Growth and differentiation of adult rat hepatocytes regulated by the interaction between parenchymal and non-parenchymal liver cells

We have devised a medium which supports the continuous growth of hepatocytes without losing their replicative potential and differentiation capacity for a longer period. The medium HCGM, contains four key substances in addition to foetal bovine serum. They are epidermal growth factor, nicotinamide, ascorbic acid 2-phosphate and dimethylsulphoxide. When a non-parenchymal cell fraction containing small hepatocytes and non-parenchymal cells was cultured in HCGM, small hepatocytes grew clonally and differentiated into cells expressing either mature hepatocyte marker proteins or biliary cell marker proteins. Thus, for the first time, we showed the presence of a small compartment of bipotent and highly replicative clonogenic hepatocytes in the rat adult liver. HCGM also supported the growth of stellate cells (Ito cells) which were in the original preparation, suggesting the important role of stellate cells for the successful cultivation of hepatocytes. Together, these results suggest that a microenvironment is produced as a result of cooperative interactions between hepatocytes and stellate cells: one which stimulates the growth and differentiation of clonogenic hepatocytes.     

Experimental uremia in male rats: effect of interval between partial nephrectomies on testicular function

Testicular function in stepwise-nephrectomized rats, with a different interval between the two operations, was studied suing male Wistar rats. Serum levels of urea nitrogen and creatinine in stepwise-nephrectomized rats were significantly elevated compared to those in sham-operated rats ( p  < 0.001). With a 1-day interval between the two operations, these concentrations were considerably higher ( p  < 0.001) than those in 7-day interval rats. While serum LH levels were significantly reduced ( p  < 0.001) in 1-day interval rats, FSH levels in this group were considerably higher ( p  < 0.001) than in other groups. Serum concentrations of androstenedione in 1-day interval rats were significantly suppressed compared to other groups ( p  < 0.01). Serum testosterone levels in stepwise-nephrectomized rats were considerably lower ( p  < 0.001) than in sham-operated rats. It is assumed that testicular function in stepwise-nephrectomized rats is influenced by the interval between the two operations.     

Steroid Therapy in IgA Nephropathy: A Prospective Pilot Study in Moderate Proteinuric Cases

Forty-three patients with IgA nephropathy whose proteinuriapersisted between 1.0 and 2.0 g/day were assessed in an uncontrolledpilot study of steroid treatment. Fourteen patients receivean initial dose of 40 mg/day of prednisolone, followed by gradualreduction of the dose over an average period of about 19 months.After discontinuation of corticosteroids, they were treatedwith non-steroid anti-inflammatory drugs and/or anti-thrombocytedrugs to the end of the study. Another 29 patients receivednon-steroid anti-inflammatory drugs and/or anti-thrombocytedrugs throughout the study. Fourteen patients treated with steroidsexperienced considerable reduction in proteinuria and maintainedrenal function over 81 months. In 29 patients treated with non-steroidanti-inflammatory drugs and/or anti-thrombocyte drugs alone,proteinuria did not decrease and renal function deterioratedsignificantly during 60 months. At the end of the study, differencesin degree of proteinuria and in levels of renal function betweenthe steroid and non-steroid groups were statistically significant.In addition, these differences became more distinct in patientswith initial creatinine clearance values 70 ml/min or more inboth groups. These results suggest that treatment with steroidsin IgA nephropathy may be beneficial, especially in the earlystage of the disease.     

Chromosomally Abnormal Gametes as a Cause of Developmental and Congenital Anomalies in Humans*

ABSTRACT Human gamete chromosome studies using 702 oocytes and 15,864 spermatozoa were reviewed. These studies were chosen because they were carried out with our improved chromosomal technique, the gradual fixation-air drying method, which has been proven to be very reliable. The incidence of aneuploidy was about eight times as high in the oocytes (11.0%) as in the spermatozoa (1.4%), whereas that of structural chromosome aberrations was three times as high in the spermatozoa (14.1%) as in the oocytes (4.7%). In the spermatozoa, segregation errors leading to aneuploidy were found randomly among eight chromosome groups (A-G and sex chromosome). In contrast, they did not occur randomly in the oocytes. The observed frequency was significantly higher in group G and significantly lower in group A, as compared with the theoretical frequencies which were calculated according to the assumption that the segregation errors had taken place with an equal chance in each of 23 chromosomes. About 60% of the segregation errors were found to be due to so-called nondisjunction (loss or gain of dyads) and about 40% were due to so-called predivision (loss or gain of monads). The incidence of aneuploid oocytes increased slightly with the increase of donor age, although showing no statistical significance. The incidence of spermatozoa with structural chromosome aberrations vaned considerably from donor to donor (3.6–24.8%). However, there was no positive correlation between the occurrence of these spermatozoa and the age of donors or the habit of smoking. Incidences of chromosome aberrations in the human gametes (22.8% in oocytes and 15.5% in spermatozoa) were far higher than those in experimental animals. These seem to be associated closely with the characteristics of human reproduction and are responsible for a great part of human embryonic loss and developmental anomalies.     

Brainstem Stroke and Increased Anal Tone

After suffering a brainstem stroke, a 62‐year‐old man developed locked‐in syndrome including loss of horizontal eye movement and increased anal tone. Magnetic resonance imaging (MRI) of the patient revealed a massive stroke in the pons and right cerebellum, which seemed to involve the pontine micturition/defecation center (Barrington's nucleus) and the rostral pontine reticular formation (RPRF). As his increased anal tone was intractable to medical treatment, he required intermittent catheterization with an anal bougie tube. In light of the reported cases, our patient developed increased anal tone presumably due to pontine defecation center and RPRF lesion.     

Study of Lupus Nephritis in Males

Clinical and pathological findings were studied in 23 male patientswith lupus nephritis who were followed up for a period of 41±36months after renal biopsy. Age at renal biopsy was 31±14years and 19 patients (83 per cent) were between 15 and 50 yearsold. C3 and C4 levels were below normal in 23 (100 per cent)and 16 (70 per cent) respectively, CH₅₀ was <25 u/ml in 67per cent, and antinuclear and anti-DNA antibodies were foundin 87 per cent and 82 per cent respectively. Serum albumin levelincreased from 2.9±0.8 g/dl to 3.7±0.8 g/dl duringthe follow up period (p<0.01), while urinary protein decreasedfrom 2.0±2.3 g/day to 1.4±2.5 g/day. There wasa significant improvement in the degree of haematurai (p <0.01),but serum creatinine levels showed no change (mean 1.5 mg/ml).Active proliferative lupus nephritis of, moderate or severedegree was observed in 65 per cent of patients at the initialbiospsy. A trend to regression in this activity was seen inmost serial biopsies, but the chronicity index showed a slightincrease. These data demonstrate that systemic lupus erythematosusin males, in comparison to our previous report of the diseasein female patients, is accompanied by more active nephritis,but that is follows a benign course with therapy.