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R A Hoffman

Publications and source records attributed to R A Hoffman.

At least 73 records · Page 4Linked to original sources
PubMed1994

Long-term results of early cochlear implantation in congenitally and prelingually deafened children.

Cochlear implants have been shown to improve the speech perception and production skills in children. Data are available on congenitally and prelingually deafened children who were implanted at an older age, but data on children implanted below the age of 3 years are scarce. The present study examines the benefits obtained with early implantation of the young deaf child. Fourteen congenitally or prelingually profoundly hearing-impaired children were implanted before the age of 3 years, with the Nucleus multichannel cochlear prosthesis, and followed for 2-5 years. Results indicate an overall improvement in the perception of all aspects of the speech signal in the auditory-only condition with the cochlear implant. All the children use oral language as their primary mode of communication and attend regular schools. Based on the results of this investigation, the authors conclude that implantation of the young deaf child is beneficial to the development of auditory perceptual skills.

Age of Onset↗
PubMed1993

Characterization of the immunosuppressive effects of nitric oxide in graft vs host disease.

The generation of nitric oxide (.N = O) during in vitro assays involving lymphocyte-macrophage interaction can result in profound inhibition of lymphocyte proliferation. The present study examined whether .N = O synthesis plays a role in the suppression observed in immune function assays during graft vs host disease (GvHD). By using a parent to F1 model to induce GvHD (C57BL/6J to C57BL/6J x DBA 2J F1), a mild but transient increase in serum NO2- plus NO3- levels was observed on day 12 after inoculation. Resident peritoneal macrophages obtained from mice with GvHD demonstrated enhanced .N = O synthesis in response to LPS, compared with control F1 peritoneal macrophages. Similarly, when splenocytes from GvHD mice were cultured with Con A or LPS enhanced supernatant NO2- levels were observed, compared with control F1 mice. Addition of NG-monomethyl-L-arginine (NMA), a competitive inhibitor of .N = O synthesis, resulted in decreased NO2- levels and greatly enhanced proliferation in response to Con A. Addition of NMA to LPS-stimulated cultures did not enhance proliferation, perhaps as the result of the paucity of B cells in the GvHD population. LPS-induced .N = O synthesis by GvHD splenocytes was blocked by anti-IFN-gamma mAb, whereas Con A-induced .N = O synthesis was relatively unaffected by similar concentrations of anti-IFN-gamma mAb, suggesting different mechanisms of induction of .N = O synthesis. A proliferative response of splenocytes from mice with GvHD to third-party alloantigen was not detectable, even in the presence of NMA. The suppression observed when splenocytes from GvHD animals were added to control TNP-modified self cultures was partially reversed in the presence of NMA. These results demonstrate that .N = O synthesis in both splenocyte and peritoneal macrophage populations from GvHD mice is enhanced, revealing that in vivo priming of macrophages for .N = O synthesis occurs during GvHD. Some, but not all, in vitro tests of immune function by using GvHD splenocytes are suppressed by the generation of .N = O.

Animals↗
PubMed1993

Reactive nitrogen intermediates suppress the primary immunologic response to Listeria.

Reactive nitrogen intermediates (RNI), e.g., nitric oxide derived from a terminal guanido nitrogen atom of L-arginine, exhibit potent antimicrobial activity in vitro. The function of these intermediates in host defenses in vivo, however, is presently unclear. Experiments were undertaken to determine the role of RNI in the resolution of primary listerial infections of the liver. Serum RNI levels were elevated significantly in mice infected with Listeria monocytogenes. Moreover, a marked increase in RNI production was found in cultures of the parenchymal, as well as the nonparenchymal, liver cells obtained from Listeria-infected mice. RNI did not kill Listeria treated directly, however, nor were they a factor in the listericidal activity exhibited by hepatic cells. Rather, the elevated production of RNI during primary infection appeared to promote the replication of Listeria in vivo. Mice administered NG-monomethyl-L-arginine, a competitive inhibitor of RNI production, exhibited a 10- and a 100-fold reduction in the number of Listeria in their lives on days 3 and 7 postinfection, respectively. In vitro, NG-monomethyl-L-arginine stimulated the Ag-specific proliferation of T lymphocytes derived from Listeria-infected mice at concentrations that inhibited RNI production. These latter findings suggest that the elevated production of RNI during primary listerial infections suppresses host defenses by diminishing the proliferation and, consequently, the biologic response of immune cell populations.

