Invasion genetics of the Mediterranean fruit fly: variation in multiple nuclear introns

Biological invasions generally start from low initial population sizes, leading to reduced genetic variation in nuclear and especially mitochondrial DNA. Consequently, genetic approaches for the study of invasion history and population structure are difficult. An extreme example is the Mediterranean fruit fly, Ceratitis capitata (Medfly), for which successive invasions during this century have resulted in a loss of 60% of ancestral genetic variation in isozymes and 75% of variation in mitochondrial DNA. Using Medflies as an example, we present a new approach to invasion genetics that measures DNA sequence variation within introns from multiple nuclear loci. These loci are so variable that even relatively recently founded Medfly populations within California and Hawaii retain ample genetic diversity. Invading populations have only lost 35% of the ancestral genetic variation. Intron variation will allow high-resolution genetic characterization of invading populations in both natural and managed systems, although non-equilibrium methods of analysis may be necessary if the genetic diversity represents sorting ancestral polymorphism.     

A complex photodermatosis: solar urticaria progressing to polymorphic light eruption

Causative agents of drug eruptions are frequently unknown, and skin tests with candidate drugs would be useful before systemic challenge. It remains to be clarified how phostosentive lichenoid drug eruptions are induced, but allergy, including delayed type allergy, has been suggested. Two patients who had taken anti-tuberculous drugs developed a lichenoid drug eruption, primarily on sun-exposed skin. Patch and photopatch tests were performed with each of the ingested drugs (10% in petrolatum). Photopatch tests to isoniazid (INH) were positive. These were confirmed by oral challenge followed by irradiation with UVA. In conclusion, photopatch tests facilitated identification of the causative drug in two patients with photosensitive lichenoid eruptions to INH.     

The electrophysiology of prefrontal serotonin systems: therapeutic implications for mood and psychosis

A newly described synaptic action of serotonin (5-HT) in the cerebral cortex is reviewed, and implications for mood and psychosis are discussed. Recordings in brain slices show that 5-HT induces a rapid increase in excitatory postsynaptic potentials/currents (EPSPs/EPSCs) in virtually all layer V pyramidal cells of neocortex. This effect is mediated by the 5-HT2A receptor, which has been linked to the action of hallucinogenic and atypical antipsychotic drugs. The increase in EPSCs is seen most prominently in medial prefrontal cortex and other frontal regions where 5-HT2A receptors are enriched. The induction of EPSCs by 5-HT appears to occur through a novel mechanism that does not depend on the activation of afferent impulse flow. Instead, 5-HT appears to act presynaptically, directly or indirectly, to induce a focal release of glutamate from a subpopulation of glutamatergic terminals impinging upon the apical (but not basilar) dendrites of layer V pyramidal cells; a working hypothesis of the transduction pathway (involving asynchronous transmitter release) for this process is presented. Consistent with a focal action upon glutamatergic nerve terminals, the 5-HT-induced EPSPs can be suppressed by presynaptic inhibitory modulators such as mu-opiate or group II/III metabotropic agonists. We suggest that the suppression of 5-HT-induced EPSCs by 5-HT2A antagonists and mu-opiate agonists may underlie certain shared clinical effects of 5-HT2A antagonists and mu-opiate agonists. We suggest further that since presynaptic group II/III metabotropic glutamate agonists suppress 5-HT-induced EPSCs, metabotropic glutamate agonists may also possess antidepressant and/or antipsychotic properties.     

Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor-alpha and matrix metalloproteinase expression

High concentrations of bile acids have been reported as injurious to hepatocytes. We report the influence of various combinations of bile acids on the liver-specific function of cultured rat hepatocytes. Using 4 bile acids (glycocholate [GC], taurocholate [TC], glycohenodeoxycholate [GCDC], and taurochenodeoxycholate [TCDC]), we obtained 6 bile-acid mixtures, each containing equal amounts of 2 bile acids (total bile acids [TBA], 2 mM). Changes in gluconeogenesis, ureagenesis, DNA contents, medium alanine aminotransferase, and morphologies were compared among the paired bile acid compositions by measuring the C/CDC ratio ([GC + TC]/[GCDC + TCDC]) of each. In terms of their relative impairments of ureagenesis from greatest to least, the acids were GCDC, TCDC, and GC, which was almost the same as TC. When the C/CDC ratio was 0, the values of all parameters measured deteriorated. When the C/CDC ratio was 1 in the presence of 1 mM GCDC, only the rate of ureagenesis was diminished. When the C/CDC ratio was infinite, no hepatocellular injury was observed. GCDC and TCDC, together or separately, showed significant hepatocellular injury when the TBA concentration was 2 mM.     

Pathological changes according to the severity of asthma

BACKGROUND: There have been many studies concerning pathological changes in bronchial mucosa from asthmatics; however, few studies has been carried out to evaluate pathological changes according to the severity of asthma. OBJECTIVE: This study was designed to evaluate the cellular components in bronchoalveolar lavage fluid (BALF) and histological abnormalities in asthmatics according to the severity of asthma. METHODS: Bronchoalveolar lavages, bronchoscopic biopsies and ultrastructural examinations were performed in 13 asthmatics and 11 (BAL) or four (biopsies) non-asthmatic controls. The proportions of epithelial cells and correlations with PC20Meth which reflects bronchial hyperresponsiveness. Light microscopic examination revealed loss of epithelium, inflammatory cell infiltrations and thickening of the basement membrane which also showed significant correlation with PC20Meth. Hypertrophy of airway smooth muscles and hyperplasia of mucous glands were prominent in asthmatics but there was no difference according to the severity of asthma. Ultrastructural examination revealed that basement membrane thickening on light microscopic examination is due to the increased subepithelial collagen deposition with normal thickness of basal lamina. CONCLUSION: These data suggest that loss of epithelial cells, infiltration of inflammatory cells, especially eosinophils, and increased deposition of subepithelial collagen play major roles in determining the severity of asthma and non-specific bronchial hyperresponsiveness.     

