[Effect and safety of Lasso suture hook in transvaginal sacrospinous ligament fixation].

To investigate the feasibility and safety of the Lasso suture hook in transvaginal sacrospinous ligament fixation, a total of 38 patients with vaginal vault prolapse at or above stage Ⅱ, and aged 46-75(62.7±12.5)years, who underwent transvaginal sacrospinous ligament fixation at the Second Affiliated Hospital of Soochow University from January 2018 to January 2021 were retrospectively analyzed. After complete exposure of the right sacrospinous ligament, the cervical/uterosacral ligament was sutured to the sacrospinous ligament using Lasso hook and polypropylene sutures. The completion rate of the operation, intraoperative complications, operation time, blood loss, and postoperative situations were observed, and the objective cure rate and subjective satisfaction were followed up. Transvaginal sacrospinous ligament fixation was successfully performed in all 38 patients using Lasso suture hooks. There were no bladder or rectum injuries during the operations, and no pelvic hematoma occurred. The operation time was 15-40 (24±9.5) min; the intraoperative bleeding was 20-60 (40±12.5) ml; the visual analogue scale(VAS)score was 3-5 (3.2±1.4) points on the first day of postoperative, and 2-4 (2.2±1.8) points on the third day of postoperative. No numbness or pain in buttocks and lower limbs after the operation. The 3-month follow-up results showed that the objective surgical success rate of the postoperative pelvic organ prolapse quantitation (POP-Q) score was 100% (38/38). The 1-year follow-up results showed that the objective surgical cure rate of postoperative POP-Q score was 92.1% (35/38). The score of Pelvic Floor Distress Inventory-Short Form 20 (PFDI-20)was 42-180(120.4±44.9)before operation and 8-75 (28.0±14.3) after operation(t=15.90, P<0.001); The score of Pelvic Floor Function Impact Questionnaire-Short Form7 (PFIQ-7) was 52-214(112.8±44.5)before operation and 5-29 (14.3±6.0) after operation (t=14.40, P<0.001), and the subjective satisfaction rate is 89.5% (34/38) conducted by Patient Global Impression of Improvement (PGI-I). Transvaginal sacrospinous ligament fixation with Lasso suture hook is simple, safe, and feasible.

[Application of transvaginal morcellation within disposable extraction bag with traction wire in laparoscopic myomectomy].

To investigate the effect and clinical value of morcellation within disposable extraction bag with traction wire through posterior vaginal fornix in laparoscopic myomectomy. A total of 42 patients who underwent laparoscopic myomectomy and morcellation through posterior vaginal fornix in the Second Affiliated Hospital of Soochow University from June 2019 to June 2021 were retrospectively analyzed. After the uterine fibroids were removed, the fibroids were placed into the extraction bag, tightening the mouth of the bag with a traction wire to make it airtight. After the uterine incisions were sutured, the extraction bag was taken out through the posterior fornix of the vagina, and the fibroids were broken up with a scalpel in the bag and taken out. The fibroids were successfully removed from the 42 patients through the posterior fornix of the vagina. There were no fibroids fragments found in the peritoneal cavity and vagina. There were no malignant cells or spindle cells found in the peritoneal lavage cytology before and after the operation. After filling the extraction bags with water, there was no leakage. There were 39 cases of uterine leiomyoma, 2 cases of cell-rich uterine leiomyoma, and 1 case of smooth muscle tumor of uncertain malignant potential in postoperative pathological diagnosis. Forty-two cases were followed up for 6 to 30 months. The posterior vaginal fornix incision healed well and there was no recurrence or metastasis. Morcellation within disposable extraction bag with traction wire through posterior vaginal fornix in laparoscopic myomectomy is a safe and feasible method for fibroids removal, which may help to reduce the dissemination of iatrogenic tumors.

[Application of morcellation through small umbilical incision in laparoscopic myomectomy].

