Imported Hepatitis E Virus Genotype 1: A Rare Case of Acute Hepatitis Managed with Steroid Pulse Therapy.

A 26-year-old Indian man who had arrived in Japan 24 days prior presented to our hospital with abdominal pain and a fever. A blood test revealed marked hepatic dysfunction, and imaging tests confirmed a diagnosis of acute hepatitis. The patient's liver function and coagulability deteriorated, and his general condition was poor. Given the possibility of fulminant hepatic failure, we initiated steroid pulse therapy. Following the initiation of steroid therapy, the patient's liver function and subjective symptoms rapidly improved. Testing revealed positive findings for IgA-hepatitis E virus, and a genetic analysis of hepatitis E identified genotype 1, which is not endemic to Japan, leading to a definitive diagnosis of imported hepatitis E infection from India. The successful response to steroid therapy highlights the potential benefit of this approach in managing severe cases of acute hepatitis E, a rare occurrence in Japan. This case underscores the importance of considering hepatitis E infection in individuals with a recent travel history to regions with high prevalence and the potential benefits of steroid therapy in managing severe cases of acute hepatitis E.

Primary Peritonitis due to Group A Streptococcus Successfully Treated with Intraperitoneal Drainage.

A 42-year-old woman was admitted to our hospital because of lower abdominal pain and diarrhea. Although the initial symptoms and imaging findings were similar to those of acute enteritis, blood and ascites cultures led to the diagnosis of primary peritonitis caused by group A Streptococcus. In many cases, the disease rapidly deteriorates, and laparotomy is performed for the early diagnosis and to reduce the number of bacteria in the abdominal cavity. In the present case, intraperitoneal drainage was effective for avoiding surgery. We suggest that intraperitoneal drainage is effective for the treatment of this disease.

The association between midlife living arrangement and psychiatrist-diagnosed depression in later life: who among your family members reduces the risk of depression?

This study investigates the longitudinal association between living arrangements and psychiatrists' diagnosis of depression in the general population. In 1990, 1254 Japanese men and women aged 40-59 years were enroled and completed questionnaires on the living arrangement in the Japan Public Health Center-based Prospective Study (JPHC Study) and participated in a mental health screening (2014-2015). The study diagnosed a major depressive disorder (MDD) assessed by well-trained certified psychiatrists through medical examinations. During the follow-up, a total of 105 participants (36 men and 69 women) aged 64-84 years were diagnosed with MDD by psychiatrists. Living with a child (ren) was associated with a reduced risk of MDD for men but not for women; the respective multivariable ORs (95% CIs) were 0.42 (0.19-0.96) and 0.59 (0.32-1.09). These associations remained unchanged after adjusting for living with spouse and parent(s). In conclusion, living with a child (ren) was associated with a reduced risk of MDD in men, suggesting the role of a child (ren) in the prevention of MDD.

A mouse model of weight gain after nicotine withdrawal.

Smoking cessation increases body weight. The underlying mechanisms, however, have not been fully understood. We here report an establishment of a mouse model that exhibits an augmented body weight gain after nicotine withdrawal. High fat diet-fed mice were infused with nicotine for two weeks, and then with vehicle for another two weeks using osmotic minipumps. Body weight increased immediately after nicotine cessation and was significantly higher than that of mice continued on nicotine. Mice switched to vehicle consumed more food than nicotine-continued mice during the first week of cessation, while oxygen consumption was comparable. Elevated expression of orexigenic agouti-related peptide was observed in the hypothalamic appetite center. Pair-feeding experiment revealed that the accelerated weight gain after nicotine withdrawal is explained by enhanced energy intake. As a showcase of an efficacy of pharmacologic intervention, exendin-4 was administered and showed a potent suppression of energy intake and weight gain in mice withdrawn from nicotine. Our current model provides a unique platform for the investigation of the changes of energy regulation after smoking cessation.

Inflammatory Pseudo-tumor of the Liver Accompanied by Eosinophilia.

A 28-year-old woman was referred to our hospital for liver dysfunction and neck pain. Blood tests revealed elevated liver enzymes and eosinophilia. Ultrasonography, computed tomography, and magnetic resonance imaging showed a mass lesion near the hepatic hilus. The tumor was considered to be an inflammatory pseudo-tumor or malignancy. A liver-mass biopsy was performed and led to a diagnosis of inflammatory pseudo-tumor. In the present case, a markedly elevated eosinophil count was a characteristic clinical feature, and the patient underwent steroid therapy. Treatment resulted in a reduced eosinophil count, improved neck symptoms, and disappearance of the inflammatory pseudo-tumor.

Late-onset type-2 autoimmune pancreatitis with two mass lesions diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

A 65-year-old man with ulcerative colitis presented with aggravated diabetes. Computed tomography showed two masses in the body and tail of the pancreas. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed, with histopathological findings suggesting autoimmune pancreatitis (AIP). Type-2 AIP was suspected, and administration of prednisolone was initiated. The pancreatic masses had disappeared after the treatment. In this case, EUS-FNA was effective for the diagnosis of type-2 AIP. The two-lesion mass formation observed here is a rare presentation of the disease. In patients with a history of ulcerative colitis, the possibility of late-onset type-2 AIP should be kept in mind.

