[Salivary gland disorder: consider IgG4-related disease]. / Speekselklierafwijking: denk aan IgG4-gerelateerde ziekte.

A 73-year-old man was presented with painless, bilateral swelling of the submandibular salivary glands and unilateral swelling of the parotid gland on the right side, and complaints of dry mouth. A parotid biopsy was taken and a serologic exam was carried out, resulting in the diagnosis of IgG4-related disease. IgG4-related disease is a rare systemic disorder that can cause symptoms in the head and neck region. Usually there are complaints of bilateral, painless swelling of the submandibular, parotid and/or lacrimal glands, with or without complaints of dryness of the mouth and eyes.

Rainfall-enhanced blooming in typhoon wakes.

Strong phytoplankton blooming in tropical-cyclone (TC) wakes over the oligotrophic oceans potentially contributes to long-term changes in global biogeochemical cycles. Yet blooming has traditionally been discussed using anecdotal events and its biophysical mechanics remain poorly understood. Here we identify dominant blooming patterns using 16 years of ocean-color data in the wakes of 141 typhoons in western North Pacific. We observe right-side asymmetric blooming shortly after the storms, attributed previously to sub-mesoscale re-stratification, but thereafter a left-side asymmetry which coincides with the left-side preference in rainfall due to the large-scale wind shear. Biophysical model experiments and observations demonstrate that heavier rainfall freshens the near-surface water, leading to stronger stratification, decreased turbulence and enhanced blooming. Our results suggest that rainfall plays a previously unrecognized, critical role in TC-induced blooming, with potentially important implications for global biogeochemical cycles especially in view of the recent and projected increases in TC-intensity that harbingers stronger mixing and heavier rain under the storm.

Pulmonary dysfunction and skeletal muscle changes in horses with RAO.

BACKGROUND: Chronic pulmonary diseases (recurrent airway obstruction [RAO]) have been reported to alter skeletal muscle cells in humans. The purpose of this study was to evaluate a potential relationship between pulmonary and muscle variables in horses with a clinical diagnosis of RAO. Muscle biopsies from healthy horses and from horses with RAO were investigated and the relationship between the severity of lung disease and the degree of muscular changes was determined. HYPOTHESIS: We hypothesized that chronic pulmonary disease can lead to changes of the skeletal muscle in horses. ANIMALS: Fifteen healthy horses (control) and 50 horses with RAO were examined. METHODS: In a prospective clinical trial, a complete lung examination was performed in all horses. In all horses, muscle enzyme activity at rest and after exercise and muscle biopsies from the M. gluteus medius were examined. RESULTS: None of the horses had clinical or histologic signs of primary or neurogenic myopathies. According to the clinical, endoscopic, and radiographic findings and with a scoring system, the horses with RAO were grouped according to the severity of pulmonary findings (15 horses mild, 24 horses moderate, 11 horses severe RAO). Pathologic changes of the skeletal muscle (fiber atrophy or fiber hypertrophy, myofibrillar degeneration, hyperplasia of mitochondria, and ragged-red-like fibers) were identified in most horses with RAO but in only a few individual control horses. In addition, a marked depletion of muscle glycogen storage was evident in the RAO horses but not in the control group. Other pathologic changes of skeletal muscle such as centralized nuclei and regenerating fibers were rare, but were more frequent in horses with lung diseases than in the control group. The degree of muscle cell changes was also graded with a scoring system and correlated with the severity of pulmonary disease (r= 0.55). CONCLUSION: Chronic pulmonary disease in horses is associated with structural changes in skeletal muscle. CLINICAL IMPORTANCE: Because chronic pulmonary disease may affect muscles, early and effective therapy may prevent these changes. This finding could be of clinical importance but requires further studies.

Hammerhead ribozyme-mediated cleavage of the human insulin-like growth factor-II ribonucleic acid in vitro and in prostate cancer cells.

Insulin-like growth factor (IGF)-II plays an important role in fetal growth and development. IGFs are potent mitogens for a variety of cancer cells. A paracrine/autocrine role of IGF-II in the growth of breast and prostate cancer cells has been suggested. To test the role of IGF-II in cancer cell growth, hammerhead ribozymes targeted to human IGF-II RNA were constructed. Single (R)- and double (RR)-ribozymes were catalytically active in vitro whereas mutant ribozymes (M or MM) did not cleave IGF-II RNA. RR was more active than R. In human prostate cancer PC-3 cells, both R and RR similarly suppressed IGF-II messenger RNA (mRNA) levels (approximately 40%) compared with the level in parental or M-expressing PC-3 cells. Polymerase II and III promoter-driven R similarly suppressed IGF-II mRNA levels. Suppression of IGF-II mRNA levels by R was associated with suppression of IGF-II protein levels. R- (or RR-) expressing PC-3 cells did not grow under serum-starved conditions and showed prolonged doubling times in the presence of 10% FCS compared with those of parental or M-expressing cells. These results substantiated that IGF-II plays a critical role in prostate cancer cell growth.

Is the corrected QT interval a reliable indicator of the severity of diabetic autonomic neuropathy?

