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Liver injury may persist in patients with HBV receiving antiviral therapy who have ongoing transcription and translation. We sought to assess ongoing HBV transcription by serum HBV RNA, translation by serum hepatitis B core related antigen (HBcrAg), and their associations with hepatic HBsAg and HBcAg staining in patients coinfected with HBV and HIV.This is a cross-sectional study of 110 adults coinfected with HBV and HIV who underwent clinical assessment and liver biopsy. Immunohistochemistry (IHC) was performed for HBsAg and HBcAg. Viral biomarkers included quantitative HBsAg, HBV RNA, and HBcrAg.Participants' median age was 49 years (male, 93%; Black, 51%; HBeAg+, 65%), with suppressed HBV DNA (79%) and undetectable HIV RNA (77%) on dually active antiretroviral therapy. Overall, HBV RNA and HBcrAg were quantifiable in 81% and 83%, respectively (96% and 100% in HBeAg+, respectively). HBcAg staining was detected in 60% and HBsAg in 79%. Higher HBV RNA was associated with higher HBcAg and HBsAg IHC grades (both p 0.0001). The HBsAg membranous staining pattern was significantly associated with higher HBV-RNA and HBcrAg levels.HBcAg and HBsAg IHC staining persisted despite viral suppression, and IHC grades and staining patterns correlated with markers of transcription (HBV RNA) and translation (HBcrAg). These data indicate that apparent HBV suppression is associated with residual transcription and translation that could contribute to liver pathology. Additional antiviral strategies directed to HBV protein expression may be useful to ameliorate liver injury.

INTRODUCTION Fatty liver disease (FLD) influences liver disease progression and liver cancer risk. We investigated the impact of FLD on liver disease severity in a large North American cohort with chronic hepatitis B virus (HBV). METHODS Liver biopsies from 420 hepatitis B surface antigen-positive adults enrolled in the Hepatitis B Research Network and who were not on HBV therapy in the previous month were evaluated for inflammation and fibrosis. Steatohepatitis was based on steatosis, hepatocyte ballooning ± Mallory-Denk bodies, and perisinusoidal fibrosis. Models evaluated factors associated with steatohepatitis, and the associations of steatohepatitis with fibrosis, and longitudinal alanine aminotransferase, aspartate aminotransferase, and Fibrosis-4. RESULTS The median age was 42 years, 62.5% were male, and 79.5% were Asian. One hundred thirty-two (31.4%) patients had FLD (77 [18.3%] steatosis only, 55 [13.1%] steatohepatitis). Older age, overweight/obesity, and diabetes were associated with steatohepatitis. Steatohepatitis (vs no FLD) was associated with 1.68 times higher risk of advanced fibrosis at baseline (95% confidence interval, 1.12-2.51), and there was an indication of higher incident cirrhosis rate during follow-up. Steatohepatitis vs no FLD was also independently associated with, on average, 1.39 times higher alanine aminotransferase (P < 0.01) and 1.25 times higher Fibrosis-4 (P = 0.04) across 4 years. DISCUSSION Coexisting steatosis occurred in nearly a third of adults (13% had steatohepatitis) with chronic HBV in this North American cohort who underwent liver biopsies. Steatohepatitis was associated with advanced fibrosis and higher biochemical measures of hepatic inflammation over time. Therefore, in addition to viral suppression, screening for and managing metabolic abnormalities is important to prevent disease progression in HBV.

To determine the efficacy of oral supplementation of the gut enzyme intestinal alkaline phosphatase (IAP) in preventing antibiotic-associated infections from Salmonella enterica serovar Typhimurium (S. Typhimurium) and Clostridium difficile.The intestinal microbiota plays a pivotal role in human health and well-being. Antibiotics inherently cause dysbiosis, an imbalance in the number and composition of intestinal commensal bacteria, which leads to susceptibility to opportunistic bacterial infections. Previously, we have shown that IAP preserves the normal homeostasis of intestinal microbiota and that oral supplementation with calf IAP (cIAP) rapidly restores the normal gut flora. We hypothesized that oral IAP supplementation would protect against antibiotic-associated bacterial infections.C57BL/6 mice were treated with antibiotic(s) ± cIAP in the drinking water, followed by oral gavage of S. Typhimurium or C. difficile. Mice were observed for clinical conditions and mortality. After a defined period of time, mice were killed and investigated for hematological, inflammatory, and histological changes.We observed that oral supplementation with cIAP during antibiotic treatment protects mice from infections with S. Typhimurium as well as with C. difficile. Animals given IAP maintained their weight, had reduced clinical severity and gut inflammation, and showed improved survival.Oral IAP supplementation protected mice from antibiotic-associated bacterial infections. We postulate that oral IAP supplementation could represent a novel therapy to protect against antibiotic-associated diarrhea (AAD), C. difficile-associated disease (CDAD), and other enteric infections in humans.

