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G Herman

Publications and source records attributed to G Herman.

At least 37 records · Page 2Linked to original sources
PubMed1991

Alpha-adrenoceptor subtypes in dog saphenous vein that mediate contraction and inositol phosphate production.

1. Studies have been made of the contractile responses to the alpha-adrenoceptor agonists phenylephrine (Phen), cirazoline (Cir) or BHT-920 (BHT) in dog isolated saphenous vein (DSV) rings, using the antagonists yohimbine (Yoh), idazoxan (Idaz), prazosin (Praz), WB-4101 (WB) and nitrendipine or zero Ca2+ medium. 2. Contractile concentration-response curves to Phen or BHT were displaced to the right of controls by Yoh (0.01-3 microM) with mean apparent antagonist dissociation constants (pKBs) of 7.9 and 8.6 respectively. Yoh did not show simple competitive antagonism against either agonist, since the Schild plot slopes were significantly less than unity. Neither the antagonist affinity of Yoh against Phen, nor the slope of the Schild plot was modified in the presence of catecholamine uptake inhibitors, nor in the presence of alpha,beta-methylene ATP, which desensitizes P2-purinoceptors, suggesting that Phen does not release ATP, or noradrenaline to cause contraction in DSV. In the presence of Praz (0.3 microM) the antagonist potency of Yoh (mean pKB 7.4) against Phen was slightly decreased. Yoh had low potency against responses induced by Cir (pKB 6.3). 3. WB (0.001-1.0 microM) was a very potent antagonist of Phen-induced contractions, however, the biphasic Schild plot against Phen could be separated into two affinity sites, a high pKB of 9.3 (equivalent to that obtained using Cir as the agonist; pKB 9.6) and a lower affinity (pKB 8.6). WB showed an even lower antagonist affinity (pKB 7.4) against BHT-induced contractions, suggesting that these effects might be mediated by alpha 2A-adrenoceptors. Praz also appeared to identify two sites using Phen-induced contractions, a high pKB of 8.4 was equivalent to that obtained with Cir (pKB 8.2) and a lower affinity site (pKB 7.7; pA2 7.6; slope 1.1) at which Praz showed competitive antagonism. Higher concentrations of Praz were required to antagonize contractions to BHT (pKB 5.9). 4. Idaz was a weak partial agonist in this tissue with threshold contractile effects at concentrations in excess of 3 microM. Idaz (0.1-1 microM) competitively antagonized the contractile effects of BHT, but showed low antagonist affinity against Phen at these concentrations. 5. Contractions to Phen were slightly antagonized by nitrendipine (1 microM), with a 36% decrease in Emax. Contractions to Phen and Cir were also markedly attenuated in zero calcium medium (with EGTA), but maximum responses of 4.2 +/- 0.1 and 3.6 +/- 0.1 g, could be obtained with these agonists respectively. Only part of the contractile effects to Phen or Cir are therefore due to calcium influx (but L-type channels are not totally implicated), while the contractile effects of BHT were abolished in zero Ca2 + medium. Yoh (0.1 microm) retained its antagonist effects on Phen-induced responses in zero Ca2 + medium. 6. The formation of inositol phosphates (InsPs) in the presence of lithium (10mM) was measured after incubation of intact DSV strips with myo-2-[3H]-inositol. Phen (1-1OO0 microM) and Cir (O.O1-1O microm) induced concentration-dependent increases in total labelled InsP1_3, but BHT showed minimal InsP stimulation. InsPs were recovered after Phen (100,M) stimulation (10min) as labelled InsP1 (71%), InsP2 (25%) and InsP3 (4%). Phen (100 microM)-stimulated InsP1-3 formation was significantly antagonized by Praz (10nM), but was not fully inhibited even after Praz 1 microM. Yoh and Praz (0.1 and 1.0 microM) were equipotent inhibitors of this response, while Idaz (0.3 microM) showed no effects. 7. The receptors in DSV which are stimulated by Phen to cause contraction show characteristics of the alpha lA-adrenoceptor (high pM antagonist affinity for WB-4101 and extracellular calcium sensitivity) and the alpha lB-adrenoceptor (contraction in calcium-free medium, increase in InsP and low nm antagonist affinity of WB). The paradoxical results obtained with Yoh (potent antagonist effects on Phen-stimulated PI and pKB 7.9 on contraction) and Praz (low affinity competitive antagonist of Phen-induced contraction, pKB 7.7 and failure to inhibit completely the PI response at 1 microM), cannot fully exclude an alpha 2B-subtype characterization of these responses. These pharmacological differences suggest that the adrenoceptor involved in the contractile and in particular the second messenger effects of Phen in DSV is not typically an alpha lB-adrenoceptor.