Pemafibrate, a selective PPARα modulator, and fenofibrate suppress microglial activation through distinct PPARα and SIRT1-dependent pathways.

Pemafibrate, a selective peroxisome proliferator-activated receptor (PPAR) α modulator, is a new drug that specifically modulates PPARα conformation and co-activator recruitment, thereby lowers plasma triglycerides with less off-target effects. Classical PPARα ligands such as fenofibrate suppress inflammatory cells including microglia. However, effects of pemafibrate on microglia have never been addressed. Here we show that pemafibrate, like other PPARα ligands, potently suppressed NF-κB phosphorylation and cytokine expression in microglial cells. PPARα knockdown significantly amplified LPS-induced cytokine expression. Pemafibrate-induced suppression of IL-6 expression was reversed by PPARα knockdown. However, suppression by fenofibrate was not reversed by PPARα knockdown but by Sirtuin 1 (SIRT1) knockdown. In conclusion, pemafibrate and fenofibrate similarly suppresses microglial activation but through distinct PPARα and SIRT1-dependet pathways.

A Case of Euthyroid Graves' Ophthalmopathy in a Patient Sero-Negative for TSH Receptor Autoantibody.

We report of a case of Graves' ophthalmopathy presented solely with symptoms of the eyes with normal thyroid function tests and negative immunoreactive TSH receptor autoantibody. 40-year-old male was referred to our hospital due to 2-month history of ocular focusing deficit without any signs or symptoms of hyper- or hypothyroidism. Serum thyroid function tests and 99mTc uptake were both within the normal range. Anti-thyroid autoantibodies were all negative except for the cell-based assay for serum TSH receptor stimulating activity. Since orbital CT scan and MRI gave typical results compatible with Graves' ophthalmopathy, we treated the patients with corticosteroid pulse therapy and orbital radiation therapy, leading to a partial improvement of the symptoms. This case gives insights into the potential pathophysiologic mechanism underlying Graves' ophthalmopathy and casts light upon the difficulties of establishing the diagnosis in a euthyroid case with minimal positive results for anti-thyroid autoantibodies.

An Autopsy Case of Pulmonary Tumor Thrombotic Microangiopathy Due to Rapidly Progressing Colon Cancer in a Patient with Type 2 Diabetes.

We herein describe a case of pulmonary tumor thrombotic microangiopathy (PTTM) with rapidly progressing colon cancer. A 61-year-old man who had been receiving treatment for type 2 diabetes mellitus for 3 years was hospitalized due to critical hypoxemia. Computed tomography, which had not shown any abnormalities 3 months previously, revealed a tumor in the ascending colon, multiple nodules in the liver, and the absence of any lung abnormalities. On day 3 of hospitalization, a sudden onset of severe dyspnea and tachycardia occurred, followed by death. Autopsy revealed microscopic metastatic tumor emboli in multiple pulmonary vessels with fibrin thrombus and intimal proliferation, which led to a diagnosis of PTTM.

Tandospirone, a 5-HT1A agonist, ameliorates movement disorder via non-dopaminergic systems in rats with unilateral 6-hydroxydopamine-generated lesions.

Serotonin 1A (5-HT1A) receptors are distributed throughout the brain with their highest concentrations in the frontal cortex, subthalamic nucleus and entopeduncular nucleus as well as the dorsal and median raphe nucleus. There is growing evidence that 5-HT1A receptor agonists have an antidepressant effect in individuals with major depressive disorders. Recent clinical studies suggest that tandospirone, a highly potent and selective 5-HT1A receptor agonist used clinically as an antidepressant in Japan and China, may act as an antiparkinsonian drug. In the present study, we investigated the effect of tandospirone on contralateral rotational behavior in a unilateral hemiparkinsonian rat model produced with 6-hydroxydopamine (6-OHDA). Tandospirone, as well as 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT), significantly increased contralateral turnings in a dose-dependent manner (0.5-10 mg/kg). Tandospirone also remarkably potentiated the contralateral turning induced by 0.025 mg/kg of apomorphine. Pretreatment with WAY-100635, a 5-HT1A receptor antagonist, almost completely blocked the contralateral turning behavior evoked by tandospirone and 8-OHDPAT, but not that by apomorphine. SCH-23390, a selective dopamine D1 receptor antagonist, did not affect on the tandospirone-induced rotational behavior. These results suggested that tandospirone could act on postsynaptic 5-HT1A receptors and modulate excitatory amino acid pathways in the basal ganglia. Thus, tandospirone could have therapeutic potential for the treatment of Parkinson's disease by modulating neuronal activities of non-dopaminergic pathways.

[Sex identification from DNA in old teeth].

