Demonstration of nucleolar organizer regions in intrahepatic bile duct carcinoma by the silver-staining technique

Abstract— A silver colloid technique to identify argyrophilic nucleolar organizer region associated protein (AgNOR) was applied to 43 cases of intrahepatic bile duct carcinoma (cholangiocarcinoma, CC), 2 with bile duct adenoma (BDA), 5 with focal duct epithelial hyperplasia (FEH) associated with hepatolithiasis, 15 with posthepatitic ductular proliferation (PHDP) associated with massive or submassive hepatic necrosis and 20 of normal liver. In the present study, only discrete, easily counted black dots within nuclei and silver-stained nucleolus were counted under a magnification of X 400 without oil-immersion objectives. The mean AgNOR count of CC was significantly higher than those of BDA, FEH, PHDP and normal controls (P>0.05, P>0.001, P>0.01, and P>0.001, respectively). Among CCs the mean AgNOR numbers of papillary adenocarcinoma (pap), moderately (tub2) and poorly differentiated (por) adenocarcinoma, and adeno-squamous carcinoma (as) were significantly higher than that of normal controls (P > 0.01, P > 0.001, P > 0.001 and P > 0.001, respectively), and those of tub2, por and as were also significantly higher than those of BDA, FEH and PHDP, whereas that of well differentiated tubular adenocarcinoma (tub 1) was not different from those of BDA, FEH, PHDP and normal controls, and that of pap was not different from those of BDA, FEH and PHDP. The mean numbers of AgNORs of BDA and FEH were not different from that of normal controls, whereas that of PHDP was significantly higher than that of normal controls (P > 0.01). Interestingly, the mean AgNOR counts of tubular adenocarcinoma were increased with histologic tumor grades. All cases with AgNOR counts of more than 2.24 had CC. Furthermore, not only quantitative but also striking qualitative abnormalities of AgNORs were seen in CCs. Large and/or irregularly shaped AgNORs without uniformity in size and density were characteristic for CCs, even in well differentiated adenocarcinoma, in contrast to the small, round, regular AgNORs seen in normal bile duct epithelium and rather large but regular AgNORs seen in benign bile duct lesions. These results indicate that the enumeration of AgNORs in various bile duct lesions is useful to identify moderate and high grade CCs and to evaluate tumor grade, but not useful to discriminate well differentiated adenocarcinoma from benign lesions. In case of normal or equivocal AgNOR counts, the presence of large and/or irregularly shaped AgNORs without uniformity in size and density would favor a diagnosis of carcinoma rather than benign counterparts.     

Proliferating cell nuclear antigen and nucleolar organizer region for differential diagnosis of dysplasia and adenocarcinoma in gastric biopsies.

INTRODUCTION: The value of proliferating cell nuclear antigen (PCNA) and nucleolar organizer region (AgNOR) for differential diagnosis of normal mucosa, dysplasia and adenocarcinoma in gastric endoscopic biopsies, and correlation between these two methods were evaluated. METHODS: 15 gastric endoscopic biopsy samples from normal mucosa, 15 from areas of dysplasia and 15 from low grade adenocarcinoma were studied. AgNOR and PCNA immunostaining were applied to paraffin sections. RESULTS: Mean AgNOR value and PCNA-labeling index were the lowest in normal mucosa and the highest in adenocarcinoma. Mean (SD) AgNOR numbers were 2.9 (0.3) in normal mucosa, 5.9 (1.7) in dysplasia and 15.7 (2.8) in adenocarcinoma. PCNA-labeling index was 2.4 (1.1) in normal mucosa, 27.5 (4.6) in dysplasia and 42.1 (5.3) in adenocarcinoma. The differences between normal mucosa and dysplasia, and between dysplasia and adenocarcinoma were significant (p < 0.001). Overlapping values were observed in AgNOR counts between normal mucosa and dysplasia, and in PCNA-labeling indices between dysplasia and adenocarcinoma. No correlation was found between AgNOR and PCNA. CONCLUSION: Though mean AgNOR values and PCNA indices were significantly different between normal mucosa, dysplasia and adenocarcinoma, these could not be used in differential diagnosis because of overlapping values between groups.     

