High-yield and high-purity amide bond formation using DMTMM PF6 for DNA-encoded libraries.

In this study, we report on the ability of DMTMM PF6 to improve the amidation reaction. The on-DNA amidation reaction using DMTMM PF6 demonstrates higher conversion rates than those using HATU or DMTMM Cl, particularly with challenging sterically hindered amines and carboxylic acids. The developed method enables the expansion of available building blocks and the efficient synthesis of high-purity DNA-encoded libraries.

Primary diffuse large B-cell lymphoma of the Larynx.

The larynx is a rare site of extranodal non-Hodgkin lymphoma (NHL), accounting for less than 1% of all primary laryngeal neoplasms. We report a rare case of laryngeal diffuse large B-cell lymphoma (DLBCL) in an 85-year-old female patient, which was difficult to diagnose even after several biopsies from the primary laryngeal lesion, both under local and general anesthesia, and the diagnosis of DLBCL was obtained from the lymph node biopsy, which appeared in the proximity of the larynx 2 months after the first biopsy from the larynx. Since the diagnosis of laryngeal NHL is sometimes difficult when sufficient samples cannot be obtained, repeated biopsies may be required. Due to the small number of cases, there is no definite consensus regarding the best management of laryngeal NHL. Thus, a standard treatment option for DLBCL, such as 3 courses of R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine and prednisone) followed by Involved-field radiation therapy, or 6∼8 course of R-CHOP, are also applied for the treatment of laryngeal DLBCL. For this case, doxorubicin was not adopted and 8 courses of R-COP (rituximab + cyclophosphamide, vincristine and prednisone) at a decreased dose were chosen because of her age (85-year-old) and cardiac hypofunction.

A case report of thyroid cancer showing a remarkable effect of gefitinib.

Thyroid cancer is a common type of cancer. The most radical treatment for this type of tumor is surgical removal. Gefitinib disrupts the EGFR kinase activity. This report describes a patient with thyroid cancer who demonstrated a complete response to gefitinib. The patient was a 56-year-old woman. She had been treated for lung cancer. The lung cancer had initially disappeared following chemoradiotherapy. However, a few months later, a distant metastasis was detected on the opposite lung field. Thyroid cancer was then incidentally observed when these lesions were examined. Fine needle aspiration cytology of the thyroid tumor with ultrasonography (US) showed papillary carcinoma. Finally, all of the lesions were treated with gefitinib. Gefitinib demonstrated a remarkable effect on both the thyroid and lung lesions. The CT showed a complete resolution of the masses in the lung, neck and thyroid. The present report suggests that treatment with gefitinib is therefore an effective option for thyroid papillary carcinoma.

Biopsy of cervical lymph node.

OBJECTIVE: This report examines 60 non-cancer patients who underwent a cervical lymph node biopsy, and discusses the value of the cervical lymph node biopsy as a diagnostic tool. METHODS: Sixty patients with cervical lymph node enlargement who had lymph node biopsies at the Juntendo University between 2004 and 2007 were examined. The clinical parameters including age, size of the lymph node, white blood cell (WBC), C reactive protein (CRP), lactate dehydrase (LDH), soluble interleukin-2 receptor (sIL-2r) were measured at initial examination. Fine needle aspiration cytology was carried out in all patients. The patients were divided into 2 groups, including the malignant lymphoma (ML) group and the benign disease group. These groups were compared based on the patient's clinical parameters. RESULTS: Serum levels of LDH, sIL-2r, age and lymph node size in the ML group were significantly higher than in the benign group. WBC and CRP showed no significant differences. Simple regression analysis showed that there are correlation between the size of enlargement lymph node and serum levels of LDH and sIL-2r in ML group. CONCLUSION: The results of this study suggest that a biopsy should be considered early to patients with an advanced age, large swollen lymph nodes or high levels of serum sIL-2r or LDH.

[Method for DNA extraction and purification from corn-processed food using an ion-exchange resin type kit].

