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Biomedical subjects

G Stein

Publications and source records attributed to G Stein.

At least 379 records · Page 21Linked to original sources

[Long-term treatment of glomerulonephritis with indomethacin with special regard to quantity and selectivity of proteinuria].

In 53 patients (19 women, 34 men), of them 41 patients with an intracapillary proliferative glomerulonephritis, 9 with membranous proliferative and 3 with a membranous glomerulonephritis under an indometacin therapy examinations concerning proteinuria were carried out, partly with determination of the index of selectivity and representation of the protein clearance. In patients with a moderate proteinuria of less than 3 g a day this treatment achieved a smaller antiproteinurie effect than in patients with a large proteinuria. When a large activity of the inflammatory process was present a therapeutic success was less frequently to be proved. An unequivocal correlation between the histological course of the disease and the change of the proteinuria could not be recognized. After cautious estimation of the findings the selectivity of the proteinuria may be regarded as a certain indicator for the application of indometacin. The protein clearance, however, proved less suitable for the judgment of the treatment performed.

Adolescent↗

Conformation-dependent participation of the protein in electron equivalent transfer to cytochrome c.

When ferricytochrome c is reduced by H atoms (produced by pulse radiolysis) at neutral pH where it is in a closed protein configuration, a considerable percentage of the reduction proceeds through electron equivalent transfer via the protein. At pH 2.0, where cytochrome c is in an open configuration, H atoms reduce by adding directly to the heme porphyrin. The intermediate then observed is identified through similarity with that formed on ferriheme alone.

Cytochrome c Group↗

H/2H isotope effect in redox reactions of cytochrome c.

The rate of reaction of ferro- and ferricytochrome c (C(II) and C(III) with ferri- and ferrocyanide and of C(III) with 02- and CO2- was determined in H2O and in 2H2O in the temperature range 5-35 degrees C. No isotope effect was evident in any of the reductions of C(III); the apparent energy of activation was identical in H2O and 2H2O. An isotope effect with kH2O/k2H2O = 1.25 to 1.85, depending on pH for instance was observed in the oxidation of C(II), in the slow phase of oxidation which involves conformational changes. An interpretation (supported by evidence from previous work) involving water molecules in the close vicinity of the reaction site on the protein is discussed.

Carbon Dioxide↗

[Electron-microscopy studies of capillaries of the dialyser C-DAK 4 with reference to multiple use].

The results of the examinations show that the integrity of the wall of the capillary is not impaired by the process of purification, but, on the other hand, functional changes by thrombotic occlusion as well as disseminated deposits of protein may be expected. The temporary regime of dialysis mus consider this fact in order to achieve a constant effect. But on principle from the clinical experience and on the basis of these results of examinations a manifold use of the dialysator of the capillary in carrying out the purification measures mentioned may be recommended.

Capillary Permeability↗

Pharmacokinetics of sulfaclomide and sulfamerazine in patients with impaired renal function after first and after repeated application.

At the beginning of the therapy with sulfaclomide resp. sulfamerazine elimination half-life of sulfaclomide was prolonged significantly in patients with impaired renal function (creatinine in serum greater than 2 mg/100 ml) on 119.6+/-6.9 h in comparison to control group (83.6+/-14.5 h). Half-life of sulfamerazine (23.6+/-4.1 h) did not differ from that of the control group (20.3+/-2.8 h). Renal excretion of both sulfonamides was sharply diminished. After treatment for 11 days with sulfaclomide resp. sulfamerazine in patients with impaired renal function, half-lives were prolonged to 117.3+/-6.1% resp. 119.3+/-3.9% of the initial value. In patients with impaired renal function elimination half-life of PAH as a measure of tubular function is three times that of control group. It is not statistically significantly influenced by repeated administration of the sulfonamides. In the control group there is a shortening of the PAH-half-life under the same conditions.

Adolescent↗

[Pharmacokinetics of indomethacin and indomethacin metabolites administered continuously to patients with healthy or damaged kidneys].

After oral administration of 75 mg Indomethacin dlimination half-life of the unchanged drug is not altered in patients with severely impaired renal function. In patients with renal insufficiency half-life of Indomethacin plus metabolites is twice that of the normal value. Repeated daily administration of 75 mg for 8 days does not influence Indomethacin kinetics. In the control group and in patients with moderate by impaired renal function Indomethacin half-life does not change during chronic administration.

Half-Life↗

Reactions of the ferri-ferrocytochrome-c system with superoxide/oxygen and CO2-/CO2 studied by fast pulse radiolysis.

