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Biomedical subjects

H Jung

Publications and source records attributed to H Jung.

At least 109 records · Page 6Linked to original sources
PubMed1994

A generalized concept for cell killing by heat. Effect of acutely induced thermotolerance and decay of thermosensitization.

Acute thermotolerance was induced in Chinese hamster ovary cells by heating at 43 degrees C for 45 min followed by incubation at 37 degrees C for up to 85 h. The degree of thermotolerance induced was quantified by a second heat exposure at 43 degrees C. To study the interaction of thermotolerance and thermosensitization, thermotolerant cells (43 degrees C/45 min-->37 degrees C/10 h) were subjected to step-down heating consisting of a priming heat treatment at 43 degrees C for 45 to 300 min followed immediately by a graded test treatment at 40 degrees C. Decay of thermosensitization was assayed by separating the priming treatment at 43 degrees C for 45 or 60 min and the test treatment at 40 degrees C by incubation at 37 degrees C for up to 24 h. The experimental data were analyzed by using a mathematical model published previously (H. Jung, Radiat. Res. 106, 56-72, 1986). According to this model, cell killing by heat is a two-step process. In a first step, heating produces nonlethal lesions at a rate p which, in a second step, are converted into lethal events at a rate c. Both rates were shown to depend on temperature. Data analysis, which was performed under the assumption that the rate constant c(T) is not altered by acute thermotolerance, showed that the rate constant p(43 degrees C) decreased exponentially (half-time 1.08 +/- 0.15 h) with increasing thermotolerance development, i.e., with increasing duration of the incubation interval at 37 degrees C. The rate p(43 degrees C) approached a minimum value by 14 +/- 3 h, where it was lower by a factor of 30 compared to normally sensitive cells. For incubation times at 37 degrees C exceeding 14 h, p(43 degrees C) increased exponentially with a doubling time of 13.9 +/- 0.9 h and approached the control level by 85 h. Decay of thermosensitization was quantified by calculating the number of nonlethal lesions from the data recorded for the sequences 43 degrees C-->37 degrees C-->43 degrees C and 43 degrees C-->37 degrees C-->40 degrees C. With increasing incubation interval at 37 degrees C, the number of nonlethal lesions induced per cell by a priming heat shock at 43 degrees C for 45 min remained constant for about 1.5 h and then decreased exponentially with a half-time of 2.0 +/- 0.5 h. Thus the two processes that occur simultaneously after a heat shock at 43 degrees C for 45 min, i.e., development of acute thermotolerance and decay of thermosensitization, proceed with different kinetics as could be separated by applying the model.

Animals↗
PubMed1993

Use of site-directed fluorescence labeling to study proximity relationships in the lactose permease of Escherichia coli.

The lactose permease of Escherichia coli is a paradigm for polytopic membrane transport proteins that transduce free energy stored in an electrochemical ion gradient into work in the form of a concentration gradient. Although the permease consists of 12 hydrophobic transmembrane domains in probable alpha-helical conformation that traverse the membrane in zigzag fashion connected by hydrophilic "loops", little information is available regarding the folded tertiary structure of the molecule. In this paper, we describe an approach to studying proximity relationships in lactose permease that is based upon site-directed pyrene labeling of combinations of paired Cys replacements in a mutant devoid of Cys residues. Since pyrene exhibits excimer fluorescence if two molecules are within about 3.5 A, the proximity between paired labeled residues can be determined. The results demonstrate that putative helices VIII and IX are close to helix X. Taken together with other findings indicating that helix VII is close to helices X and XI, the data lead to a model that describes the packing of helices VII-XI.

Base Sequence↗
PubMed1993

Properties and purification of an active biotinylated lactose permease from Escherichia coli.

A simplified approach for purification of functional lactose permease from Escherichia coli is described that is based on the construction of chimeras between the permease and a 100-amino acid residue polypeptide containing the biotin acceptor domain from the oxaloacetate decarboxylase of Klebsiella pneumoniae [Cronan, J. E., Jr. (1990) J. Biol. Chem. 265, 10327-10333]. Chimeras were constructed with a factor Xa protease site and the biotin acceptor domain in the middle cytoplasmic loop (loop 6) or at the C terminus of the permease. Each construct catalyzes active lactose transport in cells and right-side-out membrane vesicles. Moreover, the constructs are biotinylated in vivo, and in both chimeras, the factor Xa protease site is accessible from the cytoplasmic surface of the membrane. Both biotinylated permeases bind selectively to immobilized monomeric avidin and are eluted with free biotin in a high state of purity, and the loop 6 chimera catalyzes active transport after reconstitution into proteoliposomes. The methodology described should be applicable to other membrane proteins.