Background: Newborn infections are responsible for approximately one-third of the estimated 4.0 million neonatal deaths that occur globally every year. Appropriately targeted research is required to guide investment in effective interventions, especially in low resource settings. Setting global priorities for research to address neonatal infections is essential and urgent. Methods: The Department of Child and Adolescent Health and Development of the World Health Organization (WHO/CAH) applied the Child Health and Nutrition Research Initiative (CHNRI) priority-setting methodology to identify and stimulate research most likely to reduce global newborn infection-related mortality by 2015. Technical experts were invited by WHO/CAH to systematically list and then use standard methods to score research questions according to their likelihood to (i) be answered in an ethical way, (ii) lead to (or improve) effective interventions, (iii) be deliverable, affordable, and sustainable, (iv) maximize death burden reduction, and (v) have an equitable effect in the population. The scores were then weighted according to the values provided by a wide group of stakeholders from the global research priority-setting network. Findings: On a 100-point scale, the final priority scores for 69 research questions ranged from 39 to 83. Most of the 15 research questions that received the highest scores were in the domain of health systems and policy research to address barriers affecting existing cost-effective interventions. The priority questions focused on promotion of home care practices to prevent newborn infections and approaches to increase coverage and quality of management of newborn infections in health facilities as well as in the community. While community-based intervention research is receiving some current investment, rigorous evaluation and cost analysis is almost entirely lacking for research on facility-based interventions and quality improvement. Interpretation: Given the lack of progress in improving newborn survival despite the existence of effective interventions, it is not surprising that of the top ranked research priorities in this article the majority are in the domain of health systems and policy research. We urge funding agencies and investigators to invest in these research priorities to accelerate reduction of neonatal deaths, particularly those due to infections.

BACKGROUND AND AIMS There is a strong epidemiologic association between diabetes mellitus (DM) and hepatitis C virus (HCV) infection. However, the pathogenetic basis for this association has not been established. We sought to evaluate the association between insulin resistance (IR), beta-cell dysfunction, and HCV among orthotopic liver transplant (OLT) recipients. METHODS We performed a cross sectional analysis comparing 39 HCV(+) with 60 HCV(-) OLT recipients. IR and beta-cell function were calculated using validated measures and were correlated with clinical variables. RESULTS By multivariate analysis of the entire cohort, HCV infection and body mass index (BMI) were independent predictors of IR (P =0.04 and 0.0006, respectively). HCV infection was associated with 35% increase in IR. Because the model used to calculate IR was derived from nondiabetic subjects, we performed additional analysis of patients who did not meet criteria for diabetes at the time of their study evaluation. In this analysis, HCV(+) subjects had greater fasting insulin and homeostasis model assessment (HOMA) IR (15.3 mu U/mL and 3.8) compared with HCV(-) patients (10.7 mu U/mL and 2.5) (P =0.03, 0.03). There was no difference in beta-cell function or hepatic insulin extraction between the HCV (+) and (-) groups. HCV (P =0.0005), BMI (P

