The immunogenicity and heterogeneity of Pseudomonas pseudomallei surface antigen 8

Surface antigen 8, one of pathogenicity factors of P.pseudomallei and having an antiphagocytic action, contains glycoprotein with a mol. wt. of 200 kD and proteins with mol wt. of 25, 30 and 34 kD. According to its chemical structure, the carbohydrate part of antigen 8 is the homogeneous polymer of 6-d-D-mannoheptose, and its protein component is a collection of monomer proteins with mol. wt. of 12-120 kD. The consecutive fractionation of antigen 8 by gel and ion exchange chromatography has made it possible to isolate its individual fragments, differing by the collection of antigenic components, as well as by their antiphagocytic and protective activity. Experiments have shown that glycoprotein with a mol. wt. of 200 kD is an active immunosuppressive agent, while protein with a mol. wt. of 34 kD produces a pronounced immunogenic effect.     

N-palmitoyl sphingomyelin bilayers: structure and interactions with cholesterol and dipalmitoylphosphatidylcholine

The structure and thermotropic properties of N-palmitoyl sphingomyelin (C16:0-SM) and its interaction with cholesterol and dipalmitoylphosphatidylcholine (DPPC) have been studied by differential scanning calorimetry (DSC) and X-ray diffraction methods. DSC of hydrated multi-bilayers of C16:0-SM shows reversible chain-melting transitions. On heating, anhydrous C16:0-SM exhibits an endothermic transition at 75 degrees C (delta H = 4.0 kcal/mol). Increasing hydration progressively lowers the transition temperature (TM) and increases the transition enthalpy (delta H), until limiting values (TM = 41 degrees C, delta H = 7.5 kcal/mol) are observed for hydration values > 25 wt % H2O. X-ray diffraction at temperatures below (29 degrees C) TM show a bilayer gel structure (d = 73.5 A, sharp 4.2 A reflection) for C16:0-SM at full hydration; above TM, at 55 degrees C, a bilayer liquid-crystal phase is present (d = 66.6 A, diffuse 4.6 A reflection). Addition of cholesterol to C16:0-SM bilayers results in a progressive decrease in the enthalpy of the transition at 41 degrees C, and no cooperative transition is detected at > 50 mol % cholesterol. X-ray diffraction shows no difference in the bilayer periodicity, position/width of the wide-angle reflections, or electron density profiles at 29 and 55 degrees C when 50 mol % cholesterol is present. Thus, cholesterol inserts into C16:0-SM bilayers progressively removing the chain-melting transition and changing the structural characteristics of the bilayer. DSC and X-ray diffraction data show that DPPC is completely miscible with C16:0-SM bilayers in both the gel and liquid-crystalline phases; however, 30 mol % C16:0-SM removes the pre-transition exhibited by DPPC.     

Combining cyclosporin with chemotherapy controls intraocular retinoblastoma without requiring radiation

Chemotherapy without radiation has not controlled most intraocular retinoblastoma, perhaps because of the common high expression of multidrug resistance P-glycoprotein that we found in retinoblastoma. Cyclosporin blocks P-glycoprotein-induced efflux of vincristine and teniposide in vitro, and possibly modulates responses to carboplatin. To avoid eye irradiation in bilateral retinoblastoma patients with RB1 germline mutations, which incurs a high second malignancy rate, we added cyclosporin A to a vincristine-teniposide-carboplatin protocol and consolidated chemotherapy responses with focal therapy. We scored patients requiring irradiation, enucleation, or focal ablation of central vision as failures. In 21 study patients, the overall relapse-free rate at a median follow-up of 3.3 years was 76%, with a rate of 92% for newly diagnosed and 50% for previously treated, relapsed retinoblastoma. Our results for the most unfavorable tumors with vitreous seeds (86% at 3.5 years) are better than published success rates of irradiation for similar tumors, or irradiation with the same chemotherapy without cyclosporin (45% at 2. 6 years). These results also exceeded our historic success rate with similar chemotherapy without cyclosporin, focal therapy, and/or radiation in 19 equivalently poor-risk patients (relapse-free rate 37% at a median follow-up of 5.6 years, P = 0.032), 16 of whom were previously untreated (relapse-free rate also 37%, P = 0.012). A better outcome occurred with higher cyclosporin blood levels and projected tissue exposure. Cyclosporin did not enhance the usual chemotoxicity. This clinical study suggests that cyclosporin improves the long-term response of retinoblastoma to chemotherapy, possibly by more than one mechanism.     

