Early onset of diabetes mellitus associated with the mitochondrial DNA T14709C point mutation: patient report and literature review.

We report a family in which a mother and son were affected with diabetes mellitus and myopathy characterized by ragged red fibers and suggestive of mitochondrial disease. Mitochondrial DNA (mtDNA) analysis of DNA isolated from peripheral blood showed a T-->C point mutation at nucleotide position 14709, in the transfer RNA gene for glutamic acid. We review the association of diabetes and mtDNA mutations.

Regulation of rat cardiac Kv1.5 gene expression by thyroid hormone is rapid and chamber specific.

Thyroid hormone affects the contractile and electrophysiological properties of the cardiac myocyte that result in part from changes in the expression of thyroid hormone-responsive cardiac genes, including those that regulate membrane ion currents. To determine the molecular mechanisms underlying this effect, expression of a voltage-gated K+ channel, Kv1.5, was measured in response to thyroid hormone.

Simultaneous strumal ovarii and lymphoma with emphasis on the diagnostic usefulness of immunohistochemical stains.

Strumal ovarii has been rarely associated with other tumors, such as carcinoid tumor, carcinoma, and primary ovarian malignant lymphoma. We report the coexistence of a strumal ovarii and ovarian involvement by malignant lymphoma in a 70-year-old woman. The tumors were detected 10 years following exposure to ionizing radiation during the Chernobyl nuclear tragedy.

Gene-enhanced tissue engineering: applications for bone healing using cultured periosteal cells transduced retrovirally with the BMP-7 gene.

Periosteum has cell populations, including osteoprogenitor and chondroprogenitor cells, that can be grown in cell culture and form both bone and cartilage under appropriate conditions. The authors have shown previously that cultured periosteal cells can be used in the tissue engineering of bone, and they demonstrated substantial bone formation in a rabbit cranial defect model. In the current study, principles of tissue engineering were combined with principles of gene therapy to produce cultured periosteal cells transduced retrovirally with the bone morphogenetic protein 7 (BMP-7) gene to be used in the treatment of bone defects.

Expression of human bone morphogenic protein 7 in primary rabbit periosteal cells: potential utility in gene therapy for osteochondral repair.

A commonly encountered problem in orthopedics is bone and cartilage tissue injury which heals incompletely or without full structural integrity. This necessitates development of improved methods for treatment of injuries which are not amenable to treatment using current therapies. An already large and growing number of growth factors which play significant roles in bone remodeling and repair have been identified in the past few years.

Identification of structural elements of the testis-specific voltage dependent calcium channel that potentially regulate its biophysical properties.

Calcium influx through voltage-dependent calcium channels regulates the physiological acrosome reaction of mammalian spermatozoa. Expression of the mRNA for these voltage-dependent calcium channels and its co-ordinated translation is initiated early in rat male germ line development and continues throughout spermatogenesis. Herein, we report the complete mRNA and deduced amino acid sequence of the alpha1c pore-forming subunit of the rat testis-specific L-type calcium channel.

CD14 plays no major role in shock induced by Staphylococcus aureus but down-regulates TNF-alpha production.

Recent in vitro studies have suggested that CD14, a major receptor for LPS, may also be a receptor for cell wall components of Gram-positive bacteria and thus play a role in Gram-positive shock. To analyze the in vivo role of CD14 in responses to Gram-positive bacteria, CD14-deficient and control mice were injected with Staphylococcus aureus, and the effects on lethality, bacterial clearance, and production of cytokines were analyzed. Survival of CD14-deficient and control mice did not differ significantly after administration of various doses of either unencapsulated or encapsulated S.

Lipopolysaccharide structure influences the macrophage response via CD14-independent and CD14-dependent pathways.

CD14, a protein expressed on the surface of monocytes and neutrophils, is a major receptor for lipopolysaccharide (LPS). Studies with normal and CD14-deficient macrophages show that responses to low concentrations of LPS require expression of CD14, whereas responses to high concentrations of LPS are CD14-independent. Since LPS isolated from different bacterial species shows structural variability, studies were performed to determine whether differences in LPS structure influence CD14-dependent and CD14-independent responses.

