Granuloma pouch and skin histamine of the rat

Using the granuloma pouch technique of SELYE, effect of modification in local histamine on the inflammatory tissue reactions was examined in rats. The increase in the weight of pouch wall and histological inflammatory changes were distinctly inhibited in either case of histamine depletion by sinomenine and of desensitization to histamine by repeated injections of histamine. In rats injected with aminoguanidine, the skin and local histamine contents increased in similar degree as those in rats receiving histamine injection, but the inflammatory tissue reactions were severer than in the control. The total histamine of the pouch wall during inflammation reached the maximum four days after the injection of croton oil and decreased thereaftcr. The prcliferative processes indicating the recovery of injured tissues in later stages of the inflammation were the most vigorous in rats treated with histamine and this was in contrast to the extreme weakness of this tendency in animals in which the local histamine had been depleted. These observations not only suggests the fairly close relationship of histamine to carly reaction of inflammation but also indicates the role of histamine in its recovery processes.</p

Effect of histamine releasers and of anti-inflammatory drugs on the egg-white edema of rat's hind paws in relation to skin histamine

1. A method was described for a fairly accurate judgement of the effect of drugs inhibiting the edema in hind paws of a rat caused by local injection of egg white. 2. The degree of inhibition of egg-white edema by single doses of sinomenine, compound 48/80, or dextran was in parallel with histamine reduction in skin and other tissues of the paws (and the skin of abdomen), although prevention of the edema by prolonged treatment with sinomenine was incomplete even when the releasable histamine of the skin was practically exhausted. 3. Sodium salicylate, aminopyrine, butazolidine sodium, cortisone, and guaiazulene were capable of inhibiting egg-white edema without modifying the content of skin histamine. These drugs and a small dose of phenergan potentiated the inhibition by dextran of egg-white edema and inhibited the release of histamine by dextran. These actions lasted for over 24 hours with the exception of guaiazulene. 4. Irgapyrin and a large dose of phenergan, which possess actions of histamine release and of histamine release inhibition and also antihistaminic action, caused a slight reduction of skin histamine and a comparatively marked inhibition of the edema. 5. In adrenalectomized or hypophysectomized rats, the edema-inhibiting effect of salicylate and aminopyrine decreased but that of cortisone increased. The effect of guaiazulene remained unchanged. 6. The observations that inhibition of egg-white edema is caused by (a) histamine releasers, (b) histamine-release inhibitor, and (c) drugs exerting both histamine release and inhibition of the release were discussed with the consideration to a relationship between egg-white edema and skin histamine.</p

Clinical evaluation of endolymphatic radiotherapy in malignant lymphoma

By endolymphatic injection of radioisotope 131I.Lipiodol, so.called endolymphatic radiotherapy, we treated 10 cases with malignant lymphoma and found a marked tumor reduction to normal size in all the 10 cases we tried. It seems that this method is one of the most effective therapeutic methods for malignant lymphoma, espe. cially invading into the retroperitoneal lymph nodes.</p

Experimental studies of the endolymphatic radiotherapy

By injecting 131I-Lipiodol into lymphatics of the dorsum of dog feet, the distribution of 13JI in the lymph nodes and other principal organs as well as its histological effect were studied periodically after the injection for the period of two months. The characteristic feature of J3JI distribution was the fact that J31I was accumulated into lymph nodes markedly higher than in any other organs and it was retained there over a long period of time. Histological examinations of the lymph nodes revealed a marked lymphocytopenia, the loss of germinal center, practically complete loss of lymphoid elements already 5 days after injection, and marked fibrosis. In the lung a considerable J3JI·distribution could be seen in early stage:, but with lapse of time it decreased rapidly. The distribution in other organs such as liver, spleen, bone marrow, kidney, ureter, bladder, thyroid gland, pancreas, testicles and small and large intestines was negligible in amount, and any specific histologic effect of irradiation could not be recognized in these organs including the lung. From these results, the authors concluded that 131I-Lipiodol has a selective activity on lymph nodes by injecting it via lymphatics and it is a safe method in clinical application to treat the patients bearing malignant lymphoma or metastatic lymph nodes.</p

