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J L Herrmann

Publications and source records attributed to J L Herrmann.

At least 55 records · Page 3Linked to original sources

Scattering of the rRNA genes on the physical map of the circular chromosome of Leptospira interrogans serovar icterohaemorrhagiae.

Leptospira interrogans is a pathogenic bacterium with a low G+C content (34 to 39%). The restriction enzymes NotI, AscI, and SrfI cut the chromosome of L. interrogans serovar icterohaemorrhagiae into 13, 3, and 5 fragments separable by one- and two-dimensional pulsed-field gel electrophoresis (PFGE). The genome is composed of a circular 4.6-Mbp chromosome and a 0.35-Mbp extrachromosomal element. A physical map of the chromosome was constructed for NotI, AscI, and SrfI by using single and double digests, or partial NotI digests obtained at random or by cross-protection of NotI sites by FnuDII methylase, and linking clones. rRNA genes were found to be widely scattered on the chromosome.

Base Sequence↗

Pulsed-field gel electrophoresis of NotI digests of leptospiral DNA: a new rapid method of serovar identification.

Fingerprints for 72 reference serovar strains of pathogenic Leptospira spp. were obtained by pulsed-field gel electrophoresis (PFGE) following NotI restriction digests of the chromosome. These strains included the serovar reference strains of serogroups Australis, Ballum, Bataviae, Grippotyphosa, Panama, Pomona, and Pyrogenes. Sixty-four serovars could be identified by a unique NotI restriction profile. The remaining serovars were differentiated by chromosomal digestion with SgrAI. These included four serovars from serogroup Australis, two serovars from serogroup Ballum, and two serovars from serogroup Bataviae. Thirteen of 18 recent clinical isolates identified by microagglutination test and cross-adsorption procedure were correctly typed by PFGE. The results indicate that PFGE, which is considerably more rapid than serology, should be useful for identification and epidemiological studies.

Animals↗

Antinociceptive (aminoalkyl)indoles.

The (aminoalkyl)indole (AAI) derivative pravadoline (1a) inhibited prostaglandin (PG) synthesis in mouse brain microsomes in vitro and ex vivo and exhibited antinociceptive activity in several rodent assays. In vitro structure-activity relationship studies of this new class of PG synthesis inhibitors revealed a correspondence in three respects to those reported for the arylacetic acids: (1) "alpha-methylation" caused an increase in PG inhibitory potency, (2) the (R)-alpha-methyl isomer was more active than the S isomer, (3) the hypothesized aroyl group conformation of the 2-methyl derivatives corresponded to the proposed and reported "active" conformations of the aroyl and related aromatic acetic acid derivatives. The 1H NMR chemical shift of the C-4 hydrogen of pravadoline in comparison to the deshielding seen with 50, which lacks a substituent at C-2, suggested that the carbonyl group of pravadoline is located near C-2 but is located near C-4 in 50. Associated with this conformational change of the carbonyl group of 1a is a diminution of PG synthetase inhibitory activity. The results of UV and difference nuclear Overhauser studies of the two compounds were consistent with these conformational assignments. The low eudismic ratios of the alpha-methyl derivatives and the observation that the side chain may be extended by three methylene groups without significant loss of PG inhibitory potency suggests that this class of inhibitors bound less strongly and less selectively to the active site of PG synthetase than do the arylacetic acids. Two AAIs, 1a and 30, were found to be metabolized to the corresponding acetic acid derivatives, both of which inhibited PG synthesis. An exception to the observation that the antinociceptive activity of the AAIs was associated with PG synthetase inhibitory activity was the 1-naphthoyl derivative 67 since neither it nor its acetic acid metabolite 74 inhibited PG synthesis. Yet 67 was antinociceptive in four different rodent assays. This naphthoyl derivative, like opioids, also inhibited electrically stimulated contractions in the mouse vas deferens (MVD) preparation. Unlike opioids, however, the inhibition was not antagonized by naloxone. A subseries of AAIs was identified, of which 67 was prototypic. These compounds lacked PG synthetase inhibitory activity, but their inhibitory potency in MVD preparations correlated roughly with their antinociceptive potency in vivo. Pravadoline was also inhibitory in the MVD. Its antinociceptive activity, therefore, may be a consequence of both its PG synthetase inhibitory potency and another antinociceptive mechanism, the latter associated with its inhibitory potency in the MVD.(ABSTRACT TRUNCATED AT 400 WORDS)

Analgesia↗

Genome conservation in isolates of Leptospira interrogans.

