Black rice bran intake reduces phosphorylated tau levels and enhances insulin signaling in the brain of aged normal mice.

This study reports that black rice bran (BRB) intake for 50-52 consecutive weeks (∼12 months) reduces tau phosphorylation with a concomitant activation of insulin signaling and subsequent PI3K/AKT pathway in the brain of aged normal mice. BRB holds promise for preventing the formation of neurofibrillary tangles consisting of hyperphosphorylated tau, a pathological hallmark of Alzheimer's disease.

Efficacy of endoscopic gallbladder drainage in patients with acute cholecystitis.

BACKGROUND: Early cholecystectomy is recommended for patients with acute cholecystitis. However, emergency surgery may not be indicated due to complications and disease severity. Patients requiring drainage are usually treated with percutaneous transhepatic gallbladder drainage (PTGBD), whereas patients with biliary duct stones undergo endoscopic stones removal followed by endoscopic gallbladder drainage (EGBD). Herein, we investigated the efficacy of EGBD in patients with acute cholecystitis. METHODS: Overall, 101 patients receiving laparoscopic cholecystectomy between September 2019 and September 2020 in our department were retrospectively analyzed. RESULTS: The patients (n = 101) were divided into three groups: control group that did not undergo drainage (n = 68), a group that underwent EGBD (n = 7), and a group that underwent PTGBD (n = 26). Median surgery time was 107, 166, and 143 min, respectively. Control group had a significantly shorter surgery time, whereas it did not significantly differ between EGBD and PTGBD groups. The median amount of bleeding was 5 g, 7 g, and 7.5 g, respectively, and control group had significantly less bleeding than the drainage group. We further divided patients into the following subgroups: patients requiring a 5 mm clip to ligate the cystic duct, patients requiring a 10 mm clip due to the thickness of the cystic duct, patients requiring an automatic suturing device, and patients undergoing subtotal cholecystectomy due to impossible cystic duct ligation. There was no significant difference between EGBD and PTGBD regarding the clip used or the need for an automatic suturing device and subtotal cholecystectomy. CONCLUSIONS: There was no significant difference between EGBD and PTGBD groups regarding surgery time or bleeding amount when surgery was performed after gallbladder drainage for acute cholecystitis. Therefore, EGBD was considered a useful preoperative drainage method requiring no drainage bag.

Pharmacological interventions versus placebo, no treatment or usual care for osteoporosis in people with chronic kidney disease stages 3-5D.

BACKGROUND: Chronic kidney disease (CKD) is an independent risk factor for osteoporosis and is more prevalent among people with CKD than among people who do not have CKD. Although several drugs have been used to effectively treat osteoporosis in the general population, it is unclear whether they are also effective and safe for people with CKD, who have altered systemic mineral and bone metabolism. OBJECTIVES: To assess the efficacy and safety of pharmacological interventions for osteoporosis in patients with CKD stages 3-5, and those undergoing dialysis (5D). SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 25 January 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials comparing any anti-osteoporotic drugs with a placebo, no treatment or usual care in patients with osteoporosis and CKD stages 3 to 5D were included. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed their quality using the risk of bias tool, and extracted data. The main outcomes were the incidence of fracture at any sites; mean change in the bone mineral density (BMD; measured using dual-energy radiographic absorptiometry (DXA)) of the femoral neck, total hip, lumbar spine, and distal radius; death from all causes; incidence of adverse events; and quality of life (QoL). Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) for continuous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Seven studies involving 9164 randomised participants with osteoporosis and CKD stages 3 to 5D met the inclusion criteria; all participants were postmenopausal women. Five studies included patients with CKD stages 3-4, and two studies included patients with CKD stages 5 or 5D. Five pharmacological interventions were identified (abaloparatide, alendronate, denosumab, raloxifene, and teriparatide). All studies were judged to be at an overall high risk of bias. Among patients with CKD stages 3-4, anti-osteoporotic drugs may reduce the risk of vertebral fracture (RR 0.52, 95% CI 0.39 to 0.69; low certainty evidence). Anti-osteoporotic drugs probably makes little or no difference to the risk of clinical fracture (RR 0.91, 95% CI 0.79 to 1.05; moderate certainty evidence) and adverse events (RR 0.99, 95% CI 0.98 to 1.00; moderate certainty evidence). We were unable to incorporate studies into the meta-analyses for BMD at the femoral neck, lumbar spine and total hip as they only reported the percentage change in the BMD in the intervention group. Among patients with severe CKD stages 5 or 5D, it is uncertain whether anti-osteoporotic drug reduces the risk of clinical fracture (RR 0.33, 95% CI 0.01 to 7.87; very low certainty evidence). It is uncertain whether anti-osteoporotic drug improves the BMD at the femoral neck because the certainty of this evidence is very low (MD 0.01, 95% CI 0.00 to 0.02). Anti-osteoporotic drug may slightly improve the BMD at the lumbar spine (MD 0.03, 95% CI 0.03 to 0.04, low certainty evidence). No adverse events were reported in the included studies. It is uncertain whether anti-osteoporotic drug reduces the risk of death (RR 1.00, 95% CI 0.22 to 4.56; very low certainty evidence). AUTHORS' CONCLUSIONS: Among patients with CKD stages 3-4, anti-osteoporotic drugs may reduce the risk of vertebral fracture in low certainty evidence. Anti-osteoporotic drugs make little or no difference to the risk of clinical fracture and adverse events in moderate certainty evidence. Among patients with CKD stages 5 and 5D, it is uncertain whether anti-osteoporotic drug reduces the risk of clinical fracture and death because the certainty of this evidence is very low. Anti-osteoporotic drug may slightly improve the BMD at the lumbar spine in low certainty evidence. It is uncertain whether anti-osteoporotic drug improves the BMD at the femoral neck because the certainty of this evidence is very low. Larger studies including men, paediatric patients or individuals with unstable CKD-mineral and bone disorder are required to assess the effect of each anti-osteoporotic drug at each stage of CKD.

