Search

A formal C‒H addition of N-heteroaromatics to aldehydeswas achieved using a binary hybrid catalyst system comprising an acridinium photoredox catalyst and a thiophosphoric acid organocatalyst. The reaction proceeded through the following sequence: 1) photoredox-catalyzed single-electron oxidation of a thiophosphoric acid catalyst to generate a thiyl radical, 2) cleavage of the formyl C‒H bond of the aldehyde substrates by a thiyl radical acting as a hydrogen atom transfer catalyst to generate acyl radicals, 3) Minisci-type addition of the resulting acyl radicals to N-heteroaromatics, and 4) a spin-center shift, photoredox-catalyzed single-electron reduction, and protonation to produce secondary alcohol products. This metal-free hybrid catalysis proceeded under mild conditions for a wide range of substrates, including isoquinolines, quinolines, and pyridines as N-heteroaromatics, as well as both aromatic and aliphatic aldehydes, and tolerated various functional groups. The reaction was applicable to late-stage derivatization of drugs and their leads.

A hybrid system accomplishing cooperativity between an organophotoredox acridinium catalyst and a chiral chromiumcomplex catalyst was developed, enabling the unprecedented exploitation of unactivated hydrocarbon alkenes as precursors to chiral allylchromium nucleophiles for the asymmetric allylation of aldehydes. The reaction proceeded under visible light irradiation at room temperature and with high functional group tolerance, affording the corresponding homoallylic alcohols with up to >20/1 diastereomeric ratio and 99% ee. The addition of Mg(ClO4)2 elicited profound enhancement of both reactivity and enantioselectivity.

Summary. A 30-year-old male attended the Toyama Medical and Pharmaceutical University Hospital with the chief complaint of infertility. Physical examination showed bilateral small testes and the semen contained no sperm. Hormonal studies revealed hypergonadotropic hypogonadism and cytogenetic studies showed a 46, XX karyotype. High-resolution banding showed no abnormalities in both of the X chromosomes. Histological examination of both testes showed germinal aplasia and the proliferation of Leydig cells. The diagnosis of XX-male was made from the above findings. A DNA hybridization study using 17Y-specific probes revealed the presence of a major part of the short arm of the Y chromosome, which had presumably been translocated to the X chromosome. The translocated Y short arm had a small deletion within it.

Summary To measure testicular volume accurately, an ultrasonographic method was developed and the results obtained from this compared with those obtained by conventional measurements, namely (1) comparison with testis models, (2) an orchidometer, and (3) measurement of testicular volume by calipers through the scrotal skin. Data from these methods were compared with the actual volume measured at operation by slide calipers placed directly on the testis. The volume obtained by comparison with testis models or with an orchidometer tended to overestimate the actual volume. The volume measured by slide calipers on scrotal skin was also found to be incorrect. On the other hand, the volume measured by ultrasonography proved to be closer to, and to correlate well with, the actual volume, and was considered to be the best method.

Low level of plasma atrial natriuretic factor (ANF) under altered dietary sodium and its elevation during bigeminy were found in a 40-year-old woman with idiopathic oedema. The natriuretic effect of this peptide and the role of renin-angiotensin-aldosterone system in oedema formation in this disorder are discussed.

Seventeen patients with hydrocele of the testis were treated by aspiration of fluid and substitution with tetracycline supplemented with 1% lidocaine. In 15 patients (88%) symptoms disappeared by sclerotherapy. After sclerotherapy scrotal ultrasonography was useful to diagnose either relapse or thickened tunica vaginalis. No side effect was noticed.

The ultrasonograms obtained from 20 cases with testicular tumors were reviewed to correlate the ultrasonographic findings with the histologic features. Some seminomas and all metastatic tumors (leukemia, malignant lymphoma and prostatic cancer) showed homogeneous and hypoechoic findings ultrasonographically. All nonseminomatous germ cell tumors had heterogeneous findings on ultrasonography. In patients with leukemia or malignant lymphoma, ultrasonography can serve as a marker in assessing the efficacy of chemotherapy or in the early diagnosis of recurrence. Scrotal ultrasonography also seems to be useful in detecting the small tumor and seems to be convenient for the follow-up of the contralateral testis of a patient who has undergone extirpation of a testicular tumor.

