Characteristics of young-onset hypertension identified by targeted screening performed at a university health check-up.

Since the prevalence and clinical characteristics of young-onset hypertension are still to be elucidated, we performed targeted-screening at an annual university health check-up for two consecutive years. Out of 16,464 subjects in 2003 and 17,032 in 2004 that were aged less than 30 years, 22 and 26 students (all males) exhibited high blood pressure (BP), respectively, on three occasions during casual BP measurements at the Tohoku University Health Center (systolic and diastolic BP of 140 and/or 90 mmHg or greater, respectively). These students were asked to measure their BP at home, and 9 subjects in total were diagnosed as having essential hypertension (EH). The remaining students were diagnosed as having white coat hypertension (WCH). In 8 out of 9 EH students, their father and/or mother had also been treated with antihypertensive medication. Adjustment by attendance ratio for each BP measurement suggested that the incidence of EH was around 0.1% and that of hypertension (EH and WCH) was around 0.5% in university students aged less than 25 years, since most of the subjects and hypertensive students were between 18 and 24 years old. Body mass index of the EH, which was more than 25 kg/m2 (overweight), was significantly higher than that with WCH. In conclusion, the combination of repeated casual BP measurements and home BP effectively identified young-onset EH. The clinical parameters indicated that male gender, genetic background, and excessive weight were risk factors for young-onset hypertension.     

Prolidase Activity in Chronic Wound and Blister Fluids

We investigated prolidase activity in samples derived from wound fluid as well as blister fluid. Prolidase activity was elevated in fluid samples collected from wounds over the levels in sera collected from patients with chronic wounds (P<0.05). Prolidase activity was also present in samples taken from blister diseases. However, prolidase activity in blister fluid was not higher than that in sera collected from patients with blister diseases. Our results indicate that prolidase may play a role in wound healing.     

Characteristics of prolidase and prolinase in prolidase-deficient patients with some preliminary studies of their role in skin

• 1) The prolidase (Pd) and prolinase (Pn) activities of cultured skin fibroblasts derived from two prolidase-deficient sisters, the elder with typical clinical manifestations [symptom (+)] and the younger with only slight clinical manifestations [symptom (–)] were examined biochemically. Pd activity against several substrates other than Gly-Pro were present to some degree in both sisters. There were no detectable differences in Pd activity between the symptom (+) patient and the symptom (–) sister. Pn activity seemed to be increased in both. The lower Pn activity found against Pro-Gly as compared with those against other substrates indicates that Pro-Gly, which has been used for Pn assays in most previous reports, may not be the best substrate for this test. Pd derived from control fibroblasts was activated by Mn²⁺ against all substrates tested in this experiment. Cu²⁺, Hg²⁺, Cd²⁺ and Zn²⁺ remarkably inhibited enzyme activity, Co²⁺ slightly inhibited it, and neither Mg²⁺ nor Fe²⁺ had any remarkable effect. The Pd derived from the prolidase-deficient patients was also activated by Mn²⁺. This Pd seemed to be more inhibited by Co²⁺ than was the control. However, we found no remarkable differences between the two patients.
• 2) We also studied Pd and Pn activities in rat skin and blood during wound healing. Pd and Pn activities adjacent to the wound increased in parallel with fibroblast proliferation. Pd activity was also detected in an extract of newborn mouse epidermis.

     

Dynamic alteration of human β-defensin 2 localization from cytoplasm to intercellular space in psoriatic skin

Defensins are cationic antimicrobial peptides with a broad spectrum. Recently human beta-defensin 2 (hBD-2) has been isolated from psoriatic skin; however, its exact localization and fate have not been fully understood. We studied the distribution pattern of hBD-2 in skin tissues of psoriasis and other inflammatory skin diseases. In the upper spinous and granular layer of psoriasis vulgaris hBD-2 was present in the cytoplasm. In the horny layer the positive signals were in a basket-weave pattern, indicating possible accumulation of hBD-2 in the intercellular space. The similar pattern of hBD-2 distribution was observed in the lesions of nummular eczema and atopic dermatitis. hBD-2 was not detected in the section of normal elbow and knee skin. When isolated psoriatic scales were stained, hBD-2 was detected in a wrapping paper-like distribution pattern surrounding the corneocytes. In horny layer of psoriatic skin hBD-2 was closely associated or colocalized with elafin, which is known to be in extracellular space, as demonstrated by double staining. Western blot analysis using cultured human keratinocytes detected hBD-2 with an expected size in the conditioned medium and in the cell lysates when stimulated with 5% FCS or IL-alpha. These results indicate that hBD-2 was synthesized and remained in cytoplasm in the upper spinous and granular layer, and then secreted into intercellular space in the horny layer. This dynamic change in hBD-2 distribution in epidermis is certainly relevant to function as an innate host defense mechanism against invading micro-organisms.     

