There are some reports indicating that the patients with chronic uremia reveal a rather suppressive immune response.
The author attemped to clarify the immunological reactivity of terminal renal failure by observing the PHA induced blastoid transformation of lymphocytes in vitro system.
In many cases peripheral lymphocytes from patients with terminal renal failure gave a decreased reaction to PHA, especially when they were incubated in the presence of their own serum.
The recombination experiments, in which lymphocytes from patients were incubated in the presence of normal serum, or lymphocytes from normal individuals in the presence of patient's serum, suggested that there might be at least two factors to cause a decreased reaction to PHA.
At first, the percentage of lymphocyte subpopulation was different between patients and normal healthy ones; sedimentation patterns and morphological studies showed that the smaller and heavier lymphocytes were relatively poor in uremic patients compared with normal. Since it is suggested that the most PHA reactive cells are contained in heavier, smaller lymphocytes, the decrease of these cells may cause the less response to PHA.
Secondly, it was assumed that patient's serum contained a factor or factors which inhibited the stimulatory effect of PHA. Gel filtration of patient's serum using Sephadex G-25 showed that the factor or factors had a smaller molecular weight and was dialysable.
These studies indicate that patients with terminal renal failure possess both a cellular and serum defect that suppresses lymphocyte transformation. In many patients it was frequently observed that the tuberculin skin reaction turned to negative. This fact also indicates the suppression of immune response in patients.

View full abstract

Adrenocortical hyperplasias experimentally produced in rats were placed in organ cultcue and studied as well as human adrenals from 16 surgical materials (5 controls; 11 hyperfunctioning human adrenocortinal tissues including 3 adenomas and each 2 hyperplasias from Cushing's syndrome and primany aldosteronism and 1 adenoma from adrenogenital syndrome) and the following results were obtained.
1. Adrenocortical hyperplasia by aniline injections was demonstrated in female rats (weight of adrenals 26.0±10.9mg by 7 day treatment; 57.0±6.0mg in controls).
2. Hyperplastic rat adrenals were cultured with and without ACTH, and the histological findings were comparatively studied. Adrenal hyperplasias cultured 7 days preserved better morphology than untreated group. The best histological preservation was found in hyperplasia cultured with 0.2IU/ml of ACTH for 7 days.
3. Sixteen human materials were cultured for 48 hour to 7 days (14 days in part) and tolerated for electron microscopy as well as routine histology.
4. Normal human adrenocortical tissues maintained the basic structures of cytoplasmic organellae during the 7 day culture period. By ACTH 0.02IU/ml in the culture media, mitochondria, smooth endoplasmic retuculi (SER) and vesicles were increasing while lipid granule decreased.
5. Adenoma cells from Cushing's syndrome maintained their basic structure with and without ACTH during the 7 day culture period. By ACTH 0.02IU/ml in the media, a better preservation of the tissues was obtained in 14 day cultures, while they tended to be degenerated by ACTH 0.2IU/ml.
6. In hyperplasias from Cushing's syndrome, the cytoplasmic basic structures were well maintained by ACTH. The optimum concentration, 0.02IU/ml of ACTH, increased the size and number of mitochondria and SER.
7. Adenoma cells from primary aldosteronism included a characteristic myelin-like structure in cytoplasm as well as non-tumor part of the adrenal before and after culture. With ACTH in the media, mitochondria as well as vesicles were enlarged.
8. In hyperplasia from primary aldosteronism, ACTH in the media decreased the size of mitochondria, which looked thinner like threads and the cristae disappeared. Lipid granules were also decreased. The results indicate the factors affecting on hyperplasia of primary aldosteronism other than ACTH.
9. Adenoma cells from adrenogenital syndrome well maintained the original structures in 48 hour to 7 day cultures. By ACTH, at a concentration of 0.02IU/ml in the media, mitochondria and lipid granules increased as well as abundant endoplasmic reticuli.
10. Characteristic myelin-like structures were seen in adenoma cells from primary aldosteronism treated with spironolactone. Similar lamellar structures were also recognized in hyperplasia of Cushing's syndrome and adenoma of adrenogenital syndrome.
11. The myelin-like structures changed the characteristic laminated configuration into fluidlike extension after culture with or without ACTH. This was more prominent in adenoma cells from adrenogenital syndrome, in which the laminated structure showed a closer relationship to SER and RER and the role of functional connection.
The above mentioned results partly disclosed the pathological physiology of adrenocortical hyperfunction, and the present research method was proved to be useful for further clnical investigation.

View full abstract

Blood transfusion is often needed in surgical operation. However, blood for transfusion is insufficient recently and furthermore blood transfusion accompanies a risk of serum hepatitis. Accordingly, various blood substitutes are devised. Plasma volume increasing agent is one of them.
I had used sodium arginate preparation, a plasma volume increasing agent, from 1964 to 1966. In 31 or 65.9 per cent of the 47 cases receiving this preparation an increase of serum nitrogen level probaly due to it was observed. It was remarkable that a variation of serum nitrogen level was relatively small in the patients with normal renal function but radical those with lowered renal function. In addition, 14 of the 47 cases given this preparation died. Four of them autopsied. In all of them basophilic substance was found in tubular spaces of glomeruli and uriniferous tubles in the kidney without combined use of KM.
Thus, I examined the influence of single use of plasma volume increasing agents and antibiotics and combined use of them upon the kidney in rats. Plasma volume increasing agents used were dextran preparation (20ml/day), sodium arginate solution (10ml/day), gelatin preparation (200ml/day) and polyvinylpyroridone preparation (20ml/day). Antibiotics used were SM (200mg/day: half dose in combined use of 2 antibiotics. The same condition was applied to the others), CP (200mg/day), KM (200mg/day) and CL (200, 000u/day). Plasma volume increasing agents were injected into the peritoneal cavity and antibiotics were intramuscularly used. Serum nitrogen level was measured and the kidney was examined histologically.
1) So-called “osmotic nephrosis” was found in rats administered with any of plasma volume increasing agents. This change was most conspicuous in rats injected with sodium arginate preparation. Serum nitrogen level was scarecely influenced by any plasma volume increasing preparations.
2) Serum nitrogen level varied most markedly in rats injected with KM or CL. Histologically all antibiotics caused the change similar to “osmotic nephrosis”. Specially strong change was observed in rats injected with KM or CL.
3) Of combined uses of 2 antibotics the combination of KM and CL had the strongest influence upon serum nitrogen level. All combinations of 2 antibiotics brought about “osmotic nephrosis”. However, this phenomenon was most conspicuous in combinations including CL.
4) Of combined uses of a plasma volume increasing agent and antibiotic the combination of sodium arginate solution and either KM or CL increased serum nitrogen to the highest level. Histologic change of the kidney was also most conspicuous in these 2 combination. The histologic change observed was so-called “osmotic nephrosis” in any combinations of a plasma volume increasing agent and an antibiotic.
5) Serum nitrogen level and histologic change of the kidney were pursuited after stopping the treatment in rats administered with either gelatin preparation or polyvinyl preparation and one of the antibiotics jointly. Serum nitrogen level tended to rise temporarily when KM was combined. It decreased gradually after stopping combined use of CL. The histologic change of the kidney was temporarily strengthened after stopping combined use of KM. Abnormal changes of the kidney returned to normal little by little after stopping combined use of SM, CP or CL.

View full abstract