Clinical and demographic features of Meige's syndrome

Fifty five patients with Meige's syndrome were examined for clinical and demographic features. The mean age of onset was 52.3 years. The peak age of onset was in the sixth decade with a male to female ratio of 1.11:1. The mean duration of illness was 3.7 years. Commonest initial symptom was increased blinking, seen in 30 cases (54.5%). Twenty five patients (45.4%) had complete syndrome of blepharospasm with oromandibular dystonia, whereas 24 patients (43.6%) had blepharospasm alone and the rest (6 patients, 10.9%) had oromandibular dystonia. The extension of spasm beyond cranial muscles was observed in 10 patients (18.1%). Eleven patients had family history of dystonia or other extrapyramidal disorders. Incidence of depression was high in these cases.     

Urate oxidase in prevention and treatment of hyperuricemia associated with lymphoid malignancies

Standard prophylaxis and treatment of malignancy-associated hyperuricemia in the USA has been allopurinol with vigorous hydration, urinary alkalinization and osmotic diuresis. Urate oxidase, the enzyme that converts uric acid to allantoin (a readily excreted metabolite that has 5- to 10-fold higher solubility than uric acid), is an alternative therapy; however, few published findings support this practice. Between February 1994 and December 1996, we administered non-recombinant urate oxidase (Uricozyme) to 126 children with newly diagnosed non-B cell acute lymphoblastic leukemia (ALL) during the first 5 days of chemotherapy with methotrexate, 6-mercaptopurine or both. Their blood levels of uric acid and other indicators of tumor lysis were measured at diagnosis and during treatment and then compared with findings in 129 similarly treated historical controls who had received allopurinol to control hyperuricemia. Clinical responses to urate oxidase were also determined in eight patients with newly diagnosed B cell ALL or advanced-stage non-Hodgkin lymphoma. Patients treated with urate oxidase had rapid and significantly greater decreases in their blood uric acid levels than did the historical controls (median maximal level during treatment, 2.3 vs 3.9 mg/dl, P < 0.001). They also had lower creatinine (0.6 vs 0.7 mg/dl, P = 0.01) and blood urea nitrogen (11 vs 24 mg/dl, P < 0.001) levels. Similar findings were made in the eight cases of B cell ALL or non-Hodgkin lymphoma. None of the patients required dialysis for acute renal failure. Six (4.5%) of the 134 children given urate oxidase had allergic reactions, manifested primarily by urticaria, bronchospasm and hypoxemia. Thus, non-recombinant urate oxidase is a more effective uricolytic agent than allopurinol but is associated with acute hypersensitivity reactions, even in patients without a history of allergy.     

Matrix induced re-differentiation of cultured rat hepatocytes and changes of CCAAT/enhancer binding proteins

Rat hepatocytes de-differentiate and proliferate when cultured on collagen-coated dishes in a chemically defined Hepatocyte Growth Medium in the presence of hepatocyte growth factor and epidermal growth factor. The addition of biomatrix derived from Engelbreth-Holm-Swarm (EHS) mouse sarcoma stops this process and leads to re-differentiation of the cells. We monitored DNA binding activity and protein levels of CCAAT/Enhancer Binding Proteins (C/EBPs) during these events by electrophoretic mobility shift assays and western blot analysis. We used plasma protein gene expression as a marker for the proliferation and differentiation phases. During the initial proliferation phase the DNA binding activity of C/EBPs decreased about 5-10 fold, mainly due to reduction of C/EBP alpha protein to nearly undetectable levels. Addition of EHS-gel prevented the further loss of C/EBP alpha protein and established a new steady state level. Since C/EBP beta proteins were affected to a much lesser extent, the C/EBP alpha:C/EBP beta ratio was greater in the presence of EHS-gel. Transferrin, alpha 1-antitrypsin, and albumin mRNA expression increased substantially. Thus stabilized C/EBP alpha expression, an increased C/EBP alpha:C/EBP beta ratio, and increased expression of liver specific mRNAs all correlated with the transition of proliferative to differentiated cells.     

Stability of sulfonamide antibiotics in spiked pig liver tissue during frozen storage

A bulk portion of homogenized pig liver tissue was spiked at room temperature with 0.2 mg/kg (twice the Australian maximum residue limit) of each of sulfathiazole, sulfachlorpyridazine, sulfadimidine (sulfamethazine), sulfaquinoxaline, and sulfadimethoxine. After subsampling and packaging, selected individual packaged units were tested to confirm homogeneity of the prepared material. The material was stored frozen at -20 degrees C and analyzed in replicate by liquid chromatography on 11 sampling dates over a period of about 6 months. Analytical data were plotted on a log-linear scale and subjected to linear regression on the basis of first-order kinetics for the decay. Storage stabilities (decay half-lives at -20 degrees C) calculated from the mean slope of regression lines were sulfadimethoxine, 567 days; sulfadimidine, 457 days; sulfachlorpyridazine, 312 days; sulfathiazole, 291 days; and sulfaquinoxaline, 271 days. Significant depletion (65% loss) of residue was observed for sulfaquinoxaline during preparation of spiked bulk liver tissue. An extension of the study to measure the storage stability of sulfaquinoxaline under accelerated decay conditions (refrigerator temperature, 4 degrees C) showed it to be relatively unstable, with a decay half-life of 11 days. Results demonstrate the need for both regulatory agencies and testing laboratories to be aware of potential errors associated with improper transport, storage, and handling of tissue samples submitted for antibiotic testing.