Human beta-glucuronidase. Studies on the effects of pH and bile acids in regard to its role in the pathogenesis of cholelithiasis.

Human bile contains a considerable amount of endogenous beta-glucuronidase. The effects of pH and bile acids on its activity have been studied in regard to its role in the pathogenesis of cholelithiasis. beta-Glucuronidase, purified from human liver to homogeneity, was structurally stable between pH 4 and 10, but was active only over a much narrower range of pH, with a pH optimum of 5.2. The inactivation below pH 4 was due to its irreversible denaturation, whereas the inactivation at higher pH was due to a true reversible pH effect on the enzyme velocity. Kinetic studies revealed that hydrogen ion acted as a substrate-directed activator of the free enzyme, but not the enzyme-substrate complex, with a molecular dissociation constant of 4 X 10(-6). The enzyme activity was not affected by unconjugated bile acids, primarily due to their extremely low water solubility. Conjugated bile acids, on the other hand, exerted heterogeneous and pH-dependent effects on the enzyme. At pH 5.2, taurocholic acid and glycocholic acid were substrate-directed activators of the enzyme; taurochenodeoxycholic acid and taurodeoxycholic acid, competitive inhibitors; and glycochenodeoxycholic acid and glycodeoxycholic acid, mixed inhibitors. At pH 7.0 all taurine and glycine conjugates behaved as substrate-directed activators. Though beta-glucuronidase activity at pH 7 was only 23% of its maximal activity at pH 5.2, conjugated bile acids tended to restore its activity to a certain extent at pH 7. Thus, endogenous beta-glucuronidase could play a significant role in pigment cholelithiasis.

Comparative studies on the effect of cholesterol feeding on biliary composition.

The gallbaldder or hepatic bile from six species of animals had a uniformly low cholesterol content far below its maximum solubility. Cholesterol feeding for more than 1 month had little effect on the biliary composition in chickens, rabbits, and rats, but selectively doubled the absolute and relative concentration of cholesterol in the biles of hamsters, and increased the cholesterol concentration to a level of its maximum solubility in gallbladder bile of ground squirrels and hepatic bile of prairie dogs. The gallbladder bile of prairie dogs reached the boundary of metastable supersaturation of cholesterol and subsequently developed cholesterol crystals and gallstones. A circadian change of the relative concentration of bile acid, cholesterol, and phospholipid in the hepatic bile of the rats with chronic biliary drainage was also observed as a consequence of cholesterol feeding.

Cholesterol contents of various tissues of chickens with exogenous or endogenous hypercholesteremia.

Cholesterol contents of 16 different tissues were determined in 12 normal roosters, 12 roosters with diet-induced, exogenous hypercholesteremia, 10 actively laying hens with minimal endogenous hypercholesteremia, and 12 nonlaying hens with hereditable extreme hyperlipidemia. The tissue cholesterol contents of the normal roosters were strikingly similar to that of the corresponding tissues of the mammals except for a low cholesterol content of the brain in chickens. The hypercholesteremia in the roosters fed a 2% cholesterol diet for 2 months was associated with an increase of cholesterol content in all tissues except the brain, muscle, and adipose tissue. The actively laying hens, on the other hand, had a decreased cholesterol content in most tissues, despite the persistence of a minimal hypercholesteremia for 18 months and significant aortic cholesterol accumulation with mild atherosclerosis. The nonlaying hens developed extreme hypercholesteremia and severe atherosclerosis but only a moderately expanded cholesterol pool in most tissues. The results indicated a remarkable difference in tissue response to diet-induced exogenous hypercholesteremia and endogenous hyperlipidemia associated with laying activity in chickens and the propensity of their aortas to accumulate excessive cholesterol in the presence of either endogenous or exogenous hyperlipidemia.

Cholesterol metabolism in patients with resection of ileum and proximal colon.

