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Biomedical subjects

W Knauf

Publications and source records attributed to W Knauf.

At least 55 records · Page 3Linked to original sources
PubMed1989

Magnetic resonance imaging of bone marrow in lymphoproliferative disorders: correlation with bone marrow biopsy.

In a prospective clinical study 10 normal volunteers and 30 patients with lymphoma--11 patients with Hodgkin's lymphoma and 19 patients with non-Hodgkin's lymphoma (11 low grade, 8 high grade)--were examined. Proximal femora, pelvis and lumbar spine were imaged with a 1.5 tesla superconducting MR imaging system (Siemens Magnetom). Areas of malignant infiltration in the bone marrow were clearly detected by visual and/or quantitative assessment. In most cases bone marrow involvement was demonstrated by both magnetic resonance imaging and bone marrow biopsies. However, in three of 30 patients magnetic resonance imaging showed evidence of lymphomatous involvement despite normal bone marrow histology. In one patient bone marrow cytology revealed malignant infiltration in the absence of MRI abnormalities. Thus, MRI is a sensitive method for detecting bone marrow infiltration by lymphoma.

Adult↗
PubMed1989

[MR tomography detection of bone marrow infiltration by malignant lymphomas].

In a prospective MRT study, both healthy volunteers (n = 10) and patients with Hodgkin and non Hodgkin lymphomas (n = 32) were examined (lumbar spine, pelvis and proximal femura). A biopsy from the posterior iliac crest was taken in all patients. About one half of the patients showed in MR-images diffuse or patchy areas of decreased signal intensity in the regions of the bone marrow, while the bone marrow of the volunteers showed an almost homogeneous pattern with high signal intensity. Our findings observed by MRT in bone marrow of these patients corresponds with pathological results obtained from crest biopsies. In order to improve the diagnostic accuracy, a quantitative evaluation of the signal intensities in selected ROIs, referring to a standard, was used. This method allows to correct variations of the signal intensity due to technical reasons. As our results show, this leads to a better differentiation of border-line cases. MRT has the advantage to detect localised lesions outside of the iliac crest. In cases of negative crest biopsies, but suspicious areas in MR-images, biopsies could be directed to these lesions.

Biopsy, Needle↗
PubMed1989

Plasma levels of soluble CD8 antigen and interleukin-2 receptor antigen in patients with hairy cell leukemia, relationship with splenectomy and with clinical response to therapy.

A soluble form of CD8 antigen (sCD8) has been shown to be released by activated CD8 + lymphocytes. Measurements of sCD8 may serve as an index of suppressor/cytotoxic cell activity. To assess the clinical significance of this observation in response to malignancy, we have investigated the sCD8 concentrations in 38 patients with hairy cell leukemia (HCL) not yet treated with any systemic therapy. The median plasma sCD8 level of the 20 nonsplenectomized patients was 1,025 U/ml and was significantly higher than that in the 18 patients who had previous splenectomy (median = 200 U/ml, p less than 0.0001), or in 14 normal controls (median = 350 U/ml, p less than 0.0001). Compared to controls, splenectomized patients had also significantly lower levels of sCD8 (p less than 0.01). The median concentration of soluble interleukin-2 receptor (sIL2R) in nonsplenectomized patients was 14,500 U/ml and was in the same range as in splenectomized patients (15,000 U/ml). There was no overlap in sIL2-R levels between controls (median = 300 U/ml) and patients. Investigation of serial plasma samples in 7 patients who received deoxycoformycin (DCF) and 11 patients treated with interferon alpha (IFN-alpha) showed a normalization of sCD8 levels and a decrease of sIL2R concentrations in those patients who showed hematological improvement. Normalization of sIL2R was, however, only observed in patients with complete remission. Our observation indicates that splenectomy might cause a reduction of the activation of suppressor/cytotoxic cells in patients with HCL. Treatment with either DCF or IFN-alpha also modulates the sCD8 levels to normal range. Measurements of sCD8 and sIL2-R might give more insight into the pathogenesis of HCL and serve as parameters for monitoring different phases of the disease and response to therapy.

