Placental extracts regulate melanin synthesis in normal human melanocytes with alterations of mitochondrial respiration

Placental extracts have been widely used as skin lightening agents in the Japanese cosmetic market. Here, we show that placental extracts contain factors that can decrease or increase melanin synthesis by normal human melanocytes in vitro in possible association with mitochondrial respiration. When normal human melanocytes were treated with a whole porcine placental extract, melanin synthesis was decreased. In contrast, a porcine placental extract in which exudates and insoluble materials including lipids had been removed increased melanin synthesis. In addition, the amount of tyrosinase, the enzyme critical for melanin synthesis, changed in accordance with the alteration of melanin synthesis. Interestingly, the amount of manganese‐dependent superoxide dismutase (MnSOD), a mitochondrial‐resident antioxidant enzyme, was increased when melanin synthesis was decreased by the whole placental extract. Mitochondrial respiration and glycolysis also changed following treatment with the placental extracts. These results suggest that placental extracts contain factors that can increase or decrease melanin synthesis by normal human melanocytes and that mitochondrial function may be associated with the placental extract‐induced regulation of melanogenesis.     

Two cases of vasa previa diagnosed prenatally using three‐dimensional ultrasonography

We report two cases in which we describe the impact of sonography (US) in the management of vasa previa. In the first case, with two‐dimensional US, the diagnosis of vasa previa was made at 21 weeks gestation. In the second case, using three‐dimensional US, the diagnosis of vasa previa was made at 19 weeks gestation. An elective Cesarean section was carried out at 34 weeks in both cases. Diagnosis of vasa previa is critical when low‐lying placenta or velamentous insertion of the umbilical cord is detected during the pregnancy. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound 38:389‐392, 2010     

Acute obstructive suppurative pancreatic ductitis (AOSPD) in pancreatic cancer treated by nasopancreatic drainage

An 80-year-old woman with pancreatic cancer was admitted with fever and abdominal pain. Blood examinations showed an elevated CRP level. On computed tomography (CT), a pancreatic tumor with a dilated upstream main pancreatic duct (MPD) was seen. Endoscopic retrograde cholangiopancreatography (ERCP) showed the strictured part of the MPD at the head of the pancreas with upstream dilatation. A nasopancreatic drainage tube was placed. Through the tube, purulent pancreatic juice was discharged and culture of the pancreatic juice grew Klebsiella pneumoniae. On the day after ERCP, the patient’s condition and the laboratory results improved. The patient’s disorder was diagnosed as acute obstructive suppurative pancreatitis with pancreatic cancer.     

Malignant lymphoma arising from heterotopic Warthin's tumor in the neck: case report and review of the literature

Warthin's tumor (WT), so-called adenolymphoma, is a benign salivary gland tumor with both epithelial and lymphoid histological characteristics, so the histogenesis remains unclear. Treatment consists primarily of tumor removal or conservative follow up. Here we present a rare case of malignant lymphoma arising from heterotopic (ectopic) WT. A 102-year-old man presented with a mass in the left side of the neck which was painless but gradually enlarged over 1 month. The mass was 2-3 cm in diameter, and freely moveable below the angle of the mandible. The mass was totally removed. The histological diagnosis was malignant lymphoma, diffuse large B-cell type, arising from heterotopic WT. Postoperative staging examination including chest radiography, bone scan, and computed tomography of the abdomen and pelvis revealed no evidence of dissemination of malignant lymphoma. Malignant transformation within WT is rarer in the lymphoid component than in the epithelial component. Only 16 cases of malignant transformation arising from WT have been reported, including only three cases of non-Hodgkin lymphoma apparently arising from heterotopic WT. Tumor removal or careful follow up is recommended in patients with WT because of the potential risk posed by such malignant transformation.     

A case of primary small cell carcinoma of the liver that was treated with chemotherapy

Primary small cell carcinoma (SSC) of the liver is very rare in Japan and only ten cases have been reported worldwide. We report herein the case of a 77-year-old man with primary SCC of the liver. He had a tumor over 10 cm in diameter which was localized in the right lobe of the liver and had invaded the right diaphragm. In laboratory tests, high serum levels of lactate dehydrase and neuron-specific enolase were observed. A biopsy specimen showed that the tumor cells were similar in cytology to a pulmonary SCC. The patient was first treated with carboplatin and etoposide according to the therapy protocol for pulmonary SCC and then with a regimen using etoposid and cisplatinum, resulting in an unfavorable outcome. We discuss the clinical course and therapy of extra-pulmonary SCC and review the literature of the cases previously reported.     

Trisomy 3 may predict a poor response of gastric MALT lymphoma to Helicobacter pylori eradication therapy

AIM: To investigate the relation of the response to Helicobacter pylori eradication therapy to the depth of tumor invasion and chromosome abnormalities in patients with mucosa-associated lymphoid tissue (MALT) lymphoma and to determine the clinical value of aneuploidy. METHODS: We studied 13 patients with localized gastric MALT lymphoma of stage E1. Before eradication therapy, the depth of tumor invasion was assessed by endoscopic ultrasonography in 8 patients and by endoscopic examination and gastrointestinal series in the remaining patients. To detect chromosomal abnormalities, paraffin-embedded tissue sections of diagnostic biopsy specimens underwent tissue-fluorescence in situ hybridization (FISH), using chromosome-specific α-satellite DNA probes for chromosomes 3,7,12, and 18 and YAC clones for t(11;18)(q21;q21). RESULTS: Seven of the 13 patients had complete regression (CR) in response to H pylori eradication therapy. No patient with CR had submucosal tumor invasion. Trisomy 18 was seen in 1 patient with CR, and both trisomies 12 and 18 were present in another patient with CR. All patients with no response or progressive disease had deep submucosal tumor invasion and showed t(11;18)(q21;q21) or trisomy 3. Trisomy 7 was not detected in this series of patients. CONCLUSION: The depth of tumor invasion is an accurate predictor of the response of stage E1 MALT lymphoma to H pylori eradication therapy and is closely associated with the presence of chromosomal abnormalities. Trisomy 3 may predict the aggressive development of MALT lymphoma.     

