In vivo kinetics and displacement study of a carbon-11-labeled hallucinogen,N,N-[11C]dimethyltryptamine

The endogenous hallucinogen, N,N-dimethyltryptamine (DMT), was labeled with carbon-11 and its regional distribution in rat brain studied. [¹¹C]DMT showed higher accumulation in the cerebral cortex, caudate putamen, and amygdaloid nuclei. Studies of the subcellular distribution of [¹¹C]DMT revealed the specific localization in the fractions enriched with serotonin receptors only when a very low dose was injected into rats. The proportions of the radioactivity in receptor-rich fractions were greatly enhanced by pretreatment with the monoamine oxidase inhibitor, pargyline. Specific binding of [¹¹C]DMT to serotonin receptors in dog brain was demonstrated by a positron emission tomographic study in which 5-methoxy-N,N-dimethyltryptamine caused approximately 20% displacement of the radioligand from the receptors.     

Successful treatment with balloon dilatation using a double‐balloon enteroscope for a stricture in the small bowel of a patient with Crohn's disease

The requirement for endoscopic access to a stricture is a major limitation of the endoscopic dilatation for the treatment of strictures in the gastrointestinal tract. We have developed the double‐balloon enteroscopy method that enables visualization of the entire small bowel. In addition, double‐balloon enteroscopy has a potential for the interventional therapy including dilatation of strictures. We present here a case of jejunal strictures in a 47‐year‐old woman with Crohn's disease successfully treated with a balloon catheter in combination with double‐balloon enteroscopy. Balloon dilation with double‐balloon enteroscopy is a promising method for the treatment of small bowel strictures in Crohn's disease.     

Myocardial 11C-diacylglycerol accumulation and left ventricular remodeling in patients after myocardial infarction.

Left ventricular (LV) remodeling after myocardial infarction (MI) is a maladaptive process that increases the risk of heart failure and death. The myocardial phosphoinositide cycle, which is located downstream from several neurohumoral factors, plays a crucial role in LV remodeling. Our animal studies demonstrated that 1-[1-11C]butyryl-2-palmitoyl-rac-glycerol (11C-DAG) can be used to visualize regions with an activated phosphoinositide cycle. Therefore, we examined whether myocardial 11C-DAG accumulation assessed by PET is relevant to LV enlargement and systolic dysfunction in post-MI patients. METHODS: We performed PET with 11C-DAG in 13 post-anteroseptal MI patients and 4 healthy volunteers. We placed regions of interest on the noninfarcted myocardium and calculated the myocardium-to-left atrial (LA) chamber ratio of 11C-DAG accumulation. RESULTS: The myocardium-to-LA chamber ratio of 11C-DAG was significantly higher in the post-MI patients (mean +/- SD, 1.73 +/- 0.35) compared with that of the healthy volunteers (mean +/- SD, 1.25 +/- 0.13; P < 0.05). In the post-MI patients, the myocardium-to-LA chamber ratio of (11)C-DAG was significantly correlated with the LV end-diastolic volume index (r = 0.79, P < 0.01) and the plasma concentration of brain natriuretic peptide (r = 0.85, P < 0.001) and negatively correlated with the LV ejection fraction (r = -0.69, P < 0.01). CONCLUSION: These findings suggest that the myocardial 11C-DAG accumulation assessed by PET is relevant to LV enlargement, LV systolic dysfunction, and humoral activation in post-MI patients. This new imaging strategy based on intracellular signaling may contribute to the assessment and treatment of post-MI patients.     

Effects of horizontal cell network architecture on signal spread in the turtle outer retina. experiments and simulations

In thePseudemys turtle retina five functionally distinct, electrically coupled networks of horizontal cells distribute signals in the outer plexiform layer. These networks differ significantly in their architecture, as determined by intracellular labeling with Neurobiotin after physiological recording and identification. The density of H1 horizontal cells is highest, ranging around 1800 cells/mm² at approximately 2.3 mm eccentricity. H1 horizontal cell somata are connected via 6–10 thin, short dendrites. The H1 horizontal cell axon terminal network is composed of thick axon terminals, forming a three-dimensional, sheath-like structure. Networks of coupled H2 and H3 horizontal cells have cell densities of around 210 cells/mm² and 350 cells/mm² respectively, at the same eccentricity of 2.3 mm. Cell bodies are connected with 6–12 long, thin dendrites. Here we report for the first time H4 horizontal cell networks. Cell density is approximately 970 cells/mm² at 2 mm eccentricity, and cell bodies are connected with 6–10 thin, short dendrites. General properties of passive voltage spread were compared for three of these horizontal cell networks using NeuronC. Realistic network architectures were obtained by digitizing the intracellularly labeled networks, respectively. One network obtained from coupled H1 horizontal cell bodies, one from coupled H1 horizontal cell axon terminals, and one from H2 horizontal cells were simulated. These three realistic networks were compared with an artificial, electrically coupled regular triangular network. Passive signal spread in these networks strongly depended on the exact network architecture using otherwise identical parameters. Changes in coupling strength affected signal spread in these networks differently. As in the experimental situation, changes in synaptic conductance influenced signal spread. Some principal effects of extensively coupled horizontal cells on photoreceptor signal processing were simulated with one type of photoreceptor connected by telodendria, synapsing onto an underlying triangular network and receiving feedback synapses. Under certain conditions, spatial information is coded in single photoreceptors. This was also the case in the experimental situation. In the simulation, spatial filter adjustment for optimal spatial coding in photoreceptors can be achieved by changing coupling strength in the horizontal cell network.     

