Generation of two murine monoclonal antibodies that can discriminate N-glycolyl and N-acetyl neuraminic acid residues of GM2 gangliosides.

Since the preliminary analyses of the glycolipids of small cell carcinomas of the lung showed an increase of GM2 ganglioside, we generated new murine monoclonal antibodies directed to GM2 to identify the molecular species of the glycolipid. The monoclonal antibodies MK2-34 and MK1-16 (both IgM), which specifically detect N-glycolyl GM2 and N-acetyl GM2, respectively, were generated by immunizing mice with liposomes containing monophosphoryl lipid A, trehalose dimycolate, and the antigenic ganglioside. Among the glycolipid preparations extracted from the cancer tissues of 39 patients with lung cancer, a significant amount of N-acetyl GM2 was detected with MK1-16 antibody in 70% of the squamous cell carcinoma cases, 50% of the lung adenocarcinoma cases, 33% of the large cell carcinoma cases, and 100% of the cases of small cell carcinoma of the lung. On the other hand, N-glycolyl GM2 which was defined by the monoclonal MK2-34 was not found in any of the glycolipid fractions prepared from the lung cancer tissues examined in this study. Immunohistochemical studies of the lung cancer tissues with the MK1-16 antibody showed that the N-acetyl GM2 was present not only in small cell carcinoma tissues as one of the antigens related to tumors of neuroectodermal origin, but also in the squamous cell carcinoma and adenocarcinoma of the lung with a comparable frequency. The appearance of the N-acetyl GM2 antigen correlated well with the degree of differentiation of the cancer cells in patients with squamous cell carcinoma and adenocarcinoma of the lung.

Shh and Ptc are associated with taste bud maintenance in the adult mouse.

In mammals, taste receptor cells are organized into taste buds on tongue. Taste buds are trophically maintained by taste neurons and under continuous renewal, even in adults. We found that the receptor for Sonic hedgehog (Shh), Patched1 (Ptc), was expressed around taste buds where cells were proliferating, and that Shh was expressed within basal cells of taste buds. Denervation caused the loss of Shh and Ptc expression before the degeneration of taste buds.

Increased expression of endothelin B receptor mRNA following subarachnoid hemorrhage in monkeys.

These studies tested the hypothesis that the cerebral vasospasm that follows subarachnoid hemorrhage (SAH) is due to alterations in endothelin (ET) and ET receptor expression. Eight monkeys underwent cerebral angiography and induction of SAH. Angiography was repeated 7 days later to confirm the presence of cerebral vasospasm, and animals were killed. RNA was isolated from right (vasospastic) and left (control) side middle cerebral arteries and surrounding cerebral cortex. The levels of prepro (PP) ET-1 (ppET-1) and ppET-3 and ETA and ETB receptor MRNAs were determined using a quantitative reverse transcriptase polymerase chain reaction-based assay. ET-1 peptide was also measured in CSF at baseline and after 7 days. Specific agonist binding to ETA and ETB receptors in both middle cerebral arteries and in surrounding brain cortex was measured in three animals by autoradiographic binding assays. Levels of ETB receptor mRNA were 3.4 +/- 2.2-fold higher in the right than in the left cerebral arteries (p < 0.01). There were no significant differences in the levels of ppET-1, ppET-3, or ETA receptor mRNA in cerebral arteries. ET-1 peptide was not elevated in CSF. Levels of ETA and ETB receptor mRNAs were 2.6 +/ 1.1- and 2.1 +/ 1.3-fold higher, respectively, in the right than in the left cerebral cortex, while the level of ppET-3 mRNA was 2.1 +/- 1.0-fold lower. There were no differences in ppET-1 mRNA levels between right and left cerebral cortex. Binding to ETA and ETB receptors in cerebral arteries and cortex did not differ significantly between right and left sides. These results do not support the hypothesis that overexpression of ET-1 is principal cause of vasospasm, but rather they suggest that SAH causes complex changes in the ET system that together are responsible for the cellular response to SAH.

p53 gene mutation in N-butyl-N-(4-hydroxybutyl)nitrosamine-induced urinary bladder tumors and N-methyl-N-nitrosourea-induced colon tumors of rats.

