Ceramicines U-Z from Chisocheton ceramicus and structure-antimalarial activity relationship study.

Ceramicines are a series of limonoids which were isolated from the barks of Malaysian Chisocheton ceramicus (Meliaceae), and were known to show various biological activity. Six new limonoids, ceramicines U-Z (1-6), with a cyclopentanone[α]phenanthrene ring system with a ß-furyl ring at C-17 were isolated from the barks of C. ceramicus. Their structures were determined on the basis of the 1D and 2D NMR analyses, and their absolute configurations were investigated by CD spectroscopy. Ceramicine W (3) exhibited potent antimalarial activity against Plasmodium falciparum 3D7 strain with IC50 value of 1.2 µM. In addition, the structure-antimalarial activity relationship (SAR) of the ceramicines was investigated to identify substituent patterns that may enhance activity. It appears that ring B and the functional groups in the vicinity of rings B and C are critical for the antimalarial activity of the ceramicines. In particular, bulky ester substituents with equatorial orientation at C-7 and C-12 greatly increase the antimalarial activity.

[Severe neuropsychiatric disorder developing during busulfan-containing regimen for stem cell transplantation].

Here we describe two patients that required interruption of a busulfan (BU) containing conditioning regimen due to severe mental disorder before stem cell transplantation. The first patient was a 66-year-old man scheduled for unrelated peripheral blood stem cell transplantation with fludarabine/BU conditioning for myelodysplastic syndrome. He received 9.6 mg/kg BU and developed hallucinations that worsened the next day. BU was stopped on the final day, but the patient became comatose (grade 4). He recovered the next day. The second patient was a 69-year-old man scheduled for autologous peripheral blood stem cell transplantation with thiotepa (TT)/BU conditioning for cerebral nervous system relapse of mantle cell lymphoma. He received 12.8 mg/kg BU and developed hallucinations. His mental symptoms worsened on the next day, and thus administration was stopped on the second day of TT. His symptoms improved the next day. Both patients were over 65 years old, and their psychiatric symptoms worsened 1-2 days after the final dose of BU. Our findings suggest that BU may cause psychiatric disorders in elderly patients. When performing BU conditioning, it may be necessary to avoid azole antifungal medication and acetaminophen and to reduce the dose or perform therapeutic dose monitoring for elderly patients.

Dystonia-like Movement Disorders Ameliorated by Shear Force and Pressure Stimulation after Small Infarction in the Left Posterolateral Thalamus.

Focal dystonia (FD) can develop after thalamic lesions. Abnormal somatic sensations were argued to be responsible for FD. Our patient experienced FD-like movement disorders, agraphesthesia, and a reduced sense of shear force on the skin and pressure to deep tissues of the right upper limb following a small infarction in the left posterolateral thalamus. FD-like symptoms improved while the skin was being pulled or the deep tissue was being pushed in a manner proportional to the strength of muscle contractions. Therefore, the lack of these sensations was suggested to be related to FD-like symptoms.

Factors influencing the development of Multicystic Dysplastic Kidney (MCDK) following urinary tract obstruction in the fetal lamb.

BACKGROUND: Creating obstructive uropathy (OU) during glomerulogenesis in the fetal lamb results in multicystic dysplastic kidney (MCDK) at term. We explored this using immunohistochemical techniques. METHOD: OU was created in fetal lambs at 60-day gestation, ligating the urethra and urachus. The kidneys of MCDK lambs, 60-day gestation fetal lambs, full-term lamb (145 days), term sham-operated lambs, and adult ewes were evaluated by HE staining, and immunohistochemistry with paired box genes 2 (PAX2) and CD10. RESULTS: Multiple cysts were found in the MCDK model. CD10 was expressed in proximal tubular epithelial cells, glomerular epithelial cells, and medullary stromal cells in the kidneys of 60-day gestation fetal lambs and full-term lambs and adult ewes. PAX2 expression was found in ureteric buds, C- and S-shaped bodies, epithelial cells of collecting ducts, and Bowman's capsule of fetal kidneys at 60-day gestation, but only in the collecting ducts of full-term fetal lambs and adult ewes. Both CD10 and PAX2 were expressed in the cystic epithelial cells of the MCDK model. DISCUSSION: PAX2 expression in cystic epithelial cells suggests that cyst formation is associated with disturbed down-regulation of PAX2 in the nephrogenic zone epithelial cells during the renal development in the OU model.

Effect of neurocognitive rehabilitation on upper limb function in community-dwelling chronic stroke patients: A pilot study.

