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Biomedical subjects

H Nunoi

Publications and source records attributed to H Nunoi.

68 records · Page 4Linked to original sources
PubMed1990

A disease with immune deficiency, skin abscesses, pancytopenia, abnormal bone marrow karyotype, and increased sister chromatid exchanges: an autosomal recessive chromosome instability syndrome?

A 19-year-old girl is described with microcephaly, short stature, mental retardation, pigmentation of the skin, and recurrent skin abscesses over the whole body. Her elder brother and sister both showed growth and developmental retardation, microcephaly, and anemia. Both died during childhood. Their parents were first cousins. Laboratory studies of the proband revealed hyperchromic erythrocytes with an increased HbF content, thrombocytopenia, an impaired mitogenic response of the PHA-stimulated lymphocytes, and partial impairment of humoral and cellular immunity. She developed pancytopenia in the terminal stage of the disease. Cytogenetic studies of the bone marrow revealed 46,XX, 15p+, -18, +mar karyotype, increased chromosomal aberrations and sister chromatid exchanges, in cultured lymphocytes and skin fibroblasts. She died at age 20. Thus, the disorder in the patient was deduced as an unclassified chromosomal breakage syndrome with an apparently autosomal recessive inheritance.

Abscess↗
PubMed1989

Genetic variants of chronic granulomatous disease: prevalence of deficiencies of two cytosolic components of the NADPH oxidase system.

Chronic granulomatous disease, a syndrome of recurrent infections and failure of oxidative microbicidal activity in phagocytes, results from defects in the gene for one of several components of an oxidase system that can undergo activation. To determine the relative prevalence of certain of the genetic variants of this disorder, we used immunoblotting to detect two specific neutrophil cytosolic proteins of 47 and 67 kd recently shown to be required for oxidase activation. Chronic granulomatous disease is usually an X-linked disorder associated with the absence of membrane cytochrome b558. Of our 94 patients with chronic granulomatous disease, however, 36 had a phenotype characterized by autosomal inheritance, normal membrane oxidase components (including cytochrome b558), and functionally defective cytosolic activity in a cell-free oxidase system. We studied 25 of these 36 patients and found that 22 lacked the 47-kd cytosolic protein, and the remaining 3 were missing the 67-kd component. Patients with chronic granulomatous disease whose functional defect was localized to the neutrophil membrane (classic X-linked cytochrome b-negative type and two other rare variants) had normal amounts of both cytosolic components. We estimate that approximately 33 percent of all patients with chronic granulomatous disease are missing the 47-kd cytosolic oxidase component and about 5 percent of patients are missing the 67-kd component. Chronic granulomatous disease caused by a defect in any cytosolic factors other than the 47-kd and 67-kd proteins, if it exists, is apparently rare.

Adolescent↗
PubMed1989

Recombinant 47-kilodalton cytosol factor restores NADPH oxidase in chronic granulomatous disease.

A 47-kilodalton neutrophil cytosol factor (NCF-47k), required for activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase superoxide (O2-.) production, is absent in most patients with autosomal recessive chronic granulomatous disease (AR-CGD). NCF-47k cDNAs were cloned from an expression library. The largest clone predicted a 41.9-kD protein that contained an arginine and serine-rich COOH-terminal domain with potential protein kinase C phosphorylation sites. A 33-amino acid segment of NCF-47k shared 49% identity with ras p21 guanosine triphosphatase activating protein. Recombinant NCF-47k restored O2-. -producing activity to AR-CGD neutrophil cytosol in a cell-free assay. Production of active recombinant NCF-47k will enable functional regions of this molecule to be mapped.

Amino Acid Sequence↗
PubMed1988

Two forms of autosomal chronic granulomatous disease lack distinct neutrophil cytosol factors.

Chronic granulomatous diseases of childhood (CGD) are a group of disorders of phagocytic cell superoxide (O2.-) production (respiratory burst). Anion exchange chromatography separated from normal neutrophil cytosol a 47-kilodalton neutrophil cytosol factor, NCF-1, that restored activity to defective neutrophil cytosol from most patients with autosomally inherited CGD in a cell-free O2.--generating system. A 65-kilodalton factor, NCF-2, restored activity to defective neutrophil cytosol from one patient with autosomal CGD. NCF-1, NCF-2, and a third cytosol fraction, NCF-3, were inactive alone or in pairs, but together replaced unfractionated cytosol in cell-free O2.- generation. Neutrophils deficient in NCF-1, but not NCF-2, did not phosphorylate the 47-kilodalton protein. It is proposed that NCF-1, NCF-2, and NCF-3 are essential for generation of O2.- by phagocytic cells and that genetic abnormalities of these cytosol components can result in the CGD phenotype.

