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Tremendous excitement has been generated by the use of botulinum toxin for the treatment of various types of urethral and bladder dysfunction over the past several years. Botulinum toxin is the most lethal naturally occurring toxin known to mankind. Why, then, would an urologist want to use this agent to poison the bladder or urethral sphincter? In this review article we will examine the mechanisms underlying the effects of botulinum toxin treatment. We will discuss the current use of this agent within the urologic community and will provide perspectives on future targets of botulinum toxin.

Leukotrienes, one of the mediators of inflammation in asthma, have a strong bronchoconstrictive effect. L-carnitine has been reported to influence respiratory functions. It has also been reported that L-carnitine inhibits leukotriene synthesis. To evaluate the effects of L-carnitine on oxygen saturation, urine leukotriene E4 levels and lung histopathology in a murine model of asthma, high IgE responder BALB/c mice (n = 24) were systemically sensitized to ovalbumin and chronically challenged with low particle mass concentrations of aerosolized ovalbumin, and then they were divided into 3 groups (study groups A, B, and C) each including eight mice. After methacholine-induced bronchoconstriction, the mice in groups A and B were given intraperitoneal L-carnitine (250 and 125 mg/kg, respectively), while the mice in group C were given placebo. Oxygen saturation of the mice was measured by pulse oxymeter before and after methacholine and after L-carnitine/ placebo application. In addition, urine leukotriene E4 levels were measured before asthma development, and 24-h after L-carnitine injection in asthmatic mice. Inflammation in the lung tissues of the sacrificed animals was scored histopathologically to determine the effect of L-carnitine on tissue level. A control group of non-sensitized mice (n = 8) treated with placebo only was used for comparison of urine leukotriene E4 levels and of histopathological parameters. Oxygen saturation of the mice in the study groups tended to decrease after methacholine and to improve after L-carnitine injection, although these changes were not significant at all time points. Urine leukotriene E4 levels of all 3 study groups increased significantly after asthma development. The rate of increment was smallest in the group given the highest L-carnitine dose (group A). Inflammation at the tissue level was also mildest in group A, and severest in the group that was not given carnitine (group C). All of the study groups and the control group differed significantly with respect to inflammation scores. In conclusion, L-carnitine improved oxygen saturation, and decreased urine leukotriene E4 levels and inflammation in lung tissues in the present murine model of asthma.

The association between depressed mood and condom use was examined among incarcerated male adolescents. One hundred and eighty male adolescents who were detained in Birmingham, Alabama in the United States were interviewed during a period of incarceration. Contrary to patterns generally found in adult samples, nearly 50% of this adolescent sample that did not use condoms regularly actually recognized the advantages of condom use. This behavior pattern was deemed "inconsistent," and those engaging in this "inconsistent" behavior pattern were found to have a higher score of depressed mood compared to participants with a "consistent" behavior pattern. As a result, a relationship between depressed mood and decisional balance for condom use within adolescents was evident. These findings suggest that assessment and treatment of depressed mood within this high-risk population could potentially contribute to a reduction in high-risk sexual behaviors.

In this study, we tested brain surface cooling as a new method of inducing selective brain hypothermia, and evaluated its effects on focal cerebral ischemia using a cat model of transient middle cerebral artery (MCA) occlusion. Cats underwent 1 h of MCA occlusion followed by 5 h of reperfusion. Brain surface cooling was induced for 4 h during and after MCA occlusion in the hypothermia group, but not in the normothermia group. Brain surface cooling was performed using saline perfusion into the subdural space. Rectal temperature, brain surface temperature, and deep brain temperature were monitored, and regional cerebral blood flow (rCBF) and somatosensory evoked potential (SEP) were serially measured. After 5 h of reperfusion, water content was also measured. Although the rectal temperature was maintained at about 37 degrees C, the brain surface temperature decreased rapidly to 33 degrees C and was maintained at that temperature. For 3 h following reperfusion, the rCBF was lower in the hypothermia group than in the normothermia group. At 4 and 5 h after reperfusion, the recovery of SEP amplitude was significantly more enhanced in the hypothermia group than in the normothermia group. In the gray matter, the water content was significantly more diminished in the hypothermia group than in the normothermia group. These results demonstrate that our method is useful for protecting the ischemic brain from a transient MCA occlusion. This method may be adapted for neurological surgery.

