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Biomedical subjects

K Wagner

Publications and source records attributed to K Wagner.

At least 289 records · Page 16Linked to original sources

Persistent production of colony-stimulating factor (CSF-1) by cloned bone marrow stromal cell line D2XRII after X-irradiation.

The adherent stromal layer in long-term bone marrow cultures (LTBMC) provides the cellular environment necessary for the in vitro proliferation and differentiation of pluripotential hematopoietic stem cells. The role of humoral hematopoietic growth factors, colony-stimulating factors (CSF) in the regulation of hematopoietic cell production in this system is poorly understood. We have recently isolated and cloned an adherent cell line, D2XRII, derived from murine LTBMC. Plateau phase 25 cm2 cultures of 2 X 10(6) D2XRII cells in 8.0 ml produced CSF-1 (M-CSF) at around 100-150 units/0.1 ml medium. Following X-irradiation there was a dose-dependent decrease in the production of CSF-1 to a plateau of 50% of control levels at 10,000 rad. Higher doses did not produce a further decrease. The X-ray dose reducing CSF-1 production to 50% was 100-fold above the lethal dose as measured by clonagenic survival following trypsinization and replating. Trypsinized replated viable adherent but nondividing X-irradiated D2XRII cells were maintained for up to 8 weeks after irradiation and demonstrated continuous production of CSF-1. The data indicate significant divergence of two biologic effects of X-irradiation on plateau-phase marrow stromal cells: physiologic function of adherence and CSF-1 production, versus proliferative integrity. This divergence of effects may be very relevant to understanding the mechanism of X-irradiation-associated marrow suppression and leukemogenesis.

Animals↗

Tetraploid partial hydatidiform moles: two cases with a triple paternal contribution and a 92,XXXY karyotype.

In the course of a systematic study of cytogenetics, morphology, and clinical follow-up of hydatidiform moles we encountered two unusual cases of partial hydatidiform moles each with a 92,XXXY karyotype. Previously reported cases of tetraploidy, of 92,XXXX or 92,XXYY karyotype, resulted from a failure of the first mitotic division of a normal zygote. This is to our knowledge the first report of tetraploidy with XXXY sex chromosomes. Study of chromosomal heteromorphisms, isozymes, and restriction fragment length polymorphisms reveal that both present cases resulted from a combination of a haploid ovum with three haploid sets of paternal chromosomes either by the mechanism of trispermy (involving three separate haploid spermatozoa) or through dispermy (involving one haploid and one diploid sperm). Both cases resembled closely partial moles in their morphology; one gave a highly typical clinical picture while the other was recognized at an early voluntary abortion. Partial moles are ordinarily triploids of nearly always diandric constitution that evince focal villous swelling with cistern formation and focal trophoblastic hyperplasia. The findings here presented point to an association of molar phenotype with an excess of paternal over maternal haploid sets.

Adolescent↗

[Biological value of various bone substitutes in the treatment of bone defects. Animal experiment studies].

In clinical practice, biologic and synthetic substances have been used more and more as bone substitutes during the last few years. Different properties of the implant material are required according to the various fields of application. This implies a precise investigation of the biologic value by adequate experimentations on animals. It has been demonstrated in a bioassay with several synthetic implant materials, especially ceramics made of calcium phosphate, powders and granulated materials of tricalcium phosphate, and hydroxylapatite with different pore sizes and numbers, that there is only poor or even not any biologic activity in these substances which would produce an orthotopic stimulation of osseous formation. The application of these substances as bone substitutes can only be recommended in an adequate transplantation bed. However, all implant materials tested by different experimentations on animals showed an incomplete absorption in the histomorphological investigation even after twelve months. The various biologic bone substitutes (autologous and homologous spongiosa, demineralized homologous spongiosa, different forms of bone gelatin) show different degrees of biologic activity. Hitherto an inducing heterotopic effect could be demonstrated for bone gelatin in rats, dogs, and sheep. The inducing effect of bone gelatin combined with soluble calcium phosphate ceramics in rats was increased as compared with autologous spongiosa. Regarding our own results as well as various communications in literature, we consider it absolutely necessary to give more attention to the objectifying criteria when describing the biologic activity of "biologic and synthetic bone substitutes".