Objective. The standard oral rehydration solution (ORS) recommended by WHO and UNICEF does not reduce the volume or frequency of stools or the length of the episode. Hospital-based studies from developing and developed countries and intestinal perfusion studies suggest a beneficial effect on water and sodium absorption with reduced osmolarity ORS as compared with standard ORS. We conducted a community-based study comparing the efficacy of reduced osmolarity ORS (224 mmol/l) with standard ORS (311 mmol/l) in acute childhood diarrhea in a West African community. Methods. Infants and toddlers age 0 to 30 months having 738 episodes of diarrhea identified by weekly household visits were randomly assigned to treatment with either standard ORS (n = 376) or reduced osmolarity ORS (n = 362). The children were followed by daily home visits to assess ORS intake and clinical characteristics. Duration of diarrhea was compared by proportional hazards regression analysis, the hazard ratio being interpreted as the relative recovery rate between the children receiving the two types of ORS. Because earlier reports have suggested that weaning status might be an important modifier for the performance of reduced osmolarity ORS, the effect was assessed overall and as an interaction between type of ORS and weaning status and age. Maternal satisfaction was assessed in a paired analysis among mothers whose children participated at least twice in the study. Results. In the overall analysis reduced osmolarity ORS was as efficacious as standard ORS as assessed by duration of diarrheal episode and total number of stool evacuations on Days 1 and 2. Non-breast-fed toddlers (i.e. children ages 12 to 30 months) treated with reduced osmolarity ORS had significantly shorter diarrheal episodes [1.14 days vs. 1.78 days with standard ORS; hazard ratio, 1.50; 95% confidence interval (CI), 1.07 to 2.09] and lower total number of stool evacuations on Days 1 and 2 (3.9 stool evacuations vs. 5.0 stool evacuations with standard ORS; ratio of geometric means, 0.77; 95% CI 0.60 to 1.01). No significant difference was found for breast-fed toddlers or for infants. There was no statistically significant difference in the ORS intake between the two treatment groups. The odds ratio for the mother preferring reduced osmolarity ORS to standard ORS was 1.92 (95% CI 0.97 to 3.85). Conclusions. Reduced osmolarity ORS was as efficacious as standard ORS. Non-breast-fed children treated with reduced osmolarity ORS had significantly shorter diarrheal episodes and a tendency toward lower stool frequency. These findings may be of importance, especially in developing countries where early weaning is common.

Fibrosing cholestatic hepatitis (FCH) has recently been described after solid organ transplantation in patients with hepatitis C virus (HCV) infection. Typically, FCH is characterized by an ominous clinical course leading to progressive hepatic failure and death if liver transplantation is not performed. Two HCV-infected patients underwent cadaveric renal transplantation for end-stage renal disease resulting from membranous nephropathy and diabetic nephropathy. The time intervals between transplantation and the biopsy diagnosis of FCH for the two patients were 7 months and 10 years. Both patients presented with jaundice, hyperbilirubinemia, and mild-to-moderate elevations in serum aspartate aminotransferase. One patient was also found to have type II mixed cryoglobulinemia. Interferon-α therapy was begun after a diagnosis of FCH was established by liver biopsy. Liver test abnormalities normalized rapidly. When cholestatic hepatic deterioration develops in an HCV-infected organ allograft recipient, the diagnosis of FCH should be considered and a liver biopsy performed. Our observations indicate that FCH can respond to antiviral therapy.

Three cases of chondromyxoid fibroma arising in the skull base are reported. The tumors arose in females 34, 65, and 66 (median 55) years of age. Two women presented with headaches, and one with nasal obstruction. Radiographic studies revealed that all three lesions were expansile soft tissue masses centered in the clivus, at least 4 cm in greatest diameter. One lesion involved primarily the clivus, the others extended from the clivus into the sphenoid and ethmoid sinuses. Two of the three cases were initially misdiagnosed as chordoma or chondrosarcoma. The initial treatment was curettage of gross disease in all three cases. One patient also received radiation therapy. One patient had local progression of disease, which was treated with surgery and radiation therapy. All patients are clinically free of disease 11 to 26 months following the most recent treatment. Chondromyxoid fibroma can and should be distinguished from chondrosarcoma and chordoma, two tumors which more commonly arise in the skull base and which have the potential to metastasize.