Animals↗
PubMed1993

Phase-resolved fluorescence lifetime measurements for flow cytometry.

A flow cytometer capable of measuring fluorescence lifetimes by the phase shift method has been built and evaluated. Under optimal conditions, the resolution of the fluorescence lifetime measurement is shown to be under 200 picoseconds. Pulse intensity variations are normalized using limiting amplifiers and electronic filtering. Normalization of signal intensities provides a lifetime measurement that is independent of fluorescence intensity over at least a 50-fold (17 dB) range in fluorescence intensity. The fluorescence lifetimes of unbound dye, fluorescent beads, cells stained with ethidium bromide, propidium iodide, and phycoerythrin-conjugated monoclonal antibodies have been measured. The fluorescence lifetimes measured for these particles are well correlated with lifetime measurements made using a standard fluorimeter. Cells stained with ethidium bromide and propidium iodide at various nucleotide-to-dye ratios are shown to exhibit similar behavior to static cuvette measurements. The fluorescence lifetime parameter is also shown to resolve phycoerthyrin fluorescence from propidium iodide fluorescence.

Cells, Cultured↗
PubMed1993

Macrophages produce nitric oxide at allograft sites.

OBJECTIVE: The current study was designed to determine which cytokines produced during an alloimmune response stimulate macrophage nitric oxide (.N = O) production at allograft sites. SUMMARY BACKGROUND DATA: Previous work has demonstrated that rat sponge matrix allograft infiltrating cells produce more .N = O on stimulation with alloantigen than syngeneic graft-infiltrating cells. Addition of NG-monomethyl-L-arginine (NMA), an inhibitor of .N = O synthesis, promotes allospecific cytolytic T-lymphocyte effector function. METHODS: Polyurethane sponges were implanted subcutaneously in recipient Lewis rats and injected with 10 x 10(6) ACl splenocytes. On various days after grafting, graft-infiltrating cells were harvested for in vitro study. Adherent macrophages from the graft infiltrating cell population were obtained by a 2- to 3-hour incubation to plastic dishes with subsequent washing to remove nonadherent cells. RESULTS: Stimulation of unseparated graft-infiltrating cell populations with lipopolysaccharide or interferon-tau resulted in enhanced .N = O synthesis by allograft infiltrating cells compared with syngeneic graft-infiltrating cells, early after grafting. Macrophages recovered from an allograft site spontaneously produce more .N = O than macrophages recovered from syngeneic grafts (p < 0.001). Significantly enhanced levels of .N = O were produced by allograft macrophages compared with syngeneic graft macrophages on stimulation with lipopolysaccharide or interferon-tau (p < or = 0.025). CONCLUSIONS: Nitric oxide appears to be produced in response to the local cytokines secreted by an ongoing rejection reaction. Nitric oxide serves under these circumstances to modulate the alloimmune response.

Animals↗
PubMed1993

Nitric oxide production by mouse sponge matrix allograft-infiltrating cells. Comparison with the rat species.

We have recently demonstrated in the rat species that sponge matrix allograft infiltrating cells spontaneously produce nitric oxide (.N = 0) and this .N = 0 production precedes the development of CTL. Compared with our experience in the mouse species, the CTL activity recovered from rat sponge grafts is of shorter duration and less intense. Assessment of the spontaneous .N = 0 production by mouse allograft infiltrating cells reveals a more delayed time course of production, paralleling the recovery of CTL activity from the graft. The in vitro spontaneous .N = 0 production by mouse allograft-infiltrating cells was greater than the production by syngeneic graft-infiltrating cells on all days tested. Exposure of allogeneic but not syngeneic graft infiltrating cells to the sensitizing alloantigen in vitro resulted in enhanced .N = 0 synthesis. In contrast, LPS stimulated .N = 0 production by both syngeneic and allogeneic graft cells on all days postgrafting. Culture of day-14 allograft infiltrating cells with alloantigen in the absence of NG-monomethyl-L-arginine (NMA), the competitive inhibitor of .N = 0 synthesis, resulted in elevated supernatant NO2- levels and decreased 3H-TdR uptake and CTL activity compared with cultures carried out in the presence of NMA. The supernatant NO2- levels, as well as the CTL activity and 3H-TdR incorporation of the cultured cells, was dependent on the concentration of NMA present, and these effects could be reversed by excess L-arginine. Thus, the species difference in .N = 0 synthesis (rat > mouse), observed by others, is evident in the sponge allograft model and may explain why CTL activity recovered from rat allografts is of shorter duration and less intense than that from the mouse allografts.

