Effects of cocaine on dopamine receptor gene expression: a study in the postmortem human brain

The effects of chronic cocaine exposure on dopamine D1 and D2 receptor gene expression in the human brain were studied in postmortem samples from chronic cocaine abusing and matched control subjects. Using in situ hybridization of receptor autoradiography to examine messenger ribonucleic acid (RNA) and binding sites, respectively, neither D1 nor D2 receptor expression was found to be changed in the nucleus accumbens, caudate, putamen, or substantia nigra of the cocaine-exposed subjects. Although chronic cocaine exposure can produce alterations in dopaminergic neurotransmission, sustained compensatory changes in dopamine receptor expression do not appear to occur in the human.     

Abnormal selection of antibody repertoires in retrovirus-induced murine AIDS

The mature B cell repertoire in the course of murine AIDS (MAIDS) was investigated. The polymerase chain reaction (PCR) was used to amplify a large diversity of rearranged Ig H chain genes in normal or infected mice, 2 and 8 wk after virus inoculation. Libraries were constructed from the polymerase chain reaction products. By sequencing V-D-J clones in these libraries and analyzing the respective complementary determining region 3 (CDR3), we have shown at 8 wk the emergence of a population of B cells with significantly less N diversity, some sequences lacking any N addition, a typical feature of fetal repertoires known for degeneracy, and autoreactivities. This decreased N diversity was not present 2 wk after inoculation and could not be related to a defect in terminal deoxytransferase expression because the steady-state levels of terminal deoxytransferase mRNA were found normal in MAIDS bone marrow 8 wk after inoculation. FACS analyses revealed a decreased number of bone marrow B cells (B220+, sIgM+) in MAIDS already present at 2 wk, suggesting an alteration in the pathway of B cell differentiation and resulting in a decrease of peripheral B cells renewal. A relative enrichment of spleen cells in long lived B cells as a consequence of this blockade may participate in the abnormal antibody repertoire selection occurring in MAIDS. These data suggest in the MAIDS pathogeny the relationship between an abnormal repertoire selection and the pathologic process.     

Toward global advancement of medicine: the International Society of Nephrology experience

BACKGROUND: Since its foundation in 1960, the International Society of Nephrology (ISN) has pursued the worldwide advancement of education, science and patient care in nephrology. This goal was achieved by means of the Society's journal and the organization of international congresses and symposia. In order to better reach its colleagues and patients in economically less developed countries, the ISN expanded its activities as of 1980 by a large number of specific programs aimed at these regions. METHODS: The first phase of activities included teaching programs, fellowship and visiting scholar programs, and the provision of travel grants to enhance accessibility to the ISN congresses. A second phase consisted of the creation of a library enhancement program, a commission on acute renal failure and--to improve the organization and efficiency--a central commission on global advancement of nephrology (COMGAN). Currently, a third phase has been entered in which all activities have been intensified: (1) under the guidance of COMGAN, supported by a large number of teaching programs and fact finding missions; (2) by establishing a renal sister program; and (3) by initiating commissions on informatics and on clinical trials. RESULTS: As a result, the ISN has reached most parts of the world, previously deprived of contact with renal science and renal patient care. The fellowship program now counts 160 fellows, who spend one or two years in training. The library enhancement program reaches 218 institutions worldwide. ISN membership has soared over the past two years with over 2,500 new members, mostly in the developing countries. They receive Kidney International and other relevant forms of information. Thus far, 135 pairs of renal units in developing and developed countries have been linked for support on a more continuous basis. ISN-sponsored congresses, symposia, and courses are being held in increasing numbers in the developing world. In many of its activities, the ISN closely collaborates with sister organizations, which also contribute financially. In total, the ISN spends annually over $1 million US from its own budget on the programs described above. CONCLUSION: The various programs and initiatives are proving helpful in advancing renal medicine in areas in need. Expansion into supporting similar programs within other medical subspecialties is being explored.     

D-lactic acidosis: a treatable encephalopathy in pediatric patients

Isolation of Salmonella from the feces of impounded dogs was carried out to make clear the recent microbiological condition of dogs introduced into our facilities. Salmonella was isolated from 10 out of 283 samples (3.5%). Inparticular, during the first week after introduction, Salmonella was isolated from nine out of 74 dogs (12.2%). The isolation rate during the first week after introduction was significantly higher than that for dogs introduced later. No isolates were detected from dogs reared for more than 3 weeks after introduction. This study indicates that impounded dogs had the highest risk of infecting a person with Salmonella during the first week after introduction into our laboratory animal facilities, and that we need to pay attention to this fact when handling them.     

Late complication of laparoscopic salpingoophorectomy: retained foreign body presenting as an acute abdomen

The technique of immunocytochemistry was used to identify myoglobin in kidney, confirming a diagnosis of neuroleptic malignant syndrome following an otherwise obscure autopsy in a decomposed body. The features of neuroleptic malignant syndrome are reviewed with a differential diagnosis of myoglobin renal casts. The report emphasizes a thorough and detailed assessment of deaths which occur during treatment with neuroleptic drugs.     

