Different capacities for amino acid transport in periportal and perivenous hepatocytes isolated by digitonin/collagenase perfusion

Periportal and perivenous hepatocytes were isolated from rat liver by digitonin/collagenase perfusion for investigating the acinar heterogeneity of amino acid transport activities related to glutamine and ammonia metabolism. Immunocytochemical staining of the respective subpopulations for glutamine synthetase demonstrated that periportal subpopulations were essentially free of glutamine synthetase-positive cells, whereas perivenous subpopulations showed a 2- to 3-fold enrichment of glutamine synthetase-positive hepatocytes. The high perivenous/periportal ratio of 59 found for glutamine synthetase activity as well as the perivenous/periportal ratios of other marker enzymes further indicated the good separation of periportal and perivenous cells. alpha-Aminoisobutyric acid, histidine and glutamate were used to determine the distribution pattern of amino acid transport systems A, N and G-, as well as of the sodium-independent uptake of these compounds 1 hr after isolation and after maximal hormonal stimulation during primary culture. The strong heterogeneity of the sodium-independent transport of histidine, characterized by higher perivenous transport rates [perivenous/periportal ratio: 1.5 (1 hr) to 3.5 (48 hr)], suggests a significant role of facilitated diffusion, presumably in glutamine export. Conversely, the strong heterogeneity of the sodium-dependent glutamate transport (System G-) characterized by higher uptake rates in nonstimulated [perivenous/periportal ratio: 6.6 (1 hr)] and in hormonally treated perivenous hepatocytes (perivenous/periportal ratio: 2.2) reflects its possible significance with respect to the substrate availability for glutamine synthesis. The observed heterogeneities provide a basis for understanding how substrate fluxes related to glutamine metabolism might be established and regulated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dopamine: its potential for inducing ischemic left ventricular dysfunction

As an agent potentially capable of inducing ischemia in patients with coronary artery disease, dopamine administered intravenously was evaluated as a pharmacologic stress agent by supine radionuclide angiography, and the results were compared with ergometer exercise. In a preliminary group of 11 subjects (4 normal subjects and 7 patients with coronary disease), dopamine alone was administered in increments of 2.5 micrograms/kg per min to a maximum of 15 micrograms/kg per min. There were significant differences between exercise and dopamine in maximal stress heart rates, 129.3 +/- 30.0 versus 88.0 +/- 35.8 beats/min (p less than 0.05) in normal subjects and 118.9 +/- 21.1 versus 87.6 +/- 22.6 beats/min (p less than 0.05) in patients with coronary disease, as well as in maximal stress rate-pressure products, 213.3 +/- 51.4 versus 155.0 +/- 52.5 mm Hg/min X 10(2) (p less than 0.02) in normal subjects and 216.0 +/- 45.6 versus 161.0 +/- 48.6 mm Hg/min X 10(2) (p less than 0.003) in patients with coronary disease. As a result, in these patients the ejection fraction response was significantly different: -3.3 +/- 4.5% with exercise versus + 6.3 +/- 4.6% with dopamine (p less than 0.05). In a second group of 41 subjects (9 normal subjects and 32 patients with coronary disease), atropine (0.6 mg) was administered intravenously before and after every second dopamine dose increment. This produced statistically similar maximal stress heart rates as compared with exercise in all subjects, rate-pressure products in normal subjects and slightly higher values with dopamine in patients with coronary disease: 200.3 +/- 47.2 versus 183.1 +/- 43.0 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Frequency and Late Results of Local Recurrence and Metachronous Distant Metastases in Rectal Cancer

Over a 5-year period (1990 to 1995) 425 patients were operated on for rectal cancer. There were 48 local recurrences, 15 with additional distant metastases, 61 patients only had distant metastases. In our patients we found as a well known fact an increasing number of local recurrences and distant metastases with an increasing T- or N stage, no metastases in cases of low tumor grading (28/425 G1), but a high increase comparing patients with or without blood vessel invasion (V 12.3%, V1 42.9%). Lymphatic vessel invasion also shows a higher rate of local recurrences and distant metastases, even in nodal and blood vessel negative patients (L0, N0, V0, L1, N0, V0 60%).L- and V-positive patients should be included in a postoperative adjuvant therapy regime as well (together with all cases Stage II and III UICC), even in nodal negative cases.     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Duodenal pancreatectomy with occlusion of the pancreatic duct

In 1978 partial duodenopancreatectomy with Ethibloc duct occlusion of the pancreatic remnant was introduced for use in patients with severe chronic cephalic pancreatitis. Our intention was to remove the largely destroyed part of the gland, and to induce controlled glandular atrophy in the residual portion in order to prevent further recurrence of pancreatitis. Since then this surgical procedure has been performed in 328 patients. The perioperative mortality was 1.2%, the complication rate requiring relaparotomy 7.1%. So far pancreatitis has recurred in only 2.2% of cases, due, we believe, to incomplete ductal block. Some 53% of the patients remained free of pain and symptoms, while 35% have occasional minor complaints. In a prospective follow-up study of 23 patients, Ethibloc duct occlusion was shown to be highly effective in inducing controlled atrophy of the gland and thereby terminating the inflammatory process. Endocrine function was preserved at the post-resectional level.