Validation of a Brief Structured Interview: The Children's Interview for Psychiatric Syndromes (ChIPS).

Evidence-based assessment is important in the treatment of childhood psychopathology. While researchers and clinicians frequently use structured diagnostic interviews to ensure reliability, the most commonly used instrument, the Schedule for Affective Disorders and Schizophrenia for School Aged Children (K-SADS) is too long for most clinical applications. The Children's Interview for Psychiatric Syndromes (ChIPS/P-ChIPS) is a highly-structured brief diagnostic interview. The present study compared K-SADS and ChIPS/P-ChIPS diagnoses in an outpatient clinical sample of 50 parent-child pairs aged 7-14. Agreement between most diagnoses was moderate to high between the instruments and with consensus clinical diagnoses. ChIPS was significantly briefer to administer than the K-SADS. Interviewer experience level and participant demographics did not appear to affect agreement. Results provide further evidence for the validity of the ChIPS and support its use in clinical and research settings.

Restoration of Firearm Rights in New York.

The National Instant Criminal Background Check System (NICS) Improvement Amendments Act of 2007 encouraged states to create processes by which individuals who have lost their rights to firearm possession for mental-illness-related reasons could receive relief from restrictions. Over 20 states have created relief processes for this sub-group, but there still exists considerable state-by-state heterogeneity. The spectrum ranges from states that require a physician's opinion regarding appropriateness for restoration to those that rely solely on judicial proceedings without input from psychiatrists or other mental health professionals. This article reviews the restoration process in New York State, a model in which psychiatrists participate in the process of assessing whether an individual's firearm rights can be restored. It discusses the legislative background of these regulations, the specific policies and procedures governing the restoration process, and clinical considerations for the forensic evaluation.

Attention-Deficit/Hyperactivity Disorder Symptoms and Externalizing Progression in the LAMS Study: A Test of Trait Impulsivity Theory.

OBJECTIVE: To test differential prospective prediction of growth in externalizing behavior, including oppositional defiant disorder, conduct disorder, and substance use disorders, by earlier hyperactive-impulsive (HI) vs inattentive (IN) symptoms of attention-deficit/hyperactivity disorder (ADHD). METHOD: Participants in the Longitudinal Assessment of Manic Symptoms (LAMS) Study (N = 685 at study entry), including 458 boys and 227 girls ages 6-12, completed full parent report and self-report assessments every year for 8 years on the Schedule for Affective Disorders and Schizophrenia for School-Age Children. Three sets of analyses were conducted. First, hierarchal regression (block entry) was used to test independent associations between HI symptoms and later externalizing outcomes, controlling for IN symptoms, and IN symptoms and later externalizing outcomes, controlling for HI symptoms. Second, logistic regression was used to test progression of DSM externalizing disorders. Third, tests of mediation were used to assess potentiation of externalizing progression through environmental risk mediators (eg, family environment, neighborhood violence). RESULTS: Consistent with hypotheses derived from trait impulsivity theories of externalizing behavior, HI symptoms of ADHD were associated independently with long-term externalizing outcomes, whereas IN symptoms were not. Between months 48 and 96, ADHD-HI/combined symptom subtype diagnoses predicted later oppositional defiant disorder diagnoses, oppositional defiant disorder diagnoses predicted later conduct disorder diagnoses, and conduct disorder diagnoses predicted later substance use disorder diagnoses. Evidence for environmental risk mediation (eg, parental monitoring, neighborhood violence) was also found. CONCLUSION: Findings support trait impulsivity models of externalizing progression, whereby ADHD-HI/combined symptoms subtypes predispose to increasingly severe externalizing behaviors, which are magnified in contexts of environmental risk.

The ant abdomen: The skeletomuscular and soft tissue anatomy of Amblyopone australis workers (Hymenoptera: Formicidae).