Reference strains for each of the 23 serogroups of Leptospira interrogans yielded different pulsed-field gel electrophoresis patterns of NotI digestion products. This was also the case for the 14 serovars belonging to serogroup Icterohaemorrhagiae (with one exception). The NotI restriction patterns of 45 clinical leptospiral isolates belonging to serovar icterohaemorrhagiae were analyzed and compared with those of type strains. No differences were observed between isolates from countries of different continents, namely, France, French Guiana, New Caledonia, and Tahiti. The pattern was indistinguishable from that of the reference strain of serovar icterohaemorrhagiae.

Biological Evolution↗

Antiandrogenic steroidal sulfonylpyrazoles.

The steroidal sulfonylpyrazole 1 bound to the rat ventral prostate androgen receptor in vitro; it inhibited testosterone propionate induced increases in ventral prostate weight in vivo in the castrated, immature male rat with an ED50 of 15 mg/kg po. Compound 1 lacked androgenic activity in vivo in contrast to the parent steroidal pyrazole 5, which was both androgenic and antiandrogenic. The 2'- and 5'-methylsulfonyl isomers 6 and 6a did not bind to the androgen receptor. Introduction of an alkylsulfonyl at the N-1'-position has served, therefore, to isolate the intrinsic antiandrogenic properties of the steroidal heterocycle free of apparent hormone agonist properties. Structure-activity relationship studies revealed that a methylsulfonyl group at N-1' together with a C-17 alpha-substituent were the optimal combination for in vitro androgen receptor binding, in vivo antiandrogenic potency, and a lack of androgenic activity.

Androgen Antagonists↗

[Activity of cefapirin against bacterial strains isolated from acute otitis media in children].

The antibacterial activity of cefapirin was tested against 210 strains isolated from the auricular exudate of childrens' acute otitis media. For 112 strains of Haemophilus studied (20% secreted a beta-lactamase), the MIC 50 and 90 of cefapirin were 2 and 4 mg/l respectively. Ten strains of Branhamella catarrhalis were tested (9 secreted a beta-lactamase) and the MIC ranged from 0.25 to 4 mg/l. Against Streptococcus pneumoniae, cefapirin has an extremely high activity with MIC 50 and 90 less than 0.06 mg/l. Of the strains of Staphylococcus aureus sensitive to meticillin, one had a MIC less than 0.06 mg/l, and 11 had a MIC = 0.25 mg/l. For 14 strains of Enterobacteriaceae studied, we obtained a MIC 50 of 8 mg/l and a MIC 90 of 32 mg/l. The results show that cefapirin is an antibiotic particularly suitable for the treatment of acute otitis media.

Anti-Bacterial Agents↗

[Activity of cefuroxime against bacterial strains isolated from acute otitis media].

The acute otitis media is a frequent infantile disease and, in 80% of cases, a bacterial strain can be isolated from the otorrhoea. Haemophilus influenzae and Streptococcus pneumoniae are the two major species isolated from auricular exudate, and represent two thirds of all isolated strains, with the others comprising Staphylococcus aureus, Branhamella catarrhalis, Pseudomonas aeruginosa, Enterobacteriaceae and corynebacteria. The treatment of this disease is based principally on beta-lactams (aminopenicillins, cephalosporins) administered by the oral route. Cefuroxime is a cephalosporin which is absorbed via the digestive tract in the form of cefuroxim-axetil. The activity of this compound was studied against 210 strains isolated from otorrhoea, collected from children who presented an acute otitis media during the first half of 1989. These strains were: 112 strains of H. influenzae, of which 23 produced a beta-lactamase; 21 strains of Streptococcus pneumoniae; 3 strains of Streptococcus pyogenes; 10 strains of Branhamella catarrhalis of which 9 produced a beta-lactamase; 18 strains of S. aureus; 14 strains of Enterobacteriaceae, and 32 strains of corynebacteria. The minimal inhibitory concentration (MIC) of cefuroxime-axetil was measured by dilution in agar. The MICs of cefuroxime against H. influenzae were low and similar (MIC 50 = 1 mg/l; MIC 90 = 1 mg/l) regardless of whether the strain secreted a beta-lactamase. Overall, 90% and 98% of the 210 strains tested here were inhibited by 1 and 4 mg/l of cefuroxime respectively. These results show that the antibacterial spectrum of cefuroxime-axetil appears to be ideally suited to the bacterial strains isolated from acute otitis media.

