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.     

Long-term vardenafil therapy improves hemodynamics in patients with pulmonary hypertension.

The phosphodiesterase-5 (PDE-5) inhibitor, sildenafil, has been reported to produce sustained pulmonary vasodilatation in patients with pulmonary hypertension (PH). Recently, vardenafil, a more potent and selective PDE-5 inhibitor than sildenafil, has been approved for the treatment of erectile dysfunction. However, the long-term effects of oral vardenafil in patients with PH are unknown. We studied five consecutive patients with PH; one with primary pulmonary hypertension, two with chronic pulmonary thromboembolism, one with Eisenmenger syndrome (ventricular septal defect) and one with secondary pulmonary hypertension after a ventricular septal defect closure operation. In an acute hemodynamic trial, vardenafil (5 mg) significantly decreased both the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) with an increase in cardiac output. In a chronic hemodynamic trial, the maintenance dose of vardenafil (10 to 15 mg) for 3 months significantly decreased the PVR, but not the SVR, with a 20.7% reduction of the PVR/ SVR ratio. Plasma brain natriuretic peptide (BNP) levels were also significantly decreased after 3 months. This pilot study demonstrates that long-term oral vardenafil therapy may be a safe and effective treatment for patients with PH.     

Study on the lymphatic flow of the lower gastric region for radical lymphadenectomy in advanced lower gastric cancer

A prognosis of patients with a curative resected advanced cancer of the lower gastric region was worse than that of the other region of the stomach. The 5 year survival rate was only 47.3%. One of the main reasons was that a rate of lymph node recurrence was higher. In this point of view, we studied on lymphatic flow of the lower gastric region using an activated carbon particle (CH40). Lymph nodes were stained black soon after the injection of CH40 into the lower gastric wall at laparotomy. The black stained rate of an each regional lymph node was as follows. 3. 58%, 4. 17%, 5. 50%, 6. 25%, 1. 21%, 7. 58%, 8. 83%, 9. 58%, 11. 17% and 12. 33% in case of injection into the greater curvature and and 4. 31%, 6. 100%, 8. 25%, 9. 25%, 14V and 56% in case of injection into the lesser curvature. The stained rate was relatively high in 12 and 14V lymph node which we had not routinely dissected. The rates of lymph nodes stained black were related to those of cancer metastasis. The results suggest that lymphadenectomy of 12 for the cancer at the lesser curvature and that of 14V for the cancer at the greater curvature might make a prognosis of lower gastric cancer better.     

Clinical phase I study of T-2588

A clinical phase I study for T-2588 was carried out in 25 healthy male volunteers. Each volunteer received T-2588 in one of the following doses: 100 mg capsule or tablet as a single oral administration in fasting or non-fasting state, 200 or 400 mg capsule as a single oral administration in non-fasting state or 300 or 600 mg daily for 14 approximately 15 days as a repeated administration in non-fasting state. The results are summarized below. No subjective or objective adverse effects were noted after a single oral administration. But repeated dose of 300 mg daily for 15 days and 600 mg daily for 14 days brought about abdominal distension in 1 case and soft stool in 1 case, respectively. As an abnormal change in clinical laboratory findings, 1 case with slight increase in transaminase after a single administration and 3 cases with slight increases in transaminase after repeated doses were observed. Time to reach a maximum concentration of T-2525 in blood (Tmax) was longer in subjects at non-fasting states than subjects in fasting states. Maximum blood concentration was lower in the latter than in the former. Urinary excretion rate in 8 hours after an oral administration was 19 approximately 28% and it was higher in non-fasting subject than in fasting subject. No accumulation of T-2588 was noted after repeated doses.     

Monoclonal antibody to human pancreatic carcinoma cells

A monoclonal antibody (MoAb, SK-930) of the IgG2a subclass to human pancreatic carcinoma cells (MIA-PaCa 2) was obtained by hybridization of spleen cells from immunized Balb/c mice with murine myeloma cells. SK-930 was investigated for reacting in indirect immunofluorescence on FACS against a panel comprising 12 types of different origin. SK-930 reacted with seven out of 11 tumor cells and with one PBL. Immunoperoxidase techniques (ABC method) showed that SK-930 antigen was present on pancreatic adenocarcinoma cells, but could not be detected on normal pancreatic tissue. Immunoprecipitation experiments and SDS-PAGE analysis revealed that SK-930 recognized 134K dalton peptide on tumor cells. These results suggest that SK-930 reacts with a novel pancreatic cancer-associated antigen.     