Recent studies of insect anatomy evince a trend towards a comprehensive and integrative investigation of individual traits and their evolutionary relationships. The abdomen of ants, however, remains critically understudied. To address this shortcoming, we describe the abdominal anatomy of Amblyopone australis Erichson, using a multimodal approach combining manual dissection, histology, and microcomputed tomography. We focus on skeletomusculature, but additionally describe the metapleural and metasomal exocrine glands, and the morphology of the circulatory, digestive, reproductive, and nervous systems. We describe the muscles of the dorsal vessel and the ducts of the venom and Dufour's gland, and characterize the visceral anal musculature. Through comparison with other major ant lineages, apoid wasps, and other hymenopteran outgroups, we provide a first approximation of the complete abdominal skeletomuscular groundplan in Formicidae, with a nomenclatural schema generally applicable to the hexapod abdomen. All skeletal muscles were identifiable with their homologs, while we observe potential apomorphies in the pregenital skeleton and the sting musculature. Specifically, we propose the eighth coxocoxal muscle as an ant synapomorphy; we consider possible transformation series contributing to the distribution of states of the sternal apodemes in ants, Hymenoptera, and Hexapoda; and we address the possibly synapomorphic loss of the seventh sternal-eighth gonapophyseal muscles in the vespiform Aculeata. We homologize the ovipositor muscles across Hymenoptera, and summarize demonstrated and hypothetical muscle functions across the abdomen. We also give a new interpretation of the proximal processes of gonapophyses VIII and the ventromedial processes of gonocoxites IX, and make nomenclatural suggestions in the context of evolutionary anatomy and ontology. Finally, we discuss the utility of techniques applied and emphasize the value of primary anatomical research.

Admixture mapping of ankle-arm index: identification of a candidate locus associated with peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) is associated with significant morbidity and mortality, and has a higher prevalence in African Americans than Caucasians. Ankle-arm index (AAI) is the ratio of systolic blood pressure in the leg to that in the arm, and, when low, is a marker of PAD. METHODS: The authors used an admixture mapping approach to search for genetic loci associated with low AAI. Using data from 1040 African American participants in the observational, population based Health, Aging, and Body Composition Study who were genotyped at 1322 single nucleotide polymorphisms (SNPs) that are informative for African versus European ancestry and span the entire genome, we estimated genetic ancestry in each chromosomal region and then tested the association between AAI and genetic ancestry at each locus. RESULTS: The authors found a region of chromosome 11 that reaches its peak between 80 and 82 Mb associated with low AAI (p<0.001 for rs12289502 and rs9665943, both within this region). 753 African American participants in the observational, population based Cardiovascular Health Study were genotyped at rs9665943 to test the reproducibility of this association, and this association was also statistically significant (odds ratio (OR) for homozygous African genotype 1.59, 95% confidence interval (CI) 1.12 to 2.27). Another candidate SNP (rs1042602) in the same genomic region was tested in both populations, and was also found to be significantly associated with low AAI in both populations (OR for homozygous African genotype 1.89, 95% CI 1.29 to 2.76). CONCLUSION: This study identifies a novel region of chromosome 11 representing an area with a potential candidate gene associated with PAD in African Americans.

Recent advances of genetic ancestry testing in biomedical research and direct to consumer testing.

In the post-Human Genome Project era, the debate on the concept of race/ethnicity and its implications for biomedical research are dependent on two critical issues: whether and how to classify individuals and whether biological factors play a role in health disparities. The advent of reliable estimates of genetic (or biogeographic) ancestry has provided this debate with a quantitative and more objective tool. The estimation of genetic ancestry allows investigators to control for population stratification in association studies and helps to detect biological causation behind population-specific differences in disease and drug response. New techniques such as admixture mapping can specifically detect population-specific risk alleles for a disease in admixed populations. However, researchers have to be mindful of the correlation between genetic ancestry and socioeconomic and environmental factors that could underlie these differences. More importantly, researchers must avoid the stigmatization of individuals based on perceived or real genetic risks. The latter point will become increasingly sensitive as several 'for profit companies' are offering ancestry and genetic testing directly to consumers and the consequences of the spread of the services of these companies are still unforeseeable.

The Impact of the Psychiatrist on the Life Care Plan.