Bacterial Proteins↗
PubMed1993

Bioequivalence study of nalidixic acid tablets: in vitro-in vivo correlation.

The USP dissolution test was used to select seven products with a wide range of dissolution characteristics for in vivo examination. The bioequivalence of seven (500 mg) products was evaluated in two crossover urinary excretion experiments. In each study three products were compared with the innovator product (Negram-Winthrop-Breon) in 12 subjects according to a 4 x 4 latin square design. Significantly different, lower bioavailability was observed in two products in relation to that of the innovator product. Linear in vitro-in vivo correlations were found between the cumulative amount excreted at 24 h and the log of the amount dissolved at 30 min and between log of the cumulative amount excreted up to 24 h and the log of the amount dissolved at 45 min.

Adult↗
PubMed1993

What's new with lactose permease.

The lactose permease of Escherichia coli is a paradigm for polytopic membrane transport proteins that transduce free energy stored in an electrochemical ion gradient into work in the form of a concentration gradient. Although the permease consists of 12 hydrophobic transmembrane domains in probable alpha-helical conformation that traverse the membrane in zigzag fashion connected by hydrophilic "loops", little information is available regarding the folded tertiary structure of the molecule. In a recent approach site-directed fluorescence labeling is being used to study proximity relationships in lactose permease. The experiments are based upon site-directed pyrene labeling of combinations of paired Cys replacements in a mutant devoid of Cys residues. Since pyrene exhibits excimer fluorescence if two molecules are within about 3.5A, the proximity between paired labeled residues can be determined. The results demonstrate that putative helices VIII and IX are close to helix X. Taken together with other findings indicating that helix VII is close to helices X and XI, the data lead to a model that describes the packing of helices VII to XI.

Amino Acid Sequence↗
PubMed1993

Synthesis of L-carnitine by microorganisms and isolated enzymes.

L-Carnitine, a quaternary ammonium compound, plays an important role in beta-oxidation of fatty acids in mammals. The increasing demand for this compound in medicine has led to the development of numerous procedures for L-carnitine production. This review discusses the possibilities of microbial and enzymatical synthesis of L-carnitine and gives an overview on the pathways of L-carnitine metabolism and related enzymes in microorganisms.

Acyltransferases↗
PubMed1993

Correlation between thermal radiosensitization and heat-induced loss of DNA polymerase beta activity in CHO cells.

The increase in radiosensitivity caused by various kinds of single and combined heat treatments was studied in CHO cells and related to the heat-induced loss of the DNA polymerase beta activity. Thermal radiosensitization was quantified by the thermal enhancement ratio TER10% determined on the 10% survival level and by the parameters alpha and beta obtained from fitting cellular survival data to the equation -ln(S/S0) = alpha D + beta D2. The values for TER10% and the alpha-term showed only a poor correlation with the inverse of polymerase beta activity; the data for single heating at temperatures exceeding 41.5 degrees C and the data for thermotolerant cells fell on the same straight line, whereas for single heating at T < or = 41.5 degrees C and for cells exposed to a high-to-low temperature sequence (step-down heating) the increase in TER10% and alpha was much steeper than found for the other heat treatments. By contrast, a linear relationship was shown to exist between the beta-term of cellular radiosensitivity and the loss of polymerase beta activity as expressed by the reciprocal value of the enzyme activity. This relationship was the same for all kinds of heat treatments applied, suggesting that for CHO cells the increase in the beta-term observed after combined treatment with heat and radiation might be causally related to the heat-induced loss of polymerase beta activity.

Animals↗
PubMed1993

Pharmacokinetic comparison of two albendazole dosage regimens in patients with neurocysticercosis.

To evaluate two different dosage regimens for albendazole (7.5 mg/kg twice a day or 5.0 mg/kg three times a day), a study was performed in 10 patients with a diagnosis of parenchymal brain cysticercosis. Each patient received both regimens sequentially according to a randomized, crossover design. Blood and urine samples were taken once the drug steady state had been reached. Plasma levels of albendazole sulfoxide at steady state were determined using a HPLC method. In spite of a great intersubject variability observed with both regimens in the area under the curve (AUC) and in the minimum steady-state plasma concentration (Cp min ss), no statistically significant differences were found in these parameters. We suggest that a regimen of 7.5 mg/kg every 12 h can favorably replace the currently used regimen of 5 mg/kg every 8 h.

Adolescent↗
PubMed1992

Clinical pharmacokinetics of albendazole in patients with brain cysticercosis.

