Research review: DNA polymerases as molecular markers of the regenerating capacity of hepatocytes

Hepatocyte regeneration has been widely investigated, with the mitotic index and the incorporation of [³H]thymidine being used as regeneration markers. We focused on the induction of DNA replication enzymes, particularly DNA polymerases (pol) α, δ, and ε. Using rat models, we have shown that the activity of pol α in crude liver extract well represents the regenerating capacity of hepatocytes. Using pol α as an indicator, we analyzed liver regeneration in rat models under various conditions: obstructive jaundice, external or internal biliary drainage, and the obstruction of portal vein branches. It has been revealed that the ligation of the common bile duct alone induces a certain amount of hepatocyte proliferation. It was striking that external biliary drainage suppressed regeneration capacity in cholestatic rat liver after partial hepatectomy. The strong regeneration in nonligated lobes induced by portal branch ligation was similar to the liver regeneration seen after partial hepatectomy with respect to the induction of DNA polymerases. Taken together, the aspects of DNA replication, particularly the induction of DNA polymerases, may contribute to shedding new light on the regeneration of human liver. This work was supported in part by a Grant-in-Aid for General Scientific Research and for Cancer Research from the Ministry of Education, Science and Culture, Japan, and by grants from the Uehara Memorial Foundation     

A case of renal pelvic carcinoma in situ]

A 72-year-old female visited our hospital with the complaint of macroscopic hematuria on Jan. 29, 1990. Cystoscopic examination revealed hematuria flowing out from the left ureteral orifice. A 1 cm mass was found in the left upper calyx by retrograde pyelography (RP). Urine cytology obtained by RP was class IIIb. Later, the mass was found in the left middle calyx by CT. Repeated RP revealed no mass and the wall of the left upper calyx was irregular. Washing cytology from the left renal pelvis was class V. Left total nephroureterectomy was performed on Feb. 2, 1990. Macroscopically, no tumor mass was apparent. Microscopically, transitional cell carcinoma in situ was widely spread from the left renal pelvis to the middle ureter. The preoperative upper calyceal mass was thought to have been a blood clot. At twelve months after the operation, there has been no evidence of tumor recurrence.     

Radial shortening for Kienb?ck's disease: factors affecting the operative result

The operative results of radial shortening in 23 patients with Kienb?ck's disease were analysed on the basis of age, stage of disease, ulnar variance and the amount of radial shortening. The patient's age was found to be the factor which affected the operative result most and unsatisfactory results were obtained in patients over 30 years old. However, neither the clinical stage nor ulnar variance affected the results significantly and the results in patients with ulnar zero or plus were no worse than in patients with ulnar minus. The risk of ulnar wrist pain was increased when the radius was shortened more than 4 mm in patients with positive or zero ulnar variance. This was an important cause of unsatisfactory operative results.     

Practical guidelines for physicians in the management of febrile seizures

Recent studies have shown that adequate medication can prevent the recurrence of febrile seizures (FS). It has also been clarified that the vast majority of, though not all, FS patients follow a benign course. Then, questions arise as to whether or not FS should be prevented, particularly in light of the risks of side effects from drugs. Which kinds of FS can be prevented, if necessary? The guidelines presented here are aimed primarily at helping general practitioners in considering how to manage FS most appropriately. The guidelines stress that judgements should be individualized, while referring to a few specific ‘warning factors’. The guidelines follow a ‘laissez-faire’ principle for the majority of FS cases, whereas intermittent therapy with diazepam and continuous medication with either phenobarbital or valproate are indicated in other limited cases meeting respective definite criteria.     

Off-pump resection of a coronary arterial fistula using the Harmonic Scalpel

Off-pump surgery was performed in a patient with post-infarction angina complicated with aneurysmal coronary-pulmonary arterial fistula. Epicardial echocardiography localized the artery feeding the fistula in the myocardium, which had not been revealed by visual inspection, palpation, or transesophageal echocardiography. The patient underwent off-pump coronary artery bypass grafting concomitant with aneurysmectomy. The feeding arteries were dissected easily using a Harmonic Scalpel and ligated. The flow in the aneurysm disappeared immediately and aneurysmectomy was performed without bleeding.     

Mouthguards: difference in longitudinal dimensional stability between single- and double-laminated fabrication techniques

Abstract –  Though the use of mouthguards (MGs) has increased with the increase in sporting activities, little is known about the influence of their fabrication methods on longitudinal dimensional stability. The objective of this study was to compare the difference in the longitudinal dimensional stability between single and laminated MGs. Single-layer MGs were made from a 4.0 mm thick ethylene vinyl acetate (EVA) sheet and laminated MGs were made from two 2.0 mm thick sheets of EVA. MGs were kept in a 37°C water bath for 60 h, equivalent to the time period of 3-months inter-oral use. MG deformation was analyzed by measuring designated points on the MG border using a profile projector (J-12, Nikon Inc., Tokyo, Japan) before and after the water immersion. A finite-element model was also created to examine the time course of stress accumulation during the sheet forming process using Finite Element software. Longitudinal deformation was smaller in the laminated MGs than in the single-layer MGs in the anterior area ( P  < 0.05). Finite element method (FEM) analysis also showed the largest stress accumulation in the anterior incisal area where deformations were mainly observed. Laminated double layer MGs have advantages over single-layer MGs in terms of longitudinal stability due to lower stress accumulation during the fabrication process.     