Levels of alpha-fetoprotein (AFP), its glycoforms AFP-L3 and AFP-P4, and proteins induced by vitamin K absence or antagonist-II (PIVKA-II) were determined in sera obtained from patients in Yangon General Hospital (20 with hepatocellular carcinoma (HCC), 29 with chronic liver diseases, including 3 with chronic hepatitis and 26 with cirrhosis of the liver, and 9 with other hepatobiliary diseases). Forty-five percent of the patients with HCC had serum AFP levels above 10,000 ng/ml, indicating that nearly half of the HCC patients were at an advanced stage of the disease. Thus, the AFP sensitivity was as high as 70% with 100% specificity for a cutoff level of 200 ng/ml. The sensitivity of AFP-L3 was 75% and a specificity 90% for a cutoff level of 15%. AFP-P4 showed a higher sensitivity of 80% and a similar specificity of 86% for a cutoff level of 12%. Combined evaluation of AFP-L3 and/or AFP-P4 increased the sensitivity to 90% with the same specificity of 86%, indicating that AFP-L3 and AFP-P4 are useful as adjuncts for diagnosis of HCC in the present population. PIVKA-II had a high sensitivity of 90%, although the specificity was lower than 45%, probably due to the low cutoff level, as some cholestatic patients were included in the control group.

Transforming growth factor-beta1 (TGF-beta1) exerts potent immunosuppressive effects. In this study, we investigated the potential role of TGF-beta1 produced by hepatocellular carcinoma (HCC) cell lines in immunosuppression mechanisms. Using the Mv1Lu cell-growth inhibition assay and an enzyme-linked immunosorbent assay (ELISA), we detected optimal levels of TGF-beta1 in the culture supernatants conditioned by the HCC cell lines PLC/PRF/5, Hep3B, and HepG2. To determine the biological activity of TGF-beta1 in the supernatants, we examined the effects of the culture supernatants on the production of interferon (IFN)-gamma induced during the culture of peripheral blood mononuclear cells (PBMCs) stimulated with interleukin (IL)-12. IFN-gamma production of IL-12-stimulated PBMCs in the 1:1 dilution of the acid-activated conditioned medium of PLC/PRF/5, Hep3B, and HepG2 reduced to 14.7 +/- 0.8, 17.3 +/- 9.0, and 35.9 +/- 14.6%, respectively, compared with the value in the culture with control medium (complete culture medium). These results suggest that HCC cells producing TGF-beta1 may reduce the generation or activation of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells, and thus could enhance their ability to escape immune-mediated surveillance.

The ferric nitrilotriacetate-induced carcinogenesis model is unique in that reactive oxygen species-free radicals are involved in the carcinogenic process. But the effects of iron-withdrawal in the progression of renal cell carcinoma are not well understood. We performed repeated phlebotomies on animals that had been administered ferric nitrilotriacetate in the initiation stage of renal cell carcinoma (phlebotomy group), and compared the development of renal tumors with those not receiving repeated phlebotomies (non-phlebotomy group). Ferric nitrilotriacetate-treated male Wistar rats were randomly divided into 2 groups: a phlebotomy group (21 rats) and a non-phlebotomy group (17 rats). Ten age-adjusted normal rats were also observed as a normal group. Hematocrit was maintained under 25% in the phlebotomy group. Hematocrit levels in the normal group and in the non-phlebotomy group were not significantly different. As a result, the incidence of renal cell carcinoma was not significantly different between phlebotomy and non-phlebotomy animals. However, the total weight of the renal cell carcinoma was significantly heavier in the animals from non-phlebotomy group than in those from the phlebotomy group (23.64 g +/- 18.54 vs. 54.40 g +/- 42.40, P < 0.05). The present study demonstrated that phlebotomy after the administration of ferric nitrilotriacetate did not reduce the incidence of renal cell carcinoma. In addition, we showed that iron withdrawal at the promotion stage of carcinogenesis will retard tumor growth.

We have previously developed an enzyme-linked immunosorbent assay (ELISA) to measure stool decay-accelerating factor (DAF) and found that stool DAF concentrations were significantly elevated in patients with colorectal cancer, suggesting that the measurement of stool DAF may be valuable for the detection of colorectal cancer. In order to refine the assay for the measurement of stool DAF, we investigated 1) effects of centrifugation of stool samples, 2) effects of detergents, and 3) adequate combination of various anti-DAF monoclonal antibodies for the ELISA system using only monoclonal antibodies. We found that high-speed centrifugation could be omitted and that only the removal of large undigested food residues by centrifugation of short duration in a low-speed benchtop microcentrifuge sufficed to adequately prepare the stool samples. Addition of 2 detergents, octyl beta-glucoside and sodium deoxycholate, known to solubilize glycosyl-phosphatidylinositol-anchored proteins such as DAF, did not influence stool DAF values. By using 2 mouse anti-DAF monoclonal antibodies (clone 4F11 and 1C6), we were able to achieve a stable ELISA for the measurement of stool DAF using a uniform source of antibodies. The results should allow us to consistently apply the DAF assay for routine use in the detection of colorectal cancer.

