Yoshihide Ogawa

Growth Inhibition of Human Prostate Cancer Cells in Human Adult Bone Implanted into Nonobese Diabetic/Severe Combined Immunodeficient Mice by a Ligand-Specific Antibody to Human Insulin-Like Growth Factors

Advanced prostate cancer frequently involves the bone that has the largest content of insulin-like growth factors (IGFs). However, the role of bone-derived IGFs in bone metastasis of prostate cancer has not been studied extensively because of the lack of a reliable animal model. Therefore, we investigated whether a novel antibody directed against human IGF-I and IGF-II (KM1468) could inhibit the development of new bone tumors and the progression of established bone tumors in nonobese diabetic/severe combined immunodeficient mice implanted with human adult bone. We first confirmed that KM1468 bound specifically to human IGF-I, human IGF-II, and mouse IGF-II but not to insulin. It also blocked autophosphorylation of the type I IGF receptor induced by the binding of IGFs in human-type I IGF receptor-overexpressing BALB/c 3T3 cells, and it inhibited the IGF-stimulated growth of MDA PCa 2b cells in vitro. Then mice were injected intraperitoneally with KM1468 once weekly for 4 weeks either immediately or 4 weeks after inoculation of MDA PCa 2b cells. KM1468 markedly and dose-dependently suppressed the development of new bone tumors and the progression of established tumor foci, as determined by histomorphometry, and it also decreased serum prostate-specific antigen levels, compared with the control. This is the first report of an IGF ligand-specific inhibitory antibody that suppresses the growth of human prostate cancer cells in human adult bone. These results indicate that the IGF signaling axis is a potential target for prevention and treatment of bone metastases arising from prostate cancer.

Effects of intrathecal injection of tamsulosin and naftopidil, alpha-1A and -1D adrenergic receptor antagonists, on bladder activity in rats.

The effects of intrathecal injection of tamsulosin (an alpha-1A adrenergic receptor antagonist) and naftopidil (an alpha-1D adrenergic receptor antagonist) on isovolumetric bladder contraction were investigated in rats under urethane anesthesia. Intrathecal injection of tamsulosin (10-30 microg) or naftopidil (0.1-30 microg) transiently abolished isovolumetric rhythmic bladder contraction. Following the recovery of bladder contraction, the interval between contractions was the same as the control value before the injection. The amplitude of bladder contraction was decreased by intrathecal injection of naftopidil (3-30 microg), but not by tamsulosin. Therefore, in addition to the antagonistic action of these agents on the alpha-1 adrenergic receptors of prostatic smooth muscle, both agents (especially naftopidil) may also act on the lumbosacral cord, and thus may improve collecting disorders in patients with benign prostatic hyperplasia.

Oxalate-Degrading Enterococcus faecalis

An oxalate‐degrading Enterococcus faecalis was isolated from human stools under anaerobic conditions. The bacteria required a poor nutritional environment and repeated subculturing to maintain their oxalate‐degrading ability. The E. faecalis produced 3 proteins (65, 48, and 40 kDa) that were not produced by non‐oxalate‐degrading E. faecalis as examined by SDS‐PAGE. Antibodies against oxalyl‐coenzyme A decarboxylase (65 kDa) and formyl‐coenzyme A transferase (48 kDa) obtained from Oxalobacter formigenes (an oxalate‐degrading anaerobic bacterium in the human intestine) reacted with 2 of the proteins (65 and 48 kDa) from the E. faecalis as examined by Western blottings. This is the first report on the isolation of oxalate‐degrading facultative anaerobic bacteria from humans.