Animals↗

Induction of growth alterations in factor-dependent hematopoietic progenitor cell lines by cocultivation with irradiated bone marrow stromal cell lines.

We studied the production of hemopoietins by x-irradiated plateau-phase cultures of cloned marrow stromal cell lines derived from C3H/HeJ marrow, termed D2XRII and clone 11. The production of CSF in agar overlay of control or 10,000 rad irradiated stromal cultures was quantitated by induction of colonies in: overlaid fresh marrow, IL-3-dependent cell line 32D cl 3, or GM-CSF/IL-3-dependent cell lines FDCP-1 or bg/bg cl 1. Conditioned media were tested for CSF by bioassay using fresh marrow cells, for M-CSF (CSF-1) by RIA, and for IL-3 and GM-CSF by microwell proliferation assay with 32D cl 3 and FDCP-1 cells, respectively. X-irradiation to doses that decreased CSF-1 to 40% of control levels (greater than 5,000 rad) resulted in a 30-fold increase in growth of FDCP-1 or bg/bg cl 1 cells in liquid co-culture or agar culture overlay with no detectable growth of 32D cl 3. The frequency of subculture of nonautocrine, factor independent (FI) variant clonal lines of FDCP-1 or bg/bg cl 1 cells was increased over 1000-fold by 15 weeks cocultivation with irradiated stromal cell cultures. FI subclonal lines formed tumors in syngeneic mice and contained no detectable poly A messenger RNA for GM-CSF or IL-3, and no elevation in c-myc, c-abl, c-src, or erb-B onc gene-specific messenger RNA compared to parent factor-dependent lines. These data indicate that x-irradiated plateau phase marrow stromal cells produce increased levels of cell contact-mediated biologically active hemopoietin(s) other than M-CSF, GM-CSF, or IL-3 and induce nonautocrine factor-independent malignant cell lines in vitro.

Animals↗

Effects of recombinant human GM-CSF on proliferation of clonogenic cells in acute myeloblastic leukemia.

Proliferation of acute myeloblastic leukemia (AML) cells in vitro is limited in most cases to a small subset of blasts that have several properties of stem cells. These leukemic colony-forming cells (AML-CFU) generally require addition of exogenous growth factors for proliferation in agar or methylcellulose. These factors can be supplied by media conditioned by phytohemagglutinin-stimulated normal leukocytes or by CSF-secreting tumor cell lines. However, the exact factor or factors required for stimulation of AML-CFU growth have not been defined. We compared the AML-CFU stimulatory activity of a human recombinant GM-CSF with that of GCT-CM, Mo-CM, and the PHA-leukocyte feeder system in 15 cases of AML. In each of the 12 cases that required exogenous growth factors for maximum AML-CFU growth, recombinant GM-CSF could replace either GM-CSF or Mo-CM, and could partially replace the PHA-leukocyte feeder system. These results indicate that this GM-CSF is a growth promoter of AML-CFU in these culture systems.

Adult↗

[Significance and scope of interdisciplinary cooperation in the specialty of internal medicine (inpatients)].

In a department of internal medicine of a district hospital all consultations given by representatives of non-internal medical specialties and by specialized or highly specialized representatives of the subject of internal medicine in a period of five months were registered. In 29% of all patients attended in the period of observation consultation achievements were demanded. 65% of these achievements could be realized by physicians working in hospitals or outpatient departments of the district. 23% of the consultations were carried out by specialists from institutions conducted by county authorities. 11% of the consultations were carried out by highly specialized physicians of university clinics and academy institutes. The investigation confirms the high significance of the inter-disciplinary cooperation for the subject of internal medicine. cooperation for the subject of internal

Female↗

Glucose, lactate, and ketone body utilization by human mammary carcinomas in vivo.

The glucose uptake rate of human mammary carcinomas transplanted into nude rats is comparable to values obtained in isotransplanted rodent tumors. The glucose uptake decreases with increasing tumor wet weight and is linearly related to the glucose availability. Most tumors release lactate, the rate being linearly related to the glucose uptake rate. Tumors use acetoacetate and beta- hydroxybutyrate as substrates. Additionally, human mammary carcinomas may have the ability for ketogenesis probably depending on the metabolic state. Using the epigastric pouching technique, human mammary carcinoma xenografts in nude rats seem to be a valid model for systematic investigations of the energy supply of human tumors.

