immunoreactive levels of dynorphin in plasma and ventricle are increased after heart transplantation, suggesting a possible pathophysiological role for dynorphin in the heart.

Adolescent↗
PubMed1993

Ventricular expression of brain natriuretic peptide gene following orthotopic cardiac transplantation in children--a three year follow up.

OBJECTIVE: The aim was to examine ventricular brain natriuretic peptide (B-type natriuretic peptide, BNP) gene expression and to determine its relationship with ventricular BNP and circulating BNP levels in paediatric cardiac transplant recipients, over a three year period after transplantation. METHODS: Total RNA extracted from endomyocardial right ventricular biopsy tissues (n = 26) of 13 cardiac transplant recipients (age range 5-17 years) and 10 normal hearts obtained at necropsy (age range 19-76 years) as controls was analysed by northern and slot blot hybridisations. Specific radioimmunoassay techniques were used to determine levels of BNP and atrial natriuretic peptide (A-type natriuretic peptide, ANP) in plasma (n = 26) and ventricular biopsy (n = 26) samples. RESULTS: Ventricular BNP messenger ribonucleic acid (mRNA) levels from slot blot hybridisations in the transplanted heart [122(3) arbitrary units, range 97-143] were significantly higher (p < 0.01) than in the normal heart [63(5) arbitrary units, range 37-98]. Northern blot hybridisations confirmed this result and gave a major BNP mRNA transcript of approximately 900 nucleotides. There was no significant relationship between ventricular BNP mRNA levels and ventricular BNP (r = 0.15, p = 0.5, n = 26) or plasma BNP levels (r = 0.16, p = 0.4, n = 26). There was also no significant relationship between ventricular BNP mRNA levels and any of the haemodynamic variables, or immunosuppressive drugs. A ventricular ANP RNA transcript of approximately 900 nucleotides was detected in the transplanted heart but was below the limit of detection in the normal heart. For the long term study, increased levels of BNP and ANP in both plasma and ventricular samples were observed in the first year after transplantation, with a significant reduction (p < 0.01) in levels three years later. CONCLUSIONS: Ventricular BNP gene expression is increased at the mRNA level after heart transplantation in children. Expression of both ventricular BNP mRNA and ANP mRNA in the transplanted heart may be an important response in the modulation of cardiac function after transplantation.

Adolescent↗
PubMed1993

Cardiac transplantation affects ventricular expression of brain natriuretic peptide.

OBJECTIVE: The aim was to examine the ventricular expression of brain natriuretic peptide (BNP) in the transplanted human heart. METHODS: Serial right ventricular biopsies (n = 68) and plasma samples (n = 68) were obtained for measurement of BNP and atrial natriuretic peptide (ANP) from 14 orthotopic cardiac transplant recipients from 1-74 weeks after transplantation. Right ventricular specimens (n = 10) were also obtained from normal hearts during necropsy as controls. RESULTS: Mean ventricular BNP in cardiac transplant recipients was higher (p < 0.05) than in normal hearts, at 13531(SEM 2244) pg.mg-1 soluble protein (range 3232-109448) v 56(11) pg.mg-1 (range 16-91). Ventricular BNP and ANP values were correlated (r = 0.57, p < 0.05). Plasma BNP concentrations were higher (p < 0.05) than plasma ANP concentrations, at 202(16) pg.ml-1 (range 84-655) v 100(12) pg.ml-1 (range 8-484), and were raised (p < 0.05) in comparison with normal plasma BNP concentrations of 20(1.8) pg.ml-1 (range 10-23). Mean ventricular BNP was correlated with time after transplant (r = 0.72, p < 0.05, n = 68) and with mean plasma BNP (r = 0.80, p < 0.05, n = 14). There was no significant relationship between BNP levels and intracardiac or systemic blood pressure, or prednisolone dose (0.1-0.3 mg.kg-1.d-1). The increase in ventricular BNP with time after transplant was not explained by cardiac rejection assessed from histology, and plasma BNP was not significantly increased during rejection episodes. CONCLUSIONS: High levels of BNP are synthesised and secreted by the transplanted human ventricle, and the transplanted ventricle may be an important source of circulating BNP. The significant positive association between ventricular BNP and time after transplant suggests a possible self compensatory mechanism or functional adaptation of the transplanted heart which may be beneficial to ventricular function.