BACKGROUND: Although it has been reported that neurocognitive rehabilitation is effective for improving upper limb function in acute and subacute stroke patients, its effectiveness has not been clarified in community-dwelling chronic stroke patients. OBJECTIVE: To examine the effect of neurocognitive rehabilitation on upper limb function in community-dwelling chronic stroke patients. METHODS: Eight community-dwelling chronic stroke patients participated in the study. The mean period from the stroke onset to the start of the intervention was 425.3 days (approximately 14 months post-stroke). All patients received neurocognitive rehabilitation for 60 min, twice per week, for 3 months. Fugl-Meyer Assessments (FMA) were performed, and the amount of use (AOU) and quality of movement (QOM) of the Motor Activity Log (MAL) were measured before and after the intervention. We used the Wilcoxon signed-rank test to analyze the data. RESULTS: The total, shoulder/elbow/forearm, and wrist scores of the FMA, MAL-AOU, and MAL-QOM significantly improved after the intervention compared to those before the intervention. However, significant improvement was not observed in the hand score of the FMA. CONCLUSION: Neurocognitive rehabilitation could be effective for improving upper limb function in community-dwelling chronic stroke patients.

The triangular cord ratio and the presence of a cystic lesion in the triangular cord. Suggested new ultrasound findings in the early diagnosis of Biliary Atresia.

BACKGROUND: In biliary atresia (BA), the ultrasonic triangular cord (TC) sign is positive at ≥ 3 mm, but sometimes there is BA even if it is ≤ 3 mm. For improving the ultrasonographic diagnosis, we have established a new evaluation, adding the ratio of the anterior/posterior thickness (TC ratio) in the hyperechoic area and the presence of a cystic lesion in the triangular cord (TCC). METHODS: We examined 24 cases of suspected BA who demonstrated acholic stools from 2006 to 2020. We retrospectively reviewed the timing of ultrasonographic diagnosis, the gallbladder diameter, gallbladder mucosal irregularity, the TC sign, TCC, and the TC ratio. RESULTS: In the BA group (n = 10) vs the Non-BA group (n = 14), the age at ultrasonography was 75 ± 41.7 vs. 81 ± 39.1 days (p = 0.72), the gallbladder diameter was 12.1 ± 9.7 vs. 24.2 ± 6.96 mm (p = 0.02), irregularity of gallbladder mucosa was 7 cases vs. 1 case (p < 0.01), and TC sign was 3.9 ± 1.3 vs. 2.0 ± 0.49 mm (p = 0.01), respectively. TCC was observed in 8/10 cases in the BA group and none in the Non-BA group (p < 0.01). TC ratio was 3.40 ± 0.68 (BA group) and 1.59 ± 0.41 (Non-BA group) (p < 0.01). CONCLUSION: The ultrasonic TC ratio improves the diagnostic accuracy of BA. TCC is a specific finding in the BA group.

The Expression of Transcription Factors in Fetal Lamb Kidney.

(1) Background: Renal development involves frequent expression and loss of transcription factors, resulting in the activation of genes. Wilms' tumor 1 (WT1), hepatocyte nuclear factor-1-beta (HNF1ß), and paired box genes 2 and 8 (Pax2 and Pax8) play an important role in renal development. With this in vivo study, we examined the period and location of expression of these factors in renal development. (2) Methods: Fetal lamb kidneys (50 days from gestation to term) and adult ewe kidneys were evaluated by hematoxylin and eosin staining. Serial sections were subjected to immunohistochemistry for WT1, HNF1ß, Pax2, and Pax8. (3) Results: Pax2, Pax8, and HNF1ß expression was observed in the ureteric bud and collecting duct epithelial cells. We observed expression of WT1 alone in metanephric mesenchymal cells, glomerular epithelial cells, and interstitial cells in the medullary rays and Pax8 and HNF1ß expression in tubular epithelial cells. WT1 was highly expressed in cells more proximal to the medulla in renal vesicles and in C- and S-shaped bodies. Pax2 was expressed in the middle and peripheral regions, and HNF1ß in cells in the region in the middle of these. (4) Conclusions: WT1 is involved in nephron development. Pax2, Pax8, and HNF1ß are involved in nephron maturation and the formation of peripheral collecting ducts from the Wolffian duct.

Differences in post-operative complications after reconstruction for congenital biliary dilatation in a single institution-Roux-en-Y hepaticojejunostomy versus hepaticoduodenostomy.

