Acquired resistance to chemotherapeutic drugs by tumor cells is an important obstacle to effective therapy of human malignancy. We now describe a vincristine (VCR)-induced multidrug-resistant (MDR) human acute lymphatic leukemia cell line, the sustained in vitro growth of which is dependent on vincristine. The doubling time for parental drug-sensitive cells (L0) is 40.2 +/- 13.2 h and for the MDR subline (L100) 62.5 +/- 11.3 h. L100 cells have similar G2 and mitotic phase to parental cells, express the MDR phenotype, and are characterized by novel morphologic features with multilobulated nuclei and multiple small nucleoli. Compared with L0 cells which have 2-3 nucleoli per cell, L100 cells have 7-8 nucleoli per cell. Average nucleolar area is 11.3 +/- 7.3 microns 2 for L0 and 2.5 +/- 2.4 microns 2 for L100 cells determined by the laser scanning method. The striking morphologic abnormalities of L100 cells suggest a drug-induced cytoskeletal abnormality. The relationship of these abnormalities to the VCR growth dependence of L100 cells is discussed.

Cell Cycle↗

PubMed1992

Anticlastogenic effects of 13-cis-retinoic acid in vitro.

The anticlastogenic effects of 13-cis-retinoic acid were studied in four human lymphoblastoid cell lines and in primary lymphocyte cultures derived from the peripheral blood of 11 study subjects. Cells were pre-incubated with 13-cis-retinoic acid in the concentration range of 10(-8)-10(-5) mol/l for 24 h and the numbers of chromatid breaks per cell induced by bleomycin were determined. The presence of 13-cis-retinoic acid decreased the number of breaks per cell by 13.0 to 59.5% in lymphoblastoid cell lines and by 0 to 57.4% in primary lymphocyte cultures (in the concentration ranges of 10(-8)-10(-6) mol/l and of 10(-8)-10(-5) mol/l, respectively). Regression analysis showed that there was a statistically significant correlation between the presence of 13-cis-retinoic acid and protection against bleomycin-induced clastogenicity. These data give additional information to the knowledge of possible chemopreventive mechanisms of action of 13-cis-retinoic acid.

Antimutagenic Agents↗

PubMed1992

[Clinical analysis of urolithiasis in Poh Ai Hospital of I-Lan, Taiwan, R.O.C.--a comparative study with urolithiasis in Japan].

Between August 1987 and December 1990, 546 patients were admitted to the department of Urology at the Poh Ai Hospital of I-Lan, Taiwan, R.O.C. for the treatment of urinary stones. These urinary stone cases accounted for 50 to 60% of all urology patients admitted. The incidence of urolithiasis in I-Lan was estimated at 147/100,000 population in 1990. There were 402 male patients and 144 female patients, The male to female ratio was 2.8: 1. There were 450 upper urinary tract stones (kidney, ureter) in 314 males and 136 females, and 79 lower urinary tract stones (bladder, urethra) in 72 males and 7 females. The ratio of upper to lower urinary tract stones was 6:1. Endourological treatments such as percutaneous nephrolithotripsy and transurethral ureterolithotripsy have increased rapidly in recent years. A summary of the present analysis for composition of 365 stones follows. The most frequent type was calcium-containing stone (92.3%), followed by infection stone (4.7%), then uric acid (UA) stone (3.0%). There were no UA stones found in the female patients. According to urinalysis criteria of more than 10 WBC/HPF (x 400), pyuria was found in 67 cases of 334 metabolic stones (20.1%), and 11 cases of 17 infection stones (67.7%). There were neither pediatric case of stone formation nor cystine stones.

Adolescent↗

PubMed1992

A novel, highly conserved structural motif is present in all members of the steroid receptor superfamily.