We analyzed p53 mutations in 17 N-butyl-N-(4-hydroxybutyl) nitrosamine-induced bladder transitional cell carcinomas (TCCs) with or without areas of squamous cell carcinoma (SCC) of Long-Evans Cinnamon (LEC) and F344 rats, and in 7 N-methyl-N-nitrosourea-induced colon adenocarcinomas of LEC rats by polymerase chain reaction-single strand conformation polymorphism analysis and DNA sequencing. Of these bladder tumors, one TCC with moderately differentiated SCC had a T to G transversion mutation at codon 141, leading to a Val to Gly amino acid change. No p53 mutation was found in colon adenocarcinomas. Thus a p53 gene mutation seems infrequent in these rat bladder and colon carcinogenesis models even in the late stage.

Change in the Triglyceride Level in Sea Urchin Eggs and Embryos During Early Development: (sea urchin egg/triglycerides/lipid metabolism/early development).

Triglycerides in the embryos of the sea urchin, Anthocidaris crassispina, analyzed by gas-liquid chromatography, distributed in a range of carbon numbers between 42 and 58 in the sum of three fatty acid residues. During the development until gastrulation, the levels of triglycerides with 48, 56 and 58 carbon numbers decreased at constant rates and the levels of the others decreased at specific stages different with one another, respectively. Thereafter, the amounts of all triglycerides decreased simultaneously. The amount of oxygen consumed in the embryos is enough for the oxidation of mobilized triglycerides during post-hatching period but is not during pre-hatching period. The levels of neutral glycerides increased gradually during pre-hatching period and thereafter decreased. The fatty acid level also increased during pre-hatching and post-hatching period. These suggest that the cleavage of triglycerides and the oxidation of their cleavage-products occur during whole span of early development. During pre-hatching period, the break down of triglycerides is probably higher in its rate than the rate of their oxidation, resulting in the increase in the levels of neutral glycerides, as well as fatty acids.

Stimulation of protein synthesis in round spermatids from rat testes by lactate. II. Role of adenosine triphosphate (ATP).

The stimulatory effects of glucose and lactate on protein synthesis by round spermatids (steps 1-8) were further studied. When the cells were incubated with lactate, the response of protein synthesis in round spermatids was closely related to the intracellular level of ATP. The ATP level in spermatids increased to 3.13 +/- 0.20 nmol/10(6) cells from 0.37 +/- 0.02 nmol/10(6) cells after incubation of the cells at 34 degrees C for 60 min in the presence of lactate (20 mM). However, the ATP level fell rapidly to an undetectable level (less than 0.02 nmol/10(6) cells) during incubation for 30 min at 34 degrees C without lactate. The ATP level and the rate of protein synthesis in spermatids increased rapidly when lactate (20 mM) was added to the control cells during incubation. It was also found that incorporation of 32P into ATP was increased by treatment with lactate (20 mM), but glucose (10 mM) had no effect on 32P incorporation into ATP. When the rates of utilization of glucose and lactate by spermatids were examined, using 14C-labeled glucose and lactate, the rate of utilization of lactate was faster than that of glucose. These results suggest that the ATP is probably a major factor in the stimulation of protein synthesis in round spermatids.

Inhibition by palmitoyl CoA of dynein ATPase from sea urchin spermatozoa.

ATPase of 14S dynein, extracted from spermatozoa of the sea urchin, Hemicentrotus pulcherrimus, and partially purified by sucrose density gradient centrifugation, was inhibited non-competitively by palmitoyl CoA at concentrations higher than 20 microns, and was stimulated at concentrations between 2 microns and 10 microns. The effects of palmitoyl CoA on dynein ATPase were reversed by bovine serum albumin (1 mg/ml) and spermine (0.1 and 1 mM). Myristoyl CoA exerted effects similar to those of palmitoyl CoA. Short chain fatty acyl CoAs, such as butyryl CoA, propionyl CoA and acetyl CoA, CoA, Na-palmitate, Na-myristate, and palmitoyl carnitine had hardly any effect on dynein ATPase. Palmitoyl CoA failed to inhibit purified CF1 ATPase from chloroplasts of spinach, ATPase of rat liver mitochondria and alkaline phosphatase from calf intestine.

Stimulation of protein synthesis in round spermatids from rat testes by lactate.

