A case of HBs antigen negative fulminant hepatitis with IgM antibody to hepatitis B core antigen persisting more than seven years

A 33-year old dentist developed fulminant hepatitis. At admission, a test for IgM antibody to hepatitis B core antigen (IgM anti-HBc) was positive, while tests for HBsAg and HBeAg were negative. He was cured of the disease, but in follow-up examinations from 1983 to 1990 IgM anti-HBc was continuously detected with radioimmunoassay while HBsAg and HBV-DNA were absent in the serum. However, HBcAg was found in a biopsied liver specimen and a small quantity of HBV-DNA was detectable by polymerase chain reaction assay. These observation suggest that the continuous detection of IgM anti-HBc without HBsAg in serum is due to persistent HBV infection and HBV replication in the liver.     

Amelioration of Skewed Th1/Th2 Balance in Tumor-Bearing and Asthma-Induced Mice by Oral Administration of Agaricus blazei Extracts

We showed in a previous study that hot-water extracts of Agaricus blazei (Agaricus extracts) had anti-tumor activity to Meth A fibrosarcoma, but it remains unclear whether the Agaricus extracts ameliorate the skewed balance of type-1 T helper (Th1) and type-2 T helper (Th2) cells. We examined whether Agaricus extracts effect the skewed Th1/Th2 balance in tumor-bearing and asthma-induced mice. When Meth A-bearing mice were given orally either Agaricus extracts or water once a day starting 5 days after tumor implantation, spleen T cells, prepared from tumor-bearing mice treated with Agaricus extracts, in response to anti-CD3 monoclonal antibody produced significantly higher levels of interferon γ (IFN-γ) than that of controls. The mRNA expression of IFN-γ-inducing protein 10 and the frequency of CD69⁺ or CD49d⁺ cells, among activated T cells infiltrated into tumors, significantly increased in Agaricus-treated mice, compared with those of tumor-controls. In asthma-induced mice, treatment with the Agaricus extracts caused significant downregulation of OVA-specific antibody responses of IgG1 and IgE but not of IgG2a, and significantly decreased total cell numbers, levels of interleukin 5, and eosinophil numbers in bronchial alveolar lavage fluids. IFN-γ production by anti-CD3-stimulated spleen cells, obtained from Agaricus-treated mice, significantly increased. Our results strongly suggest that oral administration of Agaricus extracts ameliorates the Th1/Th2 balance from the Th2-skewed conditions.     

Hemangiopericytoma of the Greater Omentum

A 41-year-old Chinese woman was admitted to our hospital with epigastric pain. Computed tomography detected a heterogeneous enhancement tumor fed by the left gastroepiploic artery in the left lower quadrant and cholelithiasis. Excision of the tumor in the greater omentum and cholecystectomy were performed laparoscopically. Histological findings confirmed a diagnosis of hemangiopericytoma with low-grade malignancy. To our knowledge, hemangiopericytoma of the greater omentum is very rare, and only 12 cases were reported in English literature. We report a case of hemangiopericytoma arising in the greater omentum and review the literature.     

Clinical significance of mucinous components in rectal cancer after preoperative chemoradiotherapy

Purpose

The clinical implications of mucinous components in rectal tumors, especially with regard to the efficacy of neoadjuvant chemoradiotherapy, remain unclear.

Methods

One hundred and thirty rectal cancer patients who received curative resection after neoadjuvant chemoradiotherapy were retrospectively reviewed. Patients were classified into 3 groups according to the proportion of extracellular mucin: low (<5 %), moderate (5–25 %), and high (>25 %).

Results

There were 82 (63.1 %), 26 (20.0 %), and 22 (16.9 %) patients in the low, moderate, and high mucin groups, respectively. Patients with a high mucinous tumor component were significantly more likely to have an advanced tumor stage (p = 0.010) and a shorter disease-free (p = 0.002) and distant recurrence-free survivals (p < 0.001), whereas the mucinous tumor component showed no correlation with local recurrence (p = 0.101). A high mucinous component was also an independent predictive factor for a shorter disease-free survival (p = 0.041, hazard ratio = 2.56) and distant recurrence-free survival (p = 0.001, hazard ratio = 5.74) according to a multivariate analysis.

