[Functional outcomes of 100 patients with adenocarcinoma of the esophagogastric junction undergoing Cheng's GIRAFFE(®) reconstruction after proximal gastrectomy].

Objective: To investigate the functional outcomes and postoperative complications of Cheng's GIRAFFE reconstruction after proximal gastrectomy. Methods: A descriptive case series study was conducted. Clinical data of 100 patients with adenocarcinoma of the esophagogastric junction who underwent Cheng's GIRAFFE reconstruction after proximal gastrectomy in Cancer Hospital of University of Chinese Academy of Sciences (64 cases), Zhejiang Provincial Hospital of Chinese Medicine (24 cases), Lishui Central Hospital (10 cases), Huzhou Central Hospital (1 case) and Ningbo Lihuili Hospital (1 case) from September 2017 to June 2021 were retrospectively analyzed. Of 100 patients, 64 were males and 36 were females; the mean age was (61.3 ± 11.1) years and the BMI was (22.7±11.1) kg/m(2). For TNM stage, 68 patients were stage IA, 24 were stage IIA and 8 were stage IIB. Postoperative functional results and postoperative complications of radical gastrectomy with Giraffe reconstruction were analyzed and summarized. Gastroesophageal reflux disease questionnaire (RDQ) score and postoperative endoscopy were used to evaluate the occurrence of reflux esophagitis and its grade (grade N, grade A, grade B, grade C, and grade D from mild to severe reflux). The continuous data conforming to normal distribution were expressed as (mean ± standard deviation), and those with skewed distribution were presented as median (Q1, Q3). Results: All the 100 patients successfully completed R0 resection, including 77 patients undergoing laparoscopic surgery and 23 patients undergoing laparotomy. The Giraffe anastomosis time was (38.6±14.0) min; the blood loss was (73.0±18.4) ml; the postoperative hospital stay was 9.5 (8.2, 13.0) d; the hospitalization cost was (6.0±0.3) ten thousand yuan. Fourteen cases developed perioperative complications (14.0%), including 7 cases of pleural effusion or pneumonia, 3 cases of anastomotic leakage, 2 cases of gastric emptying disorder, 1 case of gastrointestinal hemorrhage and 1 case of anastomotic stenosis, who were all improved and discharged after symptomatic management. Patients were followed up for (33.3±1.6) months. Eight patients were found to have reflux symptoms by RDQ scale six months after surgery, and 11 patients (11/100,11.0%) were found to have reflux esophagitis by gastroscopy, including 6 in grade A, 3 in grade B, and 2 in grade C. All the patients could control their reflux symptoms with behavioral guidance or oral PPIs. Conclusion: Cheng's GIRAFFE reconstruction has good anti-reflux efficacy and gastric emptying function; it can be one of the choices of reconstruction methods after proximal gastrectomy.

Freestream velocity-profile measurement in a large-scale, high-enthalpy reflected-shock tunnel.

ABSTRACT: We apply Krypton Tagging Velocimetry (KTV) to measure velocity profiles in the freestream of a large, national-scale high-enthalpy facility, the T5 Reflected-Shock Tunnel at Caltech. The KTV scheme utilizes two-photon excitation at 216.67 nm with a pulsed dye laser, followed by re-excitation at 769.45 nm with a continuous laser diode. Results from a nine-shot experimental campaign are presented where N 2 and air gas mixtures are doped with krypton, denoted as 99% N 2 /1% Kr, and 75% N 2 /20% O 2 /5% Kr, respectively. Flow conditions were varied through much of the T5 parameter space (reservoir enthalpy h R ≈ 5 - 16  MJ/kg). We compare our experimental freestream velocity-profile measurements to reacting, Navier-Stokes nozzle calculations with success, to within the uncertainty of the experiment. Then, we discuss some of the limitations of the present measurement technique, including quenching effects and flow luminosity; and, we present an uncertainty estimate in the freestream velocity computations that arise from the experimentally derived inputs to the code.

Inhibition of the Gab2/PI3K/mTOR signaling ameliorates myeloid malignancy caused by Ptpn11 (Shp2) gain-of-function mutations.

