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A 66-year-old man was admitted with destructive arthropathy, and calcium pyrophosphate dihydrate was demonstrated in the synovial fluid specimen. He was found to have a hyponatremia. The serum sodium concentration was 121 mmol/l, plasma arginine vasopressin (AVP) 6.6 pmol/l, and serum interleukin (IL)-6 96 pg/l. The clinical findings suggest the diagnosis of syndrome of inappropriate secretion of antidiuretic hormone (SIADH). However, destructive arthropathy with increased values of C-reactive protein and IL-6 is the only background of SIADH in this patient. We suggest the possibility that IL-6 produced at inflammatory lesions may have stimulated an excessive release of AVP resulting in the hyponatremia and hypochloremia of SIADH.

The effect of bezafibrate on plasma lipoproteins was investigated in Japanese familial combined hyperlipidemic patients with or without an impaired glucose tolerance accompanied by a low-density lipoprotein subclass, with the major gradient gel peak at a particle diameter of less than 25.5 nm. Bezafibrate treatment at a dose of 400 mg/d for 12 weeks produced an antiatherogenic effect on lipoprotein profiles, as reflected by a decrease in plasma triglyceride levels, an increase in plasma high-density lipoprotein-cholesterol levels, induction of the large-size subclass of low-density lipoprotein, and disappearance of intermediate-density lipoproteins. The plasma total and low-density lipoprotein-cholesterol-lowering effect of bezafibrate was significant in patients without impaired glucose tolerance but was not significant in patients with impaired glucose tolerance. Bezafibrate increased lipoprotein lipase activity and decreased the activity of cholesteryl ester transfer protein, both in patients with or without impaired glucose tolerance. There was no difference in the distribution of signal peptide insertion/deletion or Xbal polymorphisms of the apolipoprotein B gene in patients with or without impaired glucose tolerance. Mechanisms other than lipoprotein lipase, cholesteryl ester transfer protein activities, and an apolipoprotein B gene polymorphism may be responsible for the resistance to lowering of plasma total and low-density lipoprotein cholesterol levels with bezafibrate treatment in familial combined hyperlipidemic patients with impaired glucose tolerance.

The proliferation of vascular smooth muscle cells (VSMCs) plays an important role in the formation of atherosclerotic lesions and restenosis after angioplasty. It has been suggested that probucol inhibits VSMCs proliferation, but this effect has not been directly demonstrated. In this study we investigated the effect of probucol on neointimal formation after balloon injury in normocholesterolemic rabbits and examined whether probucol could inhibit the proliferation of rabbit cultured VSMC stimulated by fetal bovine serum (FBS). Probucol inhibited the formation of neointima by about 63% 2 weeks after balloon injury. Probucol inhibited the increase in the number of cultured VSMCs and bromodeoxyuridine (BrdU) incorporation stimulated by 10% FBS in a dose-dependent manner. Also, 10% FBS stimulated the activities of mitogen-activated protein kinase (MAP kinase) and protein kinase C (PKC) in cultured VSMCs. Probucol inhibited these activities in a dose-dependent fashion. These results suggest that probucol may inhibit neointimal formation after balloon injury in normocholesterolemic rabbits by preventing the proliferation of VSMCs via inactivation of MAP kinase and PKC.

We studied the effects of intracarotid papaverine and prostaglandin E1 incorporated in lipid microsphere (Lipo-PGE1) in relation with transcranial Doppler parameters such as mean flow velocity (MFV) and pulsatile index (PI) of the proximal segment of the middle cerebral artery. Eighty patients with subarachnoid hemorrhage (SAH) were included in this study. In the case of angiographic vasospasm, papaverine at 7 mg/min with total dose below 300 mg per artery and 10-20 micrograms of Lipo-PGE1 were injected in the supraclinoid portion of the internal carotid artery. Vasospasm was improved in 24 patients (63%), however, it was unchanged in 14 patients (37%). The former patients had more favorable outcomes than the latter patients (p < 0.005). After intracarotid injection therapy, the correlation between MFV and PI was classified into three types: type 1, both MFV and PI decreased; type 2, MFV decreased but PI increased; and type 3, both MFV and PI fluctuated. The Glasgow Outcome Scale 3 months after SAH was as follows: type 1 (n = 15), good in 14 (93%) and moderate disability in one (7%); type 2 (n = 9), good in eight (89%) and vegetative state in one (11%); and type 3 (n = 14), moderate disability in five (36%), severe disability in seven (50%), and death in two (14%). Chi-square analysis showed significant differences between type 1 and type 3 (p < 0.005), and type 2 and type 3 (p < 0.005). In conclusion, intracarotid papaverine combined with Lipo-PGE1 was effective for vasospasm but type 3 patients require a different treatment protocol.