Albendazole pharmacokinetics were studied in eight patients who were receiving albendazole in doses of 15 mg/kg per day for 8 days as treatment of brain cysticercosis. Albendazole was not detected in plasma, but its main metabolite albendazole sulphoxide could be measured. Maximum plasma levels for albendazole sulphoxide ranged from 0.45 to 2.96 micrograms/mL. The half-life of albendazole sulphoxide was between 10 and 15 hours. A double peak was found in three patients. Mean residence time values were from 14 to 20 hours. Plasma levels of albendazole sulphoxide at the steady state showed great intraindividual variability. The results suggest that albendazole can be administered twice daily rather than three times as is currently done.

Administration, Oral↗
PubMed1992

Light and lithium effects in the rat retina: modification by the PAF antagonist BN 52021.

We tested the effect of an antagonist of platelet-activating factor (PAF), BN 52021, on both acute light-induced and light plus lithium-induced rod outer segment (ROS) lesions. Rats were fed lithium carbonate (2.6 g/kg chow) for 3 weeks. Half of the lithium-treated rats received BN 52021 (25 mg/kg) via gastric intubation prior to light exposure. Control and treated rats were exposed to 400-450 lux (measured at the eye level of the rats) of diffuse, white fluorescent light for 30 min, followed by 2 h of darkness and then decapitated. The eyes were removed and prepared for light and electron microscopic observation. The structural alterations of ROS were quantified from electron micrographs using a multifunctional computer image-analysis system. Our data show a significant reduction of ROS lesions by BN 52021, and this is most pronounced in light plus lithium-treated rats. Furthermore, in confirmation of previous studies, chronic lithium treatment significantly augmented light-elicited phagosome numbers, and BN 52021 reduced this effect. Our findings thus suggest that light and lithium may act via PAF responses in the rat retina.

Analysis of Variance↗
PubMed1992

A long-term survey of morphine in cancer pain patients.

We surveyed 550 cancer patients who experienced pain and were treated with morphine for a total of 22,525 treatment days. Sufficient pain relief was achieved during more than 80% of this time using an average oral morphine dose of 82.4 mg--significantly lower than other studies. The use of this low dose, which was possible due to the concomitant administration of nonopioids and specific coanalgesics in most patients, resulted in a low incidence of side effects. Constipation and nausea/vomiting were the most common of these side effects. Physical dependence posed no practical problem in discontinuation of morphine treatment. Long-term opioid intake and development of tolerance did not appear to be linked; an increase in morphine dosage was most often explained by progression of the terminal disease. Addiction was a negligible problem, with only one observed case.

Analgesics↗
PubMed1992

[Therapy for symptomatic pain in advanced breast cancer].

From 1983-1989, 106 patients with breast cancer were treated in our pain management unit on 6767 treatment days. Pain was caused by bone metastasis in 73% of patients. Neuropathic pain was reported by 32% of the patients. In all but four of these patients, new tumour growth was diagnosed. Patients were treated according to WHO analgesic guidelines with non-opioids on 16% of the days, non-opioids in combination with weak opioids on 36% and with strong opioids on 38% (orally 90%, parenterally 4% of the days). Due to the prevalence of bone pain non-steroidal antiinflammatory drugs were given on 56% of the days. The high incidence of neuropathic pain led to frequent use of co-analgesics (antidepressants 17%, anticonvulsants 12%, steroids 12% of the days). Adjuvant therapy for symptoms other than pain was given on 86% of the days. Whilst 92% of patients reported more than moderate pain on admission, 45% obtained complete pain relief beginning from the first days of treatment. On 92% of the days, patients described their pain as moderate or less. Side effects were treated symptomatically and played a minor role in a reason to change therapy.

Adult↗
PubMed1992

Effect of thermotolerance and step-down heating on thermal radiosensitization in CHO cells.

Chinese hamster ovary cells were exposed to single or fractionated heat treatments followed by irradiation on ice with graded doses of X-rays. The dose-response curves obtained were fitted by the linear-quadratic equation -ln(S/S0) = alpha D + beta D2 and analysed in terms of TER10%, alpha and beta. Thermal enhancement ratio, TER10%, was reduced when heat sensitivity was lowered either by chronic (pretreatment 40 degrees C, 16 h) or acute (43 degrees C, 45 min-37 degrees C, 10 h) thermotolerance, but was enhanced after step-down heating (43-40 degrees C or 45-40 degrees C). It could be shown that thermal radiosensitization, as expressed by TER10%, is modified by thermotolerance or step-down heating only to the extent to which cellular survival is modified by the corresponding pretreatments. However, the relative change of alpha and beta was found to be different for thermotolerance and step-down heating. For thermotolerant cells the values for alpha and beta were reduced by about the same factor, whereas step-down heating caused an increase in both parameters, which was greater for alpha than for beta. Data analysis showed that the modification of thermal radiosensitization by thermotolerance can be interpreted as if the cells were heated at the given temperature for a shorter time, whereas after step-down heating the cells responded as if they were exposed to a higher temperature prior to irradiation.