The utility of quantitative body surface isoarea mapping for predicting ventricular tachyarrhythmias.

Noninvasive techniques, such as the signal averaged ECG, have been used to assess risk of ventricular tachyarrhythmias (VT). However, these methods produce false positive and negative results. The purpose of this study was to develop body surface map algorithms which would enhance prediction of susceptibility to VT.

Combined effect of high-fat diet and copper deficiency during gestation on fetal copper status in the rat.

We have previously shown that a low-copper (Cu) diet produced alterations in placental Cu transport and fetal Cu stores. Because Cu deficiency has been associated with lipid deposition in rat dam liver, we hypothesized that a high fat intake, a prevalent dietary habit in many populations, may worsen fetal Cu status and its closely linked iron (Fe) deposits. Pregnant rats were fed one of four diets during the second half of gestation: NFNCu: normal fat (7%), normal Cu (6 mg/kg); HFNCu: high fat (21%), normal Cu; NFLCu: normal fat, low Cu (0.

Acquired factor VIII inhibitors--successful treatment with an oral outpatient regimen.

A rare cause of a spontaneous, life threatening coagulopathy in adults is the development of autoantibodies to factor VIII. We recently had the opportunity to treat seven patients with this disorder. After stabilization, they were given a regimen consisting of prednisone and oral cyclophosphamide.

Anticipation in Crohn's disease may be influenced by gender and ethnicity of the transmitting parent.

Objective: We sought to examine whether anticipation (an earlier age of onset in succeeding generations) is observed in Crohn's disease (CD) patients within the New York metropolitan area, and whether there are differences in the degree of anticipation with respect to gender and ethnicity of the affected parent.

Methods: Sixty-one parent-child pairs both affected by CD were identified; about half of the pairs were of Ashkenazi Jewish descent. An additional 17 pairs of second-degree relatives with CD were also identified.

Voltage dependent calcium channels in mammalian spermatozoa.

Calcium influx is an absolute requirement for the physiological acrosome reaction in sperm from all sources examined, both invertebrate and mammalian. Pharmacological studies suggest that the major channel in the sperm head plasma membrane responsible for modulating calcium entry and intracellular ionized calcium levels could be either an L-type (a class of high voltage-activated) or a T-type (low voltage-activated) voltage-dependent calcium channel. Patch clamp analysis of calcium currents in immature spermatogenic cells demonstrates the presence of T-type currents.

Immunophenotypic analysis of peripheral blood mononuclear cells undergoing in vitro apoptosis after isolation from human immunodeficiency virus-infected children.

Lymphocytes of human immunodeficiency virus (HIV)-infected individuals undergo accelerated apoptosis in vitro, but the subsets of cells affected have not been clearly defined. This study examined the relationship between lymphocyte phenotype and apoptotic cell death in HIV-infected children by flow cytometry. Direct examination of the phenotype of apoptotic lymphocytes was accomplished using a combination of surface antigen labeling performed simultaneously with the Tdt mediated Utp nick end-labeling (TUNEL) assay.

Fetuin (alpha2-HS-glycoprotein) opsonizes cationic macrophagedeactivating molecules.

Macrophages become activated by bacterial endotoxin (lipopolysaccharide) and other stimuli to release proinflammatory cytokines and NO. To prevent release of toxic or potentially lethal quantities of these factors, the state of macrophage activation is counter-regulated by anti-inflammatory mediators (e.g.

Comparison of seven quantitative assays to assess lymphocyte cell death during HIV infection: measurement of induced apoptosis in anti-Fas-treated Jurkat cells and spontaneous apoptosis in peripheral blood mononuclear cells from children infected with HIV.

The study of apoptosis in relation to various human disease states, particularly HIV infection, has seen a tremendous increase in activity. In this article, values obtained by seven different assays, designed to quantify apoptosis and applicable to the study of HIV infection, are compared in two cell systems: (1) stimulus-induced apoptosis in Jurkat cells treated with anti-Fas antibody and (2) spontaneous apoptosis in PBMCs isolated from HIV-infected children. The methods used included measurement of cells with subdiploid DNA content, labeling of DNA strand breaks by the TUNEL reaction, annexin V surface labeling for the detection of exposed phosphatidylserine, cytoplasmic antigen labeling with the apoptosis-specific antibody Apo 2.