Lactate markedly increased the rate of [3H]leucine incorporation into the protein of isolated round spermatids (steps 1-8) from rat testes. Four kinds of hexoses, glucose, fructose, galactose, and monnose, also stimulated [3H]leucine incorporation, but to much lesser extents than lactate. Ribose had no effect. The glucose-induced stimulation of protein synthesis was entirely suppressed by iodoacetate and NaF, whereas iodoacetate and NaF were without effect on the lactate-induced increase in protein synthesis. Lactate stimulated both protein synthesis and ATP production in the spermatids. However, both of these stimulatory effects of lactate were completely blocked by DNP and rotenone. Rotenone entirely blocked oxygen consumption, as expected, whilst DNP enhanced it additively with lactate. Moreover, lactate was without influence on either transport of alpha-[3H]AIB into spermatids or incorporation of [3H]leucine into protein of a cell-free system of spermatids. These findings suggest that lactate may increase the protein synthesis of spermatids in the same fashion as glucose, and that the effect of lactate in increasing the level of ATP during incubation in vitro may be a major factor in the mechanism of stimulation of protein synthesis in the spermatids.

Purification and characterization of two Ca(2+)-dependent lectins from coelomic plasma of sea cucumber, Stichopus japonicus.

Two structurally distinct lectins were purified from the coelomic plasma of holothurian, Stichopus japonicus, by affinity chromatography on a porcine stomach mucin-conjugated agarose column, gel filtration on a Superose 6 column, and ion-exchange chromatography on a HiTrap Q-FPLC. The two lectins showed apparent molecular masses of about 400 kDa (SPL-1) and 60 kDa (SPL-2) on gel filtration, but about 17 kDa on SDS-PAGE under reducing conditions. Both lectins showed hemagglutination activity toward rabbit erythrocytes in the presence of Ca2+ ions. The N-terminal amino acid sequences were highly homologous to but distinct from those of a Ca(2+)-dependent (C-type) lectin named SJL-I purified from the same species. In addition to porcine stomach mucin, the hemagglutination activity of SPL-1 was strongly inhibited by uronic acids such as galacturonic acid, and glucuronic acid, while the activity of SPL-2 was inhibited by GalNAc and galactosides. Both lectins were adsorbed on clotted coelomocytes in the presence of Ca2+ but not in the presence of inhibitory sugars or EGTA, suggesting the presence of an endogenous carbohydrate ligand(s) for plasma C-type lectins in the clot. However, coelomocyte clotting occurred normally even in the presence of inhibitory sugars, but was strongly inhibited by synthetic GRGDSP peptide or EGTA, suggesting the participation of integrin but not the lectin-carbohydrate interaction in the clotting events.

Effects of deoxycholic acid and its epimers on lipid peroxidation in isolated rat hepatocytes.

We studied the effects of deoxycholic acid and its three epimers with beta-hydroxyl groups (3alpha,12beta-, 3beta,12alpha-, and 3beta,12beta-dihydroxy-5beta-cholan-24-oic acids), which were hydrophilic and less cytotoxic, on lipid peroxidation to elucidate the relationship between structural features of bile acids and their effect on lipid peroxidation. Taurodeoxycholate markedly increased the production of thiobarbituric acid-reactive substances, end products of lipid peroxidation, in isolated rat hepatocytes, whereas epimers of taurodeoxycholate did not. Deoxycholic acid inhibited mitochondrial NADH dehydrogenase and NADH:ferricytochrome c oxidoreductase activities, leading to free radical generation, whereas epimers of deoxycholic acid had no effect on mitochondrial enzymes. These findings suggested that hydrophobic bile acids cause lipid peroxidation by impairment of mitochondrial function, leading to the generation of free radicals; and epimerization of alpha-hydroxyl groups in the steroid nucleus to beta-hydroxyl groups results in a decrease of the toxic effects of deoxycholic acid on lipid peroxidation.

Cytokines induce thymidine phosphorylase expression in tumor cells and make them more susceptible to 5'-deoxy-5-fluorouridine.

The present study shows that various cytokines such as tumor necrosis factor (TNF alpha), interleukin-1 alpha (IL-1 alpha), and interferon-gamma (IFN gamma) make tumor cells much more susceptible to the cytostatic 5'-deoxy-5-fluorouridine (5'-dFUrd) than to 5-fluorouracil (5-FUra) and other cytostatics. These three cytokines increased the susceptibility of human cancer cell lines (COLO201, MKN45 and WiDr) but did not affect that of normal fibroblast WI38 cells. The cytokine mixture induced a 50-fold increase in the susceptibility of COLO201 to 5'-dFUrd, whereas a 12-fold increase and a less than 5-fold enhancement in the susceptibility to 5-FUra and other cytostatics, respectively, were observed. The increased susceptibility would be a result of the induction of thymidine phosphorylase (TdR Pase), which is the essential enzyme for the conversion of 5'-dFUrd to 5-FUra. The cytokine mixture increased TdR Pase activity by up to 47 times and greatly induced its mRNA expression in the cancer cell lines. These results suggest that the therapeutic benefit of 5'-dFUrd would be improved by its use in combination with the cytokines.

