Operation of female stress incontinence--comparison between Raz procedure and Gittes procedure]

We performed Raz procedure and Gittes procedure for female stress incontinence since October 1986. Raz procedure was performed on 19 patients between October 1986 and February 1990, and Gittes procedure was performed on 18 patients between June 1990 and May 1991. We followed up 17 patients who underwent Raz procedure and all the patients who underwent Gittes procedure at the time August 1991. Disappearance or marked improvement of incontinence was confirmed in 12 patients by Raz procedure, and 16 patients by Gittes Procedure. No serious complications were recognized. The reason why the result of Raz procedure was not sufficient was due to our immature operative technique and incorrect patient selection in our early experience. From this experience, we believe that both procedures can be very useful and minimal invasive operation for female stress incontinence.     

Asymptomatic primary mucinous cystadenocarcinoma of the appendix with a large abdominal mass: Report of a case

A case of cystadenocarcinoma of the appendix with a large cystic lesion is reported. A 49-year-old man undergoing a routine ultrasonic scan was incidentally found to have an abdominal mass measuring some 30 cm in size. The clinical presentation was asymptomatic, and the patient underwent a laparotomy without ascertaining a diagnosis preoperatively. The lesion, which derived from the appendix, was removed and was found to be cystic and contained huge amounts of mucin. The histological findings revealed a well-differentiated cystadenocarcinoma of the appendix, and immunohistochemical staining of the epithelium and mucinous implants in the mass demonstrated a positive reaction for carcinogenic antigens, including carcinoembryonic antigen and carbohydrate antigen.     

Four cases of lung cancer associated with idiopathic interstitial pneumonia

It is well known that lung cancer develops frequently in patients with idiopathic interstitial pneumonia (IIP) (9.8-22.8%). We investigated 4 patients who developed lung cancer among the 28 patients with IIP (14.3%) who were admitted to our hospital from June 1981 to March 1989. Many reports have pointed out the clinical features of lung cancer associated with IIP as male sex, old age, heavy smoking, and poor prognosis. Our 4 series were agreed with these clinical features. Lung cancer associated with IIP have been often reported to occur in the lower and peripheral regions of the lung, and honeycomb structures are frequently seen. But we found that lung cancer in IIP could actually occur in both the lower and upper regions of the lung and does not occur only in the honeycomb structures. There was no obvious dominance of any histological type among the tumors. If lung cancer is suspected in a patient with IIP, tumor markers are of some value for diagnosis, but are not sensitive enough to be used alone.     

Functional linkage of the cardiac ATP-sensitive K+ channel to the actin cytoskeleton

The role of the cytoskeleton in the rundown and reactivation of adenosine triphosphate (ATP) sensitive K⁺ channels (KATP channels) was examined by perturbing selectively the intracellular surface of inside-out membrane patches excised from guinea-pig ventricular myocytes. Actin filament-depolymerizing agents (cytochalasins and desoxyribonuclease I) accelerated channel rundown, while actin filament stabilizer (phalloidin) or phosphatidylinositol biphosphate (PIP₂; inhibitor of F-actin-severing proteins) inhibited spontaneous and/or Ca²⁺-induced rundown. When rundown was induced by cytochalasin D or by long exposure to high Ca²⁺, channel activity could not be restored by exposure to MgATP, but application of F-actin with MgATP could reinstitute channel activity. The processes of rundown and reactivation of cardiac K_ATP channels may thus be influenced by the assembly and disassembly of the actin cytoskeletal network, which provides a novel regulatory mechanism of this channel.     

B7.2-Ig fusion proteins enhance IL-4-dependent differentiation of tumor-sensitized CD8+ cytotoxic T lymphocyte precursors

The B7/CD28 co-stimulatory pathway plays a critical role in T cell activation and differentiation. Our previous study demonstrated that administration of B7.2-Ig fusion proteins to tumor-bearing mice elicits IL-4-dependent, CD8+ T cell-mediated tumor regression. Here, we investigated whether B7.2-Ig stimulation of tumor-sensitized CD8+ CTL precursors during in vitro antigen re-sensitization actually results in their differentiation into mature CTLs and if so, whether such a process depends on IL-4 signals. Splenocytes from tumor-sensitized (tumor-bearing or tumor-immunized) mice exhibited low levels of anti-tumor CTL responses upon culturing alone, but induced strikingly enhanced CTL responses when stimulated in vitro with B7.2-Ig fusion proteins. Because CTLs were not generated from normal splenocytes even by B7.2-Ig stimulation, the expression of the B7.2-Ig effect required the in vivo tumor sensitization of CD8+ CTL precursors. Administration of anti-CD4 or anti-CD40 ligand (CD40L) to mice before tumor sensitization resulted in almost complete inhibition of CTL responses generated in the subsequent culture containing B7.2-Ig. In contrast, anti-IL-4 did not influence in vivo tumor sensitization required for CTL induction. However, B7.2-Ig stimulation of tumor-sensitized splenocytes enhanced IL-4 production and neutralization of this IL-4 with anti-IL-4 potently down-regulated CTL responses. These results indicate that B7.2-Ig enhances IL-4-dependent differentiation of anti-tumor CD8+ CTL precursors that can be sensitized in vivo depending on collaboration with CD4+ T cells involving CD40L function.     