Activating mutations, such as E76K and D61Y, in PTPN11 (SHP2), a protein tyrosine phosphatase implicated in multiple cell signaling processes, are associated with 35% of patients with juvenile myelomonocytic leukemia (JMML), an aggressive childhood myeloproliferative neoplasm (MPN). Here we show that the interaction between leukemia-associated mutant Shp2 and Gab2, a scaffolding protein important for cytokine-induced PI3K/Akt signaling, was enhanced, and that the mTOR pathway was elevated in Ptpn11E76K/+ leukemic cells. Importantly, MPN induced by the Ptpn11E76K/+ mutation was markedly attenuated in Ptpn11E76K/+/Gab2-/- double mutant mice-overproduction of myeloid cells was alleviated, splenomegaly was diminished and myeloid cell infiltration in nonhematopoietic organs was decreased in these double mutants. Excessive myeloid differentiation of stem cells was also normalized by depletion of Gab2. Acute leukemia progression of MPN was reduced in the double mutant mice and, as such, their survival was much prolonged. Furthermore, treatment of Ptpn11E76K/+ mice with Rapamycin, a specific and potent mTOR inhibitor, mitigated MPN phenotypes. Collectively, this study reveals an important role of the Gab2/PI3K/mTOR pathway in mediating the pathogenic signaling of the PTPN11 gain-of-function mutations and a therapeutic potential of Rapamycin for PTPN11 mutation-associated JMML.

Transcriptome analysis of skeletal muscle at prenatal stages in Polled Dorset versus Small-tailed Han sheep.

The objectives of the present study were to identify additional genes that may play important roles in the regulation of skeletal muscle growth and development, and to provide fundamental information for understanding the underlying molecular mechanisms. Eighteen cDNA libraries were constructed from the longissimus muscle of Polled Dorset (PD) and Small-tailed Han (SH) fetuses. To reveal the differences between the two species, we analyzed the differences in gene expression in 60-, 90- and 120-day fetal skeletal muscle by applying Agilent ovine genome-wide microarray. In this study, we obtained 17,704 genes using a chip containing 39,242 probes. There were 88 differentially expressed genes in the 60-day group (P < 0.05), 128 genes in the 90-day group (P < 0.05), and 340 genes in the 120-day group (P < 0.05) between the two breeds. The differentially expressed genes were grouped in different GO categories and signaling pathways. These results suggested that there are many genetic differences in the muscle growth and development transcriptomes between these two breeds. This study laid the foundation for future genomic research in sheep.

Incidence of nasopharyngeal carcinoma in Chinese immigrants, compared with Chinese in China and South East Asia: review.

OBJECTIVES: To evaluate the literature and to compare published data on age-standardised incidence rates of nasopharyngeal carcinoma in Chinese people living in and outside China. DESIGN: Systematic review of incidence rate studies and statistical incidence data concerning nasopharyngeal carcinoma in Chinese populations from 1960 to 2008. DATA SOURCES: Sixteen papers were identified from the PubMed, Embase and Scopus electronic databases and from a hand search of the reference lists of the retrieved papers. Further searches for raw data on age-specific and age-standardised incidence rates of nasopharyngeal carcinoma were conducted. Textbooks on relevant subjects were referred to for background information. A total of 19 papers met the inclusion criteria. RESULTS: Seven studies included raw data on age-specific and age-standardised incidence rates of nasopharyngeal carcinoma in Chinese people. Twelve other studies reported on changes in the incidence of nasopharyngeal carcinoma in Chinese populations in selected countries or regions. Studies on age-specific and age-standardised rates obtained data from individual registries. Studies on incidence rates obtained data from hospital records, cancer notifications (from all sections of the medical profession), pathology records and death certificates. The results showed a decline in age-standardised incidence rates of nasopharyngeal carcinoma in Chinese immigrant populations, compared with Chinese people in China. There was also a trend towards decreasing incidence the further the population had immigrated. Thus, the incidence of nasopharyngeal carcinoma in Singaporean Chinese was higher than that in Hawaiian Chinese, and that in Hawaiian Chinese was higher than that in Californian Chinese. CONCLUSION: This review found a decreasing trend in the incidence of nasopharyngeal carcinoma in Chinese migrants living in countries with a low risk of the disease.

Long-term outcome and neuroradiological findings of 31 patients with 6-pyruvoyltetrahydropterin synthase deficiency.