Ejaculated spermatozoa from an infertile patient were examined by scanning and transmission electron microscopy. All spermatozoa had abnormalities in the tail region. The abnormalities were divided into three types: (a) spermatozoa with a spherical tail. The tail was larger than the head in volume. This type of abnormality accounted for about 60% of the population; (b) spermatozoa with a blunt tail. The tails were about 2 microns in diameter and about 7 microns in length. This type of abnormality accounted for about 30% of the population of an ejaculate; (c) spermatozoa without a tail. Some of these had only a rudimentary tail. About 10% of the population belonged to this type. In types A and B, all components of the tail, except for dynein arms, were observed, but they were severely disarranged. Biopsy specimens of the testes and of the nasal mucosa of this patient were also investigated. The testicular biopsy showed defects in manchette formation. Normal development of the manchette could not be observed. The nasal epithelium showed absence of the inner dynein arms in the cilia.

Summary A case of headless or decapitated spermatozoa of an infertile man is reported. The 33-year-old patient showed almost normal spermi-ogram except for a high percentage (more than 90%) of headless spermatozoa. Both hypoosmotic swelling and zona-free hamster egg tests showed that most headless spermatozoa appeared to be normal in their function as tails. The ultrastructure of the ejaculated spermatozoa was observed using a surface replica method and by conventional ultrathin sectioning. The headless spermatozoa were almost normal in structure except for the absence of the head. Tailless heads were rarely observed. Varieties of ultrastructural abnormalities were observed in spermatozoa heads. Among them, abnormalities in the nuclear membrane covering the posterior pole of the nucleus were prominent. The implantation fossa and the basal plate were not formed. Instead, the nuclear membrane with numerous nuclear pores was found in this region. The decapitation seemed to take place between the region of the basal plate and the proximal centriole.

Epidermal growth factor (EGF), a polypeptide hormone originally discovered in the mouse submaxillary gland, stimulates growth in a variety of tissues in several species. This hormone has recently been identified in human urine. Herein, radioimmunoassay (RIA) for human EGF (hEGF) has been developed, using human recombinant EGF as reference standard and radioiodinated tracer and antibodies raised against hEGF. Its sensitivity was somewhat higher than that of RIAs reported formerly. This method had no cross reactivity with high molecular weight EGF. Urinary concentrations of hEGF in normal males and females were 30.2 +/- 13.0 ng/mg creatinine and 46.4 +/- 17.4 ng/mg creatinine, respectively. Urinary concentration of hEGF in patients with renal cancer was somewhat low. The patients with bladder cancer had lower urinary excretion of hEGF than normal adults (p less than 0.05). However, the role of hEGF in health and disease remains to be determined.

From 1977 to 1986, in the Chiba University Hospital, 107 cases of prostatic cancer with bone metastasis were experienced. In 10 of them spinal paralysis caused by spinal metastasis of prostatic cancer was observed. Untreated five cases received endocrine therapy. One of them also underwent spine laminectomy and spinal instrumentation and regained the ability to walk. But the other cases treated by endocrine therapy showed only insufficient improvement of paralysis. Five cases with spinal paralysis which were resistant to endocrine therapy were treated by chemotherapy or radiation to the site of bone metastasis. One of them underwent laminectomy and spinal instrumentation. However, most cases showed no improvement of paralysis. It is concluded that spinal surgery is recommended in untreated cases for the sake of quality of life, but in cases with hormone resistance spinal surgery should cautiously be applied.

A 33-year-old male presented to the Chiba University Hospital with the main complaint of right flank pain. Bilateral vas deferens were not palpable. Hormonal examination revealed hypergonadotropic hypogonadism and cytogenetic studies a 47,XXY karyotype. The significance of the association of this karyotype with the absence of vas deferens is discussed.

RU 27987 is a new ligand for progesterone receptor and binds in high affinity to nuclei of target tissues of progesterone. Using this compound, progestin-binding components in the benign hypertrophic human prostate were studied, and compared with those examined with R 5020, a conventional ligand, in the study of progesterone receptor. In cytosols, the binding affinity of RU 27987 was higher than that of R 5020, and the number of maximum binding sites for RU 27987 seemed to be large but correlated well with those of R 5020. The binder for RU 27987 sedimented at 8.6 S, and the binding was specific to progestational steroids, indicating that binding properties of this binder in the cytosols are identical to those for R 5020. Although there was no binding with R 5020 in the nuclear extract, a small amount of specific binding with RU 27987 was detected. However, the cytosol bound with RU 27987 was not retained in DNA Sepharose and no specific binder for RU 27987 in the nuclear extract was observed in a sucrose density gradient centrifugation. From these observations, it was assumed that the nuclear binding observed was attributable to contamination of the cytosolic binder. The results obtained in the present study suggest that the progestin-binding component in the benign prostatic hypertrophy is not the progesterone receptor but a high affinity binder for progestins whose physiological role is not clear at present.