Adolescent↗
PubMed1993

Therapeutic possibilities and limits in multiple primary carcinomas: consideration of 38 cases.

The authors report their experiences of 38 cases of multiple primary carcinomas, of which 17 were synchronous and 21 metachronous. Some of them were localized to the same organs and others on different organs. It is important that diagnosis be established in due time for the first and most of all, for the second or third tumour. Surgery by tumour exeresis constitutes the main treatment, being associated with radiotherapy and chemotherapy as adjuvants. The results recorded here may be considered to be quite good, since many patients reached 5 years of survival, both after the first and after the second operation. Thus, mean survival was 5.53 years in the 17 patients with synchronous carcinomas and more than 10 years in the 21 cases of metachronous carcinomas, i.e. 8.9 years after the first operation +4.05 years after the second operation with a 2.63 mortality rate.

Adult↗
PubMed1992

Localised deep microwave hyperthermia in the treatment of benign prostatic hyperplasia: long-term assessment.

A group of 133 patients with benign prostatic hyperplasia who were either poor operative risks or who had refused surgery underwent localised deep microwave hyperthermia, without supplementary drugs. In 59% of patients who had had an indwelling catheter, freedom from urological obstruction and satisfactory voiding were maintained for 7 years and catheterisation was not required. In patients with severe prostatic symptoms, 65% showed general improvement and satisfactory voiding for 8 years. There were no side effects. Patients who relapsed were given a second course of treatment and 75% responded positively. This positive response and the lack of side effects suggest that localised deep microwave hyperthermia may be an effective alternative to surgery in the management of high risk patients and those who are reluctant to undergo surgery.

Aged↗
PubMed1992

NaCl-dependent expression of amiloride-blockable Na+ channel in Xenopus oocytes.

RNA was isolated from chicken lower intestine (both colon and coprodeum) and injected into Xenopus oocytes. 22Na+ fluxes measured after 1-4 days demonstrated the induction of an amiloride-blockable pathway. The Na+ transporter expressed by the exogenous RNA had a high affinity to amiloride (inhibitory constant less than 0.1 microM), but was insensitive to ethylisopropyl amiloride, i.e., it is likely to be the apical Na+ channel. Functional channels were readily expressed in oocytes injected with RNA derived from chickens fed a low-NaCl diet. On the other hand, no channel activity was detected in oocytes injected with RNA isolated from chickens fed a high-NaCl diet. Thus the previously reported regulation of transport by the dietary NaCl intake involves modulations in the level of mRNA that codes either for the Na+ channel or a posttranscriptional regulator of the channel.

Amiloride↗
PubMed1992

Influence of pH management on hemodynamics and metabolism in moderate hypothermia.

In moderate hypothermia, three different concepts of pH management have been described to date: pH-stat, alpha-stat, and alkalinity. In our study these pH strategies were compared in adult sheep, with animals serving as their own controls for direct comparability. Hemodynamic parameters, such as mean aortic pressure (from 109 +/- 12 to 72 +/- 23 mm Hg), cardiac output (from 5.55 +/- 1.25 to 4.5 +/- 0.82 L/min), and systemic oxygen consumption (from 3.73 +/- 0.8 to 1.81 +/- 0.4 ml/kg/min), decreased significantly with alpha-stat at 28 degrees C from values for normothermia. No marked or even significant differences were found among the three pH strategies in any value, with the exception of body oxygen consumption. The difference of 2% between pH-stat and alpha-stat, at 0.06 ml oxygen/kg/min, was significant (p < or = 0.05), however of no practical relevance because hypothermia itself caused a decrease of nearly 52%. With regard to myocardial parameters, pH-stat impaired myocardial function compared with both alpha-stat and alkalinity. At nearly identical mean aortic pressures and cardiac outputs, myocardial oxygen consumption reached the highest level in pH-stat (7.65 ml oxygen/100 gm/min; alpha-stat, 6.76 ml oxygen/100 gm/min; p < or = 0.05). Myocardial efficiency thus decreased from 21% (alpha-stat) to 17% (pH-stat). No evident changes in hemodynamic and metabolic values were found for alkalinity vs alpha-stat. The best response to continuously infused epinephrine, however, was found with alkalinity. According to our data there was an impairment of myocardial function without any evident further reduction in body metabolism with pH-stat vs alpha-stat. There were, however, no marked metabolic or hemodynamic differences between alkalinity and alpha-stat, with the exception of a better preservation of sensitivity to adrenergic stimuli with alkalinity.