Recent developments in the pharmacology of anticancer drugs in the elderly.

The aging of the population has focused interest on the care of elderly cancer patients. Data are becoming available that will better guide the use of chemotherapy. Recent studies are presented discussing new pharmacokinetic data on a number of chemotherapeutic agents, with an emphasis on those recently entering clinical practice.

Membrane and soluble forms of Fas (CD95) and Fas ligand in peripheral blood mononuclear cells and in plasma from human immunodeficiency virus-infected persons.

The expression of membrane-bound Fas ligand (FasL) and Fas in lymphocytes and monocytes and levels of soluble forms of FasL (sFasL) and Fas (sFas) in plasma from human immunodeficiency virus (HIV)-positive and -negative subjects was evaluated. Surface FasL was detectable on monocytes, but poorly so on lymphocytes, even in the presence of KB8301, a metalloproteinase inhibitor. Unexpectedly, monocytes of HIV-positive subjects expressed less FasL than those of HIV-negative volunteers.

Cephalhematoma and caput succedaneum: do they always occur in labor?

Objective: Our purpose was to analyze our experience with cephalhematomas detected prenatally by ultrasonography.

Study Design: Seven cases of cephalhematomas were identified prenatally among 16,292 fetuses having comprehensive ultrasonographic examinations between 1993 and 1996. The course of pregnancy and the neonatal outcome were reviewed in each case.

Cerebral glucose metabolism in women with panic disorder.

Objective: This study was undertaken to clarify earlier inconsistent findings in brain metabolic topography in panic disorder patients at rest.

Method: Positron emission tomography (PET) with [18F]fluorodeoxyglucose was used to determine cerebral metabolic activity in six female patients with a DSM-III-R diagnosis of panic disorder and in six healthy female volunteers. All patients with panic disorder were medication free and were sensitive to lactate infusion.

Dose and dose intensity as determinants of outcome in the adjuvant treatment of breast cancer. The Cancer and Leukemia Group B.

Background: Both total dose and dose intensity of adjuvant chemotherapy are postulated to be important variables in the outcome for patients with operable breast cancer. The Cancer and Leukemia Group B study 8541 examined the effects of adjuvant treatment using conventional-range dose and dose intensity in female patients with stage II (axillary lymph node-positive) breast cancer.

Methods: Within 6 weeks of surgery (radical mastectomy, modified radical mastectomy, or lumpectomy), 1550 patients with unilateral breast cancer were randomly assigned to one of three treatment arms: high-, moderate-, or low-dose intensity.

Mineral composition of meconium: effect of prematurity.

Objectives: We hypothesized that the concentration of major essential mineral elements in meconium correlate with gestational age (GA) or birth weight. To verify this premise we determined the concentration in meconium of calcium, magnesium, phosphorus, copper, zinc, iron, and manganese.

Methods: Thirty-four appropriate for age singleton infants without major congenital anomalies were divided into four GA groups (in weeks): 24 to 28; 29 to 33; 34 to 37; 38 to 42, or in birth weight groups (in g): < 1500; 1500-1999; 2000-2499; > or = 2500.

Proabsorptive effects of modified tapioca starch as an additive of oral rehydration solutions.

Background: Partially hydrolyzed starches from staple cereals, obtained by heat or by enzymatic treatment, are often used in the formulation of homemade or extemporaneously used oral rehydration solutions used in developing countries. Conflicting or anecdotal results obtained thus far could be clarified with a standardized preparation tested under well-controlled laboratory conditions.

Methods: A modified commercial tapioca starch was tested.

Insulin-like growth factor-I and high protein diet decrease calpain-mediated proteolysis in murine muscular dystrophy.

In muscular dystrophy (MD) the imbalance between muscle protein synthesis and degradation may be an important factor leading to muscle wasting. The three major pathways of muscle proteolysis identified in skeletal muscle are: the lysosomal cathepsin pathway, the calcium-dependent calpain pathway, and the ATP-dependent ubiquitin pathway. Insulin-like growth factor I (IGF-I) and a high-protein diet (HPD) have been shown to reduce proteolysis in skeletal muscle.