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Biomedical subjects

A Bakka

Publications and source records attributed to A Bakka.

At least 55 records · Page 3Linked to original sources

[Acute non-calculous cholecystitis].

We report a ten-year series of 18 patients treated for acute acalculous cholecystitis. 12 were males and six females, ranging in age from 23 to 77 years, with a mean of 64. 13 underwent major surgical procedures, two for multiple injuries. An additional four patients were also treated for multiple injuries. Clinical knowledge and a critical attitude are essential for the diagnosis. Blood tests are unreliable, since the result may be affected by other complications or associated diseases. It is therefore necessary to use diagnostic imaging. The treatment of choice is percutaneous bile drainage.

Acute Disease↗

Endoscopic treatment of colorectal carcinoma.

All malignant pedunculated polyps of the colon can be removed totally by colonoscopy alone. Resection of the colon is only necessary in those few instances where the cancer portion is poorly differentiated and where there are cancer cells in lymphatic or vascular channels. Malignant well differentiated sessile polyps are adequately managed by the endoscopic technique as well if the polypectomy is believed to have been complete and this can be confirmed by follow-up biopsies after 4-8 weeks. In these patients Laser therapy may also be of value. Endoscopic Laser therapy may be of value as a symptomatic treatment in patients with advanced malignant disease with obstruction or bleeding.

Adenocarcinoma↗

Routine double contrast barium enema and fiberoptic colonoscopy in the diagnosis of colorectal carcinoma.

The diagnostic efficacy of routine double-contrast barium enema and fiberoptic coloscopy for detection of cancer was retrospectively studied in 303 patients consecutively operated for colorectal adenocarcinoma in a 52-month period from January 1980. Double-contrast barium enema was performed in 180 patients with 184 carcinomas, 157 (85%) of which were revealed by this examination. The detection rate of carcinoma according to site was 89% between cecum and descending colon, 92% in sigmoid colon and 71% in rectum. Fiberoptic colonoscopy was done in 176 patients with 181 carcinomas, 163 (90%) of which were detected by the endoscopical examination. The detection rate of carcinoma according to site was 86% between cecum and descending colon, 90% in sigmoid colon and 95% in rectum. The two methods were equally effective in detecting carcinoma of the colon. Colonoscopy was superior to barium enema in detection of rectal carcinoma.

Adenocarcinoma↗

Massive gastric bleeding from exulceratio simplex (Dieulafoy).

Massive upper gastrointestinal haemorrhage may be caused by ulcus simplex Dieulafoy. Of 144 patients consecutively operated on for benign gastric ulcer in 1975-1980, 29 were admitted as emergencies because of massive bleeding from the stomach. Six had the Dieulafoy lesion. Identification of the source of bleeding was made by fibreoptic endoscopy in five of these cases, while wide gastrotomy was required in one case. All were successfully treated, one with gastroscopic coagulation and the others surgically. Hitherto there has been no recurrence of bleeding. Diagnostic and therapeutic problems are described. The Dieulafoy lesion may be life-threatening. A century after it was first reported, reminder of the lesion is still necessary, since it probably is more rarely recognized than rare.

Adult↗

Effect of cadmium and colcemide on the mitoses of a human epithelial cell line with high content of cytoplasmic metallothionein.

Cultures of cell strains with and without metallothionein were exposed to CdCl2 in doses ranging from 10 mu mol/l to 200 mu mol/l . Cell growth parameters were monitored by flow cytometric DNA-measurements, cell counts and counting of mitoses during the first two days after exposure. CdCl2 inhibited cell growth in a dose dependent way. The cadmium resistant cells were inhibited with concentrations above 100 mu mol/l, the concentration which the metallothionein-containing cells had previously been adjusted to. Microscopy of the cell cultures showed a dose dependent accumulation of cells in the mitotic prophase, whereas the other phases of the cell cycle were unaffected as measured by flow cytometry. When exposed to colcemide, however, the two cell strains showed identical responsiveness.

Cadmium↗

Stability of cadmium resistance and metallothionein levels in vitro and in vivo.