Compartmental analysis of the disappearance curve of serum cholesterol specific activity after an intravenous administration of a tracer does of cholesterol-4-14C was carried out in five patients with resection of the distal small intestine, cecum, and proximal colon. The data fit best a two compartment model in all five cases with the rapidly exchangeable pool of 16.6+/-3.2 g (mean +/- SD, 60% of the mean of 15 normal subjects) and the slowly exchangeable pool of 31.5 +/- 10.9 g (65%). The reduction of the pool sizes was associated with a shorter mean transit time of cholesterol, 22.15 +/- 8.07 days (40%) and increased turnover rate, 2.42 +/- 0.72g/ day (172%). Direct fecal analysis for the neutral sterols and bile acids derived from the exchangeable pool confirmed the turnover rate obtained from the compartmental analysis. The increased fecal excretion was mainly in the bile acid fraction. The study suggests that the ileal and proximal colon resection results in bile acid malabsorption which, in turn, increases hepatic cholesterol and bile acid synthesis. The synthetic rates, however, could not compensate totally for the excretory rate. Therefore, the pool size decreased to a new low steady state of equilibrium.

Intestinal regulation of hepatic cholesterol synthesis: an hypothesis.

The serum cholesterol level in man is predominantly dependent on the rate of endogenous synthesis. The liver is the main site of cholesterol synthesis and this activity is in turn intimately related to the ingestion of food. When no food is present in the intestine, as during periods of total parenteral nutrition, both normal individuals and patients with familiar hypercholesterolemia show a pronounced lowering of their serum cholesterol. The establishment of a portacaval shunt makes this a permanent change. This and other evidence lead us to postulate the existence of an intestinal factor capable of stimulating hepatic cholesterogenesis. The function of this factor would be to increase the synthesis of chol

Bile acid pool size in relation to functional status of gallbladder and biliary lipid composition in Chinese.

Bile acid pool size was measured in 10 Chinese without gallstones, 14 with pigment stones, and 10 with mixed stones by an isotope dilutin technique. Functional status of gallbladder was evaluated by intravenous cholecystogram and its gross appearance at surgery. Biliary lipid composition was also determined. The control subjects had a bile acid pool size comparable to that of Caucasians. Regardless of the nature of gallstones, bile acid pools of stone patients with functioning gallbladder were within normal range, whereas the pools of those with non- or poorly-functioning gallbladder diminished to about two-thirds of the control. Thus, the diminution of bile acid pool size was apparently the consquence of loss of storage function of gallbladder rather than the cause of production of lithogenic bile. The common bile duct bile obtained from stone patients with nonfunctioning gallbladder had a relatively high lithogenic index, at least partly related to its low total lipid concentration.

Neurologic, audiologic, and electrophysiologic sequelae of bilateral temporal lobe lesions.

A 67-year-old woman with demonstrated intact peripheral and brain-stem auditory pathways presented with sudden deafness secondary to sequential bilateral temporal lobe infarcts. Initial examination revealed no behavioral response to sounds and a mild Wernicke's aphasia. Hearing gradually returned but auditory agnosia persists. Changes seen on the computed tomographic scan and the middle latency auditory evoked response over a seven-month period were analyzed and suggest that the peak component of the middle latency response arises from Heschl's gyrus.

Chinese-white differences in the distribution of occlusive cerebrovascular disease.

The distribution of cerebrovascular lesions is affected by race. Blacks and Japanese have more intracranial occlusive cerebrovascular disease, while whites have more extracranial disease. Despite a high incidence of stroke in China, there are few formal studies of the distribution of vascular occlusive disease in Chinese populations. We compared clinical and angiographic features of 24 white and 24 Chinese patients with symptomatic occlusive cerebrovascular disease. In symptomatic vascular territories, whites had more severe (greater than or equal to 50% stenosis) extracranial lesions, while Chinese had more severe intracranial lesions. When we counted mild and severe lesions in a symptomatic territory, whites had more extracranial lesions while Chinese had more intracranial lesions. When we combined symptomatic and asymptomatic territories, whites had more extracranial lesions, while Chinese had more intracranial lesions. White patients reported more transient ischemic attacks. The distribution of lesions, however, was not explained by differences in incidence of transient ischemia, hypertension, diabetes, hypercholesterolemia, or ischemic heart disease between the groups. The preponderance of intracranial vascular lesions in Chinese patients is similar to that seen in blacks and Japanese. Racial differences in the occurrence of extracranial and intracranial lesions raise the possibility of a different underlying pathophysiology for the 2 locations.