Adrenergic alpha-Agonists↗
PubMed1989

Colchicine analogues that bind reversibly to tubulin define microtubular requirements for newly synthesized protein secretion in rat lacrimal gland.

The role of microtubules in 3H-labeled protein secretion in rat lacrimal glands was probed by the use of colchicine and two of its analogues that reversibly bind to tubulin. These analogues were 2-methoxy-5-(2,3,4,4'-trimethoxyphenyl)-2,4,6-cycloheptatriene-1-o ne and 2,3,4,4'-tetramethoxy-1,1'-biphenyl, the latter having been synthesized for these studies. Immunofluorescence revealed that untreated exocrine acinar cells contained an intact microtubule network, which was totally abolished by drug addition. Subsequent drug removal restored the network for the two reversibly binding drugs--more rapidly so for the biphenyl, but this was not the case with colchicine. The protein-secretory process was examined by adding the three drugs at various stages--prepulse incubation, pulse, maturation, apical storage of granules, and discharge under cholinergic stimulation. Comparison with the kinetics of microtubular network restoration, which differed for the two reversibly binding drugs, led to the conclusion that the microtubular system is critical to the maturation phase of secretion.

Animals↗
PubMed1989

Carbon monoxide and myonecrosis: a prospective study.

Myonecrosis has been reported to occur in patients with carbon monoxide (CO) poisoning, and last year we reported a case of non-traumatic rhabdomyolysis in a patient with CO poisoning secondary to smoke inhalation. We prospectively studied the association between CO poisoning and rhabdomyolysis by obtaining serum creatine kinase (CPK) levels on 65 of 81 consecutive patients (range 20-1315 IU/L) who presented to the University of Illinois Hospital Emergency Room during a 3-month period with CO levels greater than 5.0% (range 5.0%-63.9%). Thiocyanate levels were obtained on 45 patients (range 0-3.5 mg/dl). We found no statistically significant correlation by linear regression analysis between CO level and CPK level in these patients. A subjective complaint of weakness was obtained in 4 patients and physical evidence of weakness was found in 1 of these (this was felt to be secondary to a cerebrovascular accident). In none of these 4 patients was an elevated CPK level noted. We did, however, note an association between thiocyanate level and CPK level by linear regression analysis (p less than 0.02). A power curve was a better fit for this data (r2 = 0.7). This data suggests that serum CPK levels should not be routinely obtained on patients with CO poisoning and that cyanide may play a more important role in non-traumatic rhabdomyolysis associated with toxic inhalation than had previously been suspected.

Carbon Monoxide↗
PubMed1988

Glucose tolerance, fetal growth, and pregnancy complications in normal women.

Currently, gestational diabetes is often defined by the criteria of O'Sullivan, with those patients not included as gestationally diabetic being considered normal. Recently, Tallarigo and coworkers reported that serum glucose variations within the normal range could affect the birthweight of the neonate and also could relate to the frequency of complications often associated with diabetes in pregnancy. This study confirms the correlation between the plasma glucose concentration at 2 hours on the 100 gm, 3-hour glucose tolerance test and birthweight. When women demonstrating 2-hour glucose values of 139 mg/dl or less are compared with those demonstrating values 140 mg/dl or greater, fetuses from the group with higher plasma glucose values had higher birthweights (+211 gm) and were more often macrosomic (24.4 versus 8.6%). We were unable to identify any relationship between these small variations of glucose tolerance and pregnancy complications, such as delivery by cesarean section, birth trauma, pregnancy-induced hypertension, or congenital anomalies.

Birth Weight↗
PubMed1988

[In vitro effect of pentoxifylline on the metabolism of glycogen and the secretory process in the parotid and lacrimal extraorbital glands in rats].

In the present work, we have shown that pentoxifylline (BL 191) and propentofylline (HW 285) penetrate very fast, without storage, in rat parotid and lacrimal gland cells. As phosphodiesterase inhibitor, pentoxifylline induces an increase of cAMP intracellular concentration. Pentoxifylline has a slight but sustained effect on 45Ca efflux and triggers a substantial labeled protein secretion and important glycogenolysis. Taken together, these data could be explained as a synergism between the different regulation routes involving calcium and cAMP.

Animals↗
PubMed1987

Newly synthesized protein secretion in rat lacrimal gland: post-second messenger synergism.