Animals↗
PubMed1993

Hyaluronic acid and purine nucleoside phosphorylase in vascular and luminal effluents of small bowel grafts as parameters of preservation injury.

Reliable parameters reflecting the degree of graft injury after small bowel preservation are currently not established. We investigated hyaluronic acid (HA) and purine nucleoside phosphorylase (PNP) as indicators of preservation injury before small bowel transplantation. In the first part of the study, intestinal grafts were harvested, perfused with saline, and flushed either immediately or after 1, 6, 12, 24, and 48 hr of cold storage (n = 6/group). HA and PNP were assayed in vascular and luminal effluents. In the second part of the study, 24 grafts were transplanted after preservation periods of 1, 6, 9, and 12 hr (n = 6/group) to assess if HA and PNP are predictors of postoperative graft survival. HA levels in vascular effluents and PNP activities in luminal effluents correlated with duration of preservation time and predicted graft survival. Utilizing both parameters significantly increased the predictive accuracy.

Animals↗
PubMed1993

Evidence for early Th 2 T cell predominance in xenoreactivity.

Two distinct subsets of CD4+ Th lymphocytes have been characterized by their cytokine profiles: Th 1 (TH1) and Th 2 (TH2). While TH1 cells predominate in cell-mediated responses, TH2 cells support the humoral response. We have examined the mRNA cytokine profile of normal mouse lymphocytes in response to alloantigen versus xenoantigen (rat) in MLC, and present evidence to suggest that early in proliferative responses, alloreactivity is dominated primarily by TH1-type lymphocytes, while xenoreactivity is predominantly TH2. Normal mouse lymphocyte-responding cells were cultured in a one-way MLR with either allo or xeno antigen and examined for production of mRNA for cytokines characteristically produced by TH1 (IL-2, IFN-gamma) or TH2 (IL-4, IL-10) cells. Semiquantitative reverse transcription-polymerase chain reaction analysis was performed for mouse IL-2, IL-4, IL-10, and IFN-gamma mRNA. In the mouse anti-rat xeno response, mRNA for TH2 gene products were upregulated, with greater levels of IL-4 and IL-10 at 24 and 48 hr when compared with controls. In contrast, upregulation of mRNA for TH1 gene products occurred in the mouse anti-mouse allo response, with higher levels of IL-2 and IFN-gamma at 24 and 48 hr. In the anti-xeno response, upregulation of all 4 cytokines occurred by day 4 and peak levels of mRNA for all cytokines examined were 2-3 times that seen for the peak anti-allogeneic response. These data suggest that early xenorecognition may differ from allorecognition by differential activation of the TH2 subset. A better understanding of the balance between Th subset function and cytokine profile in allo and xeno reactivity may allow a more targeted and specific approach to control the early events in xenograft rejection.

Animals↗
PubMed1993

Cross-species graft-versus-host-disease is accompanied by a donor-derived cellular immune response.

Acute graft-versus-host-disease is classically described as reactivity of donor lymphocytes to recipient alloantigens. To date there is debate as to whether GVHD can be induced across a species barrier. We recently reported the induction of stable xenogeneic chimerism (rat-->mouse) and donor-specific transplantation tolerance using the transplantation of untreated rat bone marrow cells into B10 mouse recipients. Survival of chimeras was excellent, and there was no evidence of GVHD. We now describe the induction of xenogeneic GVHD by transplanting large numbers of donor rat spleen cells with the bone marrow inoculum. All chimeras that received bone marrow and untreated spleen cells developed an external appearance compatible with GVHD and had a median survival time of 14 days. Mice that received equivalent numbers of untreated rat bone marrow alone appeared healthy, had no evidence for GVHD, and survived > 90 days. The usual epithelial target tissues for allogeneic GVHD in those mice that received xenogeneic bone marrow and spleen cells showed the presence of tissue injury and histologic features compatible with GVHD. Donor rat MHC class I and class II positive cells were prominent cell types present in the tongues of mice that developed features of GVHD, and this was accompanied by a significant inflammatory tissue response with loss of the dermal-epidermal architecture. In contrast, fully xenogeneic chimeras without GVHD had no evidence for tissue injury or pathologic cellular infiltrates when examined by immunohistochemical analysis. These data suggest that although fully xenogeneic chimeras resist GVHD, GVHD can be induced across a species barrier if sufficient numbers of donor rat spleen cells are added to the bone marrow inoculum. Further comparisons of these models may provide an approach to study the mechanisms responsible for xenoreactivity in vivo.

