Okayama University Medical School

Excised extensor retinacula of the first compartment and tenosynovium from 35 patients (6 men and 29 women) with de Quervain's disease were examined by light and electron microscopy to investigate the pathogenic mechanism. The patients, aged from 22-78 years, averaging 50 years, comprised the study group. Two hundred and thirty-two specimens from cadavers of 95 men and 75 women were macroscopically examined as the control. In the study group, the extensor retinaculum and tenosynovium were macroscopically thickened, and were histologically classified into 4 groups based on presence or absence of septum, and the location of retinacular thickening. Morphologically, the thickening of the tenosynovium and retinaculum was due to fibrosis in every layer, although fibroses were seen mainly in the middle layer. The ratios of proliferation of fibroblasts, myxoid changes and/or hyaline degeneration, and vascular proliferation were varied between layers. Minimal round cell infiltration was found in the retinaculum as well as in the tenosynovium. The results also indicate that the Iwahara-Nozue test can be used to accurately predict relatively greater thickening of the retinaculum on the extensor pollicis brevis side. Based on clinicopathological analyses, it appears that de Quervain's disease is induced not only by extrinsic factors such as superficial friction but also by intrinsic factors.

The effects of the combination of natural human tumor necrosis factor-alpha (nHuTNF-alpha) and natural human interferon-alpha (nHuIFN-alpha) on the induction of apoptosis were investigated by immunohistochemical analysis with BM-1/JIMRO monoclonal antibody in RPMI 4788 tumor cells. Few tumor cells in the control culture could spontaneously undergo apoptosis. The number of positive cells increased at 2 and 4 h after treatment with nHuTNF-alpha (1 x 10(5) U/ml) and nHulFN-alpha (1 x 10(5) IU/ml). This effect was clearly maintained from 8 h up to 72 h of culture. The number of apoptotic cells also greatly increased with doses, suggesting that the apoptosis induced by nHuTNF-alpha and nHuIFN-alpha in combination was dose-dependent. nHuTNF-alpha or nHuIFN-alpha alone could induce apoptosis, but the induction increased significantly when the two cytokines were combined. These findings indicate that by combining nHuTNF-alpha and nHuIFN-alpha apoptosis can be synergistically induced in RPMI 4788 tumor cells, and may have specific therapeutic implications for clinical treatments using these two cytokines.

To study changes in hemorheologic properties during pregnancy, erythrocyte deformability was measured by an electron spin resonance (ESR) method. The results obtained by this method showed that erythrocyte deformability in normal pregnancy decreased significantly in the first trimester compared with nonpregnant controls, and continued to decrease slightly as pregnancy progressed. On the other hand, erythrocyte deformability in severe pregnancy-induced hypertension (PIH) was significantly lower than that in the third trimester of normal pregnancy. Additionally, we found that the hematocrit level needed for erythrocytes to exhibit high deformability is lower during pregnancy. These results suggest that hemodilution in normal pregnancy, so-called hydremia, compensates for the decrease in erythrocyte deformability. Conversely, since erythrocytes become less deformable in a hemoconcentration condition in severe PIH, microcirculatory disturbance of various organs, including the uteroplacental unit, may occur. The lowered erythrocyte deformability may be one of the important pathologic features in PIH.

The antidonor immune response was examined in a one haplotype-mismatched renal transplant recipient with an allograft that had been well-functioning for more than 10 years. Although the relative response of the mixed lymphocyte reaction (MLR) was (45.8)% and the MLR responder cells stimulated by donor cells produced measurable amounts of interleukin-2 (IL-2) (11.6 U/ml), the cytotoxic T lymphocytes (CTL) could not be generated against donor cells, even with exogenous IL-2. These results indicate that antidonor CTL precursors were either deleted or inactivated in this recipient.