A transplantable tumor CUB-II, a subline derived from the Dunning R 3327 rat prostatic adenocarcinoma, contains a unique sex steroid-binding protein. The protein possesses binding sites for androgens as well as for estrogens, and the binding affinity to androgen is higher than that to estrogen. The sedimentation coefficient of the protein is 10S. Sodium thiocyanate inhibits the binding to both sex steroids. This type of binding is not present in the 0.4 M KCl extract of nuclei. These results suggest that the binding protein is not the receptor for steroid hormones in spite of its high affinity binding to androgens and estrogens. Since the original tumor does not contain such protein, production of this binding protein seems to take place during culture in vitro and/or serial transplantations of the tumor.

The effect of testosterone treatment on the cytosolic androgen receptor in an androgen-dependent tumor (Shionogi Carcinoma 115, SC 115) and its sublines of altered hormone-dependency (CS 1, less androgen-dependent, and CS 2, androgen-independent) was examined. In all tumors examined a single, high-affinity binding to 3H-R 1881 was detected in cytosols. The size of the maximum binding sites was in the order SC 115, CS 1 and CS 2. Inhibition experiments revealed that the binding to 3H-R 1881 in cytosols of these tumors was attributable to the androgen receptor. The amount of the androgen receptor in cytosols was decreased at 1 hr after testosterone injection, then replenished gradually towards the pretreatment level. Depletion of the androgen receptor was dependent on the dose of testosterone administered. Multiple injections of testosterone depressed the replenishment of the receptor. Treatment with actinomycin D or cycloheximide did not alter the dynamics of the androgen receptor. Therefore, it was concluded that the depletion and replenishment of the androgen receptor in cytosols of the tumors were caused by receptor recycling. Because a similar pattern of depletion and replenishment of the androgen receptor was also observed in the less androgen-dependent tumors, the growth of tumors was felt to be unrelated to the receptor dynamics.

Cytosol of the benign hypertrophic human prostate was prepared in a low salt medium and then the concentration of salt was increased to 0.4 M with KCl (0.4 M KCl-cytosol). This preparation showed a high affinity binding to R 1881 and the binding was specific for androgens. These results suggest that the binding of the preparation to R 1881 was due mainly to the cytosolic androgen receptor. The R 1881 binding component in the 0.4 M KCl-cytosol was sedimented at 3S by sucrose density gradient centrifugation. The small sedimentation coefficient of the binder seems to be due to the high concentration of salt and not to degradation by proteolytic enzymes in the preparation. The molecular weight, Stokes radius and frictional ratio of this binding component were 32, 000, 25.9 A and 1.24, respectively.

Blood was collected from 20 patients with varicocele (15 in the infertile group and 5 in the incidental varicocele group) at the time of high ligation by insertion of a catheter into the internal spermatic vein toward the renal side. Simultaneously, blood was obtained from the antecubital vein. The levels of cortisol, prostaglandin (PG)(A + B), PGE, and PGF in these blood samples were measured. Although no differences in cortisol and PG(A + B) levels were observed between internal spermatic and peripheral vein bloods in varicocele patients examined, PGE and PGF levels were higher in internal spermatic venous bloods than in peripheral venous bloods. Differences in PGF levels between the samples of blood from the internal spermatic vein and from the peripheral vein in cases of the infertile group were larger than those of the incidental varicocele group. PGE and PGF in internal spermatic vein blood samples were correlated. The possibility that PGE and PGF, refluxed from the renal vein to the testes via the internal spermatic vein in varicocele patients, disturbs spermatogenesis is discussed.

A 20-year-old male with complaints of dysuria and a sense of residual urine was diagnosed as having benign prostatic hypertrophy. He was treated by suprapubic prostatectomy. Benign prostatic hypertrophy in young men is very rare; this case seems to be the largest (380 g) among juvenile benign prostatic hypertrophy reported in the literature so far.

