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Biomedical subjects

G Dietz

Publications and source records attributed to G Dietz.

At least 37 records · Page 2Linked to original sources

De novo synthesis of type-I collagen in bone biopsy material.

A simple and rapid method was established for the cultivation of bone cell tissue. Human bone tissue derived from orthopaedic surgery was cultivated in the presence of 14C-proline and beta-aminopropionitrile. De novo synthesized collagen was extracted from the tissue and quantified by determination of radioactivity in the purified protein. Measurements of the oxygen consumption of the tissue provided evidence that the physiological conditions for the tissue were optimal. The tissue was vital over a period of as long as 7 days, showing normal respiration and a constant rate of collagen synthesis. The observed levels of alkaline phosphatase and acid phosphatase activity clearly demonstrated that mainly osteoblasts were involved in metabolic activity. The described system is suitable for investigations of bone cell metabolism under quasiphysiological conditions.

Acid Phosphatase↗

Characterization and transfusion of in vitro cultivated hematopoietic progenitor cells.

Our study is to show the safety of transfusion and the number, phenotype, and proliferative potential of in vitro cultivated autologous hematopoietic peripheral blood progenitor/stem cells (PBPCs). An in vitro long-term liquid culture using PBPC suspension from consenting patients with metastatic breast cancer was established. The medium was supplemented with a variety of hematopoietic growth factors. The mononuclear cells (MNCs), their viability, CD34+ subsets, clonogenic cells, and neutrophil function were measured prior to, during, and after liquid culture for 14 days. The total cell number increased during incubation in vitro from 2.5 x 10(8) to 5 x 10(9). The clonogenic and CD34+ cells increased during the first week 6- and 3.5-fold, respectively, and were almost undetectable after 2 weeks. Maturation into the myeloid cell series was demonstrated by standard cytology and increase of CD33+ and CD38+ cell numbers. On average, 1.5 x 10(9) cells were transfused to consenting patients with metastatic breast cancer after high-dose chemotherapy and PBPC transplantation at nadir of WBC < or = 0.1/nL. One hour later, the mean WBC was measurable at 0.3/nL. Subsequently, WBC counts dropped to 0.2/nL and 0.1/nL at 6 and 24 h post transfusion. No side effects and complications were observed. In summary, an in vitro expansion can produce a > or = 20-fold increase of maturing PBPCs for an effective and safe autologous transfusion. This unique approach, when refined, could lead to a safer post-transplant period and a decrease of complications due to neutropenic fever.

Adult↗

Intraarticular hip treatment with triamcinolonehexacetonide in juvenile chronic arthritis.

To evaluate the effect and tolerance of intraarticular Triamcinolonehexacetonide (TCH) in the course of chronic coxitis in juvenile chronic arthritis (JCA) in an open uncontrolled study. Since 1990 we treated patients < 16 years of age suffering from chronic coxitis with 1 mg/TCH/KG body weight. The patients were checked again 4-8 weeks after the treatment. Clinical and ultrasound courses were recorded with the help of ultrasound and joint scores. The evaluation took place 6, 12, 24 and 36 months after the treatment. At that time we give a report on the 12 months follow-up of 37 hip joints and the 24 months follow-up of 20 hip joints. The immediate effect of TCH influencing mobility, pain sensitivity and joint effusions of the patients is impressing. The long term effect of TCH has to be evaluated by regular check ups for at least 2 years. An individual comparison with the not treated contralateral joint would be desired if ethically justifiable. Most patients suffering from polyarticular diseases with a long course of coxitis needed more than one injection of TCH (mean reinjection time 5.8 months). Any avascular necrosis of the femoral heads or other complications were not observed.

Adolescent↗

The dopamine D2 receptor (DRD2) as a major gene in obesity and height.

Dopamine plays a major role in the regulation of appetite and growth hormone. Dopaminergic agonists suppress appetite and dopamine D2 receptor antagonists enhance it. We examined the hypothesis that allelic variants of the DRD2 locus may be associated with weight and height. Sarkar and Sommer described two DRD2 polymorphisms that could be haplotyped by PCR. For weight, the mean Z score (National Center for Health Statistics) for 208 subjects without haplotype 4 was 0.086 versus 0.557 for 280 subjects with haplotype 4, P = 0.0003. Two separate sets of subjects were studied and these results were significant for both, providing an internal replication. For height, the mean Z score for 164 subjects without haplotype 4 was 0.1677 versus 0.6885 for 219 subjects with haplotype 4, P < 0.00001. These and other data suggest that the 4 haplotype is in linkage disequilibrium with allelic variants of the DRD2 gene that play a major role in the regulation of weight (obesity) and height, and may serve as a risk factor in late-onset non-insulin-dependent diabetes mellitus (NIDDM).