Tetrahydrobiopterin (BH(4)) deficiency is an autosomal recessive disorder caused by enzyme defects in the biosynthesis or recycling of BH(4). Patients with BH(4) deficiency present with severe neurological signs and symptoms and require a different treatment from classical phenylketonuria. During the last 12 years, 31 cases of BH(4) deficiency were identified in our department. They were all classified as 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency. They were diagnosed at the ages of 2.5-48 months and treated with BH(4), L-dopa and 5-hydroxytryptophan immediately after diagnosis. The average development quotients (DQ) at diagnosis and after treatment for more than 3 years were 53+/- 16, and 78+/- 15, respectively. A significant negative correlation was observed between the level of the DQ and the age at which treatment was commenced (r = -0.751, p = 0.002). Developmental profiles were uneven. Language, adaptability and at later age mathematics were particularly weak areas. Only two patients achieved a good performance in mathematics. Eleven patients who were treated with drugs from ages of 2.9-48 months had neuroradiological scanning. Computed tomography disclosed calcification in lentiform nuclei in one patient and magnetic resonance imaging disclosed delayed myelination and abnormal high intensity signal in cerebral white matter in all of them. Even though most of abnormalities were reversible, small patchy or spotted areas were still present on these regions after treatment for 10-46 months. In summary, our study supports the substantial efficacy of the current therapeutic approach in PTPS deficiency of normalizing amine neurotransmitters with three drugs as early as possible. For the first time, calcifications could be detected in patients with PTPS deficiency. Abnormalities in white matter on magnetic resonance imaging were not related to clinical manifestations and most were reversible.

Identification of three novel 6-pyruvoyl-tetrahydropterin synthase gene mutations (226C>T, IVS3+1G>A, 116-119delTGTT) in Chinese hyperphenylalaninemia caused by tetrahydrobiopterin synthesis deficiency.

The enzyme 6-Pyruvoyl-tetrahydropterin synthase (PTS) deficiency is the major cause of BH(4)-deficient HPA. The frequency of BH(4)-deficient HPA was estimated to be around 30% among Chinese HPA population in Taiwan, which is much higher than that in Caucasian population (1.5-2% of HPA). Approximately 86% of Chinese BH(4)-deficient HPA was found to be caused by PTS-deficiency. Seven mutations - namely R25G, N52S, V56M, V70D, P87S, D96N, and T106M - had been identified in Chinese PTS-deficient patients previously. In this study, five additional mutations in the PTS gene, namely 200C>T (T67M), 226C>T (L76F), IVS3+1G>A (K54X), 116-119delTGTT (K38X) and 169-171delGTG (V57del), were identified by PCR and DNA sequencing in Chinese PTS-deficient patients. The 116-119delTGTT introduces a frameshift stop after lysine of codon 38 (K38X). The G-to-A transition at the consensus sequence of splicing donor site of exon 3 (IVS3+1G>A) resulted in exon 3 skipping of the PTS transcript and caused a frameshift stop after lysine of codon 54 (K54X). The T67M and V57del mutations have been found in Caucasian PTS deficient patients, while the L76F, IVS3+1G>A, and K38X mutations are novel. None of 100 normal alleles screened was found to have the L76F substitution, which indicated that the L76F substitution is a mutation causing PTS deficiency. Hum Mutat 18:83, 2001.

Arachidonic acid induces endothelin-1 gene expression in vascular endothelial cells.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide synthesized and secreted by vascular endothelial cells. Regulation of ET-1 production occurs at the level of gene transcription. We previously demonstrated a role for arachidonic acid as an intracellular mediator in the regulation of gene expression. This study investigated the role of arachidonic acid in induction of ET-1 production in endothelial cells. Challenge of bovine aortic endothelial cells (BAECs) with arachidonic acid induced a dose- and time-dependent increase in the amount of immunoreactive ET-1 in the supernatant. The maximum effect was observed at concentrations of 20 microM. Release of ET-1 by arachidonic acid was preceded by induction of ET-1 gene expression. Arachidonic acid increased ET-1 gene expression by increasing transcription of the ET-1 gene. The effect of arachidonic acid was mimicked by other polyunsaturated fatty acids, whereas saturated fatty acids had no effect. Moreover, inhibitors of the lipoxygenase pathway blocked arachidonic acid-induced release of ET-1. These results suggest that arachidonic acid stimulated the production of ET-1 in BAECs by inducing ET-1 gene transcription. Arachidonic acid-induced production of ET-1 is dependent on lipoxygenase products of arachidonate metabolism.

