Norihiko Okuda

Epidemic of Gastrointestinal Tract Infection Including Hemorrhagic Colitis Attributable to Shiga Toxin 1-producing Escherichia coli O118:H2 at a Junior High School in Japan

Background.  An epidemic of gastrointestinal disturbances related to food ingestion occurred at a junior high school in Komatsu, Japan, and was caused by specifically Shiga toxin (Stx) 1-producing Escherichia coli O118:H2, which has not been reported previously in humans. No outbreak ofE coli-producing Stx 1 alone had occurred. Methods.  A total of 526 students and 35 adult staff members who ate the same food at lunch in the school were investigated. Questionnaires about food consumption at lunch were given to all 561 subjects as well as to clinics and hospitals that had treated 79 patients. Stool specimens from 525 subjects, and food, water, and environmental specimens, including cooking utensils, were collected in an attempt to identify the pathogen. Results.  A total of 126 subjects (22.5%) developed a diarrheal illness. The pathogen was isolated from the stool in 131 subjects, 49 of which were asymptomatic, and from a dipper. Salads served over several days were identified as high-risk from food analysis. Gastrointestinal symptoms resembled those associated with previous infections of Stx-producing E coli, but were mild. No cases of the hemolytic–uremic syndrome developed. Headache was present in 87 patients. Three patients underwent surgery for acute appendicitis during this epidemic. Four of five carriers had received an antibiotic effective against the pathogen. Conclusions.  This outbreak of E coliO118:H2 demonstrated the clinical and epidemiologic features of infection by E coli that produces Stx 1 alone. Infections with such organisms are being recognized increasingly, and the pattern of disease observed may differ from the pattern observed with E coli O157:H7.

Central hypothyroidism resulting from pituitary suppression and peripheral thyrotoxicosis in a premature infant born to a mother with Graves disease

We observed the sequential changes in serum thyroid hormones and thyroid-stimulating hormone receptor antibodies in an infant born at 30 weeks of gestation to a mother with florid Graves disease. Transient central hypothyroidism caused by pituitary suppression was observed after the resolution of peripheral thyrotoxicosis induced by thyroid-stimulating antibody. Central hypothyroidism became overt when the suppression of the pituitary gland after fetal thyrotoxicosis was combined with weak activity of thyroid-stimulating antibody after birth.

Periodic ACTH discharge

A 9 1/2-year-old girl is presented who had cyclical attacks of abdominal pain, vomiting, emotional disturbance, and marked weight change for two years. Associated findings were facial plethora, hypertension, transient hyperglycemia and glycosuria, elevated plasma ACTH, cortisol, and urinary 17-OHCS excretion, and low plasma osmolality with hyponatremia. Urinary excretion of catecholamines and porphyrin metabolites was not increased. Between episodes, she showed no abnormal clinical signs or laboratory data. The attacks were effectively suppressed with the administration of chlorpromazine. The disorder appears to be due to the periodic release of excessive ACTH; the cause remains unknown.

A CASE OF MOSQUITO HYPERSENSITIVITY TERMINATING AS MALIGNANT HISTIOCYTOSIS

A patient with a 5 year history of hypersensitivity to mosquitoes developed a skin nodule on the chest, high fever, and hepatosplenomegaly. The diagnosis of malignant histiocytosis was made, based upon histological examination of the skin and cytological study of the pleural effusion. Immunological studies revealed the impaired activity of both T and B cells. After four weeks of no response to chemotherapy, the patient died. Autopsy revealed malignant histiocytes invading the bone marrow, liver, spleen, lung, adrenal glands, lymph nodes and skin. The possible relationship of immunodeficiency to malignant histiocytosis is discussed.

Hematologic findings associated with thrombocytopenia during the acute phase of exanthem subitum confirmed by primary human herpesvirus-6 infection.

Purpose To elucidate the mechanism underlying thrombocytopenia during the acute phase of exanthem subitum (ES), the associated hematological findings were investigated. Patients and Methods Five infants with thrombocytopenia during the acute phase of ES serologically confirmed by primary human herpesvirus-6 (HHV-6) were examined and followed-up. Results Thrombocytopenia was accompanied by neutropenia, leukopenia, and decreased reticulocyte fraction during the acute phase. These changes were self-limiting, and the sequential changes of platelet, neutrophil count, and reticulocyte fraction were closely linked. Slight but significant decreases in hemoglobin in the convalescent phase and mild increases in atypical lymphocytes after subsidence of the fever were observed. Hemophagocytosis and increase in atypical lymphocytes in the bone marrow suggested that bone marrow cells were influenced by primary HHV-6 infection. Platelet-associated immunoglobulin G and indirect antiplatelet antibody were negative. Plasma levels of fibrinogen and D-dimer of fibrinogen degradation products were within normal ranges. Conclusions Thrombocytopenia is a complication of ES, and this may result from bone marrow suppression rather than from immune-mediated peripheral consumption seen in acute idiopathic thrombocytopenic purpura or from disseminated intravascular coagulation.