A case of embryonal carcinoma arising in the basal ganglia of the cerebrum]

The occurrence sites of intracranial primary germ cell tumors are most often the pineal and suprasellar regions. The histological type observed most frequently in these tumors is germinoma. Cases of embryonal carcinoma arising in the basal ganglia are rarely reported. To our knowledge, only 4 such cases have been previously reported in the literature. A case of an embryonal carcinoma arising in the basal ganglia is reported. A 17-year-old boy was admitted to our hospital on July 30, 1988 because of headache and vomiting, and a right hemiparesis. On admission, physical inspection showed no abnormalities and neurological examination revealed obtunded consciousness, a right central facial paresis and a right hemiparesis with Hoffman and Babinski reflexes. Noncontrast CT scan showed a large mass of low-to slightly high-density in the region of the left basal ganglia accompanied with midline shift and ventricular dilatation. Enhancement of the lesion was made by contrast CT scan. It was not homogeneous. Cerebral angiogram displayed a contralateral shift and an unrolling of the anterior cerebral artery, a lateral stretch of middle cerebral artery, a downward stretch of anterior choroidal artery and a tumor stain fed by the Heubner artery. On August 3, left frontotemporal craniotomy was performed. The tumor was totally removed in a piecemeal manner using microsurgical techniques. Histopathological diagnosis was mixed-type of germ cell tumor comprising embryonal carcinoma and teratoma. Postoperative CT scan showed complete disappearance of the tumor. A course of radiation of 4950 rads and two courses of a combination chemotherapy with cis-platinum, vinblastine and bleomycin were given within 3 months after the operation.(ABSTRACT TRUNCATED AT 250 WORDS)     

A surgical case of aortic regurgitation with Beh?et disease

A case of Beh?et disease associated with aortic valve regurgitation treated with aortic valve replacement is reported. The patient was treated successfully with special surgical techniques for prevention of post operative paravalvular leakage and occurrence of pseudo aneurysm because the patient was under long-term steroid therapy for Beh?et disease.     

Effect of 1α-hydroxyvitamin D3 on bone metabolic disorders in gastrectomized rats

The effect of 1α-hydroxyvitamin D₃ (1α(OH)D₃) on the metabolic bone disorders developed in gastrectomized rats were investigated biochemically and histomorphologically. 1α(OH)D₃ was suspended in 0.2 % Triton-X-100 aqueous solution after dissolving in a very small amount of ethanol, was given orally to the rats for 10 weeks. The sham operated animals and the gastrectomy control animals received the vehicle alone. Gastrectomy was followed by the development of the metabolic bone disorders after 10 weeks of observation. This was characterized by reduction in ash content of the femur and histologically by a disappearance of the trabecular bone in tibial metaphysis. Decrease Ca absorption from the intestines was demonstrated by a radiotracer technique. Biochemical studies showed significant decreases in serum 25(OH)D concentration in gastrectomized rats. These findings suggest that gastrectomy partially impairs intestinal absorption of calcium and results in a negative calcium balance, which may contribute to the development of bone metabolic disorders in rats. The administration of 1α(OH)D₃ increased dose-dependently serum calcium and Ca absorption from the intestine and prevented the development of bone metabolic disorders histomorphologically.     

Predictive factors of etiologic agents of community-acquired pneumonia presenting at a district general hospital]

Community-acquired pneumonia is one of the major respiratory diseases causing hospital admission in previously healthy patients. Prompt and appropriate antibiotic selection is essential for recovery. The authors tried to determine the distribution of the etiologic agents of community-acquired pneumonias and to analyze predictive factors. Out of 188 cases of community-acquired pneumonia presenting to our hospital, etiologic agents were determined in 106 cases (56%). Twenty-nine cases were due to Streptococcus pneumoniae, 27 cases due to Mycoplasma, 17 cases due to Haemophilus influenzae and 21 cases due to Mycobacterium tuberculosis. M. tuberculosis was the cause in 11% of all cases and the importance of pulmonary tuberculosis must be emphasized as a community-acquired pneumonia. Out of 58 cases under 50 years old, Mycoplasma pneumoniae was the etiologic agent in 23 cases (40%) and S. pneumoniae in 7 cases (12%). Out of 62 cases not less than 70 years old. M. tuberculosis was the most common etiologic agent (15 cases, 24%). S. pneumoniae followed, being causative in 13 cases (21%). M. tuberculosis was the cause in 10 cases out of 31 cases who did not complain of fever at presentation. In 86 cases who did not show leukocytosis on admission, 21 cases were due to Mycoplasma (24%) and 15 cases were due to M. tuberculosis (17%). In particular 17 cases were due to Mycoplasma among 28 cases under 50 years old without leukocytosis (61%), and 11 cases were due to M. tuberculosis in the 27 cases no less than 70 years old without leukocytosis (41%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Social desirability and irritable bowel syndrome.

The Marlowe-Crowne Social Desirability Scale, a 33-item self-report questionnaire, was administered to an age-matched sample of twenty-five irritable bowel syndrome (IBS) patients, twenty-four psychiatric patients meeting a diagnosis of major depression, and nineteen controls. As predicted, planned comparisons analysis showed a significant group effect: IBS group scores were significantly higher than both depressed and control group scores (p less than .05). Implications of this social desirability response set for the psychological assessment and treatment of IBS are discussed.