Testicular development was studied in prepubertal boys with retractile testes. Testicular volume, the diameter of the seminiferous tubules and the number of spermatogonia in the tubules were decreased in cases of unilateral retractile testis, when compared with values for the contralateral normally descended testis. On the other hand, in patients with a unilateral retractile testis and contralateral inguinal testis, there was no difference in the developmental parameters between the two testes. These results suggest that the retractile testis has developmental failures characteristic of a cryptorchid testis and therefore requires orchiopexy.

The binding nature of mibolerone in cytosols and nuclear extracts from hypertrophic human prostate was examined in comparison with that of R 1881. The binding of mibolerone in the cytosol and nuclear extract was single and of high affinity when evaluated by the method of Scatchard (1949). Binding of mibolerone with testosterone-binding globulin was not detected. The sedimentation coefficients of the binder for mibolerone in the cytosol and nuclear extract were 10.6 S and 3.6 S, respectively. When triamcinolone acetonide was induced in the binding medium, inhibition of mibolerone binding in the cytosol by testosterone and dihydrotestosterone was potentiated and this may imply that the binding observed in the presence of triamcinolone acetonide was responsible for the binding of the androgen receptor. In the nuclear extract, the binding was attributable mainly to the androgen receptor irrespective of the presence or absence of triamcinolone acetonide. These properties of the binding observed in the hypertrophic human prostate were almost same as those of the binding with R 1881. Although maximum binding sites measured using mibolerone were correlated with those using R 1881 in the cytosols as well as in the nuclear extracts, the values obtained with mibolerone were slightly greater than those with R 1881. Thus, mibolerone seems to be a suitable ligand for measuring the androgen receptor, but when compared with R 1881 no special merits in using mibolerone were detected.

Androphilic protein in prostatic cancer was histochemically observed with dihydrotestosterone (DHT), R 1881, and mibolerone as ligands. Cancer cells were equally stained with fluorescent R 1881 and mibolerone, and this fluorescence seems to be made up of both the androgen receptor and progestin-binding protein. The staining with fluorescent DHT was weak. Sixty-two Stage D2 prostatic cancer patients were examined with histochemical androphilic protein, and they then received endocrine therapy. The presence of fluorescence of R 1881 was not correlated with grade, but a relationship between the presence of fluorescence and the response to endocrine therapy was noticed 6 months after the start of treatment. Moreover, fluorescence-positive patients showed better survival than fluorescence-negative patients. An examination with fluorescent DHT revealed a similar tendency to that of R 1881, but the frequency of positive fluorescence was lower, indicating that R 1881 is a suitable ligand in this type of study.

Comparison of the grades classified by Gleason with R-1881 binding which was attributable to total androphilic proteins in tissues was performed in 42 untreated and 13 relapsed prostatic cancers. Increasing malignancy correlated with loss of staining on R-1881 binding when examined both in primary pattern and in individual tumor cell clusters. In relapsed cancer, however, there was no R-1881 binding irrespective of any grades.

Bilateral seminal vesicle puncture and injection of drugs with ultrasound guidance were performed in patients with hemospermia resistant to conservative therapy and with dilated seminal vesicles. Of 7 patients 6 had resolution of hemospermia for 2 to 3 months and then relapse. No side effect was noted. (J. Urol., 140: 991–992, 1988)

We present a case of acute pyelonephritis with right hydronephrosis in a middle-aged woman, who had suffered from rheumatoid arthritis and Sjögren's syndrome. She had successfully treated with antibiotics, however, ureteral stenosis sustained. She underwent ureteroscopy and stenting of right ureter. Biopsy specimen revealed submucosal amyloid deposition in the interstitium overlying a benign urothelium. Amyloid protein was positive for transthyretin (TTR) by immunohistochemistry and amyloid deposition was not demonstrated in other organs. The patient's TTR genes were wild type and she was diagnosed with wild-type ATTR (ATTR wt) amyloidosis. This is the first report about symptomatic ATTR wt amyloidosis, which was also called 'systemic senile amyloidosis (SSA)' in the ureter. We should aware that SSA can occur at younger age and cause symptomatic ureteral stenosis. Further investigation is needed to clarify the association of autoimmune diseases to develop ATTR wt amyloidosis.