Characterization of glycosaminoglycans in rabbit plasma and leukocytes at disaccharide subunit level

Abstract The glycosaminoglycans in rabbit plasma were found exclusively in the protein fraction precipitated with trichloroacetic acid. The concentration, estimated as glucuronic acid, was approximately 100 μg per 100 ml of plasma. Electrophoretic characteristics and disaccharide subunit assay with chondroitinase indicated that the major glycosaminoglycans in rabbit plasma were chondroitin 4-sulfate and undersulfated chondroitin 4-sulfate. Although electrophoretic mobility and enzymatic susceptibility suggested the presence of a small amount of hyaluronic acid in rabbit plasma, the disaccharide subunit assay failed to demonstrate the existence of this material. The glycosaminoglycan content of rabbit marrow cells was about 150 μg of glucuronic acid per 100 mg dry weight. The disaccharide subunit assay indicated the major glycosaminoglycan in rabbit marrow cells to be chondroitin 6-sulfate. Chondroitin 4-sulfate, dermatan sulfate and hyaluronic acid were also identified as minor constituents. The chondroitinase AC-II digests of the glycosaminoglycans in marrow cells contained another ultraviolet-absorbing spot which was slower in migration rate on chromatography than the reference disaccharides and was completely degraded by chondroitinase ABC. These results suggest that a hybrid structure might be present in dermatan sulfate obtained from rabbit marrow cells but the exact nature of this material is still to be elucidated.

Presence of Turner stigmata in a case of dysgenetic male pseudohermaphroditism with 45,X/46,X+mar karyotype

A case is reported of dysgenetic male pseudohermaphroditism (DMPH) having Turner stigmata and 45,X/46,X+mar karyotype. The marker chromosome of this patient consisted of most if not all of the short arm, including the sex determining region of the Y chromosome. Although this karyotype is relatively common in Turner’s syndrome and occasionally observed in mixed gonadal dysgenesis, DMPH is usually exemplified by a 46,XY karyotype except for one patient reported with 45,X/46,XY mosaicism. Turner stigmata have not previously been reported in DMPH. The present patient is an intermediate case between mixed gonodal dysgenesis and typical DMPH, and this indicates that 45,X/46,X+mar karyotype abnormality can result in a wide range of phenotype such as DMPH, mixed gonodal dysgenesis and Turner’s syndrome.

Transient increase of IgG Fc receptor-bearing T lymphocytes following positive PPD skin testing.

In tuberculin‐sensitive individuals, IgG Fc receptor (FcR)‐hearing lymphocytes in the peripheral blood increased transiently following PPD‐tuberculin skin test. This rise in circulating FcR‐bearing cells appeared to peak about 36–48 h after the intradermal inoculation of PPD and seemed to occur largely in the T cell population. Skin test‐negative individuals showed no significant changes in their circulating FcR‐bearing cells following PPD inoculation. Peripheral blood lymphocytes from PPD‐sensitive individuals were fractionated into non‐T cell and T cell‐enriched populations by E rosette sedimentation technique. FcR‐bearing cells in the T cell‐enriched population were eliminated by EA rosette sedimentation: i. e. FcR‐negative T cells. Then, equal numbers (1 × 105 cells each) of non‐T cells and unfractionated or FcR‐negative T cells were recombined in culture. Prior to PPD inoculation, there was no significant difference between these two cell mixtures in the in vitro cellular response to PPD or mitogens. When these cell populations were obtained. 16–48 h after PPD inoculation, however, the combination of non‐T tells and FcR‐negative T cells responded to PPD much better than the combination of non‐T cells and unfractionated T cells, whereas the mitogen‐induced cellular proliferation of these two cell mixtures did not differ from each other.

Induction of Suppressor Activity on B‐Cell Differentiation in Human T‐Cell Subset without Fc(IgG) Receptors by Levamisole Administration

A single oral dose of 150 mg levamisole was administered to five healthy adults. Circulating Fc(IgG) receptor‐bearing T cells (Tγ cells) increased for 5 days after levamisole intake, but total E rosette‐forming cells showed no significant alterations. The generation of immunoglobulin‐producing cells in the peripheral blood lymphocytes (PBL), which was induced in the in vitro pokeweed mitogen (PWM)‐stimulated cultures, was significantly suppressed for 5 days after levamisole administration. Suppressor T‐cell activity on B‐cell differentiation, which was induced by levamisole intake, was evaluated by co‐culturing with allogeneic untreated adult PBL in the PWM system in six other volunteers. A seemingly dose‐dependent suppression on B‐cell differentiation was exerted by T cells isolated on day 3 of levamisole treatment, but not by T cells which were isolated before or on day 14 of the experiment. When T cells were fractionated into two subsets with regard to the presence or absence of Fc(IgG) receptors, suppressor T‐cell activity appeared to be generated by levamisole largely in T cells lacking Fc(IgG) receptors, but not in Tγ cells.

Blocking effect of human T lymphocyte extracts on E-rosette inhibition by sheep red cell fragments

Abstract Rosette formation, particularly active rosette formation, of human peripheral blood lymphocytes with sheep red blood cells (SRBC) was inhibited by the pretreatment of lymphocytes with sonicated SRBC fragments. However, when SRBC fragments were pretreated with a freeze-thawed extract of unfractionated peripheral blood lymphocytes, the inhibitory activity of SRBC fragments on E-rosette formation was abolished. Based on the different rosetting abilities, peripheral lymphocytes were separated into the populations enriched with active rosette-forming cells, late rosette-forming cells, and non-rosette-forming cells by rosette formation with SRBC followed by gradient centrifugation. A soluble extract of each population was prepared by extensive freeze-thawing in phosphate-buffered saline and the activity of each extract was assayed with the blocking effect on E rosette inhibition by SRBC fragments. This blocking activity was identified in the extract from the population enriched with active rosette-forming cells as well as in the extract from unfractionated peripheral blood lymphocytes, but not in the extracts from the other cell populations. These results suggest that the active rosette-forming cells of human lymphocytes have a unique receptor activity for SRBC fragments, presumably for intact SRBC, and the active materials in this cell population, although dissociated from the cells. retain their ability to bind competitively to SRBC fragments.