Small cell carcinoma of the esophagus: evidence for a unified histogenesis.

Four cases of small cell carcinoma of the esophagus, histologically indistinguishable from oat cell carcinoma of the lung, were studied by electron microscopy. Three were composed largely of small cells with neurosecretory granules characteristic of APUD (amine precursor uptake and decarboxylation) cells. Two of these three cases also contained foci of squamous or glandular differentiation, or both. The fourth case was classified as reserve cell carcinoma with squamous differentiation, since the tumor cells were devoid of neurosecretory granules but contained desmosomes and bundles of intracytoplasmic tonofilaments. The evidence provided by these four cases and also by the 48 cases previously reported in the literature supports our hypothesis that a totipotent primitive cell serves as the common precursor for squamous cell, adeno-, and small cell carcinoma of the esophagus. The latter can be subdivided into oat cell and reserve cell carcinomas, both having the propensity for further squamous and glandular differentiation. The hypothesis can also be applied to lung cancer.

Chronic systemic Dacron and Teflon embolization of a Beall model 103 mitral valve prosthesis.

A case is presented of chronic systemic Dacron and Teflon embolism arising from a Beall Model 103 mitral valve prosthesis installed 11 years earlier. The emboli induced intense foreign body reaction resulting in numerous microgranulomas throughout the body. Multiple microinfarctions in the brain accounted for repeated episodes of transient ischemic attacks. Wearing of the prosthesis with consequent embolic complications seems to be the inevitable terminal fate of such early models of the Beall valve. Regular assessment of the functional status of such prostheses, particularly those in place for more than 5 years, is strongly recommended.

Bronchiectasis in patients with alpha 1-antitrypsin deficiency. A rare occurrence?

The chest radiographs and computed tomographic (CT) scans of seven patients with homozygous proteinase inhibitor phenotype Z (PiZZ) alpha 1-antitrypsin deficiency were reviewed. All patients except one showed severe emphysema with or without bullous change. Bronchiectasis was detected in three patients by CT but only in two patients by chest radiography. A young patient developed bronchiectasis before symptomatic emphysema. We stress that patients with PiZZ are susceptible to bronchiectasis, and the widespread use of CT should reveal its true incidence which might not be as low as generally believed.

Fluid bronchogram. A common finding in opacified lung requiring contrast medium administration for demonstration.

One example was selected to demonstrate the requirement of intravenous administration of contrast medium for visualization of the fluid bronchogram in opacified lung, as is the case in most patients. Another example was chosen to show that on rare occasions, a faint fluid bronchogram could be detected without contrast medium because of marked dilation of the bronchi. The mechanism for the computed tomographic demonstration of the fluid bronchogram and it significance were discussed.

Diverse roentgenographic manifestations of the rare pulmonary involvement in myeloma.

Roentgenographic manifestations of two cases of pulmonary involvement with myeloma were presented. One showed a nodular mass lesion extending from an extramedullary mediastinal plasmacytoma into the lung parenchyma while the other showed diffuse reticulonodular infiltrate by myeloma cells in association with alveolar septal amyloidosis. These two cases demonstrate the extreme variability of pulmonary involvement by myeloma, which can mimic a solitary tumor or an inflammatory infiltrate.

Pulmonary malacoplakia associated with Rhodococcus equi infection in a patient with AIDS.

An AIDS patient with a cavitary lung lesion was found to have pulmonary malacoplakia associated with Rhodococcus equi infection. The diagnosis was based on the typical histologic features of transbronchial biopsy and a positive bacterial culture. All 13 reported cases of AIDS patients with pulmonary malacoplakia were associated with R equi. The recognition of this unique entity is important because of its responsiveness to therapy.

Computed tomographic detection of cavitary lung lesion complicating use of flow-directed balloon-tipped catheter.

