Cyclosporin-A nephrotoxicity and acute cellular rejection in renal transplant recipients: correlation between radionuclide and histologic findings

Serial radionuclide studies using both Tc-99m DTPA (perfusion) and I-131 hippuran (tubular function) were correlated with histologic findings in 25 patients with renal transplants. These cases included 15 cases of cyclosporin-A nephrotoxicity (CsA-NT) and ten cases of acute cellular rejection that were retrospectively selected on the basis of biopsy findings and favorable clinical response to therapy specific for each of these conditions. The serial radionuclide studies enabled the correct diagnosis in 12 of 15 cases of CsA-NT and eight of ten cases of acute rejection. Posttherapy radionuclide studies, furthermore, demonstrated improvement consistent with clinical response. In all cases, the radionuclide results were available at least 24 hours before biopsy findings. These results indicate that serial radionuclide studies evaluating interval changes in both perfusion and tubular function are of significant value in the diagnosis and follow-up of CsA-NT and acute cellular rejection in transplant recipients. This initial experience suggests a sensitivity of 80%.     

Percutaneous femoral artery coronary arteriography. 300 consecutive cases with French 5 catheters

Owing to the ever growing practice of coronary angioplasty, each patient is subjected to multiple examinations and it has become imperative, both for ethical and functional reasons, to reduce the morbidity of coronary arteriography. For this purpose, reduction in the caliber of catheters is a step forward which must be made without altering the procedure and even while making it simpler (shorter stay in bed and in hospital). Between april, 1986 and january, 1987, 300 consecutive coronary arteriographies were performed in a uniform manner and using 5 French catheters in 239 men (mean age 55.4 years) and 61 women (mean age 60.3 years). There were 13 "failures" (4 p. 100) in the sense that the examination was pursued with conventional 7 F or 8 F catheters, or that the brachial route was used. Bilateral femoral puncture was necessary in 6 cases (2 p. 100), and 2 complications (0.7 p. 100) were observed: subacute femoral thrombosis in one case, and regressive cerebral vascular accident in another patient. Thus, it seems permissible and more convenient nowadays to perform all coronary arteriographies with a 5 French catheter. The femoral route can be used in ambulatory patients who get up 4 hours after the procedure.     

The RNA helicase, nucleotide 5'-triphosphatase, and RNA 5'-triphosphatase activities of Dengue virus protein NS3 are Mg2+-dependent and require a functional Walker B motif in the helicase catalytic core

The nonstructural protein 3 (NS3) of Dengue virus (DV) is a multifunctional enzyme carrying activities involved in viral RNA replication and capping: helicase, nucleoside 5'-triphosphatase (NTPase), and RNA 5'-triphosphatase (RTPase). Here, a 54-kDa C-terminal domain of NS3 (DeltaNS3) bearing all three activities was expressed as a recombinant protein. Structure-based sequence analysis in comparison with Hepatitis C virus (HCV) helicase indicates the presence of a HCV-helicase-like catalytic core domain in the N-terminal part of DeltaNS3, whereas the C-terminal part seems to be different. In this report, we show that the RTPase activity of DeltaNS3 is Mg2+-dependent as are both helicase and NTPase activities. Mutational analysis shows that the RTPase activity requires an intact NTPase/helicase Walker B motif in the helicase core, consistent with the fact that such motifs are involved in the coordination of Mg2+. The R513A substitution in the C-terminal domain of DeltaNS3 abrogates helicase activity and strongly diminishes RTPase activity, indicating that both activities are functionally coupled. DV RTPase seems to belong to a new class of Mg2+-dependent RTPases, which use the active center of the helicase/NTPase catalytic core in conjunction with elements in the C-terminal domain.     

Interchromosomal duplications of the adrenoleukodystrophy locus: a phenomenon of pericentromeric plasticity

A 9.7 kb segment encompassing exons 7-10 of the adrenoleukodystrophy (ALD) locus of the X chromosome has duplicated to specific locations near the pericentromeric regions of human chromosomes 2p11,10p11, 16p11 and 22q11. Comparative sequence analysis reveals 92-96% nucleotide identity, indicating that the autosomal ALD paralogs arose relatively recently during the course of higher primate evolution (5-10 million years ago). Analysis of sequences flanking the duplication region identifies the presence of an unusual GCTTTTTGC repeat which may be a sequence-specific integration site for the process of pericentromeric- directed transposition. The breakpoint sequence and phylogenetic analysis predict a two-step transposition model, in which a duplication from Xq28 to pericentromeric 2p11 occurred once, followed by a rapid distribution of a larger duplicon cassette among the pericentromeric regions. In addition to facilitating more effective mutation detection among ALD patients, these findings provide further insight into the molecular basis underlying a pericentromeric-directed mechanism for non- homologous interchromosomal exchange.      

