Nephrogenic diabetes insipidus in mice lacking all nitric oxide synthase isoforms

Nitric oxide (NO) is produced in almost all tissues and organs, exerting a variety of biological actions under physiological and pathological conditions. NO is synthesized by three different isoforms of NO synthase (NOS), including neuronal, inducible, and endothelial NOSs. Because there are substantial compensatory interactions among the NOS isoforms, the ultimate roles of endogenous NO in our body still remain to be fully elucidated. Here, we have successfully developed mice in which all three NOS genes are completely deleted by crossbreeding singly NOS-/- mice. NOS expression and activities were totally absent in the triply NOS-/- mice before and after treatment with lipopolysaccharide. Although the triply NOS-/- mice were viable and appeared normal, their survival and fertility rates were markedly reduced as compared with the wild-type mice. Furthermore, these mice exhibited marked hypotonic polyuria, polydipsia, and renal unresponsiveness to an antidiuretic hormone, vasopressin, all of which are characteristics consistent with nephrogenic diabetes insipidus. In the kidney of the triply NOS-/- mice, vasopressin-induced cAMP production and membranous aquaporin-2 water channel expression were reduced associated with tubuloglomerular lesion formation. These results provide evidence that the NOS system plays a critical role in maintaining homeostasis, especially in the kidney.     

Age-related changes in osseous anatomy, alignment, and range of motion of the cervical spine. Part I: Radiographic data from over 1,200 asymptomatic subjects

Purpose

This study aimed to establish radiographic standard values for cervical spine morphometry, alignment, and range of motion (ROM) in both male and female in each decade of life between the 3rd and 8th and to elucidate these age-related changes.

Methods

A total of 1,230 asymptomatic volunteers underwent anteroposterior (AP), lateral, flexion, and extension radiography of the cervical spine. There were at least 100 men and 100 women in each decade of life between the 3rd and 8th. AP diameter of the spinal canal, vertebral body, and disc were measured at each level from the 2nd to 7th cervical vertebra (C2–C7). C2–C7 sagittal alignment and ROM during flexion and extension were calculated using a computer digitizer.

Results

The AP diameter of the spinal canal was 15.8 ± 1.5 [mean ± standard deviation (SD)] mm at the mid-C5 level, and 15.5 ± 2.0 mm at the C5/6 disc level. The disc height was 5.8 ± 1.3 mm at the C5/6 level, which was the minimum height, and the maximum height was at the C6/7 level. Both the AP diameter of the spinal canal and disc height decreased gradually with increasing age. The C2–C7 sagittal alignment and total ROM were 13.9 ± 12.3° in lordosis and 55.3 ± 16.0°, respectively. The C2–C7 lordotic angle was 8.0 ± 11.8° in the 3rd decade and increased to 19.7 ± 11.3 in the 8th decade, whereas the C2–C7 ROM was 67.7 ± 17.0° in the 3rd decade and decreased to 45.0 ± 12.5 in the 8th decade. The extension ROM decreased more than the flexion ROM, and lordotic alignment progressed with increasing age. There was a significant difference in C2–C7 alignment and ROM between men and women.

Conclusions

The standard values and age-related changes in cervical anatomy, alignment, and ROM for males and females in each decade between the 3rd and 8th were established. Cervical lordosis in the neutral position develops with aging, while extension ROM decreases gradually. These data will be useful as normal values for the sake of comparison in clinical practice.     

Solitary epidural amyloidoma of C2–4 without osteolysis of the spine in a multiple myeloma patient

Spinal cord compression sometimes occurs in patients with multiple myeloma (MM), and it usually involves bone infiltration from proliferative plasma cells leading to vertebral collapse, with the occasional extradural extension of a plasmacytoma [1]. However, a localized amyloid tumor, also known as an amyloidoma in the spine, is rare, and a few patients [2, 3] had underlying multiple myeloma (MM). The present case was unique in the form without osteolysis or vertebral collapse, which did not originate from adjacent spinal vertebrae, in a patient with a known diagnosis of MM.     

Three patients who spontaneously developed persistent hypothyroidism during or following treatment with antithyroid drugs for Graves' hyperthyroidism.

