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Biomedical subjects

D Ziegler

Publications and source records attributed to D Ziegler.

At least 91 records · Page 5Linked to original sources

Evaluation of thermal, pain, and vibration sensation thresholds in newly diagnosed type 1 diabetic patients.

Small and large fibre function was studied in 40 non-ketotic, newly diagnosed Type 1 diabetic patients and 48 age-matched controls, using 12 quantitative tests for assessment of cutaneous sensation. Patients were aged 10-39 years and had been treated with insulin for 4-31 days. Thermal discrimination (foot), warm and cold thermal perception (thenar eminence and foot), and heat and cold pain perception thresholds (thenar eminence) were significantly elevated in the patients as compared with the controls (p less than 0.05 to p less than 0.001). No significant differences in thermal discrimination (thenar), heat and cold pain perception (foot), and metacarpal as well as malleolar vibration perception thresholds were noted between the groups. The rates of abnormalities among the individual tests ranged from 0% to 27.5%, being lowest for vibration perception and highest for thermal perception thresholds after cold stimuli. The results in nine of 12 tests correlated significantly with age, but only two were related to HbA1c. Thus, sensory neural functions transmitted by small fibres, but not those transmitted by large fibres, were impaired in newly diagnosed Type 1 diabetics after the correction of initial ketosis and hyperglycaemia. Cooling perception tests were most sensitive in detecting abnormality. An age-related involvement of different small fibre functions was present in these patients.

Adolescent↗

In vitro effects of anthraquinones on rat intestine and uterus.

Isolated uterus and colon segments were taken from sennoside-pretreated female rats. They indicate a possible decrease in spontaneous contractility of both organ segments. Addition of rhein-Na, as one of the probable active metabolites of sennosides, into the bath medium of isolated colon and ileum segments of untreated rats showed a reduction in contractility at concentrations of more than 10(-5) and 10(-4) mol/l, respectively. Though rhein-Na in concentrations of more than 10(-4) mol/l impaired acetylcholine-mediated contractures of isolated colon, the antagonism was obviously partial and noncompetitive. Isolated uteri from previously estrogen-treated rats did not show a change in the contractile behaviour up to concentrations of 10(-4) mol/l rhein-Na, whereas higher concentrations induced an increase in contractions. The importance of this finding is not clear.

Acetylcholine↗

Somatic and autonomic nerve function during the first year after diagnosis of type 1 (insulin-dependent) diabetes.

Somatic and autonomic nerve function was assessed by motor and sensory nerve conduction velocities (MNCV; SNCV), beat-to-beat variation at rest, speed of pupillary dilation, and pupillary latency time in 35 newly diagnosed type 1 diabetic patients aged 12-36 years. The nerve function tests were performed 18 +/- 2 (mean +/- SEM) days after the correction of initial ketosis and hyperglycaemia and again after 3 and 12 months of insulin therapy. Mean HbA1 levels of months 3 and 12 within the normal range less than 8.6% (mean: 7.2 +/- 0.2%) were observed in 24 patients (group 1) and greater than or equal to 8.6% (mean: 10.1 +/- 0.6%) in 11 patients (group 2). Group 1 showed no significant changes from baseline in the mean nerve conduction and autonomic functions after 3 and 12 months. In group 2 there was no change until three months, however, at 12 months there was a significant decrease in mean MNCV in the median, ulnar and peroneal nerves (p less than 0.05) and in mean SNCV in the median (p less than 0.05) and sural nerves (p less than 0.01), when compared to the baseline values. The autonomic function tests remained unchanged. No patient had symptoms of neuropathy during the period studied. These findings suggest that the deterioration of motor and sensory nerve conduction precedes that of cardiac and pupillary autonomic function in poorly controlled asymptomatic type 1 diabetic patients during the first year of the disease. Effective glycaemic control prevented progression of subclinical neuropathy, but did not reverse abnormalities which were present at diagnosis.

Adolescent↗

Peripheral and autonomic nerve function in long-term insulin-dependent diabetes.

In a cross sectional study, motor nerve conduction velocity (MNCV) and sensory nerve conduction velocity (SNCV), beat-to-beat variation (BBV) at rest and speed of pupillary dilatation (SPD) have been investigated in 127 nonketonuric long-term insulin-dependent diabetics aged 19-72 yr and in age-matched control subjects. 84% of the patients had electrophysiologic abnormalities, 58% had symptomatic peripheral neuropathy, 35% had abnormal cardiac parasympathetic tests and 26% had abnormal pupillary tests. The most frequent pathologic feature was a decreased sural SNCV (66%). Among the patients without symptomatic peripheral neuropathy, 71% showed electrophysiologic abnormalities. MNCV and SNCV in median, peroneal and sural nerves correlated with BBV (p less than 0.005), but only peroneal MNCV was related to SPD (p less than 0.005). There was also a relationship between BBV and SPD (p less than 0.05). Glycosylated hemoglobin (HbA1) levels correlated inversely with median MNCV (p less than 0.001), and SNCV (p less than 0.03), peroneal MNCV (p less than 0.05) and sural SNCV (p less than 0.05). Patients with abnormal peripheral or autonomic nerve function tests or symptomatic peripheral neuropathy had significantly higher HbA1 levels than those with normal tests (p less than 0.04) or asymptomatic patients (p less than 0.01). Median MNCV and SNCV, sural SNCV and BBV deteriorated with age (p less than 0.05) and median SNCV and peroneal MNCV deteriorated with the duration of diabetes (p less than 0.001). Our findings show an association between peripheral and autonomic nerve dysfunction in long-term insulin-dependent diabetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[H-NMR spectroscopy. Specificity of microbial sialidases against complex substrates].

