Distribution of HIV type 1 (HIV-1) in blood components: detection and significance of high levels of HIV-1 associated with platelets

BACKGROUND: Although inactivation of enveloped viruses transmitted by plasma derivatives has been successful, no methods for virus inactivation or removal have been established for platelet concentrates or red cell (RBC) components. Relatively little is known regarding the extent or significance of virus interactions with the cellular constituents in these components. STUDY DESIGN AND METHODS: Units of whole blood were collected from six HIV type 1 (HIV-1)-positive, asymptomatic individuals and separated into peripheral blood mononuclear cells (PBMNCs), cell-free plasma, white cell-reduced platelet concentrate, and white cell-reduced RBCs. DNA and RNA polymerase chain reaction and virus culture methods were used to study the compartmentalization of HIV-1 immediately after component preparation and after storage. RESULTS: As expected, HIV DNA and infectious virus were detected in fresh blood and in PBMNCs, and virion-associated RNA was detected in fresh plasma from all six donors. The levels of viral nucleic acids in these preparations remained relatively stable with 4 degrees C storage, whereas infectivity of PBMNCs was rapidly lost. Washed RBCs tested negative for HIV in all assays at all time points. Platelets retained high levels of HIV RNA (but not infectivity) after extensive washing, as well as after storage at 4 and 22 degrees C. High-level platelet-associated HIV-1 was also demonstrated in samples collected during early seroconversion. Periseroconversion and postseroconversion levels of platelet-associated HIV-1 correlated with the level of plasma viremia and with the rate of progression to AIDS. Cell-free virus from donor plasma and tissue culture fluid rapidly and firmly attached to platelets from noninfected donors. Infectivity of tissue culture virus bound to platelets was demonstrated in vitro. CONCLUSION: Significant levels of HIV-1 are associated with platelets during all stages of infection. Platelet-associated HIV could either mediate virus clearance or facilitate virus dissemination and expanded tropism. Finally, virus inactivation research must address virus associations with platelets.     

Rolandic type cerebral palsy in children as a pattern of hypoxic-ischemic injury in the full-term neonate

Magnetic resonance images (MRIs) of the brains of 11 patients aged from 1 week to 12 years with a distinctive type of cerebral palsy were selected based on distribution of cerebral lesions, which were restricted to bilateral perirolandic cortical and subcortical regions, including frequent symmetric involvement of basal ganglia and ventrolateral nucleus of thalami. Retrospectively, the perinatal history and clinical features were reviewed to correlate clinical data with this distinctive pattern of brain injury. Clinically affected neonates had an encephalopathy associated with a severe perinatal asphyxial event. Older children with cerebral palsy survived a similar perinatal course and demonstrated spastic quadriparesis with bulbar or pseudobulbar involvement, lack of verbal speech and variable delays in cognitive development. The distribution of hypoxic-ischemic lesions involving bilateral perirolandic regions, basal ganglia, and thalami, appears to correlate with increased metabolic areas of primary myelination in full-term neonates, but not with arterial border zones nor a single cerebral artery distribution. Myelination is a critical process in maturing brain associated with marked increase in tissue respiration and thus greater susceptibility to oxygen deprivation. It is believed that the extent of hypoxic-ischemic brain injury is determined principally by brain maturity and regional metabolic rates at time of insult and this correlates with active myelination in full-term neonates. This study confirms previous data from neuropathologic literature and recent reports of neuroimaging studies of asphyxiated neonates. In addition, retrospective analysis of the clinical data enables recognition of a type of cerebral palsy that might be the hallmark of hypoxic-ischemic injury in term neonates.     

Breast disease: dynamic spiral MR imaging

The cochleo- and tonotopic organization of the second auditory area (AII) was investigated in cats anaesthetized with pentobarbital using a combination of macro- and microelectrode recording technique. The results obtained following electrical stimulation of the neural fibres innervating different regions of the organ of Corti indicate the existence of two complete representations of the cochlea in area AII: one in the dorsocaudal portion, the other in its ventrorostral portion. These two cortical representations of the cochlea differ in size and spatial orientation. The dorsocaudal projection area extends over a distance of 2.6-3.2 mm from the basal to the apical focus and is arc-shaped. The spatial orientation of cochlea representation within the dorsocaudal region of AII is similar to that described in AI, in that stimulation of the cochlea base results in maximal responses in the more rostral portion of AII and stimulation of the apex evokes cortical responses more caudally. The ventrorostral region within AII is smaller (1.4-2.5 mm length), and has the opposite cochleotopic orientation (base and apex stimulation represented caudally and rostrally, respectively). In both AII zones, there was a proportionally greater cortical representation of basilar membrane than of middle and apical portions. Although two distinct zones with the overall cochleotopic pattern described above were noted in all cats, their precise size and location considerably varied in different animals. Using microelectrode recordings, a cortical tonotopic organization can be observed that was consistent with and expanded on the earlier cochleotopic data. Within the dorsocaudal region of AII, neurons with higher best frequency responses were located in more rostral regions, while those with lower best frequencies were located caudally. An orderly progression of best frequency responses was noted as serial recordings carried out along the full extent of the representation. Neurons within the ventrorostral region of AII also displayed an orderly progression of best frequencies, but in the opposite direction, with higher best frequencies noted more caudally and lower best frequencies more rostrally.     