Animals↗
PubMed1992

Kinetics of depopulation, repopulation and host cell infiltration in the rhabdomyosarcoma R1H after 14 MeV neutron irradiation.

The kinetics of depopulation and repopulation of the solid transplantable rhabdomyosarcoma R1H in the rat was studied following irradiation with 5 Gy of 14 MeV neutrons. Several parameters were sequentially measured over a time period of 4 weeks after irradiation: the tumour volume was assessed by in situ caliper measurements; the numerical density of tumour cells was obtained by morphometry; the clonogenic fraction of tumour cells was derived from in vitro colony assay; and the numerical ratio of host to tumour cells was determined by flow cytometry. From these primary parameters the number of clonogenic tumour cells, non-clonogenic tumour cells, and nucleated host cells per tumour, as well as their variation with time, were derived. The results were compared with two sets of data obtained previously for the same tumour exposed to 15 Gy of 200 kVp X-rays. Survival of tumour cells was reduced to 5.5 +/- 0.5% by 5 Gy neutrons and to 4.5 +/- 0.5% by 15 Gy X-rays, i.e. an RBE of close to 3. There was a lag period before the onset of repopulation (4.9 +/- 0.4 days and 4.9 +/- 0.5 days, respectively), followed by a high initial rate of repopulation corresponding to a doubling time of 2.0 +/- 0.2 days for neutrons and 2.1 +/- 0.2 days for X-rays. The rate of depopulation was significantly different for the two treatment modalities; the halving time for the number of non-clonogenic tumour cells was 11 +/- 4 days for neutrons and 2.8 +/- 0.5 days for X-rays.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Nitro group orientation, reduction potential, and direct-acting mutagenicity of nitro-polycyclic aromatic hydrocarbons.

Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are widespread genotoxic environmental pollutants. We have been interested in determining the structural and electronic features that may be useful in predicting the direct-acting mutagenic activity of nitro-PAHs in Salmonella typhimurium. In this study, a series of structurally related nitro-PAHs were used to determine the relationships among direct-acting mutagenicity, orientation of the nitro group, and reduction potential of the nitro group. The compounds consisted of isomeric mononitrated and dinitrated benzo[e]pyrenes, their derivatives, and other nitro-PAHs ranging from two to five aromatic-ring molecules in size. A general finding is that nitro-PAHs with their nitro substituent oriented perpendicular to the aromatic system exhibit either very weak or no direct-acting mutagenicity in S. typhimurium strains TA98 and TA100. However, if a nitro-PAH of this type has a relatively low first half-wave reduction potential, it may be direct-acting. Furthermore, a positive correlation between the first half-wave reduction potential and direct-acting mutagenicity is found only when the compounds are structurally similar. Consequently, the correlation cannot be made using nitro-PAHs with different molecular size. Nitro-PAHs having a perpendicular nitro orientation always have a higher (absolute value) first half-wave reduction potential than the isomer(s) with a parallel orientation. Perhaps due to electron-withdrawing by the second nitro group, dinitro-PAHs always have a lower first half-wave reduction potential than their mononitro analogues. These findings provide a useful molecular basis for interpreting and predicting the direct-acting mutagenicity of nitro-PAHs.

Benzo(a)pyrene↗
PubMed1991

Thermal radiosensitization in CHO cells by prior heating at 41-46 degrees C.

CHO cells were exposed to heat at temperatures ranging from 41 degrees C to 46 degrees C followed by irradiation on ice with graded doses of X-rays. The dose-response curves obtained were analysed in terms of D10%, D0 and Dq and thermal enhancement was expressed by the corresponding values TER10%, TEF and TEQ, respectively. TER10% and TEF were shown to increase linearly with heating time, the increase being steeper at higher temperatures. The dose-response curves were also analysed using the equation -ln(S/S0) = alpha D + beta D2; the values of alpha and beta obtained from curve-fitting were found to increase with heating time. For temperatures below 43 degrees C the relative increase in alpha was greater than that in beta; the Arrhenius activation energies were Ea = 890 kJ mol-1 for alpha and Ea = 1830 kJ mol-1 for beta. At temperatures exceeding 43 degrees C the relative increase of alpha and beta was similar and the corresponding activation energies were about the same (Ea approximately 700 kJ mol-1). The increase in the alpha-term was attributed to a depressed repair of double-strand breaks, whereas the increase of beta was assumed to be a consequence of an insufficient repair of base damage.

Animals↗