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Biomedical subjects

R M Stewart

Publications and source records attributed to R M Stewart.

At least 19 recordsLinked to original sources

Complications of surgical endoscopy. A decade of experience from a surgical residency training program.

BACKGROUND: This study examines the notion that gastrointestinal endoscopy performed by supervised surgical residents is safe. METHODS: We reviewed all gastrointestinal endoscopic procedures performed by surgical residents with faculty supervision for complications and deaths occurring up to 30 days following the procedures. RESULTS: The overall complication rate for 9,201 upper and lower endoscopy procedures was 1.4% and 0.42%, respectively. Overall mortality rate was 0.76% for upper endoscopy and 0.6% for lower endoscopy. No mortality was a direct result of a procedure-related complication. Intestinal perforation, drug overdose, bleeding, and aspiration were the most common procedure-related complications. Each resident completed an average of 75 upper endoscopies and 79 lower endoscopies during their training period. CONCLUSIONS: Gastrointestinal endoscopy can be performed safely by surgical residents with appropriate supervision. The higher morbidity and mortality of upper endoscopy are most likely related to the underlying disease rather than the procedure. Awareness of common complications and application of appropriate precautions and instruction are critical for minimizing complications.

Adult

Lysosome-associated membrane proteins h-LAMP1 (CD107a) and h-LAMP2 (CD107b) are activation-dependent cell surface glycoproteins in human peripheral blood mononuclear cells which mediate cell adhesion to vascular endothelium.

Lysosome-associated membrane proteins (LAMPs) are transmembrane lysosomal glycoproteins which are detectable at the cell surface of lymphocytes in patients with scleroderma and systemic lupus erythematosus. While these proteins have been shown to mediate adhesion of tumor cells to vascular endothelial selectins, the function of LAMPs expressed at the cell surface of peripheral blood lymphocytes has not been previously examined. In the present study, the role of lamp2 (CD107b) in lymphocyte adhesion to vascular endothelium and the factors which influence in vitro cell surface expression of both lamp1 (CD107a) and lamp2 (CD107b) are examined. Freshly isolated PBMCs and unstimulated PBMCs in the culture had low levels of cell surface lamp1 and lamp2 expression which were significantly increased following PHA stimulation (P < 0.0001). A dose-dependent response to PHA and the effect of varying concentrations of serum were defined. Kinetic analysis revealed that the majority of the increase in both lamp1 and lamp2 occurred within the first 2 hr of incubation and that a subset of PBMCs maintained expression for at least 96 hr. Incubation of cells with colchicine and cycloheximide modified the cell surface expression of these proteins. Interleukins 2, 4, 6, and 8 had only a modest effect on the degree of cell surface lamp1 and lamp2 expression, though they did significantly affect the distribution of expression among different subtypes of lymphoid cells. Under the conditions utilized in this study, cell surface LAMP expression was confined primarily to CD56+ cells and to CD3+ cells. Functional analysis utilizing a fluorescence-based adhesion assay revealed that cell surface lamp2 mediates adhesion of PBMCs to vascular endothelium, possibly by interacting with endothelial selectins. LAMPs likely contribute to the migration of activated leukocytes to sites of inflammation in vivo.

Adult

Marginal fit of electroformed ceramometal crowns.

PURPOSE: A method of fabricating ceramometal crowns using gold copings produced by an electroforming process has been described, which purportedly results in restorations exhibiting an excellent marginal fit. This study compares the fit of electroformed ceramometal crowns with ceramometal crowns fabricated using conventional lost wax casting techniques. MATERIALS AND METHODS: Electroformed and conventional ceramometal crowns were fabricated for prepared extracted teeth. Specimens were cemented, embedded in acrylic resin, sectioned, polished, photographed, and measured to compare marginal fit. RESULTS: Marginal fit of electroformed ceramometal crowns was superior to the fit of ceramometal crowns fabricated using conventional casting techniques. The difference was statistically significant at a P = .05 level. CONCLUSIONS: Crowns utilizing copings fabricated by electroforming methods appear to have a fit superior to conventional ceramometal crowns fabricated using copings made by lost wax casting. The ease in laboratory electroforming techniques and the esthetic advantages of a gold-colored coping can be capitalized on without concerns of a poorer fit.

Crowns

Complications of needle catheter jejunostomy in 2,022 consecutive applications.