Thirty-three highly cellular leiomyomas of the uterus from patients 29 to 65 (mean, 46) years of age and six endometrial stromal nodules from patients 41 to 53 (mean, 46) years of age are described. The patients usually presented with irregular uterine bleeding. Twenty-eight of the leiomyomas were intramural and five, submucosal. Eleven of 18 whose consistency is known were soft, fish-flesh, or rubbery, 10 were yellow or yellow-tan; one had a prominent cystic component. The tumors ranged from 0.5 to 15 cm (mean, 4.6 cm) in maximum dimension. On microscopic examination, they were densely cellular and composed of cells that ranged from round to spindle-shaped and had scanty cytoplasm. A focal fascicular pattern was present in all of the cases. Blood vessels were typically large; thick muscular walls and focally dilated lumens were a conspicuous feature of the majority of the neoplasms. Arterioles were evident focally in most of the tumors but were prominent in only one of them. Cleft-like spaces, some representing compressed vessels, others due to internodular edema, were present in 24 of the tumors and were conspicuous in 15 of them. The neoplasms typically exhibited focal irregular extension into the adjacent myometrium, and this feature was conspicuous in 18 of them. They often merged almost imperceptibly with the adjacent myometrium. All tumors were immunoreactive for desmin and 32 of 32 for alpha-smooth muscle actin. Two of the stromal nodules were polypoid intracavitary masses, three were submucosal, and one intramural. Five were completely or predominantly solid with cysts present focally in three of them; one tumor was predominantly cystic. The solid tissue was frequently yellow. Microscopic examination disclosed a diffuse growth of closely packed small cells with scanty cytoplasm and nuclei that lacked atypia. Three neoplasms contained cells with abundant foamy cytoplasm that were immunoreactive for CD68, indicating that they were histiocytes and not neoplastic cells. All the neoplasms had a prominent component of arterioles, which in one tumor had hyalinized walls. Five tumors were entirely well circumscribed and one predominantly well circumscribed with limited extension into the adjacent myometrium. The tumors were immunohistochemically negative for desmin.(ABSTRACT TRUNCATED AT 400 WORDS)

Epithelioid hemangiomas are benign vascular tumors that usually occur in the skin and subcutis. They have been infrequently recognized in bone. Because of their unusual cytologic appearance and growth patterns, they are commonly confused with malignant tumors. We report a series of 12 epithelioid hemangiomas of bone occurring in adult patients, including five males and seven females whose ages at presentation ranged from 24 to 74 years, with a mean of 46 years. Five tumors were associated with involvement of the adjacent soft tissue. A single patient had multifocal bone disease. The most common presenting symptom was localized pain. Treatment of the patients varied widely; however, none of the tumors behaved aggressively. In 11 cases, adequate tissue was available for immunohistochemical analysis, which revealed positive staining for the epithelial markers cytokeratin and epithelial membrane antigen in nine cases. All 11 tumors stained for factor VIII-related antigen and Ulex europeus agglutinin. We believe that many of the vascular tumors of bone that have been reported as low-grade malignant hemangioendotheliomas probably represent examples of epithelioid hemangiomas. We recommend that the criteria for diagnosing vascular tumors of bone conform to those used for morphologically similar tumors that arise in the soft tissues.

Overgrowth of aerobic and anaerobic bacteria in the upper small intestine is a common finding in persistent diarrhea. We hypothesized that a large dose of broad spectrum, nonabsorbable oral antibiotic would hasten recovery from persistent diarrhea by eradicating aerobic bacterial overgrowth. Sixty-eight patients were randomly assigned to treatment with either oral gentamicin (n = 33) or placebo (n = 35) for a period of 6 days. The two groups were comparable in their clinical features, stool weights, duodenal and fecal microflora, during an initial 24 h observation period before randomization. The proportion of patients recovering within 6 days post-treatment was similar in the antibiotic (45.2%) and placebo (50%) groups. The stool weights in the two groups during 24-72, 72-120, and 120-168 h of the study did not differ significantly. The percent mean weight gain (g) at 168 h post-treatment in the antibiotic (1.0 +/- 5.1) and placebo (1.4 +/- 5.3) groups also did not differ significantly (p = 0.8). A similar proportion of antibiotic- (61.3%) and placebo- (60.7%) treated patients had started to gain weight by the last day of the study. We conclude that oral gentamicin was no more effective than placebo in reducing purge rates, in achieving earlier recovery from diarrhea, and in promoting the earlier onset of weight gain in this study.

