Chemokine receptor CCR6 as a prognostic factor after hepatic resection for hepatocellular carcinoma

Background and Aims: Chemokines and their receptors have recently been shown to have major roles in cancer metastasis. The aim of this study was to determine whether the interaction between chemokine receptor 6 (CCR6) and its ligand, macrophage inflammatory protein‐3 alpha (MIP‐3α), correlates with metastasis of hepatocellular carcinoma (HCC). Methods: To observe the reaction of CCR6 expressed cancer cells to MIP‐3α stimulation, chemotactic and actin polymerization assays for both CCR6 high cells (HepG2) and CCR6 low cells (MCF‐7) were performed. CCR6 mRNA levels in tumor specimens from 30 HCC patients were quantified by real‐time polymerase chain reaction. Patients were classified into two groups, high (≥ 20 copies; n = 10) CCR6 and low (<20 copies; n = 20) CCR6 on the basis of CCR6 expression, and the groups were compared with respect to clinicopathological features. Results: When HepG2 cells (CCR6 high) were stimulated with MIP‐3α, they migrated in a dose‐dependent manner, and formation of pseudopodia was observed. These phenomena were not observed in the CCR6 low cells. The incidence of intrahepatic metastasis was higher in the high CCR6 expression group than in the low CCR6 expression group (P < 0.05). Disease‐free survival was significantly poorer in the high CCR6 expression group than in the low CCR6 expression group (P < 0.05). Conclusions: It was indicated that CCR6 might be associated with intrahepatic metastasis of HCC and might be able to become one of the prognostic factor after hepatic resection for HCC.     

Microvascular disturbances in the colonic mucosa in antibiotic-associated haemorrhagic colitis: Involvement of platelet aggregation

An ultrastructural study of the colonic mucosa was performed in four patients with antibiotic-associated haemorrhagic colitis and new findings are reported. Colonoscopy was performed and biopsy specimens were obtained within 24 h of the onset of bloody diarrhoea. Colonoscopy demonstrated diffuse oedematous and haemorrhagic mucosa with erosions and white coat. Light microscopy revealed mucosal haemorrhage and inflammatory cell infiltration. Ultrastructurally, platelet aggregation was frequently present in the lumina of colonic mucosal capillaries, causing engorgement of red blood cells in adjacent microvessels. Mild to severe damage was observed in capillary endothelial cells, including discontinuity of basement membranes, gaps between endothelial cells and the destruction of capillaries. There was no evidence of microvascular spasm. In conclusion, our findings suggest that antibiotics directly or indirectly cause microcirculatory disturbances, which result in tissue damage and haemorrhage, in the colonic mucosa.     

Bacterial invasion into the colonic mucosa in ulcerative colitis

Abstract This study investigated interactions between mucosal lesions and bacterial invasion in ulcerative colitis using the acridine-orange staining method. In all 16 cases of ulcerative colitis, the mucosa was found to be invaded by small rods and cocci. In five of 10 controls, bacteria were seen only adhering to the mucosa and no bacteria were detected in the five remaining cases. It is suggested that the presence of bacteria in the colonic mucosa may be a factor responsible for the persistence or aggravation of ulcerative colitis.     

Clinical Trial with Authentic Recombinant Somatropin in Japan

Recombinant somatropin, produced by recombinant DNA technology, was administered by injection in daily doses of 8 IU to six healthy young volunteers. Daily injection for 4 days did not cause any significant change in the results of physical examination, blood count or urinalysis. Non-esterified fatty acid levels increased significantly from 0.45 ± 0.16 to 1.08 ± 0.12 mEq/litre (mean SEM) at 4 hours after the first injection (p<0.001). Plasma IGF-1 levels increased from 0.80 ± 0.14 units/ml to 1.72 ± 0.50, 3.22 ± 1.02, 3.17 ± 1.20 and 3.63 ± 0.78 units/ml at 24 hours after each daily injection for 4 days (p<0.001). Plasma hGH reached peak levels at 3 hours after intramuscular injection of recombinant somatropin, 4 IU, and this peak value was 57.3 ± 2.8 ng/ml. A total of 21 patients with pituitary dwarfism were also treated with recombinant somatropin for 6 months at a dose of 0.5 IU/kg/week. Their heights increased by 2.2–5.0 cm during the 6 months of treatment, which was calculated to be equivalent to 4.4–10.0 cm/year with a mean growth rate of 7.4 ± 0.4 cm/year. Anti-hGH antibody with a titre of 10 was observed in two patients at the end of 6 months of treatment.     