Antigens↗
PubMed1988

Centroblastic lymphoma of the thyroid supervening long-lasting chronic lymphocytic leukemia (B-CLL) demonstration of biclonality by immunohistochemical and gene rearrangement analysis.

A 67-year-old woman suffering since 5 years from a so far nontreated B-CLL underwent hemithyroidectomy for a rapidly enlarging tumor. Histologically, the coincidence of a centroblastic lymphoma and thyroidal infiltration by the CLL was diagnosed. Immunohistology revealed typical immunoprofils for both, B-CLL and centroblastic lymphoma on the background of B cell differentiation antigens. The bitypical immunoglobulin light chain expression--lambda on the B-CLL cells and kappa on the centroblasts--suggested biclonality. This was confirmed by gene rearrangement analysis of peripheral leukemia cells and tumor tissue. Thus, the final diagnosis of a primary thyroidal lymphoma of the centroblastic type (stage IE) arising independently from a preexisting B-CLL was achieved. Consequently, the patient received local radiotherapy. In our opinion, the designation "Richter's Syndrome", readily applied in the literature, is inappropriate for this tumor constellation.

Aged↗
PubMed1987

Combination of low-dose cytarabine and 13-cis retinoic acid in the treatment of myelodysplastic syndromes.

Responses have been reported in patients with myelodysplastic syndromes (MDS) after low-dose cytarabine (Ara-C) or 13-cis-retinoic acid (13-CRA) therapy. Recently, combination of these two substances in vitro was shown to produce a synergistic effect on differentiation of leukemic cells. We conducted a phase II trial with low-dose Ara-C (5 mg/m2 per 12 h s.c.) and 13-CRA (60 mg/m2 per day orally) in 14 patients with MDS, six of whom had refractory anemia with excess of blasts (RAEB), seven had RAEB in transformation (RAEBt) and one chronic myelomonocytic leukemia (CMML). The drugs were administered from day 1 to 14 and the treatment courses repeated every 4 to 8 weeks. One partial response and one minor response could be achieved. Major toxicity included dry skin, mucositis and cheilitis in 11 of the 14 patients. The response rate is no better than the results reported in the literature with either drugs alone. As yet there is no satisfactory treatment for MDS.

Adult↗
PubMed1987

Androgen binding in cultured human fibroblasts from patients with idiopathic hypospadias.

Androgens stimulate development and growth of the external male genitalia. Since hypospadias represents the most common congenital abnormality in the male newborn and the mechanism of action in this disorder is still unclear, androgen binding was assessed in cultured fibroblasts from biopsies from genital skin of 10 patients with idiopathic hypospadias. For comparison, binding was determined in corresponding samples from 8 males with normal penile development and from 9 patients with known androgen resistance syndromes (testicular feminization, Reifenstein syndrome, pseudovaginal perineoscrotal hypospadias). Finally, binding was measured in 10 samples of nongenital skin. Maximum specific binding (Bmax) in idiopathic hypospadias varied from 3.2 to 15.5 (median 6.6) fmol.mg protein-1. Bmax in samples of persons with normal genital development was between 12.2 and 17.9 fmol.mg protein-1 (median 13.2). Bmax in samples of patients with known androgen resistance syndromes was exactly in the range reported previously in the literature. It is evident that Bmax in samples of patients with idiopathic hypospadias differs significantly (P less than 0.01), (Mann Whitney U-test) from those with normal genital development. Thus it seems reasonable to conclude that in some patients with idiopathic hypospadias the genital defect is caused by receptor deficiency.

Adolescent↗
PubMed1986

[Clinical significance of human papilloma virus (HPV) infections of the lower genital tract].

Using filter in situ hybridisation for HPV-DNA detection we found among 217 women with positive cervical cytology a positive result in 152 cases (70%). The distribution of the different HPV types showed an association of HPV 6/11 mainly with benign lesions and of HPV 16/18 with obligatory precancer and invasive cervical cancer. In 2652 swabs of cytologically negative patients HPV-DNA was identified in 9.5%. The infection rate for HPV 16/18 in pregnant women was 6.4% against 2.3% in nonpregnant women. In a number of the patients with positive cervical cytology we additionally examined smears from the vagina and vestibulum for HPV-DNA: in 42% of the cases a positive HPV result was obtained in these areas as well. In about 50% of 39 male partners peniscopy revealed penile lesions and HPV-DNA was found in penile smears. A prospective cytological and virological study of cytologically positive patients showed a clear association of HPV 16/18 with progression of cervical lesions. In a cytologically negative group, follow-up examinations revealed HPV-DNA in 31%.

