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Biomedical subjects

H Kolbe

Publications and source records attributed to H Kolbe.

At least 37 records · Page 2Linked to original sources
PubMed1994

123I-IBZM SPECT: reconstruction methodology and results in parkinsonism and dystonia.

In 58 patients with Parkinsonism or dystonia striatal dopamine D2 receptors were investigated using 123I-iodobenzamide (123I-IBZM) single-photon emission computed tomography (SPECT). The influence of SPECT reconstruction methodology on semiquantification and the clinical value of 123I-IBZM SPECT were evaluated. Delineation of the striatal uptake and striatum/frontal cortex (ST/FC) ratios were improved by the use of compensation procedures for scatter and attenuation as well as the choice of an adequate filter. Satisfactory results were achieved using a Metz prefilter with a comparatively high order number (i.e. high cut-off and low suppression of higher frequencies via roll-off). Regarding clinical diagnoses it was not possible to differentiate between advanced idiopathic Parkinson's disease (IP) and Parkinsonism of other aetiology (OP) on the basis of 123I-IBZM SPECT. But patients with IP and favourable response to L-Dopa showed significantly higher ST/FC ratios than those with fluctuating response. In patients with dystonia ST/FC ratios were significantly higher compared to patients with IP or OP.

Adult↗
PubMed1992

Study of the interaction of HIV-1 and HIV-2 envelope glycoproteins with the CD4 receptor and role of N-glycans.

In order to further characterize the interaction of human immunodeficiency viruses (HIV) with the CD4 receptor at the molecular level, a binding test was performed using iodine-labeled glycoproteins, 125I-gp160 from HIV-1 and 125I-gp140 from HIV-2, to bind to lymphoid cells expressing the CD4 receptor. The inhibition of binding of the radiolabeled glycoproteins to CD4+ cells by increasing concentrations of nonradiolabeled gp160 or gp140 was used to determine the affinity of the interaction between the glycoproteins and CD4. The gp-CD4 association occurs with a high affinity: K0.5 gpHIV-1 = 9 x 10(-9) M and K0.5 gpHIV-2 = 7 x 10(-8) M, indicating that the affinity of the interaction between HIV-2 gp140 and CD4 is 10 times lower than that observed with HIV-1 gp160. The N-linked glycans of the HIV-1 and HIV-2 glycoproteins account for a high proportion of their molecular mass (about 50%). Total deglycosylation of gp160 and gp140 by enzymatic treatment with Endo F-N glycanase occurred under nondenaturing conditions, indicating the high accessibility of the N-linked glycan chains in the three-dimensional structure of the molecule. Moreover, the deglycosylated proteins retained a significant binding capacity to CD4. These results show that the carbohydrate chains of HIV-2 gp140, as those of HIV-1 gp160, do not play a major role in the gp-CD4 interaction.

CD4 Antigens↗
PubMed1991

Immunization of chimpanzees confers protection against challenge with human immunodeficiency virus.

Sustained high titers of neutralizing antibodies were elicited in three chimpanzees after sequential injections of different human immunodeficiency virus 1 (HIV-1) antigen preparations derived from the HIV-1 BRU strain that included whole inactivated virus or purified recombinant proteins and then synthetic peptides identical to the major HIV-1 neutralizing epitope V3. The animals were challenged i.v. with 40 chimpanzee infectious doses (equivalent to 100 tissue culture 50% infectious doses) of a stock of HIV-1 IIIB isolate. After 6 mo of follow-up, all three animals appeared uninfected by serologic and virologic criteria, including polymerase chain reaction analysis and failure to isolate virus from peripheral blood lymphocytes, bone marrow, and lymph node tissue. Of two chimpanzees monitored for 1 yr, virus was isolated initially from one animal at 32 weeks, but the second chimpanzee was virus negative by all assays through 12 mo; the third animal has remained virus negative through 9 mo of follow-up. These results indicate that it is possible to elicit protection against, or significantly delay infection of, HIV-1 by immunization, thus laying the foundation for development of an HIV-1 vaccine.

Amino Acid Sequence↗
PubMed1991

Confronting the hypervariability of an immunodominant epitope eliciting virus neutralizing antibodies from the envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-1)--II. Synthetic peptides linked to HIV-1 carrier proteins gag and nef.