OBJECTIVE: We investigated whether the corrected QT interval correlated with two other tests for diagnosing autonomic dysfunction in 60 type I diabetic patients with proven peripheral neuropathy. The mean age +/- SD was 48.3 +/- 11.2 yr, the mean duration of diabetes was 24.9 +/- 11.4 yr, and the mean HbA1 was 9.3 +/- 2.4%. RESEARCH DESIGN AND METHODS: All patients underwent three autonomic function tests: 1) the standard five cardiovascular Ewing tests, each scored 0 (normal), 0.5 (borderline), or 1.0 (abnormal). We used the sum of the abnormal findings for the analysis, the cardiovascular autonomic score; 2) measurement of the corrected QT interval taken from a routine electrocardiogram recording; and 3) static and dynamic pupillometry: measurement of dark adapted pupil diameter as percentage of total iris diameter and of pupil constriction latency using an infrared light reflex technique. RESULTS: No significant correlation was found between age, duration of diabetes, or HbA1 and any of the autonomic function tests, except for one between age and cardiovascular autonomic score (r = 0.3202, P = 0.0126). Corrected QT interval did not correlate with cardiovascular autonomic score, pupil diameter, or constriction latency. A significant inverse correlation was found between cardiovascular autonomic score and pupil diameter (r = -0.4861, P < 0.001) and constriction latency (r = 0.3783, P < 0.001). Pupil diameter and constriction latency correlated well (r = -0.4276, P < 0.001). CONCLUSIONS: The corrected QT interval did not correlate with cardiovascular autonomic tests nor pupillometry results. The corrected QT interval therefore should not be used for the diagnosis of the severity of diabetic autonomic neuropathy.

Plasma carotenoid profiles in normals and patients with cancer.

Most human cancers arise in epithelial tissues, which are critically dependent on vitamin A for normal differentiation and proliferation. Dietary carotenoids consist of individual retinoids--pro-vitamin A precursors and non-pro-vitamin A precursors-displaying different biological activity. Although epidemiological data suggest that low serum vitamin A levels were associated with an increased risk of cancer, it is not known whether one specific or all vitamin A carotenoids are involved. To assess whether the plasma carotenoids are related to the nutritional or cancer-bearing state, a study was conducted to measure total and individual carotenoids in four groups: cancer-bearing, malnourished; cancer-bearing, well-nourished; non-cancer, malnourished; and well-nourished volunteers of comparable age and sex. There was no difference in total carotenoids and pro-vitamin A precursors between the well-nourished--both normal volunteers and cancer patients. Malnourished cancer and non-cancer patients had significantly (p less than 0.05) lower value of both. Most of the circulating carotenoids in all groups were the non-pro-vitamin A precursors. Both malnourished cancer and non-cancer patients had lower values than well-nourished (p less than 0.05). Differences were related to nutritional state, rather than presence of cancer.

Ceruloplasmin: plasma inhibitor of the oxidative inactivation of alpha 1-protease inhibitor.

When leukocyte lysosomal extracts are used as a source of elastase and are combined with a fraction of plasma containing sufficient alpha 1-protease inhibitor (alpha 1-Pi) to inhibit all but 30 to 40% of the elastase amidase activity, elastolysis occurs at 69% of the rate of the uninhibited elastase controls (0.125 M NaCl; pH, 6.5). Proteolysis of elastin requires the presence of NaCl. At pH 8.6, elastolysis is decreased to 30 to 40% of free elastase controls by 1.0 M NaCl. At pH 6.5, on the other hand, elastolysis is increased to 83% of the control values by these higher NaCl concentrations. The activity of human leukocyte myeloperoxidase is optimal at pH 6 to 6.5 and at NaCl concentrations between 0.25 and 1.0 M. Purified myeloperoxidase, alpha 1-Pi, and elastase, in the presence of NaCl and hydrogen peroxide, can reproduce this phenomenon at pH 6.5, suggesting that the occurrence of elastolysis in lysosomal extract-plasma mixtures may in part be a result of the oxidative inactivation of alpha 1-Pi by myeloperoxidase present in the lysosomal extract. Human ceruloplasmin, the major antioxidant of plasma, inhibits this myeloperoxidase-dependent reaction, without interfering either with free elastase activity or with the appearance of activity in plasma-lysosomal extract mixtures at pH 8.6. The "antioxidant" activity of ceruloplasmin is inhibited by azide. These results suggest that antioxidants such as ceruloplasmin may be an important determinant of lung defense in persons chronically exposed to oxidants.

[Hemostaseopathies in chronic, azotemic renal insufficiency. Pathogenesis, diagnosis, treatment (author's transl)]. / Hämostaseopathien bei chronischer, azotämischer Niereninsuffizienz. Pathogenese--Diagnostik--Therapie

A brief survey on the current concepts of diagnosis and pathogenesis of platelet dysfunction in chronic renal insufficiency is given on the basis of clinical hemostaseological investigations. Phenolic compounds, guanidine succinate and fibrin decomposition products are prominent in the discussion of uremia toxins possibly involved in disorders of thrombocytic function. Clinically practicable methods of analysis are briefly presented and the still imperfect status of therapy is emphasized.