Genetic variations of HSD11B2 in hypertensive patients and in the general population, six rare missense/frameshift mutations.

Mutations in the gene encoding 11beta-hydroxysteroid dehydrogenase type 2, HSD11B2, cause a rare monogenic juvenile hypertensive syndrome called apparent mineralocorticoid excess (AME). In AME, defective HSD11B2 enzyme activity results in overstimulation of the mineralocorticoid receptor (MR) by cortisol, causing sodium retention, hypokalemia, and salt-dependent hypertension. Here, we have studied whether genetic variations in HDS11B2 are implicated in essential hypertension in Japanese hypertensives and the general population. By sequencing the entire coding region and the promoter region of HDS11B2 in 953 Japanese hypertensives, we identified five missense mutations in 11 patients (L14F, n = 5; R74H, n = 1; R147H, n = 3; T156I, n = 1; R335H, n = 1) and one novel frameshift mutation (4884Gdel, n = 1) in a heterozygous state, in addition to 19 genetic variations. All genetic variations identified were rare, with minor allele frequencies less than 0.005. Four of 12 patients with the missense/frameshift mutations showed renal failure. Four missense mutations, L14F, R74H, R147H, and R335H, were successfully genotyped in the general population, with a sample size of 3,655 individuals (2,175 normotensives and 1,480 hypertensives). Mutations L14F, R74H, R147H, and R335H were identified in hypertensives (n = 6, 8, 3, and 0, respectively) and normotensives (n = 8, 12, 5, and 0, respectively) with a similar frequency, suggesting that these missense mutations may not strongly affect the etiology of essential hypertension. Since the allele frequency of all of the genetic variations identified in this study was rare, an association study was not conducted. Taken together, our results indicate that missense mutations in HSD11B2 do not substantially contribute to essential hypertension in Japanese.     

Spontaneous Uterine Venous Rupture During Labour: A Case Report With Postoperative Ultrasonographic Findings

EDITORIAL COMMENT: We accepted this case for publication to remind readers that although uterine rupture during labour in a primigravida is extremely uncommon it does occur, or at any rate nulliparas can develop abdominal pain and shock in labour with a haemoperitoneum resulting from a tear in a vein in the lower posterior uterine wall. When one sees the hugely dilated uterine and ovarian venous plexuses at Caesarean section it is easy to believe that bleeding from such a vessel during labour could be prodigious. This case suggests that a dilated vein with blood flow derangements may be the cause. Nonetheless, as the authors warn us, the necessary response is not a precise diagnosis, but rapid laparotomy. See also Editorial Comment to Chin MMS, Harvey JA, Duffy BL. Uterine rupture during labour in a primigravida. Aust NZ J Obstet Gynaecol 1996; 36: 210.     

Antibodies to HTLV-1 in saliva of seropositive individuals from Japan

Secretory antibodies protect mucosal surfaces against transmission of many viruses. Human T-lymphotropic Virus, Type I (HTLV-I) is transmitted via blood products and via sexual contact across mucosal surfaces. We investigated the presence of HTLV-I-specific antibodies in whole saliva samples from 10 seronegative and 28 seropositive volunteers from a hospital in southern Japan. Antibodies directed to HTLV-I antigens were found in the salivas from 22 of 28 (79%) of the seropositive subjects. None of the seronegative individuals showed evidence of salivary antibodies. Antibodies directed to the envelope antigens of the virus were found in 21 of 22 positive saliva samples. Secretory antibodies may be important in preventing mucosal transmission.     

Resected cases of middle lobe primary cancer

Of 200 lung cancer lesions resected in our hospital, there were 15 cases (7.5%) with middle lobe origin. The histological types were adenocarcinoma in 13 patients (4 patients with alveolar cell carcinoma), squamous cell carcinoma in one and large cell carcinoma in one. These patients were classified into two groups according to the type of operation they received and each group was evaluated. Group I (resection of the middle lobe) included 8 patients. Each one of Stage IIIB and Stage IV received the operation to improve their symptoms. The six patients of Stage I received only middle lobectomy as absolute curable cases. Group II (resection of the middle and lower lobes) included 7 patients, who had preoperative diagnosis of stage III. Two of them were postoperatively found to be cases of Stage I and Stage II. Although it was still short-term, the follow-up evaluation proved that these patients survived without local recurrence and distant metastasis, except for two with pleural dissemination and one with cerebral metastasis, who had received lobectomy as palliative operation. No difference was observed between the two groups receiving different types of operation.     

