Myocardial and coronary vascular responses to insulin in the diabetic lamb.

Diabetes mellitus was produced in 9 lambs by giving alloxan monohydrate, 150 mg/kg, 24 h prior to study, and these were compared with 12 control animals. Responses to insulin, 20 U/kg, were studied in each. Measurements of LV dP/dtmax, coronary sinus flow (CF) and myocardial extraction and uptake of O2, glucose and fatty acids (NEFA) were made using a hemodynamically controlled preparation described previously (Am. J. Physiol. 244: 1381, 1973). Initial arterial glucose (G) averaged 328 mg/dl in the diabetics compared with 110 mg/dl in controls. G fell to 160 mg/dl 90 min after insulin in the diabetics, and to 25 mg/dl in the controls. Initial LV dP/dtmax values were identical in both groups and showed similar increases of about 800 mmHg/s 30 min after insulin (P less than 0.001). However, initial CF was lower and resistance higher in diabetics than controls. After insulin, CF increased 50% in controls but only 10% in diabetics. Because inotropic responsiveness and O2 metabolism were the same in both groups, altered coronary vascular smooth muscle reactivity in the diabetics may explain these findings.     

Observer variability in the histopathological reporting of abnormal rectal biopsy specimens.

AIMS--To study the consistency of reporting of abnormal rectal biopsy specimens, especially in the differentiation of inflammatory bowel disease from other causes of abnormality. METHODS--Sixty rectal biopsy specimens were identified from patients presenting with bloody diarrhoea. These were then circulated to the 11 consultant pathologists in the study who filled in a proforma with a list of 12 diagnostic categories and 22 features. RESULTS--Forty one of the 60 cases were examples of inflammatory bowel disease. In 33 of these cases nine or more pathologists had made the diagnosis. Further categorisation into ulcerative colitis and Crohn''s disease showed better recognition of ulcerative colitis. In the 19 cases of non-inflammatory bowel disease recognition of pseudomembranous colitis and solitary rectal ulcer syndrome was good, but the results were poorer in the case of infective colitis. CONCLUSION--The findings suggest that a group of consultant pathologists can differentiate between inflammatory bowel disease and other causes of an abnormal rectal biopsy specimen and can also recognise pseudomembranous colitis and solitary rectal ulcer syndrome satisfactorily.     

The response of Golgi tendon organs to single motor unit contractions.

1. Cross-correlation analysis has been used to quantify the responses of cat soleus tendon organs to repetitive twitch contractions of: (a) different motor units within the muscle, (b) single motor units at different muscle lengths, and (c) single motor units when the pulse-train pattern of stimulation delivered to the motor unit axon was altered. 2. Ib afferents were observed which responded to each of several hundred successive motor unit twitches with identical numbers of spikes and with relatively invariant latencies. 3. The present results show that tendon organs are sensitive to subtle alterations in motor unit twitch wave form and amplitude, and that this sensitivity is reflected in the precise timings of their afferent discharge. 4. Examination of these tendon organ responses indicates that the forces produced by single motor units couples to the receptor capsule are well above threshold. Calculations based on these results, and earlier soleus motor unit and muscle fibre data, suggest that the absolute force threshold for tendon organs may be as little as 4 mg, which is less than the estimated minimum twitch force generated by individual soleus muscle fibres. 5. Considering the number of tendon organs in a muscle, and the likelihood that every motor unit is connected with at least one receptor, the sensitivity of tendon organs ensures that every twitch of every motor unit will be reflected in the population of afferent signals projecting to the spinal cord.     

Xanthii Fructus Inhibits Inflammatory Responses in LPS-Stimulated Mouse Peritoneal Macrophages

Xanthii Fructus (XF) is an herb widely used in medicine for the treatment of a variety of inflammatory pathologies. In this study, using mouse peritoneal macrophages, we have examined whether XF affects nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-12p40 production induced by interferon (IFN)-γ and lipopolysaccharide (LPS). XF inhibits IFN-γ and LPS-induced NO production in a dose dependent manner. The decrease in NO synthesis was reflected as a decreased amount of inducible NO synthase protein. Furthermore, we also found that XF inhibits pro-inflammatory cytokine TNF-α production. However, treatment of XF in peritoneal macrophages had no effect on IL-12p40 production. These findings suggest that XF may be used in controlling macrophages-mediated inflammatory diseases.     

Clonorchiasis and cholangiocarcinoma: etiologic relationship and imaging diagnosis

Despite a gradual decrease in prevalence, clonorchiasis is still prevalent in East Asia. A large and compelling body of evidence links clonorchiasis and cholangiocarcinoma, although the mechanisms involved are not completely understood. Clonorchiasis induces biliary epithelial hyperplasia and metaplasia, and this could facilitate at least one stage of the carcinogenesis, which is promoting effect. In areas of endemic infection, more clonorchiasis cases are now diagnosed incidentally during radiological examinations such as cholangiography, ultrasonography, and computed tomography. Radiological findings are regarded as pathognomonic for clonorchiasis since they reflect the unique pathological changes of this disorder. These radiological examinations currently play important roles in the diagnosis, staging, and decision-making process involved in the treatment of cholangiocarcinoma. The morphological features and radiological findings of clonorchiasis-associated cholangiocarcinoma are essentially combinations of the findings for the two diseases. The morphological features of clonorchiasis- associated cholangiocarcinoma, observed in radiological examinations, do not differ from those of the usual cholangiocarcinoma. In patients diagnosed with or suspected to have clonorchiasis, radiological findings should be carefully scrutinized for occult cholangiocarcinoma.     