Acid-Base Equilibrium↗
PubMed1991

The roles of the subunits in the function of the calcium channel.

Dihydropyridine-sensitive voltage-dependent L-type calcium channels are critical to excitation-secretion and excitation-contraction coupling. The channel molecule is a complex of the main, pore-forming subunit alpha 1 and four additional subunits: alpha 2, delta, beta, and gamma (alpha 2 and delta are encoded by a single messenger RNA). The alpha 1 subunit messenger RNA alone directs expression of functional calcium channels in Xenopus oocytes, and coexpression of the alpha 2/delta and beta subunits enhances the amplitude of the current. The alpha 2, delta, and gamma subunits also have pronounced effects on its macroscopic characteristics, such as kinetics, voltage dependence of activation and inactivation, and enhancement by a dihydropyridine agonist. In some cases, specific modulatory functions can be assigned to individual subunits, whereas in other cases the different subunits appear to act in concert to modulate the properties of the channel.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Tissue-specific expression of high-voltage-activated dihydropyridine-sensitive L-type calcium channels.

The cloning of the cDNA for the alpha 1 subunit of L-type calcium channels revealed that at least two genes (CaCh1 and CaCh2) exist which give rise to several splice variants. The expression of mRNA for these alpha 1 subunits and the skeletal muscle alpha 2/delta, beta and gamma subunits was studied in rabbit tissues and BC3H1 cells. Nucleic-acid-hybridization studies showed that the mRNA of all subunits are expressed in skeletal muscle, brain, heart and aorta. However, the alpha 1-, beta- and gamma-specific transcripts had different sizes in these tissues. Smooth muscle and heart contain different splice variants of the CaCh2 gene. The alpha 1, beta and gamma mRNA are expressed together in differentiated but not in proliferating BC3H1 cells. A probe specific for the skeletal muscle alpha 2/delta subunit did not hybridize to poly(A)-rich RNA from BC3H1 cells. These results suggest that different splice variants of the genes for the alpha 1, beta and gamma subunits exist in tissues containing L-type calcium channels, and that their expression is regulated in a coordinate manner.

Amino Acid Sequence↗
PubMed1991

The genotoxicity of nitrilotriacetic acid (NTA) in a somatic mutation and recombination test in Drosophila melanogaster.

The genotoxicity of a chelating agent, the trisodium salt of nitrilotriacetic acid (NTA), was assessed in a somatic mutation and recombination test (SMART) in Drosophila melanogaster employing the wing hair markers mwh and flr3. The experiments were performed in parallel in two different laboratories (Padua, Italy and Schwerzenbach, Switzerland). The effectively absorbed doses of NTA, which was administered by feeding to larvae, were determined by a sensitive method employing [3H]leucine which allowed individual consumption levels to be measured. The particular pattern of clone induction produced by this compound suggests that NTA is active in inducing mitotic recombination and possibly aneuploidy in somatic cells of Drosophila. This is discussed in relation to the data present in the literature regarding the genotoxicity of NTA in a variety of experimental systems.