The Sites of Action of some Histamin-Releasing Substances in the Dog

1. The rates of histamine release from the liver, skin and muscle by four kinds of histamine-releasing substances, sinomenine, compound 48/80, tween 20 and polyvinylpyrrolidone (PVP), were compared by intravenous injection in dogs, each in a dosage to cause a fall of approximately 80 per cent in the arterial blood pressure. 2. By compound 48/80, the rates were especially marked from the liver and muscle and only slight from the skin, while those by sinomenine, tween 20 and PVP were largest from the skin, followed by those from the liver and muscle, in that order. The rate of histamine release from the skin by PVP was characteristic in that it was far larger than that by other releasers. 3. On direct application of the drug solutions to the excised tissues of the liver and skin the rates of release of histamine differed only slightly by the tissue in any of these releasers 4. Some considerations were given on the reason for the different ratios by the organ of in vivo histamine release though as yet no definite conclusion could be drawn.</p

Histamine release inhibition in anti-inflammatory mechanism

Rats were depleted of skin histamine by more than 80 % by intraperitoneal injections of sinomenine with daily increasing doses for 6 days. In these rats, egg-white edema induced in the hind paws was inhibited by 68 % of control. The weight of the wall of granuloma pouch made by croton oil was also evidently smaller in the rat treated similarly with sinomenine than that of control. This suggests an important role of histamine participating in the inflammation. It has been observed that a variety of non-steroidal anti-inflammatory drugs inhibited both degranulation and histamine release induced by compound 48/80 of mast cells isolated from rat peritoneal fluid. The degranulation inhibiting actions of anti-inflammatory drugs were markedly decreased in the presence of glucose as in cases of dinitrophenol, dicumarol and warfarin which are known uncouplers of oxidative phosphorylation. Also, prevention of edema provoked by anti-rat serum is roughly correlated to a potency of degranulation inhibiting effect of anti-inflammatory agents. These observations suggest that there is a common mechanism between these two phenomena, and the prevention of mast cell degranulation by the anti-inflammatory agents is, at least, partially due to their uncoupling effects. A working hypothesis explaining the process of edema formation at the inflammatory site has. been made based on the data of the present experiment and other ob3ervations: a leakage of plasma into the tissue space from the gap between two adjacent endothelial cells which are contracted by released histamine may activate a kinin-forming system in the plasma, and kinin(s) may further aggravate a leakage. The mechanism of action of anti-inflammatory agents, which interfere with the histamine effect in inflammation, should be understood in twofold: one is prevention of histamine release from the tissue, mainly by inhibiting mast-cell degranulation, and the other is prevention of the contraction of endothial cells by their uncoupling activities.</p

The Role of Marrow Architecture and Stromal Cells in the Recovery Process of Aplastic Marrow of Lethally Irradiated Rats Parabiosed with Healthy Litter Mates

Bone marrow aplasia was induced in rats by whole body lethal irradiation (1,000 rads by x-ray), and rats died of irradiation injury within 7 days. Correlative studies at light (LM), transmission (TEM) and scanning electron microscopy (SEM) demonstrated swelling of endothelial and reticular cells and hemorrhage due to detachment of sinus endothelial cells on days 1 and 2. With time, structural recovery occurred without hemopoietic recovery. Reticular cells developed small intracytoplasmic lipid droplets on days 3 and 4. This resulted in fatty a plastic marrow within 7 days. On the other hand, in the marrow of irradiated rats parabiosed with healthy mates by aortic anastomosis, hemopoiesis was initiated by adhesion of nucleated blood cells to fine cytoplasmic pseudopods of fat-stored cells on days 1 and 2 after parabiosis. On days 3 to 5, reticular cells with large lipid droplets and fine pseudopods increased, then hemopoietic foci became clear and extensive. On day 8 after parabiosis, the a plastic bone marrow recovered completely both its structure and hemopoietic activity. Thus, hemopoietic recovery in lethally irradiated marrow begins with recovery of vascular endothelial cells, re-establishment of sinusoidal structure, and morphological and functional recoveries of reticular cells from fat-storage cells by releasing intracytoplasmic lipid droplets. Marrow stromal cells, namely reticular, fat-storage and fibroblastoid cells, share a common cellular origin, and regain their structure and function when fat-storage cells and fibroid cells are placed in contact with hemopoietic precursor cells