Involvement of the ventrolateral medulla in parkinsonism with autonomic failure

OBJECTIVE: To determine whether patients with PD and autonomic failure (AF), manifested primarily with orthostatic hypotension (OH), have a consistent loss of tyrosine hydroxylase (TH) neurons in the rostral ventrolateral medulla (RVLM), similar to that occurring in patients with multiple system atrophy (MSA) and AF, and to determine whether there is loss of nicotinamide, adenine dinucleotide phosphate (NADPH) diaphorase (NADPH-d) RVLM neurons in both groups of patients. METHODS: The numbers of TH and NADPH-d neurons in the RVLM was assessed in brain sections obtained at autopsy from five patients with suspected PD and OH, six patients with MSA, two patients with corticobasal ganglionic degeneration and no AF, and 10 control subjects with no history of neurologic disease. Cell numbers were compared among groups and correlated with their final neuropathologic diagnosis. RESULTS: The number of TH neurons in the RVLM of patients with PD and OH were not significantly different from control subjects, and there were marked individual variations. The TH cell numbers in the RVLM were significantly higher (p < 0.06) in patients with PD than in patients with MSA, despite a similar degree of severity of OH. As a group, patients with PD and OH had reduced numbers of NADPH-d cells in the RVLM compared with control subjects, but again there were marked individual variations. NADPH-d cell numbers were reduced consistently and more markedly in patients with MSA. CONCLUSION: Unlike the case in patients with MSA, the number of TH neurons in the RVLM is highly variable in patients with PD and is unlikely to contribute significantly to the pathophysiology of OH. As a group, patients with PD have reduced numbers of NADPH-d neurons in the RVLM, but some patients had cell counts similar to control subjects. On the other hand, NADPH-d cell depletion in the RVLM is a consistent finding in MSA and may contribute to cardiorespiratory dysfunction in this disorder.     

Peripheral neuroimmune interactions: selected review and some clinical implications

Clinical Autonomic Research - To provide a brief and focused review on peripheral neuroimmune interactions and their implications for some clinical disorders. Narrative review of the literature...     

Parabrachial nucleus involvement in multiple system atrophy

Multiple system atrophy (MSA) is associated with respiratory dysfunction, including sleep apnea, respiratory dysrhythmia, and laryngeal stridor. Neurons of the parabrachial nucleus (PBN) control respiratory rhythmogenesis and airway resistance. Objectives: The objective of this study is to determine whether there was involvement of putative respiratory regions of the PBN in MSA. Methods: We examined the pons at autopsy in 10 cases with neuropathologically confirmed MSA and 8 age-matched controls. Sections obtained throughout the pons were processed for calcitonin-gene related peptide (CGRP) and Nissl staining to identify the lateral crescent of the lateral PBN (LPB) and the Kölliker-Fuse nucleus (K-F), which are involved in respiratory control. Cell counts were performed using stereology. Results: There was loss of CGRP neurons in the PBN in MSA (total estimated cell counts for the external LPB cluster was 12,584 ± 1146 in controls and 5917 ± 389 in MSA, p < 0.0001); for the external medial PBN (MPB) cluster it was 15,081 ± 1758 in controls and 7842 ± 466 in MSA, p < 0.001. There was also neuronal loss in putative respiratory regions of the PBN, including the lateral crescent of the LPB (13,039 ± 1326 in controls and 4164 ± 872 in MSA, p < 0.0001); and K-F (5120 ± 495 in controls and 999 ± 308 in MSA, p < 0.0001). Conclusions: There is involvement of both CGRP and putative respiratory cell groups in the PBN in MSA. Whereas the clinical implications of CGRP cell loss are still undetermined, involvement of the LPB and K-F may contribute to respiratory dysfunction in this disorder.     

Treatment of Acquired Bilateral Nevus of Ota-Like Macules (Hori''s Nevus) with a Combination of the 532 nm Q-Switched Nd:YAG Laser Followed by the 1,064 nm Q-Switched Nd:YAG Is More Effective: Prospective Study

BACKGROUND: Acquired bilateral nevus of Ota-like macules (Hori's nevus) is a common dyschromatosis among Asian women. Q-switched lasers have been used successfully as a treatment modality. OBJECTIVE: The purpose of this study was to compare the efficacy of using the Q-switched 532 nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser followed by the 1,064 nm laser versus the Q-switched 1,064 nm Nd:YAG laser alone in the treatment of Hori's nevus. METHODS: This is a prospective left-right comparative study. Ten women with bilateral Hori's nevus were recruited and treated with a combination of the Q-switched 532 and 1,064 nm Nd:YAG lasers on the right cheek and the Q-switched 1,064 nm Nd:YAG laser alone on the left cheek. Only one laser treatment session was performed. The degree of pigmentation was objectively recorded with a mexameter. Subjective assessment was made by both patients and two blinded, nontreating dermatologists. RESULTS: At 6 months, there was a statistically significant difference (p = .009) of 35.10 points using objective mexameter measurements between the two sides, favoring the side treated with a combination of 532 and 1,064 nm laser treatment. Subjective grading by the patients and blinded dermatologists also confirmed that combination therapy was more successful after one treatment. Although combination treatment had a higher incidence of mild postinflammatory changes, this disappeared within 2 months. CONCLUSIONS: Concurrent use of the Q-switched 532 nm Nd:YAG laser in combination with the 1,064 nm laser is more effective in pigment clearance than the Q-switched 1,064 nm Nd:YAG laser alone for Hori's nevi.     

Segmental analysis of neuropeptide concentrations in normal human spinal cord

We concurrently measured, by radioimmunoassay, levels of substance P (SP), somatostatin (SST), methionine-enkephalin (Met-Enk), cholecystokinin (CCK), peptide hystidyl-isoleucine (PHI), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY) in the ventral and dorsal gray matter at each segment of the cervical, thoracic, lumbar, and sacral spinal cord, obtained within 6 hours of death from 4 subjects (ages 17 to 55) with no neurologic disease. Levels (pmol/g gray matter) of SP, SST, and Met-Enk throughout and PHI, VIP, and NPY in lumbar and sacral cord were significantly higher in dorsal than in ventral gray matter. PHI, VIP, and NPY were significantly higher in lumbar and especially sacral cord than in cervical and thoracic segments. In rats, a postmortem delay of up to 8 hours did not affect SP, Met-Enk, PHI, or NPY and decreased SST, CCK, and VIP levels. Thus, there is a characteristic profile of neuropeptide distribution in gray matter, which emphasizes the neurochemical heterogeneity along the rostrocaudal and dorsoventral extent of normal human spinal cord.