Current work environments: What problems are being faced by Japanese urologists?

Computer technology has contributed to innovative progress in industrial infrastructures and has had a major influence on various work environments. Evaluations of work environments are routinely carried out in Western countries, but historically there has been resistance to such evaluations in Japan. In this mini‐review, we discuss the current work environments of urologists in Japan. The number of urologists has increased each year, and the population density of urologists was 5.4 (per 100 000 people) in 2014. The average age of urologists in Japan was 48.9 years, and the percentage of female urologists was just 5.3%. Additionally, the geographic distribution of urologists was uneven in Japan. From projections based on population dynamics, the need for more urologists in the near future will probably increase. Because medical environments vary depending on the country, it is necessary to understand current work environments in greater detail initially. Furthermore, we should determine original measures for the establishment of satisfactory urological work environments in Japan.     

Radiochemical microassay of delta-aminolevulinic acid dehydratase activity in whole blood and bone marrow

We describe an assay for delta-aminolevulinic acid dehydratase (EC 4.2.1.24) activity. Radioactive [14C]porphobilinogen, formed by action of this enzyme on [14C]delta-aminolevulinic acid, is purified by passage through an ion-exchange chromatographic column before measurement with a liquid scintillation counter. The radioactive substance in the final solution was identified as solely [14C]porphobilinogen by paper-chromatographic analysis. The present assay procedure requires only a 0.1-microL sample of blood and is about 100-fold more sensitive than the conventional colorimetric methods involving Ehrlich's reagent. Using this method, we found that activity of this enzyme in the bone marrow of rats decreases abruptly and sharply two weeks after birth.     

Conduction velocity in various regions of the renal pelvis and ureter

Conduction velocity of excitation in various regions of the canine pelviureter was studied through the simultaneous recordings of electromyograms at four sites of the canine pelvicalyceal preparation. The pelviureteral system was maintained in the condition which was similar to in vivo situation by infusion of oxygenated Krebs-Ringer solution into the renal pelvis at the average flow rate of living dogs. The conduction velocity was slowest in the proximal region of the pelvis where the pacemaker was located, i.e., about 5.8 mm/sec on an average. The velocity gradually increased in the distal region of the pelvis and the ureter. It was suggested that the conduction velocity of excitation was significantly different in the proximal area of the pelvis, the distal area of the pelvis and the ureter.     

Regulatory expression of lipoxin A4 receptor in physiologically estrus cycle and pathologically endometriosis.

Expression of receptors for prostaglandin (PG) and leukotriene (LT) has been reported to detect in endometrium and smooth muscle of uterus, suggesting involvement of these arachidonic metabolites in endometrial pathology and reproductive biology. Lipoxin (LX), which is produced by lipoxygenases from arachidonic acid, has been characterized as an anti-inflammatory lipid mediator. Biological actions of Lipoxin A4 (LXA4) are mediated through the specific receptor. In order to know roles of LXA4 in female genitalia, expression of LXA4 receptor mRNA was quantified by real-time polymerase chain reaction. Significantly higher expression of the receptor was detected in endometrium and myometrium than ovary in normal rats. Expression of the receptor in endometrium was increased at stage of proestrus cycle under physiological condition. Exogenous administration of progesterone into female rats significantly reduced the expression, while administration of estradiol or pregnant mare serum gonadotropin (PMSG) did not. Both, endometrium in experimental endometriosis induced in rats and the tissues from patients with ectopic endometriosis showed a higher expression of LXA4 receptor compared to the normal tissues. In contrast, expressions of BLT1 and BLT2, receptors for leukotriene B4, did not change in the endometriosis. These observations suggest a possible role of LXA4 and the receptor under physiological estrus cycle and pathological condition as endometriosis.     

Effect of cimetidine on the density of adrenergic alpha-1 and alpha-2 receptors in the rat whole prostate.

In order to study the antiprostatic effect of cimetidine, we measured adrenergic alpha-1 and alpha-2 receptors of the whole prostate of cimetidine-administered rats using radioligand binding techniques. Saturation experiments using 3H-prazosin and 3H-yohimbine revealed that there were significant amounts of alpha-1 and alpha-2 receptors in the rat whole prostate. There were more alpha-1 receptors than alpha-2 receptors in both the control and treated groups. In the treated group, the density of alpha-1 receptors showed little change, while that of alpha-2 receptors showed a significant decrease in comparison to the control group without changes in KD values. These data suggest that cimetidine affects the prostatic alpha receptors and consequently decreases the density of adrenergic alpha-2 receptors in the prostate.     

Nitrous oxide has multiple deleterious effects on cobalamin metabolism and causes decreases in activities of both mammalian cobalamin-dependent enzymes in rats.