Conclusions

Because the mucinous components showed little correlation with local recurrence, mucinous cancer should not be a determining factor for chemoradiotherapy. However, the frequent occurrence of metachronous distant metastasis among patients with a high mucin component makes this a possible indicator for more robust postoperative adjuvant treatment and close surveillance of recurrence.

     

Reverse geometrical selectivity in glucuronidation and sulfation of cis- and trans-4-hydroxytamoxifens by human liver UDP-glucuronosyltransferases and sulfotransferases

The phenolic active metabolites, cis-4-hydroxytamoxifen (cis-HO-TAM) and trans-4-hydroxytamoxifen (trans-HO-TAM), of the anti-breast-cancer drug, trans-tamoxifen (TAM), were geometrically selectively glucuronidated in the manner of cis>trans by microsomes and sulfated in the manner of trans>cis by cytosol from the liver of 10 human subjects (7 females and 3 males). There was a large individual difference in the microsomal glucuronidation of cis-HO-TAM, which correlated well with glucuronidation of 4-hydroxybiphenyl by human liver microsomes. However, there was only a slight correlation between the glucuronidation of cis-HO-TAM and trans-HO-TAM or 4-nitrophenol (NP). A small individual difference was observed for the human liver cytosolic sulfation of trans-HO-TAM, which correlated well with the sulfation of NP. Recombinant human UDP-glucuronosyltransferase (UGT)2B15 catalyzed the cis-selective glucuronidation of geometrical isomers of HO-TAM. UGTs1A1, 1A4, 1A9 and 2B7 had weak activity toward HO-TAMs with a much smaller cis-selectivity than did UGT2B15. UGTs1A3 and 1A6 had no detectable activity toward these substrates. Among the four known major sulfotransferases (SULTs) occurring in the human liver, SULT1A1 was strongly suggested to play the most important role in the hepatic cytosolic trans-selective sulfation of HO-TAM isomers. A good correlation was observed between the hepatic cytosolic sulfation of trans-HO-TAM and NP, a standard substrate for SULT1A1. SULT1E1 had slight activity toward the HO-TAMs. SULTs1A3 and 2A1 had no detectable activity toward HO-TAMs.     

RhoA/Rho-kinase as a therapeutic target in asthma

Rho-kinase is an effector molecule of RhoA, a monomeric GTP-binding protein, and causes Ca(2+) sensitization via inactivation of myosin phosphatase. The major physiological functions of Rho-kinase include contraction, migration, and proliferation in cells. These actions are thought to be related to the pathophysiological features of asthma, i.e., airflow limitation, airway hyperresponsiveness, beta-adrenergic desensitization, eosinophil recruitment and airway remodeling. Here, the roles of RhoA/Rho-kinase in the pathophysiology and treatment of asthma were investigated. In airway smooth muscle, pre-exposure to chemical mediators released from inflammatory cells markedly enhances methacholine-induced contraction without elevating intracellular concentrations of Ca(2+). This augmented responsiveness to methacholine involves the phosphorylation of myosin phosphatase targeting protein 1 (MYPT1) via Rho-kinase, however, it is attenuated by pre-treatment with Rho-kinase inhibitors such as Y-27632 and HA-1077. Airway smooth muscle contraction due to asthma-related substances such as contractile agonists and reactive oxygen species is suppressed by these Rho-kinase inhibitors. Reduced responsiveness to beta-adrenergic receptor agonists occurs via Ca(2+) sensitization, after exposure to lysophospholipids and proteases released from inflammatory cells. This beta-adrenergic desensitization is also attenuated in the presence of Y-27632. Furthermore, the proliferation of airway smooth muscle cells is elevated by Rho-kinase, however, it is markedly suppressed by Y-27632. Antigen challenges cause hyperresponsiveness and eosinophilia in the airways; however, these reactions are markedly suppressed by these Rho-kinase inhibitors. These findings indicate that RhoA/Rho-kinase is involved in the pathophysiology of asthma, and suggest that Rho-kinase inhibitors have therapeutic potential for prohibiting these features. In conclusion, RhoA/Rho-kinase is a novel target molecule for the treatment of asthma.     