Cefuroxime↗

[Effects of captopril on hemodynamics, gas exchange and exercise capacity in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease].

Captopril, a potent inhibitor of angiotensin converting enzyme, was tested in patients with COPD (means forced expired volume in the first second--FEV1 = 0.73 l) and pulmonary hypertension (PAP = 41.3 mmHg). In the first phase of the experiment, patients underwent and incremental exercise test to the limit of tolerance. These were double blind, randomized, cross-over studies, where the patients received oral placebo (Pl) or captopril (Cp) 25 mg, on different days. In a second phase, the patients were submitted to hemodynamic and gasometric studies in the supine position, before placebo, the 60 min after and immediately after exercise (cycling-like leg movements). After 30 min of rest the same protocol was repeated with oral administration of 25 mg of captopril. In the metabolic evaluation (cycloergometry) captopril increased significantly exercise tolerance (means VO2-uptake at maximal exercise: CP = 0.81 vs Pl = 0.73 1/min), associated with a slower heart rate and higher O2-pulse at maximal exercise. In the hemodynamic study, when the effects of Cp and Pl were compared, the mean values of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) were similar at rest, but significantly lower during exercise, after captopril (means PAP Cp = 41.3 vs Pl = 51.2 mmHg; XPVR Cp = 278 vs Pl = 392 dyn. sec. cm5). There were similar systemic hemodynamic effects after Cp, but these were more intense in the pulmonary circulation (lower PVR/SVR ratio post-Cp in relation to post-Pl, during exercise). The cardiac index, systemic O2 transport and arterial and mixed venous blood gases were similar at rest and during exercise, with Pl or Cp.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effects of glucose on myocardial substrate utilization in acute myocardial infarction or angina pectoris.

Infusion of glucose-insulin-potassium during acute myocardial infarction has favorable clinical and hemodynamic effects, presumably as a result of decreased myocardial utilization of free fatty acids. In 14 patients with coronary artery disease, hypertonic glucose (a bolus of 10 g followed by infusion of a 30% glucose solution at a constant rate of 10 mg/kg/min) was infused and arterial and coronary sinus levels of glucose, lactate and free fatty acids were measured before and after 15 and 30 minutes of infusion. Arterial glucose and lactate levels increased significantly after glucose infusion, whereas free fatty acid levels decreased significantly. Modest but significant correlations also existed between glucose arterial levels and the arterial-coronary sinus glucose difference (r = 0.53, p less than 0.001); arterial lactate and the arterial-coronary sinus lactate difference (r = 0.35, p less than 0.01); arterial free fatty acids; and the arterial-coronary sinus free fatty acid difference (r = 0.62, p less than 0.001). These results with a hypertonic glucose infusion are similar to those reported after infusion of glucose-insulin-potassium without the potential for harmful adverse effects from infusions of insulin or potassium. Therefore, infusion of hypertonic glucose may be beneficial in patients with coronary artery disease. Further work is necessary to study its effects in different subgroups of patients with coronary artery disease.

Aged↗

TNF alpha, IL-1 beta and IL-6 plasma levels in neutropenic patients after onset of fever and correlation with the C-reactive protein (CRP) kinetic values.

Cytokines, especially tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) play an important role in the genesis and progression of the septic shock syndrome. We performed a study monitoring levels of these three cytokines in ten neutropenic oncology patients in whom an infectious syndrome was suspected. A comparison was made with a population of nine non-neutropenic patients on the intensive care unit. Unfortunately the results of this study do not allow specific profiles to be established for each cytokine in the populations studied. Levels of IL-6, TNF alpha and IL-1 beta were not statistically higher in the non-neutropenic patients when compared with the neutropenic group. However, the highest IL-6 levels were observed for four non-neutropenic patients, three of whom died. High levels of C-reactive protein (CRP), haptoglobin and fibrinogen were found, reflecting the inflammatory status of each patient. CRP levels were higher in the non-neutropenic patients and correlated with IL-6 levels, indicating the importance of CRP determination in this group of patients.

Acute-Phase Proteins↗