In man, use of the general anesthetic nitrous oxide, N2O, is associated with hematologic and neurologic abnormalities that mimic those seen in cobalamin (Cbl, vitamin B12) deficiency. We have measured a number of aspects of Cbl metabolism in rts exposed to various concentrations of N2O for various periods of time. As little as 2% N2O given for 15 h resulted in 30% inhibition of methionine synthetase (MS) in rat liver. With 50% N2O, inhibition of 70% occurred with 1 h and did not change during the next 48 h. Under these conditions, no inhibition of methylmalonyl-CoA mutase (MMCoAM) was observed. The recovery of MS activity was slow and was only 80% of control values 72 h after N2O was stopped. Studies employing rats previously injected with [57Co]Cbl showed that N2O displaced [57Co]Cbl from MS in a manner that temporally and quantitatively paralleled the loss of MS activity. Recovery of MS activity paralleled the reappearance of [57Co]Cbl on MS. N2O also caused the hepatic content of CH3-[57Co]Cbl to decrease by 20-60%. When [57Co]-Cbl was extracted from liver and analyzed by paper chromatography, [57Co]Cbl analogues were present (10-40% of total [57Co]Cbl) in rats exposed to N2O, but not in control animals. When rats were exposed to 50% N2O for 33 d, the total of endogenous Cbl and Cbl analogues in liver decreased to 35% of control values and endogenous Cbl decreased to 10% of control values. At this time, MS activity was 15% of control values and MMCoAM was only 26% of control values. We conclude that N2O causes multiple defects in Cbl metabolism that include the following: (a) rapid inhibition of MS activity with a slow recovery when N2O is stopped; (b) displacement of Cbl from MS; (c) decreased CH3-Cbl; (d) conversion of Cbl to Cbl analogues; (e) the gradual development of Cbl deficiency and (f) an eventual decrease in MMCoAM activity with a further decrease in MS activity.     

Rejection monitoring by lymphocyte blastogenesis assay in canine lung allotransplantation

Seventy-seven adult mongrel dogs underwent left lung transplantation to study the immunological detection of posttransplant rejection response using the lymphocyte blastogenesis assay. Experimental animals were divied into 3 groups; control autotransplantation (4 dogs), control allotransplantation (32 dogs) and immunosuppressed allotransplantation (41 dogs). The lymphocyte blastogenesis assay included mixed lymphocyte reaction (MLR), lymphocyte reactivity to lectins (PHA, ConA and PWM) and spontaneous blastogenesis in peripheral lymphocyte culture methods. The latter two tests were performed in serial blood samples up to the 38th posttransplant day. In the control autotransplant group there were no particular changes in posttransplant PHA reactivities. In the animals with lung allograft, results of preoperative MLR between donor and recipient showed no particular relationships to posttransplant rejection response. The recipient, however, showed a decreased response to PHA and an increased spontaneous blastogenesis at the period undergoing rejection which were confirmed by blood samples taken within 2 days before sacrifice of animals whose transplant specimens showed apparent histologic findings of rejection. In the immunosuppressed allotransplantation group, those findings of PHA response and spontaneous blastogenesis had often preceded the rejection episode detected on chest x-ray films, whereas there were no particular changes in both parameters of dogs bearing enhanced allografts. The serial detection of spontaneous blastogenesis and PHA reactivity in peripheral lymphocyte may be one of the useful methods for early prediction of rejection episode in lung transplantation.     

Production of bone-resorbing activity and colony-stimulating activity in vivo and in vitro by a human squamous cell carcinoma associated with hypercalcemia and leukocytosis.

A squamous cell carcinoma of 33-yr-old patient who developed marked leukocytosis and hypercalcemia was transplanted into nude mice in which more marked leukocytosis and hypercalcemia also developed. This tumor (LJC-1-JCK) produced a colony-stimulating factor (CSF) and formed a cyst in the tumor from which a CSF-producing cell line (T3M-1) was established. The CSF causes predominantly formation of granulocytic colonies in addition to macrophage colonies. Bone-resorbing activity (BRA) was detected in the cystic fluid and was eluted as two separate peaks with proteins of an apparent molecular weight of 30,000-50,000 and 10,000-20,000. Colony-stimulating activity (CSA) was eluted at an apparent 30,000 mol wt. The conditioned medium of the T3M-1 cells also contained a BRA with an apparent 14,000 mol wt, whereas CSA eluted at an apparent 30,000 mol wt. PTH, epidermal growth factor, transforming growth factor-alpha, prostaglandin Es, and vitamin D could not account for the powerful BRA. In contrast to CSA, BRA was not inactivated by trypsin and more stable at 70 degrees C. When T3M-1 cells were transplanted into nude mice, marked hypercalcemia developed in addition to granulocytosis. Our findings suggest that the tumor produces and secretes a powerful BRA in vivo and in vitro, which is different from CSA in terms of molecular weight, heat stability, and trypsin treatment. We speculate that the synergistic action of CSF that stimulates macrophage colony formation and recruits osteoclast precursors, and BRA, which stimulates mononuclear phagocytes and/or osteoclasts were responsible for a marked increase in osteoclastic bone resorption and humoral hypercalcemia in the patient.     

A common truncated variant of lipoprotein lipase in the Japanese population is characterized by pattern B phenotype.

To investigate the relationship between the lipoprotein lipase Ser447Ter (S447X) mutation, lipid profiles and risk of atherosclerotic disease, we studied two groups of Japanese subjects. These groups consisted of a dyslipidemic group (triglyceride (TG) > 1.69 mmol/l and high-density lipoprotein-cholesterol (HDL-C) < or = 0.91 mmol/l; n = 106) and a control group (TG < or = 1.69 mmol/l and HDL-C > or = 1.16 mmol/l; n = 106). All subjects in the control group were confirmed to the pattern A phenotype (normal low-density lipoprotein (LDL) pattern), and 21 individuals in this group were heterozygous for the S447X mutation, but not homozygous. In the patient group, pattern A was shown by 44 of 106 patients. The rest were of the pattern B phenotype, which is associated with an increased risk of coronary heart disease. Homozygosity was concentrated in the patient group (p < 0.05) and in those with the pattern B phenotype (p < 0.05). In contrast, heterozygosity between both groups was not statistically significant. In conclusion, heterozygous and homozygous status with respect to the LPL S447X mutation appears to have different meanings with respect to biochemical and clinical phenotypes of atherosclerosis.