Patients with renal cysts associated with renal cell carcinoma and the clinical implications of cyst puncture: a study of 223 cases

OBJECTIVES To clarify the association between renal cysts and renal cell carcinoma (RCC), we analyzed patient demographics, types of cystic disease, and modes of cyst-tumor coexistence along with the results of cyst puncture. METHODS A total of 507 hospitals provided information regarding clinical experiences with RCC and cyst puncture over a 2-year period. RESULTS Renal cysts were identified by preoperative imaging in 223 (4%) of 5721 patients with RCC. Histologic examination revealed cystic RCC in 56 patients (25%) and RCC associated with cystic diseases in 167 (75%). Cystic disease included simple cysts in 72 patients (32%), acquired cystic disease of the kidney (ACDK) in 62 (28%), multilocular renal cysts in 20 (9%), polycystic kidney in 3 (1%), and unspecified or miscellaneous in 10. Cyst puncture performed in 47 (21%) of 223 patients demonstrated bloody fluid in 20 cases and nonbloody fluid in 27. Cytologic analysis of cystic fluid obtained from 37 patients revealed a malignancy in 5 (14%), accounting for 25% of the bloody and 4.8% of nonbloody specimens. Cytology failed to detect RCC in ACDK and multilocular cysts but was positive in cases of cystic RCC and solitary cysts. Four of 5 cytology-positive cases comprised those of tumor in cyst and cyst within tumor. CONCLUSIONS Simple cysts and ACDK accounted for 60% of the renal cysts associated with RCC. Cystic RCC was involved in 25% of cases. Positive cytology may be expected in select cases, including those with close cyst-tumor relationships and those involving bloody cyst fluid. However, negative cytology does not exclude RCC.

EVIDENCE FOR INVOLVEMENT OF THE SUBCOERULEUS NUCLEUS AND NUCLEUS RAPHE MAGNUS IN URINE STORAGE AND PENILE ERECTION IN DECEREBRATE RATS

PURPOSE Micturition and male sexual activity require the lower urinary tract to function. During the sexual act, micturition must be inhibited and urine stored in the bladder. We studied the role of the brainstem in relation to both micturition/urine storage and penile erection in rats. MATERIALS AND METHODS Wire electrodes were placed on the dorsal nerve of the penis and microelectrodes for stimulation were introduced into the brainstem in decerebrate male rats. Electrical stimulation was used to locate optimally responding sites by monitoring the isovolumetric intravesical pressure and intracavernous pressure. RESULTS Electrical stimulation of the dorsal nerve of the penis, the subcoeruleus nucleus in the rostral pons, and the nucleus raphe magnus in the caudal pons increased intracavernous pressure, but inhibited rhythmic bladder contractions. Electrical stimulation of Barringtons nucleus (the pontine micturition center in the rat) in the rostral pons induced bladder contraction. Stimulation of the pontine reticular formation did not increase intracavernous pressure. Acute transection of the thoracic spinal cord eliminated rhythmic bladder contractions, but gave rise to sporadic increments of intracavernous pressure. CONCLUSIONS This electrophysiological study demonstrated that the subcoeruleus nucleus and nucleus raphe magnus are involved in both urine storage and penile erection, and that their physiological functions are reciprocally controlled; so that erection leads to inhibition of micturition.

Lack of evidence for the transmission of JC polyomavirus between human populations

SummaryHuman polyomavirus JC virus (JCV), the causative agent of progressive multifocal leukoencephalopathy, is ubiquitous in humans, infecting children asymptomatically then persisting in renal tissue. Since JCV DNA can readily be detected from urine, it should be a useful tool with which to study the mode of virus transmission in humans. Based on this notion, we examined the extent to which JCV was transmitted from the American to Japanese populations in Okinawa Island, Japan. (A population of about 50 000 American soldiers and families have been stationed in Okinawa since 1945.) Four JCV types (A to D) were identified in American populations in U.S.A., whereas only type B was prevalent in elder Japanese in Okinawa who had reached adulthood by 1945. Thus, types A, C, and D served as indicators of the transmission of JCV from American to Japanese populations. We then examined whether types A, C, and D were detectable in Japanese in Okinawa aged 30–50 years who may have been in contact with Americans during childhood. However, all the 125 isolates from the younger Japanese population were type B without exception. From this finding, we concluded that JCV is rarely transmitted between human populations.