The effects of cerivastatin sodium (BAY w 6228), a new type of inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on plasma cholesterol concentrations and the induction of hepatic LDL receptors were investigated with beagle dogs and Hep G2 cells. Oral administration of cerivastatin (0.01, 0.03, and 0.1 mg/kg per day) for 3 weeks reduced plasma total and very low-density lipoprotein plus low-density lipoprotein (VLDL + LDL) cholesterol concentrations and increased hepatic LDL receptor binding activity in dogs. Scatchard plot analysis revealed a 1.9-fold increase in the maximum binding capacity of hepatic LDL receptors in cerivastatin-treated animals. Similar results were obtained by administration of pravastatin (1.0 and 5.0 mg/kg/day) for 3 weeks. Binding activity of the LDL receptor, as well as receptor mRNA and protein concentrations, were increased in a dose-dependent manner (0.01-1.0 microM) by exposure of Hep G2 cells to cerivastatin. The results suggest that cerivastatin reduces plasma cholesterol concentrations by increasing hepatic LDL receptor expression. The mechanism of lowering cholesterol concentration by cerivastatin was the same as with the other previously examined HMG-CoA reductase inhibitors, but the effects with cerivastatin were apparent at doses much lower than the effective doses of the other drugs. Cerivastatin, therefore, shows potential for clinical use as a potent and efficacious plasma cholesterol-lowering drug.

The extensive sequence homology that exists among the catalytic domains of phosphatidylinositol 3- and 4-kinases allowed us to clone a novel human gene encoding a putative phosphatidylinositol kinase, NPIK. Among other known phosphatidylinositol 3- and 4-kinases, NPIK was most closely related to yeast PIK1 phosphatidylinositol 4-kinase. Several forms of NPIK cDNAs were isolated, and expression of NPIK message was detected in a wide variety of tissues. Fluorescence in situ hybridization and radiation hybrid analyses assigned the NPIK gene to human chromosome 1. Recombinant NPIK protein catalyzed a conversion from phosphatidylinositol to phosphatidylinositol 4-phosphate. The catalytic activity of NPIK was augmented by Triton X-100, and was reduced in the presence of adenosine. Using green fluorescent protein system we determined that NPIK is localized in the cytoplasm. Taken together, the data suggest that NPIK may play a pivotal role in regulating the synthesis of phosphatidylinositol 4-phosphate at the site(s) accessible from cytoplasm.

We determined the most effective dosage of pentaerythritol tetranicotinate (niceritrol) to reduce plasma lipoprotein(a) [Lp(a)] levels in 44 Japanese patients (16 men and 28 women; mean age, 59.2 +/- 10.8 years) with hyperlipidemia types IIa, IIb, and IV. Patients received oral niceritrol at a dosage of 750 mg (3 tablets)/d for 8 weeks, followed by 1,500 mg (6 tablets)/d for 8 weeks. Administration of niceritrol 750 mg/d for 8 weeks decreased total and low-density lipoprotein (LDL) cholesterol in patients with type IIa hyperlipidemia and decreased triglycerides in patients with type IV hyperlipidemia, but did not affect Lp(a). However, niceritrol 1,500 mg/d for 8 weeks decreased Lp(a) in patients with initial Lp(a) levels greater than 30 mg/dL in addition to decreasing total and LDL cholesterol and triglycerides. These results suggest that the effective dosage of niceritrol to reduce the serum Lp(a) concentration in Japanese hyperlipidemic patients with a high Lp(a) level (> or = 30 mg/dL) is greater than 1,500 mg/d.

