Molecular heterogeneity of somatostatin analogue BIM-23014C receptors in human breast carcinoma cells using the chemical cross-linking assay.

Distinct proteins complexed with somatostatin and the somatostatin analogue BIM-23014C were revealed in human breast cancer cells using the cross-linking assay. One BIM-23014C-specific complex (Mr 57,000) was observed in MCF-7 (monolayer, nodule, and tumor) and T47D. Growth inhibition of MCF-7 tumor xenografts by BIM-23014C was dose related in the 6-day subrenal capsule assay. Three complexes (Mr 27,000, 42,000, and 57,000) were detected in MDA-MB-231, and no complex was visible in HBL-100. No correlation was found between receptors for BIM-23014C and epidermal growth factor in these lines. Twenty-seven of 30 human breast tumors (90%) had at least one BIM-23014C receptor. Sixteen had three complexes (Mr 27,000, 42,000, and 57,000). Six had the two complexes (Mr 27,000 and 57,000), two had Mr 42,000 and 57,000 complexes, two had just the Mr 27,000 complex, and one had just the Mr 42,000 complex. The presence of the three BIM-23014C receptors was positively correlated (P less than 0.05) to the low amount of sex steroid receptors (less than 20 fmol/mg) [seven of eight (estrogen receptor negative, progesterone receptor negative) versus four of 14 (estrogen receptor positive, progesterone receptor positive)]. Another positive correlation was established between the absence of progesterone receptors and the presence of these three complexes [12 of 16 (progesterone receptor negative) versus four of 14 (progesterone receptor positive)]. This high percentage of BIM-23014C receptor-positive biopsies and its inhibitory activity would support its clinical potential for the treatment of breast cancer.     

Kinetics and enzyme involvement in the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in microsomes of rat lung and nasal mucosa.

The rat lung and nasal cavity are two target organs for carcinogenesis by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In order to characterize further the enzymes involved in the bioactivation of NNK, detailed kinetic and inhibitory studies were conducted with rat lung and nasal mucosa microsomes, and the results were compared with previous studies. The enzymes in rat lung microsomes catalyzed the alpha-hydroxylation, pyridine N-oxidation and carbonyl reduction of NNK. The apparent Km for the formation of the NNK-derived keto aldehyde, NNK-N-oxide, the NNK-derived keto alcohol and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol were 28.8, 10.4, 7.0 and 178.1 microM respectively. In rat nasal microsomes, alpha-hydroxylation was the predominant pathway and the rate was approximately 200 times higher than that in lung microsomes. The apparent Kms for keto aldehyde and keto alcohol formation in rat nasal microsomes were 9.6 and 10.1 microM respectively. The cytochrome P450 inhibitors metyrapone and carbon monoxide markedly inhibited the metabolism of NNK in both rat lung and nasal microsomes. In rat lung microsomes, alpha-naphthoflavone and monospecific antibodies against P450s 1A2, 2A1 and 2B1 inhibited the formation of keto aldehyde by 39, 46, 64 and 23% respectively. In rat nasal microsomes, alpha-naphthoflavone and antibodies against P450s 1A2, 2A1 and 3A inhibited the metabolism of NNK by 80, 35, 20 and 14% respectively. The results indicate that cytochromes P450 play a major role in the metabolic activation of NNK in rat lung and nasal microsomes, and that there are tissue-related differences in NNK metabolism.     

Changes in muscle morphology in dialysis patients after 6 months of aerobic exercise training.

BACKGROUND: In the present study we investigated the effect of a 6-month aerobic exercise programme on the morphology of the gastrocnemius muscle of end-stage renal disease (ESRD) patients. METHODS: Twenty-four ESRD patients volunteered to participate in the training programme and underwent muscle biopsy before training. Eighteen patients completed the training programme of whom nine agreed to a post-training biopsy (one woman and eight men, mean age 56 +/- 15 years). Data are presented for the nine subjects who were biopsied before (PRE) and after training (POST) and separately for the 15 subjects for whom we only have a biopsy before training (cross-sectional group). RESULTS: There were no significant differences (P > 0.05) in fibre type distribution or myosin heavy chain (MyHC) expression between the cross-sectional and PRE/POST groups. The mean cross-section fibre area after training (POST) increased by 46% compared with the PRE training status (P < 0.01). The proportion of atrophic fibres decreased significantly after training in type I, IIa and IIx fibre populations (from 51 to 15%, 58 to 21% and 62 to 32%, respectively). Significant differences were also found in capillary contact per fibre (CC/F), with the muscle having 24% (P < 0.05) more CC/F compared with the PRE training status. No significant differences in cytochrome c oxidase concentration were found between the groups. CONCLUSIONS: In conclusion, exercise appeared to be beneficial in renal rehabilitation by correcting the fibre atrophy, increasing the cross-section fibre area and improving the capillarization in the skeletal muscle of renal failure patients.     

Decrease of glucose in the human visual cortex during photic stimulation.