Genetic evidence that Shp-2 tyrosine phosphatase is a signal enhancer of the epidermal growth factor receptor in mammals.

By using both genetic and biochemical approaches, we have investigated the physiological role of Shp-2, a cytoplasmic tyrosine phosphatase with two Src homology 2 domains, in signaling pathways downstream of epidermal growth factor receptor (EGF-R). In previous studies, a targeted deletion mutation in the SH2-N domain of Shp-2 was introduced into the murine Shp-2 locus, which resulted in embryonic lethality of homozygous mutant (Shp-2(-/-)) mice at midgestation. By aggregating Shp-2(-/-) embryonic stem cells with wild-type embryos, we created Shp-2(-/-)/wild-type chimeric animals. Most chimeras had open eyelids at birth and abnormal skin development, a phenotype characteristic of mice with mutations in EGF-R signaling components. In genetic crosses, a heterozygous Shp-2 mutation dominantly enhanced the phenotype of a weak mutant allele of EGF-R (wa-2), resulting in distinctive growth retardation, developmental defects in the skin, lung, and intestine, and perinatal mortality that are reminiscent of EGF-R knockout mice. Biochemical analysis revealed that signal propagation proximal to the EGF-R upon EGF stimulation was significantly attenuated in wa-2 fibroblast cells, which was exacerbated by the additional Shp-2 mutation. Thus, we provide biological evidence here that protein-tyrosine phosphatase Shp-2 acts to enhance information flow from the EGF-R in mouse growth and development.

Arachidonic acid induces mobilization of calcium stores and c-jun gene expression: evidence that intracellular calcium release is associated with c-jun activation.

Arachidonic acid (AA) plays a signaling role in the induction of several genes. We previously demonstrated that AA induces c-jun gene expression in the stromal cell line +/+.1 LDA 11 by a signaling pathway involving activation of the c-jun amino-terminal kinase (JNK). This study investigated the role of calcium in AA signaling of c-jun activation in +/+.1 LDA 11 cells. AA (10-50 microM) caused a rapid dose-dependent rise in cytosolic calcium. AA-induced calcium mobilization involved both influx of extracellular calcium and the release of intracellular calcium. The importance of calcium was investigated by variation of the extracellular calcium concentration, chelation of intracellular calcium and by calcium ionophore-induced influx of extracellular calcium. AA-induced c-jun gene expression and increased luciferase activity of a construct containing the high affinity AP-1 binding site was decreased in cells preincubated with the intracellular calcium chelator 1,2-bis(o-aminophenoxy)-eThane-N,N,N',N',-tetraacetic acid tetra(aceToxymethyl-esTer) (BAPTA-AM, 10 microM) prior to stimulation with AA. Similarly, chelation of intracellular calcium decreased AA-induced JNK activation. On the contrary, changes in the extracellular calcium concentration had no effect. Also, ionophore A23187 failed to induce c-jun and JNK activation either alone than in combination with AA. These results suggested that calcium was required for AA-dependent activation of c-jun, but that calcium alone was insufficient to induce activation of c-jun. Thus, release of calcium from intracellular stores is implicated in the signaling pathway of AA-induced c-jun activation in stromal cells.

Pharmacoeconomics of lipid-lowering agents for primary and secondary prevention of coronary artery disease.

