STUDIES ON PEPTIDES

The octacosapeptide amide corresponding to the entire amino acid sequence of chicken VIP was synthesized in a conventional manner, using a new arginine derivative, N^G -mesitylene-2-sulfonylarginine, Arg(Mts). Treatment of a fragment, Z(OMe)-Thr-Asp-Asn-Tvr-NHNH₂ with methanesulfonic acid or HBr was found to give a product with a low recovery of Asp, after aminopeptidase digestion. Ring closure of the Asp-Asn unit seemed to be responsible for this phenomenon. Deprotection with HF or TFA exhibited definitely less such a tendency. In the final step of the synthesis, all protecting groups, including the Mts group, were removed by HF in the presence of m-cresol and the deprotected peptide was purified by ion-exchange chromatography on CM-cellulose followed by isoelectric focusing in Ampholine pH 9–11. Synthetic peptide exhibited the identical Rf value with that of natural chicken VIP and was active as the natural peptide.     

Complex of subtilisin BPN‘ with Streptomyces subtilisin inhibitor

Structure of the complex of Streptomyces subtilisin inhibitor (SSI) with subtilisin BPN' was studied by examining the thermal denaturation and reducibility of disulfide bonds. The denaturation temperature of the complex was significantly higher than that of the enzyme. Two disulfide bonds localized in the inhibitor side were completely reduced in the complex, whereas only one of them was reduced in the free SSI. Gel filtration of the reduced complex solution showed clearly that the main products of reduction of the complex were two peptide fragments of SSI divided at the active site. The resistive disulfide bond in the complexed inhibitor became accessible as a result of a large conformational change due to splitting of the half-reduced inhibitor.     

Extramedullary Plasmacytoma of the Mediastinum

A case of extramedullary plasmacytoma originating from the uppermediastinum is described. Its pathologic, cytologic and immunohistopathologicfindings were distinctive. The neoplastic cells had dense bodiesin the cytoplasm. Neither M-protein in the serum nor Bence Jonesprotein in the urine was detected. However, cellular IgG, havinga lamda-type light chain was shown, by immunohistochemical stainingfollowing trypsin digestion, to be present in the tissue sections.     

An early gallstone clearance following repeat piezoelectric lithotripsy

Piezoelectric extracorporeal litotripsy was performed in 128 symptomatic patients with radiolucent gall-bladder stones to assess the significance of disintegration in fragment clearance. Up to 10 repeat lithotripsy sessions were scheduled to achieve a fragment target size of <3 mm. Fragmentation assessed by the size of the largest fragments after the last session was graded into three classes. I: sludge-like disintegration, 18%; II: <3 mm (mean ± s.d., 1.7 ± 0.5 mm), 56%; and III: < 3 mm (3.3 ± 0.6), 26%. All patients were initially subjected to lithotripsy alone. Bile acid dissolution therapy was started only when ultrasonography failed to show the evidence of decrease in the <3 mm fragments during a 1 month follow up. Finally, 69 patients (54%) were treated by lithotripsy alone, and the remaining 59 received additional dissolution therapy at a mean period of 2.5 months after the initial lithotripsy. The rate of complete clearance in class I, II and III patients was 91, 42 and 10% at 6 months and 100, 68 and 49% at 18 months, respectively. Significant differences were noted between the three fragmentation grades (I vs II, III, P <0.0001; II vs III, P <0.02). The patients with complete clearance within 6 months were seen only in those treated by lithotripsy alone, while the majority (87%) of patients with complete clearance during the later period were seen in those treated by additional dissolution therapy. We conclude that a high degree of fragmentation appears to lead stones to an earlier period clearance, and reduce the need for dissolution therapy.     

CT examination of the manipulation system in the giant panda (Ailuropoda melanoleuca)

The manipulation mechanism of the giant panda ( Ailuropida melanoleuca ) was examined by means of CT (computed tomography) and 3-dimensional (3-D) Volume Rendering techniques. In the 3-D images of the giant panda hand, not only the bones but also the muscular system was visualised. Sections of the articulated skeleton were obtained. It was demonstrated that the hand of the panda is equipped with separately moulded manipulation units as follows: (1) the radial sesamoid (RS), the radial carpal, and the first metacarpal (R–R–M) complex; and (2) the accessory carpal (AC) and the ulnar (A–U) complex. When the giant panda grasps anything, the R–R–M complex strongly flexes at the wrist joint, the RS becomes parallel with the AC, and the phalanges bend and hold the object. It is shown that the well-developed opponens pollicis and abductor pollicis brevis muscles envelop and fix the objects between the R–R–M complex and the phalanges during grasping.     