Effect of parenteral hydration therapy based on the Japanese national clinical guideline on quality of life, discomfort, and symptom intensity in patients with advanced cancer.

CONTEXT: Although an evidence-based clinical guideline for parenteral hydration therapy was established in Japan, the efficacy of the guideline has not been assessed. OBJECTIVES: Our purpose was to explore the effect of parenteral hydration therapy based on this clinical guideline on quality of life (QoL), discomfort, symptoms, and fluid retention signs in patients with advanced cancer. METHODS: This multicenter, prospective, observational study included 161 patients with advanced abdominal cancer who received guideline-based hydration therapy. We evaluated the longitudinal changes of the global QoL (Item 30 of European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire-C30); the Discomfort Scale; the intensity of seven physical symptoms; and the severity of fluid retention signs. We also evaluated patient satisfaction and the feeling of benefit from hydration one week after the study commenced, and bronchial secretions, hyperactive delirium, communication capacity, and agitation 48 hours before a patient's death. RESULTS: The global QoL, the Discomfort Scale, and the intensities of all physical symptoms, except for vomiting and drowsiness, were stable throughout the study period. More than 80% of patients maintained all fluid retention signs. Patient global satisfaction was 76.4 (0-100) and feeling of benefit was 5.43 (range 0-7). CONCLUSION: Guideline-based parenteral hydration therapy contributed to maintaining global QoL and provided satisfaction and a feeling of benefit without increasing discomfort and worsening symptoms and fluid retention signs in patients with advanced cancer.

Hepatitis C virus infection causes hypolipidemia regardless of hepatic damage or nutritional state: An epidemiological survey of a large Japanese cohort.

AIM: Infection with hepatitis C virus (HCV) is the leading cause of liver cirrhosis that develops into hepatocellular carcinoma. Previous studies have shown in vitro that lipids within hepatocytes are crucially important for a series of HCV infection-proliferation-release processes. On the other hand, in the patients with HCV, the serum total cholesterol (Total-C) and low-density lipoprotein cholesterol (LDL-C) levels have been reported to be lower. We conducted an epidemiological survey of a large cohort and investigated whether the lower serum lipid levels were caused by a direct or the secondary effects of HCV infection (i.e. hepatic damage or nutritional disorder). METHODS: Among 146 857 participants (male, 34%; female, 66%) undergoing public health examinations between 2002 and 2007 in Ibaraki Prefecture, Japan, the HCV positive rates determined by HCV antibody/antigen and/or RNA tests were 1.37% and 0.67% in males and females, respectively. RESULTS: In addition to Total-C and LDL-C, serum high-density lipoprotein cholesterol and triglyceride concentrations were also significantly lower in the HCV positive subjects compared with the negative subjects, regardless of sex, age or nutritional state evaluated by body mass index. Multivariate analysis showed that HCV infection was the strongest among the factors to be significantly associated with the lower level of these lipids. Particularly, the hypolipidemia was also confirmed in the HCV positive subjects with normal aminotransferase levels (alanine aminotransferase ≤30 and aspartate aminotransferase ≤30). CONCLUSION: This epidemiological survey in a large Japanese cohort suggests that the HCV infection itself might directly cause hypolipidemia, irrespective of host factors including age, hepatic damage and nutritional state.

