MUC-1 mucin expression in invasive areas of intraductal papillary mucinous tumors of the pancreas

The expression of MUC-1 mucin (membrane-associated mucin) and MUG2 much (secretory mucin) were immunohistochemically examined in 46 invasive ductal carcinomas (IDC) and 16 intraductal papillary mucinous tumors (IPMT) of the pancreas. lntraductal papillary mucinous tumors usually reveal expansive growth. However, of the 16 IPMT examined in the present study, three showed an invasive growth pattern, which was similar to 'mucinous carcinoma', around the non-invasive growth areas. Of 46 IDC, MUCl much detected by monoclonal antibodies, DF3 and MY.1E12, was expressed in 44 cases (96%) and in 45 cases (98%), respectively, whereas MUC-2 mucin detected by polyclonal antibody, anti-MRP, was not expressed in any of the cases (0%). In contrast, in the non-invasive growth areas of the 16 IPMT, MUG1 much detected by DF3 and MY.1 E12 was expressed in four cases (25%) and in six cases (38%), respectively, whereas MUG2 mucin detected by anti-MRP was expressed in 13 cases (81%). The invasive growth areas of the three IPMT showed positive expression of MUG-1 mucins detected by DF3 and MY.1E12, although the non-invasive growth areas showed negative expression of MUG1 muclns, except for their focal positive expression in one of the three cases. These findings indicate that the invasive growth areas of IPMT acquire a characteristic of MUC-1 much expression that is usually seen In IDC.     

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.     

Serum Levels of Polyamines in Cancer Patients

Serum polyamines were determined by Samejima's method.
Total putrescine, cadaverine and spermidine in healthy adults were 0.29±0.08, 0.11 ± 0.08. and 0.43 ± 0.15 nmoles/ml. respectively. Spermidine was not detected in the serum by this method. About half of total polyamines existed in free form in the serum. No significant elevation of serum polyamines was observed in chronic hepatitis and liver cirrhosis. Increased serum putrescine was observed in some cases of malignancies, such as hepatomas (0.76 nmoles/ml. 0.62 nmoles/ml), pharyngeal carcinoma (0.66 nmoles/ml), peritonitis carcinoma (0.60 nmoles/ml) and colon carcinoma (0.45 nmoles/ml). Determination of serum polyamines. especially of putrescine, may provide a potential indicator in some cases of malignancy.     

TREATMENT OF POLYCYSTIC OVARIAN DISEASE BY INDUCING OVULATION WITH PULSATILE SUBCUTANEOUS ADMINISTRATION OF HUMAN MENOPAUSAL GONADOTROPHIN ASSOCIATED WITH LUTEINIZING HORMONE-RELEASING HORMONE ANALOGUE

Treatment with a combination of luteinizing hormone-releasing analogue (GnRHa, Buserelin) and pulsatile administration of hMG (Group I) were used to induce ovulation in nine patients with polycystic ovary syndrome (PCO). The same patients were also treated with pulsatile hMG administration alone (Group II). Ovulation was observed in all twelve treatment cycles in Group I, and there were two pregnancies. In Group II, ovulation occurred in 22 of 26 treatment cycles. Ovarian hyperstimulation occurred in one cycle of Group I and in 5 of 26 cycles of Group II. The total dose per cycle of hMG to induce ovulation in Group I was significantly lower than that needed when only pulsatile hMG administration was used. In response to Buserelin administration, the concentrations of serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) increased transiently and then declined to the normal range observed in the early follicular phase. The concentrations of FSH increased in response to hMG administration, resulting in a normal LH/FSH ratio. The present data demonstrated that pulsatile subcutaneous administration of hMG in addition to Buserelin was effective in inducing follicular maturation and ovulation in patients with PCO with a lower incidence of serious side-effects.     

Muscarinic Receptor Binding and Plasma Drug Concentration after the Oral Administration of Propiverine in Mice

Objectives: The current study was undertaken to characterize the binding of propiverine to muscarinic receptors in mouse tissues by measuring plasma concentrations of the drug and its metabolite. Methods: At 0.5–24 h after the oral administration of propiverine at pharmacologically relevant doses, muscarinic receptors in tissue homogenates were measured by a radioligand binding assay using [N‐methyl‐ ³H]scopolamine (NMS), along with the drug's concentration in plasma by the liquid chromatography‐tandem mass spectrometric method. Results: In the in vitro experiments, propiverine and its metabolite 1‐methy‐4‐piperidyl benzilate N‐oxide competed with [³H]NMS for binding sites in the bladder, submaxillary gland and heart of mice in a concentration‐dependent manner. After the oral administration of propiverine, dose‐ and time‐dependent increases in the dissociation constant for specific [³H]NMS binding were observed in the bladder and other tissues of mice, indicating that orally administered propiverine and/or its metabolite undergo significant binding to muscarinic receptors in mouse tissues. A longer‐lasting binding of muscarinic receptor was seen in the bladder than in the submaxillary gland at relatively low doses of propiverine. Furthermore, the decrease in maximal number of binding sites values for [³H]NMS binding was more remarkable in the bladder than submaxillary gland of propiverine treated mice. There was a dose‐dependent rise in the plasma concentrations of propiverine and 1‐methy‐4‐piperidyl benzilate N‐oxide in mice after the oral administration of propiverine. Conclusion: The oral administration of propiverine exerts a more prominent and longer‐lasting effect in the bladder than in the submaxillary gland of mice. The N‐oxide metabolite may contribute significantly to the blockade of muscarinic receptors caused by oral propiverine.     

Propofol has anti‐inflammatory effects on alveolar type II epithelial cells

Background: We investigated whether lipopolysaccharide (LPS) induced inflammation in alveolar epithelial type II (ATII) cells is through cluster of differentiation 14 (CD14) and Toll‐like receptor 4 (TLR4) and the effect of different dosages of propofol on the inflammation in primary cultured rat ATII cells. Methods: Cultured ATII cells were randomly assigned to one of the following five groups: Group C: untreated group (control) cultured in the absence of propofol and LPS; Group LPS: treated with 1 μg/ml LPS; Group P1: treated with 1 μg/ml LPS and 25 μM propofol; Group P2: treated with 1 μg/ml LPS and 50 μM propofol; Group P3: treated with 1 μg/ml LPS and 100 μM propofol. ATII cells in all groups were cultured at 37 °C for 3 h. CD14 and TLR4 mRNA was detected using real‐time polymerase chain reaction. Western blot was used to detect CD14 and TLR4 protein expression. CD14 and TLR4 expression on the ATII cells was imaged using immunofluorescence. Tumor necrosis factor‐α (TNF‐α) production was determined using an ELISA kit. Results: LPS stimulation resulted in an increased CD14 and TLR4 expression and increased TNF‐α production in ATII cells. Propofol, at concentrations ≥50 μM, significantly (P<0.05) and dose‐dependently decreased CD14 and TLR4 mRNA expression and protein expression in ATII cells. This was accompanied by a decrease in TNF‐α production (P<0.05). Conclusion: These results suggest that propofol, at clinically relevant concentrations, can reduce inflammatory responses in LPS‐induced ATII cells injury through downregulation of CD14 and TLR4 expression.