Akikuni Yagita

Evaluation of antitumor activities of hyaluronate binding antitumor drugs: synthesis, characterization and antitumor activity.

To enhance the selective delivery of antitumor drugs into regional lymph nodes and cancerous tissues via a hyaluronate (HA) receptor (CD44), we synthesized HA-mitomycin C complex and HA-epirubicin complex. To investigate the specific distribution of HA into regional lymph nodes and to evaluate the HA receptor on lewis lung carcinoma cells, we also synthesized 14C-labelled HA and fluorescent HA (FR-HA). The metabolic studies of 14C-HA and HA-epirubicin complex were performed in rats. The specific distribution of both compounds to the lymph nodes were observed after sc treatment. Internalization mechanisms of HA into carcinoma cells (lewis lung carcinoma) via HA receptor was investigated using fluorescent HA (FR-HA) in vitro. Internalization of FR-HA following binding to the cell surfaces was observed. HA-Mitomycin C (MMC) exhibited potent anti-metastatic effects against lewis lung carcinoma implanted in mice at an extremely low dose (0.01 mg/kg) whereas free MMC had no effects.

Analysis of genes within the HLA region affecting susceptibility to ulcerative colitis

To clarify the molecular relationship between HLA loci and ulcerative colitis (UC) in Japanese patients, we performed HLA-DP genotyping by the PCR-RFLP method and studied tumor necrosis factor beta-chain genetic polymorphism by Southern hybridization, in addition to conventional serologic typing. Significant increase was observed in Bw52, DPw9 (DPB1*0901), and DR2 (DRB1*1502) in Japanese patients with UC. Linkage analysis indicated that A24-Bw52-DR2-DPw9 alleles constitute a common haplotype in Japanese UC patients. Among the patients not carrying Bw52, B13 was significantly increased and B44 was relatively increased. These Bw52, B13, and B44 alleles share the unique amino acids, serine and aspartic acid at positions 67 and 77, respectively. These positions are in the second hypervariable region of the alpha 1-domain of the HLA-B13, B44, Bw52, and B49 antigens (B49 is quite rare in the Japanese population). The inflammatory region in UC patients was found to vary depending on their HLA-B alleles. These results suggest that the HLA-B locus itself plays an important role in the susceptibility to Japanese UC.

Granulomatous cheilitis and Crohn's disease

A case of granulomatous cheilitis is reported in whom investigations showed intestinal involvement compatible with Crohns disease, although the patient had no gastrointestinal symptoms.

Linear IgA bullous dermatosis associated with rheumatoid arthritis.

A case of linear IgA bullous dermatosis associated with rheumatoid arthritis is described. The eruption consisted of multiple irregular erythematous plaques and small numbers of tense vesicles mainly on the trunk. An immunofluorescence study showed linear IgA and IgG deposition along the basement membrane zone, whereas C3 deposition was not found. IgA or IgG anti-basement membrane zone antibody was not detected in the serum. Treatment with dapsone resulted in good control of the eruption. Coexistence of linear IgA bullous dermatosis and rheumatoid arthritis has not been reported previously.

Erythema nodosum, Lichen planus and Lichen nitidus in Crohn’s Disease: Report of a Case and Analysis of T Cell Receptor V Gene Expression in the Cutaneous and Intestinal Lesions

A wide variety of cutaneous manifestations have been described in association with Crohns disease (CD). We describe a patient with a 2-year history of CD who developed both lichen planus (LP) and lichen nitidus (LN) in addition to erythema nodosum (EN) lesions. The clinical course of EN reflected the activity of the bowel disease, whereas LP and LN appeared to persist independently of the ongoing disease activity. Immunohistochemical studies of the infiltrates in these cutaneous and intestinal lesions showed that the majority of the infiltrates were T cells expressing T cell receptor (TCR)-alpha beta. Analyses of TCR V gene expression in these infiltrating T cells demonstrated a different pattern of V beta expression that provides an explanation for the difference in the clinical courses of these lesions. LP and LN lesions are likely to be mediated by T cells with antigen specificity distinct from those that cause EN and intestinal lesions.

Lichen spinulosus in a patient with Crohn's disease.

ridging. The roseate color was seen through the nail plates. No other developmental defects were observed. On laboratory examination, erythrocytes, white blood cell count, hemoglobin, hematocrit, erythrocyte sedimentation rate, serum protein electrophoretic pattern, blood sugar, serological test for syphilis, urinalysis, stool examinations for parasites, fungus culture, trichomonas, and chest roentgenograms were negative or within normal limits. A biopsy of the lower lip was refused by the patient.

Mouse Colitis Induced by Escherichia coli Producing Yersinia enterocolitica 60-Kilodalton Heat-Shock Protein (Light and Electron Microscope Study)

In patients with inflammatory bowel disease(IBD), including ulcerative colitis (UC), heatshockprotein (Hsp) 60 has been detected in serum and theintestinal tract. Our mouse colitis model wasestablished using Escherichia coli transformed withYersinia enterocolitica Hsp60 gene as an immunizingantigen, and examined light and electron microscopicallyas compared with lesions of UC. The large intestine of mice injected with Hsp60 antigen showed swollengoblet cells, glandular dilation, erosion, ulceration,and infiltration of inflammatory cells. The change likecrypt abscesses was also found, and various phases of inflammation were observedsimultaneously in individual mice. In addition, thereticulum fibers were absent ultrastructurally in thesubepithelial reticular layer. Hyperplasia of the thymuswas found in antigentreated mice. These lesionswere similar to those of UC. These results suggest thatUC-like enteritis in mice was induced by using Hsp60,considered as one of the pathogens for UC.

Complete resolution of psoriasis vulgaris after excision of thyroid cancer.

A 61‐year‐old woman was seen with a 1‐month history of a widespread eruption over the trunk and extremities. She also had an asymptomatic tumor in the neck that had developed 8 years earlier. Examination revealed generalized, erythematous scaling plaques over the trunk, arms, and extremities (Fig. 1). An ultrasound and radioisotope scan of the neck disclosed a soft tissue mass compatible with thyroid carcinoma.