The yield of genomic DNA extracted from corn-processed foods, such as corn flake and one of the corn snack what is called "Jumbo corn", using an ion-exchange resin type kit (Gtip) has been reported to be very low, and it is thought to be difficult to detect the intrinsic corn gene "Zein" in the foods. Therefore, we developed a new method using Gtip, which we called the "KNG-Gtip method," by modification of the Ministry of Health, Labour and Welfare (MHLW) method using Gtip (MHLW-Gtip method). We compared the KNG-Gtip method, MHLW-Gtip method, the Gtip method for detection of allergen (ALG-Gtip method), and the Gtip method according to the Ministry of Agriculture, Forestry and Fisheries (MAFF) (JAS-Gtip method) in terms of the yield and quality of genomic DNA and the detection probabilities of the PCR-amplified Zein gene. The concentrations of DNA and the detection probabilities of the PCR-amplified Zein gene of genomic DNA extracted from 4 g corn flake and 4 g Jumbo corn by the KNG-Gtip method were larger than those by using the conventional methods. In addition, the PCR-amplified Zein gene from 4 g of corn starch could be detected by the KNG-Gtip method. We propose that the KNG-Gtip method, in which requires sample weight of four grams, is practical and useful to extract genomic DNA from corn flake and Jumbo corn.

Concurrent weekly docetaxel and hyperfractionated radiotherapy for advanced head and neck cancer.

BACKGROUND: This study was designed to evaluate the concomitant use of weekly docetaxel and hyperfractionated radiotherapy for the treatment of head and neck cancer (HNC). PATIENTS AND METHODS: Twenty-five patients with advanced squamous cell HNC were treated with hyperfractionated radiotherapy (72 Gy at 1.2 Gy twice per day) and weekly chemotherapy with docetaxel (10 mg/m2). RESULTS: Toxicity was significant, with grade 2 to 4 mucositis observed in 100% and lymphopenia in 84%. Seventeen patients (68%) received the full chemotherapy regimen as planned. The initial overall response rate was 88.0%, while the complete response rate was 68.0%. At a median follow-up period of 10 months, the 2-year Kaplan-Meier projected overall survival was 47.3%, and the cause-specific survival was 81.8%. CONCLUSIONS: This study demonstrated that hyperfractionated radiotherapy with weekly docetaxel achieved better initial response than conventional radiotherapy. In addition, the acute toxicity of this regimen was within the acceptable limits of severity.

No association between the CNTF null mutation and schizophrenia or personality.

The ciliary neurotrophic factor (CNTF) is a neurotrophic cytokine that plays a critical role in neurodevelopment. On the basis of neurodevelopmental hypothesis, the CNTF gene has been a candidate locus for schizophrenia. Several studies have investigated the association between the null mutation of the gene and schizophrenia, however, with inconsistent results. In the present study, we investigated the association in 222 Japanese patients with schizophrenia and 237 controls. The association between the mutation and personality traits was also studied, to investigate the effect of the mutation in participants from the general population. As a result, no association was observed between the mutation and schizophrenia nor personality traits, evaluated by using the Revised NEO Personality Inventory scores. The present study did not provide evidence for the association between the CNTF gene and schizophrenia or personality traits in the Japanese population.

Renal transcatheter arterial embolization for autosomal dominant polycystic kidney disease: report of two cases.

We report the results of renal transcatheter arterial embolization (renal-TAE) in two patients with autosomal dominant polycystic kidney disease (ADPKD) treated with hemodialysis (HD). A 73-year-old man and a 65-year-old woman on HD visited our department complaining of abdominal fullness, abdominal pain and appetite loss. Abdominal computerized tomography (CT) revealed polycystic kidneys. Both patients underwent renal-TAE. Approximately 1 month later, the symptoms had improved and CT showed decreased cyst volume. These results suggest that renal-TAE is a useful therapy for patients with ADPKD.

Identification of a protanomalous chimpanzee by molecular genetic and electroretinogram analyses.

We determined the structures of long (L)-wavelength-sensitive and middle (M)-wavelength-sensitive opsin gene array of 58 male chimpanzees and we investigated relative sensitivity to red and green lights by electroretinogram flicker photometry. One subject had protanomalous color vision, while others had normal color vision. Unlike in humans, a polymorphic difference in the copy number of the genes and a polymorphic base substitution at amino acid position 180 were not frequently observed in chimpanzees.

Development of an efficient procedure for indole ring synthesis from 2-ethynylaniline derivatives catalyzed by CuII salts and its application to natural product synthesis.

The development of efficient methods for the indole synthesis catalyzed by Cu(II) salts and its applications were investigated. Cu(OAc)(2) has been proved to be the best catalyst for the synthesis of various 1-p-tolylsulfonyl or 1-methylsulfonylindoles, which have both electron-withdrawing and electron-donating groups on the aromatic ring and C2 position of indoles. For the primary aniline derivatives, Cu(OCOCF(3))(2) showed good activities, while Cu(OAc)(2) was a good catalyst for the cyclization of secondary anilines. This methodology could be applied to the sequential cyclization reaction for the compounds which have the electrophilic part in the same molecule. By prior treatment with KH, the sequential cyclization was realized to provide the tricyclic ring systems, but it was limited to five- and six-membered rings for the second cyclization. Finally, formal and total synthesis of hippadine with the Cu(II)-promoted indole synthesis as the key step was accomplished.

