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Biomedical subjects

K Langer

Publications and source records attributed to K Langer.

At least 55 records · Page 3Linked to original sources

[The clinical spectrum of mastocytosis].

Mastocytosis comprises a heterogeneous spectrum of clinical manifestations, extending from isolated, benign skin infiltrates to systemic involvement, occasionally with a fatal outcome. After a short survey of the morphology and physiology of the mast cell and the skin lesions of mastocytosis, the involvement of internal organs is reviewed and the differential diagnosis is discussed. The options for therapy are discussed, and the need for continuous monitoring of mastocytosis patients is emphasized.

Adolescent↗

[Histology of the skin and mucous membrane manifestations of AIDS].

The dermatopathologist must be aware of the wide spectrum of non-specific cutaneous manifestations, cutaneous infections and skin tumors associated with AIDS. We present the histological criteria essential for the diagnosis of early Kaposi's sarcoma, its differential diagnosis including epithelioid angiomatosis, as well as the diagnosis of oral hairy leucoplakia.

Acquired Immunodeficiency Syndrome↗

Intracellular free amino acid patterns in duodenal and colonic mucosa.

We report for the first time the concentrations of free amino acids in human intestinal biopsies obtained by routinely performed endoscopy. We studied 15 medical patients with no changes of the mucosa and six HIV-infected persons with duodenitis. The mean (and SD) sum of all amino acids, taurine excepted, was 61.9 (5.4) mmol/kg dry weight in duodenal biopsies of HIV-negative subjects (n = 11) and 82.9 (0.6) mmol/kg in colonic specimens: 50% (44%) of the total (minus taurine) consisted of aspartate and glutamate and 14% (12%), of the essential amino acids. The relative amino acid pattern in duodenum and colon differed completely from that for muscle: aspartate was fourfold higher; glutamate, phenylalanine, glycine, valine, leucine, and isoleucine were about twofold higher. In contrast, glutamine amounted only to 4% (duodenum) to 14% (colon) of muscle glutamine. In duodenal biopsies of the HIV-infected persons, we found significantly (P less than 0.01, except glutamine: P less than 0.025) increased concentrations of glutamate (24.1 vs 17 mmol/kg dry weight), ornithine (1.4 vs 0.4), valine (2.2 vs 1.7), and glutamine.

Acquired Immunodeficiency Syndrome↗

[Incorporation of 15N in VLDL and LDL: in vivo synthesis of apolipoprotein B in the post-absorptive and fasting state].

In vivo synthesis of apolipoprotein B 100 (ApoB) was recently determined in man using stable isotopes. With this procedure we analyzed (1) the effect of fasting on synthesis of ApoB from very low density lipoprotein (VLDL) and (2) tracer enrichment in low density lipoprotein (LDL). After a 36-hour fasting period and in the post-absorptive state 4 healthy subjects were given a priming dose (8.7 mumol/kg) of 15N glycine followed by a constant infusion (10 mumol/kg/h for 8 h) to achieve 5% tracer enrichment in the plasma pool of glycine. The K-values, i.e. fractional synthetic rates/hr of ApoB from VLDL were 0.53 +/- 0.26 vs. 0.43 +/- 0.16 (p greater than 0.05). Tracer enrichment in ApoB from LDL at the end of the infusions was 0.19% vs. 1.46% in ApoB from VLDL. The results indicate that (1) in young healthy postabsorptive individuals about 40% of ApoB from VLDL in plasma is synthesized per hour, (2) fasting does not materially affect fractional ApoB synthesis and (3) at 5% 15N enrichment in plasma glycine, tracer enrichment in ApoB from LDL is at the lower limit of detection for the procedure employed.

Adult↗

Metabolism of glutamine in lymphocytes.