This randomized, double-blind trial determined whether adding 90 mmol/L of alanine with a reduction in glucose to 90 mmol/L (alanine ORS) improves the efficacy of the standard oral rehydration solution (WHO-ORS). One hundred twenty-nine males aged 3-48 months with weight for length greater than or equal to 70% of NCHS, diarrheal duration less than or equal to 96 h, and clinical signs of mild to moderate dehydration were randomly allocated to either treatment group. During 0-6 h of treatment, ORS was offered at 120 ml/kg for rehydration without food or water. Beyond 6 h, ORS was offered as a volume-to-volume replacement for stool losses and a mixed diet of uniform composition was offered in amounts standardized for body weight. The most frequently isolated pathogens in alanine ORS and WHO-ORS groups were rotavirus (42 and 48%, respectively) and enterotoxigenic Escherichia coli (15 and 12%, respectively). In the 0-6 h period when food was withheld, median urine output in ml/kg (8;5, p less than 0.05) and percentage decrease in total serum solids (9:7%, p = 0.06) was significantly greater in alanine ORS than in WHO-ORS; median ORS intake and stool output were marginally lower in the alanine group but the differences were statistically not significant. Between 0 h and recovery, although the median values for duration of diarrhea (56.5 and 65.0 h), ORS consumption (260 and 323 ml/kg), and stool output (188.4 and 216.3 g/kg) were lower in the alanine ORS group, these differences with the WHO-ORS group were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Sinonasal hemangiopericytomas are rare, occasionally misdiagnosed neoplasms that have often been considered distinct from hemangiopericytomas of other sites. Eleven cases were studied. Nine arose from the nasal cavity and two from the paranasal sinuses. The patients' mean age was 58 years. In nine cases there were no appreciable mitoses; in two, mitoses were frequent. Of 10 cases studied by immunostaining, all were positive for vimentin; two had faint focal staining for actin; one focally expressed S-100 protein; all were negative for cytokeratins, desmin, and Factor VIII-related antigen; and none bound Ulex europaeus agglutinin 1. Five cases were studied by electron microscopy. The most consistent features were basal lamina-like material partly surrounding tumor cells and completely separating them from endothelium, tapered cytoplasmic extensions, and orderly bundles of filaments. Intercellular junctions and pinocytotic vesicles were present in some tumors. Of nine cases with adequate follow-up, tumors recurred in four cases (44%) after a mean of 6.5 years, and none metastasized. A review of the literature showed that high local recurrence rates, late recurrences, and low rates of metastasis were features of tumors in this location. This might be a reflection of early presentation, small tumor bulk, and difficulty of complete resection, rather than evidence for a biologically distinct neoplasm.

Efforts by developing countries, backed by international support, are helping achieve a steady decline in under-5 mortality. Recent estimates suggest that under-5 deaths fell from 9.6 million to 6.9 million between 2000 and 2011, with the under-5 mortality rate falling from 73 to 51 per 1000 live births.1 This progress, though slower than hoped in some countries, nevertheless gives cause for optimism. Of note, as postneonatal mortality has declined, an increasing proportion of under-5 deaths are occurring in the neonatal period, underscoring the importance of prevention of neonatal mortality to overall infant and under-5 mortality. Research must focus on the design of innovative solutions that are both efficacious and effective for preventing neonatal deaths. Prematurity and clinical infections are major causes of neonatal deaths. Neonatal infections, including pneumonia, sepsis and meningitis, are estimated to cause over 700,000 deaths each year.2 Until recently, neonatal deaths associated with clinical infections were considered difficult to address, but several advances are paving the way for the design of a concrete strategy and action plan to address infectious causes of neonatal mortality.

BACKGROUND: Chlamydia trachomatis infection in pregnant women is suspected to result in low birth-weight and premature infants. We conducted studies to ascertain the prevalence of this infection among pregnant women in our setting and whether its presence is a risk factor for low birth-weight or prematurity. METHODS: In the first study, 94 pregnant women between 26 and 30 weeks of gestation were screened for infection with Chlamydia trachomatis. The second investigated a cohort of 172 pregnant women presenting in spontaneous labour. The infection status was related to perinatal outcome in terms of birth-weight and gestation. In both the studies, Chlamydia trachomatis infection was diagnosed using the Chlamydiazyme test performed on endocervical swabs. RESULTS: The prevalence of Chlamydia trachomatis infection in mid-pregnancy and at labour was 17% (16/94) and 18.6% (32/172), respectively. Women with infection were relatively older than those without it [mean (SD) age: 26.6 (4.5) years v. 24.8 (3.6) years, p = 0.01]. The mean (SD) birth-weight [2869 (611) g v. 2814 (496) g], gestation [38.5 (2.6) weeks v. 38.3 (2.0) weeks], and incidence of low birth-weight [18.7% v. 20.7%] as well as prematurity [9.4% v. 10.7%] were similar among neonates born to women with or without infection. Neonates born to infected mothers experienced purulent conjunctivitis more frequently than those born to non-infected mothers [12.5% v. 2.8%, p = 0.04]. CONCLUSION: Chlamydia trachomatis is a relatively common infection in pregnant women. However, it was not associated with either low birth-weight or prematurity.