Malignant schwannoma of the esophagus with lymph node metastasis: literature review of schwannoma of the esophagus.

An extremely rare case of malignant schwannoma of the esophagus with lymph node metastasis is reported. A 49-year-old woman was found to have an abnormal shadow on a chest X-ray film taken during an annual checkup. Upper gastrointestinal series showed extrinsic pressure on the middle thoracic esophagus, without a mucosal lesion. An exploratory operation was performed, with a tentative diagnosis of esophageal leiomyoma. The tumor was enucleated with part of the esophageal mucosa, and a few enlarged lymph nodes around the tumor were dissected. The resected tumor was an elastic firm mass, measuring 8.2 x 5.8 x 3.7 cm, and had a smooth surface. Histological examination of the tumor revealed the proliferation of spindle-shaped cells with chromatin-rich nuclei. The nuclei were variable in size and showed remarkable atypia. A paraesophageal lymph node had same findings as the main tumor. Immunohistochemically, the tumor cells were diffusely positive for S-100 protein and neuron-specific enolase. The pathological diagnosis of this tumor was malignant esophageal schwannoma with lymph node metastasis. Esophageal schwannoma is extremely rare. We reviewed the literature on 19 cases of esophageal schwannoma, including that in our patient. The majority of the tumors were benign. Only three cases of schwannoma were malignant, and this is the first reported case of malignant schwannoma with lymph node metastasis.

Relationship between abnormalities of coagulation and fibrinolysis and postoperative intracranial hemorrhage in head injury.

Abnormalities of coagulation and fibrinolysis in 12 head-injured patients were studied in early (within 24 hours of onset) and late (10th to 17th day after onset) stages. alpha 2 Plasmin inhibitor (alpha 2PI), antithrombin III (ATIII), and fibrinopeptide A (FPA) and B beta 15-42 (FPB beta) were measured in particular, in addition to the usual tests (platelet count (PLT), prothrombin time (PT), partial thromboplastin time, fibrinogen, and fibrin/fibrinogen degradation products (FDP)). alpha 2PI was abnormally lower, and FPA and FPB beta were much higher; fibrinogen and ATIII were moderately lower in the early stage than in the late stage in 6 head-injured patients with postoperative intracranial hemorrhage. alpha 2PI, ATIII, and fibrinogen were moderately lower and FPA was moderately higher in the early stage than in the late stage in 6 head-injured patients without postoperative intracranial hemorrhage. PLT and fibrinogen were lower, alpha 2PI was much lower, and FPA was much higher in the 6 patients with postoperative intracranial hemorrhage than in the 6 patients without postoperative intracranial hemorrhage. One patient with acute epidural and subdural hematomas had recurrent postoperative intracerebral hematoma twice. This recurrent hemorrhage was due to disseminated intravascular coagulation (DIC) caused by primary brain damage and was associated with extremely high FPA and FPB beta levels and abnormally low alpha 2PI and PLT. Fresh-frozen plasma and intravenous low-dose heparin were administered after the two recurrent hemorrhages, after which FPA and FPB beta normalized immediately, although other screening tests showed only gradual improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

False localization of rupture site in patients with multiple cerebral aneurysms and subarachnoid hemorrhage.

OBJECTIVE: Patients with subarachnoid hemorrhage and multiple intracranial aneurysms present a unique challenge to the neurosurgeon. Unless all aneurysms can be clipped through a single craniotomy, the surgeon must accurately determine which aneurysm has ruptured. Misjudgment may result in disastrous postoperative rebleeding from the untreated but true ruptured lesion. We assessed the risk of false localization of the rupture site and subsequent rebleeding and documented the problems in predicting the true rupture site when patients have multiple intracranial aneurysms. METHOD: We reviewed the records of a consecutive series of 93 patients treated over a period of 12 years who presented with their first subarachnoid hemorrhage and who had multiple intracranial aneurysms. The rupture site was determined on the basis of computed tomographic and angiographic findings, and the supposed ruptured aneurysm was clipped within 2 days of hemorrhage in each patient. Additional aneurysms that could not be accessed in the same surgical session were operated on at a later stage. All patients' records were reviewed, and all computed tomographic scans and angiograms, including repeat studies performed in some patients, were retrospectively reevaluated by the authors, who had no knowledge of the patients' clinical information. RESULTS: The location of the aneurysm that ruptured was verified at the time of surgery or during the autopsy in 76 patients (82%). The aneurysm that ruptured was the one predicted as ruptured by the surgeon before surgery in 69 patients (91%) and in retrospect in 72 patients (95%). Five of the 6 patients in whom the ruptured aneurysm was not correctly identified were thought to have only a single aneurysm. Four patients rebled after surgery, and 2 patients died as a result of the rebleeding. CONCLUSION: In the reported series, the most common cause of rebleeding soon after aneurysm surgery was failure to obliterate the ruptured aneurysm, usually because it was missed on the initial angiogram. The results support not only meticulous radiological investigation of all intracranial arteries before surgery but also thorough surgical inspection of the target aneurysm in all cases of subarachnoid hemorrhage even after one candidate lesion has been discovered.

