The role of orally administered dimethylarsinic acid, a main metabolite of inorganic arsenics, in the promotion and progression of UVB-induced skin tumorigenesis in hairless mice.

The effect of dimethylarsinic acid (DMA) on skin tumorigenesis by UVB irradiation was examined. Hairless mice (Hos: HR-1) irradiated with UVB at a dose of 2 kJ/m(2) twice weekly, were fed with drinking water containing 1000 ppm DMA, a main metabolite of inorganic arsenics, produced more skin tumors than DMA-untreated mice. Histopathological examination revealed that the mouse malignant tumors with severe atypism appeared only in the treatment group of UVB plus 1000 ppm DMA. These positive results point out the importance of dimethylated metabolites of inorganic arsenic in the process of skin carcinogenesis.

The effects of zenarestat, an aldose reductase inhibitor, on peripheral neuropathy in Zucker diabetic fatty rats.

We studied the effects of zenarestat, an aldose reductase inhibitor (ARI), on peripheral neuropathy in Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes. ZDF rats and their lean rats counterparts were fed a sucrose-containing diet, and zenarestat was given orally once a day for 8 weeks. Motor nerve conduction velocity (MNCV), F-wave minimal latency (FML), and sorbitol concentrations in the sciatic nerve were measured. In ZDF control rats, a remarkable accumulation of sorbitol, a delay in FML, and a slowing of MNCV were observed compared with lean rats. At a dose of 3.2 mg/kg, zenarestat had no significant effect on the delay in FML and the slowing of MNCV, although the sorbitol accumulation in the sciatic nerve was partially inhibited in ZDF rats. On the other hand, 32 mg/kg zenarestat treatment improved these nerve dysfunctions in ZDF rats, along with a reduction of nerve sorbitol accumulation almost to the level of lean rats. These data showed that zenarestat improved diabetic peripheral neuropathy in ZDF rats, a type 2 diabetes model, providing evidence for the therapeutic potential of zenarestat for the treatment of diabetic neuropathy.

A new approach for accessing retroperitoneal space using a 5-mm [corrected] visual access cannula.

Retroperitoneal lymph node evaluation is a very important step in planning cancer therapy. Traditional staging laparotomy is too invasive and causes considerable morbidity. However, laparoscopic access of the retroperitoneal space offers the onco-endoscopist a unique, noninvasive, and less dangerous method for assessing and managing women with gynecologic malignancies. The retroperitoneal approach is noninvasive and less dangerous way of accessing the paraaortic space. A new minimally invasive approach of accessing the retroperitoneal space using a 5-mm visual access cannula is introduced. A complete paraaortic and pelvic lymphadenectomy was possible for 60 patients with varied gynecologic malignancies using our retroperitoneal laparoscopic approach. Less blood loss and rapid recovery was observed, and no bowel complication was encountered. The use of the 5-mm visual access cannula offers a less invasive surgical procedure and provides cosmetic advantages.

Familial risk among Japanese patients with endometriosis.

OBJECTIVES: This study was designed to examine the prevalence of endometriosis among female siblings of patients with endometriosis in Japan. METHODS: A total of 339 patients with endometriosis were questioned about endometriosis in their sisters. The control group consisted of 284 Japanese healthy fertile women with no history of endometriosis. Similarly, the controls were interviewed about their sisters. RESULTS: We detected sisters with endometriosis in 8.8% of cases and 1.5% of the control population. The relative risk of endometriosis in female siblings was 5.7. However, a significant difference was not seen in age at diagnosis and clinical stage between patients with or without a family history of endometriosis. CONCLUSIONS: These data demonstrate a familial tendency for endometriosis and suggest that endometriosis has a genetic factor in the pathogenesis.

Laparoscopic surgery for colpopoiesis with the pelvic peritoneum: first report in Japan.

Several methods have been developed for colpopoiesis in patients with vaginal agenesis. Nonetheless, various problems remain, including technical difficulty, invasiveness, operative stress, and poor cosmetic results, as well as the insufficient naturalness of the vagina itself. We have successfully completed colpopoiesis using the pelvic peritoneum in a laparoscopic surgery for Rokitansky-Küster-Hauser syndrome (RKH).

Laparoscopic ovarian cystectomy: extraperitoneal method.