Combined assessment of chronic kidney disease and subclinical peripheral artery disease used to predict future cardiac events

Background: Both the presence of peripheral arterial disease and chronic kidney disease has been reported to be independent risk factors associating with poor prognosis. However, the impact of combination of peripheral arterial disease and chronic kidney disease remains unknown. Methods: The long‐term outcome in 715 consecutive patients who had undergone coronary angiogram for the evaluation of chest pain was analyzed. Patients on haemodialysis were excluded from this analysis. Cohort patients were divided into four groups according to the Ankle Brachial Index (ABI <0.9) and glomerular filtration rate (GFR <60 mL/min per m²): group A (n= 498; ABI >0.9, GFR >60); B (n = 65, ABI <0.9, GFR >60); C (n = 99; ABI >0.9, GFR <60); and D (n = 53; ABI <0.9, GFR <60). The mean follow‐up period was 620 ± 270 days and evaluated the major cardiac adverse events included survival, stroke, acute coronary syndrome and heart failure. Results: The mean follow‐up period was 620 ± 270 days. Total long‐term event was present in 89 patients (groups A–D were 9.4%, 18.5%, 15.2% and 28.3%, respectively). Long‐term event rate was 28.3% for patients with the presence of peripheral arterial disease and chronic kidney disease, compared to 9.4% for those without peripheral arterial disease and chronic kidney disease (P < 0.0001). Kaplan–Meier event‐free survival curves also showed that the combination of peripheral arterial disease and chronic kidney disease predicted long‐term event rate. Conclusion: The combination of chronic kidney disease and ABI of less than 0.9 undergoing coronary angiogram is strongly associated with long‐term event rate.     

Inhibition of Cytotoxicity to Autologous Tumor Cells by the Regional Lymph Node Cells of Patients with Primary Lung Cancer

The regional lymph node (RL) cells of patients with primarylung cancer exhibited no cytotoxicity to autologous tumor cellsin a 4-hr ⁵¹Cr-release assay, but when cultured in the presenceof Interleukin 2 (IL2), the RL cells did become cytotoxic tothose target cells. When RL cells were included in a cytotoxictest of IL2-activated RL cells (autologous killer T cells; AK.Tcells) and autologous target cells, the cytotoxicity of theAKT cells was significantly inhibited in 27 out of a total of42 cases, but this suppression was observed against neitherallogeneic effector cells (seven out of nine cases) nor naturalkiller cells (all seven cases tested). The cytotoxicity of AK.Tcells to allogeneic target cells was inhibited by RL cells inthree out of six cases. Nylon-wool column separation indicatedthat the cell population adhering to the nylon wool mediatedthe sup-pressive effect of the RL cells. These data suggestedthe presence of nylon-wool-adherent suppressor cells in theregional lymph nodes of patients with primary lung cancer whichsuppress the cytotoxicity of autologous killer lymphocytes toautologous tumor cells.     

Peptide Hormone Production in Small Cell Lung Carcinomas with Particular Reference to Gastrin-Releasing Peptide

Tissues of 50 small cell lung carcinomas were examined for productionof 17 peptide hormones. Only when the concentration of a peptidedetected in the tumor was 10 pmol or more per g wet weight,was the peptide considered to be produced by the tumor. Thefrequency of production of at least one of these peptide hormoneswas 84%, and that of two or more hormones was 50%. These resultsindicate that peptide hormone production is a very common phenomenonin small cell lung carcinoma. Of the peptide hormones examined,gastrin-re leasing peptide is produced with the highest frequency,suggesting that this pep- tide could play an important rolein small cell lung carcinoma.     

Unicentric Castleman''s disease with leiomyosarcoma: A rare association

A 54-year-old asymptomatic woman was first diagnosed with unicentric Castleman's disease at 51 years of age. The disease was identified incidentally behind the inferior vena cava after a computed tomography (CT) scan. She was followed conservatively and no enlargement of the mass was observed. However, a follow-up CT scan revealed another solid mass in the left retroperitoneal area. Both tumors were surgically removed in the same session. The retrocaval mass was histologically confirmed to be Castleman's disease of the hyaline vascular type. Histological examination of the left peritoneal mass revealed low-grade leiomyosarcoma. We present here a case of leiomyosarcoma associated with unicentric Castleman's disease, both of which were localized in the retroperitoneum.