Adolescent↗

Identifying blood group antibodies...can a computer help?

Antibody identification is one of the last areas of laboratory medicine to embrace computerization. This is due in part to the complex nature of antibody identification. Until recently, computer programs written to assist with antibody identification have been slow and cumbersome. However, technological advances in computer hardware have greatly improved the response time for these applications. Still, blood bank technologists sometimes shun assistance from the computer because they consider anti- body investigation as an intellectually stimulating aspect of their job that they do not wish to turn over to a computer. Computer programs for antibody investigation are probably most useful for technologists who perform antibody investigations infrequently. They can also be invaluable for experienced technologists performing complex investigations. When integrated with a computerized blood bank record-keeping system, antibody investigation software can improve storage and retrieval of test results. Database applications for retrieving rare cells and sera offer the potential to improve the productivity and capability of any anti- body investigation laboratory. And word processing applications greatly enhance the potential for generating meaningful reports of test results.

Journal Article↗

Optimal timing for collections of blood progenitor cells following induction chemotherapy and granulocyte-macrophage colony-stimulating factor for autologous transplantation in advanced breast cancer.

Circulating progenitor cells collected during periods of rapid hematopoietic reconstitution can be used successfully as hematopoietic support for super-dose chemotherapy. A major problem for collection of peripheral blood progenitor cells has been determination of optimal time to start leukapheresis and of the adequate amount of progenitor cells. This study has demonstrated that an induction chemotherapy with augmented dosage of CEF (cyclophosphamide, epirubicin, 5-fluorouracil) in conjunction with granulocyte-macrophage colony-stimulating factor (CM-CSF) successfully mobilized peripheral blood progenitor cells in 15 patients with metastatic breast cancer. By monitoring the granulocyte-macrophage colony-forming units (CFU-GM), erythrocyte burst-forming units (BFU-E), and CD34+ cells in peripheral blood daily after leukocyte nadir, we have identified an optimal 'window' in which concentrations of blood progenitor cells reached a maximum range. Although the time interval between chemotherapy and the time for maximum stimulation could vary from between 13 days to 19 days, maximum mobilization started consistently 2 days after the white blood cells (WBC) recovered to > 2.0 x 10(9)/l after nadir, and remained elevated for 4 to 5 days. A significant reduction of progenitor cells in peripheral blood and in the corresponding leukapheresis products was observed, however, from cycle 1 versus subsequent cycles (p < 0.0001), but there was no significant difference between cycles 2 and 3. When used as the sole source of hematopoietic support for super-dose chemotherapy with cyclophosphamide, mitoxantrone, and carboplatin, these progenitor cells induce rapid and sustained reconstitution in all patients. The median time from reinfusion to recovery of absolute neutrophil count (ANC) to > 0.5 x 10(9)/l was 13 days (range 9-18 days) and to an unmaintained platelet count of > 50 x 10(9)/l, 12 days (range 10-35 days). Autologous transplantation with stimulated blood progenitor cells can be an efficient alternative to bone marrow transplantation. With optimal timing for collections, as few as two leukapheresis procedures are required to obtain an adequate progenitor cell dose.

Adolescent↗

Induction of intracellular and plasma 2',5'-oligoadenylate synthetase by pentostatin.

Similar to interferon alpha, pentostatin is highly effective in hairy cell leukemia and moderately active in other chronic lymphoid malignancies. In ten patients with hairy cell leukemia (HCL) and seven patients with other B-cell chronic leukemias (BCL), we have studied the intracellular 2',5'-oligoadenylate synthetase (2,5OAS) activity of the mononuclear cells before, 4 h, 24 h, and 48 h after pentostatin administration. In patients with HCL the median level of intracellular 2,5OAS increased 4.6-fold at 4 h and 11.5-fold at 24 h compared to the pretreatment value. Among the other seven patients, the median intracellular 2,5OAS remained unchanged in three patients and rose slightly by 2 to 14 times in four patients. Eleven patients (eight with HCL and two with BCL) responded to pentostatin. The median increase in 2,5OAS among the responders was 13.0-fold (range 4.8-30.0) whereas that among non-responders was 2.2-fold (range 0.2-6.3). The difference was highly significant (p less than 0.0001). In five of the total seventeen patients, the plasma levels of 2,5OAS activity were also determined and changes in plasma levels paralleled those measured intracellularly. To determine if the elevation of 2,5OAS is mediated by induction of interferon alpha, the expressions of mRNA for interferon alpha and beta were investigated by means of reverse transcription and polymerase chain reaction using the corresponding sense primers. In none of the five patients thus studied could we find an induction of mRNA for interferon alpha or beta in the leukemic cells during treatment with pentostatin. Thus, response to pentostatin correlates with induction of 2,5OAS directly and the 2',5'-oligoadenylate system seems to be involved in cytotoxicity.