Identification of nucleolar organizer regions in non-neoplastic and neoplastic hepatocytes by the silver-staining technique

Abstract— The silver staining technique to demonstrate nucleolar organizer region (NOR)-associated proteins (AgNORs) was applied to a variety of liver tissues, including chronic persistent hepatitis (CPH), chronic active hepatitis (CAH), liver cirrhosis (LC), liver cell dysplasia (LCD), focal nodular hyperplasia (FNH), adenomatous hyperplasia (AH) and hepatocellular carcinoma (HCC). In the present study, only discrete, easily counted black dots within nuclei and silver-stained nucleolus were counted under a magnification of X 400 without oil-immersion objectives. The mean AgNOR counts of HCC and LCD were significantly higher than that of normal hepatocytes, and 77% of cases of LCD and 56% of HCC had mean AgNOR counts more than 2, whereas those in CPH, CAH, LC, FNH and AH were always less than 2 and were not different from that of normal hepatocytes. Among HCC, the mean number of AgNORs increased with the grade of the tumor. However, the AgNOR counts of grade I HCC were always less than 2 and overlapped with those of normal hepatocytes and other benign categories. All cases with mean AgNOR counts of more than 2 turned out to be HCC, except LCD which exhibited characteristic histologic appearances easily distinguished from HCC. These findings suggest that AgNORs could be quantitatively useful in evaluating the grade of HCC, even under routine microscopic examination without oil-immersion objectives, and mean AgNOR counts of more than 2 per nucleus are hallmarks of HCC.     

Bile secretory immunoglobulin A in biliary infection and cholelithiasis.

Bile samples from 71 patients with cholelithiasis and a control group of 10 subjects without hepatobiliary diseases were cultured for bacteria and measured for secretory immunoglobulin A (SIgA) using enzyme immunoassay specific for SIgA. The results of bile bacterial culture were all positive in patients with primary bile duct pigment stones, and significantly lower bile SIgA levels were observed than in normal controls (P less than 0.005). It was also shown that the constitutent ratios of SIgA to total bile immunoglobulin and the bile-serum ratio of SIgA were markedly lower in these patients than in normal controls (P less than 0.001, P less than 0.001). In patients with cholecystolithiasis, bile SIgA concentrations of patients with biliary infections were remarkably lower than those of patients without biliary infection (P less than 0.01) and those of normal controls (P less than 0.01). These results suggest a close relationship between biliary tract infection and low concentrations of bile SIgA.     

Identification of nucleolar organizer regions in non-neoplastic and neoplastic hepatocytes by the silver-staining technique.

The silver staining technique to demonstrate nucleolar organizer region (NOR)-associated proteins (AgNORs) was applied to a variety of liver tissues, including chronic persistent hepatitis (CPH), chronic active hepatitis (CAH), liver cirrhosis (LC), liver cell dysplasia (LCD), focal nodular hyperplasia (FNH), adenomatous hyperplasia (AH) and hepatocellular carcinoma (HCC). In the present study, only discrete, easily counted black dots within nuclei and silver-stained nucleolus were counted under a magnification of x400 without oil-immersion objectives. The mean AgNOR counts of HCC and LCD were significantly higher than that of normal hepatocytes, and 77% of cases of LCD and 56% of HCC had mean AgNOR counts more than 2, whereas those in CPH, CAH, LC, FNH and AH were always less than 2 and were not different from that of normal hepatocytes. Among HCC, the mean number of AgNORs increased with the grade of the tumor. However, the AgNOR counts of grade I HCC were always less than 2 and overlapped with those of normal hepatocytes and other benign categories. All cases with mean AgNOR counts of more than 2 turned out to be HCC, except LCD which exhibited characteristic histologic appearances easily distinguished from HCC. These findings suggest that AgNORs could be quantitatively useful in evaluating the grade of HCC, even under routine microscopic examination without oil-immersion objectives, and mean AgNOR counts of more than 2 per nucleus are hallmarks of HCC.     

Ambulatory and exercise-induced blood pressure responses in type I diabetic patients and normal subjects