From a human fetal-brain cDNA library, we isolated and characterized a novel gene (KPNA3) encoding a protein highly homologous to certain nuclear transport proteins of Xenopus and human. The complete cDNA clone, designated karyopherin alpha 3, contained an open reading frame of 1,563 nucleotides encoding 521 amino acids. The predicted amino acid sequence showed 48%, 45% and 48% identity with Xenopus importin, yeast SRP1 and human RCH1, respectively. The similarities among these proteins suggest that karyopherin alpha 3 may be involved in the nuclear transport system. Eight repeats of the arm motif were well conserved among these proteins. The N-terminal region of the predicted karyopherin alpha 3 product was highly basic and the C-terminal region was strongly acidic. A 4.3-kb transcript was expressed in all adult human tissues examined by Northern blotting. The cDNA clone was assigned to chromosome band 13q14.3 by fluorescence in situ hybridization.

The RING-finger is a unique zinc-chelating domain involved in mediating protein-protein interactions. The extensive sequence homology within the RING-finger domain allowed us to clone a novel member of the RING-finger family of genes. This cDNA clone, designated RNF5 (Ring-finger protein 5), contained an open reading frame of 540 nucleotides. Its predicted amino acid sequence revealed significant homology to a hypothetical protein encoded by Caenorhabditis elegans cosmid C16C10.7. The expression of RNF5 was detected in a variety of human tissues. The RNF5 gene was mapped by fluorescence in situ hybridization to chromosome 6p21.31. Radiation hybrid mapping further assigned RNF5 to a region proximal to the major histocompatibility complex (MHC) on chromosome 6. RNF5 is the third RING-finger gene identified in the region proximal to MHC raising the possibility that the RING-finger family of genes may exist as a cluster in this region.

A full-length cDNA homologous to RAB7, a member of the RAB-related GTP-binding protein subfamily, was isolated from a human placenta cDNA library. This cDNA, designated RAB7L1, has an open reading frame of 609 nucleotides encoding 203 amino acids. Northern analysis showed that the mRNA is ubiquitously expressed in human tissues, although signal intensities were different among the various organs examined. This gene was located on chromosome band 1q32 by fluorescence in situ hybridization.

The antioxidative effect of monatepil maleate (CAS 103379-03-9, AJ-2615), a new antihypertensive agent, was investigated by measuring its ability to inhibit copper-induced lipid hydroperoxidation of low density lipoprotein (LDL) and was compared with those of diltiazem (Ca(2+)-channel antagonist), prazosin (alpha 1-adrenoceptor antagonist), and probucol. The concentration of AJ-2615 required to inhibit copper-induced lipid hydroperoxidation of LDL by 50% (IC50) was 28 mumol/l. The IC50 values for diltiazem, prazosin, and probucol were > 1 mmol/l, > 1 mmol/l, and 17 mumol/l, respectively. These results indicate that AJ-2615 has the same potent antioxidative effect as probucol and suggest that a previously reported ability of AJ-2615 to inhibit the progression of atherosclerosis may be due to this antioxidative property. In addition, the dihydrodibenzothiepine ring of AJ-2615 may have an antioxidative functions.

We developed a simple, sensitive and accurate method for assaying cellular free and total cholesterol by monitoring 4-cholesten-3-one, a conversion product of the cholesterol oxidase-catalyzed oxidation of the free cholesterol that has a strong chromophoric alpha, beta-unsaturated ketone at 240 nm, using a high-pressure liquid chromatographic system. This method measured picomole quantities of free and total cholesterol and precisely determined their concentrations in cells (10(4) range) in culture using 7 beta-hydroxycholesterol as an internal standard.

