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Biomedical subjects

D Jung

Publications and source records attributed to D Jung.

At least 19 recordsLinked to original sources

Purification of a group of HeLa nuclear proteins that bind to a regulatory element (-1430/-1327) of the human proliferating cell nucleolar protein P120 gene.

A group of proteins was purified from HeLa nuclear extract by DNA affinity chromatography which bind to an important regulatory element (-1430/-1327) of the P120 gene. The DNA binding activity was enriched 1075 fold. By silver staining three major polypeptides (50, 40, 37 kDa) were detected in the purified fraction. The band shift assay and the southwestern assay showed that the 50 kDa protein (P50) binds to the F1 (-1430/-1327) DNA fragment. The binding specificity of the group of proteins with F1 DNA in the presence of non-specific competitor DNA is much higher than that of P50 alone. On the basis of molecular weight and specific antibody binding, the 37 kDa protein appears to be the B23 nucleolar protein.

Amino Acids

Reproductive factors and colorectal cancer risk among Chinese females.

We report results from a population-based case-control study of colorectal cancer among Chinese women in western North America (NA) and the People's Republic of China (China). A common protocol was used to assess reproductive characteristics and hormone use of 395 Chinese women (189 from NA and 206 from China) with cancer of the colon or rectum and of 1112 age-matched Chinese controls (494 from NA and 618 from China). In NA, risks for cancers of both the colon and rectum were lower among parous compared to nulliparous women (odds ratio for colorectal cancer, 0.6, P = 0.08), but the trend in risk was not smooth with increasing number of livebirths. This association with parity was absent for both cancer sites in China. There were no consistent patterns in the relationships between other reproductive factors (including age at menarche, age at first livebirth, menopausal status) and risk of colon and rectal cancer on either continent.

Adult

Dystrophin in central nervous system: a developmental, regional distribution and subcellular localization study.

Dystrophin, the protein encoded by the Duchenne muscular dystrophy gene has been shown to be expressed in central nervous system. In the present study, polyclonal antibodies raised against 3 fusion proteins constructed from different structural domains of dystrophin were used to identify dystrophin in protein extracts from rat and mdx mouse brain. The developmental expression of the protein, its regional distribution in rat brain and its localization in rat brain subcellular fractions were also examined. We found that dystrophin or a 'dystrophin-related protein' is expressed in mdx mouse brain. Dystrophin is detectable at very early stages of rat brain development and is expressed in all adult brain regions examined, although quantitative regional differences were found. Subcellular distribution analysis indicates that dystrophin is absent in mitochondrial and synaptic vesicle-enriched fractions but is recovered in the synaptic plasma membrane fraction.

Animals

Molecular basis of IgG Fc receptor III defect in a patient with systemic lupus erythematosus.

By flow cytometry analysis we could show a decreased expression of Fc gamma receptor type III (Fc gamma RIII) on granulocytes of a patient with systemic lupus erythematosus (SLE). Therefore, we constructed a leukocyte cDNA library from this patient with the aim of investigating this defect on the molecular level. Using an Fc gamma RIII cDNA probe we isolated 15 Fc gamma RIII cDNA clones, which were all characterized by sequencing. Our sequence data revealed that the patient was heterozygous for Fc gamma RIII (NA-1/NA-2). Only clone 5 (NA-2) was a full-length cDNA clone. In contrast to the wild-type Fc gamma RIII the signal sequence is mutated, lacking the hydrophobic region essential for co-translational transport across the endoplasmic reticulum membrane. The predicted transport defect leading to the lack of membrane expression could be confirmed by immunofluorescence staining after expression of this cDNA clone in BHK cells. The cDNA clones 6 and 8 (NA-1) lack the first 45 bp of the signal sequence, but considering the flow cytometry data the signal sequence must be functional allowing the membrane expression of this receptor allele. The part of the cDNA sequence of all isolated clones coding the mature Fc gamma RIII is identical to the wild-type sequence. Therefore, we conclude that the decreased expression of Fc gamma RIII on granulocytes of this SLE patient is due to the transport defect of one of the receptor alleles.

Amino Acid Sequence

[Results of cryosurgery in the treatment of inoperable tumor stenoses of the anus and rectum].