BACKGROUND: We commonly use needle catheter jejunostomy (NCJ) for early enteral feeding in selected patients. Review of our approach was prompted by the suggestion that enteral feeding represents a "stress test" for the bowel and may be associated with a high complication rate. MATERIALS AND METHODS: We reviewed patients with NCJ inserted over the past 16 years by prospective database, chart review, and conference minutes, with emphasis on complications. RESULTS: During the conduct of 28,121 laparotomies, 2,022 NCJs inserted in 1,938 patients (7.2%) resulted in 34 NCJ-related complications in 29 patients (1.5%) The most common complication was premature loss of the catheter from occlusion or dislodgment (n = 15; 0.74%), and the most serious was bowel necrosis (n = 3; 0.15%). CONCLUSIONS: Needle catheter jejunostomy may be inserted and used with a low complication rate. Most complications were preventable through greater attention to detail and better monitoring of physical examination of patients with marginal gut function.

Catheterization

Gastric and extragastric actions of the histamine antagonist ranitidine during posttraumatic sepsis.

BACKGROUND: Histamine H2 antagonists (e.g., ranitidine) are generally thought to specifically reduce gastric acid secretion and are commonly used for stress ulcer prophylaxis in critically ill patients because of their efficacy and safety profile. A few reports suggest that ranitidine might also bind to extragastric sites and/or act as an immunomodulator. The potential effects on posttraumatic sepsis are unknown. METHODS: Mongrel pigs (n = 24) were anesthetized with fentanyl, injured by a 10 kg steel bar dropped from a height of 1 m onto the fleshy portion of the posterior thigh, and then 35% of their blood volume was drained through the arterial catheter. All the shed blood plus two times the hemorrhage volume as lactated Ringer's solution was infused after a 1-hour shock period. Either vehicle or ranitidine (1.5 mg/kg) was intravenously administered at the time of resuscitation and every 12 hours thereafter in a blinded fashion. After 72 hours a septic challenge was administered (15 micrograms/kg Escherichia coli lipopolysaccharide [LPS] x 30 min). Serial gastroscopy, gastric pH, hemodynamics, leukocyte counts, cortisol, and tumor necrosis factor were recorded for 180 minutes after LPS. RESULTS: Immediately before LPS all hemodynamic variables were identical between treatments, but gastric pH was slightly higher and stress gastritis was marginally lower with ranitidine. LPS caused profound leukopenia and a hyperdynamic circulatory response (i.e., tachycardia, increased cardiac output, and decreased peripheral vascular resistance at relatively constant blood pressure); these changes were not altered by ranitidine. Gastric pH remained elevated after LPS with ranitidine, but LPS-induced gastritis was not modified. Ranitidine delayed the LPS-induced ventilation-perfusion imbalance and attenuated the peak increase in the proinflammatory cytokine, tumor necrosis factor, without altering its antiinflammatory opponent, cortisol. Similar changes were observed in four additional animals treated with cimetidine. The proportion of circulating neutrophils and lymphocytes was slightly altered 180 minutes after LPS, but there was no obvious effect on T lymphocytes in vivo, and no effect on the LPS-induced increase in neutrophil CD18 expression in vitro was seen. CONCLUSIONS: (1) Ranitidine increased gastric pH, which blunted the stress gastritis caused by trauma but not that caused by LPS; (2) ranitidine delayed the early LPS-evoked pulmonary changes and reduced the tumor necrosis factor spike, which is consistent with a favorable immunomodulatory action that has been reported in patients who are critically ill or are undergoing an elective abdominal surgical procedure; (3) the mechanism is probably related to H2 receptor antagonism rather than to a nonspecific side effect of ranitidine, which suggests that histamine may have a previously unrecognized role in posttraumatic septic responses; and (4) the site of action is probably not in the heart or peripheral resistance vessels, but salutary effects on circulating lymphocytes or neutrophils cannot be excluded.

Acidosis

Quantitation of CD62, soluble CD62, and lysosome-associated membrane proteins 1 and 2 for evaluation of the quality of stored platelet concentrates.