The duodenal juice and fecal aerobic microflora was investigated in 54 patients with persistent diarrhea (age less than or equal to 2 years). The duodenal aspirates yielded increased aerobic bacteria (greater than 10(5) organisms/ml) in 28 (51.9%) of the patients. Established enteric pathogens were isolated from the duodenal aspirates of 12 (22.2%) of the 54 patients, viz., enteroadherent Escherichia coli (EAEC) (5), enterotoxigenic E. coli (ETEC) (3), enteropathogenic E. coli (EPEC) (1), nontyphoidal Salmonella (1), and Giardia lamblia (2). The total aerobic bacterial count was greater than 10(5) in all 12 patients positive for specific pathogens apart from one case in whom E. coli showing diffuse adherence to HEp-2 cells were identified. Among the remaining 42 specific pathogen-negative patients, 19 (45.2%) also had greater than 10(5) aerobic organisms/ml in the small bowel. Eight strains of Klebsiella from four of the patients were negative for enterotoxin production in a rabbit ileal loop assay and for adherence to HEp-2 cells. In contrast, 28/54 (51.9%) of the same patients had known enteric pathogens in their stools, viz., nontyphoidal Salmonella (8 or 14.8%), Shigella (2 or 3.7%), Campylobacter (1 or 1.9%), ETEC (4 or 7.4%), EPEC (2 or 3.7%), EAEC (7 or 13.0%), and G. lamblia and Entameba histolytica (3 or 5.6%). Further search for potential virulence factors among aerobic bacteria colonizing the upper small intestine in persistent diarrhea is warranted.

Children with acute diarrhea and moderate dehydration between 3 months and 5 years of age were randomly assigned to receive treatment with standard WHO oral rehydration solution (ORS) (n = 33) and two other solutions in which the 20 g/L glucose was substituted by 50 g/L of pop rice (n = 31) and 60 g/L of mung bean (lentil) powder (n = 29). Satisfactory oral rehydration, as assessed clinically and by changes in PCV and total serum solids (TSS), was achieved in 90.9% with WHO ORS, 96.8% with pop rice, and 96.6% in the mung bean ORS treated group (p greater than 0.05). The purging rates (ml/kg/h) until recovery were 2.49 +/- 1.5 (pop rice); 2.91 +/- 2.0 (WHO), and 3.41 +/- 1.7 in the mung bean group (p greater than 0.05). The percentage of patients recovering from diarrhea within the 72 h study period was 58.0 (pop rice), 48.4 (WHO), and 44.8 for mung bean group (p greater than 0.05). Though differences in stool volumes and duration in the three groups were not statistically different, there was a trend toward improvement in efficacy with the pop rice ORS in several parameters: greater weight gain, higher percentage decline in TSS, higher urine output despite lower ORS intake, and lower purging rates. The intake of semisolids in the 24-72 h study period was also higher in the pop rice group as compared to the other two groups (p less than 0.05). The number of breast feeds and intake of artificial milk was however similar in all groups (p greater than 0.05).