To investigate the effect of morcellation through small umbilical incision in laparoscopic myomectomy. A total of 67 patients who underwent laparoscopic myomectomy in the Second Affiliated Hospital of Soochow University from February 2018 to October 2019 were retrospectively analyzed. Fibroids were loaded into disposable laparoscopic collection bags and then retrieved through small umbilical incision. The operation of all 67 patients were successfully completed. There were no leakage of collection bags or fibroids fragments found in the peritoneal cavity and the puncture holes. There were no spindle cells or malignant cells found in the peritoneal lavage cytology before and after operation. There were 64 cases of uterine leiomyoma, 2 cases of cellular leiomyoma, and 1 case of leiomyoma with cystic degeneration in postoperative pathological diagnosis. The weight of fibroid was 110-420 (227±106) g; the operation time was 58-274 (107±45) min; the time for retrieving specimen was 8-27 (18.4±10.6) min; the time for suturing umbilical incision was 4-11 (7.8±4.6) min; the score of pain numeric rating scale (NRS) at 24 h, 48 h, 72 h after operation was 4-6 (4.5±1.2) points, 2-4 (2.7±1.1) points, and 1-2 (1.6±0.4) points, respectively; the Hollander wound evaluation score was 3-5 (4.6±0.5) points. The umbilical incisions looked and healed well after operation. Morcellation through small umbilical incision in laparoscopic myomectomy is a safe and practical method of specimen removal, which may help to reduce the dissemination of iatrogenic tumors.

FABP4 inhibitor attenuates inflammation and endoplasmic reticulum stress of islet in leptin receptor knockout rats.

OBJECTIVE: Metabolic syndrome is characterized by abdominal obesity, hypertriglyceridemia and hyperglycemia. Fatty acid binding protein 4 (FABP4), as a member of intracellular lipid chaperones, is not only engaged in lipid transport but involved in inflammation and insulin resistance. The present study was to investigate the effects of BMS309403, a specific FABP4 inhibitor, on metabolic syndrome and its possible molecular mechanisms in islets. MATERIALS AND METHODS: Leptin receptor knockout (Lepr-/-) rat, a novel and representative animal model of metabolic syndrome, was adopted in this study. Lepr-/- male rats and their wild littermates were grouped and intragastrically administered with BMS309403. Glucose Tolerance Test (GTT) and Insulin Tolerance Test (ITT) were performed on all rats. Serum insulin was detected by ELISA. The metabolic characters, as well as liver and kidney functions, were evaluated by serum biochemical assay. Immunohistochemistry and Western blot were adopted to detect the expression levels of FABP4, CD68, GRP78, ATF6, p-IRE1a, and Cleaved caspase-3. RESULTS: Lepr-/- rats showed prominent characteristics of metabolic syndrome with increased FABP4, inflammatory infiltration, ER stress and apoptosis in islets. BMS309403 administration attenuated inflammation, ER stress and apoptosis in Lepr-/- rat islets while stimulating insulin secretion as well as improving manifestation of metabolic syndrome without hepatic and renal toxicity. CONCLUSIONS: FABP4 increased in Lepr-/- rat islets and might be involved in the regulation of islet inflammation and apoptosis via ER stress. FABP4 inhibitor BMS309403 could ameliorate islet inflammation and apoptosis in metabolic syndrome through suppressing ER stress.

STMN1 in colon cancer: expression and prognosis in Chinese patients.

OBJECTIVE: To study the stathmin (STMN1) expression in colorectal cancer and tumor-adjacent normal tissue and discuss its prognostic significance in colon cancer. PATIENTS AND METHODS: STMN1 was tested with qRT-PCR in 30 samples of fresh colon cancer tissue and tumor-adjacent issue, and with immunohistochemical SP method in 105 samples of fresh colon cancer tissue and tumor-adjacent issue to analyze the association between its expression and clinical pathological parameters. Clinical data was combined to study the relationship between STMN1 expression and 5-year survival rate. Univariate analysis and Cox multivariate regression were performed to study the correlation between STMN1 expression and prognosis. RESULTS: The mRNA and protein level of STMN1 were significantly higher in colon cancer samples than tumor-adjacent normal tissues (p<0.05). STMN1 expression was independent of patient age, gender or location, but significantly related to lymph node metastasis and TNM staging (p<0.05). Survival analysis by Kaplan-Meier method showed that STMN1 expression was significantly related with the survival of colon cancer patients. The median survival time of STMN1-positive patients (37.5 months) was significantly shorter than STMN1-negative patients (57.1 months, p<0.05). Cox multivariate regression indicated that STMN1 is independent prognostic factors predicting the development, invasion and metastasis of colon cancer (p<0.05). CONCLUSIONS: STMN1 overexpression in colon cancer is independently associated with improved survival and significantly related to the development of the disease. Our findings suggest that presence of a STMN1-prognosis interaction that potentially determines clinical outcome.