A laparoscopic method for resecting benign ovarian cysts has been devised and involves excising the cyst wall extraperitoneally after aspirating the cystic fluid. In this report, the technique and clinical results are described and mini-laparotomy which is used in this technique is discussed. A total of 104patients were treated by this method. The diagnosis was simple cyst in 46,dermoid cyst in 33,and chocolate cyst in 25. The method was successful in 90 patients (87%).The remaining 14(14%)were converted to open surgery, 9 be- cause of severe adhesions. The remaining 5 patients had various complications: malignancy, bladder injury, dermoid content too solid to aspirate, and bleeding. We found endometrioid adenocarcinoma in 1 patient whose chocolate cyst could be removed completely.

Laparoscopic ovarian cystectomy using double balloon catheter: a new technical application.

In the present study, a modified application of the surgical instrument with double balloon is described in the ovarian cystectomy procedure. This technique has been proved effective and safe especially in removing chocolate-like cystoma. This new instrument, which we originally designed, has two balloons at the tip of the catheter. After a cyst is punctured, the inner and outer balloons are inflated to fix the cyst well. After fixing the cyst with two balloons, the internal needle of the instrument can be removed. This catheter, named the SAND balloon catheter, is advantageous in laparoscopic ovarian cystectomy.

[Inhibitory effect of bithionol on NADH-fumarate reductase in ascarides].

To elucidate the mechanism of anthelmintic action of bithionol, the inhibitory effect of the drug on NADH-fumarate reductase (NADH-FR) of Ascaris lumbricoides suum was examined. NADH-FR, an enzyme of anaerobic carbohydrate metabolic pathway was solubilized from the mitochondria of the worm's muscle with deoxycholate, and then partially purified with the monoethanolamine-Sepharose 4B column chromatography. Rhodoquinone (RQ), which is required for the electron transfer from NADH to fumarate, was separated from the enzyme protein and phospholipids. Although the enzyme protein fraction eluted from the above column did not show NADH-FR activity, this enzyme was reactivated by the addition of purified RQ and phosphatidylcholine. The IC50 value of bithionol for reconstituted NADH-FR was 18 +/- 2 microM. The inhibition type was competitive to RQ. Bithionol inhibited at most 30% NADH-ferricyanide reductase, which did not require RQ, even at high concentration of 150 microM. These results suggest that the pharmacological action of bithionol, a phenolic anthelmintic, depends on the inhibition of the electron transport system by the competition with RQ.

Novel technique for total laparoscopic myomectomy: the "bottom-up suture".

INTRODUCTION: As more women with symptomatic uterine myomas undergo laparoscopic management without hysterectomy, we increasingly encounter many difficult situations, such as of the need to extract large intramural myomas. Even for a skilled surgeon, laparoscopic myomectomy in such a situation is difficult. We have established a new technique for laparoscopic myomectomy to solve these issues called the "bottom-up suture" method. MATERIALS AND SURGICAL TECHNIQUE: Before complete removal of the myoma, countertraction is applied by an assistant with a claw forceps, elevating the bed of the myoma to make suturing easy. The deep myometrium can be sutured while the myoma is still attached to the uterus. DISCUSSION: This technique, the "bottom-up suture," may improve the suturing of laparoscopic myomectomies. The advantages of this technique are that it is easy to control unexpected bleeding, and dead space formation can be prevented even when the myomas have grown deep into the uterine myometrium. This technique will become a reliable standard for laparoscopic myomectomy.

Unsuspected uterine leiomyosarcoma: magnetic resonance imaging findings before and after focused ultrasound surgery.

Uterine leiomyosarcoma, initially diagnosed as leiomyoma on magnetic resonance (MR) images, was disclosed after focused ultrasound surgery (FUS). The tumor did not display high signal intensity on either T1- or T2-weighted images on the patient's first visit. Four months thereafter, T2-weighted images revealed a high signal intensity area within the tumor, while T1-weighted images showed low signal intensity. Six months after FUS, the nonperfused volume calculated on meglumine gadoterate-enhanced T1-weighted images decreased markedly and an intermediate signal intensity in a circular area on T2-weighted images appeared to be atypically increasing in volume. After laparoscopic myomectomy, this tumor was diagnosed as uterine leiomyosarcoma coexistent with leiomyoma. The early stages of uterine leiomyosarcoma are clinically difficult to diagnose; therefore, both careful monitoring during FUS and close follow-up after the procedure are vital.

[Laparoscopic resection of ovarian cysts: precautions and improvements in the procedure and application of the mini-laparotomy].