Inoperable tumor stenosis of anus and rectum may be treated surgically only by implantation of artificial anus. Cryosurgery proves to be a feasible alternative in order to maintain free passage of the gut. The cryoprobe is introduced through a rectoscopy under direct view. Visible tumor is touched with the tip of the cryoprobe and subsequently temperature is lowered to approximately -19 degrees C. Usually anesthesia is not required. From 1976 to 1989, 213 patients had been treated by cryosurgery in our department. In 23 cases the use of an artificial anus became inevitable afterwards.

Anus Neoplasms

[Advantages and disadvantages of ultrasound dissection of benign struma. A report of experiences after 2 years clinical use].

Ultrasonic dissection of goitre allows a controlled resection. This method saves time and diminuishes risk of operation. Not suturing the remnants of thyroid gland, optimal blood supply is obtained and hazard for the recurrent laryngeal nerve is decreased. Loss of blood is insignificant. To increase acceptance of this method, handling of apparatus has to be improved.

Goiter, Nodular

[The value of serum endotoxin determination after gastrointestinal interventions].

Serumendotoxins were measured in 11 patients after gut surgery and compared with healthy people as a standard. In cases of uncomplicated course 3 to 4-fold raised serumendotoxin levels were observed in a typical two-peak pattern. It was not before the fifth day following operation that serum levels declined constantly. In contrast to these findings, patients suffering from septic complications showed a permanently raised endotoxin level, which correlated well with their clinical course. Therefore single peaks of serumendotoxin measured after operation should not be overvalued. Constantly raised levels following operation, however, may indicate some kind of septic complication.

Aged

Diet, physical activity, and colorectal cancer among Chinese in North America and China.

In a population-based case-control study of colorectal cancer among Chinese men and women in western North America and the People's Republic of China, a common protocol was used to assess past life-style characteristics of 905 cases diagnosed during 1981-1986 and 2,488 controls. Risks for cancers of both the colon and rectum increased with increased food energy from fat, protein, carbohydrate, and all energy sources combined, for both sexes and on both continents. Yet, in multivariate analysis, colorectal cancer risk was significantly associated only with saturated fat; no relationships were seen with other dietary sources of energy. Colon cancer risk was elevated among men employed in sedentary occupations. On both continents and in both sexes, risks for cancers of both the colon and rectum increased with increasing time spent sitting. Further, the association between colorectal cancer risk and saturated fat was stronger among the sedentary than among the active. Risk among sedentary Chinese Americans of either sex increased more than fourfold from the lowest to the highest category of saturated fat intake. Among migrants to North America, risk increased with increasing years lived in North America. These observations suggest (a) that colorectal cancer risk increases with duration of exposure to a sedentary life-style and a diet rich in saturated fat; (b) that higher incidence among Chinese-American men relative to women is due to longer duration of these habits among men, who have lived longer in North America; and (c) that higher risk among Chinese Americans of both sexes relative to risk among the general population in China is due to differences in such habits. Attributable risk calculations suggest that, if these associations are causal, saturated fat intakes exceeding 10 g/day, particularly in combination with physical inactivity, could account for 60% of colorectal cancer incidence among Chinese-American men and 40% among Chinese-American women.

Adult

The effects of age and dietary protein restriction on the pharmacokinetics of theophylline in the rat.

The influence of dietary protein levels on theophylline kinetics was examined in male Fischer 344 virgin rats of 2, 14 and 20 months of age fed for four weeks on a 23% (control) or 5% (low) protein diet ad libitum. Protein deficiency led to a significant decrease in body weight gain for the 2 month old rats (10.9% versus 26.5%). In addition, decreases in total body weight of 7.5% and 15.3% were seen for the 14 and 20 month old rats, respectively, on a low protein diet. Total proteins and albumin levels in plasma were not significantly affected by age or dietary protein levels. After intravenous administration of 10 mg/kg aminophylline, the average mean residence time (MRT) was significantly longer in 20 month old rats as compared to the younger rats, while 14 month old rats had a greater elimination rate constant than the 2 and 20 month old rats. There were significant reductions in the mean steady-state apparent volume of distribution (Vss) in the 2 and 14 month old rats on a low protein diet of 31% and 18%, respectively, while there was no difference between the diets in 20 month old rats. In addition, the Vss decreased from 0.71 L/kg to 0.57 L/kg in the 2 and 20 month old rats, respectively, on a normal protein diet. Dietary protein deficiency led to a significant reduction of total body clearance from approximately 73 to 45 ml/hr/kg in the 2 and 14 month old rats.2+p

Aging

Role of the chest wall in detection of added elastic loads.

