Proliferation and subsequent loss of bile ductules is a common pathologic disorder in the course of fulminant hepatitis. A pathologic and electron-microscopic study was undertaken to determine the mechanism of bile ductular proliferation and loss, using seven autopsy cases of fulminant hepatitis with different times of onset. The proliferation in bile ductules was mild at 6 days from onset, but had become more severe by 37 days, and by 75 days from onset ductules were deleted. Electron microscopic findings of proliferated bile ductules resembled those of hepatocytes, but at 75 days they showed bile ductular metaplasia. Apoptotic cells were observed in bile ductules between 26-37 days, but could not be found between 6-10 days or at 75 days after onset. From these findings, the proliferated bile ductules of fulminant hepatitis were found to resemble hepatocytes, and the subsequent loss of bile ductules is due to apoptosis.

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We analyzed the proliferative activity of cells in superficial type lesions of colorectal neoplasms by immunohistological staining of proliferating cell nuclear antigen (PCNA) and by comparing labeling indices (PCNA-LI) . In particular, we compared the proliferative activities of superficial elevated type lesions in two age groups. Old age (≥70 years) and pre-old age (<70 years) . Among 43 samples there were no significant differences in the PCNA-LI between mucosal carcinoma (m-carcinoma) and adenoma, or between neoplasms that fell into two size groups (diameters ≤ 0.5 cm and ≥ 0.6 cm) . Comparison of PCNA-LI between different age groups showed a lower value (26.3%) in the old age group than in the pre-old age group (31.6%), but this difference was not significant. Of the 27 superficial elevated neoplasms, when considering the entire layer of lesion, PCNA-LI was 23.3% in the old age group and 33.2% in the pre-old age group. However, when considering the surface layer of these lesions, values were 17.0% and 32.2% in the old age and pre-old age groups, respectively. In the deep layer, values were 29.7% and 34.2% in the old age and pre-old age groups, respectively. The PCNA-LI in the surface layer was statistically significantly different between the two age groups, suggesting that proliferative activity in colorectal superficial elevated type lesions varies, depending on the age of the patient.

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Glomerulosclerosis is the final event of many chronic renal diseases. It is characterized by the accumulation of extracellular matrix (ECM) proteins. Collagen IV is one of the major ECM proteins that accumulate in glomeruli in chronic renal disease. Lysyl oxidase (LOX) -induced cross-linking of collagen may be involved in these processes. Therefore, we studied LOX mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR) in progressive proliferative glomerulonephritis (anti-Thy 1.1 nephritis induced in unilaterally nephrectomized rats) and reversible proliferative glomerulonephritis (anti-Thy 1.1 nephritis induced in normal rats) . Segmental glomerulosclerosis was observed in about 10% of glomeruli in rats with anti-Thy 1.1 nephritis induced in unilateral nephrectomy at eight weeks after disease induction. A marked increase in glomerular LOX mRNA expression was also demonstrated. In contrast, the glomerulus at 7 days after anti-Thy 1.1 nephritis induced in normal unmanipulated rats was characterized by marked glomerular cell proliferation and matrix expansion. However, there was no evidence of sclerosis in the glomerulus in this model and there was no LOX mRNA expression in glomeruli. These results suggest that expression of LOX in glomeruli may be a marker for the occurrence of glomerulosclerosis, and that LOX may also play a key role in the development of irreversible glomerular fibrosis by cross-linking of collagen fibrils.

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Calcitonin gene-related peptide (CGRP) induces vasodilation, hypotension, and tachycardia. Tachycardia induced by CGRP may be due to sympathetic activation. The volatile anesthetic sevoflurane attenuates arterial baroreflexes. We examined the hemodynamic, endocrine, and metabolic effects of CGRP infusion (4μg·kg^-1) in dogs anesthetized with sevoflurane. Hemodynamic variables, plasma catecholamine, glucose and lactic acid were measured before, during, and after CGRP infusion. Anesthesia consisted of induction with pentobarbital, followed by 2.4% sevoflurane in oxygen. The decrease in mean arterial pressure induced by CGRP was due to a reduction in systemic vascular resistance associated with an increase in cardiac index, but was not accompanied by any change in heart rate. Mean pulmonary artery and pulmonary capillary wedge pressures remained unchanged during infusion but mean pulmonary artery pressure increased after infusion. Plasma norepinephrine concentrations increased, but epinephrine levels did not increase during infusion. Plasma glucose concentrations increased only during infusion, but plasma lactic acid concentrations increased throughout the observation perod. In conclusion, the current study demonstrated that the suppression in CGRP-induced tachycardia might be due to catecholamines resulting from sevoflurane-induced sympathetic suppression. These findings suggested that CGRP may be a useful vasodilator agent during sevoflurane anesthesia.