Urinary prolactin excretion in children with renal disease

The contribution of the kidney to the metabolism of prolactin has not yet been established. In the present study, urinary prolactin concentrations in 30 children with renal disease were measured by a newly devised, highly sensitive, time-resolved immunofluorometric assay. Median prolactin concentrations in the urine of children with renal disease, were 1.86 pmol/L⁻¹ of urine (range: 0.17–546.31 pmol/L⁻¹. By stepwise regression analysis, change in urinary prolactin levels as a function of the urinary β 2-microglobulin concentrations was detected. These results indicate that prolactin urinary excretion in children with renal disease is dependent on the renal proximal tubular function.     

Jaundice and Renal Failure Following Radical Surgery for Cancer: An Analysis of Five Autopsied Cases

An analysis of postoperative jaundice and renal failure in fiveautopsied cases is presented. Two patients had total resectionof esophageal cancer, one had a subtotal gastrectomy, and theother two had radical operations for urinary bladder carcinoma.Halothane was used for anesthesia for three patients, and allfive required blood transfusions. Postoperatively, jaundiceand azotemia developed between the 1st and 7th days, with deathsix to 10 days after surgery. Total bilirubin ranged from 1.5to 13.4mg/dl despite the normal or modest rise in hepatic enzymes.BUN varied from 46 to 288 mg/dl. Pre- and postoperative ECGrevealed a prolongation of QTc in all cases. At autopsy, theliver, kidneys and heart showed a definite increase in weight.The salient hepatic pathology included diffusely dilated spaceof Disse, centrilobular bile stasis and steatosis. This, alongwith acute tubular necrosis confirmed at autopsy, was thoughtto be due to ischemia. Although the significance of prolongedQTc remains uncertain, it is worthy of attention as one of thepreoperative checks.     

An Attempt to Assess the Replacement Dose of Human Growth Hormone in the Treatment of Growth Hormone Deficient Children

Hibi, I., Tanaka, T., Yano, H., Umezawa, S., Kagawa, J., Tanae, A. and Ishikawa, E. (National Children's Medical Research Center, Tokyo, the National Children's Hospital, Tokyo and the Department of Biochemistry, Miyazaki Medical College, Miyazaki, Japan). Acta Paediatr Scand [Suppl] 337:87, 1987.
In 25 patients with hGH deficiency, who had been treated long-term with hGH, the mode of hGH administration was switched from the conventional method (0.3–0.5 IU/kg/week, in two or three divided doses, intramuscularly) to daily subcutaneous injection at 1900–2100 hours with a dose of 0.46 ± 0.07 IU/kg/week (equivalent to 14.7 ± 2.0 IU/m²/week). After 1–3 months of this new mode of hGH administration, blood and urine were sampled at 0900 hours after overnight fasting. Blood glucose, plasma insulin, plasma IGF-1 and plasma total IGF (after extraction) were analysed in blood samples. IGF-1 and hGH were measured in urine samples. These measurements indicated that the dose studied was close to a replacement one, but might be slightly higher than the exact replacement dose.     

Possible Involvement of Tissue-Type Plasminogen Activator in Gastric Ulcer Formation —Biochemical Evaluation Using Biopsy Specimens From Gastric Mucosa—

Abstract: Microvascular endothelial changes are thought to be a crucial step in the development of hemorrhagic changes in various pathological states. Tissue-type plasminogen activator (t-PA) is an endothelium-derived fibrinolytic mediator which regulates microvascular permeability. In this study, we determined the activity and amount of t-PA in the biopsy specimens taken from gastric mucosa of patients with gastric ulcers to evaluate endothelial alterations and vascular permeable changes in situ. In addition, to elucidate the relationship between local fibrinolytic disturbance and systemic blood coagulation, several factors such as plasminogen activator inhibitor were also assayed. The results of this investigation revealed that the mucosal t-PA amount in the active ulcer proved to be 2–3 folds higher than that in healthy controls, however, t-PA levels in plasma samples showed no remarkable differences among the groups. Increased t-PA activity appeared to well correlate to the degree of inflammation of gastric mucosa in contrast to t-PA amount which was still increased in healed ulcer lesion. PAI-1 in plasma samples from gastric ulcer patients showed a significantly high level as compared with healthy subjects. The present study indicates that t-PA activation may play an important role in the pathogenesis of gastric ulcer formation and that t-PA determination in gastric biopsy specimens may be useful for the evaluation of clinical activity of gastric ulcers in terms of the mucosal microvascular endothelial changes.     

A Case of Crohn's Disease which Initially Presented with Diffuse Inflammation in the Rectum and Sigmoid Colon

Abstract: This case report describes a female patient with Crohn 's disease who had diffuse proctosigmoiditis without a longitudinal ulcer or cobblestone appearance at the initial attack. She was treated with sulfasalazine on the presumptive diagnosis of ulcerative colitis. Two and a half months later, painful ulcers in the oral cavity and a deep longitudinal ulcer in the sigmoid colon were found, and a non-caseous granuloma was revealed in the biopsy specimens taken from the sigmoid colon. A definitive diagnosis of Crohn's disease was established from these findings and treatment with a corticosteroid was effective.