Cardiovascular disease is the leading cause of death and the leading source of healthcare expenditure in the US and most other industrialised countries. Cholesterol lowering by pharmacological means prevents atherosclerotic plaque progression and has been shown to reduce both fatal and nonfatal coronary events in patients with or without coronary artery disease (CAD). Because of their excellent efficacy and safety profiles, the introduction of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (also known an 'statins') in 1987 raised hopes for demonstrating the survival benefit of cholesterol reduction. In the past decade, several large-scale placebo-controlled trials with statin therapy have revisited the relationship between cholesterol reduction, cardiovascular disease and mortality. The West of Scotland Coronary Prevention Study (WOSCOPS) [pravastatin] and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) [lovastatin] have shown significant cardiovascular disease reduction in primary prevention trials of patients with elevated and normal cholesterol levels, respectively. The Scandinavian Simvastatin Survival Study (4S), the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study and the Cholesterol and Recurrent Events (CARE) trial [pravastatin] have shown significant cardiovascular disease reduction in patients with a previous history of CAD with high, moderate and normal cholesterol levels, respectively. Three of these studies (4S, WOSCOPS and LIPID) have shown significant reduction in all-cause mortality, while all the statin secondary prevention trials (4S, CARE and LIPID) have demonstrated significant reduction in cerebrovascular disease/ Earlier cholesterol reduction cost-effectiveness studies with nonstatin treatments (bile acid resins, fibrates, niacin and diet) suggested that only patients at extremely high risk could be treated with lipid therapy in a cost-effective manner. More recently, rigorous outcomes evidence demonstrates that statins, particularly for simvastatin for secondary prevention and lovastatin for primary prevention, have a broadly favourable cost-effectiveness profile. Based on US medical price levels and the available clinical trial data on statins, it would be cost effective [e.g. cost less than $US50,000/year of life saved] to intervene with statin therapy in any patient with an annual CAD risk exceeding 1%. This includes all patients with pre-existing CAD or diabetes mellitus, and many more primary prevention patients than are currently contemplated by the US National Cholesterol Education Panel treatment guidelines. Achieving such a goal will require enormous changes in patient education, clinical perspective, healthcare practice and healthcare finances. But any proven opportunity for saving the lives of 25% of those dying from cardiovascular disease each year deserves to be considered with the utmost seriousness and urgency.

Biased suppression of hematopoiesis and multiple developmental defects in chimeric mice containing Shp-2 mutant cells.

Shp-2 is a cytoplasmic tyrosine phosphatase that contains two Src homology 2 (SH2) domains at the N terminus. Biochemical data suggests that Shp-2 acts downstream of a variety of receptor and cytoplasmic tyrosine kinases. A targeted deletion mutation in the N-terminal SH2 (SH2-N) domain results in embryonic lethality of homozygous mutant mice at midgestation. In vitro embryonic stem (ES) cell differentiation assays suggest that Shp-2 might play an important role in hematopoiesis. By aggregating homozygous mutant (Shp-2(-/-)) ES cells and wild-type (WT) embryos, we created Shp-2(-/-)-WT chimeric animals. We report here an essential role of Shp-2 in the control of blood cell development. Despite the widespread contribution of mutant cells to various tissues, no Shp-2(-/-) progenitors for erythroid or myeloid cells were detected in the fetal liver and bone marrow of chimeric animals by using the in vitro CFU assay. Furthermore, hematopoiesis was defective in Shp-2(-/-) yolk sacs. In addition, the Shp-2 mutation caused multiple developmental defects in chimeric mice, characterized by short hind legs, aberrant limb features, split lumbar vertebrae, abnormal rib patterning, and pathological changes in the lungs, intestines, and skin. These results demonstrate a functional involvement of Shp-2 in the differentiation of multiple tissue-specific cells and in body organization. More importantly, the requirement for Shp-2 is more stringent in hematopoiesis than in other systems.

Mutation analysis of the 6-pyruvoyl-tetrahydropterin synthase gene in Chinese hyperphenylalaninemia caused by tetrahydrobiopterin synthesis deficiency.

Hyperphenylalaninemia (HPA) may be caused by deficiency of phenylalanine hydroxylase or tetrahydrobiopterin (BH4), the essential cofactor for the aromatic amino acid hydroxylases. 6-Pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is a major cause of BH4 deficient HPA. In this study, seven single base mutations at nucleotides 73 (C>G), 155 (A>G), 166 (G>A), 209 (T>A), 259 (C>T), 286 (G>A), and 317 (C>T) on PTPS cDNA were detected in Chinese PTPS-deficient HPA by polymerase chain reaction and solid phase DNA sequencing. These nucleotide alterations result in R25G, N52S, V56M, V70D, P87S, D96N, and T106M amino acid substitutions, respectively. The R25G, V56M, V70D, and T106M were novel mutations found in PTPS gene. By analysis of 38 PTPS mutant alleles from 19 unrelated Chinese PTPS-deficient HPA families, the allele frequency of these mutations in Chinese PTPS-deficient HPA were determined to be approximately 5.3% (R25G), 34.2% (N52S), 7.9% (V56M), 2.6% (V70D), 36.8% (P87S), 7.9% (D96N), and 2.6% (T106M), respectively. Two common mutations, N52S and P87S, were found to account for 71% of the Chinese PTPS mutant alleles. The N52S mutation accounts for 48% of the southern Chinese PTPS mutation, but only one (9%) of the northern Chinese PTPS mutant allele was found to be N52S, which suggested that the N52S mutation might be southern Chinese. Clinically, the V56M mutation was found to associate with the mild form of PTPS deficiency. However, the R25G, N52S, P87S, and D96N were found mainly in the patients with severe clinical symptom. Using polymerase chain reaction-based mutation analysis, a fetus at risk of PTPS deficiency was diagnosed prenatally to be a carrier of N52S mutation.