BACKGROUND: The standard surgical procedure for congenital biliary dilatation (CBD) consists of excision of extrahepatic bile duct and Roux-en-Y hepaticojejunostomy (HJ). However, alternative reconstructive operations for CBD includes hepaticoduodenostomy (HD). We compared postoperative complications and therapeutic outcomes of these two operations at our institution. METHODS: From 1981 to 2009, there were 23 traceable patients who underwent operation for CBD, They were divided into an HJ Group (n = 15) and an HD Group (n = 8). Demographic and outcome data were compared. RESULTS: There were no significant differences in postoperative complications (cholangitis, pancreatitis, and anastomotic stenosis) and current blood test data (AST, ALT, Total Bilirubin, Direct Bilirubin, Amylase) between the two groups. Current abdominal pain and carcinogenesis were not observed in either group. Intrahepatic stones occurred in one patient in each group, both > 25 years post-operation. CONCLUSION: HD is considered to be an acceptable reconstruction method compared to HJ, based on our results. There has been a suggestion that inadequate diversion in HD might increase the risk of cholangiocarcinoma. To date, in this series, that has not happened.

A new approach using image analysis to assess pulmonary hypoplasia in the fetal lamb diaphragmatic hernia model.

BACKGROUND: In congenital diaphragmatic hernia (CDH), there is pulmonary hypoplasia (PH) and also pulmonary vascular and bronchial abnormalities. Few studies have investigated bronchial maldevelopment in CDH. We evaluated bronchial area (BA) by bronchography in a fetal lamb DH model to develop a measure of PH. METHODS: We created DH in fetal lambs at 75 days gestation, delivering by cesarean section and killing them at term (DH, n = 12). Normal term fetuses provided controls (C, n = 5). We measured total lung volume (TLV) and performed barium bronchography. Using image analysis, BA, total lung area (TLA) and bronchial area/lung area ratio (B/L ratio) were calculated. Student's T test (p < 0.05; significant) and Spearman's correlation coefficient were performed. RESULTS: TLV (ml) was 133.3 ± 41.2 in DH and 326 ± 22.5 in C (p = 0.0000001). TLA (cm2) was 78.8 ± 17.4 in DH and 107.1 ± 10.3 in C (p = 0.006). BA (cm2) was 39.6 ± 11.9 in DH and 52.2 ± 7.7 in C (p = 0.019). The B/L ratio was 0.45 ± 0.06 in DH and 0.49 ± 0.05 in C (p = 0.28). There are correlations in DH between TLV and TLA (r = 0.79), TLV and BA (r = 0.73) and in C between TLV and TLA (r = 0.97) and TLV and BA (r = 0.67). CONCLUSION: It may be possible to assess PH on fetal MRI, given the correlation between TLV and TLA, and TLV and BA.

The role of the ureteric bud in the development of the ovine fetal kidney.

BACKGROUND: The kidney develops from an intimate interaction between the ureteric bud and the metanephric mass. We attempted to differentially stain the derivatives of the ureteric bud and the metanephric mass in ovine fetuses. METHODS: After appropriate approval, 47 fetal lambs' kidneys at 50 (4), 60 (6), 70 (5), 80 (4), 100 (10), 110 (8), 145 (10) days' gestation (term is 140-145 days) were obtained. After confirming the pregnancy, the sheep were anesthetized, and the fetuses sacrificed. The fetal kidneys were prepared for histological examination, using immunostaining for ß-catenin, Laminin, CK34ßE12, CK7, E-cadherin, and EMA. RESULTS: In the nephrogenic zone, positive staining was only seen for ß-catenin and Laminin. Areas with linear ß-catenin expression increased with increasing gestational age, whereas cytoplasmic granular expression in the nephrogenic zone diminished. At 50 days, Laminin-positive cells appeared in the ureteric bud epithelial cells, but not in the proximal tubule epithelium. They were found only in the immature collecting duct at 60 days. CONCLUSION: We have shown that the distribution of ß-catenin and Laminin positive-stained cells initially appearing in the ureteric bud changes with gestational age. Further studies may help inform the optimal timing of fetal shunt insertion in obstructive uropathy.

The effect of the broad-spectrum antibiotics for prevention of postoperative intra-abdominal abscess in pediatric acute appendicitis.