Pathways of glutamine metabolism in resting and proliferating rat thymocytes and established human T- and B-lymphoblastoid cell lines were evaluated by in vitro incubations of freshly prepared or cultured cells for one to two hours with [U14C]glutamine. Complete recovery of glutamine carbons utilized in products allowed quantification of the pathways of glutamine metabolism under the experimental conditions. Partial oxidation of glutamine via 2-oxoglutarate in a truncated citric acid cycle to CO2 and oxaloacetate, which then was converted to aspartate, accounted for 76% and 69%, respectively, of the glutamine metabolized beyond the stage of glutamate by resting and proliferating thymocytes. Similar results were obtained with the lymphoblastoid T- and B-cell lines. Complete oxidation to CO2 in the citric acid cycle via 2-oxoglutarate dehydrogenase and isocitrate dehydrogenase accounted for only 25% and 7%, respectively. In proliferating cells a substantial amount of glutamine carbons was also recovered in pyruvate, alanine, and especially lactate. The main route of glutamine and glutamate entrance into the citric acid cycle via 2-oxoglutarate in lymphocytes appears to be transamination by aspartate aminotransferase rather than oxidative deamination by glutamate dehydrogenase. In the presence of glucose as a second substrate, glutamine utilization and aspartate formation markedly decreased, but complete oxidation of glutamine carbons to CO2 increased to 37% and 23%, respectively, in resting and proliferating cells. The dipeptide, glycyl-L-glutamine, which is more stable than free glutamine, can substitute for glutamine in thymocyte cultures at higher concentrations.

Ammonia↗

Influence of molecular structure and plasma hydrolysis on the metabolism of glutamine-containing dipeptides in humans.

Glutamine-containing dipeptides may serve as a source of glutamine in parenteral nutrition solutions. To study the metabolism of glycyl-L-glutamine (gly-gln) and L-alanyl-L-glutamine (ala-gln) bolus injections of both dipeptides (0.1 mmol/kg within 40 seconds) were performed in five healthy male volunteers. Furthermore, plasma hydrolase activity against both peptides was tested by in vitro incubation. Both peptides were rapidly cleared from plasma after injection; however clearance was significantly greater for ala-gln than for gly-gln (1,595 +/- 124 v 507 +/- 14 mL/min). Arterial concentrations of constituent amino acids rose after peptide injection, indicating hydrolysis of the peptides. Glutamine concentration, for example, rose from 573 +/- 29 to a maximum of 718 +/- 34 mumol/L after gly-gln and from 570 +/- 15 to 900 +/- 53 mumol/L after ala-gln injection. Both peptides were hydrolyzed by plasma hydrolases during in vitro incubation. Hydrolysis was greater for ala-gln than for gly-gln. Half-lives of ala-gln and gly-gln were 46 +/- 3 and 553 +/- 160 minutes, respectively. For both peptides, plasma hydrolysis was too low to contribute significantly to in vivo clearance. Our results indicate that gly-gln and ala-gln are suitable sources for glutamine in parenteral nutrition solutions. Furthermore, plasma hydrolases do not play a significant role in peptide metabolism. Both peptides therefore appear to be primarily metabolized via extracellular hydrolysis, presumably by hydrolases on the cell membranes and consecutive uptake of the liberated amino acid residues.

Adult↗

Infusion of dipeptides as nutritional substrates for glutamine, tyrosine, and branched-chain amino acids in patients with acute pancreatitis.

In this study we investigated the effect of a total parenteral nutrition supplemented with synthetic dipeptides on plasma and muscle amino acid metabolism in four patients with acute pancreatitis. We infused an amino acid solution containing alanylglutamine, glycylglutamine, glycylvaline, glycylisoleucine, glylcylleucine, and glycyltyrosine for a period of five days in daily dosages of 10.3, 22.1, 68.8, 37.2, 42.5, and 15.7 mmol, respectively. The plasma levels remained below 100 mumol/L for all infused dipeptides. The plasma concentrations of alanylglutamine were not measurable. Mean peptide urine excretion remained below 5%, with the exception of glycylglutamine (8.5% +/- 5.1%). Arteriovenous concentration differences of the dipeptides across the leg were not significantly different from zero, indicating that the infused dipeptides have no important role in the nitrogen exchange of skeletal muscle. A marked intracellular glutamine deficiency in skeletal muscle was found in all four patients (5.1 +/- 0.6 mmol/L v 19.5 +/- 0.8 in healthy subjects) before infusion. Intracellular glutamine concentration was significantly higher after the infusion period (5.1 +/- 0.7 v 9.5 +/- 1.8 mmol/L, P greater than .05), but no normalization of the intracellular glutamine levels was achieved by the infusion of the two glutamine-containing peptides. We conclude that peptides are well metabolized as substrates for parenteral nutrition in catabolic patients. Furthermore, the infusion of glutamine peptides caused a significant increase in intracellular glutamine levels; however, the dosage of glutamine peptides was too low to normalize the muscular glutamine concentrations.

Acute Disease↗

Multiple apocrine hidrocystomas on the eyelids.

