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Biomedical subjects

J Krueger

Publications and source records attributed to J Krueger.

52 records · Page 3Linked to original sources

Interleukin 6 is expressed in high levels in psoriatic skin and stimulates proliferation of cultured human keratinocytes.

Psoriasis is a common papulosquamous skin disease. The histopathology is characterized by epidermal hyperplasia and inflammation. Recent studies suggest that keratinocyte proliferation and inflammation in psoriasis are manifestations of the same underlying pathological process. Interleukin 6 (IL-6), a cytokine that is a major mediator of the host response to tissue injury and infection, is produced by both keratinocytes and leukocytes in culture. IL-6 expression was studied in psoriatic plaques by immunoperoxidase staining with two different polyclonal anti-recombinant IL-6 antisera and by in situ nucleic acid hybridization with IL-6 cRNA probes. Epidermal and dermal cells in active psoriatic plaques from 35 psoriasis patients stained heavily for IL-6 as compared with nonlesional skin and with plaques after treatment with antimetabolic and antiinflammatory agents. Absorption of the anti-recombinant IL-6 antisera with purified fibroblast-derived IL-6 or with recombinant IL-6, but not bovine serum albumin, removed the immunostaining. Increased levels of IL-6 were detected in the plasma of patients with active psoriasis (mean 3 ng/ml) by using two different bioassays. IL-6 production by proliferating keratinocytes was suggested by IL-6-specific immunostaining in cultured normal and psoriatic keratinocytes and by the detection of mRNA specific for IL-6 in psoriatic epidermis by in situ hybridization. IL-6 stimulated the proliferation of cultured, normal human keratinocytes as assessed by two different assays. Thus, IL-6 could directly contribute to the epidermal hyperplasia seen in psoriatic epithelium as well as affect the function of dermal inflammatory cells.

Cell Division↗

Use of categorical and individuating information in making inferences about personality.

In three experiments, we explored the effects of categorical information (stereotypes) and case information (traits or behaviors) on judgments about an individual's characteristics. Subjects judged a target person's aggressiveness on the basis of a description containing both a broad social category and specific case information. In Experiment 1, the description included (a) a category that was either weakly or strongly related to aggressiveness and (b) a behavior that was unrelated, moderately diagnostic, or highly diagnostic of aggressiveness. Trait inferences were a function of both the stereotypic and the behavioral information. A single behavior was not sufficient to override the category effect. In Experiment 2, temporally consistent behaviors were presented as case information; under these conditions, category information had no effect on trait judgements. This finding was extended in Experiment 3 in which subjects predicted behaviors on the basis of the target person's sex and a moderately diagnostic trait.

Aggression↗

A membrane protein preferentially expressed by a subpopulation of immature lymphoid cells, epidermal basal keratinocytes, and other epithelial cells.

A murine monoclonal antibody, designated EL-1, was raised by immunization with a human malignant T cell line. It reacted specifically with a membrane antigen expressed on T and B lymphoblastoid cell lines, a subpopulation of normal thymocytes and bone marrow lymphocytes, lymphocytes from a subset of patients with non-B, non-T cell acute lymphoblastic leukemia or T cell acute lymphoblastic leukemia and epithelial stem cells. The latter reactivity was especially striking in the skin, where only basal epidermal keratinocytes and epidermal appendages, including eccrine sweat glands, sebaceous glands and hair follicles, stained positively. A human epidermoid carcinoma cell line was also stained by EL-1. Suprabasilar keratinocytes and acellular keratin did not stain. However, in vitro proliferating fetal lung fibroblasts stained positively. Membrane immunoprecipitation analysis demonstrated that the antigen recognized by antibody EL-1 is a single protein of molecular weight 105 kilodaltons which did not change with exhaustive chemical reduction. Metabolic radiolabeling studies demonstrated that this protein is synthesized by the cell and not merely taken up from the culture medium. This antibody can be useful in studying keratinocyte differentiation in epidermal malignancies and normal skin.

Animals↗

Colicin synthesis and cell death.

Colicin E1 is a small plasmid, containing the cea gene for colicin, the most prominent product of the plasmid. Colicin is a 56-kilodalton bacteriocin which is especially toxic to Escherichia coli cells that do not contain the plasmid. Under normal growth conditions very low levels of the plasmid are produced as a result of cea gene repression by the host LexA protein. Conditions that lower the concentration of LexA protein result in elevated levels of colicin synthesis. The LexA protein concentration can be lowered by exposing the cells to DNA-damaging reagents such as UV light or mitomycin C. This is because DNA damage signals the host SOS response; the response leads to activation of the RecA protease which degrades the LexA protein. DNA-damaging reagents result in very high levels of colicin synthesis and subsequent death of plasmid-bearing cells. Elevated levels of colicin are also produced in mutants of E. coli that are deficient in LexA protein. We found that comparably high levels of colicin can be produced in such mutants in the absence of cell death. In lexA strains carrying a defective LexA repressor, colicin synthesis shows a strong temperature dependence. Ten to twenty times more colicin is synthesized at 42 degrees C. This sharp dependence of synthesis on temperature suggests that there are factors other than the LexA protein which regulate colicin synthesis.