We previously devised and reported a laparoscopic resection of benign ovarian cysts. In the present paper, we report precautions and improvements in the procedure and the application of the mini-laparotomy. 1. The subjects consisted of a total of 41 cases with preoperatively diagnosed cysts. These were 17 cases with simple cysts, 15 cases with dermoid cysts, and nine cases with chocolate cysts. The present surgical procedure was performed on 34 (83%) cases. 2. One case, preoperatively diagnosed as a chocolate cyst, was diagnosed as an endometrioid adenocarcinoma. 3. Laparotomy was required in 7 cases; in four as a result of hard adhesions, in one because it was impossible to withdraw fluid, in one due to a damaged urinary bladder and in one due to endometrioid adenocarcinoma. 4. It became essential to classify the ovarian cysts into three groups according to size. 5. Mini-laparotomy was performed for two giant ovarian cysts and five ovarian cysts in pregnant women. In this procedure the goal is minimal, simple, safe and reliable surgery with results equal to those of standard laparotomy.

[Laparoscopy-guided extraperitoneal resection of ovarian cysts: surgical procedure, indications and limitations].

We designed a new surgical method for the treatment of benign ovarian cysts. We have previously reported that, with our laparoscopy-guided method, the cyst wall is pulled outside the abdominal cavity after evacuation of the cyst contents, and resection is performed by the same method as during laparotomy. The preoperative assessment and surgical findings were investigated in 16 subjects, 5 with simple cysts, 2 with para-ovarian cysts, 2 with chocolate cysts, 5 with dermoid cysts and 2 with mucinous cysts. This surgical method was applicable in 11 of the 14 patients. Laparotomy was required in the other 3, because 2 of the patients had strong adhesions and in 1 evacuation was impossible. The patients were classified into 3 grades of difficulty before surgery: Grade I; operable, Grade II; operable with special care, Grade III; laparotomy required. During surgery, the feasibility of continuing the procedure was also assessed. In this surgical procedure, through a small incision in the abdominal wall, the entire resection of an ovarian cyst is done extra-peritoneally. However, the eligibility of patients for this method needs to be very carefully examined preoperatively and reviewed throughout the procedure.

Loss of glomerular responses to vasoconstrictor agents in rabbits recovering from ARF.

Glomerular responses to angiotensin II (AII), arginine vasopressin (AVP), and norepinephrine (NE) were estimated in rabbits recovering from uranium-mediated nephropathy or ischemic acute renal failure (ARF) to examine roles of intraglomerular events in resistance to ARF. Uranyl acetate (UA, 0.8 mg/kg) produced ARF in some animals but did not in others. Rabbits recovering from UA-induced ARF were highly resistant to a rechallenge with a larger dose of the agent (2 mg/kg). Their glomeruli did not respond to AII, AVP and NE in vitro. In animals having not experienced ARF following the initial insult, however, resistance to the rechallenge was lower than in animals recovering from ARF, and the glomerular response to contractile stimuli was well sustained. A two hour clamping of the renal artery induced ARF in uninephrectomized rabbits. These animals were not resistant to an additional ischemia in the recovery phase, despite inhibited glomerular contractile responses to AII. These data indicate a nonspecific inhibition of glomerular responses to contractile stimuli in the recovery phase of ARF. It is unlikely, however, that resistance to ARF can be attributed to the loss of the glomerular contractile response.

Improvement in Raw Meat Texture of Cultured Eel by Feeding of Tochu Leaf Powder.

The muscle of eels fed tochu (Eucommia ulmoides Oliver) leaf powder was 1.8 times harder than the control. The component analysis showed no difference in moisture, lipid, or protein content between the muscles of the control and the tochu-fed eels. Not only the extracted neutral fat but also the compound fat of the raw muscles of the tochu-fed eel and the control had the same TLC patterns and fatty acid composition by gas chromatographic analysis. There was a great difference between the tochu-fed eel and the control concerning the amount of muscle protein stroma fraction which mainly consisted of collagen. The microscopic observation showed that the perimysium and endmysium which were the main components of the stroma fraction of the muscle of the tochu-fed eel were firm and thick compared to those of the control. These findings suggested that the intake of tochu leaf powder hardened the muscle.

Conformational characteristics of receptor-selective opioid peptides. 1H n.m.r. and c.d. spectroscopic studies of delta-kephalin and [Val4]morphiceptin.