Metabolic changes after revascularization in a patient with innominate artery occlusion by localized in vivo proton magnetic resonance spectroscopy

Localized in vivo proton magnetic resonance spectroscopy ((1)H-MRS) has been used to measure the metabolic status of the human brain in a non-invasive manner; thus, it is often called "a non-invasive biochemical assay". MRS is more sensitive than magnetic resonance imaging (MRI) in detecting ischemic damage by measuring the metabolic changes that occur prior to the anatomic changes. We report a patient who presented with innominate artery occlusion and symptoms of posterior circulation insufficiency and showed favorable metabolic changes by (1)H-MRS after revascularization. He showed no visible lesion in brain MRI, but in (1)H-MRS, decreased N-acetylaspartate (NAA) signal was noted in a resting state.After revascularization, both symptomatic improvement and recovery of NAA signal were observed. (1)H-MRS may provide valuable clinical information in diagnosis and management of cerebral hypoperfusion at a much earlier stage prior to the anatomic changes.     

Conversion of leukotriene D4 to leukotriene E4 by a dipeptidase released from the specific granule of human polymorphonuclear leucocytes

Leukotriene D4 (LTD4), the most active spasmogenic leukotriene constituent of the slow reacting substance of anaphylaxis was converted by suspended human polymorphonuclear leucocytes (PMNs) to a single, less polar metabolite which was not further catabolized. This product was identified as leukotriene E4 (LTE4) by its retention time during reverse phase-high performance liquid chromatography (RP-HPLC) and subsequent bioassay on the guinea-pig ileum. LTD4 with a retention time of 21 +/- 1.6 min (mean +/- SD) and a contractile activity of 5.0 +/- 0.4 u./pmol (mean +/- SD) was quantitatively converted extracellularly by PMNs to LTE4 with a retention time of 26 +/- 1.8 min and a contractile activity of 1.2 +/- 0.3 u./pmol. Subcellular fractionations of PMNs revealed the recovered LTD4-to-LTE4 converting activity, termed LTD4 dipeptidase, to be localized only in he granule fraction. There was a time- and calcium-dependent extracellular release of LTD4 dipeptidase in association with lysozyme (r = 0.97, n = 16, P less than 0.001), a constituent of both specific and azurophilic granules, in the absence of release of cytoplasmic lactate dehydrogenase (LDH) and of beta-glucuronidase from the azurophilic granule. Phorbol myristate acetate (PMA), which selectively induces secretion of specific granules, released lysozyme and the LTD4 dipeptidase in a constant dose-dependent manner from PMNs (r = 0.96, n = 8, P less than 0.001). Calcium ionophore A23187 at concentrations less than 10(-7) M stimulated the parallel secretion of LTD4 dipeptidase and lysozyme (r = 0.91, n = 9, P less than 0.005), dipeptidase and lysozyme (r = 0.91, n = 9, P less than 0.005), whereas higher concentrations resulted in secretion of beta-glucuronidase and additional lysozyme without further release of dipeptidase. Thus, human PMNs can convert LTD4 to LTE4, a less vasoactive and spasmogenic leukotriene, via the secretion of a dipeptidase associated with the specific granules.     

Ultrastructural studies of the hepatocytes after chronic exposure to low levels of halothane.

Adult rats were exposed to 10 ppm or 500 ppm halothane 8 hr/day and 5 days/wk for 8 wk or 4 wk, respectively. In the liver from animals which were exposed to 10 ppm of halothane, the rough endoplasmic reticulum in some hepatocytes accumulated a floccular, electron-dense material which gave the hepatocytes a dense and dark appearance. Increase in the matrical density and C-shaped transformation were observed in the mitochondria of some hepatocytes. In addition to these findings, areas of focal cytoplasmic degradation, dilatation of the bile canaliculi, peribiliary accumulation of lysosomes, and extensive dilatation of the smooth endoplasmic reticulum to form large cytoplasmic vacuoles were also observed in the hepatocytes of animals which had been exposed to 500 ppm halothane. Toxic potential of halothane upon chronic exposure is suggested.     

The tendon organs of cat medial gastrocnemius: significance of motor unit type and size for the activation of Ib afferents.

1. Histological and histochemical studies suggest that each tendon organ in a mixed mammalian muscle should be particularly responsive to the contraction of a discrete number of motor units (ca. ten to fifteen), each with differing mechanical properties. This report describes physiological experiments that demonstrate this arrangement for the tendon organs of cat medial gastrocnemius. 2. No correlations could be found between the intensity of discharge of a single tendon organ and the contraction strengths of motor units whose contraction excited the receptor. Tendon organs were found to be as responsive to contraction of small slow twitch units as they were to contraction of larger fast twitch units. Taking the data as a whole, the apparent sensitivity of the receptors during motor unit contractions (pps/force recorded at the tendon) was inversely related to the contraction strengths of the motor units. 3. These findings are discussed in relation to recent evidence on the territory of single motor units in medial gastrocnemius and the force producing capabilities of their individual muscle fibres. It is concluded that in general each motor unit, whose contraction excites a given receptor, contributes one muscle fibre to the receptor capsule. Further, it appears that the various excitatory effects of those muscle fibres inserting into a given receptor capsule are not simply related to their relative contraction strengths but also depend on the details of the mechanical coupling between each fibre and the Ib afferent receptor endings. 4. The results of an ensemble analysis show that despite the lack of correlation between the intensity of tendon organ discharge and the force developed at the tendon during contraction of different motor units, a correlation does appear when the responses of several tendon organs and the forces developed by the motor units which excite them are summed progressively. This finding has implications for the recruitment order of motor units in that the profile of the collective Ib response is shown to differ according to whether motor unit forces are summed randomly or in order of increasing contraction strengths.