A life care plan is a tool that is used for medical treatment planning and management purposes in many settings, including legal and forensic applications. This article summarizes the life care planning process and emphasizes the role of the psychiatrist in establishing a strong medical foundation for the plan. The psychiatrist's expertise in determining the nature and extent of the evaluee's psychiatric illness, prognosis, need for and likely benefit from treatment, and costs of care inform the life care planning process. Advising life care planners on these matters is a natural extension of the work of psychiatrists and forensic psychiatrists, who are accustomed to providing medical opinions to the courts. There are specific challenges when the psychiatrist creates recommendations for the life care plan; they include determining long-term prognosis, devising treatment plans, and identifying malingering. These questions are explored to assist the psychiatrist in providing the foundation for a life care plan.

90Y Resin Microspheres Radioembolization for Colon Cancer Liver Metastases Using Full-Strength Contrast Material.

OBJECTIVES: To assess safety and efficacy of 90Y resin microspheres administration using undiluted non-ionic contrast material (UDCM) {100% Omnipaque-300 (Iohexol)} in both the "B" and "D" lines. MATERIALS AND METHODS: We reviewed all colorectal cancer liver metastases patients treated with 90Y resin microspheres radioembolization (RAE) from 2009 to 2017. As of April 2013, two experienced operators started using UDCM (study group) instead of standard sandwich infusion (control group). Occurrence of myelosuppression (leukopenia, neutropenia, erythrocytopenia or/and thrombocytopenia), stasis, nontarget delivery (NTD), median fluoroscopy radiation dose (FRD), median infusion time (IT), liver progression-free (LPFS) and overall survivals (OS) was evaluated. Complications within 6 months post-RAE were reported according to CTCAE v3.0 criteria. RESULTS: Study and control groups comprised 23(28%) and 58(72%) patients, respectively. Median follow-up was 9.1 months. There was no statistically significant difference in myelosuppression incidence within 6 months post-RAE between groups. Median FRD and IT for study and control groups were 44.6 vs. 97.35 Gy/cm2 (p = 0.048) and 31 vs. 39 min (p = 0.006), respectively. A 38% lower stasis incidence in study group was not significant (p = 0.34). NTD occurred in 1/27(4%) study vs. 5/73(7%) control group procedures (p = 1). Grade 1-2 and grade 3-4 toxicities between study and control group patients were 36%(8/22) vs. 45%(26/58), p = 0.61 and 9%(2/22) vs. 16%(9/58), p = 0.72, respectively. There was no difference in LPFS and OS between groups. CONCLUSION: Administration of 90Y resin microspheres using UDCM in both lines is safe and effective, resulting in lower fluoroscopy radiation dose and shorter infusion time, without evidence of myelosuppression or increased stasis incidence.

Experience and Opinions of Forensic Psychiatrists Regarding PTSD in Criminal Cases.

By the end of 2014, 1.5 million veterans of the Second Iraq and Afghan wars were to have returned home, up to 35 percent with PTSD. The potential use of PTSD as the basis for legal claims in criminal defense is therefore a pressing problem. Using a Web-based survey, we examined the experiences and attitudes of members of the American Academy of Psychiatry and the Law (AAPL) regarding PTSD in the criminal forensic setting. Of 238 respondents, 50 percent had been involved in a criminal case involving PTSD, 41 percent in the previous year. Eighty-six percent of cases involved violent crime and 40 percent homicides. Forty-two percent of defendants were soldiers in active service or veterans, of whom 89 percent had had combat exposure, mostly in the Second Iraq and Afghan wars. Outcomes reported were not guilty by reason of insanity (NGRI) (7%), guilty on the original charge (40%), and pleading guilty to a lesser charge (23%). The findings suggest that many forensic psychiatrists will be asked to evaluate PTSD in the criminal setting, with a growing number of cases related to combat exposure in recent veterans. The implications of these findings for the practice of forensic psychiatry are discussed.

Cloning and characterization of the SmIMP25 integral membrane protein of the parasitic helminth Schistosoma mansoni.