The vasoactive intestinal peptide (VIP) induces a concentration-dependent secretion of newly synthesized (3H labeled) proteins from lacrimal gland fragments. Maximal secretory response is approximately 20% of total labeled proteins secreted for a 40-min stimulation and half-maximal secretory response is obtained at 3.8 +/- 0.2 nM VIP. The cholinergic (muscarinic) and VIPergic stimulations synergistically interact in eliciting newly synthesized protein secretion. Carbachol (0.3 microM) and the phorbol ester PMA (1 microM) potentiate the secretory response to VIP (10 nM), forskolin (3 microM), and dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) (0.5 mM) both in the absence and presence of 2.5 mM extracellular calcium. The calcium ionophore A23187 (1 microM) potentiates the cAMP-dependent responses only in the presence of extracellular calcium. We propose that newly synthesized protein secretion from rat lacrimal glands is controlled by two systems interacting synergistically at a step distal to the production of intracellular second messengers. The potentiating effect of agonists acting through the calcium-dependent pathway on the cAMP-dependent secretory response may involve both calcium and diacylglycerol.

Animals↗
PubMed1986

Immunohistochemical localization of a specific ileal peptide in the pig.

The tissue distribution of a polypeptide purified from pig ileal mucosa tentatively called porcine ileal polypeptide (PIP) and known to have potent acid secretagogue activity has been studied with immunohistochemical methods together with extraction of different tissues followed by radioimmunoassay for PIP content. Histochemically the peptide is found in superficial epithelial cells in the mucosa of the distal 20% of the small intestine and to some extent in the mucosa of the urinary tract. There is no staining of goblet cells or crypt cells. The staining in the urinary tract mucosa is due to antigenic peptides with Mr identical to PIP. While the presence of PIP in the ileum is compatible with a function as an enterooxyntin, it is not possible at present to explain the physiologic role of PIP entirely as a hormone regulating acid secretion in light of the immunohistochemical distribution.

Animals↗
PubMed1986

Protein secretion in lacrimal gland: alpha 1-beta-adrenergic synergism.

We have shown the existence of a homogeneous population of specific binding sites for [3H]prazosin in membranes from rat lacrimal glands. The value of the equilibrium dissociation constant was 0.186 +/- 0.07 nM, and the density of specific binding sites was 20.4 +/- 1 fmol/mg protein. Taking into account the potency sequences for adrenergic agonists and antagonists for competition with these [3H]prazosin binding sites, we identified them as alpha 1-adrenergic receptors. Moreover, we have demonstrated that the stimulation of protein discharge evoked by epinephrine could be partly attributed to the occupation of this alpha-adrenergic receptor subtype. However, the inhibition pattern of the epinephrine effect by a beta-adrenergic antagonist, 1-propranolol, and the characteristics of the secretory response observed when selectively stimulating the alpha 1- and beta-adrenergic receptors, either separately or simultaneously, suggest that 1) a simultaneous activation of both receptors is necessary to produce a maximal secretory response to catecholamines; and 2) a synergism may exist between these two routes of stimulation, leading to an amount of protein discharge higher than that expected in the case of additive effects.

Adrenergic alpha-Antagonists↗
PubMed1986

Cefoxitin versus clindamycin and gentamicin in the treatment of postcesarean section infections.

Cefoxitin, a cefamycin derivative, has demonstrated activity against a broad spectrum of aerobic and anaerobic bacterial pathogens. The efficacy and safety of cefoxitin were compared with that of the combination of clindamycin and gentamicin in the treatment of postcesarean section infection. Ninety-eight patients were evaluated. Cefoxitin cured 36 of 48 patients (75%); clindamycin/gentamicin cured 38 of 50 (76%) (P greater than .05). Febrile degree hours and length of hospital stay did not differ between the two study groups. No patient experienced abscess formation or septic pelvic thrombophlebitis. Both therapies were well tolerated. In the authors' experience, cefoxitin as a single agent was as effective in the treatment of postoperative pelvic infection as the combination of clindamycin and gentamicin.

Adult↗
PubMed1985

Extent of equilibrium perturbation of the DNA helix upon enzymatic methylation of adenine residues.

The extent of equilibrium perturbation of the DNA helix associated with enzymatic methylation of dA residues has been determined by the agarose gel electrophoresis band-shift method. Utilization of EcoRI methylase under conditions of reduced specificity together with Escherichia coli dam methylase permitted modification of up to 300 dA residues/plasmid pBR322 dimer. A conformational change associated with methylation was observed, with the magnitude of the transition being linear with extent of modification of relaxed DNA circles. The conformational change corresponds to an unwinding of the DNA helix by 0.5 degrees/methyl group transferred to relaxed molecules. The magnitude of the effect was independent of temperature from 5-37 degrees C indicating that it is not the consequence of a thermal transition within this range.