The response of the infarct-related coronary artery to acetylcholine (20, 30, 50 micrograms) was investigated in 30 patients without restenosis during a 4-month follow-up period after direct percutaneous transluminal coronary angioplasty (PTCA) of the left proximal anterior descending coronary artery. The patients were divided into two groups according to wall motion as obtained by the centerline method from a left ventricular angiogram: moderate group (n = 10) with reduced wall motion with less than 20 abnormal contraction segments (moderate reduction at the infarcted site), severe group (n = 20) with reduced wall motion with 20 or more abnormal contraction segments (severe reduction). The acetylcholine-induced percentage changes in luminal diameter were assessed at the PTCA site and the distal portion of the coronary artery and the effect of acetylcholine was compared at the two sites. Coronary artery diameter in the moderate and severe groups displayed 8.1 +/- 24.9% and 7.4 +/- 30.8% contraction at the PTCA site and 38.3 +/- 46.3% and 72.5 +/- 28.2% contraction at the distal portion, respectively. Severe group had greater contraction at the distal portion than at the PTCA site. Vasoconstriction of the patent infarct-related coronary artery tended to occur in the infarcted area where wall motion was severely affected. In addition, endothelial dysfunction appears to be induced by a lengthy interruption of epicardial coronary blood flow and is present in the patent infarcted coronary artery without restenosis.

Hyperalphalipoproteinemia (HALP) has been regarded as a beneficial state accompanied by a longevity syndrome. However, we reported the cases of markedly hyperalphalipoproteinemic subjects with juvenile corneal opacification. The patients had reduced postheparin hepatic triglyceride lipase (HTGL) activities, and one of them has recently been identified to be homozygous for a missense mutation in exon 15 (D442: G) in the cholesteryl ester transfer protein (CETP) gene. In the current study, to elucidate the clinical significance of and atherogenicity in marked HALP, we determined the incidence of atherosclerotic cardiovascular disease (ACD) in patients with marked HALP and characterized the lipoprotein abnormalities in those who had ACD, focusing especially on CETP and HTGL. The subjects were 201 patients (111 males and 90 females) with marked HALP ( > or = 2.58 mmol/L [100 mg/dL]), 67% of whom were demonstrated to have the CETP gene mutations in the intron 14 splice donor site or in exon 15. Their mean age was 54 +/- 15 years. Plasma levels of total cholesterol, HDL cholesterol, and triglyceride in all subjects were 6.28 +/- 1.78, 3.15 +/- 0.90, and 1.08 +/- 0.53 mmol/L, respectively. Ten of the male patients (9.0%) and two of the female patients (2.2%) had apparent ACD such as myocardial infarction, angina pectoris, and peripheral vascular diseases. Ten patients with HALP who had ACD were identified to be heterozygotes for CETP deficiency. To further clarify the characteristics of marked HALP in patients with ACD, we compared the plasma lipids, lipoproteins, CETP, and HTGL activities between heterozygotes for CETP deficiency who were with and without ACD.

From a human fetal-brain cDNA library we isolated a novel gene, designated RT14, whose cDNA contained an open reading frame of 375 nucleotides encoding 125 amino acids. A 71-amino-acids region of the predicted peptide sequence showed 62% identity with a putative peptide encoded in the region close to Drosophila Tra-2. It also showed significant homology with the putative peptide of T20G5.10 of C. elegans. Northern-blot analysis revealed expression of 0.7-kb and 1.1-kb transcripts in all human tissues examined.

The effects of dietary oleic acid on cholesterol metabolism were investigated and compared with those of palmitic acid in hamsters. Addition of 5% oleic acid to a 0.1% cholesterol-supplemented diet decreased plasma total cholesterol, very low density lipoprotein (VLDL) cholesterol, and low density lipoprotein (LDL) cholesterol, increased hepatic LDL receptor activity, and decreased plasma cholesteryl ester transfer protein (CETP) activity in comparison with 0.1% cholesterol alone. In contrast, addition of 5% palmitic acid to a 0.1% cholesterol-supplemented diet increased total cholesterol and LDL-cholesterol, increased plasma CETP activity, and suppressed hepatic LDL receptor activity to a greater extent than 0.1% cholesterol alone. Neither oleic acid nor palmitic acid altered hepatic microsomal 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase activity, but oleic acid increased hepatic microsomal cholesterol 7 alpha-hydroxylase activity. These results suggest that dietary oleic acid inhibits the increases in total, VLDL-, and LDL-cholesterol induced by dietary cholesterol by preventing both LDL receptor suppression and increased CETP activity, whereas dietary palmitic acid augments the cholesterol-induced increases in total and LDL-cholesterol by both further suppression of LDL receptor activity and further stimulation of CETP activity.