Combining of subtype specific peptides from the hypervariable loop of the envelope glycoprotein gp120 of divergent HIV-1 isolates may help in designing a broadly protective immunogen against HIV-1 infection. To enhance the immunogenicity of such a polyvalent antigen, in the absence of oil-containing adjuvants, it is necessary to link the peptides to a protein carrier. It is preferable to use as carriers those proteins from HIV-1 itself which may contribute to eliciting protective immunity. The structural and non-structural proteins, gag P18 and nef, respectively, which can be prepared in high yields by recombinant DNA techniques in Escherichia coli, were selected for this purpose. The corresponding peptide-protein conjugates, each containing 21 distinct peptides, were prepared using the cross-linking reagents N-succinimidyl-3-(2-pyridyldithio)-propionate (SPDP) or m-maleimidobenzoyl-N-hydroxysulfosuccinimide ester (sulfo-MBS). Conjugates prepared by the second method elicited approximately 10-100 times higher levels of antibodies recognizing the homologous peptides and the HIV-1 envelope glycoproteins. The sulfo-MBS conjugation procedure preserved the antigenicity of both gag P18 and nef and the respective conjugates elicited an immune response to these proteins. Despite the low immunization dose of single peptides (10 micrograms) present in the mixture of peptides collectively linked to the carriers, antibody responses to most of the individual peptides were high (dilution endpoints 1: greater than 16,000, 1: greater than 80,000 for the nef and gag P18 conjugates, respectively). Conjugates consisting of a multitude of HIV-1 envelope-derived peptides in combination with gag P18 and nef carriers are expected to elicit broadly protective immunity against distinct HIV-1 subtypes.

Animals↗
PubMed1991

Antibody responses of chimpanzees immunized with synthetic peptides corresponding to full-length V3 hypervariable loops of HIV-1 envelope glycoproteins.

Immunization of primates or humans with human immunodeficiency virus type 1 (HIV-1) glycoproteins usually elicited moderate immune responses to the principal neutralizing determinant (PND) located within the V3 hypervariable loop of gp120. Since an antibody response to the PND appears to be protective, experiments were carried out to determine the responsiveness of chimpanzees to immunization with synthetic peptides corresponding to the full-length V3 loop. Seven chimpanzees (4 preimmunized with gp160, 2 preimmunized with HIV-1 antigens unrelated to gp160, and 1 unimmunized) were vaccinated with a mixture of full-length V3 loop peptides from 21 distinct HIV-1 isolates (clones) either in unconjugated form or linked to carrier proteins from HIV-1 nef and gag P18, respectively. Six chimpanzees developed high levels of antibodies to the peptides (dilution endpoints 1: greater than 25,000), and 5 had high levels of antibodies to gp120 from HIV-1IIIB (endpoint titers 1: greater than 500,000). Chimpanzees immunized with peptide-carrier conjugates (4) had antibodies to the carrier proteins nef and gag P18, respectively (endpoint titers 1: greater than or equal to 35,000). Virus-neutralizing (VN) antibodies were detected in sera of 5 of 7 chimpanzees, but were present at titers of 1: greater than or equal to 400 only in sera of 2 chimpanzees. One of these was challenged with HIV-1 and was protected against infection, as reported elsewhere. The antibodies were primarily specific for the HIV-1 isolate used for primary immunization before boosting with peptides. The relatively low dilution endpoints of VN antibodies as compared with endpoints determined by site-specific immunoassays probably can be ascribed to imperfect mimicry of conformational epitopes by synthetic peptides. Nevertheless, sequential or simultaneous immunization with recombinant envelope glycoproteins of HIV-1 and selected synthetic peptides offers an approach for eliciting protective immunity against HIV-1.

Amino Acid Sequence↗
PubMed1990

Immunogenicity and epitope mapping of a recombinant soluble gp160 of the human immunodeficiency virus type 1 envelope glycoprotein.