Adenine↗
PubMed1985

Importance of state of methylation of oriC GATC sites in initiation of DNA replication in Escherichia coli.

In vivo and in vitro evidence is presented implicating a function of GATC methylation in the Escherichia coli replication origin, oriC, during initiation of DNA synthesis. Transformation frequencies of oriC plasmids into E. coli dam mutants, deficient in the GATC-specific DNA methylase, are greatly reduced compared with parental dam+ cells, particularly for plasmids that must use oriC for initiation. Mutations that suppress the mismatch repair deficiency of dam mutants do not increase these low transformation frequencies, implicating a new function for the Dam methylase. oriC DNA isolated from dam- cells functions 2- to 4-fold less well in the oriC-specific in vitro initiation system when compared with oriC DNA from dam+ cells. This decreased template activity is restored 2- to 3-fold if the DNA from dam- cells is first methylated with purified Dam methylase. Bacterial origin plasmids or M13-oriC chimeric phage DNA, isolated from either base substitution or insertion dam mutants of E. coli, exhibit some sensitivity to digestion by DpnI, a restriction endonuclease specific for methylated GATC sites, showing that these dam mutants retain some Dam methylation activity. Sites of preferred cleavage are found within the oriC region, as well as in the ColE1-type origin.

DNA Replication↗
PubMed1985

Analytical evaluation of a new latex agglutination test for quantitative determination of C-reactive protein by laser nephelometry.

A new reagent for the rapid and reliable quantitative determination of C-reactive protein (CRP), using polystyrene particles coated with antibodies against CRP, is now available. We present an analytical evaluation of this new test system. The analytical characteristics of sensitivity, linearity, precision and specificity are excellent. Samples from patients with various inflammatory conditions were tested. Correlation between the examined technique and current methods such as radial immunodiffusion, classical laser nephelometry and enzyme immunoassay were excellent.

Adult↗
PubMed1984

Protein secretion induced by isoproterenol or pentoxifylline in lacrimal gland: Ca2+ effects.

In exorbital lacrimal glands, pentoxifylline (a methylxanthine) induces labeled protein secretion in a dose-related manner: the half-maximal and maximal stimulations are at 4 and 10 mM, respectively. In the presence of papaverine (10(-5) M), a phosphodiesterase inhibitor, labeled protein discharge is strongly stimulated by isoproterenol, via beta-adrenergic receptors: the maximal response is at 10(-6) M. l-Propranolol specifically inhibits the secretory stimulation to isoproterenol in a dose-related manner: for 5 X 10(-6) M isoproterenol in the presence of 10(-5) M papaverine, the half-maximal and maximal inhibitions are at 3 X 10(-7) and 10(-5) M, respectively. The beta-adrenergic response is mimicked by the adenosine 3',5'-cyclic monophosphate (cAMP) analogue dibutyryl cAMP (DBcAMP) at a 10(-3) M concentration. The time course of labeled protein secretion induced by pentoxifylline, DBcAMP, and isoproterenol shows a latency. In the presence or absence of extracellular calcium, pentoxifylline and isoproterenol immediately increase the cAMP intracellular level. Extracellular calcium omission increases the observed latency and also affects the maximal rate of protein secretion. As opposed to the cholinergic agonist, pentoxifylline has only a slight but sustained effect on 45Ca efflux, whereas isoproterenol has none. These data suggest that labeled protein secretion, such as that of peroxidase, can also be stimulated in rat exorbital lacrimal gland, through beta-adrenergic receptors; in the stimulation evoked by a beta-adrenergic agonist, DBcAMP, or methylxanthine, calcium could play a key role.

Animals↗
PubMed1983

Forskolin as a tool to study the beta-adrenergic receptor-elicited, labeled protein secretion in rat lacrimal gland.

In rat lacrimal glands, Forskolin induces a dose-dependent [3H]protein release. This effect can be potentiated by papaverine. As for the other inducers whose effects on protein secretion are assumed to be cAMP-mediated, Forskolin secretion time course shows a latency. Isoproterenol decreases the Forskolin EC50 at least 60-times. On the other hand, Forskolin enhances the efficacy of isoproterenol without affecting its potency. As a whole, the data collected show that isoproterenol-induced [3H]protein secretion in rat lacrimal glands involved adenylate cyclase activation by coupling with beta-adrenergic receptors.

Animals↗