Interferon-{beta} inhibits bleomycin-induced lung fibrosis by decreasing transforming growth factor-{beta} and thrombospondin

Pulmonary fibrosis is the result of abnormal processes of repair that occur after lung injury. Transforming growth factor (TGF)-beta is a key molecule in the progression of pulmonary fibrosis. Although clinical use of interferon (IFN)-beta did not improve survival in patients with idiopathic pulmonary fibrosis, because some preclinical studies have suggested that IFN-beta is a potent inhibitor of fibrogenesis, beneficial effects of IFN-beta have been expected. We therefore attempted to determine effects of IFN-beta and investigated the mechanism of action of IFN-beta in bleomycin-induced pulmonary fibrosis. Bleomycin at Day 0 and IFN-beta for 4 wk were administered intravenously to ICR mice. At 28 d after bleomycin injection, histologic and chemical analysis was performed for evaluation of effects of IFN-beta. Tissue distribution and amounts of TGF-beta1 and thrombospondin (TSP)-1/2 were analyzed. IFN-beta attenuated prolylhydroxylase activity, resulting in inhibition of pulmonary fibrosis. Bleomycin-induced increase in TGF-beta1 in epithelial cells and extracellular matrix was attenuated by IFN-beta. TSP-1/2 was limited in platelets of control mice, but was present in foamy cells in fibrotic regions induced by bleomycin. These findings suggest that the antifibrotic effect of IFN-beta is inhibition of TGF-beta and its activation via decrease in TSP-1/2 in lung tissue and change in location of TSP-1/2 from platelets to foamy cells.     

Distribution of 5-hydroxytryptamine (5HT) in tissue of a mutant mouse deficient in mast cell (W/W v ). Demonstration of the contribution of mast cells to the 5HT content in various organs

The content of 5-hydroxytryptamine (5HT) in various tissues of mutant mouse (W/W ^v) deficient in mast cells and of control mouse (+/+) was determined by high performance liquid chromatography. The depletion of mast cells in the mutant mouse (W/W ^v) was expected to cause a decrease in the 5HT content. In the control mice, 5HT was most densely accumulated in the lung (9.66±5.23 g/g). Large intestine (6.40±2.61 g/g) and stomach (6.10±2.14 g/g) followed the lung in the rating of the 5HT content. The 5HT content ofW/W ^v mice was only 23.4% and 4.1% that of the control in the stomach (p<0.01) and the skin (p<0.01), respectively. The results were consistent with the expectation. In other organs (small intestine, caecum, large intestine, brain, lung, blood and salivary gland), the difference between theW/W ^v and normal mice was not statistically significant. The difference in the 5HT content of the stomach between the two genotypes was 4.67 g/g and was much larger than the 5HT content (0.49g/g) of normal mouse skin. With regard to the relatively small number of mast cells present in the stomach, the great difference in the 5HT content in the stomach between the two genotypes cannot be explained by the loss of mast cells. Hence, besides mast cells other cells may contribute to the high 5HT content of the stomach.This work was supported in part by grants from Takeda Science Foundation (1982), from the Ministry of Education, Science and Culture of Japan (Grant-in-Aid for Special Project Research. 1981–83) and from National Center of Nervous, Mental and Muscular Disorders (NCNMMD) of the Ministry of Health and Welfare, Japan (1981–83).To whom correspondence should be addressed     

Anterior urethral recurrence of superficial bladder cancer: its clinical significance

The aim of this study was to reveal the clinical features of anterior urethral recurrence in patients with superficial bladder cancer, and to determine the appropriate treatment. Three hundred and three patients with superficial bladder cancer, who were newly diagnosed and initially treated conservatively in our hospital between 1965 and 1990, were followed for at least 5 years and their clinical outcomes were analyzed. Clinical factors, including anterior urethral recurrence, were evaluated statistically regarding tumor progression. Eight patients (2.6%) had anterior urethral recurrence following superficial bladder cancer. Twenty-four patients (7.9%) had tumor progression and 149 (49.2%) had tumor recurrence. In a multivariate analysis using a logistic model, anterior urethral recurrence was the most important factor, followed by histological grade. Four of 5 patients who were treated for anterior urethral recurrent tumors by transurethral resection showed progression and died of the cancer within one year. Two of the remaining three patients who underwent radical cysto-urethrectomy at the time of anterior urethral recurrence survived. Anterior urethral recurrence following superficial bladder cancer is a predictor for rapid subsequent malignant progression. Once there is anterior urethral recurrence, radical intensive therapy, including radical cysto-urethrectomy, should be carried out immediately.     