2',5'-Oligoadenylate Synthetase↗

Alloimmunization by blood group antigens from bone allografts.

The purpose of this report is to heighten awareness of the risk of blood group antigen sensitization following hone allografting. Two Rh-negative females of childbearing age developed multiple antibodies to Rh antigens following transplantation of bone from Rh-positive donors. A previous pregnancy and/or blood transfusions were ruled out as factors influencing the antibody production. It is postulated that red cells or red cell stroma in the allografts stimulated the antibody production. Therefore, young, Rh-negative bone allograft recipients at risk (especially women) should receive Rh-negative bone allografts. Alternatively, they should receive Rh immune globulin at the time of transplanting if the allograft is from an Rh-positive donor. Bone allografts processed to deplete the hemopoietic marrow and red cells should minimize the risk of blood group antibody sensitization.

Journal Article↗

The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders.

OBJECTIVE: --The A1 allele of the Taq I polymorphism of the dopamine D2 receptor (DRD2) gene has been earlier reported to occur in 69% of alcoholics, compared with 20% of controls. Other research has reported no significant difference in the prevalence of the A1 allele in alcoholics vs controls and no evidence that the DRD2 gene was linked to alcoholism. We hypothesized that these seemingly conflicting results might be because increases in the prevalence of the A1 allele may not be specific to alcoholism. Thus, we examined other disorders frequently associated with alcoholism or those believed to involve defects in dopaminergic neurotransmission. DESIGN: --Case comparison study. To minimize the effect of racial differences in gene frequencies, the study was restricted to non-Hispanic whites. SETTING: --Ambulatory and hospitalized patients. RESULTS: --Among all known controls (n = 314), 77 (24.5%) carried the A1 allele. Of the 69 controls known not to be alcoholics, 10 (14.5%) carried the A1 allele. The prevalence of the A1 allele was significantly increased in patients with Tourette's syndrome (44.9%, n = 147), attention deficit hyperactivity disorder (46.2%, n = 104), autism (54.5%, n = 33), alcoholism (42.3%, n = 104), and posttraumatic stress disorder (45.7%, n = 35). After correction for multiple comparisons (requiring P less than .0009 for significance), all remained significant except posttraumatic stress disorder. The prevalence of the A1 allele was not significantly increased in patients with depression, panic attacks, Parkinson's disease, or obesity. The prevalence of the A1 allele in drug addiction and schizophrenia was only significant when compared with that of controls who were not alcoholics, and no correction was made for multiple comparisons. CONCLUSION: --These results suggest the A1 allele of the DRD2 gene is associated with a number of behavior disorders in which it may act as a modifying gene rather than as the primary etiological agent.

Alcoholism↗

[Pharmaceutical characterization and spectroscopy of AWD 26-06].

To fix parameters for the pharmaceutical characterization of AWD 26-06 test methods converting identification, purity, content and stability as well as their results are submitted. Spectroscopic investigations are intended to give information on the constitution of the molecule.

Anti-Ulcer Agents↗

Enzyme activities of leukemic cells and biochemical changes induced by deoxycoformycin in vitro--lack of correlation with clinical response.

Deoxycoformycin (DCF) is a specific inhibitor of adenosine deaminase (ADA) and has been shown to be active in lymphoid neoplasms. Cytotoxicity is thought to be mediated by the accumulation of deoxyadenosine (AdR) and deoxyadenosine triphosphate (dATP) which inhibits ribonucleotide reductase and DNA synthesis in rapidly proliferating cells. Others suggested mechanisms leading to cell death particularly in non-dividing cells include depletion of ATP and NAD pools, inhibition of S-adenosylhomocysteine (SAH) hydrolase and induction of DNA strand breaks. In patients with high leukemic counts who were subsequently treated with DCF, we have studied (a) the levels of ADA, ecto-5'-nucleotidase (5NT), deoxyadenosine kinase (AdR-kinase) and SAH-hydrolase in the leukemic cells; [b) the in-vitro effects of DCF on dATP, ATP, NAD, SAH-hydrolase levels and on DNA strand breaks; and (c) the correlation between these parameters with clinical response to DCF. No significant difference in ADA, 5NT, AdR-kinase and SAH-hydrolase activities could be found between responders and non-responders. Incubation of the leukemic cells in vitro with DCF caused an inhibition of ADA, an accumulation of dATP, a moderate reduction in ATP and NAD levels, a suppression of SAH-hydrolase activity and an increase in DNA strand breaks in practically all the leukemic samples, irrespective of clinical response. Our results show that neither measurement of these enzymes nor studies of these biochemical sequelae of ADA inhibition in vitro predicts clinical responsiveness to DCF therapy.