Panic Anxiety after Abrupt Discontinuation of Mianserin

Abstract: We observed a case of withdrawal after abrupt discontinuation of mianserin. A 41-year-old woman was treated according to a diagnosis of depression, which was her 6th episode. Mianserin 30 mg/day, etizolam 1 mg/day and flunitrazepam 1 mg/day were administered. When the patient discontinued taking the drugs by herself because of subsiding of these symptoms, severe panic anxiety appeared. This panic anxiety was not relieved by taking etizolam and flunitrazepam again, but subsided rapidly by the re-administration of mianserin 30 mg/day, and because of that the depressive symptom also disappeared.
From these experiences panic anxiety seemed to be a withdrawal symptom, and involvement of the noradrenergic system in panic anxiety as well as serotonergic system was suggested.     

Effects of renin-angiotensin system blockade on macrophage infiltration in patients with hypertensive nephrosclerosis.

The mechanisms of hypertensive nephrosclerosis are not fully understood. In experimental models of the disease, inflammatory reactions such as macrophage infiltration play an important role. In human hypertensive nephrosclerosis, however, there have been few studies examining the role of inflammation histologically. We investigated whether the number of infiltrating macrophages was increased in human hypertensive nephrosclerosis, and evaluated the effects of a blockade of the renin-angiotensin system on clinical and histological findings. We examined macrophage infiltration using immunohistochemistry in renal biopsy specimens obtained from 16 patients with hypertensive nephrosclerosis, 5 patients with IgA nephropathy, 5 patients with membranous nephropathy, and 5 patients with minimal change nephrotic syndrome. The number of infiltrating macrophages in glomeruli was significantly larger in the patients with hypertensive nephrosclerosis than in those with minimal change nephrotic syndrome. The patients with hypertensive nephrosclerosis were divided into groups based on their use of antihypertensive agents at the time of renal biopsy. We investigated the effects of antihypertensive agents on clinical findings, macrophage infiltration, and monocyte chemoattractant protein-1 expression. There was no difference in clinical findings between the hypertensive groups. The numbers of infiltrating macrophages and monocyte chemoattractant protein-1-positive cells in glomeruli were significantly smaller in patients treated with an angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor blocker, whereas calcium channel blockers had no influence on histological findings. In conclusion, inflammation is involved in the progression of human hypertensive nephrosclerosis and the inflammatory process is inhibited by blocking the renin-angiotensin system.     

Intrathecal landiolol inhibits nociception and spinal c-Fos expression in the mouse formalin test

PURPOSE: The purpose of this study was to determine if intrathecal landiolol, a beta1-blocker, can modulate formalin-induced nociception and spinal c-Fos expression in mice, in the absence of anesthesia. METHODS: Thirty-two mice were randomly assigned to one of four groups: the control group (n = 8) received intrathecal normal saline 10 microL, while the other three groups (n = 8 for each) received intrathecal landiolol at escalating doses of 250 microg.kg(-1), 500 microg.kg(-1) and 750 microg.kg(-1) respectively, immediately after induction of anesthesia with isoflurane. After awakening, inflammatory pain was induced by 10 microL of 5% formalin solution injected into the dorsal surface of the right hind paw. The nociceptive behaviours including licking, biting and lifting of the injected paw were cumulatively recorded as seconds of behaviours/min during phase I (0-10 min) and phase II (10-45 min). The c-Fos protein expressions in the spinal dorsal horn were detected with immunohistochemical techniques in the control and landiolol 750 microg.kg(-1) groups. RESULTS: Compared to the control group, intrathecal injection of landiolol 750 microg.kg(-1) significantly decreased pain-related behaviours in phase I, while intrathecal landiolol 250 microg.kg(-1), 500 microg.kg(-1) and 750 microg.kg(-1) significantly decreased pain-related behaviours in phase II during the formalin test. The numbers of c-Fos immunoreactive nuclei in the L5 spinal dorsal horn were significantly lower in the landiolol 750 microg.kg(-1) group compared to the control group (landiolol 750 microg.kg(-1) 2.4 +/- 1.1 vs control 9.2 +/- 3.9; P < 0.01). CONCLUSION: The present study indicates that intrathecally administered landiolol produces significant antinociceptive effects in the formalin test. Although further studies exploring the detailed mechanism are needed, these data suggest a potential role of beta1-adrenoreceptors in spinal nociceptive processing.     

A case of acute hepatitis E associated with multidrug hypersensitivity and cytomegalovirus reactivation

A 65-year-old Japanese man was hospitalized because of acute hepatitis and severe cholestasis due to hepatitis E virus (HEV) infection combined with a drug reaction to a cold preparation. He died of disseminated intravascular coagulation and severe intestinal bleeding due to systemic cytomegalovirus reactivation following the development of severe eruptions with marked eosinophilia due to drug hypersensitivity to taurine and ursodeoxycholate preparations. The close interaction between viral infection or reactivation and drug hypersensitivity was considered as a pathophysiology in this case, which emphasizes the need for further study of the immunological mechanism of the interaction.