Cultured cells can be adapted to large concentrations of the toxic cadmium ion, apparently by induction of synthesis of the Cd-binding protein metallothionein (MT). One human epithelial line derived from normal skin (HE100) and one murine fibroblast line, derived from L cells (C1 1D100), were used to study the stability of Cd resistance, the MT levels following omission of Cd, and the inducibility of MT synthesis in cells on reexposure to Cd. In the murine cells there was no significant loss of resistance during a 4-week period either after cultivation in vitro or after growing the cells in nude mice. In the human cells a decrease (50%) in resistance was noted the first week after Cd omission. After removing Cd from the cells, a rapid decrease in MT content was demonstrated. After 3 weeks of cultivation only trace amounts were left in both cell lines. However, approximately 60% (HE100) and 80% (C1 1D100) of the previous levels were demonstrated after reexposure to maximum tolerable doses for 24 hr. The data indicate that the degree of stability of Cd resistance is dependent on the capacity in cells for an immediate de novo synthesis of large amounts of MT on reexposure to Cd. The animal experiments demonstrate that Cd resistance is maintained even after growing the cells in vivo.

Animals↗

Cultured human cells with a high content of metallothionein show resistance against gold-chloride.

Resistance to gold(III)chloride was tested in cultures of human epithelial cells derived from normal skin. Two cell strains were used, a 'wild type' (HE) and a substrain, previously made resistant to 100 mumol/l of CdCl2 (HE100), with a high content of the cysteine-rich cytoplasmic protein, metallothionein. Cell growth was studied for a period of 4 days during exposition to gold-chloride (100-400 mumol/l of HAuCl4 X 4H2O). Gold-chloride produced a dose-dependent inhibition of cell proliferation of both cell strains. Compared with untreated control cells, however, the percentage survival after 4 days' treatment with 400 mumol/l was only 11% of HE cells, vis-à-vis 44% of the HE100 cells. After 24 hours' exposition to 200 mumol gold-chloride/l, the subcellular distribution of gold was determined by gel-filtration of cytosols, and subsequent analyses for Au by flame atomic absorption spectrophotometry. In the HE100 cells 30% of the cytosolic gold co-eluted with the metallothionein. In the HE cells, which do not contain detectable amounts of metallothionein, only traces of gold were found in the corresponding eluate fractions. The total amount of intracellular gold was 15% higher in HE100 than in HE cells. This study renders it probable that the binding of gold to pre-existing metallothionein in HE100 cells affords protection against otherwise lethal gold concentrations. The significance of the results is briefly discussed in relation to therapeutic use of gold substances.

Binding, Competitive↗

Increased resistance to chlorambucil in cultured cells with a high concentration of cytoplasmic metallothionein.

Cultured cells with elevated levels of cytoplasmic metallothionein (MT), a small-molecular-weight protein extremely rich in cysteine, showed resistance against the alkylating drug chlorambucil. One human epithelial line (HE) and one mouse fibroblast line (Cl 1D) were used, as well as substrains of both cell lines (HE100 and Cl 1D100). The substrains contain large amounts of MT. Dose-survival curves obtained from cloning studies with the murine cells after exposure to chlorambucil for 1 hr revealed that Cl 1D100 was approximately 3-fold more resistant than were Cl 1D cells (D0 = 32.9 and 11.6 micrograms/ml, respectively); this difference was highly significant (p less than 0.001; t test). In growth rate studies, both MT-containing strains showed resistance against chlorambucil over the total dose range of 0.5 to 100 micrograms/ml compared to the parent strains. After 4 days treatment with 25 micrograms/ml, the growth inhibition of Cl 1D was 67%, but only 13% in Cl 1D100. For HE and HE100, 50 micrograms/ml gave growth inhibitions of 83 and 65%, respectively. Following 1- and 24-hr incubations of cells with [14C]chlorambucil and subsequent ultracentrifugation and gel filtration of the cytosols, about 20 to 40% of the 14C-derived radioactivity coeluted with the MT from the resistant strains. The results indicate that intracellular MT sequesters chlorambucil or its toxic metabolites and that the protein thus contributes to the resistance against this drug.

Animals↗

Radioresistance in cells with high content of metallothionein.

An endogenous cytoplasmic protein, metallothionein (MT) apparently gave rise to radioresistance in 2 different cell lines. A dose reduction factor of 1.9 was achieved in MT-containing cells. MT accounted for a 3-4 fold increase of total sulfhydryl groups in the resistant cell strains, compared to the non-resistant lines from which they were derived. The protein is rich in cysteine (30%), an amino acid known to give radioprotection when administered exogenously. Glutathione levels and cell-cycle phase distribution showed no marked difference between resistant and corresponding non-resistant cells.

Animals↗

Ultrastructural changes in the nucleus of a human epithelial cell line exposed to cytotoxic agents. The effect of PUVA and cadmium.