We evaluated the ambulatory blood pressure (BP) readings during daily activities and compared the values with the casual office BPs in 12 type I diabetic patients and 12 age-matched, non-diabetic normal controls. The BP responses to 750 kpm/min exercise work load on bicycle ergometer were also evaluated in all the subjects. The mean ambulatory BPs were significantly higher in the diabetic patients compared with non-diabetic subjects. However, the ambulatory and casual office BPs were remarkably similar in each group. Mean peak exercise BPs were higher in the diabetics, but significantly so for diastolic BP (P less than 0.05) and mean arterial pressure (MAP) (P less than 0.01). The mean ambulatory MAP significantly correlated with the casual office MAP in both the diabetics (r = 0.75, P less than 0.005) and non-diabetics (r = 0.58, P less than 0.02). A significantly positive relationship (r = 0.87, P less than 0.001) existed between the ambulatory and peak exercise MAP in the diabetics, but not in the non-diabetic subjects. The mean peak exercise BP responses were significantly (P less than 0.01) higher in the diabetic patients with proliferative retinopathy vs. those with non-proliferative retinopathy. We conclude that casual office BPs reflect the ambulatory values in both diabetics and non-diabetics. Exaggerated BP responses to exercise are found in diabetic patients, especially in the presence of proliferative retinopathy. These findings are suggestive of possible defects in the cardiovascular, autonomic and autoregulatory mechanisms that maintain a normal MAP during daily stresses and exercise in the diabetic patients.     

Metabolism of calcium and phosphorus in Cushing syndrome with osteoporosis

52 patients with Cushing syndrome were studied. According to the appearance of X-ray film of bones, they were divided into three groups: (I) Without osteoporosis, 12 cases (23.1%), (II) Mild osteoporosis, 17 cases (32.7%), (III) Severe osteoporosis with fractured ribs and/or wedge-shaped vertebrae, 23 cases (44.2%). It was found that the mean level of serum calcium in the patients was significantly lower than that in 94 normal subjects (mean +/- S 2.3 +/- 0.2 versus 2.4 +/- 0.1 mmol/L P less than 0.001). The mean concentrations of blood alkaline phosphatase and parathyroid hormone in the patients were much higher than those in normal subjects (65.0 +/- 27.6 versus 42.6 +/- 15.6 IU/L P less than 0.001, 44.6 +/- 22.4 versus 20.6 +/- 8.0 pg/ml P less than 0.001 respectively). The mean level of serum 25 (OH)-D in the patients was significantly lower than that in controls (10.9 +/- 5.6 versus 16.2 +/- 4.6 ng/ml P less than 0.001). Urinary calcium excretion increased in the patients as compared with that in controls (P less than 0.01). The urinary calcium excretion correlated well with the blood total cortisol and urinary free cortisol. It is suggested that hypercalciuria might cause decrease of serum calcium. Thus the parathyroid glands were stimulated and the parathyroid hormone (PTH) secretion was increased. Excess of PTH stimulates bone resorption. All of these factors are involved in the pathogenesis of osteopenia in Cushing's syndrome.     

Abnormalities in erythrocyte insulin binding in offspring of conjugal non-insulin-dependent diabetic parents

Insulin binding to erythrocyte insulin receptors was studied in 23 offspring (13 men and 10 women) born of conjugal diabetic parents having type 2 diabetes. Nine of the offspring were obese and 14 were non-obese, but all had normal glucose tolerance. Twenty-three age-, sex- and weight-matched non-diabetic subjects without a family history of diabetes were studied as controls. In the non-obese offspring mean basal plasma immunoreactive insulin (IRI) was elevated (P less than 0.01), but the mean stimulated IRI showed no change in comparison to that of controls. In the obese offspring mean basal plasma IRI was similar, but the mean stimulated IRI was lower than that of obese controls (P less than 0.01). Mean specific insulin binding was decreased in both obese (P less than 0.01) and non-obese (P less than 0.01) offspring when compared with the respective controls. Scatchard analysis of the binding data and the higher insulin concentrations required to achieve 50% inhibition of tracer binding indicated decreased receptor affinity in both obese and non-obese offspring. Analysis by average affinity profiles also indicated decreased receptor affinity, as shown by a lower average affinity constant Kc for the empty sites, in the offspring in comparison to that of controls (P less than 0.001). Abnormalities in insulin binding to its receptor along with decreased affinity in the face of normal glucose tolerance may be an early biochemical marker of potential diabetes in this group at high risk of developing diabetes.     