The reduction of ferricytochrome c by O2- and CO2- was studied in the pH range 6.6-9.2 and Arrhenius as well as Eyring parameters were derived from the rate constants and their temperature dependence. Ionic effects on the rate indicate that the redox process proceeds through a multiply-positively charged interaction site on cytochrome c. It is shown that the reaction with O2- (and correspondingly with O2 of ferrocytochrome c) is by a factor of approx. 10(3) slower than warranted by factors such as redox potential. Evidence is adduced to support the view that this slowness is connected with the role of water in the interaction between O2-/O2 and ferri-ferrocytochrome c in the positively charged interaction site on cytochrome c in which water molecules are specifically involved in maintaining the local structure of cytochrome c and participate in the process of electron equivalent transfer.

Binding Sites↗

Hodgkin's disease presenting as pericarditis.

Two patients presented with initial symptoms of pericarditis. Palpable lymph nodes developed a few weeks later and a diagnosis of Hodgkin's disease was made. Although rare, this mode of presentation of Hodgkin's disease has been reported previously, and it should be considered in the differential diagnosis of any patient with pericarditis with severe general symptoms or a prolonged course.

Adult↗

The study of 1-electron equivalent oxidation-reduction reactions by fast pulse generation of reagents. Cytochrome c/ferri-ferrocyanide system.

The method of pulse radiolysis was used to generate reagents in situ in times (500 ns to 1.5 mus) short compared with the rates of the observed biochemical processes. This "instant" mixing technique is compared with rapid stopped flow measurements (limited in rates and concentrations) and T-jump measurements (limited to relaxation in the neighborhood of equilibrium) for the ferro-ferricytochrome c (C(II)-C(III))/ferro-ferricyanide (FCN(II)-FCN(III)) system. The reagents generated in situ were C(II) or FCN(III). Kinetically indistinguishable binding sites exist on C(II) and C(III) for hexacyanide anions. Reductive electron transfer to the protein proceeds within the FCN(II)-C(III) complex, with a rate of 400 s-1. The binding of FCN(II) on C(II) slows down the oxidation of C(II) by FCN(III). The sites of interaction on C(II) or C(III) with FCN(III) show effective charges of approximately +2. The association constant per binding site derived from the kinetics of electron transfer is greater than or equal to 10(4) M-1 for FCN(II)-C(II) and less than or equal to 10(4) M-1 for FCN(III)-C(III). Specific clusters of amino acids in the model of cytochrome C are suggested as binding sites. The oxidation-reduction reactions of FCN appear to involve electron equivalent transfer to and from such somewhat remote binding sites on the protein. Anions such as phosphate or sulphate also bind to these, less strongly than hexacyanides. In the presence of perchlorate the kinetics show the resolution of the pK=9.3 of C(III) into two parts: (a) optical changes at 695 nm due to ligand interchange on the heme-iron, unaffected by perchlorate and (b), a kinetic change leading to biphasic oxidation of C(II), with pK=7.4. This is attributed to the effect of perchlorate on water structure in the close environment of the binding sites. The high rate of oxidation of relaxed C(II) by FCN(III), (2 X 10(8) M-1 S-1 at mu=0) is not in agreement with an outer sphere Marcus mechanism. Nonrelaxed C(II) having a structure closer to C(III) transfers electron to FCN(III) even faster (k=3 X 10(9) M-1 S-1 at mu=0).

Anions↗

Dephosphorylation of nonhistone proteins specifically alters the pattern of gene transcription in reconstituted chromatin.

A nonhistone phosphatase devoid of detectable protease activity has been purified from nuclear sap by chromatography on DEAE-Sephadex. After linkage to an insoluble agarose matrix, this enzyme was used to dephosphorylate nonhistone proteins obtained from S-phase HeLa cells. Chromatin reconstituted with these dephosphorylated proteins exhibited roughly a 50% reduction in the overall number of initiation sites available for transcription when compared to controls. Specific measurements of transcription of histone genes with use of a complementary DNA probe showed that genes coding for histones are preferentially inhibited after nonhistone dephosphorylation. These results provide the first direct support for the theory that phosphorylation of nonhistone proteins is involved in regulating the availability of individual genes for transcription.

Cell Nucleus↗

Low dose, long-term treatment of rheumatoid arthritis with azathioprine.

Sixteen patients with classical rheumatoid arthritis which had been present for longer than two years, representing anatomic stages II-IV, were treated with azathioprine in doses of 50 to 175 mg/day. They were followed up for up to six years. Using the criterion of ability to work, 93% of the patients improved markedly during the time observed. Complement levels were low before treatment and tended to stabilize within the normal range as the disease became less active. Erythrocyte sedimentation rate (ESR) fell during therapy but changes in ESR did not correlate well with the patients' clinical states. Titers of rheumatoid agglutinins showed little change after as long as six years of therapy. When all patients were stable a double-blind cross-over study, using a placebo tablet, was instituted. Fifteen of 16 patients had a marked exacerbation of disease activity after receiving placebo for three to eight weeks. When azathioprine was reinstituted, gradual improvement again occurred so that all patients were back to their asymptomatic or mildly symptomatic state within seven months.

Adult↗