The pharmacological mechanism, and adverse effect of colchicine are described. In addition diseases which are treated with colchicine are also reported. Colchicine inhibits chemotaxis of polymorphonuclear leukocytes by blocking the assembly of microtubules. Colchicine is effective in Behcet's disease, primary biliary cirrhosis, amyloidosis, and gout. One mg of colchicine is enough as an initial dose at acute attack of gout. Colchicine should be continued for additional couple of days. There had been no effective medicines for the ocular symptoms of Behcet's disease. However, almost two-thirds of the patients with this disease responded well to colchicine. And today many doctors prescribe colchicine for the treatment of Behcet's disease. Colchicine might be used for other intractable diseases.

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Carnosine, which is a physiologically active against that promotes granulation, a tissue reaction with high potentials of immunity and tissue repair, was discovered. The agent was then found to accelerate tissue repair, regulate antibody production, and increase nonspecific immune activities. With clinical observation of these effects, carnosine was confirmed to have spontaneous healing stimulative action. We also observed a significant increase in T/C (%) in animals carrying transplanted tumor when treated with carnosine. This paper summarizes these findings, shows the importance of the connective tissue function in the control of cancer, and suggests that resistance of the host against cancer is provided not by individual attacking factors but by integrated effects of defensive functions.

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Although rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are intractable diseases due to persistent chronic inflammation, AS showing close association with HLA-B27, negative test for rheumatoid factor and radiologic sacroilitis was demarcated from RA in the newest classification of the rheumatic diseases by the American Rheumatism Association. However, histopathological differences between RA and AS remain unclear.
For purposes of comparison of inflammatory features in the joints from both diseases, 28 autopsies and 35 biopsies from patients with seropositive RA and 1 autopsy and 4 biopsies from patients with AS were studied histopathologically.
The following results were obtained: villous hyperplasia of the synovium, synovial lining cell hyperplasia, superficial fibrin deposition were found in both diseases. But scanty plasma cell infiltration around lymphoid cell aggregation, strong tendency to granulomatous inflammation accompanied by ossification and absence of rheumatoid nodules in the articular tissues of AS were distinct from RA.
These studies suggest that histopathological differences between RA and AS may be due to disparity of immunological background in both diseases.

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To investigate a physiological function of substance P (SP) presenting in the peripheral ending of sensory neurons, we determined radioimmunoassayable SP (iSP) level in the subcutaneous perfusate and the volumes of edema evoked in rat paw by noxious heat stimulation simultaneously. Results obtained were as follows: Immersion of the rat paw into hot water (47°C) for 30 min led to a significant increase of iSP in the perfusate and about 50% increase in the paw volume. The increasing effects were abolished after neonatal pretreatment with capsaicin, acute and chronic denervation of the sciatic and saphenous nerves. Intraplantal injection of SP evoked an increase in the paw volume in dose-dependent manner. This increasing effect of SP on the paw volume was more remarkable than that of histamine. The increase in the heat-evoked iSP release and edema volume were significantly inhibited by pretreatment with stem bromelain and emorfazone, and by pretreatmet with dexamethasone. A time lag was necessary for a manifestation of the inhibitory effect of dexamethasone, and this inhibitory effect of the steroid was abolished after the simultaneous application of actinomycin D.
These results suggest that (1) SP produced by noxious heat stimulation in the periphery may be released from the afferent fibers and (2) bradykinin and prostaglandins may intervene in this SP release, and (3) SP released in the periphery may be closely related to the edema formation of the thermal injury reaction.