The cDNA and genomic clones encoding a 25 kDa integral membrane protein, termed SmIMP25, were isolated from Schistosoma mansoni. The 2.2 kb SmIMP25 mRNA was found in all developmental stages of the parasite tested: miracidium, sporocyst, cercaria and adult worm. The SmIMP25 gene is at least 16 kb long and it is split by four introns ranging in size from 36 bp to > or = 9 kb. Excluding the introns, the gene and the cDNA show 100% sequence identity. The cDNA has an open reading frame encoding a protein 223 amino acids long. The predicted sequence reveals a distinct hydrophobic domain of 20 amino acids located 12 residues from the carboxyl-terminal end. The properties of this domain (marked hydrophobicity, size, flanking by charged residues and C-terminal location) are typical of the transmembrane segments of integral membrane proteins. The presence of three potential N-glycosylation sites is also consistent with membrane proteins that are often glycosylated at the extracellular domain. Accordingly we propose that SmIMP25 is an integral membrane protein in which residues 1-191 are extracellular, residues 192-211 comprise the hydrophobic domain that spans the membrane, and residues 212-223 are intracellular. The SmIMP25 was synthesized as a fusion protein in bacteria and antibodies were elicited in rabbits. Antibodies against SmIMP25 specifically precipitated a 25 kDa protein from cell-free products programmed by schistosome mRNA, in agreement with the size of the protein predicted from the cDNA sequence. Immunofluorescence studies showed SmIMP25 on the surface of the parasite. Surface molecules expressed at the host-parasite interface are likely to provide information on host parasite relationship and may serve as targets for protective immunity.

Cloning of the SmSPO-1 gene preferentially expressed in sporocyst during the life cycle of the parasitic helminth Schistosoma mansoni1.

Schistosomes are parasitic helminths with a complex life cycle in human and snail hosts. They express stage-specific genes that conceivably determine distinct properties of the parasite at different developmental stages. Here we report the stage-specific gene SmSPO-1, which is preferentially expressed in sporocysts residing in the snail host. The cDNA and the gene were cloned and sequenced. The cDNA, from cap site to the poly(A) addition site, is 498 bp long. It encodes a protein of 117 amino acids with a hydrophobic signal peptide of 18 residues, indicating that SmSPO-1 is a secreted or a membranal protein. In the gene the cDNA is split into four exons spread over 2.1 kb of chromosomal DNA.

Experimental nephrotic syndrome: removal and tissue distribution of chylomicrons and very-low-density lipoproteins of normal and nephrotic origin.

Lymph chylomicrons and plasma VLDL, 14C-labelled in vivo, were isolated from normal and nephrotic rats and injected into normal or nephrotic recipients. In normal recipients, the half-life of chylomicrons of nephrotic vs. normal origin was significantly longer (5.2 +/- 0.5 vs. 3.5 +/- 0.4 min-1). The nephrotic chylomicrons were larger in size, deficient in apo-E and apo A-I, rich in triacylglycerol and cholesterol, but poor in phospholipids, indicating that factors related to composition affected their removal. The half-life of nephrotic vs. normal VLDL, given to normal recipients, was unexpectedly shorter, (4.5 +/- 0.2 vs. 5.8 +/- 0.2 min-1). The nephrotic VLDL were also triacylglycerol- and cholesterol-rich and phospholipid-poor, but had a large diameter spread and contained a dense fraction according to the zonal ultracentrifugation pattern, suggesting the presence of faster removable IDL-like particles. When nephrotic rats received normal particles, a pronounced removal delay was seen, paralleling the extent of plasma triacylglycerol elevation. The half-life of chylomicrons was 8.3 +/- 1.4 and 15.2 +/- 2.5 min-1 in moderately and severely nephrotic rats, respectively, that of VLDL was 11.72 +/- 2.1 and 37.8 +/- 7.1 min-1 correspondingly. The chylomicron-triacylglycerol uptake was reduced both by adipose tissues and muscles of normal or nephrotic recipients, with some increase in entry into lungs, kidneys and spleen. Tissue distribution patterns of VLDL-triacylglycerol was similar to that of chylomicrons, except that the liver took up approx. 90% of the label. The low share of triacylglycerol uptake by tissues rich in lipoprotein lipase indicates that the activity of this enzyme was unlikely to limit the rate of removal. Lipoprotein lipase activity in adipose tissue and heart was slightly decreased in moderately nephrotic rats and declined only by approx. 35% in severely nephrotic ones. These results indicate that the removal defect in nephrosis seems to be due, in part, to changes in the composition of triacylglycerol-rich particles, compromising their accessibility to lipolysis and, in part, to their abundance, saturating the lipolytic capacity.