The sex determination was carried out on 80 fresh and 15 old teeth by amplifying sex chromosome specific sequences with the polymerase chain reaction. The DNA content in the tooth significantly decreases with aging. There was no correlation between days after evulsion and the amounts of DNA extracted from fresh teeth that had been preserved less than 186 days. The sex determination based on fresh teeth was successful using multi locus markers, DYZ-1 and DYZ-3 in combination with DXZ-1. However, amelogenin and pseudoautosomal boundary, both that are single locus markers and specific for both sex chromosomes with different lengths, could not be detected in three samples, of which DNA contents were extremely low. However, the sex determination by amelogenin amplified with fluorescent probes was possible in these three samples. We also determined sexes of 30 old specimens (15 teeth and 15 bones) from 15 human skulls using sex chromosomes locus markers. Prior to molecular sex determination, two forensic specialists determined the sex of the skull morphologically. From the 15 skulls, sex identification using multi locus marker (DYZ-1 or DYZ-3) was possible for 12 of 15 teeth and 7 of 15 bones. The sex was successfully determined from 11 teeth and 9 bones by amplification of the amelogenin locus. However, the coincidence rate of the molecular test with morphological examination was < 20%. In conclusion, sex determination on the fresh tooth would be successful using any sex chromosome marker. However, in cases on samples that have spent considerable years in the ground, pollution and putrefaction, especially, by humicolous, must be considered. Thus, sex determination by DNA testing should be regarded as accurate, when the results from two or more molecular markers are coincident. Hokkaido J Med Sci 80(2), 191-199, 2005

Genotyping of cytochrome p450 isoform genes is useful for forensic identification of cadaver.

Tailor-made medical treatment based on the polymorphism of genes encoding drug-metabolizing enzymes has been advocated and is being tried on an experimental basis at numerous centers. If DNA polymorphism analysis becomes routine in tailor-made medical treatment, it will be very useful in forensic identification. In this study, we determined the genotype frequencies of five p450 (CYP) isoform genes, CYP1A2, CYP2D6, CYP2E1, CYP2C9 and CYP2C19 in 196 Japanese individuals to evaluate their forensic usefulness. These genes encode the most important enzymes among the CYP superfamily that metabolize clinically used drug. The frequency of each allele agreed well with those reported previously and their genotype frequencies did not deviate from those expected from Hardy-Weinberg equilibrium. CYP2C subfamilies such as CYP2C9 and CYP2C19 on chromosome 10 showed high sequence homology, as high as over 95% in the regions flanking polymorphic sites. Although 3240 genotype combinations of these five CYP isoform genes are theoretically possible, 101 combinations were detected in this study. The genotype frequencies of these five isoform genes excluded their linkage. The following two genotype combinations showed the highest frequency of 0.036: CYP1A2*1A/*1A, CYP2D6*1/*10, CYP2E1*1/*1, CYP2C9*1/*1 and CYP2C19*1/*1 and CYP1A2*1A/*1C, CYP2D6*1/*10, CYP2E1*1/*1, CYP2C9*1/*1 and CYP2C19*1/*1. Thus, genotyping of CYP isoform genes should be useful in forensic identification.

Molecular evolution of alleles of the glycophorin A gene.

Highly-homologous Glycophorin A (GPA), B and E genes are triplicate genes, and involve many subtypes and minor antigens constructing the Miltenberger subsystem. These genes and most of the variants are hypothesized to arise by recombination, because hot spots are located in the gene sequences. By sequencing exons 1-7 and introns 1-3 of standard alleles of GPA gene, M and N alleles were classified into six variations: provisionally called MN*M101, M102, M201, M202, N101 and N102 in our previous study. Here we further investigated the sequences of introns 4-6 using GPA gene-specific primers and by DNA sequencing, and found eight, five and nine new nucleotide substitutions or deletions in introns 4, 5 and 6, respectively. Using the computer program PHYLIP 3.5, the phylogenetic trees were reconstructed. Phylogenetic analysis of the allele sequences revealed that M200s alleles arose from M101 after the separation of M101 and N101 and branched to M201 and M202 via the accumulation of point mutations. M102 and N102 alleles were estimated to generate via recombination between M101 and N101 occurred around the hot spot. The findings also suggested the existence of other GPA variants with normal antigenicity, and are quite useful in the forensic and anthropological fields.

Simultaneous analyses of hypoglycemic agents and C-peptide are essential in a homicide case with the combined dosing insulin and insulin-releasing drug.

A 5-year-old girl was given a sulfonylurea hypoglycemic agent, 25 mg of glibenclamide (ten tablets of Euglucon) with two benzodiazepine drugs, 2 mg of estazoram and 0.75 mg of triazolam (one tablet of Eurodin and three tablets of Halcion), by her 37-year-old pharmacist father and then injected with 70 units of insulin (NovoLet 40R). She died several hours after the injection of insulin. Autopsy was carried out 12 h after the death. A glibenclamide level of 103 ng/ml was detected in the serum collected from the heart at autopsy. The serum insulin and C-peptide concentrations were 295 microU/ml and 0.5 ng/ml, respectively. The high level of insulin and the low level of C-peptide indicated that most of the serum insulin was exogenous. The determination of the serum C-peptide concentration was useful to the diagnosis of hypoglycemia caused by exogenous insulin even in the case of co-administration with an endogenous-insulin-releasing agent.