Steroid and thyroid hormone receptor superfamily members are ligand potentiated transcription factors. Recent evidence indicates that one aspect of steroid receptor action is an interaction with other trans-acting factors, such as the glucocorticoid receptor with the AP1 transcription factor, for example. Using a structural approach to identify domains of the glucocorticoid receptor responsible for interactions with affiliated transacting factors and DNA, we have identified a putative helix-turn-zipper motif that is conserved in all steroid, thyroid hormone, retinoic acid, and vitamin-D3 receptors. This structural motif is also conserved among new members of the family, the peroxisome proliferator-activated receptors and the retinoid-X receptors. This structural domain is characterized by a pair of amino acids (I,L,V)P that is conserved in all superfamily members. Additional characteristics include six heptad repeats of hydrophobic amino acids, four of which form a canonical leucine zipper in the rat glucocorticoid receptor. Although this leucine repeat is not absolutely conserved among superfamily members, the periodicity of hydrophobic residues is conserved throughout. Based on sequence analyses from the GenEMBL and SwissProt databases using the Genetics Computer Group and MacVector sequence analysis software packages, and the Brookhaven structural database, we present evidence for a novel structural domain, a helix-turn-zipper that is conserved in all superfamily members, and may function in transactivation of cognate genes.

Amino Acid Sequence↗

PubMed1992

Motor unit potential analysis under submaximal contraction: ADEMG study in normal and radiculopathy subjects.

The purpose of this study was to investigate the motor unit potential (MUP) morphology in different degrees of muscle contraction. Fourteen normal volunteers and 8 patients with C7 radiculopathy were included. The extensor digitorum communis muscle was kept in minimal contraction and 5%, 10%, 30% and 50% of maximal contraction under the guidance of strain gauge. Automatic motor unit potential analysis was done by automatic decomposition electromyography for each epoch of muscle contraction in both normal and radiculopathic groups. The results revealed that as muscle contraction increased, the observed MUPs had higher amplitude, rising ratio and firing rate, while the duration became shorter, but no regular change was found in turns reading. These tendencies were found in both normal and radiculopathic groups. This study enhanced the understanding of morphology of MUPs with higher threshold, and proved the usefulness of ADEMG in differentiating normal from cervical chronic radiculopathy condition. It is suggested that the examiner should observe both lower and higher threshold MUPs during clinical needle examination to make diagnosis more accurately.

Adult↗

PubMed1991

Endogenous modulators of glucocorticoid receptor function also regulate purified protein kinase C.

Modulator-1 and -2, proposed to be novel ether-linked aminophosphoglycerides, were originally identified as regulators of glucocorticoid receptor function (Bodine, P. V., and Litwack, G. (1990) J. Biol. Chem. 265, 9544-9554). We now demonstrate that these modulators are also potent new stimulators of protein kinase C activity in vitro. These endogenous biomolecules regulate purified protein kinase C activity in a biphasic and dose-dependent pattern, as determined by histone phosphorylation. Modulators, at concentrations within their apparent cellular range, stimulate protein kinase C-catalyzed histone phosphorylation 2-4-fold when added separately, or 10-12-fold when added together. This enhancement of kinase activity apparently is specific for protein kinase C, since neither protein kinase M, nor cAMP-dependent protein kinase A are stimulated by the modulators. The stimulation of purified protein kinase C occurs only when the enzyme has been initially activated by calcium, phosphatidylserine, and diacylglycerol, indicating that the modulators do not simply substitute for one of the enzyme cofactors. In addition, the modulators appear to interact directly with protein kinase C, perhaps with the regulatory domain of the enzyme, since these biomolecules inhibit the binding of phorbol ester to purified protein kinase C. Finally, time-course studies of protein kinase C-catalyzed histone phosphorylation indicate that the velocity of the enzyme reaction is increased by the modulators. Taken together, these results suggest that the modulators are a new class of regulators of protein kinase C.

Animals↗

PubMed1991

Quantitative comparison of motor unit potential parameters between monopolar and concentric needles.

