Gestational diabetes: a red flag for future Type 2 diabetes in pregnancy? A retrospective analysis.

AIMS: This study sought to understand the relationship between Type 2 diabetes in pregnancy and previous gestational diabetes (GDM), and determine whether a previous pregnancy with GDM was associated with subsequent better pregnancy planning. METHODS: A retrospective review of medical records of women with Type 2 diabetes in pregnancy was conducted at three teaching hospitals to ascertain whether they had earlier GDM, and to determine whether this is associated with differences in measures of pregnancy planning and diabetes management. RESULTS: Of 172 index pregnancies affected by Type 2 diabetes, in 76 (44%) cases, the mother had a previous history of GDM. Within this cohort, a diagnosis of 'overt diabetes in pregnancy', made on the basis of a GTT result during pregnancy in the WHO diabetic range with persistent diabetes post partum, was more common among women who had previous GDM than women who had not had GDM (20% vs 7%, P = 0.02). Women who previously had GDM did not exhibit a higher incidence of preconception planning or folate supplementation. CONCLUSIONS: It is common for women with Type 2 diabetes in pregnancy to have had GDM previously. The diagnosis of GDM is an opportunity to improve future pregnancy planning and outcomes for women with Type 2 diabetes in pregnancy. This goal is yet to be realized.

Promising Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Human Immunodeficiency Virus Associated Non-Hodgkin's Lymphoma.

This case report explores the potential role of FDG PET/CT in HIV -associated systemic non-Hodgkin's lymphoma (HIV-NHLs). In our locality, there are a cumulative total of 5523 reported HIV infections cases since 1984. We reported a case of HIV-related Burkitt's lymphoma (BL) and a case of diffuse large B-cell lymphoma (DLBCL) that underwent PET/CT examination in our PET centre. In HIV-NHLs patients, we must be reminded that not all hypermetabolic foci represent lymphomatous lesions. There is a close correlation between the pattern of lymphoid tissue activation in FDG PET/CT and HIV progression in patients without HIV-related malignancy. The unique patterns of lymphoid tissue activation observed in HIV-infected patients have great clinical implications. Secondly, HIV-infected patients are prone to suffer from opportunistic infections due to immunosuppression, particularly in those with high levels of HIV viral loads. FDG PET/CT cannot reliably differentiate metabolic active lymphoma from other benign diseases such as inflammation in the context of low CD4 count and high viral loads. In those cases, benign markedly hypermetabolic foci can be erroneously interpreted as lymphoma, particularly in those normal-sized lymph nodes. Furthermore, FDG PET/CT may be useful for assessing the efficacy of HAART in suppressing HIV replication and detecting its complication such as lipodystrophy. FDG PET/CT may play a potential useful role in staging and management of HIV -associated systemic non-Hodgkin's lymphoma. Plasma variables such as viral loads and CD4 count must be taken into account during image interpretation. FDG PET/CT as a potential useful tool for diagnosis, treatment response assessment and disease relapse detection in HIV -associated systemic non-Hodgkin's lymphoma worth to be further explored.

Synergistic effects of genetic beta cell dysfunction and maternal glucose intolerance on offspring metabolic phenotype in mice.