BACKGROUND: Platelets become activated during storage, which results in secretion of granules, vesiculation of microparticles, secretion of protein, and a number of other biochemical and morphologic processes that decrease the utility of platelet concentrates stored for transfusion. STUDY DESIGN AND METHODS: To evaluate the quality of stored platelet concentrates, the cell surface expression of specific activation-dependent antigens (CD62 and lysosome-associated membrane proteins 1 and 2 [LAMP-1, LAMP-2]) on platelets stored in a hospital blood bank over a 7-day period was examined. Relative microparticle counts and the expression of CD62 by microparticles, as well as platelet concentrate supernatant levels of soluble CD62, were determined. RESULTS: The percentage of platelets expressing CD62 increased significantly from Day 1 to Day 5 (p < 0.05) of storage; the mean fluorescence values for CD62 did not. In contrast, the mean fluorescence values of LAMP-1 and LAMP-2 rose significantly (p < 0.01 and p < 0.05, respectively) between Days 1 and 5. Significant declines in CD62, LAMP-1, and LAMP-2 percent expression and mean fluorescence were seen on Day 6 of storage (p < 0.001). Microparticle numbers increased significantly during storage and correlated with levels of CD62 protein (free and membrane-bound) (r = 0.95 vs. Day 2, p < 0.05; r = 0.88 vs. Day 5, p < 0.05). CONCLUSION: Flow cytometric evaluations of the expression of cell surface CD62, LAMP-1, and LAMP-2 are complementary tests that, especially when used in conjunction with the quantitation of CD62 protein, provided a simple and effective means of evaluating the quality of platelet concentrates stored for transfusion.

Antigens, CD

Actions of prostaglandin E1 on lipopolysaccharide-evoked responses in vivo and in vitro following resuscitated trauma.

Prostaglandins of the E series (PGE1, PGE2) have well-described immunosuppressive (antiinflammatory) as well as vasodilator (pro-inflammatory) actions. The net effect on an acute inflammatory response would depend on the dose, timing, and site of action. Egg phosphatidyl liposomes are novel drug delivery vehicles that can alter the in vivo disposition of PGE1. The purpose of this study was to explore the therapeutic potential of PGE1, with or without liposome encapsulation, on the systemic inflammatory response evoked by endotoxin following trauma. Anesthetized pigs received a soft tissue injury + hemorrhage, and fluid resuscitation after 1 h. In one series, whole blood was incubated with PGE1 (0, 40, or 200 micrograms/mL) and Escherichia coli endotoxin (LPS; 0, 1, 5, or 10 micrograms/mL) in vitro and neutrophil CD18 adherence receptor density was measured with immunomonitoring. In another series, LPS (5 micrograms/kg) was administered 3 days following trauma to animals pretreated with either phosphate-buffered saline (PBS) + PGE1 (62 ng/kg/min x 40 min, 2.5 micrograms/kg total, n = 8), PBS (n = 12), liposomes alone (Lipo, n = 10) or liposome-encapsulated PGE1 (Lipo + PGE, n = 7). This PGE1 dose had minimal effects on blood pressure in baseline conditions. Hemodynamics, cell differential counts, plasma cortisol, and plasma tumor necrosis factor (TNF) were measured for 3 h post-LPS. LPS in vitro caused a dose-related increase in neutrophil CD18 expression that was not altered by < 200 micrograms/mL PGE1 before or after trauma.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil

Natural killer cells and gamma delta T cells in scleroderma: relationship to disease duration and anti-Scl-70 antibodies.

OBJECTIVES: To examine the expression of the natural killer (NK) antigen CD56, and T cell receptor delta chain antigen (TCR delta), expressed on the gamma delta T cell subset, in patients with scleroderma, and to correlate levels of expression with clinical characteristics. METHODS: Peripheral blood mononuclear cells (PBMCs) from 15 patients with scleroderma and 11 controls were obtained from heparinised blood on a ficoll/hypaque gradient, stained with monoclonal antibodies, and examined by flow cytometry for expression of CD56 and TCR delta. RESULTS: Overall, the proportion of PBMCs expressing CD56 in the patient group (14.4 (SEM 2.6)%) was not significantly different from controls (8.75 (2.6)%). The greatest levels of expression were found in patients late (more than three years) in their disease course (18.1 (3.3)%) and in patients who did not express anti-Scl-70 antibodies (17.1 (3.5)%). The proportion of gamma delta T cells was significantly lower in the patient group (1.61 (0.52)% v control 2.61 (0.46)%) (p < 0.05). Patients early in their disease or with anti-Scl-70 antibodies accounted for the reduction in gamma delta T cells (0.71 (0.29)% and 0.96 (0.41)% (p < 0.01 and p < 0.05, respectively). CONCLUSIONS: This study emphasis that NK and gamma delta T cell numbers vary depending upon patient characteristics and may help explain prior contradictory reports. Decreased numbers of gamma delta T cells were seen in scleroderma patients, especially those with anti-Scl-70 antibodies and a disease duration of less than three years.