Maximal exercise in children with aortic regurgitation: an adjunct to noninvasive assessment of disease severity

Twenty-five asymptomatic children with chronic aortic regurgitation were evaluated by graded bicycle exercise testing and standard resting M-mode echocardiogram. These results were compared to those of 35 normal controls matched for age and body surface area. Twenty-one patients underwent cardiac catheterization to rule out associated lesions. Patients fell into two groups based upon the left ventricular end-diastolic volume per body surface area (LVEDVI): group I (n = 10) had LVEDVI less than or equal to 2 SD from the mean of normal; group II (n = 15) had LVEDVI greater than or equal to 4 SD from the mean of normal. All had normal shortening fraction and velocity of circumferential fiber shortening. At maximal exercise, patients in group I were found to have no significant differences from normals in maximal workload, total work, percent maximal oxygen consumption, heart rate, blood pressure, or ST segment depression. However, patients in group II had blunted mean maximal exercise heart rate (p less than 0.001), systolic hypertension (p less than 0.05), and increased frequency and maximal amplitude of ST depression (p less than 0.01, p less than 0.001, respectively) compared to normal controls. Within group II the mean maximal amplitude of ST depression was significantly related to increasing LVEDVI (r = 0.53, p less than 0.05). The mean maximal exercise heart rate, systolic blood pressure, and maximal amplitude of ST segment depression were significantly related to LVEDVI for patient groups and normal controls together (r = -0.384, p less than 0.01; r = 0.28, p less than 0.05; r = 0.70, p less than 0.001, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Haemodynamic basis of early modifications of the large arteries in borderline hypertension

Quantitative evaluation of brachial artery diameter, blood velocity and flow (pulsed Doppler velocimetry) and of forearm arterial compliance (FAC)--mathematical analysis of the simultaneous diastolic pressure and flow according to a first-order arterial model--was carried out in 10 normotensive controls, and in 23 borderline hypertensive patients, of the same age. Using a value of 2 standard deviations above the average cardiac index of 20 normotensive subjects, enabled us to classify 12 patients as having a normal cardiac output and 11 patients as having a high cardiac output. Each group was of similar age and pressure. FAC was lower in patients with a normal cardiac output than in normal controls (P less than 0.01) and also lower than in patients with high output (P less than 0.01). Brachial artery diameter and flow were higher in patients with high output than in normal controls (P less than 0.01, P less than 0.001) and also higher than in patients with a normal output (P less than 0.001). A positive correlation (r = 0.55; P less than 0.01) was found between heart rate and brachial artery diameter in the 23 patients. These results demonstrate a non-homogenous pattern of brachial artery characteristics of patients with borderline hypertension. Patients with normal cardiac output exhibited a clear reduction of the distensibility of the forearm arteries while patients with high cardiac output had strong dilation of the brachial artery.     

Study on urinary function and metabolism of water and electrolytes in primary hypothyroidism

Water excretion in 16 patients with primary hypothyroidism was lower in amount and more delayed (P less than 0.05) than that in 5 normal controls after acute water ingestion. The mean plasma osmolality of the patients was lower than that of normal controls both before and after water loading. However, the mean urine osmolality was not decreased but rather elevated. The clearance of free water in the patients was lower than that in normal controls before loading, Although the clearance of osmolality in the patients was higher than that in the controls, the difference was insignificant. These two clearance rates were lower than those in the controls after loading. The fractional excretion of sodium (P less than 0.05) and chloride (P less than 0.01) in the patients was significantly higher than that in the controls before loading and both of them remained elevated after loading. Most of the parameters mentioned above improved in 9 patients after treatment with desiccated thyroid.     

Hepatic mean transit time of 99mTc-EHIDA estimated by deconvolution analysis

Clinical usefulness of mean transit time (MTT) through the liver was evaluated by deconvolution analysis using 99mTc-EHIDA hepatobiliary scintigraphy in 82 patients with various hepatobiliary diseases and 18 normal controls. Initial transfer factor was also obtained according to the method of Rutland. Results obtained were as follows. 1) Effect of the age on MTT was not observed in normal controls. 2) MTT in left lobe of normal controls was significantly prolonged compared with that of right lobe (P less than 0.01). This kind of difference was not observed in patients with liver cirrhosis. 3) MTT in patients with obstructive jaundice, chronic liver diseases, liver cirrhosis at decompensative state and primary biliary cirrhosis was significantly prolonged compared with that in normal controls (P less than 0.01). 4) MTT in patients with liver cirrhosis at compensative state showed normal values, although blood clearance rate in those patients was significantly decreased (P less than 0.05). 5) Positive correlation was observed between MTT and values of T-Bil, ALP, LAP, and gamma-GTP. Negative correlation was observed between MTT and value of cholinesterase. 6) Initial transfer factor correlated with blood clearance rate. (r = 0.76, P less than 0.01). 7) Initial transfer factor in left lobe of normal controls was significantly decreased compared with that of right lobe (P less than 0.01). This kind of difference was not observed in patients with liver cirrhosis. 8) Initial transfer factor in patients with liver cirrhosis in both compensative and decompensative states and PBC was significantly decreased compared with that in normal controls. Estimation of MTT and initial transfer factor could be a useful parameters to assess transfer function of the liver.     