Changes in respiratory mechanical loads are readily detected by humans. Although it is widely believed that respiratory muscle afferents serve as the primary source of information for load detection, there is, in fact, no convincing evidence to support this belief. We developed a shell that encloses the body, excluding the head and neck. A special loading apparatus altered pressure in proportion to respired volume (elastic load) in one of three ways: 1) at the mouth only (T), producing a conventional load in which respiratory muscles are loaded and airway and intrathoracic pressures are made negative in proportion to volume, 2) both at the mouth and in the shell (AW), where the same pattern of airway and intrathoracic pressure occurs but the muscles are not loaded because Prs (i.e., mouth pressure minus pressure in the shell is unchanged, and 3) positive pressure in proportion to volume at the shell only, loading the chest wall but causing no change in airway or thoracic pressures (CW). The threshold for detection (delta E50) with the three types of application was determined in seven normal subjects: 2.16 +/- 0.22, 2.65 +/- 0.54, and 6.21 +/- 0.85 (SE) cmH2O/l for T, AW, and CW, respectively. Therefore the active chest wall, including muscles, is a much less potent source of information than structures affected by the negative airway and intrathoracic pressure. The latter account for the very low threshold for load detection.

Adult

Ketorolac tromethamine pharmacokinetics and metabolism after intravenous, intramuscular, and oral administration in humans and animals.

In humans, ketorolac is completely bioavailable and its kinetics are linear. It is absorbed rapidly (half-life for absorption 3.8 min) after oral (fasting) and intramuscular administration; food delays but does not reduce its absorption. The drug is highly protein bound in humans (greater than 99%). The mean plasma elimination half-life is 5-6 hours, and ketorolac is not extensively distributed outside the vascular compartment (Vd beta 15 L). Virtually all of the drug-related material circulating in plasma is in the form of ketorolac (greater than 96%), with the only metabolite the pharmacologically inactive p-hydroxyketorolac (PHK). Humans excrete about 90% of the administered dose in urine. About 60% of drug-related material recovered from urine is ketorolac, about 12% is PHK, and 28% represents polar, glucuronide conjugates of ketorolac. The animal models in which ketorolac's metabolism and kinetics are most similar to those in humans are the mouse and monkey, respectively.

Administration, Oral

Pharmacokinetics of norethindrone: effect of particle size.

In 24 healthy women between the ages of 19 and 35 years who had not used oral contraceptive preparations for at least 60 days, it was found that the smaller the particle size of norethindrone (NET) administered, the higher was the plasma NET level obtained. Three different preparations having particle sizes of NET smaller than 250 microns, 44 microns or 10 microns were tested in a crossover pattern. The time required to reach maximum plasma concentration (Tmax) became shorter with decreasing particle size, 1.69 hr, 1.52 hr and 1.06 hr, respectively. As particle size was reduced, the maximum NET plasma concentration (Cmax) increased for the 3 different 1 mg NET preparations, i.e. 8.66 ng/ml, 10.53 ng/ml and 15.73 ng/ml. A trial with a 2 mg NET preparation made with NET utilizing the 44 microns same material displayed a Tmax similar to the 1 mg NET preparation having the same particle size while the Cmax reached a level of 17.56 ng/ml. The area under the plasma concentration versus time curve from 0-24 hrs and the extrapolated total area under the curve, increased with decreasing particle size. The use of a smaller particle size allows for more rapid dissolution or oral contraceptive tablets when measured in vitro; however, there is no evidence that such faster dissolution leads to a significant difference in efficacy. Oral contraceptive tablets have, since their inception, utilized both large and small NET particle size material in various preparations.

Administration, Oral