The human immunodeficiency virus 1 envelope glycoprotein is synthesized as a precursor, gp160, which is subsequently cleaved to generate the external gp120 and the transmembrane gp41. Both of these cleavage products are known to mediate critical functions of the virus. In order to define the best strategy for the development of a vaccine against human immunodeficiency virus 1, it could be important to map the crucial epitopes on gp160. This entire gp160 is uneasy to purify because it is readily subjected to proteolytic cleavage. Furthermore, it is anchored on the cell membrane and needs detergent treatment for purification. We thus used a recombinant gp160 which was engineered to remove the cleavage sites between gp120 and gp41 and the hydrophobic transmembrane in order to investigate the murine immune response. We selected a panel of 8 monoclonal antibodies which recognize different epitopes on the immunizing recombinant soluble gp160. The reactivity of the monoclonal antibodies was checked on virus-derived gp160, gp120, and gp41. Three antibodies reacted only with gp120 but the others were shown to react with gp41 epitopes or with discontinuous epitopes bridging gp120 and gp41. One subregion of these epitopes was located using a synthetic peptide corresponding to the sequence of gp41. This epitope is apparently part of an immunodominant site since it is recognized by three different monoclonal antibodies. We used competitive inhibition experiments to map the epitopes on recombinant gp160; therefore, the results are probably indicative of the folding of the recombinant soluble gp160 used for immunization.

Animals↗
PubMed1988

[Technic and clinical use of radioactive labelling of autologous granulocytes].

Gamma-camera imaging after injection of radiolabelled autologous leucocytes can be very helpful in the diagnosis, localization and further clinical treatment of inflammatory diseases. We present a technique allowing sterile separation of white blood cells and labelling with 99mTc-phytate or -oxine and with 111In-oxine, -oxine sulphate or -tropolone. The method is non-invasive and the radiation dose amounts to less than 80 mrad using 100 microCi 111Indium. The use of radiolabelled granulocytes is of particular diagnostic value in patients with septicaemia of unknown origin. Whole body scanning allows not only visualization of enhanced splenic uptake in septicaemia, but also localization of an inflammatory process. Preferential indications for a diagnostic approach using radiolabelled granulocytes are inflammatory abdominal processes which cannot easily be documented by means of other non-invasive techniques, such as inflammatory bowel disease (Crohn's diseases and ulcerative colitis), arthritic processes and abscesses of the liver and spleen, as well as subphrenic and retroperitoneal abscesses. Untreated osteomyelitis can be located with the help of labelled granulocytes, but in patients treated with antibiotics a false negative result is obtained in approximately 50% of cases for as yet unknown reasons, even in the presence of a still active osteomyelitic process.

Abscess↗
PubMed1985

[EHDP (ethylidene-1-hydroxy-1,1-diphosphonate) in the treatment of polyosseous Paget disease].

13 patients with polyosseous Paget's disease were treated for a mean period of 7 months with disodium etidronate (EHDP, ethylidene-1-hydroxy-1,1-diphosphonate); the average daily dosage was 5 mg/kg body weight. Subjectively, all patients reported a considerable improvement, in particular with regard to pain. Objectively, a significant decrease in plasma alkaline phosphatase activity and in urinary hydroxyproline excretion was observed. Bone scintigraphy showed a decreased activity of bone lesions after therapy, but no clear-cut regression was found radiologically. No serious side-effects were observed during treatment with EHDP and oral administration of the drug proved to be advantageous.

Aged↗
PubMed1984

[Technic of radioactive labeling of autologous human thrombocytes using 111-indium-oxine and 111-indium-oxine-sulfate and their clinical use].

Using 111indium oxine and 111indium oxine sulphate as platelet labels, maximal labelling efficiency can be achieved already after 3 minutes at an incubation temperature of 37 degrees C. Mean labelling efficiency values of about 90% are reached at a platelet count of greater than 10(9) platelets/ml, but the labelling efficiency is satisfactory also at a rather low platelet count of about 10(6) platelets/ml (71% on average). Platelet labelling with these tracers allows the calculation of platelet half-life in vivo, and gamma-camera imaging of platelet aggregates in thrombosis and renal transplant rejection as well. In the present study, the platelet half-life is significantly shortened in patients with coronary heart disease (n = 15), peripheral vascular disease (n = 13) and primary hyperlipoproteinaemia (n = 32) in comparison with 106 controls. No age dependence of platelet half-life was found in the different groups of patients whereas in the control group, a significant negative correlation between age and platelet half-life was observed.

Adult↗
PubMed1984

[In vitro and in vivo studies using 111 indium oxine, 111 indium oxine sulfate and 99m Tc oxine in erythrocyte labeling].