Adult

Alteration in lymphocyte phenotype associated with administration of adjuvant levamisole and 5-fluorouracil.

Levamisole (LMS) and 5-fluorouracil (5FU) administered adjuvantly are effective in reducing the relapse rate following surgical resection of Duke's stage C colon carcinoma. It has been postulated that LMS acts to stimulate the immune system and that this is one mechanism through which this drug exerts its antitumor effects. In this study, peripheral blood mononuclear cells (PBMC) were analyzed in nine patients with surgically resected colon carcinoma prior to initiation of adjuvant LMS/5FU and at several subsequent times while patients were on therapy. Changes in lymphocyte phenotype and soluble interleukin-2 receptor (sIL-2R) between pre-study samples and samples obtained during adjuvant LMS/5FU were evaluated. Significant increases were seen in the proportion of PBMC expressing natural killer (NK) antigen CD56 (14.7 +/- 2.4% versus 18.1 +/- 2.6%; P < 0.05) and surface IL-2R (CD25; 0% versus 0.42 +/- 0.15%; P < 0.05), in sIL-2R (314 +/- 86 U/ml versus 736 +/- 173 U/ml; P < 0.05), and in the CD4:CD8 ratio (2.34 +/- 0.93 versus 3.47 +/- 1.23; P < 0.01). A significant decrease in the proportion of CD8+ PBMC (24.7 +/- 3.8% versus 18.8 +/- 2.6%; P < 0.01) and total CD8+ PBMC (537 +/- 118 versus 324 +/- 37; P < 0.01) was seen. The increase in CD56+ cells correlated with sIL2R levels (r = 0.46; P < 0.05). No changes were noted for CD3, CD4, CD5, CD14, CD16, CD19, CDw49a, or TCR delta. The greatest increase in CD56+ cells and the smallest reduction in CD8+ cells were seen in the subgroup of patients who remained disease-free following adjuvant chemotherapy. This study suggests that adjuvant LMS/5FU has significant stimulatory effects on the immune system, which correlate with patient outcome and may account at least in part for its clinical efficacy.

Antigens, CD

The effect of laparoscopic cholecystectomy on resident training.

BACKGROUND: The purpose of this study was to determine the impact of laparoscopic cholecystectomy (LC) on resident training. MATERIALS AND METHODS: We reviewed our experience over an 11-year period, from academic years 1982 to 1992, with 3,046 patients who underwent elective open cholecystectomy (OC) and 640 patients who underwent LC. RESULTS: Prior to LC, junior residents performed 80% of all cholecystectomies, with a morbidity and mortality rate of 4% and 0.04%, respectively, compared with 11% and 0.3%, respectively, for senior residents who operated on higher-risk patients. Since the introduction of the technique, there has been a 25% increase in cholecystectomies per year, and a reduction in junior resident OC experience by 67%. Currently, 72% of all cholecystectomies are performed laparoscopically by senior residents. CONCLUSION: The replacement of OC by LC has produced a qualitative change in the operative experience of our junior residents and a delay in acquisition of operative skills. The reduction in OC experience by residents may jeopardize their ability to perform the difficult open cases.

Cholecystectomy

Is resection with primary anastomosis following destructive colon wounds always safe?

Resection with primary anastomosis was associated with a 14% anastomotic leak rate in this review of 60 patients with destructive colon wounds. The presence of an underlying medical illness or massive blood transfusion was associated with anastomotic complications. In the high-risk subset of patients who had one or both of these risk factors, the anastomotic leak rate was 42%. The incidence of anastomotic leak in previously healthy patients without massive transfusion was 3%. Ileocolostomies were no safer than colocolostomies. We conclude that resection with anastomosis should not be performed on all patients with destructive colon injuries, as the risk of anastomotic leak is prohibitive in those with either massive blood loss or underlying medical illness. We continue to perform primary anastomosis in healthy patients without excessive blood loss.

Adolescent

Social drinking and the immune response: impairment of lymphokine-activated killer activity.