An investigation on the conformations of highly receptor-selective opioid peptides was carried out to gain further understanding of the structure-activity relationship of endogenous enkephalins. The preferred conformations of a highly mu-selective [Val4]morphiceptin and a highly delta-selective delta-kephalin have been probed by 1H n.m.r. solvent-, concentration- and temperature-dependences of amide protons to take the folded conformations stabilized by an intramolecular hydrogen bond and the anti-parallely extended dimeric structures respectively. Their possible stereo-conformations were proposed, based on the analyses of the vicinal coupling constants (JHNC alpha H). The conformational difference between the mu- and delta-selective opioid peptides was further ascertained by the c.d. measurements. The c.d. spectra of the mu-selective peptides show negative bands in the range of 210-230 nm, while those of the delta-selective ones show the opposite positive bands. A correlation between c.d. spectra and receptor-selectivity was possible.

[Bovine cervical mucus as a substitute of human cervical mucus].

The sperm penetration test (SPT) in cervical mucus (CM) is an important test in screening for sperm-CM incompatibility. For a routine SPT, a sufficient amount of preovulatory CM is necessary, but the amount of human CM is often inadequate. We examined estrous bovine CM as a substitute for human CM in the SPT. Preovulatory human CM and estrous bovine CM were collected and stored frozen at -20 degrees C until use. After being thawed at room temperature, the two CM samples were compared as to their pH, spinnbarkeit and ferning patterns, and it was found that they are quite similar. In Kremer's method of SPT, sperm penetration distance, density and motility were similar in human and bovine CM for 12 hours, but thereafter sperm motility became much lower in bovine CM than in human CM. The results of SPT with spermatozoa from patients with oligozoospermia were quite similar in both CMs. When spermatozoa pretreated with antisperm antibody were used for SPT, sperm penetration was completely blocked in human CM, but no inhibition was seen in bovine CM. From these results, we conclude that bovine CM can be substituted for human CM for some, but not all, purposes.

Glomerular refractoriness to contractile stimuli in rabbits recovering from ischemic acute renal failure.

The present work was performed on uninephrectomized rabbits recovering from ischemic acute renal failure (ARF) in an attempt to elucidate whether or not intraglomerular events are a determinant factor in the development of resistance to ARF. 14 days after a 2-hour clamping of the renal artery (the recovery phase), the animals did not show resistance to an additional ischemia. On the other hand, glomeruli derived from normal kidneys displayed a contractile response to angiotensin II, arginine vasopressin or norepinephrine in Eagle's minimum essential medium, whereas glomeruli from rabbits recovering from ischemic ARF were refractory to the vasoconstrictor agents. The findings suggest that glomerular refractoriness to contractile stimuli does not provide resistance to an additional renal ischemia in the ischemic model of ARF.

Application of the quantitative sperm immobilization test for follow-up study of sperm-immobilizing antibody in the sera of sterile women.

For quantitative estimation of sperm immobilizing antibody, a new assay method was developed and applied to a follow-up study of antibody titers in the sera of sterile women. The 50% sperm immobilization units (SI50) estimated by the quantitative method ranged from 1.2 to 97.3 in the sera from 16 sterile women who showed relatively high antibody activities in the previous semiquantitative sperm immobilization test. When the quantitative antibody titers, SI50, were followed over 3 years in sterile women with the sperm immobilizing antibody, the antibody titers were found to be unstable, and undulated over a period of several months. Therapy consisting of use of a condom seemed to be ineffective in decreasing the antibody titers.

[Detection of early pregnancy factor in the sera of conceived women before nidation].

In order to apply the early pregnancy factor (EPF) to early diagnosis of fertilization, the establishment of optimal conditions for assay of EPF was attempted, and then EPF in the sera of contracepted and conceived women 4 to 6 days after ovulation were measured. For assay of EPF, 0.25 ml of 1:2 step diluted anti-human lymphocyte serum (ALS), 0.05ml of guinea pig serum as complement and 0.1ml of lymphocytes suspension (1 X 10(7)/ml) pretreated with test serum were mixed and then incubated at 37 degrees C for 90 min. To this mixture 0.1ml of sheep red blood cell suspension (2 X 10(9)/ml) was added and the rosette formation was counted after centrifugation. The rosette inhibition titer (RIT) was expressed as reciprocal of ALS dilutions which resulted in less than 75% of rosette formation as compared with the control. RITs of the conceived women who were assayed on the 5 th day after ovulation were in the range from 16 to 32 X 10(3), while that of the control contraceptive women who were assayed on the same day was in the range from 2 to 4 X 10(3). The sterile women who received AIH but failed to conceive all showed less than 4 X 10(3) as RIT. These results suggest that the assay of EPF is valuable in detecting the early stage of fertilization and possibly may help to differentiate the impairment of embryo implantation from non-fertilization of the ovum as a cause of sterility.