Prevention of Tumor Metastasis after Surgical Removal of Primary Tumor by Using In Vitro Activated Macrophages

In vitro activation of peritoneal macrophages by Propionibacteriumacnes and its immunotherapeutic potential for inhibiting metastasiswas investigated. C3H/HeN mouse adherent peritoneal exudatecells as a source of macrophages were treated in vitro withP. acnes. These P. acnes-activated macrophages were tested fortumoricidal activity in vitro and antimetastatic activity invivo. In vitro cytotoxicity tests revealed that they had potentcytotoxicity. Surgical resection of X5563 tumors in syngeneicC3H/HeN mice 10 days after the tumor implantation failed torescue the hosts from tumor metastasis despite successful removalof the primary tumor. When the activated macrophages were transferredintravenously into C3H/HeN mice following the surgical operation,an appreciable number of mice survived without exhibiting anysign of metastasis. Thus, these results demonstrate that macrophagescan be activated in vitro by utilizing appropriate stimulatingreagents, and that these activated macrophages have a potentantimetastatic effect.     

The safety of a nitric oxide inhalation system with high frequency oscillatory ventilation

Nitric oxide (NO) inhalation and high frequency oscillatory ventilation (HFOV) has been indicated in infants with severe respiratory failure. The purpose of the present study was to evaluate the safety of an NO inhalation system with HFOV in terms of nitrogen dioxide (NO₂) production. The NO inhalation system consisted of a high frequency oscillatory ventilator, a neonatal circuit and a test lung. The NO concentration was changed from 0 to 19 p.p.m. At each level of NO, the oxygen (O₂) concentration was changed from 21 to 100%. The NO and NO₂ concentrations were measured with a chemiluminescence analyzer using a molybdenum converter. The NO₂ concentration was increased when either the O₂ or the NO concentration was increased. The interposition of the endotracheal tubes increased NO₂ concentrations at 4 p.p.m. NO. The high stroke volume and high mean airway pressure produced a significant increase in NO₂ production at 4 p.p.m. NO. The increase in NO₂ production was prevented by placing a one-way valve at the joint of the NO gas line to the inspired limb. It was concluded that the NO inhalation system with HFOV can be safely used when a one-way valve is placed at the joint of the NO gas line to the inspired limb and when inhaled NO is at a relatively low concentration.     

Assessing the clinical utility of the magnetic stimulator for measuring response latencies in the laryngeal muscles

Our purpose was to assess the use of magnetic stimulation for measuring conduction time of the recurrent and superior laryngeal nerves in 10 normal volunteers (7 male, 3 female). Subjects underwent laryngeal electromyography and magnetic stimulation of the vagus nerve bilaterally at the mastoid tip with a figure 8 coil. Mean muscle response latencies were measured and examined for consistent differences. Thyroarytenoid muscle response latencies were consistently longer than those in the cricothyroid muscle. Left thyroarytenoid muscle latencies were consistently longer than those on the right in agreement with bilateral asymmetry of these nerves. No appreciable differences were observed in cricothyroid muscle latencies when the right side was compared with the left. Results were consistent and reproducible within a broad range, but appreciable intersubject variability was observed. The limited sample size was unable to support a correlation with anthropometric variables, although an association was indicated. Magnetic stimulation with this technique has great potential for use in neurolaryngologic studies. (Otolaryngol Head Neck Surg 1996;114:761-7.)     

A multicenter,randomized, controlled trial of intravenous gamma globulin therapy in children with acute Kawasaki disease

We studied the effect of intravenous, polyethyleneglycol-treated, human immunoglobulin, administered at 200 mg/kg per day (group A: n = 147; male 86, female 61; age < 1 year, 50) or 400 mg/kg per day (group B: n = 152; male 87, female 65; age < l year, 52) for five consecutive days and compared it with freeze-dried, sulfonated human immunoglobulin [group C: n = 152; male 87, female 65; age < 1 year, 51), administered at 200 mg/kg per day for five consecutive days, on the prevention of coronary artery abnormalities in Kawasaki disease. Echocardiograms were interpreted blindly and independently. Proportions of 87.1%, 95.4%, and 82.3% in groups A, B, and C, respectively, had no coronary artery abnormalities. The confidence limits of difference between the proportions of groups A and C, groups B and C, and groups B and A were −4.4% and 10.4%, 7.8% and 15.9%, and 4.0% and 10.8%, respectively. Duration of fever and serum immunoglobulin G (IgG) levels were correlated with the prevalence of coronary artery abnormalities. We concluded that intravenous, polyethyleneglycol-treated, human immunoglobulin and freeze-dried, sulfonated human immunoglobulin had clinically equivalent effects on coronary artery abnormalities, and that five daily doses of 400 mg/kg of intravenous, polyethyleneglycol-treated, human immunoglobulin is more effective than that of 200 mg/kg gamma globulin.     

Morphological Variation of Nonreentrant Idiopathic Ventricular Tachycardia Originating from the Right Ventricular Outflow Tract and Effect of Radiofrequency Lesion

RF catheter ablation was performed in 16 patients with nonreentrant idiopathic VT originating from the RVOT. All documented VT was monomorphic, but subtle morphological variation in the VT-QRS complex was observed in 10 (63%) of 16 patients. Through endocardial mapping, VT origin was determined within a narrow site (< 0.5 ± 0.5 cm) in 4 of the 10 patients with the morphological variation. In the other 6 of 10 patients, the origin extended to an area of > 0.5 ± 0.5 cm. In VT with morphological variation, the local electrogram at the site of VT origin also showed variation in morphology and activation sequence. For VT of narrow origin, RF application to the site eliminated the VT. However, in VT from a wide arrhythmogenic area, RF current had to be delivered to 3–7 distinct sites to cover the possible origin, and specific QRS configuration of VT and/or PVC was ablated at each of the earliest activation site. All but one VT were successfully ablated by RF current. Subtle morphological variation was frequent in this type of VT, and about half were associated with a wide arrhythmogenic area. Precise mapping and analysis of the efficacy of each BF application might be helpful to better understand the relationship between subtle changes of VT-QRS morphology and their origins.     