The preS2 region of the hepatitis B virus (HBV) has been reported to have human polymerized albumin receptor (PAR) activity, which correlates with viral replication. Here, we studied the genomic sequence of the preS region from rare patients lacking PAR activity, despite active viral replication. PAR and DNA polymerase activity was identified in 178 HBe antigen-positive HBV carriers, and a significant correlation between 2 markers was shown, except in 2 hepatitis patients lacking PAR activity. Nucleotide sequences of the preS region of HBV from both patients were examined by direct sequencing of PCR products. In one patient, a 45-base deletion was found to overlap half of the putative polymerized human albumin binding site in the preS2 region. In the other patient, a point mutation at the first nucleotide of the start codon of the preS2 region of HBV was found. There was no such genomic change in the 3 control HBV sequences. These results indicate that the preS2 region is necessary for binding of polymerized human albumin, and this is the first report of naturally existing mutant virus with no or low PAR activity.

We developed a monoclonal antibody (MoAb) (clone 5E8) against an antigen on the bile canalicular membrane of rat hepatocyte. By immunoblotting, MoAb 5E8 detected a band of 110 kD. In this study, we used the phage display technique to identify the target antigen recognized by MoAb 5E8. We screened a random phage display library expressing 12-mer peptide sequences and identified a peptide sequence, FHFNPYTGHPLT, as an epitope. We compared this peptide sequence with those of dipeptidyl peptidase IV (DPP IV, E.C.3.4.14.5) and Cell-CAM105, which proteins were located by a database search based on the information of tissue localization and approximate molecular weight of the MoAb 5E8 antigen, and sequence similarity with a region in DPP IV (amino acids 225-233) but not with Cell-CAM105 was found. In addition, we immunohistochemically stained various tissues (liver, small intestine, and kidney) of Japanese Fischer 344 rats, known to be deficient for DPP IV, with MoAb 5E8 and showed that the expression of MoAb 5E8 antigen was negligible or weak. In contrast, tissues sampled from the same organs of Sprague-Dawley rats, known to express DPP IV, were positively stained. These findings suggest that the antigen recognized by MoAb 5E8 is DDPIV and its major epitope is located in amino acids at positions 225-233.

To compare morphological changes in the umbilical cords from chronic hypertensive and preeclamptic patients having normal or pathological umbilical artery Doppler ultrasonographic results. Umbilical cords from 34 normotensive, 31 chronic hypertensive and 70 preeclamptic women with normal and abnormal Doppler flow velocity waveforms (FVW) at 35-40 gestational weeks were studied. Morphological changes in the umbilical cords were examined on formalin-fixed, paraffin-embedded sections. The total umbilical cord area, total vessel area, and wall thickness of umbilical vessels were measured in systematic random samples using unbiased stereology methods. An ANOVA test was used for statistical analysis. In the chronic hypertensive and preeclamptic groups with normal Doppler FVW, the thickness of the umbilical cord vessels remained nearly constant, whereas both the total area and the lumen area were reduced. These changes correlate with the histopathological findings, suggesting a mainly vasoconstrictive effect. By contrast, analysis of the preeclamptic group with pathologic Doppler FVW showed a comparable reduction of all parameters of the umbilical cord. Histopathological findings were related to smaller, contracted smooth muscle cells of the vessel wall, which is suggestive of a predominant hypoplastic mechanism. As a result of reduced uteroplacental perfusion, fetal hypoxia and intrauterine growth retardation become unavoidable in preeclampsia. The histopathological changes in the umbilical cord between the chronic hypertensive and preeclamptic patients depend on the Doppler results. In conclusion, the umbilical artery Doppler FVW indices provide good values for predicting intrauterine growth retardation in preeclamptic patients.

Dynamin is a protein essential to endocytosis. Dynamin 2, a dynamin isoform, is expressed most intensely in testicular tissue; however, precise localization has never been studied. Therefore, we investigated the expression of dynamin 2 in rat testicular tissue using immunohistochemical methods, and discuss here the physiological function of this protein. Testicular tissues were obtained from Wistar rats at 10, 21 and 63 days of age. Immunohistochemistrical examination and Western blot analysis were conducted using dynamin 2 specific antibody. Western blot analysis showed that expression in 21- and 63-day-old rats was more intense than that in 10-day-old rats. Dynamin 2 expression was observed using immunohistochemical method in the seminiferous tubules of all rats. In the 63-day-old rats, the expression was intense, especially in spermatids in the earlier maturation stages and in spermatocytes, and was observed in Sertoli cells. However, in spermatids, the expression gradually declined as spermatids matured to spermatozoa. In the 21-day-old rats, the expression was evident in spermatocytes and Sertoli cells, but that in the 10-day-old rats was weak. Intense expression of dynamin 2 during spermatogenesis suggests that this protein plays an important role in this process.