The specificities of one viral and five bacterial sialidases were investigated by 1H-NMR-spectroscopy with substrates or substrate mixtures containing two sialic acid residues of different linkage types. This technique allows - in contrast to the methods used before - the simultaneous determination of the rates of hydrolysis of both NeuAc linkages in a single experiment. The substrate specificities of the enzymes are discussed on the basis of the relation of the rate constants k/k'. The data obtained are more exact and more informative than those of separate experiments as reported previously. Among the enzymes investigated, i.e. sialidases of fowl plague virus (FPV = VKH), Clostridium perfringens (CP), Vibrio cholerae (VC), Bifidobacterium bifidum var. pennsylvanicum (BBif), Bifidobacterium lactentis (BLac), and Arthrobacter ureafaciens (AU), the activity of the viral sialidase VKH shows the highest, the activities of the Bifidobacterium sialidases the lowest dependence on the nature and on the linkage type of the different substrates. All sialidases preferentially cleave the NeuAc alpha 2-3-Gal linkage with the exception of the enzyme of Arthrobacter ureafaciens (AU) which shows a higher affinity to alpha 2-6 linkages. However, this does not apply to the side-arm-linked NeuAc alpha 2-6 structure in NeuAc alpha 2-3 Gal beta 1-3 (NeuAc alpha 2-6)-GlcNAc beta 1-3Gal beta 1-4Glc (Substrate B). This substrate in generally cleaved very slowly and is hardly affected by the viral enzyme. After the alpha 2-3 linkage, the alpha 2-8 bond in NeuAc alpha 2-8 NeuAc alpha 2-3 Gal beta 1-4Glc(Substrate A) is most susceptible for the sialidases VKH, CP and VC. An elongation of the carbohydrate chain (Substrate D) is accompanied by a reduction of the rate of cleavage for all enzymes. The experiments with alpha 1-acid glycoprotein, fetuin, and with the glycopeptides obtained by proteolytic degradation of the latter, revealed the same specificity towards the alpha 2-3 and the alpha 2-6 linkages as the oligosaccharides. Influenced by the chemical nature and the size of the substrate, NeuAc is released from the native alpha 1-acid glycoprotein more quickly than from the corresponding glycopeptide. All sialidases investigated so far are strictly exo-enzymes as could be demonstrated by the cleavage of NeuAc alpha 2-8 NeuAc alpha 2-3 Gal beta 1-4Glc (Substrate A).

Arthrobacter↗

Success in strabismus therapy: a literature review.

The purpose of this study was to review the literature pertaining to non-surgical cure rates for strabismus published since 1958 and compare it to Flom's prognostic model. However, no studies were found that could be compared directly to Flom's model. One reason for this was due to the use of different definitions of a cure by different clinicians. Another reason was the failure to categorize the data according to the effect that retinal correspondence, frequency, and direction of the deviation had on the cure rates. From the studies which specified Flom's functional cure or its equivalent, it was determined that strabismic cure rates could be broken down as follows: Constant esotropia-29%; Intermittent esotropia-73% Constant exotropia-53%; Intermittent exotropia-62% Suggestions were made for the reporting of data to make future research more comparable and useful to the practitioner.

Adolescent↗

[1H-NMR spectroscopy--a potent method for the determination of substrate specificity of sialidases (author's transl)].

We describe here the application of 1H-NMR spectroscopy to determine the substrate specificity of sialidases using a 1:1 mixture of NeuAc alpha 2-3Gal beta 1-4Glc and NeuAc alpha 2-6Gal beta 1-4Glc, one viral and five bacterial sialidases. This method utilizes the separate signals in NMR spectra, characteristic for the different alpha ketosidically linked NeuAc residues and also for bound and free NeuAc. The signals generally most suitable for these purposes are those of H3a, H3e and NCOCH3. By observation and integration of these signals we can follow--qualitatively and quantitatively--which and how many NeuAc residues of the substrates are hydrolized. In contrast to the generally used colorimetric tests it is now possible to investigate with this method substrates containing two or more NeuAc residues and to determine the corresponding rate constants for hydrolysis of the differently bound NeuAc molecules. The six sialidases used show large differences in their specificity as compared with our "model substrate": The sialidase from fowl plague virus hydrolizes NeuAc alpha 2-3Gal beta 1-4Glc nearly 18 times and the enzyme from Clostridium perfringens four times, from Vibrio cholerae two times faster than NeuAc alpha 2-6Gal beta 1-4Glc. On the contrary, the sialidase from Arthrobacter ureafaciens hydrolizes the alpha 2-6 linkage six times faster than the alpha 2-3 linkage. The sialidases from Bifidobacterium show no obvious differences in their specificities relative to the linkage.