Subcutaneous administration of liposomes: a comparison with the intravenous and intraperitoneal routes of injection.

The development of long-circulating liposomes containing lipid derivatives of poly(ethylene glycol) (PEG), termed Stealth liposomes, has considerably improved the prospects for therapeutic applications of liposomal drug delivery systems. We have examined the pharmacokinetics and biodistribution of long-circulating, as compared to conventional, liposomes after subcutaneous (sc) administration in mice. Results obtained after subcutaneous administration were compared to those obtained after intravenous (iv) and intraperitoneal (ip) administration. Liposomes, following sc administration, appeared intact in the circulation subsequent to moving down the lymph node chains that drain the site of injection. Liposomes containing PEG-distearoylphosphatidylethanolamine (PEG-DSPE) resulted in the highest levels of small (80-90 nm) liposomes in the blood, with up to 30% of vivo label appearing in the blood at 12 to 24 h post-injection. In the absence PEG-DSPE approx. 4-fold lower levels of liposomes were found in the blood. Small size of the liposomes was critical to their ability to move into the circulation, with liposomes above 110-120 nm not appearing in blood to any significant extent. The presence of PEG-DSPE and cholesterol was important for the in vivo stability of the liposome after sc administration. Although liposome levels were significantly higher in the draining lymph nodes after sc administration, levels associated with other tissues were proportionately reduced relative to the iv and ip routes of administration. Liposomes appeared in blood after ip and sc administration with half-lives of approx. 0.6 and 9 h, respectively, and subsequent to appearing in blood had similar biodistribution, pharmacokinetics and half-lives (20.4 h) to liposomes given by the iv route.

Cardioprotection by liposome-conjugated sialyl Lewisx-oligosaccharide in myocardial ischaemia and reperfusion injury.

OBJECTIVES: Selectins are important adhesion molecules which utilize a carbohydrate ligand such as sialyl Lewisx (SLex). Our objective was to study the effects of a liposome-conjugated SLex (Lipo-SLex) in myocardial ischaemia (MI) and reperfusion (R) injury in order to further clarify the actions of this carbohydrate. METHODS: We studied the efficacy of Lipo-SLex in a feline model of MI (90 min) and R (270 min) injury in vivo. Lipo-SLex (400 micrograms SLex/kg, iv) was administered intravenously 10 min prior to R. We also utilized an in vitro system of neutrophil adherence to thrombin-stimulated coronary endothelium to validate the efficacy of Lipo-SLex. RESULTS: Lipo-SLex significantly attenuated myocardial necrosis (8.6 +/- 1.2 vs. 29.5 +/- 3.1% of area-at-risk, P < 0.01) and plasma creatine kinase activities (P < 0.01) compared to vehicle (liposome alone). Moreover, endothelium-dependent relaxation to acetylcholine and A23187 in ischaemic-reperfused coronary rings obtained from cats treated with Lipo-SLex was significantly preserved compared to cats given liposomes without SLex (P < 0.01). After reperfusion, ex vivo PMN adherence to ischaemic-reperfused coronary endothelium was significantly increased in vehicle-treated cats, however, this was significantly attenuated in Lipo-SLex-treated cats (82 +/- 7 vs. 28 +/- 3 PMNs/mm2, P < 0.01). Myeloperoxidase activity in the ischaemic myocardium, a marker of PMN accumulation, was also significantly attenuated in Lipo-SLex-treated cats compared to liposomes without SLex (P < 0.01). CONCLUSIONS: Liposome-conjugated SLex-oligosaccharide attenuates myocardial necrosis and preserves coronary endothelial function following MI/R in vivo. The mechanism appears to be mediated by inhibition of the initial PMN-endothelial interaction and eventual accumulation into the ischaemic cardiac tissue. The liposome-SLex complex may be an efficient drug formulation for acute inflammatory diseases.

Amphotericin B colloidal dispersion: an improved antifungal therapy.