AIMS/HYPOTHESIS: Diabetes in pregnancy is linked to development of obesity in the offspring, but the mechanisms are not fully understood. Gestational diabetes mellitus (GDM) occurs when beta cells are unable to compensate for the normal insulin resistance of late pregnancy. In this study, we used a murine model of beta cell dysfunction to examine the effects of maternal GDM on phenotype in male offspring with and without an inherited predisposition for beta cell dysfunction. METHODS: Beta cell-specific aryl-hydrocarbon receptor nuclear translocator-null (ßArnt) mice develop GDM from beta cell dysfunction. ßArnt and control female mice were used to induce GDM and non-diabetic pregnancies, respectively. RESULTS: Offspring from GDM pregnancies became spontaneously obese on a normal-chow diet. They were heavier than offspring from non-diabetic pregnancies, with increased body fat. Respiratory exchange ratio (RER) was higher, indicating decreased capacity to switch to lipid oxidation. Metabolic rate in GDM offspring was decreased prior to onset of obesity. The phenotype was more pronounced in ßArnt GDM offspring than in GDM offspring of control genotype, demonstrating an interaction between genotype and pregnancy exposure. ßArnt GDM offspring had increased hypothalamic neuropeptide Y (Npy) and decreased pro-opiomelanocortin (Pomc) expression. Weight, body fat, insulin sensitivity and RER in all mice, and hypothalamic Npy in ßArnt mice were significantly correlated with AUC of maternal late pregnancy glucose tolerance tests (p < 0.01), but not with litter size, maternal weight, triacylglycerol or pre-pregnancy glycaemia. CONCLUSIONS/INTERPRETATION: In ßArnt mice, exposure to GDM and inheritance of genetic beta cell dysfunction had additive effects on male offspring obesity; severity of the offspring phenotype correlated with maternal glycaemia.

Consolidation therapy with autologous blood stem cell transplantation in a patient with primary plasma cell leukaemia.

Primary plasma cell leukaemia (PPCL) is a rare form of plasma cell dyscrasia. Conventional melphalan-based treatment is often ineffective, with a reported median survival of 2-7 months only. We report a 53-year-old man with PPCL who was treated with four cycles of combination chemotherapy including vincristine, adriamycin and dexamethasone that resulted in a good partial remission. High-dose melphalan 200 mg/m2 and autologous peripheral blood stem cell (PBSC) rescue was then given 6 months after diagnosis. Maintenance interferon-alpha was started 8 weeks after transplantation with good drug compliance. Complete remission was achieved and molecular remission was documented 11 months after autologous PBSC transplantation. In conclusion, high-dose therapy followed by autologous stem cell rescue is a feasible option for PPCL that can result in a reasonably sustained remission.

A genomics approach to the comprehensive analysis of the glutathione S-transferase gene family in soybean and maize.

By BLAST searching a large expressed sequence tag database for glutathione S-transferase (GST) sequences we have identified 25 soybean (Glycine max) and 42 maize (Zea mays) clones and obtained accurate full-length GST sequences. These clones probably represent the majority of members of the GST multigene family in these species. Plant GSTs are divided according to sequence similarity into three categories: types I, II, and III. Among these GSTs only the active site serine, as well as another serine and arginine in or near the "G-site" are conserved throughout. Type III GSTs have four conserved sequence patches mapping to distinct structural features. Expression analysis reveals the distribution of GSTs in different tissues and treatments: Maize GSTI is overall the most highly expressed in maize, whereas the previously unknown GmGST 8 is most abundant in soybean. Using DNA microarray analysis we observed increased expression among the type III GSTs after inducer treatment of maize shoots, with different genes responding to different treatments. Protein activity for a subset of GSTs varied widely with seven substrates, and any GST exhibiting greater than marginal activity with chloro-2,4 dinitrobenzene activity also exhibited significant activity with all other substrates, suggesting broad individual enzyme substrate specificity.

Parvovirus B19 infection in a human immunodeficiency virus-infected patient with anemia.

Anemia is generally attributed to zidovudine therapy in human immunodeficiency virus (HIV)-infected patients, although parvovirus B19 infection has been reported as a rare cause. We report on a 24-year-old homosexual man infected with HIV who presented with anemia. He had received aggressive daily antiretroviral therapy (zidovudine 600 mg, lamivudine 300 mg, and saquinavir 1,800 mg) for 2 years. At the time of admission, his CD4+ count was 10 x 10(6) cells/L. A bone marrow aspirate smear showed a marked decrease in erythropoiesis and immunocytochemical staining for parvovirus B19 was positive. Parvovirus B19 viral DNA was detected in the peripheral blood using a polymerase chain reaction-based assay. Serologic studies were positive for parvovirus B19 immunoglobulin (Ig)M antibodies, but negative for IgG antibodies. The patient was treated with packed red blood cell transfusion. Zidovudine was stopped and replaced with zalcitibine 2.25 mg daily after anemia occurred. He did not receive intravenous Ig therapy because of its cost. After discontinuation of zidovudine for 1 year, anemia persisted and the patient depended on regular blood transfusions to control the anemia. This case emphasizes that, in addition to drug-related causes, parvovirus B19 infection should be included in the differential diagnosis of chronic anemia in HIV-infected individuals.