Changes of bone remodeling immediately after parathyroidectomy for secondary hyperparathyroidism

BACKGROUND Successful parathyroidectomy for secondary hyperparathyroidism alleviates bone pain and is followed by the development of hypophosphatemia and hypocalcemia, as well as an increase in bone mineral density. An increase in osteoblast surface (Ob.S/BS) is not observed several months after surgery. In this study, we investigated early bone changes at 1 week after parathyroidectomy and the mechanism underlying an increase in bone mineral density. METHODS Fourteen patients with severe secondary hyperparathyroidism underwent iliac bone biopsy before and 1 week after parathyroidectomy. Changes in histomorphometric parameters, including osteoclast surface (Oc.S/BS), eroded surface (ES/BS), erosion depth (E.De), fibrosis volume (Fb.V/TV), Ob.S/BS, osteoid volume (OV/BV), osteoid surface (OS/BS), and osteoid thickness (O.Th), were investigated. Changes in texture of mineralized bone and osteoid seams were also investigated. RESULTS Oc.S/BS (P < 0.001), ES/BS (P < 0.01), and E.De (P < 0.001) decreased, but Fb.V/TV did not change at 1 week postoperatively. In particular, osteoclasts disappeared in almost all patients. Ob.S/BS (P < 0.001) increased, and cuboidal osteoblasts were proliferating on the trabecular surface where osteoclasts had existed before parathyroidectomy. As a result, newly developed osteoblasts coexisted with fibrous tissue after surgery. OV/BV (P < 0.005), OS/BS (P < 0.005), and O.Th (P < 0.005) increased, with lamellar osteoid volume showing a particular increase. Bone mineralization continued despite the low postoperative serum parathyroid hormone level. CONCLUSION A rapid decrease in serum parathyroid hormone level after parathyroidectomy appears to suppress bone resorption, as well as cause a transient marked increase in bone formation and an increase in normal lamellar osteoid seams.

Urolithiasis in Okinawa, Japan : A relatively high prevalence of uric acid stones

Aim:  The aim of the present study was to investigate the composition of urinary tract stones in patients from Okinawa, the most southern island group of Japan.

Inhibitory effect of intrathecal glycine on the micturition reflex in normal and spinal cord injury rats

We examined the influence of lumbosacral glycinergic neurons on the spinobulbospinal and spinal micturition reflexes. Female rats were divided into intact rats, rats with acute injury to the lower thoracic spinal cord (SCI), and rats with chronic SCI. Under urethane anesthesia, isovolumetric cystometry was performed in each group before and after intrathecal (IT) injection of glycine or strychnine into the lumbosacral cord level. The glutamate and glycine levels of the lumbosacral cord were measured after injection of glycine or strychnine in intact and chronic SCI rats. Expression of strychnine-sensitive glycine receptor alpha-1 (GlyR alpha1) mRNA in the lumbosacral cord was also assessed in both rats. In chronic SCI rats, the interval and amplitude of bladder contractions were shorter and smaller when compared with intact rats. IT glycine (0.1-100 microg) prolonged the interval and decreased the amplitude of bladder contractions in both intact rats and chronic SCI rats. IT strychnine (0.01-10 microg) elevated the baseline pressure in intact rats and induced bladder contraction in acute SCI rats. On amino acid analysis, IT glycine (0.01-100 microg) decreased the glutamate level of the lumbosacral cord in intact rats, but not in chronic SCI rats. The glycine level of the lumbosacral cord was 54% lower in chronic SCI rats when compared with intact rats, while the GlyR alpha1 mRNA level did not change after SCI. These results suggest that glycinergic neurons may have an important inhibitory effect on the spinobulbospinal and spinal micturition reflexes at the level of the lumbosacral cord.

Influence of hypertension on lower urinary tract symptoms in benign prostatic hyperplasia

Aim:  To clarify the influence of hypertension on lower urinary tract symptoms (LUTS) we examined the relationship between blood pressure, LUTS, and the effect of terazosin on LUTS in patients with benign prostatic hyperplasia (BPH).