99mTc-DTPA-galactosyl human serum albumin (Tc-GSA) is a new liver-imaging agent which binds specifically to hepatic binding protein. The purpose of this study was to evaluate the usefulness of Tc-GSA in quantitatively evaluating hepatic ischemia-reperfusion injury in the rat. Regional hepatic ischemia was induced by clamping the left hepatic artery and the left portal vein for 5 to 45 min. A hepatic accumulation index (t90) was obtained on the basis of the dynamic data. A significant difference of this index was observed between all ischemic groups and the control. In conclusion, 99mTc-GSA appears useful for evaluating the hepatic ischemia-reperfusion injury.</P>

Iliac arteries were occluded in adult mongrel dogs to investigate pelvic hemodynamics. When the unilateral common iliac artery was occluded, the blood flow making a "stopover" within the pelvis was found to be significantly less than that of anatomical hemodynamics even under a resting condition. The blood flow decreased more significantly under exercise loading than under a resting condition, which demonstrates the presence of the "steal" phenomenon. This only occurs in the collateral circulation in the pelvis formed by two arterial systems which are related in a series. In deciding the appropriacy of reconstruction for the internal iliac artery in patients with aorto-iliac occlusive disease, this "steal" phenomenon should be kept in mind. In most cases, ischemic symptoms in pelvic organs may be due to a simple decrease of the blood flow supplied to the pelvis, or due to the "steal" phenomenon. If the pelvic region is in the state of ischemia owing to the "steal" phenomenon, reconstruction of the blood vessels flowing into the pelvis is not required.

A 40-year-old man with valvular heart disease was successfully treated using a left ventricular assist device (LVAD) after open heart surgery. Echocardiography revealed left ventricular ejection fraction (LV-EF) at LVAD on/off: 23.4%/14.6% on the 4th, 23.8%/23.8% on the 5th, and 23.8%/26.8% on the 6th postoperative day (POD), respectively. The patient was weaned from LVAD on the 8th POD and discharged from the hospital on the 58th POD. The LV-EF improved to 54% 6 months after surgery and increased from 57% to 64% in response to exercise stress testing 1 year after surgery.

Membrane fluidity in human erythrocytes was measured by a spin label method using an electron spin resonance spectrometer in healthy volunteers after ingestion of alcohol (1.5 ml of whisky/kg body weight). Fluidity in the lipid bilayer closer to the hydrophilic face decreased at 30 min and 90 min, and fluidity in the hydrophobic core decreased at 90 min after ingestion of alcohol. In the same experiment, the level of thiobarbituric acid reactive substances in the serum decreased 30 min after ingestion of alcohol, and the triglyceride level increased and free fatty acid level decreased, and serum superoxide dismutase activity increased 150 min after ingestion. Furthermore, membrane fluidity in human erythrocytes was examined in patients with alcohol dependence syndrome who had not any alcohol for about 26 months. Erythrocyte membrane fluidity of patients with alcohol dependence syndrome was not different from that of healthy controls. However, erythrocyte membrane fluidity of the lipid bilayer closer to the hydrophilic face increased in patients who had concomitant liver cirrhosis compared with those who did not. These results suggest that alcohol affects temporal change of membrane fluidity in human erythrocytes.

To investigate the role of vitronectin in the progression of diabetic nephropathy, plasma concentrations of vitronectin were measured by enzyme-linked immunosorbent assay in patients with diabetes mellitus and compared with normal control subjects. In diabetic patients with normoalbuminuria and microalbuminuria, plasma concentrations of vitronectin were significantly higher than those of control subjects. Plasma concentrations of vitronectin in diabetic patients with chronic renal failure were significantly lower than those with normal renal function. There was a significant positive correlation between plasma concentration of vitronectin and blood platelet counts. In the early stage of diabetic nephropathy, vitronectin may be increased caused by synthesis from activated platelets. With progression of diabetic nephropathy, plasma vitronectin may be decreased because of accumulation in sclerotic glomeruli and arteriosclerotic lesions. In conclusion, the plasma concentration of vitronectin appears to be an important marker for the progression of diabetic nephropathy.

A carboxyfluorescein (CF)-enveloping soybean phosphatidylcholine liposome was used as a model of physicochemical damage of biomembranes. The liposomes were exposed to a metal-chelate complex [2 mM of ferric nitrilotriacetate (FeNTA) or cupric nitrilotriacetate (CuNTA)] plus a reductant (2 mM of ascorbate or various concentrations of reduced glutathione), and CF release from damaged liposomal membranes and the generation of thiobarbituric acid-reactive substances (TBARS) were measured. In the presence of a reducing agent, both FeNTA and CuNTA stimulated markedly CF release and an increase in the TBARS level, while in the absence of a reducing agent both of the chelate complexes showed little CF release and TBARS. The effects of H2O2 addition to the reaction system containing liposome with FeNTA or CuNTA plus ascorbate were also examined. The CF release was slightly increased by the addition of a smaller dose (0.5 mM) of H2O2 and it was inhibited by 8 mM of H2O2. A similar result was obtained in the TBARS test. These results suggest that FeNTA- or CuNTA-mediated lipid peroxidation can damage liposomal membranes physicochemically, and the redox reaction of the chelated metal itself is more important than a Fenton-type reaction in the process.