We have designed to apply 2-pyridine aldoxime methiodide(PAM), considered to be a cholinesterase reactivator in vitro, both to the laboratory rabbits poisoned by parathion and to the patients of parathion poisoning, and obtained the following results: 1. With administration of PAM, a prompt and complete dispersion of symptoms of the poisoning can be realized. 2. Cholinesterase activity of red blood cell has instantly and completely recovered, and that of serum transiently. 3. The amount of serum mucoprotein and the activity of active protein-SH-radical of serum varied in direct proportion to the activity of serum cholinesterase. 4. Generally, an intravenous injection of 1g. PAM is sufficient even in the severe case and it may be increased when necessary. 5. The ill effect has not been encountered in the PAM administration. 6. PAM exerts no influence on the cholinesterase activity of normal blood. 7. PAM is expected to play an important role as a prophylactic agent of alkylphosphate poisoning. From these results it seems clear that PAM is a specific and effective antidote against alkylphosphate intoxication.

To reveal the relationship between the morphologic structure and the functioning of cells it is of great importance to know the molecular arrangement in cytoplasm. For this purpose the observation by polarization microscope is one of the most exellent methods. There are several excellent works on nerve fibre done using polarized lightl,2,3,4 but there is no report concerning the nerve cell itself. It is the purpose of this paper to show our data obtained on ganglion cells and nerve fibres with the deduced speculation on the structural arrangement of lipoprotein in the protoplasm of nerve cells and fibres.

The existence of autonomic adjustment functions of eye pressure was demonstrated in various ways, both clinically and experimentally. It is possible to consider that in normal condition, I.O.P. is controlled autonomically like cardiac or respiratory rate irrespective of the internal or external influences of the body. The auther calls such a phenomenon "autonomic eye pressure adjustment function". The mechanism of this physiological function will be reported on in articles to follow.

1. The shell of the ova of Enterobius vermicularis is composed of two chitinous layers, a compact outer layer and a looser inner layer. Both surfaces of the two layers have a dense border. 2. The outer layer has innumerable tubules about 0.2 micron in diameter, and only those tubules found in the thinner part of the layer open to the outside and inside. 3. The outer layer of mature eggs is about 0.45 micron and the inner layer about 2 to 6 microns, in thickness. 4. The chitinous microfibrils in both layers form a rcticular structure which contains very fine granules in the mesh.

In 1955 SANO found mitochondria by the supravital stain with Janus green B in the basophilic stippled cells from the circulating blood of the lead intoxicated rabbitsl , and in 1956 by means of electronmicroscope VALLEJO-FREIRE, BRUNNER et al. found mitochondria in the reticulocytes2,3, and later at the end of 1956 BRAUNSTEINER et al. also succeeded in revealing mitochondria and the vesicular structure by electron microscope in the ultra thin section of young red cells4. We also have found the mitochondria and the endoplasmic reticulum in young red cells. It has been discussed long whether the reticulum of reticulocytes is a preexistent structure or an artifact. The fact that the mitochondria exist in the reticulocyte seems to support strongly the preexistence theory of the reticulum, substantia reticulo filamentosa. However, the fact that the reticulum has several characteristics different from the general mitochondria5,6 can not be ignored. In this paper we should like to demonstrate the photos of mitochondria and the endoplasmic reticulum in the denucleated red cells revealed by electron microscope comparing to the picture of reticuluocyte appeared by supravital stain.

The evaluations of the basal metabolism before the operation, at the completion, and at the follow-up examinations, have been conducted on the patients with cervical carcinoma, all under the age of 50 years, and operated on in the Clinics of Obstetrics and Gynecology, Okayama University Medical School and the following results are obtained: 1. The basal metabolism of the patients with cervical carcinoma of either stage I or stage II as compared with that of the normal women is more accelerated; while the basal metabolism of the cervical carcinoma of stage II. is more augmented than that of the cervical carcinoma stage I. 2. The basal metabolism at the completion of operation is markedly lower than that before the operation. 3. In those who received the autotransplantation of the ovary concomitantly with operation, the basal metabolism once increases at the 4th month after the operation and after that it maintains a low stable state. 4. The basal metabolism of those who received the operative castration continues increasing up to the 8th month after the operation and thereafter it returns to a rather balanced state. 5. From the aspects of the fluctuations of the basal metabolism, it has been recognized that the autotransplantation as compared with the castration exerts less influences on the somatic system and for a shorter period of time, and also the endocrine system of the former returns to the balanced condition earlier.

1. Adversive movements were induced by electrical stimulation and metrazol injection on area 4c of the cerebral cortex. 2. The adversive movement from area 4c does not pass through the thalamus, nucleus caudatus, nucleus lenticularis or superior collicuIus, but through direct efferent pathways in the internal capsule. 3. The adversive movement from area 4c passes through the pyramidal tract.