Guidelines for management of left-sided prosthetic valve thrombosis: a role for thrombolytic therapy. Consensus Conference on Prosthetic Valve Thrombosis

OBJECTIVES: We sought to form a consensus recommendation for management of prosthetic valve thrombosis (PVT) from previous case and uncontrolled reports from a consensus of international specialists. BACKGROUND: PVT and thromboembolism relate to inadequate anticoagulation and valve type and location. PVT is suspected by history (dyspnea) and auscultation (muffled valve sounds or new murmurs) and confirmed by Doppler echocardiography showing a marked valve gradient. METHODS: A consensus conference was held to recommend management of left-sided PVT. RESULTS: Transesophageal Doppler echocardiography is used to visualize abnormal leaflet motion and the size, location and mobility of thrombus. Thrombolysis is used for high risk surgical candidates with left-sided PVT (New York Heart Association functional class III or IV) because cerebral thromboembolism may occur in 12% of patients. Duration of thrombolysis depends on resolution of pressure gradients and valve areas to near normal by Doppler echocardiography performed every few hours. Lysis is stopped after 72 or 24 h if there is no hemodynamic improvement (operation indicated). Heparin infusion with frequent measurement of activated partial thromboplastin time (aPTT) begins when aPTT is more than twice control levels and can be converted to warfarin (international normalized ratio [INR] 2.5 to 3.5) plus aspirin (81 to 100 mg/day). Patients in functional class I or II have lower surgical mortality, and those with large immobile thrombi on the prosthetic valve or left atrium have responded to endogenous lysis with combined subcutaneous heparin every 12 h (aPTT 55 to 80 s) plus warfarin (INR 2.5 to 3.5) for 1 to 6 months. Operation is advised for nonresponders or patients with mobile thrombi. CONCLUSIONS: Thrombolysis, followed by heparin, warfarin and aspirin, is advised for high risk surgical candidates with left-sided PVT.     

Identification of a gene that causes primary open angle glaucoma

Glaucoma is a major cause of blindness and is characterized by progressive degeneration of the optic nerve and is usually associated with elevated intraocular pressure. Analyses of sequence tagged site (STS) content and haplotype sharing between families affected with chromosome 1q-linked open angle glaucoma (GLC1A) were used to prioritize candidate genes for mutation screening. A gene encoding a trabecular meshwork protein (TIGR) mapped to the narrowest disease interval by STS content and radiation hybrid mapping. Thirteen glaucoma patients were found to have one of three mutations in this gene (3.9 percent of the population studied). One of these mutations was also found in a control individual (0.2 percent). Identification of these mutations will aid in early diagnosis, which is essential for optimal application of existing therapies.     

Peptide YY inhibition of rat gastric enterochromaffin-like cell function

The present study determined tumorigenicity, tumor classification and DNA damage induced in infant mice by benzo[a]pyrene (B[a]P) or Manufactured Gas Plant (MGP) residues after a single exposure. Male and female B6C3F1 mice were exposed to B[a]P or MGP residue from a single environmental site (MGP-4) and males were also exposed to MGP residue composite from seven different sites (MGP-M7). At 26, 39 and 52 weeks after exposure tumorigenesis was assessed in lung, forestomach and liver. Formation and persistence of DNA adducts were quantified by 32P-postlabeling. Exposure of males to B[a]P induced liver tumors in a dose and time dependent manner. MGP induced more advanced tumors than B[a]P. Only a single liver tumor was found in MGP-4 treated females. No forestomach and few pulmonary adenomas were induced in males or females. MGP-4, MGP-M7 or B[a]P induced DNA adducts in males and females. Adducts in liver, lung and forestomach peaked on different days and decreased at different rates. At 24 h post-exposure, no significant differences in initial DNA adduct levels occurred in males and females exposed to MGP-4 or B[a]P. Lack of DNA damage (adducted DNA) did not account for non-responsiveness of lung and forestomach in B6C3F1 genders as well as in liver in females. MGP tumorigenicity could not be accounted for solely by B[a]P content nor did it reflect additivity of B[a]P and other carcinogenic polycyclic aromatic hydrocarbons (PAHs) in MGP. Synergy among MGP-PAHs, presence of unidentified carcinogens and/or promoters in MGP may account for MGP potency. The B6C3F1 infant male model is a convenient and rapid assay for assessing MGP liver tumorigenicity and potency.     

Homonucleotide tracts, short repeats and CpG/CpNpG motifs are frequent sites for heterogeneous mutations in the neurofibromatosis type 1 (NF1) tumour-suppressor gene

Glutamatergic synaptic potentials induced by micromolar concentrations of the potassium conductance blocker 4-aminopyridine (4-AP) were recorded intracellularly from rat neostriatal neurons in the presence of 10 microM bicuculline (BIC). These synaptic potentials originate from neostriatal cortical and thalamic afferents and were completely blocked by 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) plus 100 microM D-2-amino-5-phosphonovaleric acid (2-APV). Their inter-event time intervals could be fitted to exponential distributions, suggesting that they are induced randomly. Their amplitude distributions had most counts around 1 mV and fewer counts with values up to 5 mV. Since input resistance of the recorded neurons is about 40 M omega, the amplitudes agree to quantal size measurements in mammalian central neurons. The action of a D2 agonist, quinpirole, was studied on the frequency of these events. Mean amplitude of synaptic potentials was preserved in the presence of 2-10 microM quinpirole, but the frequency of 4-AP-induced glutamatergic synaptic potentials was reduced in 35% of cases. The effect was blocked by the D2 antagonist sulpiride (10 microM). Input resistance, membrane potential, or firing threshold did not change during quinpirole effect, suggesting a presynaptic site of action for quinpirole in some but not all glutamatergic afferents that make contact on a single cell. The present experiments show that dopaminergic presynaptic modulation of glutamatergic transmission in the neostriatum does not affect all stimulated afferents, suggesting that it is selective towards some of them. This may control the quality and quantity of afferent flow upon neostriatal neurons.