Animals↗
PubMed1990

[Noninvasive, local microwave hyperthermia for deep-seated tumors: III. Benign prostatic hyperplasia].

Poor operative risk patients with benign prostatic hyperplasia were treated as outpatients with local hyperthermia without sedation, for 1 hour, twice weekly. As a result of the treatment it was possible in 61% to remove indwelling catheters and voiding was resumed for up to 61 months after treatment. 70% of those without indwelling catheters improved clinically and remained so for 67 months after completion of treatment. There were no side-effects or sequellae of the treatment. Because of its safety, simplicity of application and good results, it is recommended as the treatment of choice for poor operative risks.

Catheters, Indwelling↗
PubMed1990

Inactivation of calcium-activated chloride conductance in Xenopus oocytes: roles of calcium and protein kinase C.

Inactivation of Ca2(+)-induced Cl- currents was studied in Xenopus oocytes using the two-electrode voltage-clamp technique. In oocytes permeabilized to Ca2+ by treatment with the ionophore A23187, Ca2+ influx caused by the addition of 2.5-5 mM Ca2+ to the extracellular solution elicited Cl- currents consisting of two components: a fast, transient one (Ifast) and a slow one (Islow). In response to a subsequent application of the same dose of Ca2+, Ifast and Islow were reduced (inactivation phenomenon). The inactivation did not depend on the direction of current flow, but did depend on the duration of the first exposure to Ca2+. The extent of inactivation of Ifast was more significant than that to Islow. Both Ifast and Islow fully recovered from inactivation in less than 30 min. Intracellular injections of 100-400 pmol CaCl2 evoked large inward currents but did not reduce the amplitude of currents evoked by Ca2+ influx. The activator of protein kinase C, beta-phorbol dibutyrate, caused full inhibition of Ifast without any change in Islow. H-7 (1,5-isoquinolinesulfonyl-1,2 methylpiperazine), an inhibitor of protein kinases, strongly reduced the extent of inactivation. Our results suggest that elevation of intracellular Ca2+ by Ca2+ influx through the plasma membrane causes inactivation of the Ca2(+)-dependent Cl- conductance via activation of a Ca2(+)-dependent protein kinase, possibly protein kinase C, whereas Ca2+ arriving at the membrane from inside the cell does not initiate the processes leading to inactivation.

Animals↗
PubMed1990

Short- and long-term desensitization of serotonergic response in Xenopus oocytes injected with brain RNA: roles for inositol 1,4,5-trisphosphate and protein kinase C.

In Xenopus oocytes injected with rat brain RNA, serotonin (5HT) and acetylcholine (ACh) evoke membrane responses through a common biochemical cascade that includes activation of phospholipase C, production of inositol 1,4,5-trisphosphate (Ins1,4,5-P3), release of Ca2+ from intracellular stores, and opening of Ca-dependent Cl- channels. The response is a Cl- current composed of a transient component (5HT1 or ACh1) and a slow, long-lasting component (5HT2 or ACh2). Here we show that only the fast, but not the slow, component of the response is subject to desensitization that follows a previous application of the transmitter. The recovery of 5HT1 from desensitization is biphasic, suggesting the existence of two types of desensitization: short-term desensitization (STD), which lasts for less than 0.5 h; and long-term desensitization (LTD) lasting for up to 4 h. The desensitization between 5HT and ACh is heterologous and long-lasting. We searched for (a) the molecular target and (b) the cause of desensitization. (a) Pre-exposure to 5HT does not reduce the response evoked by intracellular injection of Ca2+ and by Ca2+ influx. Cl- current evoked by intracellular injection of Ins1,4,5-P3 was reduced shortly after application of 5HT, but fully recovered 30 min later. Thus, the Cl- channel is not a target for desensitization. Neither Ins1,4,5-P3 receptor nor the Ca2+ store is a target of LTD but they may be the targets of STD. (b) Ca2+ injection did not inhibit the 5HT response, suggesting that Ca2+ is not a sole cause of STD or LTD.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