An autopsy case of lymphomatosis cerebri showing pathological changes of intravascular large B-cell lymphoma in visceral organs.

We describe the case of a 61-year-old man presenting with subacute encephalopathy. The clinical manifestations included progressive dementia and pyramidal and extrapyramidal tract signs. Brain CT scan and MRI showed diffuse bilateral white matter changes in the cerebral hemispheres, basal ganglia, thalamus and brainstem. No contrast-enhanced lesion was observed. Peripheral blood studies, CSF analysis, and brain and muscle biopsies were nonspecific and failed to reveal diagnostic evidence of any specific disease. The patient was diagnosed with and treated for a cerebral demyelinating disorder. Post mortem examination showed diffuse infiltration of lymphoma cells without mass lesions in the extensive cerebral white and gray matter with minimal intravascular patterns, particularly in the perivascular and periventricular spaces. These findings were consistent with lymphomatosis cerebri (LC). In other visceral organs such as the lungs, liver, kidneys and adrenal glands, blood vessels were plugged by numerous neoplastic cells which were morphologically and immunohistochemically similar to those observed in the CNS, consistent with intravascular malignant lymphoma (IVL). To our knowledge, this is the first autopsy report showing the coexistence of LC and IVL. This case suggests a possible link between LC and IVL.

Substrate specificity of Rv3378c, an enzyme from Mycobacterium tuberculosis, and the inhibitory activity of the bicyclic diterpenoids against macrophage phagocytosis.

The Rv3378c gene product from Mycobacterium tuberculosis encodes a diterpene synthase to produce tuberculosinol (3), 13R-isotuberculosinol (4a), and 13S-isotuberculosinol (4b) from tuberculosinyl diphosphate (2). The product distribution ratios are 1 : 1 for 3 to 4 and 1 : 3 for 4a to 4b. The substrate specificity of the Rv3378c-encoded enzyme was examined. The 3 labdadienyl diphosphates, copalyl diphosphate (CDP) (7), ent-CDP (8), and syn-CDP (9), underwent the conversion reaction, with good yields (67-78%). Copalol (23) and manool (24) were produced from 7, ent-copalol (25) and ent-manool (26) from 8, and syn-copalol (27) and vitexifolin A (28) from 9. The ratio of 23 to 24 was 40 : 27, that of 25:26 was 22 : 50, and that of 27:28 was 16 : 62. Analysis on a GC-MS chromatograph equipped with a chiral column revealed that 24, 26, and 28 consisted of a mixture of 13R- (a) and 13S-stereoisomers (b) in the following ratio: ca. 1 : 1 for 24a to 24b, ca. 1 : 5 for 26a to 26b, and ca. 1 : 19 for 28a to 28b. The structures of these products indicate that the reactions of the 3 CDPs proceeded in the same fashion as that of 2. This is the first report on the enzymatic synthesis of natural diterpenes manool, ent-manool, and vitexifolin A. Both Rv3377c and Rv3378c genes are found in virulent Mycobacterium species, but not in avirulent species. We found that 3 and 4 inhibited the phagocytosis of opsonized zymosan particles by human macrophage-like cells. Interestingly, the inhibitory activity was synergistically increased by the coexistence of 3 and 4b. Other labdane-related diterpenes, 13-16 and 23-28, had little or no inhibitory activity. This synergistic inhibition by 3 and 4 may provide further advantage to the impairment of phagocyte function, which might contribute to pathogenicity of M. tuberculosis.

Late recurrence of precursor B-cell acute lymphoblastic leukemia 9 years and 7 months after allogeneic hematopoietic stem cell transplantation.

We present the case of a 15-year-old adolescent boy with recurrent precursor B-cell acute lymphoblastic leukemia, which appeared 9 years and 7 months after a first unrelated allogeneic hematopoietic stem cell transplantation (HSCT). The patient received chemotherapy and a subsequent second unrelated allogeneic HSCT, and was free of the disease 3 years after the second HSCT. A molecular study revealed the same rearrangement pattern at IGK@ in both the first relapse and the later relapse, confirming the common origin of the leukemic blasts at different time points. However, a new Vδ2-Dδ3 rearrangement of TRD@ emerged at the later relapse. A subsequent, more sensitive examination revealed a minor subpopulation with rearrangements at both IGK@ and TRD@, even during the first relapse. This finding suggests that the minor clone, related to the major clone, was present at the first relapse, leading to the later recurrence, even though the major clone at the first relapse had been eradicated by the first allogeneic HSCT. Although a later relapse after allogeneic HSCT is a rare phenomenon, clinicians should keep in mind that later relapses can occur, even after allogeneic HSCT.