Localized proton NMR spectroscopy was used to study cerebral metabolism in the visual cortex of healthy adults during rest and photic stimulation. Basal lactate levels showed considerable interindividual differences ranging from below detectability (less than 0.3 mM) to about 1 mM without consistent alteration during photic stimulation. Local brain glucose levels were significantly reduced (approximately 50%) during the entire period of photic stimulation and recovered to resting levels (approximately 0.8 mM) within 10 min after the end of stimulation. This decrease reflects the establishment of a new equilibrium due to enhanced delivery (blood flow) and enhanced consumption. The absence of lactate accumulation supports the hypothesis of a rapid efflux of lactate from brain tissue under activated conditions.     

Complications of whole abdominal and pelvic radiotherapy following chemotherapy for advanced ovarian cancer.

We examined the records of 105 patients with advanced ovarian cancer who had been treated with cisplatin combination chemotherapy followed by abdominopelvic radiotherapy. The purpose was to define the morbidity of this approach, and identify those factors predictive of toxicity. Acute toxicity resulting in delay or failure to complete treatment was most commonly due to myelosuppression. Nine of 105 patients (8.6%) required surgery for bowel obstruction that was not due to recurrent disease, 3 had an episode of bowel obstruction that settled conservatively, and a further 5 underwent surgery for obstruction due to recurrent tumor. The presence of both a dose of abdominopelvic radiotherapy over 2250 cGy, as well as a second-look laparotomy prior to radiotherapy, was associated with an increased risk of serious bowel complications. The increased frequency of late bowel morbidity seen in the combined modality group is likely explained by the presence of these two factors, rather than the exposure to chemotherapeutic agents per se. These observations are supported by the published literature.     

Periodontal status of a subject sample of Yemen

Abstract From August to October 1991, the periodontal status of 1001 Yemenis representing the age groups 12-14, 15-19, 20-24 and 35-44 years was recorded and evaluated with preference to the CPITN, the calculus index and clinical attachment levels. The impact of chewing khat, the leaves of a cultivated, alkaloid shrub, and of using the traditional miswak chewing stick for oral hygiene purposes were investigated. The results show that 6.9% of the juvenile probands (15-19 years) had healthy periodontal tissue (CPITN 0). whereas bleeding on probing and calculus (CPITN 1+2) were registered in 86.2%. In the 35-44 year age group. 1.7% were periodontally healthy, whereas 84.5% displayed plaque retention or shallow pocketing (CPITN 2-3) and 12.5% deep pocketing (CPITN 4). The treatment needs in all age groups are confined primarily to calculus removal and instruction in oral hygiene. The clinical attachment level and the calculus index revealed age-related attachment loss and calculus formation, primarily among male probands. The higher khat consumption among the male population is reflected in its detrimental effect on the periodontal tissue, especially among younger probands. Oral hygiene aids have also an influence on periodontal status, with a toothbrush proving more efficient than the miswak. WHO efforts directed towards prophylactic programs need to be intensified but can be staffed by dental hygienists.     

Current management of varicoceles

In spite of all that has been written about the varicocele, it is still not clear who will benefit from occlusion of the spermatic vein or why improvement in semen takes place in some patients but not in others. Because fertility is usually assessed in the framework of a couple who are trying to establish a pregnancy, it is important to evaluate both partners before making any recommendations regarding therapy. If the man is found to have a varicocele and semen analyses that indicate deficits in either the quantity or quality of the sperm, surgical ligation or transvenous occlusion should be considered as one appropriate form of therapy. Varicocele ligation and embolotherapy both can be performed as an outpatient procedure with minimal morbidity and equal effectiveness regarding pregnancy outcome. The cost, if the procedures are done in an outpatient facility, should be approximately equal. The obvious benefits of the percutaneous technique are a slightly lower recurrence rate and a more rapid return to full physical activity. The surgical procedure described by Marmar and associates appears to have a similar rate of recurrence and short postoperative period of recovery. Greater experience by more urologists using this technique needs to be gained to compare it adequately with the other methods described. Varicocele ligation by the inguinal or retroperitoneal routes is familiar to most urologists and does not require the operating microscope or other special instruments. With greater understanding of the venous anatomy and with careful dissection, the persistence and recurrence rate can be acceptably low and the postoperative recovery relatively rapid and smooth.     

Effect of 5-azacytidine on metallothionein inducibility and sensitivity to lethality of cadmium in rat osteosarcoma (ROS 17/2.8) cells.

ROS 17/2.8 cells, a cloned rat osteoblastic osteosarcoma cell line, were found to be extremely sensitive to the lethal effects of cadmium and to synthesize little, if any, metallothionein in response to cadmium exposure. Culture of cells for 24 h in the presence of 1 microM 5-azacytidine, a cytidine analog, increased the inducibility of metallothionein by cadmium and significantly reduced (P less than 0.001) cytotoxicity. Anion exchange chromatographic analysis of cadmium binding to low molecular mass cytotoxicity. Anion exchange chromatographic analysis of cadmium binding to low molecular mass cytosolic proteins showed that cells treated with cadmium and 5-azacytidine expressed at least 2 isoforms of metallothionein. One isoform of metallothionein with a low affinity for cadmium was constitutively expressed by these cells. The association of poor inducibility of metallothionein by cadmium with extreme sensitivity of cells to cadmium emphasizes the role of this protein in the cellular response to this toxic metal. The modulation of metallothionein inducibility and sensitivity to cadmium by 5-azacytidine treatment suggest that metallothionein gene structure and regulation are altered in ROS 17/2.8 cells.