The present study examines the developmentally regulated expression pattern of an Ig superfamily member, KG-CAM, in the neostriatum of the rat. KG-CAM is a 90-kDa glycoprotein that is related to the DM-GRASP/Neurolin family of adhesion molecules. In the embryonic and early postnatal neostriatum, the distribution of KG-CAM correlates with the distribution of dopaminergic terminals. Early in neostriatal development, KG-CAM is found in the tyrosine hydroxylase-positive patches. In the maturing neostriatum, the levels of KG-CAM remain high within the patches, and KG-CAM upregulates in the matrix compartment. As the neostriatum is reaching its adult morphology, 5 weeks postnatal, the expression of KG-CAM in the matrix is approximately equal to that of the patches. When the distribution of KG-CAM is examined at the ultrastructural level, the immunoreactivity is localized to the external surface of neuronal and glial profiles in the neuropil. KG-CAM does not appear to be associated with the guidance of dopaminergic axons from the substantia nigra to the striatum, for this pathway is not immunopositive for this member of the Ig superfamily. The present study identifies an Ig superfamily member, KG-CAM, that appears to play a major role in the development of the neostriatum. Furthermore, the high levels of KG-CAM in the adult neostriatum suggest that this Ig superfamily member may be involved in maintaining the integrity of this structure in the adult rat.

The effects of administration of pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on hepatic cholesterol 7 alpha-hydroxylase and acyl-coenzyme A: cholesterol acyltransferase (ACAT) activities and bile lipid secretion were investigated in Syrian golden hamsters. Continuous administration of pravastatin induced no significant changes in hepatic cholesterol content, ACAT and cholesterol 7 alpha-hydroxylase activities, or bile lipid and acid composition. Abrupt withdrawal of pravastatin induced increases in hepatic cholesterol content and ACAT activity and no change in hepatic cholesterol 7 alpha-hydroxylase activity, and increased cholesterol saturation in bile. Hepatic cholesterol 7 alpha-hydroxylase activity paralleled hepatic mRNA levels of this enzyme. These results suggest that a change in hepatic cholesterol metabolism induced by continuous administration of pravastatin maintains a constant net balance of hepatic cholesterol content. In addition, the drug has no deleterious influence on metabolism of bile lipids and acids and related enzymes, except for a transient increase in cholesterol saturation in bile induced by an inappropriate increase in hepatic cholesterol content and a lack of response of cholesterol 7 alpha-hydroxylase activity to changes in hepatic cholesterol content upon abrupt withdrawal of pravastatin.

Purpose: The utility of subperiosteal tissue expansion (STE) for mandibular augmentation with hydroxylapatite (HA) particles was evaluated experimentally in two groups of dogs., Materials and Methods: Eight grams of solid HA particles were implanted in previously formed bilateral subperiosteal expanded beds on the mandible. In one group, the HA particles were implanted in the intact subperiosteal expanded bed and in the other the newly formed capsule overlying the bone was removed before implantation of HA., Results: Despite marked augmentation with a large number of HA particles, there was neither deformity nor infection of the implants, which maintained the original desired contour. The firm fibrous capsule formed by STE allowed consolidation of the HA particles and prevented their migration. In the first group, although histologic evidence of bony union of the implanted particles was not seen even after 2 months, clinical immobilization of the grafts was achieved in 1 to 2 months. After 1 year, substantial bone growth into the implants was observed. In the second group, clinical immobilization was observed even after 2 weeks. Histologic evidence of bony union of the particles located along the surface of the mandible was observed after 1 or 2 months. In these specimens, however, marked bone resorption of the mandibular cortex, was also noted. No evidence of bone or osteoid formation on the expanded periosteal side was noted in either group., Conclusion: These results provide fundamental data regarding mandibular augmentation using STE, and indicate that the subperiosteal expanded bed is an excellent recipient site for onlayed implants.