EXCRETION OF BIKUNIN AND ITS FRAGMENTS IN THE URINE OF PATIENTS WITH RENAL STONES

PURPOSE: Bikunin is a Kunitz-type protease inhibitor found in serum and urine. It has been implicated in urinary stone formation. This study was designed to investigate the role of urinary bikunin in stone formation. MATERIALS AND METHODS: Urinary concentrations of bikunin were measured in 18 male formers of urinary stones 28 to 74 years old and in 77 healthy controls, including 39 males and 38 females, without urological abnormality. A sensitive competitive solid phase enzyme immunoassay was established for urinary bikunin. Bikunin was also qualitatively assessed by Western blot analysis. RESULTS: The mean urinary bikunin-to-creatinine ratio plus or minus standard deviation in stone formers was significantly elevated compared with that in healthy male and female controls (52.9 +/- 46.0 microg./mg. creatinine versus 28.0 +/- 30.4 and 26.5 +/- 21.7, p = 0.005 and 0.006, respectively). By Western blot analysis all urine samples contained authentic 40 kDa. bikunin species. However, a significantly higher proportion of patients was found to have aberrant 25 kDa. bikunin species compared with controls (10 of 18 or 55.6% versus 15 of 77 or 19.5%, p = 0.002). Experiments on de-glycosylation with chondroitinase ABC, amino acid sequencing of the aberrant bikunin species and calcium oxalate crystal growth inhibition assay demonstrated that the 25 kDa. bikunin fragment was identical to de-glycosylated bikunin and less inhibitory on calcium oxalate crystal growth. CONCLUSIONS: If urinary bikunin is important in the pathogenesis of urolithiasis, its effect is probably attributable to the concentration and degree of glycosylation.     

Outcomes of infants whose mothers are positive for human herpesvirus-6 DNA within the genital tract in early gestation

It has been reported that HHV-6 (human herpesvirus-6) DNA has been identified within the female genital tract. However, the clinical significance of this finding has been unclear. The clinical outcome of the presence of HHV-6 DNA in the genital tract of pregnant women on their infants was evaluated in the present study. One hundred and ten pregnant women were enrolled. Vaginal swabs were collected between 4 and 8 weeks of gestation and the presence or absence of HHV-6 DNA was evaluated by nested polymerase chain reaction (nPCR). The swabs were cultured to isolate the virus. The women were divided into two groups: HHV-6 DNA-positive, and negative. The outcome variables of the infants of these two groups were statistically estimated at birth and at 1 month of age. Saliva and blood cells were collected from the infants at birth and at 1 month of age and were also evaluated by nPCR. HHV-6 DNA was detected in the vaginal swabs of 28 pregnant women (25.5%), but was not detected in any other samples, including saliva and blood cells from their infants. Virus could not be isolated from any vaginal samples. Any outcome variables were not significantly different between the two groups. The presence of HHV-6 DNA within the genital tract of pregnant women did not affect the health of their infants. It is suggested that HHV-6 transmission to infants through the genital tract of their mothers during pregnancy does not occur, or only very rarely.     

Human B-Cell Clones Expressing Lupus Nephritis-Associated Anti-DNA Idiotypes are Preferentially Expanded without Somatic Mutation

Human monoclonal anti-single/double-stranded (ss/ds) DNA anlibodies (NE-1 and NE-13) expressed cross-reactive idiotypes (Id), NE-1 Id, which have been delected on the lupus glomeruli-deposited anti-DNA antibodies. The nucleotide sequences of the variable regions of NE-1 and NE-13 clones were analogous except for one nucleotide difference in the V_k region. The V_H and V_k gene segments of NE-13 clone were identical with germline genes VH4.21 and Vb(or Vb'). respectively. CDR3sof NE-l and NE-13 heavy chains were arginine rich and CDR1s contained an amino acid stretch. SGYY, the inverted sequence of YYGS. which was shared among CDR3s of several anti-DNA antibodies. Clonal frequency analysis using a limiting dilution method revealed that NE-1 Id-positive clones at precursor cell level increased in lupus patients. These findings suggest that some IgM anti-DNA clones which express NE-1 Id associated with lupus nephritis use germline genes without mutation and they may be preferentially expanded at the precursor cell levels as well as at the mature cell level.     

Immunohistochemistry of collagen types II and X, and enzyme-histochemistry of alkaline phosphatase in the developing condylar cartilage of the fetal mouse mandible

We investigated the immunohistochemical localisation of types II and X collagen as well as the cytochemical localisation of alkaline phosphatase in the developing condylar cartilage of the fetal mouse mandible on d 14–16 of pregnancy. On d 14 of pregnancy, although no immunostaining for types II and X collagen was observed, alkaline phosphatase activity was detected in all cells in the anlage of the future condylar process. On d 15 of pregnancy, immunostaining for both collagen types was simultaneously detected in the primarily formed condylar cartilage. Alkaline phosphatase activity was also detected in chondrocytes at this stage. By d 16 of pregnancy, the hypertrophic cell zone rapidly increased in size. These findings strongly support a periosteal origin for the condylar cartilage of the fetal mouse mandible, and show that progenitor cells for condylar cartilage rapidly or directly differentiate into hypertrophic chondrocytes.