Dysautoregulation in patients with ruptured aneurysms: cerebral blood flow measurements obtained during surgery by a temperature-controlled thermoelectrical method.

We used a temperature-controlled thermoelectrical method, induced hypotension, and CO2 inhalation to obtain cerebral blood flow (CBF) measurements during surgery for investigation of the state of brain vasoreactivity in subarachnoid hemorrhage patients. The study included 11 patients who underwent 12 operations for ruptured intracranial aneurysms. The CBF data were analyzed to investigate the neurological state, presence or nonpresence of vasospasm, timing of the operation, and outcome of each patient. Autoregulation disturbance, in terms of reaction to hypotension, was consistently seen in patients in poor neurological states, and this disturbance was correlated with poor outcome. This simple monitoring system, used during emergency operations for ruptured aneurysm, was useful in predicting outcome.

Changes in endothelial nitric oxide synthase mRNA during vasospasm after subarachnoid hemorrhage in monkeys.

OBJECTIVE: We attempt to determine whether changes in messenger ribonucleic acid (mRNA) for nitric oxide synthase (NOS) and soluble guanylate cyclase, enzymes that mediate endothelium-dependent vasodilation in cerebral arteries, occur after subarachnoid hemorrhage (SAH) in monkeys. METHODS: Baseline cerebral angiograms were obtained, and right-sided SAH was induced by microsurgically placing autologous blood clot against the right anterior circle of Willis in seven monkeys. Seven days later, angiographic studies were repeated and the animals were killed. Right (vasospastic) and left (control) middle cerebral arteries and underlying cortex were removed. The competitive reverse transcriptase polymerase chain reaction was used to quantify mRNA for soluble guanylate cyclase and two isoforms of constitutive NOS in these tissues. RESULTS: Comparison of angiograms at baseline and after 7 days showed a 41 +/- 7% (mean +/- standard error of the mean, P < 0.05, Wilcoxon test) decrease in diameter of the right middle cerebral artery. After the animals were killed, comparison of right and left middle cerebral arteries showed a 56 +/- 11% decrease (P < 0.005, paired t test) in endothelial NOS mRNA. There was a 142 +/- 39% (P < 0.05) increase in right cortex endothelial NOS mRNA compared to the left cortex. There were no significant differences between right and left sides in mRNAs for soluble guanylate cyclase or brain NOS. CONCLUSION: Decreased endothelial NOS mRNA in cerebral arteries 7 days after SAH may be caused by endothelial cell damage and could contribute to vasospasm after SAH. Increased endothelial NOS in brain tissue may reflect a compensatory vasodilator mechanism of the brain against the cerebral ischemia associated with vasospasm and SAH.

Metabolic and hemodynamic aspects of peritumoral low-density areas in human brain tumor.

With the use of positron emission tomography, regional cerebral blood flow, oxygen utilization, and glucose utilization were measured in the peritumoral low-density areas on x-ray computed tomographic images in 23 patients with supratentorial brain tumors: 7 meningiomas, 11 malignant gliomas, and 5 metastatic brain tumors. Findings on positron emission tomography in these areas revealed characteristic patterns associated with the types of tumor and the degree of mass effect. It is likely that two different types of pathophysiological states exist in "peritumoral edema": 1) primary ischemia caused by mechanical compression by the tumor mass in meningiomas; and 2) primary metabolic suppression (mainly in oxygen metabolism) in malignant brain tumors.

Positron emission tomographic studies on cerebral hemodynamics in patients with cerebral contusion.