A 31-year-old man with multiple cystic tumors symmetrically distributed on his eyelids is presented. Histopathology and immunohistochemistry suggest the diagnosis of apocrine hidrocystomas. Apocrine hidrocystomas occur frequently on the face, but multiple and symmetrical occurrence on the eyelids has not been reported up to now.

Adult↗

Nitrogen absorption in pancreatectomized patients: protein versus protein hydrolysate as substrate.

To investigate nitrogen absorption in the absence of the pancreas, six patients with total pancreatectomy, all in stable nutritional and metabolic condition, underwent two periods of enteral nutrition identical in all respects except for the nitrogen source. Nitrogen source was either lactalbumin or its hydrolysate. The quantity and quality of calories infused simulated the patient's usual diet, which was a high-protein diet (2.0 +/- 0.4 gm/kg body weight). Pancreatic enzyme replacement therapy was discontinued during each period of enteral nutrition. All patients had greater nitrogen absorption during the enteral nutrition with lactalbumin hydrolysate than that with lactalbumin (91% +/- 2% vs 61% +/- 6% of nitrogen intake, p less than 0.02). Despite this difference in absorption, nitrogen balances during the two periods of enteral nutrition were not significantly different. This appeared to be caused by a urea production rate that was greater during the enteral nutrition with lactalbumin hydrolysate than the rate during that with lactalbumin (26 +/- 1 gm/24 hr vs 16 +/- 3 gm/24 hr, p less than 0.05). Plasma concentrations of amino acids and proteins did not differ significantly during the two treatments. In conclusion, the data suggest that (1) the intestine plays a significant role in protein digestion and that (2) enteral feeding with a protein hydrolysate could eliminate the need for a high-protein diet in patients with pancreatic insufficiency.

Absorption↗

Protein-restricted diets in chronic renal failure: a four year follow-up shows limited indications.

Several retrospective and prospective studies confirmed the beneficial effect of dietary protein restriction (DPR) on the downhill course of renal function in chronic kidney disease. The long-term results of this therapeutic modality may be different than the short-term effects. In our nephrology outpatient department, a prospective randomized trial has been in progress since April, 1982. In 1984, we reported a general beneficial effect of our diet after two years of follow-up. Two hundred and forty-eight patients with initial creatinine clearances between 10 and 60 ml/min entered the trial. Patients were stratified for sex, age and degree of renal insufficiency. One hundred and twenty-nine patients were randomly assigned to a DPR-group (0.4 to 0.6 g/kg/day); 118 patients to a control group. Patients on DPR visited the dietitian every three months during the first 24 months of the study; thereafter, as with the controls, the dietitian visits were only for specific needs. Urea excretion decreased significantly in DPR patients as a sign of good compliance and stayed at that level, even without frequent visits to the dietitian. Biochemical parameters showed no signs of malnutrition. Amino acid profiles were related to the degree of renal failure. The diet appeared to have a selective effect on the progression rate of renal failure: only patients with primary glomerular disease responded to the diet. Furthermore, there were striking intersex differences. Males showed a more rapid decline towards end-stage renal failure, but responded in a positive way to the diet, whereas female patients did not benefit from the dietary manipulation at all.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Calcium-free dialyzate: development and applications.

A calcium-free, bicarbonate-containing concentrate was prepared for hemodialysis, which, after dilution, gave analyzed concentrations of sodium of 146 mmol/l, Cl 110 mmol/l, HCO3 of 35 mmol/l and pH of 8.3. When compared with standard bicarbonate dialysis, no important differences in blood chemistries, symptoms or signs were seen. The solution has been trouble-free in over 300 dialyses. Total amount of calcium lost uncorrected for time, dialyzer or blood flow was 40.6 +/- 1.1 mmol, n = 62. This loss was replaced by a calcium infusion into the venous line giving 40 mmol calcium over 4 h. The dialyzate calcium loss could be accurately predicted by sampling without collecting the total dialyzate volume. The uses of this concentrate for bicarbonate dialysis, citrate anticoagulation and avoidance of hypercalcemia in patients treated with oral calcium for phosphate binding is discussed.

Bicarbonates↗

Influence of two glutamine-containing dipeptides on growth of mammalian cells.