Identification and expression of isoflavone synthase, the key enzyme for biosynthesis of isoflavones in legumes.

Isoflavones have drawn much attention because of their benefits to human health. These compounds, which are produced almost exclusively in legumes, have natural roles in plant defense and root nodulation. Isoflavone synthase catalyzes the first committed step of isoflavone biosynthesis, a branch of the phenylpropanoid pathway. To identify the gene encoding this enzyme, we used a yeast expression assay to screen soybean ESTs encoding cytochrome P450 proteins. We identified two soybean genes encoding isoflavone synthase, and used them to isolate homologous genes from other leguminous species including red clover, white clover, hairy vetch, mung bean, alfalfa, lentil, snow pea, and lupine, as well as from the nonleguminous sugarbeet. We expressed soybean isoflavone synthase in Arabidopsis thaliana, which led to production of the isoflavone genistein in this nonlegume plant. Identification of the isoflavone synthase gene should allow manipulation of the phenylpropanoid pathway for agronomic and nutritional purposes.

Outcomes of Aeromonas bacteremia in patients with different types of underlying disease.

Over a 6-year period, 42 patients with different underlying diseases developed Aeromonas bacteremia in our hospital. The male to female ratio was 2:1. The vast majority of these patients had underlying diseases, including various types of neoplasm (n = 14), liver cirrhosis (n = 11), biliary tract disorder (n = 10) and other illnesses (n = 7). Community-acquired bacteremia was predominant (33 cases, 79%). Aeromonas hydrophila was the most common species isolated (88%). Monomicrobial bacteremia was more common than polymicrobial bacteremia (64% vs 36%). Monomicrobial bacteremia was associated with neoplasm or liver cirrhosis in 80% of patients. Polymicrobial bacteremia was more common in patients with biliary tract disorder than in patients from other groups (60% vs 40%). Escherichia coli (60%) was the predominant concomitant organism isolated. The major clinical manifestations were fever (74%), jaundice (57%), and abdominal pain (45%). Recognized infection sites included biliary tract, soft tissue involvement, peritoneal involvement, while 50% of patients had no recognized infection site. Eight patients (80%) received cholecystectomy due to gall stone with acute cholecystitis. However, none of the cirrhotic patients with necrotizing fasciitis received surgical treatment. The mortality attributed to Aeromonas bacteremia was 70%. Patients with liver cirrhosis or malignancy had a higher acute mortality (death within 7 days after admission) than the other patients (89% vs 11%). We conclude that Aeromonas bacteremia can cause a rapidly fatal outcome and should be considered an important pathogen for septicemia in patients with liver cirrhosis or neoplasm.

An unusual site of chigger bite in a patient with scrub typhus.

A 70-year-old female farmer was admitted to the hospital because of fever, headache, and diarrhea for 7 days. Hypotension, right-sided pleural effusion with respiratory distress and leukocytosis were noted. She was initially treated as systemic bacterial infection by i.v. administration of ampicillin/sulbactam and amikacin. Because fever persisted in spite of aggressive treatment, a repeat thorough physical examination was done. An eschar was found over the left-sided labium majus and an enlarged lymph node was noted over the left inguinal region. Under the impression of scrub typhus, minocycline was administered. The patient's clinical condition improved dramatically within 3 days. The diagnosis was later confirmed by a serologic test for Rickettsia tsutsugamushi.