A case of laryngeal carcinoma in a young adult with dyskeratosis congenita.

Dyskeratosis congenita (DC) is an inherited disorder that is characterized by the triad of skin pigmentation, nail dystrophy, and mucosal leukoplakia. Individuals with DC suffer from premature mortality because of bone marrow failure, pulmonary disease, or malignant transformation within the areas of mucosal leukoplakia, caused by telomerase dysfunction. We present a case of a 31-year-old Japanese man with DC who developed laryngeal cancer (supraglottic T4aN0M0). To avoid the serious risks of accelerating the DC-associated complications by DNA-damaging therapies, he was treated with a total laryngectomy plus right modified neck dissection (levels IB, IIA, III, and IV). A contralateral nodal metastasis appeared 4 months after initial surgery and was salvaged by a left radical neck dissection. Our strategy to spare DNA-damaging therapies has proven effective so far. This is the first reported case of laryngeal cancer in a patient with DC in the English-language medical literature.

Comparative quantitative analysis of 14 types of human papillomavirus by real-time polymerase chain reaction monitoring Invader reaction (Q-Invader assay).

Human papillomavirus (HPV) is associated with several cervical diseases. A simple, rapid, cost-effective assay for identifying viral genotypes would greatly aid efforts for early detection and disease prevention. A real-time polymerase chain reaction monitoring Invader reaction assay (Q-Invader assay) was developed for genotyping and comparative quantitative analysis of 14 high-risk HPV genotypes (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 67, and 68). A total of 131 cervical samples containing HPV in Japan were examined by Q-Invader assay, and the results were compared with those from sequencing with consensus and genotype-specific primers. Genotypes determined by Q-Invader agreed with those of sequencing in all samples. Coinfections with multiple high-risk genotypes were correctly identified by Q-Invader assay in 27 samples. In addition, the relative ratios of the genotypes were determined. Thus, Q-Invader assay is a useful tool for genotyping and comparative quantitative analysis of high-risk HPV types.

Quantitation of viral load by real-time PCR-monitoring Invader reaction.

With its broad effective range for fluorescence detection, real-time PCR is one of the most valuable techniques for quantitation in molecular biology. A modified real-time PCR assay is described for determining viral load. The assay uses fluorescence to measure the number of PCR amplicons by monitoring the Invader reaction in four steps in the thermal cycle. The Invader reaction with its cleavase was performed at moderate temperature after the amplicon was denatured at a high temperature. The method was as effective as real-time PCR with a TaqMan probe in determining the quantity of virus in samples of human papillomavirus type 16. Importantly, the assay allows the use of a common probe for multiple reactions. Thus, this method is a rapid inexpensive assay with a common fluorescence probe that does not depend on the conformation of the target DNAs.

Highly sensitive analysis of sterol profiles in human serum by LC-ESI-MS/MS.

We have developed a highly sensitive and specific method for the analysis of serum sterol profiles. Sterols in 1 mul of dried serum were derivatized into picolinyl esters (3beta-picolinate) and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using the electrospray ionization (ESI) mode. In addition to cholesterol, 19 cholesterol precursors, cholestanol, campesterol, sitosterol, and sitostanol were identified simultaneously. Quantitative analyses for the picolinyl esters of 11 available sterols were performed, and detection limits were found to be less than 1 pg on-column. Reproducibilities and recoveries of 8 noncholesterol sterols were validated according to one-way layout and polynomial equation, respectively. The variances between sample preparations and between measurements by this method were calculated to be 1.6% to 8.2% and 2.5% to 16.5%, respectively. The recovery experiments were performed using 1 mul aliquots of normal human serum spiked with 1 ng to 6 ng of sterols, and recoveries of the sterols ranged from 88.1% to 102.5% with a mean recovery of 98.1%. The present method provides reliable and reproducible results for the identification and quantification of neutral sterols, especially in small volumes of blood samples, which is useful for serological diagnosis of inherited disorders in cholesterol metabolism and for noninvasive evaluation of cholesterol biosynthesis and absorption in humans.

Distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic body cancer: long-term results.

OBJECTIVE: To analyze the long-term results of distal pancreatectomy with en bloc celiac axis resection (DP-CAR), a newly designed extended surgical procedure for locally advanced cancer of the pancreatic body. SUMMARY BACKGROUND DATA: Pancreatic body cancer often involves the common hepatic artery and/or the celiac axis and is regarded as an unresectable disease. We previously reported the feasibility and safety of DP-CAR in 10 patients and 3 preliminary cases; however, the long-term results are unknown. METHODS: Between May 1998 and September 2005, 23 patients underwent DP-CAR. No reconstruction of the arterial system was required because of early development of the collateral arterial pathways via the pancreatoduodenal arcades from the superior mesenteric artery. We routinely used preoperative coil embolization of the common hepatic artery to enlarge the collateral pathways. RESULTS: The postoperative mortality rate was 0%, despite a high morbidity rate (48%). The chief postoperative complications were pancreatic fistula and ischemic gastropathy. Contrary to expectations, postoperative diarrhea was mild. Preoperative intractable abdominal and/or back pain in 10 patients was completely alleviated immediately after surgery. The surgical margins were histologically negative in 21 patients (91%). The estimated overall 1- and 5-year survival rates were 71% and 42%, respectively, and the median survival was 21.0 months. The sites of recurrence were the liver in 6 patients and local recurrence in 2. CONCLUSIONS: DP-CAR offers a high R0 resectability rate and may potentially achieve complete local control in selected patients. The persisting early hepatic recurrence may indicate DP-CAR for the treatment of less advanced disease.

[Mediastinal dissection for patients with differentiated thyroid carcinoma: sternotomy vs VATS (video-assisted thoracoscopic surgery)].

We here present two cases of differentiated thyroid carcinoma with mediastinal lymph nodes metastases below level 106 according to the classification of the Guidelines for the Clinical and Pathologic Studies for Carcinoma of the Esophagus (9 th edition) edited by the Japanese Society for Esophageal Diseases. For Case 1, we adopted a conventional anterior approach with resection of the right half of the manubrium and sternum to the level of the second intercostal space and medial half of the right clavicule. Case 2 underwent a combined cervical approach and video-assisted thoracoscopic surgery (VATS). In Case 1, the lymph nodes around the subclavian vein, 105R, 106pre and 106recR were successfully dissected under clear view. However, through this case, the difficulty in the dissection of 106tbR was recognized, because it is quite challenging to gain an adequate surgical view in this small compartment by this approach. Conversely, in Case 2, in which mediastinal lymph nodes extended to level 107, the lymph nodes were relatively easily dissected by VATS under excellent surgical views of 106tbR and 107. Although VATS is associated with difficulty in en bloc resection, requirements of a thoracotomy, changes of body position and an intubation tube during the surgery, this approach is of great use for the dissection of 106tbR and 107.

Hyaline vascular-type Castleman's disease in the hepatoduodenal ligament: report of a case.

Castleman's disease is an uncommon lymphoproliferative disorder, which occurs most commonly in the mediastinum. Sporadic reports of its occurrence in the hepatoduodenal ligament and other extrathoracic locations have also been documented. Ultimately, Castleman's disease can develop anywhere lymphoid tissue is found, and the preoperative diagnosis is often difficult. We report a case of hyaline vascular-type Castleman's disease in the hepatoduodenal ligament. An asymptomatic 26-year-old woman was admitted to our hospital for further examination of a mass found on ultrasonography. A contrast-enhanced computed tomography scan confirmed a hypervascular mass in the hepatoduodenal ligament, and angiography showed that the mass was receiving its blood supply from various arteries. These findings suggested a diagnosis of Castleman's disease and we removed the tumor without resecting any other organs. Computed tomography and angiography were helpful in establishing a correct preoperative diagnosis, which minimized the magnitude of surgery.

Structure and expression of two genes encoding secreted acid phosphatases under phosphate-deficient conditions in Pholiota nameko strain N2.

Twenty-three polypeptides secreted in response to a deficiency of inorganic phosphate (Pi) were previously found by two-dimensional polyacrylamide gel electrophoresis analysis in mycelia of Pholiota nameko strain N2. In this study, N-terminal sequencing revealed three of them to be identical to known acid phosphatases of P. nameko strain N114. Two cDNAs and the corresponding genomic DNAs of genes PNAP1 and PNAP2 which encode two of the three acid phosphatases were cloned. The deduced amino acid sequences of PNAP1 and PNAP2 showed high similarity to other fungal acid phosphatases and contained a putative catalytic active site of acid phosphatase. PNAP1 and PNAP2 are comprised of five and seven exons interrupted by four and six introns, respectively. Their promoter regions include two cis-acting elements found in Pi deficiency-inducible genes of Saccharomyces cerevisiae, together with several known functional elements such as a TATA box. Northern blot analysis showed that PNAP1 and PNAP2 are expressed in response to a deficiency of Pi.

