Influence of differences in tumor vascularity upon the effects of hyperthermia

Summary Utilizing two types of human renal carcinoma heterotransplanted in nude mice, we investigated the variations in hyperthermic effects (42.5°C for 30 min) caused by differences in tumor type with special reference to variations in tumor vascularity. In the hypovascular JRC1 strain, sporadic vascular dilation was observed throughout the tumors after heating. Destruction of tumor cells was observed mainly in the region of dilation. In the hypervascular JRC11 strain, homogenous vascular dilation was observed immediately after heating, mainly at the periphery of tumors. There was a decrease in the viability of cells in the center of the tumor. Therefore, the hypervascular tumors showed greater destruction mainly at the center where blood circulation was reduced. The range of necrosis was also greatly affected by the extent of vascular dilation caused by heating in hypovascular tumors.     

Hard metal asthma: cross immunological and respiratory reactivity between cobalt and nickel?

Eight asthmatic patients with hard metal asthma due to cobalt underwent bronchial provocation challenge with nickel sulphate. Seven patients developed a fall in FEV1 of 20% or more after inhaling nickel sulphate, four showing an immediate response and three a late response. Eight control subjects, including six asthmatic patients, with no history of hard metal exposure, showed no bronchoconstriction in response to a provocation challenge with nickel sulphate. Specific antibodies to nickel conjugated human serum albumin were present in four of the eight patients with sensitivity to cobalt conjugated human serum albumin but were absent from the serum of 60 unexposed asthmatic patients and 25 exposed symptom free workers. These results suggest that nickel as well as cobalt sensitivity plays a part in hard metal asthma.     

Growth factors induce actin disruption in cultured human retinal pigment epithelial cells

Exposure of cultured human retinal pigment epithelial cells to platelet-derived growth factor, nerve growth factor or epidermal growth factor resulted in a time- and dose-dependent alteration in the distribution of actin stained by rhodamine-phalloidin. These growth factors (platelet-derived growth factor of 80 ng/ml, nerve growth factor of 10 ng/ml or epidermal growth factor of 10 ng/ml) caused disappearance of actin filaments from the peripheral region of a cell in 1 or 2 h and change of cell configuration to spindle shape in 3 or 4 h. Other growth factors, fibroblast growth factor of 10 ng/ml and insulin of 25 mumol/ml had no effect on actin distribution. The alteration of actin and the change of cellular shape might be associated with stimulation of cell growth and migration of retinal pigment epithelial cells.     

Dual effects of 5-hydroxytryptamine on the release of gamma-aminobutyric acid from myenteric neurones of the guinea-pig ileum.

The effects of 5-hydroxytryptamine (5-HT) on the release of gamma-aminobutyric acid (GABA) were examined in the longitudinal muscle-myenteric plexus (LM-MP) preparation of guinea-pig ileum. 5-HT increased the spontaneous release and inhibited the electrically-evoked release of [3H]-GABA. The 5-HT-evoked release was Ca2+-dependent and tetrodotoxin-sensitive, and was antagonized by (3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester (ICS 205-930), but not by methysergide and ketanserin. The inhibitory effect of 5-HT was antagonized by methysergide, but not by ketanserin and ICS 205-930. 8-Hydroxy-2-(di-n-propylamino)tetralin mimicked the inhibitory effect of 5-HT. Thus, 5-HT may exert an excitatory effect on the enteric GABAergic neurone via the 5-HT3 receptor and an inhibitory effect via the 5-HT1A receptor.     