Animals↗
PubMed1993

Evidence that small bowel preservation causes primarily basement membrane and endothelial rather than epithelial cell injury.

The main site of injury induced during small bowel preservation is perceived to be the basement membrane and the endothelium of the highly vascularized mucosa, an aspect evaluated here in further detail. The effects of preservation were studied using a specific basement membrane stain (laminin antibody), an endothelial cell stain (factor 8 antibody) and standard histology. In addition, mucosal glutaminase activity reflecting enterocyte integrity was measured as monitor of the extent of preservation injury. Using a rat model, small bowel grafts were harvested, the vascular bed and bowel lumen were flushed, and the grafts were stored (4 degrees C) for 1, 6, 9, and 12 hr and transplanted into syngeneic hosts. After cold storage prior to transplantation, full-thickness small bowel biopsies were obtained for the various tissue preparations. Histologic evaluation at the end of the preservation period revealed separation of the villous epithelium from the lamina propria that increased with extending preservation time. Tissue staining with the laminin antibody disclosed progressive changes with increasing preservation intervals. Staining with the factor 8 antibody demonstrated also progressive changes, but failed to reflect in a gradual fashion increasing endothelial cell injury. Histologic injury became more pronounced after transplantation and reperfusion, then showing destruction of epithelial cells; the extent of injury correlated with the duration of preservation. Glutaminase activity was maintained after cold storage, indicating that the enterocytes remained intact during this period, but when assayed after reperfusion, glutaminase decreased with increasing preservation intervals and increasing histologic mucosal damage. We conclude that cold ischemic injury involves primarily the endothelium and the basement membrane, which progresses to global mucosal impairment with reperfusion.

Animals↗
PubMed1993

Surgical complications of multichannel cochlear implants in North America.

By paying careful attention to the details of surgical technique, many of the complications which have occurred to date may be avoided. Some, such as late electrode and receiver/stimulator migration, device failures, and late flap necrosis due to excessive magnetic forces cannot be avoided by the surgeon, but may be prevented by further advances in implant designs. Although the incidence of life-threatening complications is minimal, and that of major complications is acceptable, every effort should be made by the surgeon, audiologist and manufacturer to further diminish these problems.

Adult↗
PubMed1993

Petrous jugular malposition (diverticulum).

Jugular bulb anatomy is variable. A "high-riding" bulb extending into the tympanic cavity is a well-described anomaly. Petrous jugular malposition (diverticulum) (PJMD), however, is rare. The relationship between PJMD and clinical symptoms is questionable because the differentiation between PJMD as an anatomic variant and pathologic process is unproved. A literature review reveals 14 previously documented cases. We report an additional four cases. Diagnostic and management dilemmas are discussed, with the importance of high-resolution CT stressed.

Adult↗
PubMed1993

Surgical pitfalls in cochlear implantation.

Increasing experience with cochlear implantation has led to the identification of potential surgical pitfalls: improper patient selection, poor flap design and handling, facial nerve injury, improper electrode placement, and improper seating of the receiver stimulator. Each of these areas of potential difficulty are reviewed, emphasizing methods of avoidance and management of adverse outcome.

Cochlear Implants↗
PubMed1992

Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin.

Nitric oxide (NO) is a short-lived biologic mediator that is shown to be induced in various cell types and to cause many metabolic changes in target cells. Inhibition of tumor cell growth and antimicrobial activity has been attributed to the stimulation of the inducible type of the NO synthase (NOS). However, there is limited evidence for the existence of such inducible NOS in a human cell type. We show here the induction of NO biosynthesis in freshly isolated human hepatocytes (HC) after stimulation with interleukin 1, tumor necrosis factor (TNF), IFN-gamma, and endotoxin. Increased levels of nitrite (NO2-) and nitrate (NO3-) in culture supernatants were associated with NADPH-dependent NOS activity in the cell lysates. The production of NO2- and NO3- was inhibited by NG-monomethyl L-arginine and was associated with an increase in cyclic guanylate monophosphate release. The data presented here provide evidence for the existence of typical inducible NO biosynthesis in a human cell type.

Amino Acid Oxidoreductases↗