We have examined the nature and kinetics of T cell infiltration into murine first-set skin allografts across a variety of histocompatibility differences. Both Ly 1+2- and Ly 2+ cells migrate into grafts that differ with respect to discrete class I, class II, or minor H barriers. The lymphoid cells in the allograft did not express MEL 14 or the B cell antigen B220. The cells in the graft progress from the vascular anastomosis region into the dermis with apparent homing and clustering about hair follicles and epithelial cells at the dermoepidermal junction. Microscopic necroses appear in a patchy distribution in these areas. The intensity of the infiltrate is related to the nature of the alloantigen recognized but it does not correlate with the tempo of rejection. Class II-disparate allografts evoke a peak response (mean 62 +/- 34 T cells/0.1 mm2) that is 2-6-fold greater than class I-disparate allografts or syngeneic control peak responses (mean 14 +/- 2.4 T cells/0.1 mm2). Although a difference at a minor H antigen evoked an intense peak T cell response (192 +/- 33 T cells/0.1 mm2), the mean survival time of the allografts was significantly longer than that observed with class I or class II differences. The IL-2 receptor+ subset of activated T cells is extremely rare in syngeneic grafts, but ranges from 0 to 56% of infiltrating T cells in allografts. We conclude that all major T cell subsets contribute to the in situ response to all classes of alloantigens, but at the apparent exclusion of the MEL 14+ T cell pool and B cells.

Plasmacytoid T cells in two cases of Castleman's disease were stained with a panel of monoclonal antibodies to hematopoietic cell-associated antigens, using an immunoperoxidase technique on frozen sections. The immunohistologic phenotype of these cells was T4/Leu-3+, HLA-DR+, T1/Leu-1-, T3/Leu-4-, T8/Leu-2-, T11/Leu-5-, B1-, B2-, Leu-14-, Ig-, CALLA-, OKM1-, Leu-M1-. In contrast to plasma cells of B lineage, plasmacytoid T cells were T200+, T10-. The phenotype was similar to that of two previously reported lymphomas of plasmacytoid T cells. Plasmacytoid T cells appear to be a unique subset of lymphoid cells, whose function remains to be established.

We analyzed the distribution and immunologic phenotype of the neoplastic cells in eight cases of mantle-zone lymphoma. Although in all the cases the follicle centers appeared reactive on routine histologic examination, polyclonal staining for immunoglobulin was found in the follicle centers in only five of the eight cases; in the other three cases the follicle centers were monoclonal. In three cases, the immunologic phenotype was that of centrocytic (diffuse small cleaved cell) lymphoma: IgM+IgD+B1+B2+Ia+Tl+. In one case the phenotype was that of a follicular (centroblastic/centrocytic) lymphoma: IgG+B1+B2+Ia+CALLA+. In the other four cases, the phenotype was IgM+B1+B2+ or B2-Ia+; this phenotype can be seen in diverse B cell lymphomas. The phenotype of normal mantle-zone cells (IgM+IgD+B1+B2+Ia+) was not reproduced by any of the lymphomas. A mantle-zone pattern may be produced by either follicular or diffuse lymphomas of predominantly small cleaved cell type, and does not indicate an origin from the cells of the normal mantle zone.

This review has pointed out the good correlation frequently observed between ATPase activity of various contractile protein preparations and contractile function of various muscles including the myocardium. Some of the variables in the measurement of the various ATPases and the relationship of these measurements to physiological ATPase in the intact myofibril have been mentioned. The possible roles of changes in the light chains of sulfhydryl groups in the control of ATPase activity have been outlined. The possibility that phosphorylating reactions might exert control over physiological activity remains to be clarified. It is evident that, despite the large amount of research that has been done, our understanding of how the biochemistry of contractile proteins relates to physiological function is in its infancy, and only with a more complete elucidation of the underlying biochemistry of the components of contractile proteins of physiological and pathophysiological adaptations become evident.

An immunoperoxidase study, using the Avidin-Biotin-Peroxidase complex method and the monoclonal antibodies, anti-carcinoembryonic antigen (CEA) and anti-carbohydrate determinant 19-9 (CA 19-9), was carried out on 108 common epithelial tumors of the ovary and 13 epithelial tumors metastatic to the ovary. Primary mucinous tumors were positive in 62% of the cases (benign, 15%; borderline, 80%; and carcinomatous, 100%) with anti-CEA. None of the serous tumors were positive with anti-CEA, but 27% (benign, 23%; borderline, 40%; and carcinomatous, 20%) were positive with anti-CA 19-9. With anti-CEA, 30% of the endometrioid carcinomas, 50% of the malignant mesodermal mixed tumors, 14% of the clear cell carcinomas, 36% of the Brenner tumors, and 83% of the metastatic carcinomas from the large intestine were positive. With anti-CA 19-9, 76% of the mucinous, 40% of the endometrioid, 25% of the malignant mesodermal mixed tumors, 57% of the clear cell carcinomas, 45% of the Brenner tumors, and all the metastatic carcinomas from the large intestine were positive. All the undifferentiated carcinomas were unreactive with both antibodies. Although neither CEA nor CA 19-9 is a specific marker for any type of ovarian tumor or for malignancy per se, the presence of the former antigen can be useful in differentiating serous from mucinous tumors. Moreover, demonstration of either antigen in a variety of tumors may indicate its potential value as a serum marker in monitoring the course of the patient.