Genetic characterization of hantaviruses transmitted by the Korean field mouse (Apodemus peninsulae), Far East Russia

In an epizootiologic survey of 122 rodents captured in Vladivostok, Russia, antibodies positive for hantavirus were found in Apodemus peninsulae (4/70), A. agrarius (1/39), and Clethrionomys rufocanus (1/8). The hantavirus sequences identified in two seropositive A. peninsulae and two patients with hemorrhagic fever with renal syndrome (HFRS) from the Primorye region of Far East Russia were designated as Solovey and Primorye, respectively. The nucleotide sequences of the Solovey, Primorye, and Amur (obtained through GenBank) sequences were closely related (>92% identity). Solovey and Primorye sequences shared 84% nucleotide identity with the prototype Hantaan 76-118. Phylogenetic analysis also indicated a close relationship between Solovey, Primorye, Amur, and other viruses identified in Russia, China, and Korea. Our findings suggest that the Korean field mouse (A. peninsulae) is the reservoir for a hantavirus that causes HFRS over a vast area of east Asia, including Far East Russia.     

Perforation of the colon in neonates

Purpose

Gastrointestinal perforation is a catastrophic condition in neonates, especially in premature neonates. Although perforation is commonly observed in the small intestine during the neonatal period, perforation of the colon is a rare condition. This study analyzed the clinical findings and results of perforation of the colon in neonates.

Methods

Between 1989 and 2004, 8 neonates were treated for spontaneous perforation of the colon at our institute. These patients were retrospectively reviewed.

Results

Gestational ages ranged from 36 to 41 weeks. Seven patients weighed above 2500 g, whereas one patient weighed 1800 g at birth. Perforations developed within 7 days after birth in 6 patients and before birth in two. Associated bowel diseases included rectosigmoid type of Hirschsprung's disease in two patients, immature ganglia in one, imperforate anus in one, colonic atresia in one, and necrotizing enterocolitis in one. An obvious cause was not identified in the remaining two. Six patients without definite anatomic obstructions, such as imperforate anus or colonic atresia, required evaluations for suspected Hirschsprung's disease. All 8 patients underwent colostomy and recovered from peritonitis. Seven survived, but one died of sudden infant death syndrome.

Conclusions

In this study, perforation of the colon during the neonatal period mostly occurred in term or near-term neonates and carried a good prognosis. During management, it was important to identify Hirschsprung's and its allied disorders as a cause of perforation.     

Effects of mood stabilizers on the disruption of prepulse inhibition induced by apomorphine or dizocilpine in mice

The prepulse inhibition of the startle response provides an operational measure of sensorimotor gating in which a weak stimulus presented prior to a startling stimulus reduces the startle response. Prepulse inhibition deficits were observed in patients with several neuropsychiatric disorders, including schizophrenia and acute manic bipolar patients. Valproic acid, carbamazepine and lithium carbonate are frequently used as mood stabilizers in patients with bipolar affective disorder and schizophrenia. However, little is known about the mechanisms of action of mood stabilizers on prepulse inhibition deficits. In this study, we investigated the effects of mood stabilizers on the disruption of prepulse inhibition of the acoustic startle response induced by either apomorphine or dizocilpine in mice. Valproate (30-300 mg/kg, i.p.), carbamazepine (3-30 mg/kg, i.p.) and lithium carbonate (10-100 mg/kg, p.o.) had any effect on prepulse inhibition by itself. Valproate, carbamazepine and lithium carbonate reversed the disruption of prepulse inhibition induced by apomorphine (1 mg/kg, s.c.). Although valproate and carbamazepine had no effect on the disruption of prepulse inhibition induced by dizocilpine (0.3 mg/kg, s.c.), lithium carbonate exacerbated the dizocilpine-induced disruption. These results suggest that valproate, carbamazepine and lithium carbonate reverse the disruption of prepulse inhibition through the dopaminergic system.