The authors dissected the cervical spine and its surrounding structures from 40 adult cadavers under a surgical microscope. The anterior part of the spine and spinal cord was examined after vertebrectomy. The posterior longitudinal ligament (PLL) consists of two layers; the anterior one is termed the deep layer, and the posterior one is termed the superficial layer. These two layers adhered together loosely. In the lateral portion of the spinal canal, the superficial layer joined the periradicular sheath at the level of the intervertebral disc spaces and joined the dura mater at the level of the vertebral bodies. After the removal of the deep layer, the anterior internal vertebral venous plexus was seen on top of the lateral part of the superficial layer. The venous plexus was embedded between the double-layered PLLs, was not located in the epidural space, and was not seen in the medial part of the PLL. The PLL without venous channels on top of it was about 10 mm in width at the levels of the intervertebral disc and about 5 mm at the levels of the vertebral body. The anterior root exit zone (AREZ) was an elliptical shape; the transverse length of the AREZ was about 2 mm, and the longitudinal length was 10 to 15 mm. The average number of anterior rootlets on the AREZ was 17 to 25 and tended to decrease in the lower cervical spinal cord. The posterior structures were examined after en bloc laminectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

We investigated types of lipoprotein receptors on Hep G2 cells using a monoclonal antibody against the LDL receptor. IgG-C7 inhibited the binding and internalization of 125I-labeled low density lipoprotein (LDL) in Hep G2 cells with upregulated and downregulated LDL receptors by 90% of control values. Binding and internalization of 125I-labeled chylomicron remnant in Hep G2 cells with upregulated and downregulated LDL receptors was 50% and 85%, respectively, of control values after exposure to IgG-C7. Excess unlabeled chylomicron remnant inhibited binding and internalization of 125I-labeled chylomicron remnant in Hep G2 cells with downregulated LDL receptors completely. Pronase treatment abolished binding and internalization of 125I-labeled LDL and 125I-labeled chylomicron remnant in Hep G2 cells. When solubilized fractions of Hep G2 cells were immunoprecipitated with IgG-C7, the binding activity of 125I-labeled chylomicron remnant to reconstituted vesicles was unchanged. 45Ca blotting analysis showed the presence of 45Ca binding protein (approximately 600 kDa) in Hep G2 cells. The amount of 45Ca binding protein was not affected by cholesterol and was abolished by pronase treatment. These results suggest the existence of a functional receptor other than the LDL receptor that catabolizes chylomicron remnant in Hep G2 cells and that this receptor may correspond to LDL receptor-related protein.

An animal model for subperiosteal tissue expansion is described. Small tissue expanders were placed bilaterally and inflated in the buccal subperiosteal pockets of the mandible. Additionally, subcutaneous expansion was performed in the breast region. Twenty-one dogs were used in three experimental groups to evaluate the optimal size of an expander for this model, the optimal inflation regimen, and the histologic changes following subperiosteal expansion. Hemicylindrical expanders, 20 mm in width, 10 mm in height, and 30 mm in length, inflated with 1 mL saline every four days, were used for this model. It was found that the periosteum was replaced by fibrous connective tissue during expansion. Capsule formation following subperiosteal expansion was much more rapid than that following subcutaneous expansion. A greater increase in vascularity was noted in the subperiosteal expansion group and the subperiosteal control group than in the subcutaneous expansion group. In the subperiosteal expansion group, a thick fibrous capsule, with minimal inflammatory response, was observed 1 week after full inflation. Leaving the fully inflated subperiosteal expanders in place more than 1 month accelerated the resorption of the underlying bone. These results support the previously reported empirical regimens of subperiosteal tissue expansion. Furthermore, the excellence of the subperiosteal expanded bed as a recipient site for onlay grafting was confirmed.

The effect of fluvastatin sodium (XU62-320), a new type of inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A, on the induction of LDL receptor in the human liver-derived cell line HepG2 was investigated. Fluvastatin sodium produced marked inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and induction of LDL receptor on HepG2 cells at a concentration of 0.1-1.0 microM. These results suggest that fluvastatin sodium has potential for use as a strong plasma cholesterol-lowering drug.