Bacterial Proteins↗

Startle reflex inhibition in the rat: its persistence after extended repetition of the inhibitory stimulus.

Startle reflexes to intense sound bursts are inhibited by weak stimuli that briefly precede their elicitation. In three experiments the startle stimulus (a 110-dB SPL tone burst) was presented 100 ms after the final link in a train of stimuli, the length of the train varying from 1 to 1,000, its repetition rate varying from 1 per s to 10 per s, and its constituents being 40 dB or 50 dB white noise bursts of 25 ms duration. Inhibition was invariant across train length and repetition rate. In a final experiment the startle stimulus was presented a variable interval after the final link, from 40 ms to 1280 ms, with 1 or 100 noise bursts (50 dB) in the train. Inhibition developed more rapidly following the last member of the 100-stimulus train, suggestive of a "priming" or sensitization effect of stimulus repetition, but its overall strength and subsequent rate of decay were not different in the two conditions. The general persistence of inhibition following these extended series of stimuli reveals that reflex inhibition must be the outcome of a fixed and obligatory process associated with sensory input.

Acoustic Stimulation↗

Load and time considerations in the force-length relation of cardiac muscle.

A study of the end-systolic force length relations in isolated mammalian myocardium was undertaken in an effort to clarify controversies concerning the uniqueness of this relationship for a given state of contractility. In studies of cat and rat papillary muscles, differences between isometric and isotonic end-systolic force length relations in twitch contractions were shown to be due to different levels and durations of mechanical activity engendered by the different modes of contraction. This was further supported by the constancy of end-systolic force-sarcomere length relation in small well-oxygenated muscles, and tetanic force-length relations in larger muscles. The dependence of the end-systolic force-length relation on total load was shown not to vary with length or load history during the contraction if the final total load or length was achieved prior to 75% of time to peak tension. Beyond this point, end-systolic force-length relations in isolated muscle become load and time-dependent. The results from isolated muscle studies can be closely correlated qualitatively with results from studies of the intact ventricle, and this analogy may help to further explain observations of ventricular performance in conditions such as heart failure or cardiomyopathy, where significant alterations in the intensity and time course of mechanical activity are known to occur. Additional studies of intact ventricular performance are needed to confirm whether or not the ventricle behaves like its component muscle in a simplified model-independent way.

Animals↗

Calcium distribution within human erythrocytes.

In order to study 45Ca distribution within erythrocytes, a method was devised that had minimal deleterious effects on the treated erythrocytes. It was observed that newly introduced 45Ca was predominantly recoverable from the cytosol and exchanged relatively slowly with membrane-associated Ca. Younger erythrocytes appeared to have relatively more 45Ca in membrane-associated sites. Erythrocytes from patients with sickle cell anemia had significantly more 45Ca in membrane-associated sites than did normal controls or patients with reticuloctosis due to a variety of disorders. There are theoretical reasons for considering the possibility that the distribution of 45Ca between cytosol and membrane-associated sites could modulate some of the properties of the erythrocyte membrane.

Anemia, Sickle Cell↗

Calcium distribution within human erythrocytes during endocytosis.

In order to study 45Ca movements within erythrocytes, a method was devised that had minimal deleterious effect on the treated erythrocytes. Agents that induce endocytosis in intact erythrocytes (primaquine, vinblastine, and chlorpromazine) caused a prompt movement of 45Ca from cytosol to membrane-associated sites. This drug-induced movement of 45Ca to membrane sites was blocked by depleting erythrocytes of adenosine triphosphate (ATP) or by incubating them with known inhibitors of endocytosis, NaF of N-ethylmaleimide (NEM). It appears that endocytosis in intact human erythrocytes involves the movement and redistribution of 45Ca from cytosol to membrane-associated sites. Therefore, in the erythrocyte, as in perhaps other cells, movement of Ca from one site to another may modulate important cellular biologic functions.

Adenosine Triphosphate↗

Requirements of drug-induced endocytosis by intact human erythrocytes.

