Utility of immunostaining for S-100 protein subunits in gonadal sex cord-stromal tumors, with emphasis on the large-cell calcifying Sertoli cell tumor of the testis

This study concerns the immunohistochemical localization of S-100 alpha, S-100 beta, and whole brain S-100 (wbS-100) in testicular large-cell calcifying Sertoli cell tumor (LCCSCT). We examined 8 LCCSCTs (7 benign and 1 malignant), 6 Sertoli cell tumors not otherwise specified (SCTs-NOS), 6 Leydig cell tumors (LCTs), 5 ovarian Sertoli-Leydig cell tumors (SLCTs), and 7 gonadoblastomas (GBLs). The 8 LCCSCTs showed immunoreactivity for S-100 alpha, S-100 beta, and wbS-100. Five of the 6 LCTs and the Leydig cell components in the ovarian SLCTs stained positively for S-100 alpha and wbS-100 but were negative for S-100 beta. SCTs-NOS and the Sertoli cell components in the SLCTs occasionally showed focal and weak/moderate positivity for S-100 alpha, S-100 beta, and wbS-100. Sex cord cells of the GBLs were positive for S-100 beta and wbS-100 and negative for S-100 alpha. Germ cell elements of the GBLs were negative for S-100 alpha, S-100 beta, and wbS-100. In nonneoplastic testicular parenchyma adjacent to the above-mentioned tumors, there was S-100 alpha reactivity in Leydig cells, rete testis, and a few Sertoli cells. S-100 beta reactivity was seen in a few Sertoli cells, Schwann cells, and some endothelial cells. WbS-100 reactivity was present in Leydig cells, a few Sertoli cells, rete testis, Schwann cells, and some endothelial cells. The results indicate that S-100 alpha and S-100 beta can potentially be used as immunohistochemical markers for LCCSCT, especially when differentiating it from LCT, which may mimic LCCSCT on routine histopathology. Although the biological significance of both S-100 subunits expression in LCCSCT remains unknown, these notable calcium-binding proteins may be associated with the characteristic calcification in LCCSCT through regulation of calcium levels in the tumor cells.     

Significance of aberrant (cytoplasmic/nuclear) expression of beta-catenin in pancreatoblastoma

This study concerns the significance of aberrant (nuclear/cytoplasmic) expression of beta-catenin in pancreatoblastoma (PBL). On immunohistochemistry, all seven PBLs examined showed nuclear/cytoplasmic expression of beta-catenin, predominantly in the squamoid corpuscles (SCs). In areas with acinar/ductular differentiation, few tumour cells displayed nuclear/cytoplasmic expression of beta-catenin and more than half of the tumour cells showed membranous expression. Two out of five (40%) tumours examined showed missense mutations in codons 33 and 37 of exon 3 of the beta-catenin gene. No mutation of the adenomatous polyposis coli (APC) gene was detected in two of the remaining three tumours. Amplifiable DNA for APC analysis was not obtained from the one other tumour. Immunoreactivity for cyclin D1, one of the nuclear targets of beta-catenin, was found predominantly in the SCs of the seven tumours. In contrast, the Ki-67 labelling index was 2-4% (median 3%) in the SCs and 8-18% (median 12%) in the other areas, indicating a negative correlation with nuclear cyclin D1 reactivity. These results imply that in PBLs, nuclear/cytoplasmic accumulation of beta-catenin and overexpression of its target gene cyclin D1 are not associated with the induction of tumour cell proliferation. Nuclear/cytoplasmic accumulation of beta-catenin may be related to the morphogenesis of the SCs that are considered most characteristic for PBL.     

Droperidol inhibits tracheal contraction induced by serotonin,histamine or carbachol in guinea pigs

Purpose

Droperidol (D) is effective in the treatment of patients with status asthmaticus. It has been reported that D inhibits the bronchoconstriction induced by serotonin (5-HT) but not that by histamine (H) or acetylcholine. However, haloperidol, another butyrophenone, is known to interact with and inhibit calmodulin, an intracellular Ca⁺⁺-binding protein which is important in the contraction of smooth muscles. The present study was designed to investigate the effects of D on tracheal contractions induced by 5-HT, H or carbachol (C) and to determine the contribution of α-adrenoceptors to the relaxant effect of D in vitro.

Methods

Tracheas of female guinea pigs were cut spirally into strips and mounted in water-jacketed organ baths in Tyrode’s solution, aerated with a mixture of 95% O₂ and 5% CO₂ at 37°C. The changes in isometric tension induced by each spasmogen in the strips were measured with a transducer and a polygraph.

Results

We found that D inhibited the tracheal contractions induced by 5-HT, H or C in a concentration-dependent manner. At 1.25 × 10^?6 M D blocked the effect of 10^?4 M 5-HT by 44.1 ± 4.3% and at 2.5 × 10^?6 M by 63.8 ± 3.8%. Similarly, at 5.0 × 10^?6 M concentration, D blocked the effect of 10^?5 M H by 27.7 ± 5.3% and at 10^?5 M by 56.2 ± 2.6%. Furthermore, 5 ×10^?6 M of D reduced the contractions produced by 10^?7 M C by 37.1 ± 3.0% and 70^?5 M of D by 76.1 ± 3.2%. The inhibiting effect of D was strongest on contractions induced by 5-HT. Prazosin (70^?6 M) affected neither 5-HT-induced contractions nor the inhibition by D.

Conclusion

Our data indicate that D partially blocks the contractile responses not only to 5-HT, an effect which would be mediated through a blockade of the 5-HT receptors, but also to H or C, probably through inhibition of calmodulin. Our data support previous reports indicating that droperidol may be an important therapeutic agent in the treatment of patients with hyperreactive airways.     