Determination of ferritin in serum and in synovial fluids of patients with rheumatoid arthritis

Ferritin in sera and in synovial fluids were determined by method of immunoradiometric assay (IRMA) and of radioimmunoassay (RIA). These methods have been proved to be reproducible. The coefficient variation was 7.4 to 9.9% in IRMA and 5.6 to 8.0% in RIA. There were a good correlation between methods of IRMA and of RIA (r=0.989). The mean recovery rate of ferritin in serum was 101.2% in IRMA and 101.0% in RIA, respectively. The determination of serum ferritin revealed a 16% reduction in average after preservation at -20℃ during over 100 days. The levels of serum ferritin in healthy controls were 131.4±52.1 ng/ml in 34 males and 58.4±39.9 ng/ml in 38 females. The sex differences were statisticalIy significant (p<0.01). Ferritin levels were shown to be below 30 ng/ml (the state of iron deficiency) in 2 of 34 (5.9%) males and in 8 of 38 (21%) females of healthy controls. The levels of serum ferritin in patients with rheumatoid arthritis (RA) were 337.0±293.4ng/ml in 10 males and 181.4±329.9ng/ml in 25 females. The serum ferritin in RA was significantly higher than in healthy controls of both sexes. The levels of ferritin in synovial fluids of patients with 14 RA and with 12 osteoarthritis were 2894±3017 ng/ml and 1429±1005 ng/ml, and no differences were observed in both groups

Antitumor activity of neocarzinostatin, effect on Rauscher leukemia in mice

Neocarzinostatin (NCS), an antibiotic with a high molecular weight, showed an inhibittory effect on Rauscher mouse leukemia. In normal mice, no significant changes were found in peri· pheral blood pictures except a tendency of lymphocytopenia, when O. 05mg/kg/day and O.50mg/kg/day of NCS were injected intraperi. toneally to two groups of mice for three days. On the other hand, peripheral nucleated cells of Rauscher leukemic mice decreased after intraperitoneal administration of NCS in a dose over O.25mg/kg/day for three days. The cells affected by NCS were mainly erythroblasts and smudged cells. Spleens of Rauscher leukemic mice treated with NCS have been reduced in weight, and histological examinations of livers showed a signicant decrease of infiltrating cells. In three groups treated with 0.25mg/kg/day of NCS for seven days, O.25mg/kg/day for three days and O.50mg/kg/day for three days, the.5()% survival time was longer than in the control group. Particularly, the 50% survival time in Rauscher leukemic mice treated with 0.50 mg/kg/day for three days was over twice that of the control group.</p

A case of SLE with non-erosive joint deformity -Jaccoud's type arthropathy-

A case of SLE in a twenty-eight year old woman, who had polyarthritis with non-erosive joint deformity, was reported. Differential diagnosis in this case included (1) rheumatoid arthritis (2) postrheumatic fever arthritis (Jaccoud's arthritis) and (3) the overlap syndrome between SLE and rheumatoid arthritis. Laboratory findings on this patient and review on literature, however, strongly suggested that this lady had been suffering from Jaccoud's type arthropathy of SLE. Corticosteroid therapy was initiated and the clinical course of the patient thereafter has been more than favorable