Endoscopical segmental piecemeal tumorectomy (ESPT) for nodular elevation of colorectal tumor is advantageous in terms of minimizing both surgical invasion and postoperative burden to the patients. Nodular elevation of colorectal tumors is said to occur when the body of the tumor is adenomatous and the surface of the focal cancer grows more horizontally into the lumen than vertically. We report here four cases of nodular elevation of colorectal tumors which were each treated by different surgical procedures.

An anodal direct current of 3.0 microA or 30.0 microA was unilaterally applied for 30 min or 3 h to the surface of the sensorimotor cortex of rats, and the effects of polarization on the morphology of brain cells were examined by light microscopy. After five repeated anodal polarization trials, dark neurons appeared mainly in the polarized neocortex regardless of the intensity and duration of the polarizing currents. Such dark neurons were scarce in the control animals or the animals receiving only one trial of polarization. The dark neurons were most abundant in the second to fourth layers of the ipsilateral superior-lateral convexity of the frontal cortex, but a few were present in the contralateral cortex. The dark neurons began to appear 24 h after the last polarization; thereafter almost all of these neurons gradually reverted to their normal morphological profiles through a transitory state within 1 month of the last trial of repeated polarization. No morphological changes were apparent in any of the brain structures other than the cerebral cortex. These findings indicate that repeated anodal polarization has reversible morphological effects on the cortical neurons, suggesting that the appearance of dark neurons after anodal polarization is an important index for evaluation of cortical plastic change induced by polarization.

Recently, factors predicting the response to interferon (IFN) therapy against hepatitis C virus (HCV) have received much attention. To evaluate the usefulness of the quantitation of intrahepatic HCV RNA as a predictive marker of the response to IFN therapy, we compared the amount of intrahepatic HCV RNA with serum levels in 16 patients. Eleven patients who had 10(10) copies/g or more of intrahepatic HCV RNA had increased level of serum alanine aminotransferase (ALT) after IFN therapy, while 4 of 5 patients who had less than 10(10) copies/g of intrahepatic HCV RNA achieved sustained normalization of serum ALT level and were designated as complete responders. Four complete responders possessed significantly less HCV RNA in the liver parenchyma than partial and nonresponders (P = 0.010, Mann-Whitney U-test), but the amount of HCV RNA in the serum was not significantly different between those groups. In conclusion, the results suggest that the quantitation of intrahepatic HCV RNA is a better indicator of the response to IFN therapy than serum HCV RNA.

The growth and rupture of 40 cerebral aneurysms was studied in 36 patients (14 men, 22 women; were average age, 51.8 years). Aneurysms were classified into five types according to the intraoperative findings: type 1, uniformly thin, smooth surface; type 2, thin neck and thick wall, smooth surface with or without red and/or transparent portions; type 3, uniformly thick wall, smooth surface with or without red portions; type 4, thick neck, bubbled or loculated thin wall at dome with or without red and/or transparent portions; type 5, thick wall in entirety, irregular surface with or without red portions. Five were type 1, six type 2, and 12 type 3. In four of the type 2 aneurysms, turbulence could be seen at the neck. In seven of the type 3 aneurysms, red and/or transparent portions were observed in the wall. Thirteen were type 4; nine of which had a bubbled or loculated wall with or without red and/or transparent portions. Four were type 5, with scattered red portions but a thick wall. Type 1 aneurysms were 2-5 mm, most of types 2 and 3 were 3-6 mm, type 4 were 3-13 mm, and type 5 were more than 9 mm. Types 1 and 2 had few local changes in the wall, suggesting that aneurysms at this stage are stable. Type 3 is considered to be a transitional stage to type 4 from type 2. Type 4 aneurysms had some local changes within the wall including bubbles or loculi. We concluded that aneurysms exceeding 4 mm have local pathologic changes in the wall and are critical.(ABSTRACT TRUNCATED AT 250 WORDS)