Positron emission tomography is currently one of the most useful methods for measurements of cerebral hemodynamics and oxygen metabolism, because it facilitates accurate analysis of the local cerebral circulation in three-dimensional quantitative images. In this study, we performed positron emission tomography studies to measure cerebral circulation in a total of 11 patients who sustained head injuries with contusion. Several parameters were measured including regional cerebral blood flow, regional cerebral blood volume, permeability, and regional cerebral metabolic rate for oxygen. Data from brains both with and without contusion were analyzed for chronological changes, in the subacute stage from the 8th to 29th day and in the chronic stage until 360 days after the injury and compared with similar data in a group of normal subjects. It was concluded that in the subacute stage, regional cerebral blood flow decreased (26 +/- 7 and 39 +/- 10 ml/100 g/min) and regional cerebral blood volume increased (5.6 +/- 1.8 and 5.4 +/- 0.9 ml/100 g) both in areas of cerebral contusion and in areas remote from cerebral contusion and that permeability increased in areas of contusion but not in remote brain areas. In the chronic stage, these parameters showed a tendency for recovery.

Prospective, randomized, double-blind trial of BQ-123 and bosentan for prevention of vasospasm following subarachnoid hemorrhage in monkeys.

Thirty-one monkeys were randomly divided into three groups to undergo baseline cerebral angiography followed by induction of subarachnoid hemorrhage by placement of autologous blood clot along the right-sided arteries of the anterior circle of Willis (Day 0). The monkeys were then given drug vehicle or one of two endothelin (ET) antagonists, BQ-123 (6 mg/kg/day) or bosentan (5 mg/kg/day) intracisternally. The BQ-123 was administered by continuous infusion from a subcutaneous pump and the bosentan was given by twice-daily injections into an Ommaya reservoir in the subcutaneous space with a catheter along the right middle cerebral artery (MCA). Seven days later (Day 7), angiography was repeated and the animals were killed. Comparison of arterial diameters shown on angiograms between Day 0 and Day 7 groups given placebo and bosentan showed significant reductions in the diameters of the right intradural internal carotid (28% +/- 6% and 30% +/- 6%, respectively, paired t-test, p < 0.05), anterior cerebral artery (29% +/- 8% and 32% +/- 6% respectively +/- 6%, respectively) and MCA (34% +/- 6% and 46% +/- 4%, respectively). Animals injected with BQ-123 had significant narrowing of the right extradural internal carotid artery (7% +/- 6%) and the basilar artery (11% +/- 3%), but not of the right MCA. Comparison of arterial diameters between groups at Day 7 showed significant variance in the right extradural internal carotid, both intradural internal carotid, right middle cerebral, and left anterior cerebral arteries; the animals injected with BQ-123 developed significantly less arterial narrowing these those receiving bosentan and placebo. Bosentan was not detected in the cerebrospinal fluid aspirated from the cisterna magna on Day 7, whereas BQ-123 was detected in two animals. We can infer from these results that BQ-123 prevents vasospasm following subarachnoid hemorrhage in monkeys, that further investigations of ET antagonists are warranted, and that ET may be an important pathophysiological mediator of vasospasm. The lack of efficacy of bosentan may be related to inadequate cerebrospinal fluid levels obtained by administration twice-daily through an Ommaya reservoir.

Bile acid sulfonate and 7-alkylated bile acid analogs: effect on intestinal absorption of taurocholate and cholesterol 7alpha-hydroxylase activity in cultured rat hepatocytes.

The effects of sulfonate analogs of cholic (C), chenodeoxycholic (CDC), and ursodeoxycholic acid (UDC) and three 7-alkylated CDCs--7-methyl-, 7-ethyl-, and 7-propyl-CDCs--on taurocholate absorption from rat terminal ileum in situ and on cholesterol 7alpha-hydroxylase activity in primary culture of the rat liver were investigated. The sulfonate analogs of two dihydroxy bile acids CDC and UDC, but not C, significantly decreased the absorption of taurocholate. Taurine conjugates of 7-alkylated CDC slightly decreased the taurocholate absorption, and tauro-7-propyl-CDC significantly suppressed the absorption. Although the sulfonate analogs of C and CDC reduced cholesterol 7alpha-hydroxylase activity by 40% and 60% compared to control, UDC-sulfonate analog did not affect enzymatic activity. These results were consistent with those of the lead compounds, C, CDC, and UDC. The introduction of methyl group at C-7 position of CDC attenuated the reduction in cholesterol 7alpha-hydroxylase activity by CDC. However, elongation of the alkyl group resulted in an inhibitory effect. The present study revealed the following: 1) bile acid sulfonates act on cholesterol and bile acid metabolism in a similar manner as taurine conjugated bile acids; and 2) the biologic properties of CDC could be altered by the introduction of alkyl group at C-7 position.