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For the purpose to study on the distribution and role of polymorphonuclear leukocytes (PML) in the junctional epithelium (JE) in gingivitis, morphological changes of the rat molar JE following topical application of sterile saline, squid ink, latex particles, hyaluronidase and lipopolysaccharide were examined by light and electron microscopy. Ultrastructure of the gingival pocket induced by experimental plaque accumulation on the rat molar teeth was also studied. Small numbers of PML were always revealed under phygiologcal condition in the JE and gingival sulcus, while they rapidly increased in number and extent of distribution after topical application of those substances. In the gingival pockets, regardless of their depth or width, and pocket-lining epithelium, numerous PML were also present and formed a dense layer surrounding the bacterial plaque. Desmosome-like structures were often demonstrated on the closely adjoining cytoplasmic membranes between PML around the plaque. PML within gingival sulcus and/or pocket were often found to phagocytose bacteria, squid ink and latex particles. These observations strongly suggested that PML in the JE, gingival sulcus, and even in the gingival pocket as well as the pocket epithelium might form a strong protective barrier against the irritants from the oral cavity.

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We assessed natural killer (NK) cells in the peripheral blood of 55 patients with ocular Behçet's disease.
The numbers of NK cells as well as their activity were measured by immunofluorescence employing three monoclonal antibodies and ⁵¹Cr release assay using K 562 cells, respectively.
A numerical abnormality of NK cells was present especially in the remission stage. Most of NK cell activity, on the contrary, were limited to the normal range independent of disease activity.
In light of clinical ocular activity, a close relationship between the frequency of the fundus type ocular attacks and the numericl abnormality of NK cells was suggested. It is also suggested that NK cell activity might be an indicator of disease activity with respect to the ocular attacks, since a significant (p<.05) decrease was found to occur over a seven-day period following the onset of the ocular attacks.
The results seem to support the hypothesis that an abnormality in both the numbers and the activity of NK cells in patients with Behçet's disease might be related to the disease itself.

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Endotoxin-activated serum, but not endotoxin or serum alone, had a stimulatory effect on acetyltransferase activity (AT) of neutrophils, which is a key enzyme in biosynthesis of platelet-activating factor. The AT stimulatory factor in endotoxin-activated serum was heat-stable, undialysable, and its activity was linear to that of endotoxin between 0.05-5μg/ml. Zymosan-activated serum, which is known to contain a substantial amount of C5a, induced superoxide anion production and degranulation of neutrophils, but did not elevate the AT level of neutrophils. On the other hand, endotoxin-activated serum did not induce superoxide anion production or degranulation. These findings provided evidence against the role of C5a in induction of AT. Sephadex G-200 gel chromatograhy and protein A affinity chromatograhy suggest that modified IgG molecules play a role in elevating the AT level of neutrophils.

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Copper, zinc-superoxide dismutase (Cu, Zn-SOD) was purified from rat liver using Tsuchihashi fractionation, acetone treatment, ion exchange chromatography (DE-52, CM-52) . The purified enzyme showed 2bands in polyacrylamide gel electrophoresis (PAGE), but in SDS-PAGE and isoelectric focusing showed a single band (M.W. 16, 000, pH 5.1) . It was found that Cu, Zn-SOD had electrophoretic variants and there was no immunological difference among the variants.
Immunolocalization in various organs of rat was investigated using antiserum against Cu, Zn-SOD. Localization in rat organs was almost the same as that in human, previously reported.
Cu, Zn-SOD was seen in the cells which function was related to the transport of electrocyte and water in the cases of parietal cells, duct epithelium of salivary gland and pancreas, intrahepatic biliary duct, epithelium of intestine, distal convoluted tubles and Henle's loops.
Futhermore, localization of the islets of Langerhans and the medulla in adrenal gland may show that superoxide radical plays a role in the function of the endocrine cells.
On the other hand, localization in the SOD positive cells was found in the cytoplasm and partially in the nucleus. SOD in the nucleus may protect the nucleic acid from the damage by superoxide radical.
In conclusion, superoxide radical and SOD plays an important role in various organs.

