Hepatocyte differentiation from embryonic stem cells and umbilical cord blood cells

With the development of regeneration medicine, many researchers have attempted hepatic differentiation from nonhepatic-origin cell sources. The differentiation of embryonic stem (ES) cells into hepatocyte-like cells has been reported in several papers. Mouse ES cells have shown a potential to develop into hepatocyte-like cells in vitro on the basis of hepatic gene expression after adding several growth factors. We transplanted cultured embryoid body (EB) cells (male) into female mice. A liver specimen of the recipient was examined by immunohistochemical staining for albumin and fluorescence in situ hybridization for the Y chromosome after transplantation. Both Y chromosome- and albumin-positive cells were recognized in the recipient female liver, and were considered to be hepatocyte-like cells derived from ES cells containing the Y chromosome. Many groups, including ourselves, have studied hepatocyte-like cell differentiation from umbilical cord blood cells (UBCs). We cultured nucleated cells isolated from UBCs. Using immunostaining, ALB-positive and CK-19-positive cells were recognized in the culture. Dual staining of ALB and CK-19 demonstrated that ALB was coexpresed with CK-19, suggesting the existence of hepatic progenitors. In this review, we consider recent studies of the differentiation of hepatocytes from nonhepatic origins, especially ES cells and umbilical cord blood.     

Single-channel properties of volume-sensitive Cl- channel in ClC-3-deficient cardiomyocytes

It is controversial whether the ClC-3 protein, which is one of the voltage-dependent chloride channel ClC family members, is a candidate for the volume-sensitive outwardly rectifying (VSOR) Cl(-) channel per se or its regulator. Here, for the first time, we examined the single-channel properties of the VSOR Cl(-) channel in ventricular myocytes isolated from ClC-3-deficient mice. The single-channel current induced by cell swelling exhibited Cl(-) selectivity, mild outward rectification, and an intermediate unitary conductance (around 38 pS). A Cl(-) channel blocker, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), reversibly inhibited the outward current. These single-channel properties were identical with those in ClC-3 expressing wild-type ventricular myocytes. These results indicate that the single-channel activity of the VSOR Cl(-) channel is independent of the expression of ClC-3 proteins in mouse ventricular myocytes.     

Treatment duration and cost of work-related low back pain in Korea

The purpose of this study is to present the information on the duration of treatment and the cost of work-related low back pain. Using the compensation-database for 1997 work-related low back pain (n=9,277), this study estimated the duration of treatment, the cost of work-related low back pain, the relationship between them, and probability of being off treatment at different intervals. The mean and the median of the treatment duration are 252.6 days and 175 days. The mean and the median of the cost of total insurance benefit are 37,700,000 won and 14,400,000 won. The treatment duration of 51% of the study subjects was less than 6 months and their cost accounted for 10.2% of the total insurance benefit. The subjects who were treated more than 24 months were 5.8% but it accounted for 29.2% of the cost. It was found that approximately 50% of the subjects who will remain on treatment at the end of n months would be off treatment at the end of n+5 months. This study presents the point in time when the low back pain (LBP) workers need to prepare to return to work by forecasting their off-treatment period. From the treat duration and cost perspectives, this study may be utilized as evidence for active management of work-related LBP.     

First prospective study of the recognition process of melanoma in dermatological practice

BACKGROUND: Early detection is crucial to improve melanoma prognosis. Different diagnostic guides such as the ABCD rule (asymmetry [A], irregularity of borders [B], unevenness of distribution of color [C], and diameter [D]) have been proposed to identify melanoma, but their efficacy in real life is questionable. We investigated the recognition process of melanoma by dermatologists to use as a model to improve self-detection in the general population and to train students and general practitioners. OBJECTIVES: To understand the major principles of the recognition process of nevi and melanoma unconsciously used by dermatologists. DESIGN: Prospective survey recording the immediate perceptions of dermatologists of the morphologic features of the lesion and intuitive diagnostic opinion about 4036 consecutive resected nevi and melanoma. SETTING: One hundred thirty-five volunteer dermatologists in their daily practices. MAIN OUTCOME MEASURES: Perceptions of the image best explaining the diagnostic opinion and best predicting the final diagnosis by univariate and multivariate analysis. RESULTS: The immediate diagnostic opinion of the dermatologist is mainly explained by an unconscious reference to the overall pattern compared with the common nevi, but also compared with the other nevi of the individual (the "ugly duckling sign"). The dermatologist's ability to discriminate between nevi and melanoma relies on the assessment of the overall pattern, the ugly duckling sign, and the knowledge of a recent change. A separate or combined analysis of individual morphologic criteria such as ABCD does not seem to play a major role in this recognition process. CONCLUSIONS: Persons most skilled at the clinical detection of melanoma seem to unconsciously rely on cognitive (overall pattern) and comparative (ugly duckling sign) processes rather than an algorithm of morphologic criteria (ABCD). These concepts could be tested in the medical training of general practitioners and education of the general population, where they might be more efficient than algorithms such as the ABCD criteria.     