A partial cDNA clone encoding cholesterol 7 alpha-hydroxylase (pHA 7 alpha-3) was isolated from a hamster liver cDNA library using rat P-450 ch7 cDNA (p 7 alpha-11) as a probe. In comparison with the complete base sequence of p 7 alpha-11, pHA 7 alpha-3 lacked about 500 base pairs at the 5' end. Circadian rhythms of mRNA for hamster liver 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol 7 alpha-hydroxylase were investigated with cDNA clones encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase (pRed-227) and pHA 7 alpha-3. Typical circadian rhythms of mRNA for both enzymes and a time lag between the two circadian rhythms were observed. The circadian rhythm of activity for each enzyme corresponded to that of each mRNA.

The mechanism for the damage to the alanine-preferring amino acid transport system (A system) of guinea pig intestinal brush border membrane vesicles induced by active oxygen species was studied in vitro. The transport activity of L-proline, which is a model amino acid for the A system, and the tryptophan fluorescence intensity of intestinal brush border membrane vesicles were decreased, and lipid peroxidation of these membrane vesicles was induced by ultraviolet irradiation, which generated active oxygen species. Thiourea (hydroxyl radical scavenger) protected L-proline transport activity and tryptophan fluorescence intensity of intestinal brush border membrane vesicles and also inhibited lipid peroxidation in these membrane vesicles in the presence of active oxygen radicals. alpha-Tocopherol (singlet oxygen radical scavenger) inhibited lipid peroxidation of intestinal brush border membrane vesicles but protected neither L-proline transport activity nor tryptophan fluorescence intensity in these membrane vesicles in the presence of active oxygen radicals. Catalase and superoxide dismutase showed no protective effect on L-proline transport activity, tryptophan fluorescence intensity, or lipid peroxide formation in intestinal brush border membrane vesicles in the presence of active oxygen radicals.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of dietary hydrogenated corn oil (trans-octadecenoate-rich oil) on plasma cholesterol and triglyceride concentrations was compared with dietary palmitic acid in hamsters given a cholesterol-rich diet. The addition of dietary palmitic acid and hydrogenated corn oil accelerated the increase in plasma VLDL- and LDL-cholesterol levels and plasma triglyceride level induced by dietary cholesterol loading. Dietary cholesterol, palmitic acid and hydrogenated corn oil showed no effect on plasma HDL-cholesterol concentration. A decrease in hepatic LDL receptor activity was seen in animals fed a diet supplemented with cholesterol in combination with palmitic acid or hydrogenated corn oil in comparison with animals fed a diet supplemented with cholesterol alone. Hydrogenated corn oil (trans-octadecenoate-rich oil) appears to potentiate the effect of dietary cholesterol in elevating the plasma VLDL- and LDL-cholesterol levels through the suppression of hepatic LDL receptor activity. trans-Octadecenoate in dietary hydrogenated corn oil may be as atherogenic as dietary palmitic acid due to a suppression of hepatic LDL receptors in the presence of dietary cholesterol loading.

Our findings revealed the nucleus ventralis lateralis pars oralis (VLo) projection to motor area, and the nucleus ventralis anterior pars principalis (VApc) projections to the premotor and supplementary motor areas (SMA). The VLo gave rise to thalamocortical projections terminating in the superficial half of layer I, mainly in the forelimb motor area. The VApc gave rise to the superficial projections to the post-arcuate premotor area around the arcuate genu and arcuate spur as well as SMA. We suggested that the medial pallidal segment projects to the motor area via VLo, and to the premotor area and SMA via VApc. We also proposed that the premotor area and SMA receive cerebellar afferents via nucleus ventralis lateralis pars caudalis and area X.

The authors report a case of repeated brain metastases from hepatocellular carcinoma (HCC) in a 70-year-old male, who had underwent liver segmentectomy for HCC 5 years earlier. He developed intracerebral hemorrhage in the right parietal region, which was considered to be intratumoral because the metastatic tumor was detected in the same region. Total removal of the tumor and hepatic artery embolization followed by ethanol injection for recurrent HCC were performed. One month later, a metastatic tumor was discovered in the upper vermis and was totally removed. Both metastatic brain tumors were histologically verified as Edmondson grade 2 HCC. Four months later, multiple metastases to the left frontal region and the upper vermis occurred, and he died of pneumonia. Brain metastasis from HCC is rare; nine such cases have been reported in the literature, of which eight cases developed intracranial hemorrhage as in the present case.