An established human epithelial cell line was exposed to cytotoxic doses of photo-activated 8-methoxy psoralen (PUVA) and to cadmium (Cd++) and the cells' nuclear ultrastructure were compared with controls. PUVA and Cd++ have some common biological features. Both substances induced nuclear indentations and cytoplasmic invaginations, while only PUVA caused an increase in nuclear bodies. After cadmium exposure, clusters of large-sized perichromatin granules (PG) were seen as well as an increase in chromatin margination. After PUVA, an increase in singularly distributed PGs was observed. The nuclear envelope was not affected by PUVA while Cd caused extensive disruption of this membrane. A strain of the epithelial cell line was made resistant to 100 mumol Cd/l and its nuclear ultrastructure was examined. An increase in chromatin margination was seen compared with its parent line. When this Cd resistant cell strain was exposed to 200 mumol Cd/l no ultrastructural changes took place. An attempt to produce a PUVA resistant epithelial cell strain was unsuccessful. Some functional aspects of the different morphological parameters observed are discussed.

Cadmium↗

Metabolism of zinc and copper in the neonate: accumulation and function of (Zn, Cu)-metallothionein in the liver of the newborn rat.

1. Measurements were made of the hepatic concentrations and contents of total and thionein-bound zinc and copper in late foetal and newborn rats and of the distribution of these metals between the particulate and soluble components of the liver. 2. The decrease in the hepatic concentration of thionein-bound Zn, which occurred with age after birth, was proportional to the increase in liver weight until the 16th day post partum; thereafter it was greater. 3. Throughout the period from birth to 25 d of age the Zn concentration remained constant in the cytosolic non-thionein fraction (i.e. total cytoplasmic Zn--thionein-bound Zn), but decreased in other compartments of the liver. 4. The same constant concentration of cytoplasmic non-thionein-bound Zn also was observed in animals with reduced total hepatic Zn contents, but normal body-weights, and in 20-d-old Zn-deficient pups. 5. The concentration of thionein-bound Cu increased significantly only between the 6th and 14th day post partum. The age-related variations in Cu contents of the particulate components closely paralleled those in the whole liver, whereas the Cu contents of the cytosolic thionein and non-thionein fractions did not increase appreciably until after the 10th day. 7. It is concluded that the cytosolic non-thionein fraction of newborn rat liver may contain particularly important metabolic sites that require Zn and a major function of Zn-thionein is to regulate the supply of the metal to these sites. As, from birth to 26 d of age, the sum of the concentrations of thionein-bound Zn and Cu was correlated with whole liver Zn, the accumulation of Cu as a soluble metallothionein seems to be a secondary event, dependent on the hepatic Zn concentration.

Aging↗

Influence of certain chelating agents on egress of cadmium from cultured epithelial cells containing high amounts of metallothionein: a screening of Cd-releasing and toxic effects.

Cells cultures have been used to study the effect of 6 different metal chelating compounds on the efflux of Cadmium (Cd) from the cells and on cell growth. The cells had previously been made resistant to high levels of Cd (100 mumol/1) in the medium. They contain large amounts of intracellular Cd (40-50 nmol Cd/mg cell protein), the main part of which is bound to cytoplasmic metallothionein. Among the different monothiol and dithiol compounds tested are some old, well-known and to some extent therapeutically tried substances, i.e. 2,3-dimercapto-1-propanol (BAL), D-penicillamine (PA), N-acetyl-DL-penicillamine (NAPA) and some newer metal chelators, i.e. 2,3-dimercaptopropane-1-sulphonate (BAL-Sulph), mercaptosuccinic acid (MSA) and meso-2,3-dimercaptosuccinic acid (DMSA). The three latter ones all showed better effect on the egress of Cd than PA and NAPA and less toxic effect than BAL on an equimolar basis. All the agents tested increased the efflux of Cd from metallothionein-containing cell cultures which seem to be justified as a test system for primary screening of effect and toxicity of new chelators.

Cadmium↗

Uptake and egress of cadmium in cultures of cadmium-resistant and the corresponding "wild-type" cells.

Development of resistance against the highly toxic Cd++ion has been described earlier both in animals, cell cultures and in bacteria. In this paper we have tested if decreased intracellular concentration of Cd plays a role in resistance to Cd in three mammalian cell cultures. The cells originated from different tissue and from two different species. Cd-resistant and corresponding "wild-type" strains were used. The results from all three lines show essentially the same, namely that there is no significant difference in Cd content between the Cd-resistant and the non-resistant cells. The resistant cells from all three lines grow continuously with a cellular Cd-content which is several times higher than that killing all cells of the non-resistant "wild-type".

Animals↗