A classic case of Swan-Ganz catheter-induced pulmonary infection was studied with both conventional chest radiography and computed tomography (CT). Chest radiography initially showed a fan-shaped opacity in the right middle lobe which later became somewhat rounded with no discernible cavitation. However, a cavitary lung lesion with a bulls-eye appearance was clearly demonstrated by CT. We speculate that such a cavitary lung lesion might be quite common in catheter-induced pulmonary infarction when CT is widely applied to such cases.

Apical Pneumocystis carinii pneumonia in AIDS patients not receiving inhaled pentamidine prophylaxis.

Isolated apical Pneumocystis carinii pneumonia might develop in AIDS patients receiving aerosolized pentamidine prophylaxis. Demonstrated here are two cases of apical P carinii pneumonia occurring in patients not receiving inhaled pentamidine prophylaxis. Such isolated apical localization of P carinii should be differentiated from tuberculosis and fungal infection.

Unusual initial calcification of primary and metastatic seminomas. Detection by computed tomography.

Rare large ab initio calcifications of a primary mediastinal seminoma in a 16-year-old boy and of para-aortic nodal metastatic ovarian seminoma in a 14-year-old girl are demonstrated with CT but not with conventional radiography. They are most likely dystrophic calcifications because of the absence of other germ cell tumor components and infective granulomatous disease. Routine use of CT might detect more such calcifications in untreated seminoma.

Bochdalek hernia of diaphragm in the adult. Diagnosis by computed tomography.

Two cases of asymptomatic Bochdalek hernia in adults with identical roentgenographic findings are reported. Computed tomography (CT) in each case revealed a round mass with a low attenuation coefficient identical to that of adipose tissue, abutting the thoracic surface of the diaphragm and connecting with the subdiaphragmatic density through a diaphragmatic defect. A case of diaphragmatic lipoma was also presented for demonstration of the CT differentiation between lipoma and hernia of the diaphragm. The CT findings for a Bochdalek hernia are characteristic enough for making a definite diagnosis and render other diagnostic modalities unnecessary.

Squamous cell carcinoma of the uterine cervix. Patterns of thoracic metastases.

RATIONALE AND OBJECTIVES: Distant metastasis of cervical cancer, once considered rather uncommon, has become more common in recent years because of longer survival of the patients. The purpose of this study is to evaluate the radiographic patterns of its thoracic metastases correlating with the pathways of metastatic tumor spread. METHODS: The conventional radiographs (62 cases), thoracic computed tomography images (20 cases), and medical records of 62 patients with advanced squamous cell carcinoma of the uterine cervix with thoracic metastases who died of extensive disease and its complications during a recent 5-year period were reviewed retrospectively. RESULTS AND CONCLUSIONS: In addition to the most typical pattern of multiple pulmonary nodules (71%), mediastinal and hilar lymphadenopathy (32%) and pleural metastases (27%) were frequently observed. Rare findings included bone metastases (6%), endobronchial obstruction (5%), and lymphangitic carcinomatosis (3%). The mechanisms of metastasis in relation to the above manifestations are proposed.

Hormone-producing capabilities of renal cell carcinomas. Correlation with ultrastructural findings.

A retrospective study was conducted to evaluate ultrastructural aspects of hormone production by renal cell carcinomas. Fifteen renal cell carcinomas examined ultrastructurally were retrieved from the files. Six cases revealing abundant and diffusely distributed secretory granules in the neoplastic cells were found and correlated with clinical manifestations and laboratory findings. Five of these patients were hypercalcemic; the sixth patient was asymptomatic, and no abnormalities were detected in routine laboratory workup. Two additional cases showed focal aggregates of electron dense neurosecretory granules. These last 2 patients had no biochemical abnormalities and were entirely asymptomatic. The size and ultrastructural morphology of the cytoplasmic granules identified in the renal neoplasms were compared with the usual granular morphology associated with the specific hormones involved. Immunohistochemistry was used to confirm the parathormone hormone content of the granules in 7 of the 8 cases presented. The other case revealed granules with ultrastructural characteristics of prostaglandin granules.