Recombinant human granulocyte colony-stimulating factor enhanced cytotoxicity of Ara-C in Ara-C-resistant leukemic cells from a patient with biphenotypic leukemia in cell kinetic quiescence.

In vitro preincubation with recombinant granulocyte colony-stimulating factor(rhG-CSF, 100 ng/ml) enhanced the cytotoxicity of 1-beta-D-arabinofuranosylcytosine(Ara-C) in leukemic cells resistant to Ara-C from a patient with biphenotypic leukemia. Treatment of the cells with rhG-CSF resulted in a 17-fold increase in DNA synthesis, 4.6-fold increase in percentage of S-phase, and a two-fold increase in Ara-CTP formation. Maximal effect was observed at 72 h of incubation. Combination chemotherapy with rhG-CSF and Ara-C to the patient showed remarkable cytoreduction. These results indicate that recruitment of resistant leukemic cells in cell kinetic quiescence is inducible by rhG-CSF and that it is possible enhancement of the cytotoxicity to cell cycle-specific drugs such as Ara-C.     

Intraocular pressure and aqueous humor flow during a euglycemic-hyperinsulinemic clamp in patients with type 1 diabetes and microvascular complications

Background  

Microvascular complications, including retinopathy and nephropathy are seen with type 1 diabetes. It is unknown whether functional changes in aqueous humor flow or intraocular pressure (IOP) develop in parallel with these complications. This study was designed to test the hypothesis that clinical markers of microvascular complications coexist with the alteration in aqueous humor flow and IOP.     

An intracellular antigen that reacts with MO2, a monoclonal antibody to CD14, is expressed by human lymphocytes

CD14, a lipopolysaccharide (LPS) receptor, is present on the surface membrane of phagocytic leukocytes; it is also present in a soluble form in serum. Recently published results confer to this molecule novel functions that are linked to T-cell activation and to apoptosis. We report here that we have defined and characterized a novel lymphocyte population in human peripheral blood, a population that expresses an intracellular antigen detectable with MO2, a monoclonal antibody directed against the human CD14 molecule. This population is composed primarily of CD8-positive T-cells. We found surprisingly that this novel MO2-positive population of lymphocytes was greatly enhanced in asymptomatic, untreated HIV-positive individuals.     

Studies on the Level of Natural Antibodies Reactive with Various Tumor Cells during Urethane Carcinogenesis in BALB/c Mice

Serum from young normal BALB/c mice was found to contain IgM antibodies able tomediate complement-dependent lysis of certain syngeneic or allogeneic tumor target cells. The titer of such naturally occurring antitumor antibodies (NATA) was found to increase with aging.A longitudinal serological study comparing the cytotoxicity potential of NATA fromnormal and from urethan-treated BALB/c mice was performed. It was found that urethan-treated mice that did not develop primary lung-adenomas within the duration of the experi-ment had significantly lower NATA titers, against one out of 4 target cells assayed, than urethan-treated animals that developed lung adenomas. This difference was evident in two independent experiments. The results suggested that the lower NATA activity of the urethan-treated mice that did not develop tumors existed even before exposure to the carcinogenic insult. This raises the possibility that certain populations could be segregated according to their natural antibody profile into those individuals which will develop primary tumors within a certain period if exposed to a subthreshold amount of carcinogen, and those which will not.     

Analysis of wild-type and e antigen-defective hepatitis B viruses during the course of a short-term corticosteroid therapy in chronic hepatitis B

Hepatitis B virus (HBV), with a G-to-A point mutation at nucleotide 83 in the precore region (mutant HBV83), accounts for most cases of hepatitis B e antigen (HBeAg)-defective HBV. However, it is still not clear how mutant HBV83 is associated with HBe seroconversion. Twenty-six HBeAgpositive patients with chronic hepatitis B who received oral prednisolone (30 mg/day) for 3 weeks were studied to clarify the prevalence of mutant HBV83 during the treatment using polymerase chain reaction with a restriction fragment length polymorphism assay. Twelve (46%) patients seroconverted to anti-HBe 1 year after treatment, whereas 14 (54%) did not. The proportion of mutant HBV83 to whole HBV remained unchanged in both groups during an acute exacerbation induced by withdrawal of corticosteroids. Among 12 anti-HBe-0seroconverted patients, five (56%) of nine patients with only wild-type HBV at baseline developed detectable levels of mutant HBV83 while all three patients with a mixed viral population of wild-type HBV and mu tant HBV83 at baseline developed a higher pro portion of mutant HBV83 one year after treat ment. In contrast, these changes were observed in only one (14%) of seven who failed to seroconvert. The results indicate that a flare-up of hepa titis precedes emergence or selection of mutant HBV83, followed by HBe seroconversion in patients with chronic hepatitis B. © 1995 WiIey-Liss, Inc.