The effect of limited and intermittent alcohol ingestion on the immune response in humans has not been extensively studied. The authors, in this study, evaluate peripheral blood mononuclear cell cytotoxicity before and after alcohol ingestion in a setting designed to mimic social drinking. Eleven healthy volunteers consumed two 12 oz (355 mL) cans of beer in 30 minutes while eating pizza. Five control individuals ingested non-alcoholic beverages. Natural killer and lymphokine-activated killer activity were determined for peripheral blood mononuclear cells obtained before and 30 minutes after alcohol ingestion. Interleukin 2-induced lymphokine-activated killer activity was significantly reduced in blood samples obtained after alcohol ingestion when compared with pre-alcohol samples (p < 0.01). Natural killer activity (unstimulated) was not affected by alcohol ingestion. The authors demonstrate that ingestion of a small amount of alcohol impairs the cytotoxic capacity of peripheral blood mononuclear cells. Alcohol in the context of social drinking may have deleterious effects on the immune system's ability to clear virus-infected cells or cells that have undergone neoplastic transformation, especially for individuals with pre-existing immunosuppression.

Adult

Neutrophil CD18 expression and blockade after traumatic shock and endotoxin challenge.

OBJECTIVE: The expression of the leukocyte CD18 adhesion complex on polymorphonuclear leukocytes (PMNs) was measured, and the physiologic effects of blockade of the complex were studied after trauma and sepsis. SUMMARY BACKGROUND DATA: Margination of PMNs occurs early during inflammation and depends, in part, on expression of the CD18 adhesion complex. Blockade of this adherence complex can reduce PMN-mediated damage. This study tests the hypothesis that PMN activation after resuscitated trauma produces an occult endothelial injury that increases the vulnerability to a delayed inflammatory stimulus. METHODS: Anesthetized (fentanyl) mongrel pigs were sham injured or fluid resuscitated from soft tissue injury +35% hemorrhage. Systemic blood was collected at 24-hour intervals from awake animals. The CD18 density on circulating PMNs was determined with flow cytometry using mean channel fluorescence (MCF). The CD18 receptors were blocked with monoclonal antibodies either immediately before trauma or immediately before an endotoxin (lipopolysaccharide [LPS]) challenge that was administered to all groups 3 days after the shock episode. Bronchoscopy was performed before trauma, pre-LPS, and post-LPS, and protein content was measured in bronchoalveolar lavage (BAL). RESULTS: Mean channel fluorescence was reduced on PMNs for 48 hours in animals with trauma versus animals with sham injuries. Anti-CD18 therapy produced higher circulating PMN counts compared with nontreated sham or shock groups. The incremental rise of BAL protein after shock was prevented with anti-CD18; the increment after LPS was attenuated. Anti-CD18 was administered before trauma and reduced the fluids necessary to maintain cardiac filling pressures after LPS. CONCLUSIONS: These data suggest that PMNs are activated after resuscitation from traumatic shock and that these cells produce an endothelial injury that may increase the vulnerability to a septic challenge. The broad implication is that temporarily blocking PMN adhesiveness at the time of trauma might salvage some host tissue and reduce the incidence of septic complications in the post-trauma period.

Animals

Analysis of charges associated with diagnosis of nosocomial pneumonia: can routine bronchoscopy be justified?

Many ventilated trauma patients thought to have nosocomial pneumonia have pulmonary contusion or systemic inflammatory response syndrome with tracheobronchial colonization. Fiberoptic bronchoscopy with quantitative culture techniques of protected specimen brush (PSB; threshold 10(3) cfu/mL) or bronchoalveolar lavage (BAL; threshold 10(5) cfu/mL) can potentially eliminate the false positive cultures of the upper airway seen with routine sputum aspirates (RS). However, bronchoscopy is expensive, and routine use may not be cost effective. This prospective study evaluated the patient charges associated with bronchoscopy and quantitative cultures compared with RS for the diagnosis of nosocomial pneumonia. Specimens were obtained by RS, PSB, and BAL from the lower airway in 107 trauma patients (136 sets of triplicate cultures). All patients had clinical evidence suggestive of pneumonia (fever, leukocytosis, purulent sputum, abnormal roentgenographic findings). Typical oral flora were considered contaminants; no gram-negative specimens were excluded. Mean age was 40 years and mean ISS was 29. Seventy-eight percent had blunt injuries, 22% penetrating, and 42% had chest injuries. The incidence of nosocomial pneumonia according to each method was: RS-73%; PSB-34%; BAL-25%. Considering all charges involved (bronchoscopy, equipment, microbiologic analysis, and antibiotics), and based on a 14-day course of ceftazidime and vancomycin, the charges for PSB were 58% of RS, and charges for BAL were 43% of RS. We conclude that the charges associated with bronchoscopy are high, but can be offset by antibiotic savings. Side effects of unnecessary antibiotic therapy would be avoided. Further study is needed to determine the efficacy of PSB or BAL in trauma patients.