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The glutamate receptors in the nervous system are related to nociceptive response. These receptors include the AMPA (α -amino-3-hydroxy-5-methyl-4-isoxazolepropionate) receptor and the NMDA (N-methyl-D-aspartate) receptor. The purpose of this study was to investigate whether novel antagonists of these glutamate receptors could inhibit the nociceptive response in the spinal cord of male Wistar rats. Rats intrathecally (i.t.) received 0.1 to 10 pmol of Ly-2935582 (a novel AMPA antagonist) and 10 to 1000 pmol of Ly-233053 (a novel NMDA antagonist) dissolved in 50 μl of physiological saline. A 50-μl volume of 2.0% formalin solution was injected as a noxious stimulus into the hindpaw 15 min after the i.t. injections. We measured the total time the animal spent licking the hindpaw in the first 5 min (early phase) and from 10 to 30 min (late phase) after formalin injection. Controlled total licking time was 103±13 sec (mean ± SE) (early phase) and 151±86 sec (late. phase) . The licking time during the early phase was significantly and dose-dependently decreased with intrathecal administrations of both Ly-293558 and Ly-233053 (p<0.05) . However, Ly-293558 induced this effect at much lower concentra-tions. During the late phase, only the highest dose of each antagonist significantly shortened licking time. Our results indicate that these two novel AMPA and NMDA receptor antagonists when intrathecally administrated could induce antinociceptive effects during both the acute phase (peripheral sensitization) and late phase (central sensitization) of formalin-induced nociceptive stimulation without producing motor dysfunction.

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Shoulder-hand syndrome (SHS), which is a sequela of cerebrovascular disorders, was treated by stellate ganglion block (SGB) or polarized infrared ray irradiation near the stellate ganglion (PIRISG) . A total of 14 cases were treated by SGB (SGB group) and 12 cases by PIRISG (PIRISG group) . Therapy was carried out twice per week on average in both groups. After the completion of 20 rounds of treatments, the pain score was determined in each patient by a 10-step method. The condition prior to the initiation of therapy was defined as 10, and at the termination of 20 treatments, the pain score was calculated based on a questionnaire on subjective pain given to patients. Background factors of patients including age, sex, causes of cerebrovascular disorder, degree of pain at the first visit to hospital, Brunnstrom stage (BS) on upper limbs at the visit, and the period from onset of the disease to the initiation of therapy were recorded. There was no significant difference between the two groups in any of these background factors. The degree of remission in the pain score was significantly better in the SGB group than in the PIRISG group (p< 0.05) . This may be due to the different effects between these two groups on the autonomic nervous system.

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The immunohistochemical detection of aromatase was performed in breast carcinoma specimens obtained from 55 patients. Thirty-nine carcinomas were from postmenopausal women and 16 from premenopausal women. Aromatase immunoreactivity was observed in 33 of 55 cases (60%) . The positivity for aromatase staining was 64% in the postmenopausal group and 50% in the premenopausal group. The postmenopausal group tended to have a significant positive association between estrogen receptor expression and aromatase positivity (p=0.035) . The immunohistochemical detection of aromatase expression may be useful in the monitoring of postoperative endocrine therapy in women with breast carcinoma.

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Thirty bleeding cases after therapeutic endoscopy for 2916 colorectal lesions were analyzed. The therapeutic endoscopy method, size of lesions, anatomic location, latency between endoscopic therapy and rectal bleeding were recorded for each case. The bleeding rate by hot biopsy was 0.4% (5 lesions), by polypectomy 1.4% (20 lesions) and by endoscopic mucosal resection 1.7% (5 lesions) . The bleeding rate was associated with the size of the colorectal polyp. Sessile lesions on the cecum and ascending colon had the highest incidence of bleeding after therapeutic endoscopy. Pedunculated lesions bled more than any other lesions in the rectosigmoid region. A 93% bleeding rate was recognized within the ninth day after therapeutic endoscopy. Endoscopic clipping was the most effective for bleeding after endoscopic resection. None of our cases underwent surgical operation for bleeding after endoscopic resection. Based on these results, we would perform endoscopic clipping to prevent bleeding after removal of any lesion more than 1.0cm in size, such as a sessile lesion on the cecum and ascending colon, or a pedunculated lesion on the rectosigmoid region.

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Selective portal vein occlusion (PVO), which produces the regeneration of the residual liver, prior to extended hepatectomy, reduces postoperative morbidity and mortality rates. However, the mechanisms by which PVO leads to hypertrophy of the remnant liver and atrophy of the liver to be resected have not been clarified. We studied the association between liver regeneration and hepatic reduced glutathione (GSH) in lobes supplied by branches of the portal vein that had been occluded (POL) or not occluded (PNOL) in rats. The changes in liver weight and liver function, and hepatic GSH levels in both POL and PNOL were determined before and after portal vein occlusion. The regeneration in PNOL was accompanied by an increase in GSH production, whereas POL showed atrophic changes with a continuous decrease in GSH. These results might suggest one of the mechanisms by which preoperative portal vein embolization prevents liver failure after extended hepatectomy and improves clinical outcome.

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