Robert G. Strickland

Studies of human lymphocytes in the newborn and the aged

Proportions and absolute numbers of T and B lymphocytes were determined among 30 newborn infants and group of 77 elderly patients 60 to 95 years of age. Total lymphocytes in the cord blood of the newborn showed a distinct elevation in total numbers of T and B lymphocytes (p less than 0.005) as compared to that in blood from normal adult controls, reflecting the relative lymphocytosis of infancy. Proportions of cord blood T lymphocytes as reflected by the sheep cell rosette technic were considerable lower than those in lymphocytes from normal adult controls, however, proportions of cord blood T lymphocytes as determined by indirect immunofluorescence were not significantly different from those in controls. Old people showed a significant reduction in total numbers of lymphocytes (p less than 0.005) when compared with those in normal adult controls 18 to 51 years of age. Moreover, there was a significant increase in the relative proportions of peripheral blood B lymphocytes in the elderly although the absolute numbers of B lymphocytes in the elderly although the absolute numbers of B cells did not differ from those in younger controls. A significant decrease in total numbers of T cells as measured both by sheep cell rosettes and indirect immunofluorescence was recorded among older patients (p less than 0.001). In addition, there was a broad increment in the incidence of various autoantibodies (anti-nuclear, andi-IgG, antismooth muscle, antimitochondrial and antiparietal cell) among the old people studies. No direct correlation could be determined between relative B-cell percentage increase or T-cell decrease and the presence of various autoantibodies in individual patients. Diminution in total lymphocyte counts as well as absolute numbers of T cells in the elderly may provide the cellular basis for an increased susceptibility to neoplasia and infection.

Tissue T and B cell infiltration of primary and metastatic cancer.

Immunofluorescent techniques were utilized to identify the types of infiltrating lymphocytes adjacent to human malignant tumors arising from a wide range of anatomic sites. 24 of 29 primary tumors and 5 of 8 metastatic lesions showed varying degrees of lymphocytic infiltration. T cells predominated in the infiltrates in primary tumors (mean 80%, range 50-100%) and this pattern was evident regardless of anatomic site or the presence or absence of metastatic spread. By contrast, B cells predominated at the margins of three of five tumor metastases. Mononuclear cells bearing the Fc receptor were not a prominent component of the infiltrates associated with either primary tumors or metastases, but tumor cell binding of fluoresceinated IgG aggregates was observed in 12 of 29 primary tumors. A significant reduction in peripheral blood T cell numbers occurred in a third of the patients studied. This decrease was not clearly related either to the extent of local tumor T cell infiltration or to the presence of disseminated disease. These preliminary findings provide a descriptive analysis of the local and systemic distributions of immunocompetent cells in cancer.

Inhibitors of leukocyte chemotaxis in alcoholic liver disease

Twenty-one of 42 patients (50 per cent) with alcoholic liver disease showed serum chemotactic inhibitory activity (CIA). CIA was not related to any single biochemical or histologic feature in the patients studied. The frequency of CIA was greatest in those with active infection. Serial studies demonstrated that CIA may be a transient phenomenon, associated with active alcoholic liver disease or appearance of infection. Nine of 15 patients showed skin test anergy; CIA was present in 8 of these 9 patients. Serum immunoglobulin A (IgA) and G (IgG) concentrations were significantly higher in patients with CIA when compared to those without CIA. Sucrose density gradient centrifugation of serums showing CIA yielded three peaks of inhibitory activity. Two had sedimentation coefficients of 10.7S and 6.8S, and the third was approximately 3S. The two higher molecular weight inhibitors were predominant in the 50 per cent ammonium sulfate precipitate. Immunoabsorption by anti-IgA but not by anti-IgG or IgM columns removed the ammonium sulfate precipitable chemotactic inhibitors. The appearance of chemotactic inhibitors in patients with alcoholic liver disease may have relevance to their apparent susceptibility to serious infections.

Lymphocytotoxic Antibody in Inflammatory Bowel Disease: A Family Study

The prevalence of lymphocytotoxic antibody in inflammatory bowel disease is 40 per cent. Twenty-seven of 90 relatives of 23 probands with the disease (30 per cent) demonstrated lymphocytotoxic antibody, as contrasted with only three of 69 control family members (4 per cent) (P less than 0.0001). Decreased lymphocytotoxicity against lymphocytes from patients with inflammatory bowel disease as compared to normal donor lymphocytes previously demonstrated in the serum of probands was also observed in the serums from family members of the probands. Nineteen of the 48 household contacts of probands (40 per cent) were positive for antibody, whereas eight of 42 nonhousehold contacts (19 per cent) demonstrated it (P less than 0.05). Eight of 16 spouses (50 per cent) of probands showed antibody. The increased prevalence of lymphocytotoxic antibody in family members of probands and its occurrence mainly in household contacts (consanguineous and non-consanguineous) may indicate the exposure of probands and their family members to a common environmental agent.

T and B lymphocytes in acute and chronic hepatitis.

Abstract Peripheral blood thymus-dependent (TL) and bone marrow-dependent lymphocytes (BL) were measured in healthy control subjects and patients with acute or chronic hepatitis with and without hepatitis B antigen (HBAg) and in two chronic carriers of HBAg. A significant decrease in TL occurred in patients with acute or chronic hepatitis but not in healthy HBAg carriers. The decrease occurred in all forms of acute hepatitis and was transient in patients who recovered. TL depression occurred in both chronic persistent and chronic aggressive hepatitis and did not correlate with disease activity nor mode of treatment. In both acute and chronic hepatitis, decreases in TL occurred independently of serum autoantibodies. These findings emphasize the potential importance of host responses in determining the outcome of viral hepatitis.