Actinomycetaceae↗

Di- and tri-methoxystyryl derivatives of heterocyclic nitrogen compounds.

A series of mono-, di-, and trimethoxystyryl derivatives of heterocyclic nitrogen compounds were prepared to test the N-O-O triangulation hypothesis of Zee-Cheng and Cheng. Of 29 free bases submitted for KB cell culture test, only 2-(3,4-methylenedioxystyryl)benzoxazole and 4-(2,5-dimethoxystyryl)cinnoline were active (ED50 of 4 microgram/ml or less). Methiodide salts were more potent: 8 of 14 were active. 2-(2,4,6-Trimethoxystyryl)quinoline methiodide and 4-(2,4,5-trimethoxystyryl)quinoline methiodide had ED50 of 0.4 and 0.9 microgram/ml, respectively. The methiodides of 2-(2,3,4-, 4-(2,4,5-, 4-(2,4,6-, and 2,4-bis-(2,4,6-trimethoxystyryl)quinoline and 1-(2,4,6-trimethoxystyryl) isoquinoline and the propiodide of 4-(2,4,6-trimethoxystyryl)quinoline were active against P388 leukemia. Several of the active compounds do not conform to the dimensions of the Zee-Cheng and Cheng triangle.

Animals↗

Effect of cannabinoids on estrous cycle, ovulation and reproductive capacity of female A/J mice.

Virgin A/J female mice were intubated daily for 8 days (short term) or 70 days (long term) with 0, 1, 5, or 25 mg/kg delta 9-tetrahydrocannabinol (delta 9-THC) or 0, 3, 15, or 75 mg/kg crude marihuana extract (CME) in a sesame oil:polysorbate 80:saline vehicle. These dosages approximate light, moderate, and heavy human usage. Short-term exposure to CME has no significant effect on PMS-HCG-induced ovulation but appears to: (1) delay entry into proestrus at all dose levels; (2) depress serum progesterone during the luteal phase at the highest CME level used (75 mg/kg), and (3) inhibit female receptivity to males at least at the highest dosage. Long-term oral administration of CME or delta 9-thc had no significant effect on length of estrous cycles or mating (plug formation) but term pregnancies were reduced by 32 and 68% for medium and high dosages, respectively. After a 30-day recovery period, 80% of those females that failed to have successful pregnancies now became pregnant.

Animals↗

[1H-NMR-spectroscopic evidence for the release of N-acetyl-alpha-D-neuraminic acid as the first product of neuraminidase action (author's transl)].

The 1H-NMR spectroscopy was used to study the anomeric configuration of N-acetyl-D-neuraminic acid released by the action of neuraminidase. The hydrolysis of NeuAcalpha 2 leads to 3 Gal-beta 1 leads to 4Glc (20mM) by the enzymes of Clostridium perfringens and Arthrobacter ureafaciens (50 mU, 150 mU and 800 mU, respectively) in 50mM Na/K-phosphate buffer pD 5.4 was observed by recording the spectra. On the basis of the characteristic signals of the protons at C-3 (alphaNeuAc: delta[H(3e)] = 2.72, delta[H(3a)] = 1.64; betaNeuAc: delta[H(3e)] = 2.25, delta[H(3a)] = 1.84) the product of the enzymatic cleavage was identified to be the N-acetylneuraminic acid in the alpha-anomeric form. Two hypotheses are discussed to explain how the enzymatic hydrolysis may occur and how N-acetyl-alpha-D-neuraminic acid leaves the catalytic site of the neuraminidases with retention of the C-2 configuration.

Arthrobacter↗

Regulation of Ca2+ and cyclic AMP during the first meiotic division in amphibian oocytes by progesterone.

Progesterone appears to be the physiological inducer of meiosis in amphibian oocytes. In Rana pipiens, dl-propranolol mimics the action of progesterone and both agents have a common action in producing a rapid [45Ca] efflux and a fall in intracellular cAMP followed by nuclear breakdown. Comparison of the rate of hydrolysis of injected [3H]-cAMP and of the conversion of injected [3H]-ATP to [3H]-cAMP followed exposure to meiotic inducers and inhibitors indicates that adenylate cyclase and not phosphodiesterase is the rate-limiting step in regulating [cAMP]i in the oocyte. The results suggest that progesterone initiates the resumption of the meiotic divisions by down-regulation of membrane adenylate cyclase, possibly via Ca2+ release from specific membrane sites.

3',5'-Cyclic-AMP Phosphodiesterases↗