BACKGROUND: We investigated the efficacy of broad-spectrum antibiotics for prevention of postoperative intra-abdominal abscess in pediatric acute appendicitis with our 3 risk factors:-WBC > 16.5 (× 103/µl), CRP > 3.1 (mg/dl) and appendix maximum short diameter on diagnostic imaging > 11.4 mm. METHODS: Four hundred twenty-two patients were reviewed. Patients with 0-1 risk factors were assessed as low-risk and those with 2-3 were high-risk. In the low-risk group, Group A (n = 66) patients received broad-spectrum antibiotics and Group B patients (n = 265) received narrow-spectrum monotherapy. In the high-risk group, Group C patients (n = 63) received broad-spectrum antibiotics and Group D patients (n = 28), narrow-spectrum antibiotics. The outcomes were the incidence of postoperative abscess and the total duration of intravenous (IV) antibiotics. RESULTS: The incidence of intra-abdominal abscess was 6.06% in Group A versus 1.89% in Group B (p = 0.08), and 19.05% in Group C versus 3.57% in Group D (p = 0.06). Total IV antibiotic duration (days) were 6.12 ± 2.87 in Group A versus 3.83 ± 0.69 in Group B (p < 0.01), and 7.84 ± 4.57 in Group C versus 4.00 ± 0.82 in Group D (p < 0.01). CONCLUSION: Broad-spectrum antibiotics did not prevent postoperative intra-abdominal abscess in either low or high-risk groups.

Potential Tuning of Nanoarchitectures Based on Phthalocyanine Nanopillars: Construction of Effective Photocurrent Generation Systems.

Nanopillars composed of a photoresponsive phthalocyanine derivative have been conveniently fabricated using a continuous silane coupling reaction on a substrate. The chemical potentials of phthalocyanine nanopillars (PNs) are precisely controlled by changing the number of phthalocyanine derivatives on the substrate. In addition, photocurrent generation efficiencies have been strongly influenced by the number of phthalocyanine derivatives. High photocurrent conversion cells in a solid state have been obtained by the combination of PNs and a fullerene derivative.

Molecular targeting of neuroblastoma with a novel p16INK4a transporter system.

Potential molecular targets in neuroblastoma include ALK mutations, p16 deletion and CDK2A mutations; however, targeted therapeutics have not been developed for these factors. We developed Wr-T, a new system for intracellular peptide and protein delivery with a 30-residue sequence that mediates molecule entrapment and intracellular permeability. Wr-T was used to introduce the p16INK4a functional peptide to restore the tumor suppressor function of p16INK4a. Introduction of Wr-T into rats with subcutaneous grafts of neuroblastoma produced an astonishing 75.6% tumor suppression (p<0.0005). Thus, the p16INK4a functional peptide can be introduced in low doses and, because it exists in vivo, it should produce fewer side-effects than standard chemotherapy. We suggest this system could be used for molecular-targeted peptides other than p16INK4a and should be pursued for further development.

Management of intraventricular hemorrhage in preterm infants with low birth weight.

The management of posthemorrhagic hydrocephalus is difficult and not well standardized. We evaluated our management protocol for infants with intraventricular and/or periventricular hemorrhage (IVH and PVH, respectively). There were four deaths and two significant treatment-related complications in our series. We also observed two cases of isolated ventricle in patients treated with reservoir placement. After evaluating our series, we modified our protocol from reservoir placement to either cerebrospinal fluid (CSF) drainage or ventriculosubgaleal shunt directly. We will reevaluate this new protocol in the near future.

A case of metastatic brain tumor causing multifocal cerebral embolism.

The patient was a 72-year-old woman who had previously undergone treatment for femoral chondrosarcoma (histologically rated as myxofibrosarcoma). She suddenly developed left homonymous hemianopsia and was diagnosed with cerebral embolism. Because she had atrial fibrillation, we treated her for cardiogenic cerebral embolism. About 3 months later, however, she developed left hemiplegia, and head magnetic resonance imaging revealed multiple tumorous lesions affecting the previously detected infracted area and several new areas. We assumed that a tumor embolus had caused cerebral embolism, which resulted in growth of the tumor from the embolus and formation of a metastatic brain tumor. The metastatic foci formed from the tumor embolus were visualized by diagnostic imaging, and histological examination of the resected tumor confirmed that the brain tumor had occluded the brain vessel (tumorigenic cerebral embolism). No such case has been reported to date, and this case seems to be important.

Morphological and flow cytometric analysis of cell infiltration in glioblastoma: a comparison of autopsy brain and neuroimaging.