Percutaneous removal of renal and upper ureteral stones: clinical results and complications of 103 cases

We report the results and complications of 103 consecutive patients who underwent percutaneous removal of renal and ureteral stones. The overall clinical success rate was 80.6%. For the recent 33 cases in which UL-arm fluoroscopy was used, however, the success rate was as high as 87.9%, which was considered to be due to easier establishment of percutaneous direct access. The most common complications were bleeding (18.5%), extravasation (15.5%) and fever (9.7%). Four cases with significant bleeding required arteriography, but there were no sign of arteriovenous fistula nor pseudoaneurysms in any cases. To study renal parenchymal damage in the percutaneous procedures, plasma renin activities (PRA) were compared in 54 cases after six months. However, significant elevation of PRA did not occur in any case.     

Bleeding from foveolar hyperplasia developing on a gastrointestinal stromal tumor of the stomach

A 52‐year‐old Japanese woman who presented with gastrointestinal (GI) bleeding underwent a proximal gastrectomy for a gastrointestinal stromal tumor (GIST) with a foveolar hyperplasia at the apex of the tumor, 4.5 cm in size, located in the upper body of the stomach. Although GIST are often asymptomatic and are found only incidentally, clinical symptoms such as bleeding, abdominal pain, or obstruction, occasionally lead to a premorbid diagnosis. When submucosal tumors present GI bleeding, the source of the bleeding usually is an ulceration of the mucosa over the tumor. However, in the present study, it was thought that the bleeding originated from the region of foveolar hyperplasia.     

Release of endogenous excitatory amino acids from ON-type bipolar cells isolated from the goldfish retina.

Excitatory amino acids are presumed to be the transmitter of retinal bipolar cells. However, one of the essential criteria for the identification of the transmitter, its release from the cells upon depolarization, has not been demonstrated. This article examines the release of endogenous excitatory amino acids from bipolar cells and correlates this release with the influx of Ca2+. Bipolar cells with a large, bulblike axon terminal (ON-type cells with mixed inputs from rods and cones) were enzymatically isolated from the goldfish retina. Horizontal cells dissociated from the catfish retina were used as a probe of excitatory amino acids, because these cells can detect submicromolar concentrations of L-glutamate with high selectivity. An isolated bipolar cell was closely apposed to a dissociated horizontal cell, and each cell was voltage clamped by a patch pipette in the whole-cell clamp configuration. When the bipolar cell was depolarized from -60 mV to a potential more positive than -40 mV using a 500-msec voltage pulse, an outward current (greater than 20 pA) was recorded from the apposed horizontal cell, which was maintained at +40 mV. The reversal potential of the current induced by the substance released from bipolar cells (Irs) was close to 0 mV and was almost identical to the responses evoked with ionophoretically applied L-glutamate. Both reversal potentials were shifted to the same, more negative value when the external Na+ was replaced with choline. Furthermore, the Irs was suppressed reversibly by the application of kynurenic acid, a glutamate antagonist. When the Ca current (ICa) of the bipolar cell was blocked by Cd2+, the Irs also disappeared. The peak amplitude of Irs was closely related to that of the ICa. We conclude that mixed rod/cone ON-type bipolar cells of the goldfish retina release an endogenous excitatory amino acid or a closely related compound in a Ca(2+)-dependent manner.     

Intravesical combination chemotherapy with mitomycin C and doxorubicin for superficial bladder cancer: a randomized trial of maintenance versus no maintenance following a complete response

Between November 1986 and April 1989, 101 patients with superficial bladder cancer were treated with intravesical instillations of mitomycin C on day 1 and doxorubicin on day 2 of each week for 5 consecutive weeks. Of 61 complete responders, 23 patients with carcinoma in situ and 28 with papillary cancer were randomly assigned to a non-maintenance group or to a group receiving maintenance therapy consisting of monthly instillations of the same drugs for 12 months. The 2-year non-recurrence rate calculated for patients with carcinoma in situ was significantly better in the maintenance group than in the non-maintenance group. A similar tendency was observed for patients with papillary cancer, although the difference was not significant. Side effects were considerable, with moderate to severe bladder irritation occurring in approximately half of the patients. In addition to our previous findings, the present results indicate that this intravesical combination chemotherapy is effective in eliminating superficial bladder cancers and that since the effect is not durable, even in complete responders, maintenance therapy is necessary to reduce subsequent tumor recurrence.Presented at the 4th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 16–17 November 1990, Osaka, Japan