Carcinoma in Situ↗
PubMed1985

Evidence for the presence of xenopsin-related peptide(s) in the gastric mucosa of mammals.

Using immunohistochemistry and radioimmunoassay, substance(s) related to the amphibian octapeptide xenopsin (XP) were demonstrated in the gastric mucosa of humans and dogs. Immunohistochemistry localized XP-immunoreactive epithelial cells in the gastric antral mucosa. The reaction was abolished by preabsorption of the antiserum with XP but not by neurotensin or other peptides. Immunoreactive XP (iXP) was found by radioimmunoassay in extracts of both the antrum and body of the stomach prepared with acid/acetone or acetic acid. A study of its distribution in the dog indicated that the level of iXP was highest in the stomach, lower in the pancreas and duodenum, and not measurable in the jejunoileum and colon. Gel chromatography on Sephadex G-25 indicated the presence of at least two forms of iXP, one larger and the other about the same size as XP. Reverse-phase high pressure liquid chromatography on mu-Bondapak C-18 yielded several peaks of iXP, one of which eluted at the position of synthetic XP. The results of immunochemical analyses using four different antisera towards XP were consistent with structures for canine iXPs that were closely related to XP only in their C-terminal regions. These results suggest that mammalian counterparts to amphibian XP reside within endocrine cells of the gastric mucosa. It seems possible that these peptides function as gastrointestinal signals.

Amino Acid Sequence↗
PubMed1982

Atropine depresses release of neurotensin and its effect on the exocrine pancreas.

In this study the effect of 10 and 20 micrograms . kg-1 . h-1 atropine sulfate on release and pancreatic effects of neurotensin was studied in 4 dogs. Neurotensin plasma levels rose significantly when a liquid fat preparation was infused intraduodenally. This rise was almost completely abolished by simultaneous infusion of atropine. Atropine further suppressed basal and fat-stimulated output of pancreatic volume, protein, and bicarbonate; it also reduced pancreatic secretion stimulated by an intravenous infusion of low doses (2.5 to 20 pmol . kg-1 . min-1) neurotensin. The effect of higher doses (80 and 240 pmol . kg-1 . min-1 of neurotensin was less affected. As neurotensin plasma levels in contrast to normal oral feeding did not rise after sham feeding, our findings suggest that release and action of neurotensin may at least in part be dependent on a cholinergic, non-cephalic mechanism.

Animals↗
PubMed1982

Effect of neurotensin on exocrine pancreatic secretion in dogs.

The effects of various doses of synthetic neurotensin on exocrine pancreatic secretion were investigated in dogs prepared with pancreatic fistulae. Increasing doses of neurotensin infused intravenously caused a dose-dependent stimulation of exocrine pancreatic secretion. Plasma neurotensin levels determined with a radioimmunoassay kit for neurotensin were significantly correlated to the amount of neurotensin infused. Significant stimulation of exocrine pancreatic secretion was observed when 2.5 pmol kg-1 min-1 neurotensin were infused. This dose resulted in neurotensin plasma levels comparable to those observed after a meal. Combined infusions of neurotensin and the cholecystokinin analogue cerulein had synergistic effects on pancreatic bicarbonate output and raised the HCO-3:protein ratio. These observations suggest that neurotensin may play a role in the early phase of postprandial stimulation of exocrine pancreatic function.

Animals↗
PubMed1978

Endocrine effects of chlorinated hydrocarbons in rhesus monkeys.