Differences in DNA-sequence recognition between the DNA-binding domain fragment and the full-length molecule of the heat-shock transcription factor of schistosome.

Binding and inhibition studies reveal that the DNA-binding domain (DBD) fragment and the full-length molecule of the heat-shock transcription factor of schistosome (SmHSF) differ in DNA sequence recognition. SmHSF does not recognize the ideal HSE consensus sequence (nGAAnnTTCnnGAAn) but recognizes a variant HSE that contains nGTAn instead of nGAAn in the third pentamer. The DBD reacts efficiently with the ideal HSE sequence and with lower affinity with the variant HSE sequence. These findings suggest that elements inside and outside the DBD contribute to the DNA-binding specificity of HSF.

Chylomicron synthesis in experimental nephrotic syndrome.

Mesenteric lymph was collected for 48 h from rats with aminonucleoside-induced nephrotic syndrome, receiving an intraduodenal infusion of a triacylglycerol emulsion. In nephrosis, the rates of lymph flow and triacylglycerol transport were approx. 2-fold higher, but the transport of total protein and of apoproteins A-I and E was 2- to 3-fold lower than that in control rats, resulting in chylomicrons with a 3-fold approx. elevated triacylglycerol/protein ratio. Supplementation of the triacylglycerol infusate with glucose and amino acids did not increase the protein or apoA-I and apoE transport. Production or transport of B and C apoproteins in nephrotic rats was also reduced, as indicated by tetramethylurea solubility, incorporation of intraduodenally infused [3H]leucine and staining of the chylomicron proteins on SDS-PAGE gels. Apoprotein A-IV was the only chylomicron component into which the leucine incorporation was elevated, but its relative content was not increased on SDS-PAGE gels. Lymph chylomicrons of nephrotic rats were larger in size (1498 +/- 37 vs. 1235 +/- 23 A), consistent with the higher triacylglycerol/protein ratio. The concentration of all lipoprotein classes was markedly elevated in the plasma of nephrotic rats, as was that of the total A-I and E apoproteins. Intravenous injection of 125I-labelled HDL, followed by tracing of the label in lymph chylomicrons, indicated a lower rate of transfer of HDL apoproteins from plasma to lymph in nephrotic rats. We conclude that the intestinal chylomicron formation in nephrosis is characterised by an enhanced triacylglycerol transport without the appropriate apoprotein complement. This is probably due to the limited capacity of enterocytes, in marked contrast to hepatocytes, to respond to the hypoproteinemia of nephrosis with increased production and/or transport of the apoproteins.

Composition, removal and metabolic fate of chylomicrons derived from diabetic rats.