Adult

Plasma tumor necrosis factor and post-traumatic hyperdynamic sepsis evoked by endotoxin.

To examine the role of systemic plasma tumor necrosis factor (TNF) in the septic response following trauma, an endotoxin (lipopolysaccharide (LPS)) challenge was administered to anesthetized mongrel pigs 72 h following either hemorrhagic shock/resuscitation or sham shock. For TNF to be considered a mediator, at least two conditions should be satisfied: a TNF increase should precede other manifestations of the septic response and the magnitude of that increase should correlate with the symptoms. Immediately following resuscitation from shock, hemodynamics were stable, but heart rate, cardiac index (CI), and systemic oxygen delivery (DO2) were elevated 20-60%, and systemic vascular resistance (SVR) was decreased 40%, relative to the preshock baseline. After 72 h, the animals were reanesthetized, reinstrumented, and all hemodynamic values were near normal in both groups. At this point, either 1.5 (shock, n = 2; sham, n = 2), 15 (shock, n = 7; sham, n = 6) or 150 (shock, n = 11; sham, n = 4) micrograms/kg of Escherichia coli LPS was administered intravenously over 30 min. Serial hemodynamic data, complete blood counts, and TNF were recorded for 3 h post-LPS. LPS evoked profound leukopenia and pulmonary hypertension within 15 min that was followed by a hyperdynamic septic response (i.e., progressive arterial desaturation, tachypnea, tachycardia, increased CI, and decreased SVR) and rise in plasma TNF at 60-90 min. In the shock group, LPS-evoked TNF changes were less than or equal to those in the sham group, even though mortality was higher after shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Correlation of serum interleukin-8 and cell surface lysosome-associated membrane protein expression with clinical disease activity in systemic lupus erythematosus.

Cell surface expression of lysosome-associated membrane proteins (LAMPs) correlates with serum interleukin-8 (IL-8) levels, shorter disease duration, greater functional impairment from disease-related symptoms and soluble IL-2 receptor levels (sIL-2R) in patients with scleroderma. In this study of 46 patients with systemic lupus erythematosus (SLE), the relationship of serum IL-8 and cell surface LAMP to two clinical measures of disease activity, the SLEDAI and SLAM scales, was evaluated. IL-8 levels were determined on serum samples by the immunometric sandwich enzyme immunoassay technique. Cell surface LAMP expression was determined by flow cytometric quantitation of peripheral blood mononuclear cells with monoclonal antibodies directed against two of the major LAMP proteins, lamp1 and lamp2. The clinical disease activity scales correlated significantly with each other, with C3 levels, serum IL-8, C4, dsDNA and sIL-2R. Lamp1 and lamp2 expression correlated with the SLAM but not the SLEDAI scale. Serum IL-8 levels were elevated in 49 of 51 samples tested (44 of 46 patients) and had a stronger correlation with disease activity than C4, dsDNA and sIL-2R levels. Significantly higher levels of IL-8 were seen in patients with evidence of renal involvement. Serum IL-8 and cell surface LAMP expression may be useful indicators of disease activity in patients with SLE. The possible role of IL-8 in the pathogenesis of SLE requires further investigation.

Adolescent

Lysosomal enzyme activities in Chediak-Higashi syndrome: evaluation of lymphoblastoid cell lines and review of the literature.

Chediak-Higashi syndrome (CHS) is an inherited immunodeficiency disorder characterized by giant lysosomal granules in all granule-containing cells. Prior examination of lysosomal enzyme activities in granulocytes and other cells derived from patients with CHS have revealed multiple abnormalities, with the predominant finding being diminished activity of many of the enzymes tested. Abnormalities in lysosomal enzyme activity are also found in animal models of CHS (cattle, aleutian mink, and beige mice). In this study, we have examined lymphoblastoid cell lines derived from a patient with CHS and from an individual heterozygous for the CHS gene for acid phosphatase, beta-glucuronidase, and alpha-mannosidase activity. These cell lines have recently been shown to be satisfactory in vitro models for the disease. Acid phosphatase activity was increased in the heterozygous-derived cell line when compared to control while other enzyme activities were normal both in the CHS- and heterozygous-derived cell lines. We have reviewed the literature and summarized published abnormalities of lysosomal enzyme activities in humans and animals with CHS.

Acid Phosphatase