Multiple chronic subdural hematoma in shaken-baby syndrome

We described a case of shaken-baby syndrome with multiple chronic subdural hematomas. A 10-month-old male baby was admitted to our hospital because of loss of consciousness and convulsions. CT scan revealed an acute subarachnoid hemorrhage extending into the interhemispheric fissure and supracerebellar space. The patient was treated conservatively, and discharged from the hospitaL Two months after ictus, a baby was admitted to our hospital with general fatigue. CT scan demonstrated multiple chronic subdural hematomas. Burr hole irrigation and drainage brought about complete disappearance of these lesions. Retrospectively, it was found that these multiple subdural hematomas were due to shaken-baby syndrome. Shaken-baby syndrome is a form of child abuse that can cause significant head injury, and subdural hematoma is the most common manifestation. It is well known that the outcome of shaken-baby syndrome is generally not good. It is important to suspect shaken-baby syndrome when a chronic subdural hematoma is seen in a baby.     

Oxidative stress affects synaptosomal gamma-aminobutyric acid and glutamate transport in diabetic rats: the role of insulin

Evidence suggests that oxidative stress is involved in the pathophysiology of diabetic complications and that insulin has a neuroprotective role in oxidative stress conditions. In this study, we evaluated the in vitro effect of insulin in the susceptibility to oxidative stress and in the transport of the amino acid neurotransmitters gamma-aminobutyric acid (GABA) and glutamate in a synaptosomal fraction isolated from male type 2 diabetic Goto-Kakizaki (GK) rat brain cortex. The ascorbate/Fe(2+)-induced increase in thiobarbituric acid reactive substances (TBARSs) was similar in Wistar and GK rats and was not reverted by insulin (1 micromol/l), suggesting that other mechanisms, rather than a direct effect in membrane lipid peroxidation, may mediate insulin neuroprotection. Diabetes did not affect GABA and glutamate transport, despite the significant decrease in membrane potential and ATP/ADP ratio, and insulin increased the uptake of both GABA and glutamate in GK rats. Upon oxidation, there was a decrease in the uptake of both neurotransmitters and an increase in extrasynaptosomal glutamate levels and in ATP/ADP ratio in GK rats. Insulin treatment reverted the ascorbate/Fe(2+)-induced decrease in GABA accumulation, with a decrease in extrasynaptosomal GABA. These results suggest that insulin modulates synaptosomal GABA and/or glutamate transport, thus having a neuroprotective role under oxidizing and/or diabetic conditions.     

A female patient with malarial nephropathy

Malaria remains one of the worlds major health problems, particularly in developing tropical countries. Imported malaria is reportedly increasing in Western countries. Acute renal failure (ARF) is the most common cause of death in severe malaria. We report the case of a 63-year-old female patient with a history of travel to a rural area in South Africa who was in coma and had a high fever on admission. Thirty percent of her erythrocytes were infected with Plasmodium falciparum. She had cerebral malaria, malarial nephropathy, anemia, hepatic dysfunction, and disseminated intravenous coagulation (DIC). Quinine and artesunate treatment decreased the number of parasites in the blood. To manage renal failure, hemodialysis was performed for 11 days. A relationship between ARF and hepatic dysfunction was suggested. This relationship is an indication of the clinical course of the disease. In this article, we discuss the mechanism underlying the development of malarial nephropathy and its management, particularly the usefulness of hemodialysis.     

Klebsiella pneumoniae septic arthritis in a cirrhotic patient with hepatocellular carcinoma

Despite septic arthritis is increasingly being reported in elderly patients with diabetes or alcoholism, reported cases of spontaneous bacterial arthritis in cirrhotic patients are extremely rare. We present the first reported case of K. pneumoniae septic arthritis and spontaneous bacterial peritonitis in a cirrhotic patient with hepatocellular carcinoma. K. pneumoniae, one of the most common causative organisms of spontaneous bacterial peritonitis in cirrhotic patients, was isolated from both the blood and the joint fluid, which suggests that the route of infection was hematogenous. After the treatment with cefotaxime and closed tube drainage, the condition of the patient was improved, and subsequently, the joint fluid became sterile and the blood cultures were proved negative. Therefore, this case provides further evidence for the mode of infection being bacteremia in cirrhotic patients and suggests that the enteric bacteremia in cirrhotics may cause infection in different organ systems.     

Molecular mechanisms and drug development in aquaporin water channel diseases: molecular mechanism of water channel aquaporin-2 trafficking

Targeted positioning of water channel aquaporin-2 (AQP2) strictly regulates body water homeostasis. Trafficking of AQP2 to the apical membrane is critical for the reabsorption of water in renal collecting ducts. Besides the cAMP-mediated effect of vasopressin on AQP2 trafficking to the apical membrane, other signaling cascades also induce this sorting. Recently, AQP2-binding proteins that directly regulate this trafficking have been uncovered: SPA-1, a GTPase-activating protein (GAP) for Rap1, and cytoskeletal protein actin. This review summarizes recent advances related to the trafficking mechanism of AQP2 and its defect causing nephrogenic diabetes insipidus (NDI).