Tri[14C]acylglycerol-labelled chylomicrons, obtained from cannulated mesenteric lymph of streptozotocin-diabetic donor rats, when intravenously injected into non-diabetic recipient rats, disappeared from the circulation at a significantly slower rate than similarly prepared tri[14C]acylglycerol chylomicrons from non-diabetic donor rats (t1/2, 5.6 +/- 0.7 vs. 3.2 +/- 0.5 min-1, P less than 0.02). The appearance of labelled lipolysis products among plasma lipids (free fatty acid, cholesterol ester and phospholipid fractions) was delayed, indicating decreased availability for lipolysis of the chylomicron-borne triacylglycerol of diabetic origin. Tissue distribution of triacylglycerol, 15 min after the injection of chylomicrons to recipient rats, disclosed a 4-5-fold increase in uptake by muscles (heart and diaphragm) in relation to adipose tissues (epididymal and perirenal sites), in the case of chylomicrons of diabetic derivation. Since a large share of the chylomicron triacylglycerol was taken up by the liver, this tissue was perfused with chylomicron 'remnants' prepared by partial in vitro lipolysis with purified lipoprotein lipase. The 'remnants' of diabetic derivation were taken up by the liver at a 2-3-fold slower rate than those of non-diabetic origin. Chylomicrons derived from diabetic rats were found to be similar in size but markedly depleted of E apolipoproteins as determined by SDS-polyacrylamide gel electrophoresis, isoelectric focussing and a specific immunoassay. Decreases were also seen in A-I apolipoproteins by immunoassay and isoelectric focussing. Chylomicron 'remnants' were also markedly apolipoprotein E-deficient. In vitro incubation of the 'diabetic remnants' with high-density lipoproteins raised their apolipoprotein E content approx. 3-fold and considerably increased their hepatic uptake. Injection of intact chylomicrons preincubated with high-density lipoproteins likewise increased their in vivo removal rate toward the range of that of 'non-diabetic' chylomicrons. We conclude that diabetes-induced changes in the apolipoprotein composition of the chylomicrons and chylomicron remnants play an important role in their removal from the circulation. It appears that their recognition pattern is altered, reducing their ability to interact with receptor sites in the peripheral tissues and the liver, respectively.

Removal defect of very-low-density lipoproteins from diabetic rats.

The disappearance rate of triacyl[3H]glycerol carried on very-low-density lipoproteins (VLDL), isolated from diabetic rats and reinjected into normal recipient rats, was about twice as low as that of VLDL-triacyl[3H]glycerol from non-diabetic rats. The VLDL derived from diabetic rats was deficient in the apolipoprotein E component. These results indicate that the triacylglycerol removal defect in diabetes may be related to the quality of the protein carrier.

Fate of lipoprotein lipase taken up by the rat liver. Evidence for a conformational change with loss of catalytic activity.

When isolated rat livers were perfused with medium containing lipoprotein lipase, 40-60% was taken up during a single passage. This value was similar for lipoprotein lipase derived from culture medium of rat preadipocytes, and for lipoprotein lipase purified from bovine milk. It was also, similar, irrespective of the lipoprotein lipase concentration, at least up to 1 microgram/ml. Immediately following its uptake by the liver, a large fraction of the lipoprotein lipase could be released by heparin, but the magnitude of this fraction decreased with time. The enzyme lost its catalytic activity rather rapidly, but its degradation to acid-soluble products, or to larger fragments, was much slower. On heparin-agarose chromatography, the enzyme taken up by the liver eluted at a lower salt concentration than the original lipoprotein lipase preparation. This change in affinity for heparin suggests that the originally dimeric lipoprotein lipase had dissociated into monomers, in analogy to the findings in model experiments. It is suggested that the initial uptake of lipoprotein lipase occurs by binding to a polyanion at the liver cell surface. This is followed by endocytosis and dissociation of the enzyme from its heparan sulfate-like binding site. Acidification of the endosome may cause a conformational change in the lipase molecule with dissociation to inactive monomers, preceding ultimate proteolytic degradation.

Cellular mechanism of nutritionally induced insulin resistance in Psammomys obesus: overexpression of protein kinase Cepsilon in skeletal muscle precedes the onset of hyperinsulinemia and hyperglycemia.

