The role of STAT1 in activation of IL-3- and IL-5-induced eosinophils by interferon gamma

Tyrosine phosphorylation of STAT1alpha in eosinophils after IFN-gamma stimulation has been shown, but the biological significance of eosinophil STAT1alpha activation in transmitting the signals through the IFN-gamma receptor remains unknown. The purpose of this study is to determine whether STAT1 is involved in the regulation of eosinophils by IFN-gamma-IFN-gamma receptor interaction. rhIL-3- and rhIL-5-induced eosinophils from CD34+ cells of cord blood on day 28 of culture were used. The cells were washed and further incubated in IL-3- and IL-5-free medium for 48 h. The induced eosinophils constitutively expressed CD69 and lost this expression after a further 48-hour incubation without the cytokines. IFN-gamma significantly upregulated CD69 expression on the 48-hour incubated cells. In inhibitory experiments on STAT1, a phosphorothioate oligo antisense DNA against STAT1alpha was added to IL-3- and IL-5-containing medium from day 15 to day 28 of culture. The oligo DNAs altered neither the expressions of myeloid cell marker CD9 and 13 nor the expression of IFN-gamma receptor on the cells. The added STAT1alpha antisense, but not sense, DNA significantly reduced STAT1alpha mRNA expression in the cells. The STAT1 antisense also significantly inhibited IFN-gamma-induced CD69 expression on the 48-hour incubated eosinophils. In conclusion, these results indicate that IFN-gamma induces CD69 expression in the induced eosinophils through STAT1alpha, suggesting that STAT1alpha may play a significant role in eosinophil regulation by IFN-gamma.     

Fundamental and clinical studies of ceftizoxime suppositories in pediatrics

Fundamental and clinical studies were carried out on ceftizoxime suppository (CZX-S), and the following results were obtained in pediatrics. In 4 patients of the CZX-S 125 mg-administered group (9.4-9.9 mg/kg), the serum concentration of CZX reached a peak of 5.55 micrograms/ml on the average, 30 minutes after dosing, i.e. at the time of initial blood collection, and decreased gradually to 0.20 microgram/ml 6 hours after dosing. The half-life was 1.09 hours. In 5 patients of the CZX-S 250 mg-administered group (8.4-18.1 mg/kg), the serum concentration of CZX peaked at 7.07 micrograms/ml on the average and then gradually declined to 0.16 microgram/ml 6 hours after dosing. The half-life was 1.00 hour. The urinary recovery rate varied as widely as 6.5-38.0% in all the patients of both groups. CZX-S was given to total 19 patients; 8 patients with urinary tract infection (UTI), 3 with pharyngitis or tonsillitis, 4 with bronchitis, 2 with pneumonia, 1 with otitis media and 1 with staphylococcal scalding skin syndrome. The overall effect of CZX-S in 15 patients was "effective" or better response, with an effectiveness rate of 83.3%, except one who discontinued the drug because of side effects. CZX-S was given to most of the patients weighing 15 kg or higher in a dose of 250 mg 3-4 times a day and frequently to patients weighing less than 15 kg in a dose of 125 mg 3-4 times a day. As to side effects, slight diarrhea was encountered in 1 patient. Laboratory examinations disclosed an increase in GOT in 1 patient, which returned to normal after continual insertion of the suppository.     

Dietary Olive Oil Intake Improves Running Endurance with Intramuscular Triacylglycerol Accumulation in Mice

Olive oil is a functional food shown to have a variety of bioactive effects. Therefore, we expect it to be a novel functional food with an exercise-mimetic effect on skeletal muscles. This study aimed to investigate the effect of olive oil on the endurance capacity and muscle metabolism in mice. Mice fed a 7% (w/w) olive oil diet for eight weeks showed improved treadmill running endurance and increased intramuscular triacylglycerol (IMTG) accumulation in the gastrocnemius muscle compared to soybean oil diet-fed controls. The increase in running endurance with olive oil intake was independent of the muscle fiber type. To elucidate underlying the mechanism of elevated IMTG levels, we examined the expression levels of the genes related to lipid metabolism. We found that the expression of diacylglycerol O-acyltransferase1 (DGAT1) was significantly upregulated in the muscle of olive oil diet-fed mice. In addition, the olive oil diet-fed mice showed no metabolic impairment or differences in growth profiles compared to the controls. These results suggest that dietary olive oil intake affects muscle metabolism and muscle endurance by increasing energy accumulation.     

Acoustic evaluation of postoperative hoarseness in adult patients

The present study was performed to evaluate postoperative hoarseness quantitatively by means of acoustic wave form analysis. Pitch and amplitude perturbation (PPQ, and APQ), and normalized noise energy (NNE) were measured along with the frequency characteristics in 51 adult patients undergoing elective surgery. The normal values for these acoustic parameters were less than 0.5%, less than 2.0%, and less than -10 dB, respectively. Vowel sound "E" was recorded and evaluated before the induction of anesthesia and on the morning of the day after the surgery. PPQ increased from 0.39% to 1.00% (P less than 0.05), APQ increased from 3.34% to 6.62% (P less than 0.05), and NNE increased from -9.19 dB to -4.74 dB (P less than 0.05). Eighteen percent of the patients showed abnormal values in all parameters preoperatively, but 45% of the patients postoperatively (P less than 0.05). These findings suggest that even the short term intubation resulted in the postoperative hoarseness, and this method is a useful and non-invasive bed-side test to evaluate postoperative hoarseness quantitatively.     

Does calcium balanced heparin affect blood gas and electrolyte analysis?