Even when we successfully perform a total extirpation of glioblastoma macroscopically, we often encounter tumor recurrence. We examined seven autopsy brains, focusing on tumor cell infiltration in the peripheral zone of a tumor, and compared our findings with the MR images. There has so far been no report regarding mapping of tumor cell infiltration and DNA histogram by flow cytometry, comparing the neuroimaging findings with the autopsy brain findings. The autopsy brain was cut in 10-mm-thick slices, in parallel with the OM line. Tissue samples were obtained from several parts in the peripheral zone (the outer area adjacent to the tumor edge as defined by postcontrast MRI) and then were examined by H&E, GFAP, and VEGF staining. We defined three infiltrating patterns based on number of infiltrated cells as follows: A zone, 100%-60% of the cells infiltrated tumor cells compared with tumor cell density of the tumor mass; B zone, 60%-20%; C zone, 20%-0%. In the autopsy brain, the tumor was easily identified macroscopically. We found that (1) the tumor cells infiltrated the peritumoral area; and (2) tumor cell infiltration was detected over an area measuring from 6 to 14 mm from the tumor border in the A zone. When performing surgery on glioblastoma, a macroscopic total extirpation of the tumor as defined by the contrast-enhanced area in MRI is therefore considered to be insufficient for successfully reducing tumor recurrence.

[Reiter's syndrome following intravesical instillation of Bacillus Calmette-Guerin].

A 54-year-old man who had received intravesical instillation of bacillus Calmette-Guerin(BCG) after transurethral resection for bladder cancer suffered from multiple arthritis, bilateral conjunctivitis, miction pain and high fever. Under the diagnosis of Reiter's syndrome, a nonsteroidal anti-inflammatory drug, histamine antagonists, anti-tubercular agent and corticosteroid were administered. The symptoms were improved within one month. It is important in early diagnosis and treatment of Reiter's syndrome to observe carefully the complications following intravesical instillation of BCG.

Interleukin-5 and interleukin-10 are produced in central nervous system tumor cysts.

Interleukin-5 and interleukin-10, as important mediators of vascular permeability, contribute to the development of various pathologic effusions. However, little is known regarding the involvement of these two cytokines in the formation of cysts associated with central nervous system (CNS) tumors. Twenty-eight patients with various cystic CNS tumors were investigated for expression of interleukin-5 and interleukin-10 in cyst fluid and their matched cytokine receptors in tumor tissue. Interleukin-5 and interleukin-10 were detected in cyst fluid, and interleukin-5 concentration was significantly correlated with interleukin-10 concentration (r=0.508, p=0.006). Moreover, both receptors were also detectable in the tumor tissue specimens and high levels of expression were also found in perivascular cells. Therefore, the local production of interleukin-5 and interleukin-10 might be implicated in some types of cyst formation.

An immunohistochemical and electron microscopic study of atypical teratoid/rhabdoid tumor.

We report two infant cases with atypical teratoid/rhabdoid tumor (AT/RT) located in the cerebellar vermis and spinal cord. MRI showed the tumors were isointense on T1-weighted images and mixed intensity of isointense and slight high intensity on T2-weighted images. Postcontrast MRI demonstrated clear margin of tumor and heterogeneous strong enhancement. It was difficult to differentiate the tumor from medulloblastoma by hematoxylin and eosin staining. However, immunohistochemical staining showed that these tumor cells react positively for cytokeratin, smooth muscle actin (SMA), and epithelial membrane antigen (EMA) and helped us with the differentiation. Electron microscopic study has confirmed the presence of mesenchymal components, such as filaments and desmosome junctions in the rhabdoid cells, but no neuronal components. The tumors rapidly increased in size, showing high MIB-1 index, and the prognosis was gave.

The intracranial pressure of the patients with mild form of craniosynostosis.

INTRODUCTION: While raised intracranial pressure (ICP) is a well recognized complication affecting children with syndromic craniosynostosis, certain percentage of the patients with non-syndromic craniosynostosis may have some problems related to increased ICP, such as developmental delay or visual problem. However, it is still not clear how many percent of and/or which types of craniosynostosis patients suffer from those symptoms, especially in older patients. OBJECTIVE: The aim of this study was to examine the ICP of older children with mild form of craniosynostosis to determine if any of them should be surgically treated. MATERIALS AND METHODS: We measured ICP before making the decision for surgical intervention. RESULTS: Twenty-five of thirty-six patients had raised ICP in our series. DISCUSSION: All of the 25 patients were treated surgically and followed-up after more than 1 year. All patients improved in some degree. Further investigations should be performed to determine what is the threshold for raised ICP in children.