Age- and gender-related differences in carbohydrate concentrations of alpha1-acid glycoprotein variants and the effects of glycoforms on their drug-binding capacities.

OBJECTIVE: Alpha(1)-acid glycoprotein (AAG) is a major binding protein for neutral and basic drugs because of its great drug affinity. AAG has three main genetic variants--F1, S, and A variants. Several attempts have been made to elucidate the differences in compositions of the carbohydrate moiety and structure-function relationships such as drug-binding differences. However, there have been few reports on age- and gender-related differences in compositions or concentrations of the carbohydrate moiety of AAG variants. The aim of this study was to clarify the age- and gender-related differences in carbohydrate concentrations and in drug-binding capacities of AAG glycoforms. METHODS: The sera used in this study were obtained from 32 healthy subjects (17 men and 15 women, aged 16-84 years). The AAG glycoforms were isolated by hydroxyapatite chromatography. The binding capacity of AAG to disopyramide (DP), which is a basic drug, was determined using the ultrafiltration method. The concentrations of N-acetylneuraminic acid (NeuAc) and monosaccharides in AAG were determined using high-pH anion-exchange chromatography with pulsed-amperometric detection. RESULTS: The mean plasma AAG concentration in the female subjects was significantly lower than that in the male subjects (0.67 +/- 0.12 mg/ml, mean +/- SD, in females, n = 15, versus 0.81 +/- 0.17 mg/ml in males, n = 17, P < 0.05), but no age-related differences were found (0.75 +/- 0.18 mg/ml in young subjects, n = 24, versus 0.77 +/- 0.12 mg/ml in older subjects, n = 8, n.s.). However, the degree of branching of the glycan chain in the female subjects was significantly lower than that in the male subjects (1.61 +/- 0.17 mol/mol, mean +/- SD, in females, n = 15, versus 1.75 +/- 0.23 mol/mol in males, n = 17, P < 0.05). There was a significant inverse relationship between the binding capacity of AAG to DP (Cb/AAG) and the degree of branching of the glycan chain. The binding capacity (Cb/AAG) decreased as the degree of branching in AAG glycans increased. The binding capacity (Cb/AAG) in the female subjects was significantly higher than that in the male subjects (2.79 +/- 0.59 mg/g AAG in females, mean +/- SD, n = 15, versus 2.37 +/- 0.29 mg/g AAG in males, n = 17, P < 0.05). CONCLUSION. The degree of branching of the glycan chain in AAG plays an important role in drug-binding capacity. Gender-related differences in drug-binding capacity (Cb/AAG) may be caused by differences in the ratios of the extent of branching of the glycan chain in AAG.

What is an appropriate indication for endoscopic papillary balloon dilation?

OBJECTIVE: There are a number of views on the indication for endoscopic papillary balloon dilation (EPBD) in the management of bile duct stones. In this study, we have evaluated the efficacy and safety of EPBD compared with endoscopic sphincterotomy (EST). DESIGN: Prospective randomized trial. SETTING: One university hospital and one general hospital. PARTICIPANTS AND MAIN OUTCOME MEASURES: One hundred and forty patients were randomly allocated to EPBD or EST. Outcomes and complications were observed for a median period of 30 months. RESULTS: Both treatment approaches finally achieved similar success rates and needed similar numbers of treatment sessions for patients with stones less than 10 mm in diameter. However, for patients with stones of 10 mm or more, EPBD required a significantly greater mean number of treatment sessions than EST (2.4 vs 1.6, P < 0.01). Early complications occurred in seven EPBD (four pancreatitis, two cholangitis and one basket impaction) and eight EST (three pancreatitis, two bleeding and three cholangitis) patients. Late complications occurred in four EPBD (three recurrent bile duct stones and one cholecystitis) and six EST (three recurrent stones and three cholecystitis) patients. CONCLUSIONS: EPBD has little risk of bleeding. The technique removed small bile duct stones just as easily as did EST. These two procedures had approximately the same risk of pancreatitis and incidence of recurrent bile duct stones. Therefore, both procedures appear to be appropriate treatments for small bile duct stones. Whether or not EPBD becomes an established treatment will depend on further long-term studies.