This study quantitatively compared the simultaneous recording of the "same" motor unit potentials recorded by closely positioned concentric and monopolar needles. The motor unit potentials from the anterior tibialis of 12 young subjects were analyzed independently by both needles being connected to 2 sets of EMG-computer combinations. Recordings of the same motor unit potentials were confirmed by triggering and averaging of the 2 sets of motor unit potentials with identical firing patterns on both EMG screens. Automatic analysis disclosed the monopolar recordings had a significantly higher mean amplitude (2.05 times), larger surface area (2.64 times), and longer duration (1.86 times) than the concentric recordings, while the mean number of phases (1.58 times) and turns (1.35 times) revealed no statistical differences. Both active recording and reference electrodes contributed to these differences.

Action Potentials↗

PubMed1991

Effects of N-acetyl-L-cysteine and ascorbic acid on mutagen-induced chromosomal sensitivity in patients with head and neck cancers.

The protective effect of N-acetyl-L-cysteine (NAC) and ascorbic acid on mutagen-induced chromosomal breakage was determined using human lymphoblastoid cell lines as well as freshly cultured lymphocytes from patients with head and neck malignancies and healthy control subjects. Mutagen sensitivity was determined using the previously described bleomycin exposure assay. The toxicities of different concentrations of NAC and ascorbic acid, as well as both the preincubation and dose-dependent protective effects of these two agents, were analyzed. Both test drugs proved to be effective in diminishing mutagen-induced chromatid breakage in established lymphocyte cell lines. In freshly cultured lymphocytes, NAC given in doses ranging from 0.1 to 10 mmol/L decreased the number of mutagen-induced breaks per cell in a range from 23% to 73%, and ascorbic acid decreased chromosomal breakage by 21% to 58% in a dose range from 0.01 to 1 mmol/L. The results of this study demonstrate the protective effect mediated in vitro by both NAC and ascorbic acid against mutagen-induced chromosomal damage. A similar in vivo phenomenon may explain the differences in occurrence of head and neck cancer between populations with different dietary backgrounds.

Acetylcysteine↗

PubMed1991

Mitosis-arresting effects of cigarette smoke condensate on human lymphoid cell lines.

Whole-smoke condensates from the University of Kentucky reference cigarettes induced partial mitotic arrest in 4 human lymphoid cell lines. Treatment of cells for 3 h with 100 and 200 micrograms of cigarette-smoke condensate/ml of culture medium increased the frequency of metaphases and decreased the proportion of anaphases in the treated cell populations. Cytoskeletal studies using antitubulin immunofluorescence techniques and transmission electron microscopic studies demonstrated that in early stages of mitosis the formation of aster and the separation of centrosomes in condensate-treated cells were comparable to those of untreated control cells, but the poleward migration of centrosomes was inhibited. Arrested metaphases revealed two centrosomes surrounded by aggregated chromosomes in the center of each cell but the structure of the centrioles, microtubules and the kinetochores appeared normal. The results demonstrate the presence of antimitotic compounds in the tobacco-smoke condensate.

Analysis of Variance↗

PubMed1991

Calculation of bleomycin doses.

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Bleomycin↗

PubMed1991

[Electrodiagnostic evaluation of conservative treatment in carpal tunnel syndrome].

The incidence of carpal tunnel syndrome ranks first by far among all entrapment neuropathies. Many foreign studies have been reported over the years concerning the diagnosis of carpal tunnel syndrome, but very few about its treatment effects. Moreover, data have been based on the patients' subjective reports of their symptoms. Our data, however, are wholly derived from objective electromyographic examination. Five treatment approaches were compared for patients suffering from carpal tunnel syndrome in this study. Ninety-nine hands of 61 patients were divided into five treatment groups vitamins B6 & B12, steroid injection, hand splint, splint combined with vitamins, and splint combined with injection. Each patient was evaluated with electrodiagnostic study before the treatment, and 1 and 2 months after the treatment. Treatment with hand splinting, local injection at wrist, and combined therapies were all superior in effect to vitamins B6 & B12 alone in sensory nerve conduction study. The effects of treatment appeared faster in the groups with local injection and local injection combined with hand splinting in the sensory and motor nerve conduction studies. The results of this study suggest that treatment with vitamins B6 & B12 alone does not suit carpal tunnel syndrome well and that hand splint combined with steroid injection is the better conservative treatment.