Amphotericin B colloidal dispersion (ABCD) is a near 1:1 discoidal complex of amphotericin B (AMB) and sodium cholesteryl sulfate (SCS) arranged as a bilayer of SCS interspersed with AMB via noncovalent interactions. The complex is stable in blood and plasma with minimal dissociation. In vitro and in vivo studies show that ABCD is as effective and four to five times safer than conventional AMB (CAB) for fungal infection. Compared with CAB treatment, ABCD demonstrates reduced peak plasma levels, prolonged residence time, and lowered AMB levels in most tissues including kidney, the major target of toxicity for CAB. In 572 patients with systemic fungal infections secondary to severe underlying disease, ABCD doses < or = 6 mg/kg/day were well tolerated, even in those who failed to tolerate or respond to CAB. Mild-to-moderate, dose-dependent, infusion-related adverse events typically seen with CAB were also observed with ABCD, with no sign of renal or hepatic toxicity. Complete or partial recovery was seen in 57.3%. Therefore, ABCD should be considered as an alternative treatment of systemic fungal infections.

Behavioral and endocrine response to cholecystokinin tetrapeptide in patients with posttraumatic stress disorder.

BACKGROUND: Given the relationship between posttraumatic stress disorder (PTSD) and panic, it was of interest to examine whether panic provoking agents affect PTSD symptoms. We therefore investigated the behavioral and endocrine response of PTSD patients to the panicogen cholecystokinin tetrapeptide (CCK-4). METHODS: Eight patients with PTSD (DSM-IV) received 50 micrograms CCK-4 intravenously in a placebo-controlled, double-blind balanced design. Provocation of panic, anxiety, and flashbacks was assessed. Plasma adrenocorticotropin (ACTH) and cortisol levels after CCK-4 were measured and compared to healthy subjects matched for age, gender, and provoked symptoms. RESULTS: Despite significant effects of CCK-4 on anxiety and panic symptoms, no significant provocation of flashbacks emerged. CCK-4-induced panic symptoms showed an inverse correlation to trait dissociation. The ACTH response after CCK-4 was significantly lower in PTSD patients than in controls. Cortisol was similarly increased in both groups after CCK-4, but PTSD patients showed a more rapid decrease of stimulated cortisol concentrations. CONCLUSIONS: Panic symptoms or heightened anxiety are not necessarily conditioned stimuli for the provocation of posttraumatic flashbacks. Further studies in PTSD with different panicogens should be controlled for the potential interference of trait dissociation. Our hormone data show further evidence for a corticotropin-releasing hormone (CRH) overdrive and enhanced negative glucocorticoid feedback in PTSD patients.

Comparison of acetate-1-14C metabolism in uremic and nonuremic dogs.

Acetate-1-14C was infused into six anephric uremic and six anephric nonuremic dogs during a 4-hr hemodialysis against a standard acetate containing (39.5 mM) dialysis solution. Arterial acetate (nonradioactive) levels achieved a steady state by the end of dialysis indicating that the maximum rate of acetate metabolism had not been exceeded. The mean arterial acetate level at the end of dialysis was 2.6 mM in both groups of dogs. Acetate disappearance after the cessation of dialysis followed first order kinetics with a mean half-life of 3.8 +/- 0.5 min in the uremic and 3.7 +/- 0.5 min in the nonuremic dogs. Most of the infused acetate-1-14C was metabolized to 14CO2 within 8 hr after dialysis. An average of 84 and 71% of the infused acetate-1-14C was metabolized to 14CO2 in the uremic and nonuremic dogs, respectively. Small but significant amounts of radioactivity were incorporated into lipids of plasma and other tissues. Incorporation of radioactivity into total lipids of liver, omental fat, and sciatic nerve was significantly greater in the uremic as compared to the nonuremic dogs. Incorporation of radioactivity into total lipids of heart, aorta, and plasma was the same in both groups of dogs.

Increased pituitary activation following metyrapone administration in post-traumatic stress disorder.

Our previous findings have demonstrated that individuals with post-traumatic stress disorder (PTSD) show lower basal cortisol levels, a larger number of lymphocyte glucocorticoid receptors, and an enhanced suppression of cortisol following the administration of dexamethasone compared to normals and patients with major depression. We have previously suggested that these alterations reflect an enhanced negative feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) axis in PTSD. However, in the absence of direct knowledge of pituitary capability in this disorder, it has been equally likely that the alterations observed reflected either pituitary or adrenal insufficiency. In the present study, we examined ACTH release from the pituitary gland in PTSD following the administration of metyrapone. Metyrapone resulted in a significantly greater increase of ACTH and 11-deoxycortisol in combat veterans with PTSD (n = 11) compared with normal male volunteers (n = 8). When seen in the context of other abnormalities observed in PTSD, the present demonstration of increased pituitary activity in the absence of negative feedback provides unequivocal support for the hypothesis of enhanced negative feedback.