The adrenergic modulation of firings of respiratory rhythm-generating neurons in medulla-spinal cord preparation from newborn rat

We analysed the modulation of respiratory neurons by adrenaline or noradrenaline (NA) in a newborn rat brainstem-spinal cord preparation. Adrenaline or NA caused a dose-dependent depression of the respiratory rhythm and induced C4 spinal tonic discharges. The inhibitory effect of adrenaline (ED₅₀=0.5 μM) on the respiratory rhythm was stronger than NA (ED₅₀=5 μM). The adrenaline respiratory rhythm depression was partially blocked by the α₁-antagonist prazosin or by the α₂-antagonist yohimbine. The C4 tonic discharge elicited by adrenaline was blocked by the α₁-antagonist prazosin. The direct effects of adrenaline on pre-inspiratory (Pre-I) neurons were examined in a synaptic blockade solution (low Ca), and fifty-six percent of Pre-I neurons were found to continue firing. In low-Ca solution, Pre-I neurons were excited (n=29 of 39) or depressed (n=5 of 39) by adrenaline, and excited by α₁-agonist phenylephrine or depressed by α₂-agonist clonidine. These results suggest that the respiratory rhythm depression under intact network conditions is mediated by some other inhibitory system. The inhibitory effect of adrenaline on the respiratory rhythm was partially blocked by the GABA_A-antagonists bicuculline or picrotoxin, but not by the GABA_B-antagonist phaclofen. The present results suggest that: (1) respiratory rhythm generation is more sensitive to adrenaline than NA through α-adrenergic action of adrenaline; (2) the activity of Pre-I neurons could be directly regulated by excitation via α₁-receptors and inhibition via α₂-receptors; and (3) the depression of the respiratory rhythm by adrenaline is partly mediated by GABA_Aergic neurons. Received: 8 April 1997 / Accepted: 6 October 1997     

Intrinsic burst generation of preinspiratory neurons in the medulla of brainstem-spinal cord preparations isolated from newborn rats

In brainstem-spinal cord preparations isolated from newborn rats, intrinsic burst-generating properties of preinspiratory (Pre-I) neurons in the rostral ventrolateral medulla, which have been suggested to be primary respiratory rhythm-generating neurons, were studied by perforated whole-cell recordings using the antibiotic nystatin. Nystatin causes small pores to be formed in the cells, through which pass small monovalent ions. For blockade of chemical synaptic transmission, perfusate Ca²⁺ concentration was lowered to 0.2 mM and the Mg²⁺ concentration was increased to 5 mM. In Iow-Ca²⁺, high-Mg²⁺ solution (referred to here as low Ca), 10 of 55 Pre-I neurons generated rhythmic bursts (burst type), 14 fired tonically (tonic type), and 31 were silent (silent type). Burst-type neurons showed periodic depolarization of 5–12 mV in low Ca, at a rate of 12±6.5/min. Hyperpolarization of the membrane caused decrease in or disappearance of the periodic depolarization and prolongation of the cycle period. Thus, the burst generations were voltage dependent. The firing frequency of tonictype neurons was 2.3±1.6 Hz and was decreased by hyperpolarization. In 6 of these neurons, the firing patterns changed to burst patterns during continuous hyperpolarization. Membrane depolarization by continuous outward current injection into some silent-type neurons (3 of 11 tested) induced bursting activity. Activity of C4 and Pre-I neurons was completely silent with 0.1–1 M tetrodotoxin (TTX) added to the standard perfusate. In low Ca, burst-type neurons (n=3) were also silent with 1 M TTX perfusion. Inspiratory neurons either became silent (n=4) or fired tonically (n=1) in low Ca. The present study by perforated whole-cell recordings confirmed that some Pre-I neurons possess intrinsic burst-generating properties, which were not attributable to phasic synaptic inputs.     

Gangliogliomas: characterization by registered positron emission tomography-MR images

OBJECTIVE: The purpose of this study was to correlate 18F-fluorodeoxyglucose positron emission tomography (PET) and MR imaging features of cerebral gangliogliomas before and after PET-MR image registration. CONCLUSION: After registration of PET and MR images, all six gangliogliomas in our series were shown to have heterogeneous metabolic activity. Areas of hypermetabolic activity were seen in all lesions. In five of the six cases, PET-MR image registration provided information regarding tumor metabolism that was not available on nonregistered hard-copy examinations.