After the rhesus monkey was demonstrated to be a suitable model for man in both metabolic and endocrinological studies, effects of hexachlorobenzene (HCB) and polychlorinated biphenyls (PCB) on the pattern of sexual hormones in cycling female rhesus monkeys were investigated. After confirmed ovulation, four adult female rhesus monkeys were treated during the following cycle with 4 mg/kg/day of HCB, and four other monkeys were treated with the same dose of Clophen A 30. Ovulation was blocked in three PCB-treated and one HCB-treated monkeys. Whereas the levels of luteinizing hormone and follicle-stimulating hormone did not seem to be changed directly by the treatment, low estrogen levels were found during the anovulatory cycles. Studies with PCB- and HCB-treated superovulated rats indicated interaction of the chemicals with ovarian steroidogenesis. Altered hepatic steroid metabolism may also cause low estrogen levels in treated animals.

Animals↗
PubMedDate not supplied

Purine degradative enzymes in circulating malignant cells of patients with chronic B cell neoplasia.

Previous reports have shown that the purine degradative enzymes adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) and ecto-5'-nucleotidase (5'NT), play an important role in the normal development of lymphocytes and that investigations of these enzymes are of value in defining subsets of lymphoid malignancies of T-cell origin. Pharmacological inhibition of one of these enzymes has been found to be an effective treatment for a few lymphatic neoplasia. We have studied the activities of the above enzymes in the circulating malignant cells of 25 patients with B-chronic lymphatic leukemia (B-CLL), four patients with B prolymphocytic leukemia (PLL), seven patients with leukemic centrocytic lymphoma (CC), 18 patients with hairy cell leukemia (HCL) and 16 patients with immunocytoma (IC). For comparison, the blasts of nine patients with 'common' acute lymphatic leukemia (cALL) and normal T (n = 12) and B (n = 8) cells were simultaneously investigated. Despite morphologic similarity, the leukemic cells of the chronic B cell malignancies demonstrate different enzyme patterns. B-CLL is characterized by very low activities of all the enzymes ADA, PNP and 5'NT. In the cells of HCL the highest values of PNP are found. The leukemic cells of IC are characterized by low levels of ADA but moderate levels of PNP and high levels of 5'NT. Thus some of the entities of B malignancies show typical enzyme patterns which might be of importance in defining maturation stages of the disease. The differences in these enzyme patterns can also be made use of in therapy with enzyme inhibitors such as deoxycoformycin.

5'-Nucleotidase↗
PubMedDate not supplied

Initial experience with dynamic MR imaging in evaluation of normal bone marrow versus malignant bone marrow infiltrations in humans.

The purpose of this study was (a) evaluation of dynamic contrast-enhanced MR imaging of normal bone marrow versus malignant bone marrow infiltrations in patients with proven B-cell-type chronic lymphocytic leukemia (B-CLL) and (b) correlation with the clinical stage according to Binet (stages A, B, C) and response to therapy. Bone marrow imaging of the lumbar spine, pelvis, and proximal femurs was performed at 1.5 T in 45 patients without known malignancy and in 30 patients with B-CLL. The differences between opposed-phase and in-phase dynamic gradient-echo sequences before and up to 10 minutes after intravenous application of .1 mmol/kg body weight of gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) were evaluated in normal bone marrow. The contrast-enhancement patterns of normal and malignant bone marrow were compared using the opposed-phase dynamic gradient-echo sequence. Ten of the patients with bone marrow infiltrations (Binet stage C) additionally underwent MR imaging follow-up during therapy. Opposed-phase gradient echo sequences demonstrated a signal decrease of normal bone marrow, and in-phase gradient echo sequences demonstrated a signal increase of normal bone marrow after administration of Gd-DTPA. The dynamic signal intensity time courses differed significantly (P < .05) between Binet stages B and C and controls as well as among the three Binet stages of B-CLL. In the 10 patients followed during therapy, MR imaging sensitively demonstrated response (n = 6), nonresponse (n = 2), or relapse after initial response (n = 2). In out-of-phase imaging, both normal bone marrow and initial bone marrow infiltration in CLL stage Binet A show signal decrease after administration of contrast agent, whereas there is increase in signal intensity in higher-grade bone marrow infiltration in Binet stage B or C disease. The signal loss of normal bone marrow in out-of-phase imaging is a phase effect rather than a T2* effect. The differentiation of initial from higher-grade bone marrow infiltration on out-of-phase images relies solely on a shift in the fat/water ratio.

Adult↗