Anti-HIV activity of amphotericin B-cholesteryl sulfate colloidal dispersion in vitro.

We examined whether the anti-HIV-1 activity of the polyene antibiotic Amphotericin B (AMB) is retained following incorporation into sterically stabilized 'Stealth' liposomes (L-AMB) with prolonged circulation in vivo, or cholesteryl sulfate colloidal dispersions (CD-AMB). The effects of the different preparations on acute infection of H9 cells with HIV-1IIIB, spreading of the virus from chronically infected H9/HTLV-IIIB cells to SupT1 cells, and HIV-1-induced syncytium formation were evaluated. Infection was monitored by p24 levels in culture supernatants. L-AMB did not affect HIV-1 infection. When present only during initial infection, AMB (3-20 microg/ml) reduced p24 levels by 70-80% after 7 and 10 days post-infection, while CD-AMB inhibited p24 production by approximately 30-40% at day 7 and 50-60% at day 10. The inhibitory effect of CD-AMB and AMB was enhanced by continuous treatment of acutely infected cells. The reduction of p24 production during continuous treatment was not due to cytotoxicity. During spreading of infection from infected to uninfected cells, AMB almost completely inhibited virus production while CD-AMB reduced both p24 production and the cytopathic effect in a dose-dependent manner. HIV-1 induced syncytium formation was slightly inhibited by AMB but not by CD-AMB. Because CD-AMB is considerably less cytotoxic than AMB, its ability to inhibit HIV infection in vivo needs to be evaluated further.

Tocopherol-phospholipid liposomes: maximum content and stability to serum proteins.

This study addresses two questions: 1) what is the maximum amount of tocopherol that can be contained in egg phosphatidylcholine liposomes, and 2) what is the stability of these vesicles in the presence of serum proteins? These liposomes, made with a French pressure cell, can contain no more than 33 mol% of tocopherol. Tocopherol changes liposomes in a manner similar to cholesterol, making them larger, less permeable to aqueous dyes and highly resistant to protein-induced disruption. The suppression of protein-induced disruption is more pronounced with tocopherol than with cholesterol, even at lower molar ratios. Thus, liposomes containing alpha tocopherol (15 to 30 mol%) may be useful for delivering physiological quantities of this vitamin to cells in culture or to tissue in vivo.

Lipid metabolism in plasma, liver, and adipose tissue of rats with experimental chronic nephrotic syndrome.

Plasma, liver, and adipose tissue lipid composition and synthesis from [1-14C] acetate were studied three months following induction of nephrotic syndrome in rats by injection of antiglomerular basement membrane protein. Plasma triglyceride concentrations and specific radioactivities were elevated, and the triglycerides contained increased proportions of oleic acid. Plasma cholesterol and phospholipid concentrations were also increased, but free fatty acid levels were not. Liver triglyceride concentrations were decreased and incorporation of [1-14] acetate into liver triglycerides was also depressed below that of normal controls. Nephrotic rat liver triglycerides contained a higher proportion of oleic acid and lower arachidonic acid than did controls. Incorporation of [1-14C] acetate into adipose tissue lipids of the nephrotic rats was increased, and the proportion of palmitic acid was decreased. In the chronic nephrotic rat, the major source of the increased plasma triglycerudes may be fatty acids mobilized from adipose tissue stores.

Antibodies to hepatitis C virus and hepatitis C virus RNA in Chinese blood donors determined by ELISA, recombinant immunoblot assay and polymerase chain reaction.

Antibodies to hepatitis C virus (anti-HCV) were determined in Chinese blood donors from the city of Wuhan by ELISA screening tests and confirmatory recombinant immunoblot assay (RIBA). 281 and 222 sera were sampled under similar conditions in 1989 and 1990, respectively. The first collection of sera was sent to Sweden in lyophilized form, the second directly as fresh, unfrozen sera. A high proportion (22%) of the lyophilized sera were positive in the screening assay but only 6 (2.10%) were positive by RIBA with antibodies against both the C100-3 and 5-1-1 peptides. HCV RNA could be detected by polymerase chain reaction (PCR) analysis in 3 of the 6 sera and in one reacting with C100-3 only. In the second material of fresh sera only 3 were positive in the screening anti-HCV ELISA, but none was RIBA or PCR positive. Thus, the overall prevalence of anti-HCV among the 503 Chinese blood donors as identified by RIBA was 1.2%, and that of HCV RNA by PCR was 0.8%. The confirmed antibody prevalence is higher than that reported in the western literature.