Replication-defective HIV isolated from seronegative individuals at high risk for HIV infection.

We have identified a mutant human immunodeficiency virus type 1 (HIV-1) CRF01_AE that contains a single nucleotide mutation in gag gene from 4 HIV-1 seronegative drug users in Thailand. We found A to G mutation at the nucleotide position 75 of gag p17 gene (A75G) not changing the amino acid sequence. The mutant HIV-1 molecular clones were examined for their replication capability. Although the mutation dramatically reduced the level of virion production, it did not affect the amounts of viral protein synthesis within the transfected cells. In addition, this mutation did not affect the levels of Gag polyproteins. Furthermore, electron microscopic examinations have revealed a dramatic reduction of the virion production and perturbation of viral morphogenesis at the cytoplasmic membrane. These results indicate that the A75G mutation is attributable to the long-term sero-negativity of individuals at high risk of HIV-1 infection and suggest a novel mechanism that regulates HIV production.

A modified stapling technique for performing Billroth I anastomosis after distal gastrectomy.

Autosuture staplers have provided various operative and postoperative benefits in gastrointestinal surgery. We describe herein our technique of performing distal gastrectomy followed by side-to-end gastroduodenostomy. Eighteen consecutive patients with gastric cancer underwent distal gastrectomy by the staple technique. We propose a modification of the stapling technique to reduce the number of devices used. In our technique, side-to-end anastomosis is performed first, followed by gastric resection just distal to the anastomosis. By introducing the stapler through the area to be resected, we can eliminate the need to close the gastrostomy. Anastomotic stricture occurred in only 1 (5.5%) of 18 cases. There have been no other postoperative complications related to the anastomosis. We believe that our technique is superior in simplicity and security to the conventional techniques.

Clinicopathological characteristics of poorly differentiated adenocarcinoma of the colon and rectum.

BACKGROUND/AIMS: The clinicopathological significance of poorly differentiated adenocarcinoma (Por) of the colorectum remains controversial. The purpose of this study was to investigate the clinicopathological characteristics of Por by comparison with well (Well) and moderately differentiated adenocarcinoma (Mod) of the colorectum and by subclassification of Por into three types according to the amount of fibrous stroma in tumor tissue. METHODOLOGY: Eleven patients with Por, 64 with Well and 254 with Mod were clinicopathologically compared. RESULTS: Por was located predominantly in the right side of the colon. The maximal size of the tumors in Por (72.3+/-25.0 mm) was significantly larger than in Well (42.2+/-26.8 mm) and Mod (52.2+/-22.8 mm) (p=0.0009, 0.0047). The frequency of lymph node metastasis in Por was significantly higher than in Well (p=0.0009). The five-year survival rate for patients with Por was 45.5%, for Well was 71.4% and for Mod was 59.5% (NS). The medullary type of Por had a good prognosis. CONCLUSIONS: Por proliferated and metastasized more rapidly than Well. The subclassification of Por according to the amount of fibrous stroma in tumor tissue could play an important role in the clinicopathological study of colorectal carcinoma.

Determination of HIV type 1 CRF01_AE gag p17 and env-V3 consensus sequences for HIV/AIDS vaccine design.

A molecular epidemiological study of the gag p17 and env-V3 regions on HIV-infected drug users and blood donors was carried out in northern Thailand from 1998 through 2002 to determine the predominant subtype and consensus sequence (CS) for circulating HIV-1 strains. CRF01_AE was concluded to be a predominant strain and the nucleotide CSs in gag p17 and env-V3 showed only 1.26% and no difference from CS in the Los Alamos database, respectively. Our env-V3 CS was identical to the previously published CSs, suggesting that the CS was very conserved from 1990 through 2002 in Thailand. Gag p17 and env-V3 nucleotide sequences of seroconvertors in our subjects were quite similar to the CS and conserved for at least 9 and 6 years postinfection, respectively. These results suggest that the CS approach to the HIV-1 antigen design could overcome HIV diversity and help us develop an effective HIV/AIDS vaccine.