Adult↗

PubMed1991

Staged ESWL monotherapy of complete renal staghorn calculi.

A retrospective study was done on 64 patients who received staged extracorporeal shock wave lithotripsy (ESWL) monotherapy for complete renal staghorn calculi. We used laboratory-proven stone components and a regular postoperative follow-up for a minimum of 6 months. There were 46 women and 18 men. The ages ranged from 19 to 75 years (mean 48.5 years). The number of ESWL sessions ranged from 1 to 4, with a mean of 2.1 sessions. The mean cumulative hospital stay was 13.3 days (range: 6-26 days). Successful treatments were defined as debulking over 90% of the stone burden and residual fragments of less than 3 mm in the longest diameter without obstruction 6 months post-treatment. A success rate of 86% was achieved in patients who had normal or minimal hydrocalycosis and only a 14.3% success rate for the patients with moderate to severe hydrocalycosis (p less than 0.005). Five of the patients with radiant calcium oxalate monohydrate had an unfavorable outcome. The best results were observed in the patient group of magnesium ammonium phosphate/apatite with normal to minimal hydrocalycosis (94.4% successful). The stone-free rate in this series was 51.6% at 6 months posttreatment. Being the least invasive, staged ESWL monotherapy is one of the better alternatives for the treatment of complete renal staghorn calculi in a select patient group.

Adult↗

PubMed1991

Serum level of immunosuppressive acidic protein in patients with urological malignancies.

Immunosuppressive acidic protein (IAP) is a non-specific immunoreactive protein arising from inflammatory or malignant conditions in the human body. We determined the IAP levels in 65 cases with urological malignancies and in 31 cases with benign diseases as a control group during a 9-month period. There were significantly higher serum levels of IAP in cases of bladder transitional cell carcinoma (p = 0.025), prostate adenocarcinoma (p less than 0.00001) and upper urinary tract urothelial cancer (kidney and/or ureter, p = 0.013) as compared with those of the control group. Significant differences in IAP between different tumor stages were found in the bladder cancer group with high stage cases having higher IAP levels (p less than 0.0005). However, no significant differences were found between different tumor gradings. Most of the prostate cancer patients had extremely high IAP values (1,029 +/- 490 micrograms/ml) in this study. Renal cell carcinoma and testicular tumors showed no statistical differences from the control group (p = 0.89 and 0.37, respectively). No differences could be found in the different age groups (by decades) or sexes. The serum IAP level can be a good non-specific tumor marker for bladder cancer staging and probably a good follow-up tool for most urological malignancy patients.

Adenocarcinoma↗

PubMed1990

Mutagen sensitivity in patients with head and neck cancers: a biologic marker for risk of multiple primary malignancies.

Eighty-four patients with head and neck cancers were evaluated for in vitro sensitivity to mutagens and then followed longitudinally for development of multiple primary malignancies. We assessed mutagen sensitivity by exposing lymphocytes to bleomycin in vitro and quantitating the bleomycin-induced chromosomal breaks per cell. The mutagen-hypersensitive patients, ie, those who expressed greater than 1.0 break per cell, were significantly more likely to develop multiple primary cancers than were patients who were less sensitive (less than or equal to 1.0 break per cell) (relative risk = 4.4; 95% confidence limits = 1.2, 15.8). This relationship was independent of age, sex, site, and treatment of first primary cancer and tobacco or alcohol exposures. Sensitivity to bleomycin-induced chromosomal damage serves as an indicator of genetic susceptibility to multiple primary malignancies in patients with head and neck cancers.

Adult↗