Hepatitis B virus DNA detected by PCR in sera and liver tissues of Chinese patients with chronic liver diseases.

To investigate the HBV infection and its replication in Chinese patients with chronic liver disease, polymerase chain reaction (PCR) was employed to detect hepatitis B virus DNA in sera of 410 patients with chronic liver disease and liver samples from 188 patients. The HBV DNA detectability in all serum samples was 58%. Among them 100% HBeAg-positive and 58% anti-HBe cases were HBV DNA detectable respectively. However, HBV DNA was also found in 23% HBsAg-negative/anti-HBc positive chronic cases. Furthermore, 30% anti-HBs positive chronic cases who had neutralizing antibody against HBV infection, continued to contain HBV DNA. Our findings indicate that HBV infection and its replication are dominant cause of chronic liver disease and some HBV variants may escape from the protective antibody to induce chronic liver disease, even anti-HBs antibody circulated.

An effective approach to achieving low supersaturation for a/b-axis oriented YBa(2)Cu(3)O(7-δ) film growth.

Using liquid phase epitaxy, a novel approach was developed to grow a-axis oriented YBa2Cu3O7-δ films (a-films) under an air atmosphere, which has been difficult previously since its formation requires extremely low supersaturation. In our new method, instead of conventional cooling from the saturated to supersaturated state, an extremely small driving force for film growth was generated from the unsaturated through saturated to supersaturated state. By controlling the amount of fresh solvent and the melting time before cooling down the Y-Ba-Cu-O solution, a growth region width up to 30 K was acquired for preparing a-films. Significantly, this work provides a low-cost and convenient way to produce high-quality a-films, which are potentially suitable for Josephson junction devices.

Secretion of nascent lipoproteins and apolipoproteins by perfused livers of normal and cholesterol-fed guinea pigs.

Triglyceride-rich very low density lipoproteins (VLDL) are the major lipoprotein in perfusates of normal guinea pig livers. Their component apoprotein B is mainly B-100 together with some B-95. This apoprotein is actively synthesized, as are C apoproteins and small amounts of apoprotein E. Only trace amounts of intermediate density lipoproteins (IDL, 1.015 < d < 1.05 g/ml) are found in perfusates, but appreciable amounts of low density lipoproteins (LDL, 1.05 < d < 1.10 g/ml) accumulate. These LDL are not newly synthesized, but rather appear to be gradually washed out of the liver. High density lipoproteins (HDL, 1.10 < d < 1.21 g/ml) both discoidal and spheroidal, also accumulate, which contain newly synthesized apoproteins A-I, E and C. Fatty livers of guinea pigs fed cholesterol secrete less VLDL and more IDL than normals, but the combined amount of protein is unchanged. These lipoproteins contain newly synthesized apoprotein B, are enriched in cholesteryl esters and newly synthesized apoprotein E, and have reduced electrophoretic mobilities, making them resemble remnants. Large amounts of LDL also accumulate in perfusates of livers from cholesterol-fed animals, much of which does not appear to be newly synthesized, as judged from single pass perfusions. However, the LDL fraction is complex and includes particles that contain newly synthesized apoprotein B. Thus, these livers appear to secrete a spectrum of cholesteryl ester-rich particles, containing newly synthesized apoproteins B and E that span the density range of VLDL, IDL, and LDL. Livers of cholesterol-fed guinea pigs secrete large amounts of discoidal HDL with a free cholesterol-phospholipid molar ratio of 2:1. Accumulation of protein (almost entirely newly synthesized apoprotein E) in HDL is increased 25-fold over that in perfusates from normal guinea pig livers.-Guo, L.S.S., R.L. Hamilton, R. Ostwald, and R. J. Havel. Secretion of nascent lipoproteins and apolipoproteins by perfused livers of normal and cholesterol-fed guinea pigs.