Three patients with Graves' disease who spontaneously developed hypothyroidism after treatment with antithyroid drugs are described herein. Patient 1 developed a painful tender thyroid enlargement with a fever and accelerated erythrocyte sedimentation rate when she was receiving maintenance therapy with methimazole, and she progressed to persistent hypothyroidism with increased titers of antithyroglobulin and antimicrosomal antibodies and marked reduction of goiter size within the subsequent 2 months. Thyroid-stimulating hormone-binding inhibitory immunoglobulins (TBIIs) and thyroid stimulation-blocking antibody (TSBAb) were absent when she was hypothyroid. Hypothyroidism probably resulted from autoimmune thyroid destruction due to subacute aggravation of Hashimoto's thyroiditis. During the clinical course of patient 2, accelerated erythrocyte sedimentation rate and later transient increases of antimicrosomal and antithyroglobulin antibody titers were observed repeatedly (four times), and she finally fell into overt hypothyroidism. She also had negative results of tests for TBII and TSBAb. Her hypothyroidism appeared to result from repeated thyroid destruction due to aggravation of Hashimoto's thyroiditis. Patient 3 fell into hypothyroidism when receiving a small dosage of methimazole. The TBII and TSBAb were strongly active when she developed hypothyroidism, which thus seemed to be due to blocking antibody. Patients with Graves' hyperthyroidism may eventually progress to hypothyroidism later by several different mechanisms. Severe and sudden or slowly repeated thyroid destruction due to aggravation of Hashimoto's thyroiditis is one mechanism. Another may be the appearance of a blocking antibody to the TSH receptor.     

Tei index evaluated by M-mode echocardiography in patients with dilated cardiomyopathy

OBJECTIVES: The Tei index obtained by the Doppler method is effective for analysis of global cardiac dysfunction. M-mode recordings of the aortic valve and mitral valve can also provide this index. METHODS: Forty-two patients with cardiomyopathy (idiopathic 15 and ischemic 27) with left ventricular ejection fraction < 40%, and 85 normal subjects were enrolled in the study. The M-mode Tei index (Tei-M) was obtained from the ejection time and closing period of the mitral valve in the same manner as the Tei index obtained by the Doppler method (Tei-D). RESULTS: The values of Tei-D and Tei-M were closely correlated (r = 0.75, p < 0.0001). Using index > or = 0.45 as the cut off value, patients with cardiomyopathy were identified with a sensitivity of 86% and a specificity of 78% by Tei-D, and 67% and 73% by Tei-M, respectively. In patients with mitral B-bump on M-mode echogram (n = 10), there was no mitral inflow during B-bump. Thus, Tei-M was smaller than Tei-D in these patients. Using the new criteria of Tei-M > or = 0.45 and presence of B-bump, patients with cardiomyopathy were identified with a sensitivity of 86% and specificity 73% by Tei-M which were comparable with Tei-D. CONCLUSIONS: The Tei-M is a simple and effective index for the analysis of cardiac dysfunction in patients with cardiomyopathy.     

Clinical evaluation of bird related hypersensitivity pneumonitis]

We retrospectively evaluated 8 cases of bird related hypersensitivity pneumonitis in Tenri hospital, all of whom underwent surgical lung biopsy. They had a history of contacting with birds and had serological studies using lymphocyte stimulation test to pigeon serum or antibody in serum and bronchoalveolar lavage fluid to pigeon dropping extracts yielded positive results. Computed tomography revealed a radiographic pattern unlike typical UIP. The result of pathological diagnosis of surgical lung biopsy was 'others' or NSIP pattern. Only one case had pathological findings of granuloma. Four cases had an improved or stable course only offer segregation from bird antigens. The other four cases needed corticosteroids and immunosuppressants, and two of the four cases had a progressive course and died of respiratory failure.     

Influence of an oxygen‐inhibited layer on enamel bonding of dental adhesive systems: surface free‐energy perspectives

The influence of an oxygen‐inhibited layer (OIL) on the shear bond strength (SBS) to enamel and surface free‐energy (SFE) of adhesive systems was investigated. The adhesive systems tested were Scotchbond Multipurpose (SM), Clearfil SE Bond (CS), and Scotchbond Universal (SU). Resin composite was bonded to bovine enamel surfaces to determine the SBS, with and without an OIL, of adhesives. The SFE of cured adhesives with and without an OIL were determined by measuring the contact angles of three test liquids. There were no significant differences in the mean SBS of SM and CS specimens with or without an OIL; however, the mean SBS of SU specimens with an OIL was significantly higher than that of SU specimens without an OIL. For all three systems, the mean total SFE (γ_S), polarity force (), and hydrogen bonding force () values of cured adhesives with an OIL were significantly higher than those of cured adhesives without an OIL. The results of this study indicate that the presence of an OIL promotes higher SBS of a single‐step self‐etch adhesive system, but not of a three‐step or a two‐step self‐etch primer system. The SFE values of cured adhesives with an OIL were significantly higher than those without an OIL. The SFE characteristics of the OIL of adhesives differed depending on the type of adhesive.