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Clinical features of infections were observed in various types of primary functional disorders of neutrophils and monocytes in childhood. The patients included 5 with congenital neutropenia, 4 with lazy-leukocyte syndrome, 8 with hyper-IgE syndrome, 2 with defective neutrophil chemotaxis with hyper-IgM, 1 with Shwachman syndrome, 2 with Chédiak-Higashi syndrome, 1 with Strauss type of neutrophil dysfunction, and 4 with monocyte dysfunctions. Respiratory tract infections, purulent lymphadenitis, superficial abscesses, and otitis media were frequent in all types of the neutrophil disorders, and candidiasis was the most prominent infection in the monocyte disorders. It was noted that gingivitis was almost persistent and aphthous stomatitis was recurrent in congenital neutropenia and superficial abscess was the most frequent infection in hyper-IgE syndrome. Staphylococcus aureus constituted 55.0% of the pathogenic microorganisms cultured from the throat or pus samples. Gram-negative bacteria and fungi were also cultured from the infected sites. The knowledge of such clinical features of infections provides some useful information for the appropriate treatment of infections in primary functional disorders of neutrophils and monocytes.

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The effect of short and long term administration of ciclosporin (CYA) on renal functions and morphological changes were studied using Sprague Dawley rats. Serum concentrations of blood urea nitrogen and urinary excretion of N-acetyl-β-D-glucosaminidase (NAG) were increased when a high dose of CYA was administrated for a short term or a low dose of CYA for a long term. Main morphological features of the kidneys were as follows, tubular vacuolization, necrosis, and microcalcification with the dose of 25 mg/kg/day for 10 weeks or 100 mg/kg/day for 1 week, but renal lesions such as glomerulopathy, interstitial fibrosis, interstitial mononuclear cell infiltrates and arteriolopathy were appeared with the dose of 5 and 10 mg/kg/day for 24 weeks. These nephrotoxicity induced by CYA was irreversible and may be caused by disturbance of microcirculaton of nephron.

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Non-steroidal antiinflammatory drugs (NSAID) produce the acute gastric mucosal lesions in relation to the inhibition of prostaglandin (PG) biosynthesis in animals and humans. We tested the effect of pranoprofen and indomethacin on gastric mucosal damage and mucosal PGE₂ and prostacyclin (PGI₂) levels in a same antiinflammatory dose (ED₅₀ on the carrageenin-induced foot edema) in rats. The animals were intragastrically given pranoprofen three times before sacrifice in a dose of 0.58 mg/kg or indomethacin in a dose of 3.8 mg/kg. Endogenous PGE₂ and PGI₂ in fundic mucosa were determined by radioimmunoassay. Pranoprofen is less potent than indomethacin to produce the gastric mucosal lesions. The PG levels were not reduced in rats given pranoprofen but were markedly reduced in rats given indomethacin. These results suggest that the ulcerogenicity of pranoprofen is less potent than indomethacin, and this difference may be related to the PG levels in rat gastric mucosa.

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Pathogenesis of phorbol myristate acetate (PMA) -induced lung injury was cytochemically investigated. The neutrophil number of lung lavage cells in PMA-intravenously injected rabbits significantly increased, whereas no change was demonstrated in the absolute number of alveolar macrophages (AM) . Active oxygen (AO) -producing neutrophils and AM in lung lavages increased in number after the PMA-treatment. Neutrophils showed stronger AO-generating potency than AM. These results suggest that AO derived from activated neutrophils, but not AM, causes the PMA-induced lung injury.

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The role of PAF as a chemical mediator has not been fully elucidated. In the present investigation, we examined the effect of PAF on the anaphylactic release of histamine, SRS-A and LTC₄ in passively sensitized guinea-pig lung tissue.
Male guinea-pigs were killed. The lungs were removed, minced and rinced by Krebs-Henseleit solution. The minced lung tissues were passively sensitized by incubating with γ-globulin. Then the sensitized lung tissues were challenged by ovalbumin. Histamine and SRS-A were assayed by tissue bioassay system. LTC₄ was assayed by radioimmunoassay method.
It is concluded that PAF increases the release of histamine and SRS-A from passively sensitized guineapig lung tissue by the antigen challenge. In the same way, PAF increases the release of LTC₄.

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