Enhanced blood pressure response to regular daily stress in urban hypertensive men

Twenty-eight urban untreated hypertensive men (mean age: 54 years; systolic (SBP)/diastolic (DBP) blood pressure at clinic: 148/96 mmHg] and 26 age- and sex-matched normal controls (54 years, 118/78 mmHg) were examined during normal daily activities by ambulatory blood pressure monitoring. When compared with home blood pressures, clinic blood pressures were 8/10% (SBP/DBP) higher in the hypertensives, but 1/3% lower in the normotensives. The values were significantly different for both groups (P less than 0.01 for SBP; P less than 0.001 for DBP). In contrast, the blood pressures fell in a similar manner in both groups during sleep. On working days, the blood pressures during work were 10/9% higher than the corresponding home blood pressures in the hypertensives and only 3/3% higher in the normotensives. These differences were significant (P less than 0.01 for both SBP and DBP). The results show that the blood pressures of hypertensives were hyperreactive to casual daily stress. In the normotensives, left ventricular wall thickness determined by echocardiography was correlated significantly with the blood pressures during work (r = 0.5, P less than 0.05 for SBP and DBP) and at home (r = 0.4, P less than 0.05 for SBP).     

Abnormal wall shear conditions in the brachial artery of hypertensive patients

Brachial artery wall shear phenomena were studied in 20 untreated essential hypertensive patients and in 11 normotensive controls of similar age. A pulsed-Doppler velocimeter was used to measure brachial artery internal diameter and mean cross-sectional and systolic centreline blood velocities. A coaxial-cylinder viscometer was used to measure blood viscosity at a shear rate of 96 s-1. A Poiseuille model of velocity distribution across the arterial lumen was used to determine wall shear rate and stress from, respectively, the ratio of blood velocity to arterial diameter and the product of shear rate and blood viscosity. Mean and systolic shear rates and stresses were calculated using, respectively, mean cross-sectional and systolic centreline blood velocities. Hypertensive patients had larger brachial artery diameters (P less than 0.001), lower systolic centreline and mean cross-sectional blood velocities (P less than 0.001, P less than 0.05), higher blood viscosity (P less than 0.001), lower mean and systolic wall shear rates (P less than 0.01, P less than 0.001) and lower systolic wall shear stress (P less than 0.05) than normotensive controls. In all subjects, mean blood pressure was negatively correlated both with mean and systolic shear rates (r = -0.38, P less than 0.05;r = -0.45, P less than 0.01). Thus the hypertensive state was associated with decreases in both mean and systolic wall shear rates, and in systolic wall shear stress. These shear abnormalities merit attention because of the atherogenic effect of low-shear conditions.     

Decreased nocturnal surge of thyrotropin in nonthyroidal illness

To evaluate the regulation of TSH secretion in nonthyroidal illness (NTI) we studied the nocturnal TSH surge in 11 healthy controls and 26 NTI patients; none of the patients was on medication known to interfere with TSH secretion. The presence of a nocturnal TSH surge was defined as a mean nighttime TSH (the mean of 5 samples taken hourly from 0000-0400 h) significantly greater than the mean daytime TSH (the mean of 5 samples taken from 1500-1900 h). A nocturnal TSH surge was present in 11 of 26 NTI patients and in 11 of 11 controls (P less than 0.01). Both the absolute (0.3 +/- 0.1 vs. 1.0 +/- 0.2 mU/L; P less than 0.01) and relative (11 +/- 6% vs. 71 +/- 12%; P less than 0.001) nocturnal TSH surges were lower in NTI patients than in controls. NTI patients had lower plasma T3 (1.11 +/- 0.08 vs. 1.84 +/- 0.11 nmol/L; P less than 0.001) and higher plasma rT3 (0.81 +/- 0.24 vs. 0.23 +/- 0.01 nmol/L; P less than 0.001) concentrations than controls, but T4, FT4, and TSH values were similar in both groups. No differences were found between the 15 NTI patients without nocturnal TSH surge and the 11 patients with a nocturnal TSH surge in sex distribution, age, caloric intake, or plasma T4 and T3, but hospital mortality was slightly, although not significantly, higher in those with an absent nocturnal TSH surge. An absent nocturnal TSH surge occurred in 2 of 2 patients with a low TSH (less than 0.4 mU/L), in 11 of 20 patients with a normal TSH (0.4-4.0 mU/L), and in 2 of 4 patients with a high TSH (greater than 4.0 mU/L). Pituitary TSH responsiveness to TRH was similar in patients with or without a nocturnal TSH surge. We conclude that NTI is frequently associated with a decreased nocturnal TSH surge. This phenomenon is not related to ambient plasma T4, T3, or TSH concentrations or pituitary TSH responsiveness to TRH. A decreased nocturnal TSH surge appears to be one of the features of the sick euthyroid syndrome and is probably related to hypothalamic dysregulation.     