The role of enteric-type adenoviruses and rotaviruses in mild and severe acute gastroenteritis was investigated among children younger than 5 years of age seeking treatment at an urban hospital (UH) and at a rural health center (RHC) in India. There were 330 children at the UH and 340 at the RHC; 319 and 315 age matched nondiarrheal children served as controls for the respective groups. Rotavirus was detected in 15.2% of 330 cases and 1.9% of 319 controls at the UH (P less than 0.001) and in 16.5% of 340 cases and 2.9% of 315 controls at the RHC (P less than 0.001). RV excretion was 3- to 5-fold more common in severe compared with mild diarrhea at the UH and at the RHC (P less than 0.001). The detection rate for enteric-type adenoviruses was similar in patients and controls, respectively, at the UH (0.9%; 2.5%) and RHC (3.8%; 2.5%). At the RHC adenovirus types other than 40 and 41 were excreted by 8.8% of the patients and by only 1.0% of the controls (P less than 0.001). It is possible that the diarrheagenic role of adenoviruses may not be restricted to types 40 and 41.

A hospital-based case-control study including 92 children with diarrhea for longer than 14 days and 92 controls without gastrointestinal symptoms was performed to describe the association between the excretion of enteric pathogens and persistent diarrhea. In patients the most frequently isolated stool pathogens were enteroaggregative Escherichia coli (19.6%), nontyphoidal Salmonella spp. (17.4%), E. coli with diffuse adherence pattern (7.6%), G. lamblia (7.6%) and enterotoxigenic E. coli (5.4%). The excretion rates in patients were significantly greater than in controls only for nontyphoidal Salmonella spp. (P = 0.0006) and enteroaggregative E. coli (P = 0.016).

R-1 anti-reticulin antibodies (ARA) were present in sera of 10 of the 12 children who subsequently fulfilled the ESPGAN diagnostic criteria for celiac disease (CD), but was not found in any children in the age-matched control groups, viz., severely malnourished (n = 20), acute gastroenteritis (n = 23), normally nourished asymptomatic (n = 38), and 42 children with protracted diarrhoea and failure to thrive due to nonceliac causes. ARA was a highly specific (100%) and sensitive (83%) assay for the early diagnosis of CD. A positive ARA assay with an initial subtotal villous atrophy was seen to always suggest CD, and these together would provide a useful basis for instituting gluten-free diets in suspected cases of CD rather than histological findings alone, which may be often present in children in the third world with protracted diarrhoea and associated severe malnutrition.

We studied class I (A/B/C) and class II (DR) HLA antigens on human corneal cells with monoclonal antibodies using immunofluorescence and immunoperoxidase techniques. Cryostat sections of freshly harvested human corneas expressed class I HLA antigens on the corneal epithelium. Class II antigens were not detected on these corneal specimens, except for occasional, scattered positive cells in the peripheral corneal epithelium and stroma near the corneoscleral limbus. Corneal endothelial whole flat mounts from freshly excised human corneas were negative for class I and class II HLA antigens. In tissue culture, however, growing human corneal endothelial cells expressed class I HLA antigens. Crowing human corneal fibroblasts in tissue culture similarly were shown, through immunofluorescent techniques using monoclonal antibodies, to express class I HLA antigens. Fibroblasts and endothelial cells in tissue culture were negative for class II HLA antigens. We believe the low-to-nondetectable HLA antigen expression on central corneal stroma and endothelium may partly explain the immunological tolerance enjoyed by most corneal allografts.