It seems generally accepted that meningiomas are benign tumors, and that malignant meningiomas are not common. The pathological criteria for judging whether meningiomas are malignant or not are controversial. Hemangiopericytic type, high cellularity, brain invasion, high mitotic rate, necrotic foci, and papillary type are regarded as histological characteristics of malignant meningiomas. Of a series of 105 patients with surgically treated meningioma, 25 patients demonstrated malignant characteristics (24%). The overall recurrence rate in our patients was 14%. The incidence of recurrence in 25 patients with pathologically malignant characteristics, and recurrence in 80 patients with pathologically benign characteristics were 32% and 9%, respectively. In comparison with benign meningiomas, recurrent factors in malignant ones included Simpson grade II operation, attachment of skull base, and no radiation-therapy. In conclusion, our criteria for malignant meningiomas have proved to be acceptable, and these cases should be treated with radiation therapy after surgery.

A retrograde and anterograde wheat germ agglutinin-horseradish peroxidase (WGA-HRP) study in the rat indicated that some neurons in the globus pallidus (GP) sent their axons ipsilaterally to the inferior colliculus (IC). These neuronal cell bodies were located in the ventrolateral portions of the caudal part of the GP, and their axons were distributed mainly in the peripheral region of the external cortex of the IC.

An unusual case of Stafne's bone cavity which presented in the canine-premolar region of the mandible is presented. The diagnosis was confirmed using CT and sialography.

Recently, the backscattering enhancement by densely distributed particles of a size comparable to the wavelength was reported. It has been explained as the constructive interference of two waves traveling in opposite directions. This enhancement was observed only in densely distributed particles, and its existence in sparsely distributed media has not been verified yet. In this paper we present the experimental evidence of backscattering enhancement by sparsely distributed very large particles. Experiments are conducted using 45-microm latex particles which are approximately 100 times the wavelength. Both copolarized and crosspolarized components are measured for different particle concentrations. Unlike for small particles, backscattering enhancement is most noticeable when the particle concentration is low. The angular width of the peak is comparable to the ratio (wavelength)/(particle size) and is independent of the optical distance.

In the natural form of the oral commissure, the outer edges of the upper and lower lips form small triangular flaps. The white line of the lip at the commissure is web continuous with the upper and lower red lips. The lower part of this web is larger than the upper. To repair this so that there is a natural appearance, a Z-plasty and mucocutaneous flap based inferiorly is performed on the transverse facial cleft. The incision line for the Z-plasty is made though each vermilion border and is extended approximately 1.5-2 mm to create the web continuous with red lips. The mucocutaneous flap is formed when making the incision through the lower vermilion border. As the flap is elevated and sutured to the upper lip, the larger web-like skin on the lower lip is made. This skin is seen to insert boldly into the oral cavity.

The effect of l-thyroxine administration from 2 to 10 days of age (Neo-T4) on the behavioral development was studied. Serum T4 levels in Neo-T4 rats showed a marked and dose-related decrease at 15 days of age and a less marked decrease at 62 days of age. The locomotor activity of the Neo-T4 rats was higher at 13 approximately 19 days of age and tended to be lower at 62 days of age than in the controls. At 17 days of age, apomorphine (0.1 mg/kg, s.c.) induced a marked increase in the frequency of sniffing down in the control males, whereas a decrease was noted in the Neo-T4 males. Age-matched females in both groups responded to apomorphine with a slight decrease in sniffing down behavior. An increase in the frequency of sniffing down by apomorphine (0.5 mg/kg) in adult Neo-T4 rats was less marked. TRH administration failed to induce hyperthermia in adult Neo-T4 males. The results indicate that neonatal administration of T4 in the rat induces alterations in the functional development of the brain in varying degrees dependent upon the functional integration of the neurons. An involvement of sex hormones is suggested.