Adenosine Deaminase Inhibitors↗

[Effect of stress incontinence operations on urodynamic parameters. 1. Is surgical success measurable?].

Urodynamic parameters are changed by stress incontinence surgery. Our study, comparing pre- and postoperative measurements in 141 women with urinary stress incontinence, shows an increase of the transmission ratio in the proximal urethra and a decrease of depression factors in the proximal and mid urethra after surgery. The functional urethral length remains unchanged while the maximum urethral pressure decreases. Except for the maximum pressure decrease, these changes were only found after successful surgery and not in failures. Thus, effectiveness of operations can be quantificated by urodynamic measurements. The unfavourable prognostic influence of a preoperative hypotonic urethra on the results of surgery was confirmed by this study.

Female↗

X-ray studies on piroxicam modifications.

The anti-inflammatory drug piroxicam, 4-hydroxy-2-methyl-N-(2-pyridyl)2H-1,2- benzothiazine-3-carboxamide-1,1-dioxide, crystallizes in three different forms, two anhydrates and one monohydrate. Crystal structure analyses of the monohydrate and one of the anhydrate were carried out by Bordner et al. and Kojić-Prodić et al., respectively. In this paper the results of the analysis of the third piroxicam modification and of an independently performed structure determination of the monohydrate are reported. Molecular structures and hydrogen bonding of all modifications are discussed.

Chemical Phenomena↗

[X-ray crystallographic studies of diclofenac-sodium--structural analysis of diclofenac-sodium tetrahydrate].

The crystal structure of the hydrate of the antiphlogistic drug diclofenac sodium was determined to explain the unusual dissolution behaviour in ethyl acetate. The compound crystallizes in the monoclinic space group P2(1)/m with a = 9.464(2), b = 39.405(7), c = 9.972(3) A und beta = 90.74(2) degrees. The unit cell contains two symmetry independent formula units (C14H10Cl2NO2)-Na+.3,94 H2O. There are molecule layers and sodium-water layers which show order-disorder phenomena.

Crystallization↗

Clinical response to deoxycoformycin in chronic lymphoid neoplasms and biochemical changes in circulating malignant cells in vivo.

Deoxycoformycin (DCF), an adenosine deaminase (ADA) inhibitor, has been shown to be active in lymphoid neoplasms. The mechanism of cytotoxicity might involve accumulation of deoxyadenosine triphosphate (dATP), depletion of the nicotinamide adenine dinucleotide (NAD) and ATP pool, induction of double-stranded DNA strand breaks, or inhibition of S-adenosyl homocysteine hydrolase (SAH-hydrolase). We have investigated the biochemical changes in the circulating malignant cells of patients with chronic leukemia/lymphoma who were treated with DCF (4 mg/m2 weekly). Blood samples were taken from 17 patients with 60% or more circulating leukemic cells before, 4, 24, and 48 hours and five days after the first administration of DCF. Leukemic cells were separated and studied for changes in ADA, dATP, ATP, NAD, and SAH-hydrolase levels and DNA strand breaks and the data analyzed according to clinical response. Inhibition of ADA activity was found in all except one patient at 4 to 24 hours after the first administration of DCF. dATP started to accumulate at four hours, reached a maximum level between 24 and 48 hours, and returned to base values on the fifth day. Intracellular ATP and NAD levels were transiently reduced in some of the patients. However, no correlation between these changes and a clinical response could be found. DNA strand breaks could be studied in 13 patients. A significant increase in DNA breaks at 24 to 48 hours was found in six of the seven responders but only in one of the six nonresponders. At 24 hours, SAH-hydrolase levels were reduced in all seven responders studied, but only in two of the seven nonresponders. The difference in inhibition of SAH-hydrolase was statistically significant (P = .0023). These results suggest that DNA strand breaks and inhibition of SAH-hydrolase correlate with clinical response.

Adenosine Deaminase Inhibitors↗

In vivo red blood cell compatibility testing using indium-113m tropolone-labeled red blood cells.

In vivo radionuclide crossmatch is a method for identifying compatible blood for transfusion when allo- or autoantibodies preclude the use of conventional crossmatching techniques. A technique for labeling small volumes of donor red blood cells with [113mIn]tropolone is reported. The use of 113mIn minimizes the accumulation of background radioactivity and the radiation dose especially so when multiple crossmatches are performed. Labeling red cells with [113mIn]tropolone is faster and easier to perform than with other radionuclides. Consistently high labeling efficiencies are obtained and minimal 113mIn activity elutes from the labeled red blood cells. A case study involving 22 crossmatches is presented to demonstrate the technique. The radiation dose equivalent from 113mIn is significantly less than with other radionuclides that may be used to label red cells.

Adult↗