Effects of nonoxynol-9 on vaginal microflora and chlamydial infection in a monkey model

A 58-year-old male with left renal cell carcinoma and prostatic carcinoma occurring synchronously, is reported. He visited our hospital, because of the high level of serum prostate-specific antigen (PSA) pointed out in a health screening by his company. Prostatic cancer was detected in both lobes of the prostate by needle biopsy specimens and histopathology represented moderately > poorly differentiated adenocarcinoma. Magnetic resonance imaging (MRI) and computed tomography (CT) revealed no cancer invasion beyond the prostate and no lymph node metastasis. Bone scintigram showed no abnormal RI accumulation to bone. Therefore, his prostatic cancer was considered to be at stage B2. Abdominal ultrasound echogram showed the mass lesion in the left kidney. CT and angiogram also demonstrated a left renal tumor. Left radical nephrectomy was performed and histopathology showed a mixed subtype of renal cell carcinoma (stage: pT2b, pN0, pM0). Although 94 cases of double cancers associated with genitourinary organs have been reported in the Japanese literature, only 4 cases of double cancers of renal cell carcinoma and prostatic cancer have been reported.     

Autolytic degradation of skipjack tuna during heating as affected by initial quality and processing conditions

Several factors were studied as affecting protein degradation and texture of skipjack tuna muscle following ambient pressure thermal processing (precooking). These included degree of mushy tuna syndrome (MTS) evidenced in the raw meat, raw meat pH, abusive thawing/holding, and precooking temperature/time. Slurries and intact pieces from frozen skipjack tuna, either tempered for 2 h or thawed and held at 25 °C for 22 h (abusive treatment) were heated at temperatures ranging from 40 to 80 °C for up to 2 h, and also at 90 °C for 1 h, with or without prior adjustment of pH to 5 or 7 to favor cathepsin or calpain activity, respectively. Proteolysis of precooked samples was monitored by Lowry assay and SDS-PAGE; cooked texture of intact meat was measured using a Kramer shear press and by sensory profile analysis. Proteolysis maximally occurred in slurries of skipjack tuna muscle that had been abusively stored (22 h at 25 °C) and adjusted to pH 5 prior to heating at 55 °C. Intact pieces of tuna abusively thawed/held for 22 h with subsequent heating at 55 °C also evidenced the most proteolysis and were the least firm in texture. Raw fish that evidenced higher severity of MTS when raw displayed higher levels of proteolysis prior to cooking, which were further increased after cooking at 55 °C. PRACTICAL APPLICATION: The kinetic data presented here can be used to optimize processing conditions for skipjack tuna canning to minimize textural degradation and optimize quality.     

Platelet aggregation in partially obstructed vessels and its elimination with aspirin

There is a considerable controversy regarding the frequency and significance of vascular lesions in leprosy. Twenty-six cases of leprosy below the age of 40 years, without any local or systemic arterial disease and normal looking hands were subjected to brachial arteriography. One patient had posterior tibial arteriography also. The diagnosis of leprosy was confirmed by histology or bacteriological staining techniques. Biopsy material was studied from the involved areas and similar material was obtained from nine matched control subjects at autopsy. Skin thermometry and reflex vasodilatation was studied in eight cases. Arteriographic abnormalities such as occlusion, narrowing, tortuosity, dilatation, irregularity and incomplete filling were seen in more than two vessels in the hand in 50%, and in the digits in 75% of the cases. The ulnar artery was more frequently involved than the radial. Superficial and deep palmar arches were equally affected. Marked increase in arcuate vessels was noticed in nearly three-quarters of the patients, and in some, arcuate vessles were serving as collaterals. Histologically all sizes of vessles, including the capillaries, showed changes in nearly half the cases. Reflex vasodilation was lost in three cases of dimorphous leprosy and impaired or absent in three out of five cases of lepromatous leprosy. There was no predilection for any form of leprosy to show arterial changes more than the other. This study clearly demonstrates that the arterial involvement in leprosy is very frequent and must be playing an important role in causing mutilation and deformities of hands and feet.     

4-nitro-2-phenoxymethanesulfonanilide (R-805): a chemically novel anti-inflammatory agent

The anti-inflammatory activity of the sulfonanilide, 4-nitro-2-phenoxymethanesulfonanilide (R-805) has been demonstrated in conventional models (carrageenan-induced edema of the rat's paw, UV-induced erythema of guinea-pig skin, adjuvant-induced arthritis of the rat). R-805 differs from most currently available acidic anti-inflammatory drugs in that its functional acidic group is not carboxyl. The relative anti-inflammatory potency of R-805 is comparable to indomethacin. Calculation of acute therapeutic indices (LD50/ED50) for 8 acidic anti-inflammatory drugs show R-805 to possess a more favourable index than the other drugs examined.     

Skip lesions in temporal arteritis

Although isolated foci of arteritis ("skip lesions") are presumed to occur in temporal arteritis, there is little documentation of their existence or significance. We have identified skip lesions in 17 of 60 patients (28%) with temporal arteritis, based on a retrospective and prospective examination of temporal artery biopsy specimens. By examining more than 6,000 serial sections of arteries from patients with skip lesions, we have found foci or arteritis as short as 330 mu in length in an otherwise normal biopsy specimen. Our study emphasizes the need to biopsy long segments of artery, to examine multiple histologic sections, and to perform a contralateral temporal artery biopsy when frozen-section examination of the first side is normal.