The optimal conditions for red blood cell labelling using 111indium oxine, 111indium oxine sulphate and 99mTc oxine were established both in vitro as well as in vivo. The coagulant had no effect on labelling efficiency. Other variables such as the incubation time, temperature, duration, cell number and concentration of the complex exert a significant influence on labelling efficiency. Labelling efficiency of red blood cells is very high also under non-optimum conditions as compared with other cells (leucocytes, platelets).

Erythrocytes↗
PubMed1984

A simple and safe technique for sterile autologous platelet labelling using "Monovette" vials.

A simple technique of autologous platelet labelling is described, which allows labelling within 40 min, and has the advantage of low costs, as no laminar air flow is required. Blood (16 ml) was withdrawn into 4 ml ACD, 500 ng prostacyclin was added. After 10 min sedimentation the vials were centrifuged for 5 min at 150 g. The plateletrich plasma in the supernatant was centrifuged at 500 g for 10 min to obtain a platelet pellet. The platelet-poor plasma was preserved in a sterile syringe and the platelet pellet was resuspended in 1 ml tyrode buffer. The cell suspension was labelled at 37 degrees C for 5 min with 100 muCi 111In-oxine sulphate and reinjected after dilution with the plasma. Mean labelling efficiency was 90% +/- 3%, mean recovery 2 h after reinjection 76% +/- 3% (mean +/- SD).

Blood Platelets↗
PubMed1983

[Differential diagnosis of cholestasis by non-invasive methods--comparison of cholecysto-cholangiography, ultrasonics and hepatobiliary sequential scintigraphy].

The value of the three non-invasive morphological methods--cholangiography, sonography, and cholescintigraphy--in the differential diagnosis of "surgical" and "non-surgical" cholestasis was assessed prospectively in 28 patients. The main disadvantage of cholangiography was the large number of patients (11 out of 28) in whom the biliary tract could not be visualized. Correct diagnosis was achieved by sonography in 25 out of 28 and by cholescintigraphy in 23 out of 28 patients.

Bile Ducts, Intrahepatic↗
PubMed1981

Neuroleptic-induced acute dystonic reactions may be due to enhanced dopamine release on to supersensitive postsynaptic receptors.

Oral administration of butaperazine (40 mg per kilogram) to rats increased dopamine turnover, as measured by elevation of striatal and mesolimbic concentrations of homovanillic acid and 3,4-dihydroxyphenylacetic acid, for 24 to 48 hours. Initially, this dose of butaperazine inhibited stereotyped behavior in response to subcutaneous administration of apomorphine, but this effect was reversed at 12 hours. Later, animals had normal or exaggerated responses to apomorphine. The data suggest that the critical 20- to 28-hour period after butaperazine administration, when most human acute dystonic reactions occur, normal or supersensitive cerebral dopamine receptors are exposed to an excessive synaptic release of dopamine. This may be responsible for the drug-induced dystonia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1981

The endocrinology of testicular germinal cell tumors.

Oestradiol (Oe2), testosterone (T), lutenizing hormone (LH), follicle stimulating hormone (FSH), beta-human chorionic gonadotrophin (beta-hCG) and alpha-1 foetoprotein (AFP) were measured in blood samples taken from 63 patients with testicular tumours. In patients without tumour recurrence (n=31) AFP, Oe2 and T were within the normal range, beta-hCG was negative, LH levels were marginally elevated and FSH concentrations were significantly elevated. In patients with tumor recurrence (n=32) Oe2 was significantly elevated, whereas the T levels varied considerably and were therefore statistically not different from the patients without tumour recurrence. The beta-hCG positive subgroup of the recurrence group, however, demonstrated significantly elevated T levels. T levels were highest in patients with 51 to 500 U beta-hCG/1. On hand T was normal or even low normal in beta-hCG negative -AFP positive patients. In all subgroups decreasing FSH levels and decreasing LH responses to LRH were among the earliest signs of tumour recurrence. The observations suggest that moderate hCG levels are able to stimulate testicular T production, whereas high levels no longer increase T serum concentrations. Increased conversion rates form steroid precursors to oestradiol seem to be a feature of beta-hCG positive as well as beta-hCG negative testicular tumours.

Choriocarcinoma↗