The catalytic subunit of cyclic AMP-dependent protein kinase directly inhibits sodium channel activities in guinea-pig ventricular myocytes

We investigated the effects of the purified catalytic subunit (C subunit) of the cAMP-dependent protein kinase (A-kinase) on the cardiac Na⁺ channel currents. Single Na⁺ channel currents in guinea-pig ventricular myocytes were recorded using the patch clamp technique of the inside-out configuration. Application of C subunit decreased the peak average current and slowed the current decay, effects which were caused by decrease in the open probability of Na⁺ channels and increase in the first latency, whereas the unitary current amplitude and mean open times were not affected. We conclude that the cardiac Na⁺ channel is directly modulated by phosphorylation process through A-kinase.     

Rate-dependent changes in action potential duration and membrane currents in hamster ventricular myocytes

Hamsters are frequently studied as a model of cardiomyopathy, but the electrophysiological properties of a hamster heart are not well defined. We examined rate-dependent changes in action potentials and underlying ionic mechanisms in isolated ventricular myocytes from hamster hearts using the whole-cell configuration of the patch clamp technique. At 0.1 Hz stimulation, the mean action potential duration at 90% (APD90) and 20% (APD20) repolarization were 63+/-7 ms and 9+/-1 ms, respectively ( n=17). With increasing frequency of stimulation, APD progressively prolonged to 119+/-16 ms (APD90) and 36+/-7 ms (APD20) at 6.0 Hz. A further increase in the rate of stimulation to 8.0 Hz did not change APD significantly. Application of 4 mM 4-aminopyridine (4-AP) lengthened APD markedly and completely prevented the rate-dependent prolongation. Cd2+ (0.2 mM) shortened APD and generally attenuated the rate-dependent lengthening of APD up to 5.0 Hz, but unaffected the lengthening of APD with the further increase in the rate. At plateau voltages, there were two time-dependent currents, Ito1 and I(Ca,L). Recovery from inactivation for Ito1 had two components: t(slow)=980+/-129 ms accounting for 58% of the total fraction, and t(fast)=39+/-13 ms ( n=7). Recovery from inactivation for I(Ca,L) was rapid with t=20+/-4 ms ( n=6). Results suggest that the slow recovery from inactivation in Ito1 is the main reason for the rate-dependent prolongation of APD in hamster ventricular myocytes.     

Identical unitary current amplitude and Ca(2+) block of cardiac Na channel before and during beta-adrenergic stimulation

We examined the possibility of Ca(2+) permeation through cardiac Na channels ("slip mode conductance") by an analysis of the voltage-dependent block of Na channels by Ca(2+). A Ca(2+) block of Na channels was evident in rat and guinea pig ventricular myocytes during cell-attached single channel recordings with a physiological ionic environment (140 mM Na(+) and 1 to 10 mM Ca(2+) in the pipette solution). Increasing external Ca(2+) concentration ([Ca(2+)](o)) in the pipette solution reduced the unitary current amplitude predominantly at negative potentials. With [Ca(2+)](o) > 1 mM, unitary current amplitude did not increase at potentials negative to -40 mV in spite of augmented driving forces. The application of 5 microM isoproterenol potentiated the single channel activity elicited by depolarizing pulses from the holding potential of -120 mV, indicating that the channels in the patch under examination were modified by protein kinase A (PKA) stimulation. Increased activity was also confirmed with veratridine-modified Na channels, where channel openings were markedly prolonged. In either case, isoproterenol-induced potentiation neither reduced nor altered the properties of Ca(2+) block of cardiac Na channels, as evidenced by the stable unitary current amplitudes at potential levels from -60 to -20 mV. These results indicate that interactions among Na(+), Ca(2+), and the channel molecule were not modified with respect to permeation properties. They therefore argue against the "slip mode" concept of classical cardiac Na channel if a general concept of ion permeation through "multi-ion pores" is applicable to determine the ionic selectivity of Na channels.     

An Autopsy Case of Peritoneal Malignant Mesothelioma in a Radiation Technologist

A case of peritoneal maligant mesothelioma in a radiation technologist, who had worked in this field for 34 years, is reported. Histopathologically, a biopsy specimen from the retroperitoneal tumor revealed a biphasic type of malignant mesothelioma. Electron microscopy disclosed that the tumor cells contained prominent microvilli, basal laminae adjacent to the stroma, junctional complexes, desmosomes, tonofilaments, clusters of glycogen granules, welt developed rough endoplasmic reticulum (RER), confronting cisternae showing direct continuity with the RER and membrane-bound granules suggestive of secretory activity. No increased amount of asbestos was detected in autopsied lung material or the peritoneal mesothelioma. The estimated cumulative dose of occupational irradiation was calculated to be about 40 to 50 rad at most. Irradiation was discussed in relation to the etiology of the peritoneal mosothelioma. Acta Pathol Jpn 40: 57–62, 1990.