The effect of calcium-balanced heparin (471896, CIBA CORNING) on blood gas and electrolyte analysis was evaluated, by comparing with that of sodium heparin (Na heparin). One ml of whole blood was collected into a syringe, which contained calcium-balance heparin (Ca balanced heparin) or Na heparin. 122 pairs of blood samples obtained from 15 patients were analyzed for Na, K, ionized calcium (Ca(++)), total hemoglobin, pH, P(CO)(2), and P(O)(2) by an automatic blood gas and electrolyte analyzer, CIBA CORNING model 288. There was a significant difference ( P < 0.05) in pH, P(CO)(2), Na, and Ca(++) between the two different groups. Ca(++) concentration was significantly less in Na heparin group than in Ca balanced heparin group, probably due to more chelation of Ca(++) by Na heparin than Ca balanced heparin. The present study suggests that the Ca balanced heparin has minimal effect on the blood gas and electrolyte analysis, and is a suitable anticoagulant for the Ca(++) measurement.     

Comprehensive genetic screening for vascular Ehlers–Danlos syndrome through an amplification-based next-generation sequencing system

Vascular Ehlers–Danlos syndrome (vEDS) is a hereditary connective tissue disorder (HCTD) characterized by arterial dissection/aneurysm/rupture, sigmoid colon rupture, or uterine rupture. Diagnosis is confirmed by detecting heterozygous variants in COL3A1. This is the largest Asian case series and the first to apply an amplification-based next-generation sequencing through custom panels of causative genes for HCTDs, including a specific method of evaluating copy number variations. Among 429 patients with suspected HCTDs analyzed, 101 were suspected to have vEDS, and 33 of them (32.4%) were found to have COL3A1 variants. Two patients with a clinical diagnosis of Loeys–Dietz syndrome and/or familial thoracic aortic aneurysm and dissection were also found to have COL3A1 variants. Twenty cases (57.1%) had missense variants leading to glycine (Gly) substitutions in the triple helical domain, one (2.9%) had a missense variant leading to non-Gly substitution in this domain, eight (22.9%) had splice site alterations, three (8.6%) had nonsense variants, two (5.7%) had in-frame deletions, and one (2.9%) had a multi-exon deletion, including two deceased patients analyzed with formalin-fixed and paraffin-embedded samples. This is a clinically useful system to detect a wide spectrum of variants from various types of samples.     

The relation between superoxide dismutase in cancer tissue and clinico pathological features in breast cancer

The localization of Cu/Zn- and Mn-superoxide dismutase (SOD) in breast cancer tissue (12 papillotubular carcinomas, 21 solid-tubular carcinomas, 16 scirrhous carcinomas, 1 medullary carcinoma, 1 secreting carcinoma, 1 lobular carcinoma, 1 Paget's disease) was investigated via an immunohistochemical technique using antihuman Cu/Zn- and Mn-SOD antibodies in 10%formalin fixed-paraffin embedded thin sections. Both SODs stained strongly in the normal breast gland, but not clearly in many cancer tissues. Furthermore, Cu/Zn-SOD stained more strongly in well differentiated tubular carcinomas than in poorly differentiated tubular carcinomas. It tended to stain less in tumors which recurred or had a poor outcome, and in tumors with a diploid pattern on DNA flow cytometry. Mn-SOD staining was similar to that of Cu/Zn-SOD, but no significant differences among subgroups was found, since the incidence of positively staining tumors was too small in all groups. The intensity of SOD staining seems to change in relation to cell proliferation and differentiation in breast carcinoma, and may be a prognostic indicator, since SOD decreased in poorly differentiated carcinoma and in tumors which developed distant metastasis. Thus, the localization of SOD in breast cancer tissue can provide useful information for cancer treatment.     

β,β′-Iminodipropionitrile toxicity in normal and congenitally neurofilament-deficient Japanese quails

Morphological effects of a neurotoxin, ,-iminodipropionitrile (IDPN) were analyzed in normal and cogenitally neurofilament (NF)-deficient Japanese quails. These quails (6 weeks old) were injected intraperitoneally with IDPN (0.2 g/kg body weight) three times every 3 days. They were necropsied at 10 to 12 days after the first injection. In normal quails, axonal swellings were observed histologically in the ventral motoneurons, ventral root, commissura grisea and spinal ganglion in the cervical and synsacral spinal cord. Electron microscopically, the changes consisted of increased NFs, with scattered mitochondria, smooth endoplasmic reticulum and microtubules. The myelin sheaths of the involved nerves were thinner than those of the normal axons. These lesions were similar to those induced by IDPN intoxication in mammalian experimental animals. In NF-deficient quails injected with IDPN, no axonal changes were detected. These findings suggested that IDPN selectively attacked the NFs.     

Two cases of methicillin-resistant Staphylococcus aureus (MRSA) sepsis following craniotomy

We report here two cases of MRSA sepsis following craniotomy. In case 1, a petroclival meningioma was subtotally removed and lumbar drainage was inserted postoperatively to prevent cerebrospinal fluid leakage. Ventriculo-peritoneal shunt was performed after meningitis was treated with vancomycin and panipenem/betamipron. Two weeks after the procedure, the patient revealed continuous spiking fevers related to MRSA sepsis, which did not improve with vancomycin and arbekacin administration. The focus of infection was found by scintigraphy and CT by 67Ga to be spondylo-diskitis at the level of L2-L3. The lesion was removed and bone from the iliac crest grafted. In case 2, seven days after surgery for multiple meningioma, the patient exhibited spiking fevers and swelling in the left leg. The central venous catheter was removed from the left femoral vein and MRSA was found from blood culture. The patient was treated with arbekacin (200 mg/day). Venous thrombosis diagnosed by CT was treated with heparin. Symptoms related to the infection and laboratory data did not improve because the concentration of arbekacin in the blood did not reach an effective level. The symptoms markedly improved when the dose of arbekacin was doubled (400 mg/day).