The Sydney System: Auto‐immune gastritis

The association of gastric auto‐immunity with chronic gastritis has been recognized for more than 30 years. Despite this, little is known about the initiation of auto‐immune gastric mucosal injury or the role of gastric auto‐antibodies in this disease process. The current review describes recent progress in our understanding of these fundamental questions on the origin and progression of auto‐immune gastritis.

Solitary Gastric Carcinoid Tumor Associated with Long-Term Use of Omeprazole: A Case Report and Review of the Literature

Gastrin exerts trophic effects on all cells of the gastric oxyntic mucosa including enterochromaffin-like (ECL) cells. Hypergastrinemia may result from hypoor achlorhydria due to chronic atrophic gastritis, from longterm drug-induced acid suppression or from gastrinoma occurring as part of the multiple endocrine neoplasia (MEN) 1 syndrome [1]. We describe here a man who developed an atypical, benign gastric carcinoid or neuroendocrine tumor (NET), after being treated with a proton pump inhibitor (PPI) for 20 years.

Subpopulations of T cells (Tγ and Tμ) in patients with chronic liver disease

Abstract The present study has utilized cell surface markers for the Fc receptors of IgG and IgM to distinguish putative suppressor (Tγ) or helper (Tμ) T-cell subpopulations in peripheral blood lymphocyte preparations from a group of patients with chronic liver disease of diverse etiology. Proportions and absolute numbers of Tγ and Tμ cells were compared to corresponding values in healthy subjects and correlations made with levels of serum immunoglobulins and the presence of circulating autoantibodies. A marked reduction in T cells was observed in patients with liver disease, the decrease primarily being in the Tμ subpopulation. No striking correlations emerged between proportions or numbers of these T-cell subpopulations and either serum immunoglobulin levels or circulating autoantibodies.

Decompensated Liver Disease in a Patient with Neurocysticercosis

A 48-year-old man with a history of neurocysticercosis was evaluated in the gastroenterology outpatient clinic for abnormal liver tests. His past medical history included hospitalization for tonic–clonic seizures in 2010, after which he was diagnosed as having neurocysticercosis. At that time, a computed tomography (CT) scan of the head revealed numerous intra-parenchymal active cysts and edema in the right frontal lobe, but on slit lamp examination no intraocular cysts were present. The seizures were controlled and stabilized by treatment with levetiracetam. He also received short-term treatment with dexamethasone for reduction of cerebral edema and albendazole to eliminate the parasite. Following this, he did well for 4 years until he was evaluated again in November 2014 with recurrence of tonic–clonic seizures. On CT scan of the head, active intra-parenchymal brain lesions were again noted, for which he was treated with a second course of albendazole and dexamethasone. Although his liver tests were normal on admission, 25 days later he developed mild elevation in liver function, with serum concentrations of aspartate transaminase (AST) 59 unit/L (N: 6–58 unit/L), alanine transaminase (ALT) 72 unit/L (N: 14–67 unit/L), alkaline phosphatase 168 unit/L (N: 38–150 unit/L), and total bilirubin 0.8 mg/dL (N: 0.3–1.2 mg/dL). On the basis of these abnormalities, he was referred, shortly after discharge, to the outpatient liver clinic for further evaluation. In the liver clinic, he complained of worsening abdominal distension, post-prandial epigastric discomfort, early satiety, worsening lower extremity edema, and intermittent diarrhea, all for about 2-month duration. His medications included levetiracetam 1 g twice daily and aspirin 81 mg daily. Employed as a construction worker, he travelled to Mexico twice per year. He denied any significant intake of alcohol, drinking only 1–2 beers on the weekend. Family history revealed a mother with diabetes mellitus, a brother with idiopathic seizures, and a sister that died at age 30 in Mexico from liver disease of unknown etiology. On physical examination, he had visible, moderate, abdominal distention, mild diffuse tenderness on palpation (no rebound tenderness), flank dullness on percussion, and a positive fluid thrill that indicated the presence of ascites. His bowel sounds were normoactive. Over the precordium, there was a grade 2/6 systolic ejection murmur, heard best at the left upper sternal border. The skin appeared normal, but there was moderate lower limb edema bilaterally. No neurologic abnormalities were noted. His body mass index (BMI) was 32.8. Laboratory evaluation was remarkable for a platelet count of 97 9 10/lL (N: 150–400 9 10/lL), and serum concentrations of AST 72 unit/L (N: 6–58 unit/ L), ALT 70 unit/L (N: 14–67 unit/L), alkaline phosphatase 160 unit/L (N: 38–150 unit/L), total bilirubin 1.2 mg/dL (N: 0.3–1.2 mg/dL), direct bilirubin 0.5 mg/dL (N: 0.1–0.4 mg/dL), albumin 2.7 g/dL (N: 3.4–4.7 g/dL), and total protein 6 g/dL (N: 6.1–8.2 g/dL). Blood international normalized ratio (INR) was 1.3 (N: 0.8–1.2), and serum protein electrophoresis showed a polyclonal increase in the gamma globulin fraction. His model of end-stage liver disease (MELD) score was 10. & Aly M. Mohamed amohamed@salud.unm.edu