A case of Paragonimus miyazakii with migrating infiltrates: use of ELISA in diagnosis and treatment]

A 47-year-old man was referred to our clinic with abnormal chest radiographs. He was free of symptoms, but his chest CT demonstrated transient migrating infiltrates. Peripheral blood revealed eosinophilia and eosinophilic pneumonia was suspected. However, the bronchoalveolar lavage fluid showed no increase in eosinophils. Later, the patient's pleural effusion did contain eosinophils. His total IgE level was continuously elevated despite the absence of allergic disease, and so parasitic infection was suspected. Ouchterlony's double diffusion test after absorption of Paragonimus westermanii antigen was positive for Paragonimus miyazakii antigen. The ELISA values of both serum sample and pleural effusion were increased. As the ELISA value of the pleural effusion was higher than the serum one, we realised that pleural effusion was caused by Paragonimus miyazakii. Treatment with praziquantel for 3 days resulted in disappearance of the abnormal chest radiographic findings, and a reduced blood eosinophil level, IgE level and ELISA titre for Paragonimus miyazakii. We concluded that ELISA was useful in the diagnosis and assessment for treatment in Paragonimus miyazakii infections although there was no clearly relevant history.     

Plasmodium falciparum chloroquine resistance transporter is a H+-coupled polyspecific nutrient and drug exporter

Extrusion of chloroquine (CQ) from digestive vacuoles through the Plasmodium falciparum CQ resistance transporter (PfCRT) is essential to establish CQ resistance of the malaria parasite. However, the physiological relevance of PfCRT and how CQ-resistant PfCRT gains the ability to transport CQ remain unknown. We prepared proteoliposomes containing purified CQ-sensitive and CQ-resistant PfCRTs and measured their transport activities. All PfCRTs tested actively took up tetraethylammonium, verapamil, CQ, basic amino acids, polypeptides, and polyamines at the expense of an electrochemical proton gradient. CQ-resistant PfCRT exhibited decreased affinity for CQ, resulting in increased CQ uptake. Furthermore, CQ competitively inhibited amino acid transport. Thus, PfCRT is a H⁺-coupled polyspecific nutrient and drug exporter.Malaria caused by the protozoan parasite Plasmodium falciparum is one of the leading causes of mortality and morbidity in humans worldwide (1). Chloroquine (CQ) was initially a highly effective drug against this devastating disease (2). However, resistant strains of P. falciparum began to appear around 1950, and today practically all of the parasites are resistant to CQ (3–7). This has become a major threat to global public health. Extensive research identified a CQ transporter, P. falciparum CQ resistance transporter (PfCRT), which functions in resistant but not wild-type strains of the parasite (2, 8–14). The mutant transporter is expressed in the membranes of its digestive vacuoles (DV), excreting CQ from the vacuole and thus conferring resistance (15, 16). The decrease in intravesicular CQ concentration also promotes conversion of highly toxic hematin to hemozoin, generating resistance to other antimalarial drugs in addition to CQ (2, 9, 17–23). Therefore, it is important to clarify the transport mechanism of PfCRT to overcome drug resistance in malaria parasites (2, 9–11). However, the role of CQ-sensitive PfCRT transport under physiological conditions and how CQ-resistant PfCRT gains the ability to transport CQ remain unclear.Addressing the physiological relevance of PfCRT is a major issue in the area of infectious diseases. Attempts to obtain PfCRT-defective P. falciparum have been unsuccessful, suggesting that PfCRT is involved in DV transport processes that are essential for the parasites (2, 9). As CQ is a divalent amine that can freely penetrate through lipid membranes in its neutral form, but becomes impermeable upon protonation, we hypothesized that PfCRT recognizes amphipathic amines as transport substrates and acts as a polyspecific organic cation transporter. Similar to the vacuoles of yeasts and plants, the DV of the malaria parasite establishes a proton motive force or an electrochemical gradient of protons across the membrane as the sum of interior acidic pH gradient (ΔpH) and inside-positive membrane potentials (Δψ) by electrogenic proton pumps, vacuolar H⁺-ATPase, and vacuolar H⁺-pyrophosphatase to supply energy to secondary active transporters (23–27). Therefore, we also hypothesized that PfCRT may use the electrochemical gradient of protons as a driving force for transport.Recently, we have developed a transporter assay system that includes overexpression, purification, and reconstitution of eukaryotic transporters (28–30). The assay system enables us to study the mechanisms of action of transporters under defined ΔpH and Δψ. In the present study, we applied this technique to PfCRT to determine the transport properties of CQ-sensitive and CQ-resistant PfCRTs.