Induction of Growth Factor-receptor and Metalloproteinase Genes by Epidermal Growth Factor and/or Transforming Growth Factor-α in Human Gastric Carcinoma Cell Line MKN-28

We examined the effects of epidermal growth factor (EGF) and transforming growth factor-α (TGF-α) on EGF receptor (EGFR) phosphorylation and the expression of mRNAs for oncogenes, growth factors, their receptors and metalloproteinase genes by MKN-28 gastric carcinoma cells which express EGF, TGF-α and EGFR genes. Both EGF and TGF-α stimulated EGFR phosphorylation. EGF and TGF-α induced FOS, MYC and ERBB-2 oncogene expression. Interestingly, EGF increased the expression of mRNAs for TGF-α and EGFR. On the other hand, TGF-α increased TGF-α mRNA but decreased the expression of mRNAs for EGFR and TGF-β. Furthermore, mRNAs for interstitial collagenase, stromelysin and procollagen type I genes were also enhanced after treatment with EGF and TGF-α. These results indicate that EGF and TGF-α successively evoke cascade phenomena which favor tumor progression, invasion and extracellular matrix formation, acting as autocrine growth regulators for gastric carcinomas.     

A trial of the 21-aminosteroid U74006F in a primate model of chronic cerebral vasospasm

The efficacy of U74006F in the prophylaxis of chronic cerebral vasospasm (VSP) was evaluated in a randomized, double-blind, placebo-controlled trial. Forty cynomolgus monkeys were divided by restricted randomization into 2 treatment groups of 20. Five animals from each treatment group were randomized into subgroups 1 and 2. The animals of subgroup 1 were studied pathologically. Brain biopsies of the animals in subgroup 2 were performed and studied with high-performance liquid chromatography (HPLC). The remaining 20 animals supplemented the number studied angiographically. Significant VSP (P less than 0.05) was detected in the majority of vessels from the clot site (right) of both treatment groups. Electron microscopy results showed positive correlation with the angiographic data. When comparing the effects of U74006F to those of the placebo at day 7, there was a significant difference (P less than 0.05) in the degree of VSP in the right extradural internal carotid and right middle cerebral arteries. This resulted from a greater degree of VSP in placebo animals. Two animals developed delayed ischemic deficits, one from each group. The infarct of the U74006F animal was smaller than the infarct in the placebo animal. Although overall changes in phosphagen levels did not reach statistical significance, HPLC analysis of the cortical biopsies did show a decrease in the ATP/ADP +/- AMP ratio of 54% in placebo animals and only 7% in animals receiving U74006F. The middle cerebral arteries of 2 animals were also studied with HPLC.(ABSTRACT TRUNCATED AT 250 WORDS)     

Respiratory viruses and Mycoplasma pneumoniae infections at the time of the acute exacerbation of chronic otitis media

The present study was undertaken to ascertain whether or not patients with chronic otitis media are infected with viruses or Mycoplasma at the time of sudden increase in otorrhea. From 26 patients with acute exacerbation of chronic otitis media, sera were collected at the time of sudden increase in otorrhea and three to four weeks later. These paired sera were examined for antibody titer to respiratory viruses (21 species) and Mycoplasma pneumoniae. Of them, influenza B virus and RSV infections were demonstrated in four and two cases, respectively. Examinations showed no infection in 10 control cases without acute exacerbation. In 36 cases of acute exacerbation of chronic otitis media, attempts were made to isolate viruses and Mycoplasma pneumoniae from the pharynx and otorrhea. Consequently, influenza B virus was detected in pharyngeal mucous scrapings in two cases and RSV in one. The probability of respiratory virus infection leading to acute exacerbation of chronic otitis media appears to be lower than that provoking acute otitis media in children and infants. However, the present data suggest that the development of respiratory virus infection in patients with chronic otitis media may cause an increase in the otorrhea, eventually resulting in an acute exacerbation of inflammation.     

Inhibition of glucose reabsorption induced by 6-aminonicotinamide in the rat kidney

The relationship between natriuresis and glucosuria produced by administration of 6-aminonicotinamide (6-AN), was investigated in the rat. After intraperitoneal administration of 6-AN (75 mg/kg), urine was collected at intervals of 2 hours using a metabolic cage for assays. Sodium and glucose were excreted maximally into the urine at 2 to 4 and at 4 to 6 hours, respectively, after the administration of 6-AN, with a time delay being recognized between sodium and glucose in the peaks of their urinary excretions. This dissociation of the patterns on the urinary excretion between sodium and glucose led to the following conclusion that the natridiuresis induced by 6-AN was not mainly ascribed to the osmotic diuresis for glucose, but to the direct effect on the sodium transport in the kidney. Furthermore, additional experiments were carried out by loading animals with glucose after administration of 6-AN. The tolerance for glucose in the body was clearly depressed in rats in the 6-AN group, while no significant difference in the renal threshold concentration for glucose was shown in either group. The renal tubular transport maximum for glucose was also depressed in the 6-AN group. It is, accordingly, speculated that the glucosuria induced by 6-AN was not only due to the hyperglycemia, but also due to the decreased capacity of the renal tubular reabsorption for glucose.     

Mineralized phase matrix proteinases of newborn rat calvaria

Several proteinase activities associated with different molecular weight proteins were detected by substrate-gel electrophoresis using gelatin as a substrate in the 4M guanidine soluble fraction obtained from the demineralized matrix of the mineralized phase of newborn rat calvaria (mineralized phase matrix proteinases = MPM proteinases). The major gelatinase activity migrated with the molecular weight fraction of 58,000 daltons. This proteinase was active over the pH range 6–9 against gelatin. Based on the behavior against inhibitors and the differences of molecular weight, the 58kD MPM proteinase was thought to be different from the already known matrix metalloproteinases and proteinases such as kallikrain, plasmin and cathepsin B 1. Some of bone MPM proteinases may participate in the degradation of acidic proteins (sialoprotein and phosphorylated proteins) which are stained blue with Stains-all in newborn rat calvaria.     

Cranioplasty with split lateral skull plate segments for reconstruction of skull defects

This paper reports the use of cranioplasty using segments of split lateral skull plate to correct large skull defects (larger than 8 x 8 cm). The subjects consisted of 10 patients with head trauma who had undergone decompression surgery, and two patients who had undergone tumour resection. Bone grafts were obtained by cutting approximately 2 cm wide strips from the lateral skull plate using a bone saw that was inserted from a free margin of the bone defects. By cutting strips laterally from the bone defect, the necessary amount of split lateral skull plate can be obtained without performing craniotomy. The pieces of split lateral skull plate are then fixed to the defect using wire or titanium mini-plates. At this point, the selection of bone grafts that match the curvature of the dura mater is important, so that no dead spaces are created between the dura mater and the bone grafts. Infection was not detected in any of the 12 patients, and all bone grafts took completely. One of the 12 patients suffered from a pathological fracture and bone resorption 6 months after surgery. The fracture occurred because the use of basket-shaped reconstruction plates resulted in large spaces between the plate segments, and in addition the intracranial pressure was kept low by a V-P shunt, thus rendering the patient more vulnerable to atmospheric pressure.