Definition of natural T cell antigens with mimicry epitopes obtained from dedicated synthetic peptide libraries

Progress has recently been made in the use of synthetic peptide libraries for the identification of T cell-stimulating ligands. T cell epitopes identified from synthetic libraries are mimics of natural epitopes. Here we show how the mimicry epitopes obtained from synthetic peptide libraries enable unambiguous identification of natural T cell Ags. Synthetic peptide libraries were screened with Mycobacterium tuberculosis-reactive and -autoreactive T cell clones. In two cases, database homology searches with mimicry epitopes isolated from a dedicated synthetic peptide library allowed immediate identification of the natural antigenic protein. In two other cases, an amino acid pattern that reflected the epitope requirements of the T cell was determined by substitution and omission mixture analysis. Subsequently, the natural Ag was identified from databases using this refined pattern. This approach opens new perspectives for rapid and reliable Ag definition, representing a feasible alternative to the biochemical and genetic approaches described thus far.     

Hepatobiliary and intestinal clearance of amphiphilic cationic drugs in mice in which both mdr1a and mdr1b genes have been disrupted

The triumph of antibiotics over bacterial pathogens that has occurred in the latter half of this century looks increasingly threatened as we approach the new millennium. Increasing resistance in important pathogens such as Mycobacterium tuberculosis, Shigella, and Streptococcus pneumoniae threatens the lives of millions. The increasing problems with drug resistance in (C. diphtheriae, Salmonella typhi and the pneumococcus in Vietnam are presented as examples of the challenge confronting tropical countries.     

Statistical modeling using preoperative prognostic variables in predicting extracapsular extension and progression after radical prostatectomy for prostate cancer

OBJECTIVE: To predict the risk of extracapsular extension and postoperative recurrence before radical prostatectomy (RP) for prostate cancer. METHODS: We performed multivariate Cox regression analysis on preoperative variables in 260 clinically localized prostate cancer patients who underwent RP. With these data, we constructed a relative risk of recurrence (Rr) equation and an equation to predict the probability of extracapsular extension (PECE) before RP. RESULTS: Rr is calculated as exp[(0.47 x race + 0.14 x PSAST) + (0.13 x worst biopsy Gleason sum) + (1.03 x stage T1c) + (1.55 x stage T2b,c)], where PSAST indicates a sigmoidal transformation of prostate-specific antigen. PECE is calculated as 1/[1 + exp(-Z)], where Z = -2.47 + 0.15 (PSAST) + 0.31 (worst biopsy Gleason sum) + 0.18 (race) + 0.16 (stage T1c) + 0.38 (stage T2b,c). CONCLUSION: These two equations can be used preoperatively to predict the probability of extracapsular disease and the risk of prostate-specific antigen recurrence in patients undergoing RP.     

Reticulum cell neoplasms of lymph nodes: a clinicopathologic study of 11 cases with recognition of a new subtype derived from fibroblastic reticular cells

Lymph nodes contain nonlymphoid accessory cells including follicular dendritic cells (FDCs), interdigitating dendritic cells (IDCs) and fibroblastic reticular cells (FBRCs). Neoplasms derived from FDCs are uncommon, and those of IDC origin are even more rare. We report the clinicopathologic features of 11 reticulum cell neoplasms, including 2 of FBRC origin. There were seven male patients and four female patients ranging in age from 13 to 73 years. All cases involved lymph nodes (cervical or supraclavicular-6 cases), (abdominal--2 cases), epitrochlear (1 case); two had more than one site of involvement (cervical lymph node and mediastinum--1 case, cervical and abdominal lymph nodes--1 case). One case of FDC tumor had concomitant Castleman's disease, plasma cell variant. Each neoplasm showed similar histology with oval-to-spindle-shaped cells in a storiform or fascicular pattern. Based on immunophenotypic findings, the neoplasms were classified as FDC (five cases), IDC (two cases), FBRC (three cases), and reticulum cell neoplasm, not otherwise specified (one case). The FDC tumors showed immunoreactivity for CD21 or CD35, vimentin, and CD68. The IDC tumors showed strong positivity for S-100 protein and variable positivity for CD68 and CD1a. The cases derived from FBRCs were positive for vimentin, desmin, and smooth-muscle actin. The neoplasm classified as reticulum cell neoplasm, not otherwise specified had similar morphologic features but showed only equivocal positivity for CD68 and vimentin. Follow-up was available for 9 of 11 (82%) cases with a mean of 3.5 years. Four of five patients with FDC tumors were alive with disease when last seen; the fifth is alive and well with no evidence of disease at 4-year follow-up. One patient with IDC tumor had a recurrence in a different nodal site. Two patients with FBRC tumor were disease free at follow-up of 2 years and 8 years, respectively. The patient with reticulum cell neoplasm, not otherwise specified, was alive and disease free 8 years after diagnosis.