Two-photon fluorescence microscopy of laurdan generalized polarization domains in model and natural membranes.

Two-photon excitation microscopy shows coexisting regions of different generalized polarization (GP) in phospholipid vesicles, in red blood cells, in a renal tubular cell line, and in purified renal brushborder and basolateral membranes labeled with the fluorescent probe laurdan. The GP function measures the relative water content of the membrane. In the present study we discuss images obtained with polarized laser excitation, which selects different molecular orientations of the lipid bilayer corresponding to different spatial regions. The GP distribution in the gel-phase vesicles is relatively narrow, whereas the GP distribution in the liquid-crystalline phase vesicles (DOPC and DLPC) is broad. Analysis of images obtained with polarized excitation of the liquid-crystalline phase vesicles leads to the conclusion that coexisting regions of different GP must have dimensions smaller than the microscope resolution (approximately 200 nm radially and 600 nm axially). Vesicles of an equimolar mixture of DOPC and DPPC show coexisting rigid and fluid domains (high GP and low GP), but the rigid domains, which are preferentially excited by polarized light, have GP values lower than the pure gel-phase domains. Cholesterol strongly modifies the domain morphology. In the presence of 30 mol% cholesterol, the broad GP distribution of the DOPC/DPPC equimolar sample becomes narrower. The sample is still very heterogeneous, as demonstrated by the separations of GP disjoined regions, which are the result of photoselection of regions of different lipid orientation. In intact red blood cells, microscopic regions of different GP can be resolved, whereas in the renal cells GP domains have dimensions smaller than the microscope resolution. Preparations of renal apical brush border membranes and basolateral membranes show well-resolved GP domains, which may result from a different local orientation, or the domains may reflect a real heterogeneity of these membranes.

Rat liver preservation. I. The components of UW solution that are essential to its success.

A total of 278 orthotopic rat liver grafts, without arterialization, were performed, in an attempt to determine which of the individual components of UW solution are essential. Livers were preserved by in situ flushing and cold storage with the following results: 56% of rats survived for 1 week after 9 hr of preservation with UW solution as compared with 44% using Marshall solution, and 10% using Collins solution. Having established LD 50 for UW solution, we then omitted its components one at a time and found that omission of HES, raffinose, allopurinol, adenosine, phosphate buffer, or MgSO4 did not change survival after 9 hr of preservation. Omission of lactobionate, glutathione, and dexamethasone, respectively, resulted in decreased survival, whereas elimination of insulin surprisingly increased survival. In ensuing dose-response studies, the concentrations of lactobionate, glutahione, dexamethasone in UW solution proved to be optimal. Finally, livers were preserved with a solution containing only lactobionate, glutathione, dexamethasone, raffinose, and phosphate buffer, resulting in 53% animal survival, as compared with 56% for the unchanged UW solution. We conclude that UW solution can be simplified without loss of effectiveness in this model.

Increased urinary excretion of beta-hydroxyisovaleric acid in ketotic and non-ketotic type II diabetes mellitus.

To evaluate the catabolism of leucine in diabetes mellitus, the urinary excretion of beta-hydroxyisovaleric acid, a by-product of leucine catabolism, in 21 nonproteinuric type II diabetic patients with and without ketosis and 21 control subjects was measured using gas chromatography-mass spectrometry. Urinary beta-hydroxyisovaleric acid and serum leucine concentrations were higher in the 9 ketotic diabetic patients than in the 12 nonketotic diabetic patients (p less than 0.005, p less than 0.01, respectively) or in the control subjects (p less than 0.01, p less than 0.01, respectively). The serum leucine concentrations in the nonketotic diabetic patients and control subjects did not differ significantly (p greater than 0.05), but urinary beta-hydroxyisovaleric acid concentrations were significantly greater in the former (p less than 0.01). These data suggest that in type II diabetic patients the catabolism of leucine is accelerated even in the absence of ketosis and that the urinary beta-hydroxyisovaleric acid concentration is a useful marker of short-term metabolic control in these patients.