Detection of hepatocellular carcinoma after interferon therapy for chronic hepatitis C: Clinical study of 26 cases

The clinical findings in 26 patients in whom hepatocellular carcinoma (HCC) was detected after the start of interferon (IFN) therapy for chronic hepatitis C were analysed. Histological study before IFN therapy showed that 34.6% of patients were categorized as stage 3 (septal fibrosis with architectural distortion; the 0–4 scale) and 80.8% demonstrated at least some evidence of septal fibrosis or more advanced features. The AFP levels examined before IFN therapy were more than 20 ng/mL in 13 patients (84.6% of those studied). One of 26 patients had a complete response to IFN therapy, while six of 26 patients had only a partial response. HCC was detected within 1 year after the start of IFN therapy in 76.9% of patients. Thus, the possibility of the early occurrence of HCC or its existence at the time of therapy should be seriously considered when IFN therapy is contemplated. Patients with stage 3 or 3–4 histology may already have a small undetectable HCC before IFN therapy. Thus, for this reason, every patient treated with IFN should be examined at short regular intervals for the development of HCC during and after IFN therapy.     

Melatonin treatment for rhythm disorder

Abstract We tried melatonin treatment in two patients with non-24 h sleep-wake syndrome, who did not respond to treatments by vitamin B₁₂, bright light therapy, or hypnotics. In one patient, melatonin 5–10 mg improved difficulty in falling asleep and in waking, although it failed to improve the sleep-wake rhythm. In another patient, melatonin 3 mg successfully changed the sleep-wake rhythm from free-running pattern to delayed sleep phase pattern. However, melatonin re-administration after a 4-month drug-free interval failed to improve his free-running sleep-wake rhythm. These results suggest that melatonin acted as a sleep inducer in one patient and as a phase setter in the other, although the effect on the latter patient was transient.     

Effects of obstructive jaundice on neutrophil production and acquisition of chemotactic activity in the bone marrow

Background and Aims:  Increased numbers and enhanced functions of peripheral neutrophils have been observed in obstructive jaundice. However, the effects of obstructive jaundice on the bone marrow, that is neutrophil production and acquisition of neutrophil chemotactic activity, have been poorly understood. In the present study, differentials of bone marrow cells and chemotactic activity of bone marrow neutrophils were evaluated in bile duct-obstructed rats.
Methods:  Male Wistar rats underwent either bile duct obstruction for 10 days or bile duct obstruction for 4 days followed by 6 days' internal biliary drainage. Differentials of peripheral blood and bone marrow cells were sequentially determined. Chemotactic activity of peripheral and bone marrow neutrophils was evaluated with a modified Boyden method using interleukin-8 (recombinant rat Gro-β) as a chemoattractant.
Results:  Numbers of peripheral neutrophils significantly increased after bile duct obstruction. Significant increases in the myeloid/erythroid (M/E) ratio of bone marrow cells were observed after bile duct obstruction. The neutrophil proliferative pool (promyelocytes and myelocytes) increased initially, followed by an increased neutrophil storage pool (metamyelocytes, bands, and segmented neutrophils). The M/E ratio as well as the neutrophil proliferative and storage pools normalized after internal biliary drainage. Chemotactic activity was enhanced in both peripheral and bone marrow neutrophils after bile duct obstruction, and enhanced chemotaxis was alleviated with internal biliary drainage.
Conclusion:  The present results strongly suggest the principal role of the bone marrow in increasing the number of neutrophils and their chemotactic activity during obstructive jaundice.     

Reduced protein tyrosine phosphatase (PTPase) activity of CD45 on peripheral blood lymphocytes in patients with systemic lupus erythematosus (SLE)

To disclose the mechanism of aberrant function of peripheral blood lymphocytes (PBL) in SLE, we focused on the catalytic function of CD45, and determined the CD45 PTPase activity in SLE patients. The sample population consisted of 32 SLE patients with different disease activity. PTPase activity of cell lysates immunoprecipitated by anti-CD45 MoAb was assayed against phosphotyrosine analogue PNPP, followed by measuring the release of para-nitro phenol at 410 nm. CD45 PTPase activity of PBL was significantly decreased in SLE patients, compared with that of normal controls and patients with systemic sclerosis (964 ± 265, 1202 ± 172, 1210 ± 125, respectively; SLE versus normal, P < 0.05). It was correlated with SLE Disease Activity Index (SLEDAI) score (r = 0.597, P = 0.0006), but not with the dose of prednisolone (r = 0.214, P = 0.2657), indicating that CD45 PTPase activity became reduced when the disease was active, but it was not affected by prednisolone. Moreover, it was not corrected by in vitro culture with or without stimulation. The expression of CD45 on PBL was comparable between normal and SLE, raising a possibility that it may be due to aberrant regulation of catalytic function of CD45 in SLE. Given the evidence that tyrosine phosphorylation of cellular proteins by tyrosine kinases and phosphatases is one of the key biochemical events in the signal transduction pathway, the decreased CD45 PTPase activity in SLE may account for the defective signal transduction via TCR/CD3, leading to dysregulated effector function of the lymphocytes.     