The instability of the amino acid glutamine prompted us to investigate substitute compounds appropriate for culture conditions. The effect of two glutamine-containing dipeptides, alanylglutamine (Ala-Gln) and glycylglutamine (Gly-Gln), on the growth behavior of a hematopoietic cell line in culture (K562) was investigated. Growth rates and [3H]thymidine incorporation rates of cells cultivated in sterile-filtrated media, containing glutamine (Gln) or Ala-Gln or Gly-Gln, were not statistically different. Although heart-sterilization of media containing Gln caused approximately 95% decomposition of the Gln, both dipeptides remained unaltered. Consequently, cell growth was drastically decreased when autoclaved free Gln-containing media were used, but growth was unaffected in the presence of autoclaved dipeptides. Both Ala-Gln and Gly-Gln have an advantage over free Gln as growth factors for cell culture due to the stability of the dipeptides during both autoclaving and storage; the biological activity, however, is comparable.

Cell Division↗

Plasma amino and keto acids in chronic renal failure.

During both early and late stages of chronic renal insufficiency the response of BCKA to the disease state, as indicated by plasma levels, differs from that of BCAA. Val is the only BCAA whose concentration changes under the conditions of our study, and this only during the more advanced stages of disease. In contrast, all three BCKA declined, KIVA and KICA even in mild renal failure, showing that already during the early stages of the disease these BCKA levels are decreased. BCKA are more sensitive parameters than the corresponding amino acids with regard to the metabolic dysfunctions characteristic of this disease. Modern analytical methods allow more exact and reliable knowledge of these indicators and thus a better understanding of biochemical mechanisms, possibly resulting in better therapy.

Amino Acids↗

Substitution therapy of hypogonadal men with transdermal testosterone over one year.

Current testosterone substitution therapy either by injectable or oral testosterone esters suffers from markedly fluctuating serum testosterone levels often far above or below the physiological range. Recently, a transdermal therapeutic system (TTS) for the delivery of testosterone was developed which, when applied to the scrotum, provides smooth serum testosterone levels. Here we report results from seven hypogonadal men treated with the TTS for 14 months by applying a new patch every day. In all patients serum testosterone and dihydrotestosterone (DHT) determined 3-5 h after applying a new patch increased significantly and remained within the physiological range during the entire treatment period. The DHT/testosterone ratio remained constant. In 4 of these patients and 2 others under TTS treatment serum testosterone and DHT were also determined over a 24-h period at regular intervals. In these patients serum testosterone levels in the physiological range were seen during the entire observation period, whereas an increase in the DHT/testosterone ratio occurred towards the end of the one-day treatment phase. All patients in the 14-month treatment study were clinically well substituted and responded with good compliance. Clinical chemistry showed no abnormalities during treatment. Thus, the TTS appears to be an effective and safe new modality for the treatment of male hypogonadism.

Administration, Cutaneous↗

Augmentation of IgE receptor expression and IgE receptor-mediated phagocytosis of rat bone marrow-derived macrophages by murine interferons.

Receptors for IgE (Fc epsilon R) on rat bone marrow-derived macrophages (BMDM phi) were demonstrated by a rosette assay employing trinitrophenyl-coated ox erythrocytes (EoTNP) sensitized with mouse IgE anti-dinitrophenyl monoclonal antibody (EoTNP-IgE). Virtually all BMDM phi emerging from bone marrow cells cultured for 1 week in the presence of mouse L929 cell supernatant, with partially purified murine CSF-1 or recombinant murine GM-CSF, formed IgE rosettes. To study the effect of interferons (IFNs) on Fc epsilon R expression, 1-week-old rat BMDM phi were incubated with murine recombinant IFN-gamma, purified IFN-alpha or IFN-beta, and were tested for their capacity to bind and ingest EoTNP sensitized suboptimally with IgE. A marked increase in the percentage of cells forming IgE rosettes or phagocytosing EoTNP-IgE was noted after 8-72 hr incubation of BMDM phi with 0.1-1000 U/ml of IFNs. At similar concentrations IFN-gamma and IFN-beta triggered EoTNP-IgE binding or ingestion more efficiently than IFN-alpha. The enhancing effect was blocked by the respective anti-IFN antibodies, cycloheximide or actinomycin D but not by mitomycin C. The IgE rosette formation and IgE-mediated phagocytosis were dose-dependently inhibited by native rat IgE but not by heat-denaturated IgE myeloma protein IR162 or monomeric rabbit IgG. Our results demonstrate that rat BMDM phi express constitutively Fc epsilon R, and that murine IFNs augment Fc epsilon R-mediated binding and ingestion in a time- and dose-dependent manner. This effect probably reflects an increase in the number of Fc epsilon R per cell, as a result of de novo synthesis of Fc epsilon R.

Animals↗