Studies on estrogen receptor in normal and cancerous human uterine endometrium by immunological methods

The presence of cytosol estrogen receptor (ER) and the ER of nuclear extracts in normal uterine endometrium and endometrial adenocarcinoma tissues were determined by radioreceptor assay (RRA) and enzyme immunoassay (EIA). In addition the intracellular localization of ER and tissue distribution of ER positive cells was demonstrated by immunocytochemical assay (ICA). The levels of cytosol ER measured by EIA and RRA had a significant correlation in normal endometrium (r = 0.90) (P less than 0.01) and endometrial adenocarcinoma (r = 0.96) (P less than 0.01) as well as in breast cancer (r = 0.93) (P less than 0.01). The ER measured by immunocytochemical method using the monoclonal anti-ER antibody obtained from breast cancer cells was applicable to the detection of the ER in uterine endometrial tissues. In endometrial adenocarcinoma, the levels of cytosol ER in G1 (Highly differentiated adenomatous carcinoma) tissues (187.6 +/- 189.0 fmoles/mg protein) were significantly higher than those in G2 (Moderately differentiated adenomatous carcinoma with partly solid areas) tissues (15.0 +/- 31.9 fmoles/mg protein) (P less than 0.05). The levels of cytosol ER peaked in the late follicular phase (432.0 fmoles/mg protein) and remained low in the other phases. Epithelial cells in the normal endometrium were stained uniformly by ICA, in contrast, ICA stained and non-stained cells existed concurrently in the same endometrial adenocarcinoma tissues. A similar finding was also shown in breast cancer tissues and may be related to the efficacy of anti-estrogenic drugs on the growth of whole cancer tissues.     

Hypercarbic ventilatory responses of infants at risk for SIDS

We examined the hypercarbic ventilatory responses (HVR) of 143 infants at risk for sudden infant death syndrome (SIDS) and 34 normal control infants. Sixty-five of the at-risk infants had experienced apparent life-threatening events (ALTE), and 78 were siblings of SIDS victims. Twenty-three (35%) of the ALTE infants experienced subsequent apnea; one died of SIDS. Seven (9%) of the SIDS siblings experienced subsequent apnea; two ultimately died of SIDS. In the HVR studies, we measured tidal volume (VT), minute ventilation (VE), frequency of breathing (f), and end-tidal PCO2 (PETCO2) at rest and while breathing 2% and 4% CO2. Mean HVR vales for the ALTE, sibling, and control groups were all similar. The mean HVR values for those at-risk infants who experienced subsequent apnea were not different from those who did not experience subsequent apnea. However, those infants experiencing subsequent apnea had higher mean VT/kg values (P less than 0.01) and lower mean PETCO2 values (P less than 0.001) than those who did not. The SIDS siblings had significantly lower resting VT/kg values than either the near-miss infants or normal controls (P less than 0.01). We did not find depressed HVR values in infants at risk for SIDS. On the contrary, those infants who experienced subsequent apnea had evidence suggesting relative hyperventilation. SIDS siblings had evidence suggesting relative hypoventilation. These findings are interesting and thought-provoking. However, HVR studies do not appear to be sensitive, specific, or appropriate for the general screening of infants at risk for SIDS.     