To determine the allergens of mite allergic rhinitis, we studied 31 patients with mite allergic rhinitis by skin tests and nasal provocation tests (15 for skin and 16 for nasal tests) using 6 fractions of Dermatophagoides pteronyssinus (Dp) extract differing in molecular weights (15, 25, 32, 53, 95 and 190 kDMW). In skin testing, patients showed intense positive reactions to the fractions of 15, 25, 32, 95 and 190 kDMW, among which the most patients showed positive reactions to the fractions of 15 and 25 kDMW. Significant differences were found in patients' positive reactivity among each fraction and between low (15 and 25 kD) and high (95 and 190 kD) molecular weight fractions as well. In nasal provocation tests, patients showed intense positive reactions to the fractions of 15, 32, 53 and 95 kDMW, especially to the fractions of 15 and 95 kDMW. Furthermore, the insidence of positive reactions to the 15 kDMW fraction was significantly higher than that to any other fraction in the skin tests (P < 0.05). From these results, the low molecular weight fraction, 15 kDMW, is considered to be the main allergen of this mite and the high molecular weight fractions, 95 and 190 kDMW, may also be considered to be allergens of this mite.

A non-invasive method for measuring portal blood flow by magnetic resonance (MR) phase contrast was evaluated in a flow phantom and 20 healthy volunteers. In a flow phantom study, the flow volumes and mean flow velocities measured by MR phase contrast showed close correlations with those measured by electromagnetic flowmetry. In 20 healthy volunteers, the cross-sectional areas, flow volumes and mean flow velocities measured by MR phase contrast correlated well with those measured by the Doppler ultrasound method. Portal blood flow averaged during the imaging time could be measured under natural breathing conditions by using a large number of acquisitions without the limitations imposed on the Doppler ultrasound method. MR phase contrast is considered to be useful for the non-invasive measurement of portal blood flow.

The purpose of this study was to investigate the effects of topical treatment with zinc oxide (2.5%, 10%, 25% and 50%) and intraperitoneal treatment with diethyldithiocarbamate (DEDTC) (50 mg/kg, 500 mg/kg and 1,000 mg/kg) on the mitotic index of epidermal basal cells in incised and non-incised mouse skin. The present results showed that topical application of zinc oxide (25% and 50%) increased the mitotic index of epidermal basal cells in incised skin and non-incised skin. Conversely, intraperitoneal administration of DEDTC (500 mg/kg and 1,000 mg/kg) decreased the mitotic index, but only in the incised skin. These results suggest that mitosis of epidermal basal cells may be stimulated by the topical application of zinc oxide both in incised and non-incised mouse skin, and that it also may be inhibited by the intraperitoneal administration of DEDTC in incised mouse skin.

P-glycoprotein is a transmembrane protein which acts as an energy-dependent drug efflux pump for a variety of anti-cancer drugs. The mdr-1 gene which encodes P-glycoprotein was successfully cloned in 1986. To investigate P-glycoprotein expression in diverse ovarian tumors, including benign, low malignant potential and malignant, immunohistochemical study was done using a monoclonal antibody (C 219). Overall, 8 out of the 59 epithelial ovarian tumors (13.6%) expressed P-glycoprotein. It was noted that 5 of the 12 mucinous tumors were found to express P-glycoprotein, while none of the 31 serous tumors were immunohistochemically positive. In 10 malignant ovarian tumors, P-glycoprotein immunostaining was examined both prior to and after chemotherapy. Nine of them did not express any P-glycoprotein before or after chemotherapy. However, one tumor expressed P-glycoprotein after six courses of multidrug resistance-related drug administration. These findings indicate that P-glycoprotein expression is not so common in ovarian tumors, regardless of their malignant potential. Nevertheless, the results suggest a strong association between P-glycoprotein expression and certain histological cell types in epithelial ovarian tumors. It is also possible that P-glycoprotein appears as a result of chemotherapy, but such a phenomenon can not occur unless chemotherapy is administered at high doses for a long period of time.