Study of drug-induced endocytosis in intact human erythrocytes continues to provide an opportunity for correlating membrane functions such as invagination and fusion with erythrocytic energetics and other determinants of plasma membrane function like Ca++. The studies reported indicate that high concentrations of vinblastine and chlorpromazine can produce endocytic vacuoles, albeit in reduced amounts, even in severely ATP depleted erythrocytes. In contrast, primaquine-induced endocytosis seems definitely dependent upon persistence of erythrocytic ATP stores. The ionophore mediated entry of Ca++ into erythrocytes potentiates primaquine endocytosis, inhibits vinblastine endocytosis, and has no regular effect on chlorpromazine endocytosis. Sodium lactate enhances primaquine endocytosis, probably by causing an increase in the entry of primaquine into erythrocytes. Cytochalasin B neither enhances nor inhibits erythrocytic endocytosis, thereby suggesting that microfibrils or analogues of microfibrils in erythrocytes are not involved in endocytosis. Cyclic nucleotide inhibition of endocytosis is confined to a very high concentration range of nucleotides in the medium. Primaquine and chlorpromazine endocytosis are inhibited by cyclic nucleotides as is vinblastine endocytosis.

Calcium↗

Twinning frequencies in Baden-Wurttemberg according to maternal age and parity from 1955 to 1972.

The decline of the twinning rate in Germany since 1900 is exclusively due to a fall of the DZ rate. The analysis of the birth data in Baden-Württemberg from 1955 to 1972 shows that the decline of the DZ twinning rate can be explained only to a small extent by the shift of the maternal age-parity distribution towards younger mothers and lower parities. It appears reasonable that the greater part of this decline is caused by the lessening prevalence of the more fecundable, DZ twin-prone women due to the growing influence of family planning. Furthermore, it is imaginable that the probability for multiple ovulation is decreased after cessation of hormonal contraception.

Contraceptives, Oral↗

Extraction of sleep-promoting factor S from cerebrospinal fluid and from brains of sleep-deprived animals.

Sleep-promoting factor (factor S) was extracted, partially purified, and concentrated from cerebrospinal fluid and from acid-acetone extracts of brain stem anc cortex of sleep-deprived goats and sheep. 2. Solutes greater than 500 daltons were largely removed by serial ultrafiltrations through molecular sieves (Amicon membranes UM10 and UM05); solutes less than 350 daltons were largely eliminated by gel filtration through Sephadex G10 columns. Sleep-promoting activity was found in a fraction eluted prior to [14C] sucrose marker. 3. Concentrated fraction were infused intraventricularly in rats (0.1 ml in 30 min just prior to 12-h dark cycle) and in rabbits (0.3 ml in 90 min in morning). Sleep-promoting activity was assayed by decrease in nocturnal locomotor activity of rats and by duration and amplitude of slow-wave cortical EEG in rabbits.

Animals↗

A mechanical comparison of first metatarsal diaphyseal osteotomies for the correction of hallux abducto valgus.

The purpose of this study was to perform a mechanical comparison of four commonly performed diaphyseal first metatarsal osteotomies. Fifty first metatarsal-first cuneiform sawbone models were divided equally into five groups: control, offset V, inverted Z, Mau, and Ludloff osteotomy groups. All osteotomies were fixated with two 2.7-mm Synthes cortical screws. Each specimen was then stressed through a computer-controlled hydraulic tensile testing machine while recording the maximum load, energy, stiffness, and fracture pattern. The offset V was superior in terms of maximum load (137.8 N) and energy (0.86 J), as compared to the inverted Z (maximum load 74.7 N and energy 0.24 J), the Mau (maximum load 74.3 N and energy 0.15 J), and the Ludloff (maximum load 67.0 N and energy 0.32 J). The offset V (16.6 N/mm) demonstrated no significant difference in stiffness with the Mau (19.7 N/mm), and was stiffer to the inverted Z (14.4 N/mm) and the Ludloff (9.4 N/mm). We conclude that one could expect a safer and immediate return to weightbearing postoperatively with the offset V osteotomy as compared to the inverted Z, Mau, and Ludloff osteotomies.

Analysis of Variance↗

Red blood cell membrane storage lesion.

Storage of human erythrocytes in CPD produced a lesion of the erythrocyte membrane manifested by abnormal endocytosis in resealed ghosts and in intact erythrocytes. Endocytosis produced by resealing Ca, Mg, and ATP into ghosts was impaired by five weeks of storage and this defect was promptly reversed by the prior regeneration of ATP in the stored erythrocytes. Drug-induced endocytosis was studied in intact stored erythrocytes. Vinblastine endocytosis was not affected by storage. Chlorpromazine endocytosis was not affected by storage. Chlorpromazine endocytosis was variably but never completely inhibited by storage. Chlorpromazine endocytosis was variably but never completely inhibited by storage, and restoration of ATP occasionally resulted in complete restoration of chlorpromazine endocytosis to base line values. However, primaquine endocytosis was usually totally inhibited after three to four weeks of storage at a time when residual ATP levels were 30 to 50 per cent of base line values. Restoration of ATP levels to at least base line values did not completely primaquine endocytosis to control values. Study of primaquine endocytosis provides an opportunity for defining an erythrocyte membrane storage lesion.

Adenosine Triphosphate↗