3-Hydroxybutyric Acid↗

Haemodialysis in 'hepatorenal syndrome': report on two cases.

We report two patients with hepatorenal syndrome who recovered from oliguria and renal failure after temporary treatment with haemodialysis. Hepatorenal syndrome developed under diuretic treatment in both patients. Volume expansion, dopamine, and prostaglandin I2 did not improve renal function. In the one patient with alcoholic cirrhosis, renal biopsy showed only minimal alterations of glomeruli, tubuli, and arterial vessels. In the other case, the deterioration and improvement in renal function parallelled changes in acute alcohol-toxic hepatic function. We conclude that haemodialysis should be considered for treatment of hepatorenal syndrome in selected patients where reversal of liver failure can be expected.

Acute Kidney Injury↗

Beneficial effects of long-term prostaglandin E2 infusion on the course of postischemic acute renal failure. Long-term studies in chronically instrumented conscious dogs.

The effect of a continuous intra-aortal infusion of prostaglandin E2 (PGE2) (0.03 microgram . min-1 . kg-1) on the course of postischemic renal failure (180 min cessation of blood flow by inflation of a pneumatic cuff) has been investigated in 11 conscious sodium-replete dogs. The glomerular filtration rate (51Cr-EDTA: endogenous creatinine clearance) was less decreased in the PGE2 group (group B, n = 6) than in the control group (group A, n = 5; 13 ml . min-1 vs. 22 ml . min-1; p less than 0.05). Renal blood flow (electromagnetic flow probe) was markedly lower in the control group (82 ml . min-1) than in the PGE2 group (130 ml . min-1; p less than 0.05), even exceeding baseline levels in the latter group. Accordingly, the excessive rise in renal vascular resistance in the control group (+277%) was abolished in the PGE2 group (-20%) (p less than 0.05). Nitrogen retention was also markedly improved. Plasma renin activity, which was markedly raised initially (25.8 ng angiotensin I . ml-1 . h-1) was not significantly further increased during the subsequent 7 days. Urinary excretion of PGE2 was diminished in the control group and elevated following PGE2 infusion. It is suggested that the beneficial effects of PGE2 are mediated by preservation of renal perfusion. Additional effects of prostanoids on the ultrafiltration coefficient (KF) and cytoprotection by reduction of intracellular calcium accumulation must also be taken into consideration.

Acute Kidney Injury↗

[Acute intestinal invagination. Ultrasonic aspects].

The sonographic pattern of an intussusception in a 21 months old child is reported. The value and the meaning of this pattern is discussed according clinical and anatomical presentation of intussusception.

Acute Disease↗

Dietetics at work in the workplace: academia and industry cooperate in a blood pressure program.

Here is one approach to the challenge of preparing dietetic students for a rapidly changing health care system. Hypertension screening and control are the focus of a cooperative project conducted at the Saginaw-Detroit plants of General Motors Corporation by students of the Medical Dietetics Program at Wayne State University, Detroit. The project reflects implementation, over a 3-year period, of the General Motors Blood Pressure Program. A model is presented for involving students in a health-oriented program at a work site. Effectiveness of student follow-up and counseling is demonstrated in a research component involving noncompliant hypertensive employees. Outcomes of cooperative efforts include: (a) development of guidelines for management of a hypertension monitoring program involving students, (b) support for an industrial medical staff in mounting a new program, (c) extension of faculty capabilities through plant medical staff, (d) baseline data for calculating cost-benefit of a monitoring program, and (e) achievement of superior blood pressure control in comparison with other industrial programs.

Blood Pressure Determination↗

[Immunosuppressive treatment of severe aplastic anemia with high-dose methylprednisolone and antithymocyte globulin in 2 patients].

This article describes the treatment of two patients with severe aplastic anaemia (SAA) by means of high-dose methylprednisolone ( HDMP ) and antithymocyte globulin (ATG). A complete normalization of the haematological data was obtained in one patient, which has persisted now for 10 months. ATG and HDMP seem to provide an alternative mode of treatment of SAA to bone marrow transplantation if there is no histocompatible bone marrow donor available.

Adolescent↗