A phase II study of epirubicin in acute leukemia: a cooperative group study

A new doxorubicin analogue, epirubicin (EPI), was evaluated in 41 patients with acute leukemia at 11 Japanese institutions participating in a phase II study between January 1983 and July 1985; during this period 35 patients were considered evaluable. There were 25 males and 10 females with a median age of 43 years (range, 19-71 years) and the median PS of 2 (range, 0-4). EPI was given to 25 patients who had previously been treated with intensive combination chemotherapy, of whom 22 had already received anthracyclines. Ten patients had not been treated previously. Two dose schedules were explored. The higher dose schedule (18 cases) consisted of the administration of 24 to 60 mg/m2 for 3 to 5 consecutive days, and the lower dose schedule (17 cases) consisted of 11 to 20 mg/m2 for 5 to 7 days. Remissions were obtained in 7 patients (20%), 2 of whom showed complete remission and 5 partial remission. The remission duration was 2, 2, 3, 5, 16, 16 and 29+ weeks, respectively. The expected myelosuppression was universal. Stomatitis occurred in 15 patients, of which 7 cases were severe. This stomatitis occurred frequently in the higher dose schedule, and was thought to be a dose-limiting factor. In others, alopecia, G.I. symptoms, and diarrhoea (4 patients) were seen. These results from a cooperative group study indicated that EPI was an effective drug for the treatment of acute leukemia.     

Intracranial MR imaging of achondroplasia]

Intracranial MR imaging was performed in five patients with achondroplasia. All patients had narrowing of the subarachnoid space at the level of the foramen magnum that was mainly due to protrusion of the posterior aspect. Three patients had compressive deformities of the brainstem and/or upper cervical spine. Among them, two patients had deformities of the pons. Relative upward displacement of the brainstem was seen in all patients. Hydrocephalus was seen in three patients.     

Clinical evaluation of antithrombin III concentrate (BI 6.013) for disseminated intravascular coagulation in obstetrics. Well-controlled multicenter trial

Antithrombin III (AT III) is known to be the most important inhibitor of serine protease in the coagulation system. In the presence of heparin, AT III is converted from its progressive activity state to an immediate activity state. In disseminated intravascular coagulation (DIC) in the field of obstetrics, the treatment has to be initiated very early. Heparin treatment, on the other hand, is critical since frequently postpartal or postoperative wound bleeding is present. We, therefore, established diagnostic criteria for the early diagnosis of DIC and investigated the clinical efficacy of a therapy with AT III in a well-controlled comparative study versus the injectable synthetic protease inhibitor FOY. The results of the trial showed that the AT III group (92%; n = 24) was significantly (p less than 0.001) superior in clinical efficacy to the FOY group (60%; n = 15). No side effects whatsoever were observed after treatment with AT III concentrate (Behring Institute). From these results, it could be concluded that a single therapy with AT III concentrate can sufficiently control the symptoms of DIC in the field of obstetrics without the risk of increased bleeding.     

Polymorphisms in ADAM33 are associated with allergic rhinitis due to Japanese cedar pollen

BACKGROUND: A recent report provided evidence that a disintegrin and metalloprotease domain 33 (ADAM33), a member of the ADAM family, is a novel susceptibility gene in asthma linked to bronchial hyper-responsiveness. However, there has been no investigation of the genetic role of ADAM33 variants in nasal allergy. OBJECTIVE: The purpose of this study was to test the association between ADAM33 polymorphisms and Japanese cedar pollinosis (JCPsis), a most common seasonal allergic rhinitis in Japan. METHODS: We conducted a case-control association study among a Japanese population, involving 95 adult individuals with JCPsis and 95 normal healthy controls. A total of 22 single-nucleotide polymorphisms (SNPs) in ADAM33 were genotyped using PCR-based molecular methods. RESULTS: Six SNPs of ADAM33 gene, three in introns (7575G/A, 9073G/A and 12540C/T) and three in the coding region (10918G/C, 12433T/C and 12462C/T), were strongly associated with JCPsis (P = 0.0002-0.022 for absolute allele frequencies) and most of the SNPs were in linkage disequilibrium with each other. A higher frequency of the common alleles of these SNPs was noted for the subjects with JCPsis in comparison with healthy controls. We also identified a haplotype associated with the disease susceptibility. In addition, associations were found between ADAM33 polymorphisms and various cedar pollinosis phenotypes including clinical severity, eosinophil counts in nasal secretion and allergen-specific IgE levels in sera, but not total serum IgE levels. CONCLUSION: These results indicate that polymorphisms in the ADAM33 gene are associated with susceptibility to allergic rhinitis due to Japanese cedar pollen, but the functional relationship still needs clarification.