Macrophage colony-stimulating factor promotes cell survival through Akt/protein kinase B.

The signaling pathways activated by the macrophage colony-stimulating factor (M-CSF) to promote survival of monocyte and macrophage lineage cells are not well established. In an effort to elucidate these pathways, we have used two cell types responsive to M-CSF: NIH 3T3 fibroblasts genetically engineered to express human M-CSF receptors (3T3-FMS cells) and human monocytes. M-CSF treatment induced M-CSF receptor tyrosine phosphorylation and recruitment of the p85 subunit of phosphatidylinositol 3-kinase (PI3K) to these receptors. These M-CSF receptor events correlated with activation of the serine/threonine kinase Akt. To clarify that PI3K products activate Akt in response to M-CSF, NIH 3T3 fibroblasts expressing mutant human M-CSF receptors (3T3-FMS(Y809F)) that fail to activate Ras in response to M-CSF also exhibit increased Akt kinase activity in response to M-CSF challenge. Furthermore, Akt appears to be the primary regulator of survival in 3T3-FMS cells, as transfection of genes encoding dominant-negative Akt isoforms into these fibroblasts blocked M-CSF-induced survival. In normal human monocytes, M-CSF increased the levels of tyrosine-phosphorylated proteins and induced Akt activation in a PI3K-dependent manner. The PI3K inhibitor LY294002 blocked M-CSF-mediated monocyte survival, an effect that was partially restored by caspase-9 inhibitors. These data suggest that M-CSF may induce cell survival through Akt-induced suppression of caspase-9 activation.

Unilateral sacroiliitis as an unusual complication of acupuncture.

Septic sacroiliitis is an uncommon disease and is rarely reported as a complication of acupuncture. We present a case of unilateral septic sarcoiliitis, which developed as a complication of acupuncture because of failure to sterilise the skin properly before treatment. Bone scan and computed tomography were positive for sacroiliitis. After a course of antibiotics with oxacillin for 6 weeks, the condition was completely improved. This case report stresses the importance of sterilisation procedures before acupuncture therapy.

The effect of aging on the response of striatal preproenkephalin and preprotachykinin mRNA contents to chronic haloperidol treatment in rats: measurement by solution-hybridization RNase protection assay.

The preproenkephalin (PPeK) and preprotachykinin (PPT) mRNA contents in 3-, 10- and 23-month-old rats in the striatum were measured by solution hybridization-RNase protection assay after 3 weeks of haloperidol injection. Haloperidol increased striatal PPek mRNA. There was no age-related difference in the response of striatal PPeK mRNA to chronic haloperidol treatment. The PPT mRNA decreased by 21% after the haloperidol treatment in young rats only. Meanwhile, age decreased the PPT mRNA by 27 and 24% in 10- and 23-month-old rats, respectively. It is concluded that there is a difference in the effects of aging on the response of PPek and PPT mRNA contents to haloperidol and that the loss of PPT mRNA response in 10- and 23-month-old rats might be due to the change of dopamine system of the striatum in these rats.

Chronic haloperidol treatment decreases preproenkephalin mRNA in the anterior pituitary: a study by solution-hybridization-RNase protection assay.

By solution-hybridization-RNase protection assay, the preproenkephalin (PPek) mRNA in the anterior pituitary (AL) of male rats was found to decrease by 42% after 3 weeks haloperidol treatment. It is concluded that dopamine may stimulate the AL enkephalinergic system at the level of gene expression.

Activation of Src-family tyrosine kinases during Fas-induced apoptosis.