The sand rat (Psammomys obesus) is an animal model of nutritionally induced diabetes. We report here that several protein kinase C (PKC) isoforms (alpha, epsilon, and zeta, representing all three subclasses of PKC) are overexpressed in the skeletal muscle of diabetic animals of this species. This is most prominent for the epsilon isotype of PKC. Interestingly, increased expression of PKCepsilon could already be detected in normoinsulinemic, normoglycemic (prediabetic) animals of the diabetes-prone (DP) line when compared with a diabetes-resistant (DR) line. In addition, plasma membrane (PM)-associated fractions of PKCalpha and PKCepsilon were significantly increased in skeletal muscle of diabetic animals, suggesting chronic activation of these PKC isotypes in the diabetic state. The increased PM association of these PKC isotypes revealed a significant correlation with the diacylglycerol content in the muscle samples. Altered expression/activity of PKCepsilon, in particular, may thus contribute to the development of diabetes in these animals; along with other PKC isotypes, it may be involved in the progression of the disease. This may possibly occur through inhibition of insulin receptor (IR) tyrosine kinase activity mediated by serine/threonine phosphorylation of the IR or insulin receptor substrate 1 (IRS-1). However, overexpression of PKCepsilon also mediated down-regulation of IR numbers in a cell culture model (HEK293), resulting in attenuation of insulin downstream signaling (reduced protein kinase B [PKB]/Akt activity). In accordance with this, we detected decreased 125I-labeled insulin binding, probably reflecting a downregulation of IR numbers, in skeletal muscle of Psammomys animals from the DP line. The number of IRs was inversely correlated to both the expression and PM-associated levels of PKCepsilon. These data suggest that overexpression of PKCepsilon may be causally related to the development of insulin resistance in these animals, possibly by increasing the degradation of IRs.

Both insulin resistance and diabetes in Psammomys obesus upregulate the hepatic machinery involved in intracellular VLDL assembly.

OBJECTIVE: In the current study, we examined the mechanisms that regulate hepatic apolipoprotein B (apoB)-containing lipoprotein secretion in Psammomys obesus, a good animal model for the investigation of insulin resistance and diabetes. METHODS AND RESULTS: When fed chow ad libitum, 22% maintained normoglycemia and normoinsulinemia (group A), 33% exhibited normoglycemia and appreciable hyperinsulinemia (group B), and 45% developed overt diabetes (group C). Body weight gain, plasma free fatty acid elevation, hypertriglyceridemia, and hypercholesterolemia characterized groups B and C. Triton WR-1339 injection, at fasting, resulted in higher plasma VLDL-triglyceride and VLDL-apoB accumulation in groups B and C, suggesting increased VLDL production by the liver. Pulse-chase labeling experiments in cultured hepatocytes with [35S]methionine revealed reduced intracellular degradation and enhanced secretion of newly synthesized apoB in groups B and C. Concomitant with the raised triglyceride and cholesterol contents in the livers of groups B and C, there was an increase in lipogenesis and in the activity of microsomal triglyceride transfer protein, monoacylglycerol acyltransferase, and diacylglycerol transferase. Pretreatment of hepatocytes with proteasomal inhibitors eliminated the differences in apoB secretion among groups A, B, and C. CONCLUSIONS: Our data indicate that both insulin resistance and diabetes triggered the intracellular machinery involved in VLDL assembly and secretion.

Somatic DNA rearrangement generates functional rat immunoglobulin kappa chain genes: the J kappa gene cluster is longer in rat than in mouse.

The kappa immunoglobulin (Ig) genes from rat kidney and from rat myeloma cells were cloned and analyzed. In kidney DNA one C kappa species is observed by Southern blotting and cloning in phage vectors; this gene most likely represents the embryonic configuration. In the IR52 myeloma DNA two C kappa species are observed: one in the same configuration seen in kidney and one which has undergone a rearrangement. This somatic rearrangement has brought the expressed V region to within 2.7 kb 5' of the C kappa coding region; the rearrangement site is within the J kappa cluster which we have mapped. The rat somatic Ig rearrangement, therefore, closely resembles that seen in mouse Ig genes. In the rat embryonic fragment two J kappa segments were mapped at 2 and 4.3 kb 5' from the C kappa coding region. Therefore, the rat J kappa cluster extends over about 2.3 kb, a region much longer than the 1.4 kb of the mouse and human J kappa clusters. In the region between C kappa and the expressed J kappa of IR52 myeloma DNA, and XbaI site present in the embryonic kappa gene has been lost. A somatic mutation has therefore occurred in the intervening sequence DNA approx. 0.7 kb 3' from the V/J recombination site. Southern blots of rat kidney DNA hybridized with different rat V kappa probes showed non-overlapping sets of bands which correspond to different subgroups, each composed of 8-10 closely related V kappa genes.