Carnitine depletion during total parenteral nutrition despite oral L-carnitine supplementation

Carnitine (CAR) plays an important role in the β-oxidation of fatty acids. Less attention, however, has been paid to CAR compared to other nutrients even in total parenteral nutrition (TPN). To examine CAR metabolism during TPN and the effect of simultaneous oral L-CAR supplementation on CAR levels, the blood CAR level was measured in a 3-year-old boy receiving long-term TPN because of short bowel syndrome. Both the total and acyl CAR in the serum were evaluated under various nutritional conditions including oral supplementation of L-CAR. Low CAR concentrations were observed especially when lipid containing TPN regimens were in place. Oral L-CAR supplementation was not sufficient to restore the low CAR levels in the present index patient even when the dose was increased to 120 mg/kg in accordance with the result of the L-CAR absorption test that revealed poor intestinal absorption of this nutrient. Moreover, a markedly low CAR level was measured during the onset of sepsis in the patient, and the blood CAR was depleted when lipid metabolism was activated by lipid loading or sepsis. To date, the late effects of CAR depletion on child growth have not been well examined. It is recommended that the blood CAR level be maintained at normal levels before any prominent manifestations of the deficiency have developed. The intravenous administration of CAR appears to be necessary to supply a sufficient amount of CAR for patients with severe malabsorption.     

Cystic lymphangioma of the gall-bladder: A case report

Intra-abdominal cystic lymphangiomas are rare lesions that can be difficult to diagnose. We present a report of a patient with a giant multilocular cystic lesion in the abdomen. Ultrasonography and computed tomography scans of the abdomen revealed that the cyst had originated in the gallbladder fossa. There was some calcification and thickening of the cyst wall. Endoscopic retrograde cholangiopancreatography demonstrated a medially deviated common bile duct, an elongated cystic duct and an inferior compressed gallbladder. There was no apparent communication between the cyst and the biliary tract; however, an abdominal angiogram revealed that the lesion was supplied by a branch of the cystic artery. Histological findings obtained intra-operatively were consistent with a cystic lymphangioma. Its characteristic histology was observed in the subserous layer of the gall-bladder. This case is a rare instance of a cystic lymphangioma originating in the gall-bladder.     

Polysomnography and body temperature changes by phototherapy in a delayed sleep phase syndrome case

Abstract We examined polysomnography (PSG) and body temperature in a patient with delayed sleep phase syndrome who responded to phototherapy. The patient was a 31-year-old woman whose condition had slightly improved by a vitamin B₁₂ administration. Phototherapy was administered to her in combination with the vitamin B₁₂ medication, and this combined treatment successfully advanced her delayed sleep phase. On PSG, the regimen showed shortened sleep latency, decreased total sleep time and stages 1 and 2 sleep, and increased slow wave sleep. Phototherapy also improved temporal distribution of delta half-waves (0.5-2.0 Hz, 31 µV) as well as phase relationship between sleep and body temperature.     

Detection of invasive protein profile of Streptococcus pyogenes M1 isolates from pharyngitis patients

Hasegawa T, Okamoto A, Kamimura T, Tatsuno I, Hashikawa S‐N, Yabutani M, Matsumoto M, Yamada K, Isaka M, Minami M, Ohta M. Detection of invasive protein profile of Streptococcus pyogenes M1 isolates from pharyngitis patients. APMIS 2010; 118: 167–78. Streptococcal toxic shock syndrome (STSS) is a re‐emerging infectious disease in Japan and many other developed countries. Epidemiological studies have revealed that the M1 serotype of Streptococcus pyogenes is the most dominant causative isolate of STSS. Recent characterization of M1 isolates revealed that the mutation of covS, one of the two‐component regulatory systems, plays an important role in STSS by altering protein expression. We analyzed the M1 S. pyogenes clinical isolates before or after 1990 in Japan, using two‐dimensional gel electrophoresis (2‐DE) and pulsed‐field gel electrophoresis (PFGE). PFGE profiles were different between the isolates before and after 1990. Markedly different profiles among isolates after 1990 from STSS and pharyngitis patients were detected. Sequence analysis of two‐component regulatory systems showed that covS mutations were detected not only in STSS but also in three pharyngitis isolates, in which proteins from the culture supernatant displayed the invasive type. The mutated CovS detected in the pharyngitis isolates had impaired function on the production of streptococcal pyrogenic exotoxin B (SpeB) analyzed by 2‐DE. These results suggest that several covS mutations that lead to the malfunction of the CovS protein occurred even in pharyngeal infection.