Increased IgA-producing cells in the blood of patients with active Henoch-Sch?nlein purpura

Peripheral blood lymphocytes (PBL) producing IgA, IgM, and IgG, both spontaneously and after pokeweed mitogen stimulation in cell culture, were determined by a protein A hemolytic plaque assay in 20 children with active Henoch-Sch?nlein purpura (HSP), 42 with inactive disease, 22 normal controls of the same ages, and 18 children with upper respiratory tract infections (URTI). The geometric mean of circulating IgA-producing cells in active HSP (1,016 X divided by 1.55 cells/10(6) PBL) was increased when compared with the group with inactive disease (P less than 0.001), normal controls (P less than 0.001), and children with URTI (542 X divided by 2.03 cells/10(6) PBL, P less than 0.05). The number of circulating IgM-producing cells was slightly increased in active HSP (260 X divided by 2.65 cells/10(6) PBL) and URTI (256 X divided by 3.16 cells/10(6) PBL). Both values were higher than those found in the group with inactive disease (113 X divided by 2.26 cells/10(6) PBL, P less than 0.01). There were no significant differences among the 4 groups in the number of circulating IgG-producing cells. The number of cells producing each type of immunoglobulin after in vitro stimulation with pokeweed mitogen was similar in patients with active HSP, normal controls, and the group with inactive disease. These data demonstrate a selective increase in the number of circulating IgA-producing cells only during disease activity, and add further support to a possible pathogenic role of this immunoglobulin in HSP.     

Comparison of N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase activities for evaluation of microangiopathy in diabetes mellitus

The activities of urinary N-acetyl-beta-D-glucosaminidase (NAG) and alanine aminopeptidase (AAP) were measured in 207 diabetic patients and 57 healthy controls, and the relationship of these enzymes to different stages of diabetic microangiopathy was studied. Diabetics with clinical proteinuria had higher urinary NAG and AAP (17.7 +/- 1.9 and 42.8 +/- 4.9 U/g creatinine, mean +/- SE, respectively) than healthy controls (1.8 +/- 0.1 and 10.0 +/- 0.4) or diabetics without proteinuria. Among diabetics without proteinuria, NAG excretion in those with retinopathy was slightly higher than in those without (6.4 +/- 0.5 v 5.4 +/- 0.4), and AAP in those with retinopathy was significantly higher than in those without (23.0 +/- 1.5 v 17.4 +/- 0.8, P less than 0.01). Urinary albumin measured by radioimmunoassay and lysozyme in diabetics with retinopathy but without proteinuria was higher than those without retinopathy (P less than 0.001 and P less than 0.01). The increase in albumin was the greatest in diabetics with long duration of the disease (greater than or equal to 8 years); however, NAG and AAP increased more significantly in those with high hemoglobin A1c than in patients with long duration.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of retinoic acid on cell proliferation kinetics and retinoic acid receptor expression of colorectal mucosa

AIM: To investigate the effect of retinoic acid (RA) on cell proliferation kinetics and retinoic acid receptor (RAR)expression of colorectal mucosa.METHODS:One hundred sixty healthy male Wistar rats were randomly divided into 4 groups. Rats in groups Ⅰ and Ⅱ were subcutaneously injected with dimethylhydrazine (DMH) (20 mg/kg, once a week,) for 7 to 13 weeks, while groups Ⅲ and Ⅳ were injected with normal saline. Rats in groups Ⅱ and Ⅲ were also treated with RA (50 mg/kg,every day, orally) from 7th to 15th week, thus group Ⅳ was used as a control. The rats were killed in different batches.The expressions of proliferating cell nuclear antigen (PCNA),nucleolar organizer region-associated protein (AgNOR) and RAR were detected.RESULTS: The incidence of colorectal carcinoma was different between groupsⅠ(100 %) and Ⅱ (15 %) (P＜0.01).The PCNA indices and mean AgNOR count in group Ⅱ were significantly lower than those in group Ⅰ(F=5.418 and 4.243,P＜0.01). The PCNA indices and mean AgNOR count in groups Ⅰ and Ⅱ were significantly higher than those in the groups Ⅲ and Ⅳ (in which carcinogen was not used) (F=5.927and 4.348, P＜0.01). There was a tendency in group Ⅰ that the longer the induction with DMH the higher PCNA index and AgNOR count expressed (F=7.634 and 6.826, P＜0.05).However, there was no such tendency in groups Ⅱ, Ⅲ and Ⅳ(F=1.662 and 1.984, P＞0.05). The levels of RAR in normal and cancerous tissues in groups treated with RA were significantly higher than those in groups not treated with RA (F=6.343 and 6.024, P＜0.05).CONCLUSION: RA decreases the incidence of colorectal carcinoma induced by DMH. Coiorectal cancer tissue is associated with abnormal expression of PCNA, AgNOR and RAR. RA inhibits the expression of PCNA and AgNOR, and increases RAR concentration in colorectal tissues.