Stimulation of several human and murine hematopoietically derived cell lines with anti-Fas antibodies induced increased tyrosine phosphorylation of a panel of proteins observed in whole-cell lysates. In the human T cell line Jurkat, the activity of a 56-kDa tyrosine kinase was likewise activated by anti-Fas antibodies. Immunoprecipitation studies of anti-Fas-stimulated human Jurkat and murine 2B4.11 T cells revealed activation of the Src-family tyrosine kinases Lck and Fyn. Fas receptor-induced tyrosine phosphorylation of p120 c-cbl proto-oncogene product was observed in Jurkat T cells. Pharmacological experiments demonstrated that pretreatment of Jurkat cells with tyrphostins inhibited Fas-induced apoptosis; likewise, Lck activity was inhibited by tyrphostins in a dose-dependent fashion. Finally, Lck derived from unstimulated Jurkat T cells formed stable complexes with the intracellular domain of the Fas receptor. These data are consistent with the notion that expression and activation of members of the Src-family kinases is required for Fas-induced cell death in T lymphocytes and consistent with recent findings demonstrating decreased Fas-mediated thymocytic death in Fyn-knockout mice.

The effect of haloperidol on met-enkephalin, beta-endorphin, cholecystokinin and substance P in the pituitary, the hypothalamus and the striatum of rats during aging.

1. Haloperidol increased the Met-enk level in the striatum at all age groups. However, the Met-enk level was decreased in AL of young and middle-aged rats by the drug. 2. Haloperidol elevated the beta-end level in AL and CCK level in NIL in young rats only. 3. The SP content in NIL was decreased by haloperidol in all age groups. 4. With regard to the effect of aging, Met-enk level in AL of middle-aged rats was higher than that in young rats. The beta-end level in AL also increased in old rats. 5. Aging modified the haloperidol effect on beta-end level in AL and CCK level in NIL as the effect was only observed in young rats. 6. In addition, aging caused a blunted response of Met-enk level to haloperidol in the striatum but an increased response of SP content to haloperidol in the NIL.

Cytochrome P-450-catalysed monoterpenoid oxidation in catmint (Nepeta racemosa) and avocado (Persea americana); evidence for related enzymes with different activities.

A cytochrome P-450 present in ripening avocado (Persea americana) fruit mesocarp (CYP71A1) had previously been shown to metabolize the monoterpenoids nerol and geraniol (Hallahan et al. (1992) Plant Physiol. 98, 1290-1297). Using DNA encoding CYP71A1 as a hybridization probe, we have shown by Southern analysis that a related gene is present in the catmint, Nepeta racemosa. RNA blot analysis, together with Western analysis of catmint leaf polypeptides using avocado cyt P-450 antiserum, showed that a closely related gene is expressed in catmint leaves. Cytochrome P-450 in catmint microsomes catalysed the specific hydroxylation of nerol and geraniol at C-10, whereas avocado CYP71A1, in either avocado microsomes or heterologously expressed in yeast, catalysed 2,3- or 6,7-epoxidation of these substrates. These results suggest that orthologous genes of the CYP71 family are expressed in these two plant species, but catalyse dissimilar reactions with monoterpenoid substrates.

Low carbon monoxide affinity allene oxide synthase is the predominant cytochrome P450 in many plant tissues.

A cytochrome P450 with low affinity (2.9 x 10(3) M-1) for CO appears to be the major microsomal P450 in some plant tissues. The presence of low CO affinity cytochrome P450 correlates with its lack of NADPH reducibility and with the presence of high levels of 13(S)-hydroperoxy-9(Z),11(E)-octadecadienoate peroxidase activity. This activity and low CO affinity are retained by purified tulip cytochrome P450, which appears to be catalytically identical to a flaxseed-derived fatty acid allene oxide synthase P450 described previously [Song, W.-C., & Brash, A.R. (1991) Science 253, 781-784]. Other heme-binding ligands, such as CN- and imidazoles, bind weakly to the allene oxide synthase P450s, suggesting that axial coordination in the heme distal pocket may be hindered. We conclude that low CO affinity is characteristic of the allene oxide synthase P450s and that these P450s constitute a major portion of the microsomal P450 in a variety of plant tissues, particularly from monocot species.