A case of advanced gastric cancer effectively treated by combined chemotherapy of paclitaxel (TXL) and CDDP

The patient was a 73-year-old man with unresectable advanced gastric cancer and celiac and supraclavicular lymph node metastases. Neoadjuvant chemotherapy consisting of paclitaxel (TXL) and CDDP was administered. TXL (80 mg/m2) and CDDP (25 mg/m2) was administered weekly on day 1, 8 and 15 as 1 cycle. After 4 cycles of TXL/CDDP administration, the lymph node metastases and gastric tumor had decreased almost completely in size and distal partial gastrectomy was performed. After surgery, the patient was treated with 4 courses of TXL/CDDP and has survived without recurrence to the present. TXL/CDDP is associated with few adverse events in hospital visits, and is thought to be an effective chemotherapy against advanced gastric cancer.     

Applicability of (SBE)7m-beta-CD in controlled-porosity osmotic pump tablets (OPTs)

The purpose of this study was to investigate the general application of a controlled-porosity osmotic pump tablet (OPT) utilizing (SBE)7m-beta-CD as both a solubilizer and an osmotic agent for drugs with varying physical properties. OPTs utilizing (SBE)7m-beta-CD were prepared for five poorly soluble and two highly water-soluble drugs. The Japanese Pharmacopoeia dissolution method was used to study the drug and (SBE)7m-beta-CD release from the OPTs. The drug concentration in the OPT core after the OPT was placed in the release medium for two hours was assayed gravimetrically and by HPLC. An appropriate composition ratio (ACR) of (SBE)7m-beta-CD to drug at which drug release from the OPT was complete and pH-independent within the physiological pH range of the GI tract was determined for each drug. The ACR values correlate to the drug concentration in the OPT core when the OPTs were placed in the release medium for two hours. The release profiles of prednisolone (a poorly water-soluble drug) and sodium chloride (a water-soluble compound) from the OPTs were almost the same as that of (SBE)7m-beta-CD. Also, the release rate of each drug per unit membrane surface area from the OPTs was similar, regardless of the differences in drug solubility. The present results confirmed that (SBE)7m-beta-CD serves as both a solubility modulator and as an osmotic pumping agent for OPTs, from which the release rate of both water-soluble and poorly water-soluble drugs can be controlled.     

Population pharmacokinetics of theophylline in very premature Japanese infants with apnoea

OBJECTIVE: To estimate the population pharmacokinetics of theophylline in very premature infants using the non-linear mixed effects modelling. METHOD: A total of 167 serum concentration measurements obtained from routine theophylline monitoring of 107 very premature Japanese infants were collected. RESULTS: The final pharmacokinetic parameters were CL (mL/h) = [6.98 . body weight (BW) (kg)(2.17) + 0.244 . post-conceptional age (weeks)] . 1.24(oxygen support), Vd (L) = 0.492 . BW (kg) and F = 0.660, respectively. Clearance was increased by 24% for patients receiving oxygen support. The inter-individual variabilities in clearance and apparent volume of distribution were 15.6% and 80.4%, respectively, and the residual variability was 34.2% as a coefficient of variation. CONCLUSION: Application of the findings in this study to patient care may permit selection of an appropriate initial maintenance dosage to achieve target theophylline concentrations, thus enabling the clinician to achieve the desired therapeutic effect in very premature Japanese infants.     

A case of trigeminal neuralgia complicated by ipsilateral temporal arteritis

Trigeminal neuralgia (TN) complicated with temporal arteritis (TA) is not a common disease, but it is a very important syndrome to consider for diagnosing facial pain in individuals older than 50 years. We therefore report on a rare case of TN with TA that occurred simultaneously on the same side with each symptom responding to specific treatment.     

Correlation between salivary alpha-amylase activity and pain scale in patients with chronic pain

BACKGROUND AND OBJECTIVES: The visual analog scale (VAS) is commonly used to assess pain intensity. However, the VAS is of limited value if patients fail to reliably report. Objective assessments are therefore clearly preferable. Previous reports suggest that elevated salivary alpha-amylase may reflect increased physical stress. There is a close association between salivary alpha-amylase and plasma norepinephrine under stressful physical conditions. In this study, we have determined the usefulness of a portable salivary alpha-amylase analyzer as an objective biomarker of stress. METHODS: Thirty patients (male/female = 15/15, age: 60.5 +/- 15.3 years) with chronic low back or leg pain (pain (+) group) and 20 pain-free control patients undergoing elective surgery under general anesthesia with epidural analgesia (pain (-) group) were recruited. Patients received epidural block with 5 to 10 mL 1% lidocaine. VAS, blood pressure, and heart rates were assessed before and 30 and 45 minutes after the epidural block. Salivary alpha-amylase was simultaneously measured using a portable analyzer. The relationship between the VAS and salivary alpha-amylase in chronic pain patients was assessed. RESULTS: After the epidural block both heart rate and systolic blood pressure decreased by approximately 8%. In the pain (+) group, the epidural block markedly decreased the VAS pain scale and salivary alpha-amylase from 56 +/- 22 to 19 +/- 16 mm (P < .01) and from 82 +/- 48 to 45 +/- 28 U/mL (P < .01), respectively, with a significant correlation between the 2 measures (r = 0.561, P < .01). In contrast, salivary alpha-amylase did not change significantly in the pain (-) group. CONCLUSIONS: Because there was a significant correlation between VAS pain scale and salivary alpha-amylase, we suggest that this biomarker may be a good index for the objective assessment of pain intensity. In addition, a simple to use portable analyzer may be useful for such assessment.