Blotting, Western↗
PubMed1988

Severe hypoplasia of lymphoid tissues in Mo1 deficiency.

A lymph node was examined from a 4-year-old female child with documented "Mo1" (CR3) deficiency. There was hypoplasia of the lymph node, with small, poorly delineated germinal centers and overall lymphopenia. Retrospective analysis of the clinical course of a decreased elder sister of the index patient indicated that the elder sister probably also had "Mo1" deficiency. Review of findings at autopsy revealed severe hypoplasia of all lymphoid organs with lymphopenia. Our observations suggest that lymphoid tissue hypoplasia may be a feature of CR3 deficiency and is likely a result of the defective lymphocyte adherence functions to endothelium associated with absent lymphocyte function-associated antigen (LFA-1).

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Analysis of cell proteins in lymphoblasts of acute lymphocytic leukemia by two-dimensional gel electrophoresis.

The two-dimensional gel electrophoresis (2-DE) method developed by O'Farrell was used to analyze the differences of major proteins between lymphoblasts from children with acute lymphocytic leukemia (ALL) at diagnosis (lymphoblasts, n = 6), normal lymphocytes (n = 6) and lymphocytes from children with ALL in complete remission (lymphocytes in CR, n = 12). Among all the spots, those which were deeply stained and large were termed 'major spots'. Their number was 118. Two spots (No. B1 and B2) were characteristic of lymphoblasts, three spots (No. N1-N3) were characteristic of normal lymphocytes. In lymphocytes in CR, the latter spots were not always detected, and furthermore, the former spots were detected in several gels. These findings may relate to the insufficient recovery of functions of lymphocytes in CR. Several spots (No. 6, 55 and 57) in lymphoblasts were remarkably larger than those in normal lymphocytes. Spot No. 67, an actin spot, in lymphoblasts was smaller than that in normal lymphocytes. Spots No. 6, 55 and 57 in lymphocytes in CR were relatively small in size.

Adolescent↗
PubMed1986

Unusual case of diffuse connective tissue disease with nodule formations in muscle, lung, kidney and brain.

A 9-year-old boy had nodular masses in the left gastrocnemius muscle and lung, right kidney and right frontal area of the brain. Laboratory examinations, including positive anti-nuclear antibody, anti-RNP antibody, RA and CRP, hyper-gamma-globulinemia and accelerated ESR, showed characteristic of diffuse connective tissue disease (DCTD). Biopsy specimens were obtained from the thymus and from masses in the left lung and gastrocnemius muscle. The thymus showed hyperplasia, and a mass in the lung showed nonspecific inflammatory reactions such as connective tissue proliferation and cellular infiltration. Biopsied muscle also showed severe connective tissue proliferation, cellular infiltration, variation in fiber size and thickened blood vessel walls. In addition, abnormalities, including thickening of the basement membrane and an almost occluded narrow lumen of capillaries, were found on electron microscopy examination. Steroid administration led to remarkable improvement of the symptoms. These results suggested that DCTD is responsible for these symptoms.

Biopsy↗
PubMed1985

Regulation of receptors and digestive activity toward synthesized formyl-chemotactic peptide in human polymorphonuclear leukocytes.

A receptor binding and digestive activity of human polymorphonuclear leukocytes (PMNs) toward formyl-methionyl-leucyl-[3H]phenylalanine (3H-FMLP) was examined with the following results: Up- and down-regulation and recovery of 3H-FMLP binding activity were demonstrated. Both intact PMN and a lysate prepared from them cleaved the carboxyl terminal amino acid (phenylalanine) of 3H-FMLP. The digestive activity decreased as the receptor binding was inhibited by n-ethylmaleimide and 4-chloromercuribenzoate. Little digestive activity was found in the supernatant from PMN stimulated by FMLP. The released phenylalanine was found in the pellet and supernatant of PMNs. Digestive activity with cathepsin A-like characteristics was found in the lysate of PMN. These observations suggest that FMLP is internalized in lysosomes in a receptor-mediated manner and cleaved by the cathepsin A-like enzyme, the free phenylalanine is released extracellularly, and a part of the dissociated receptors with FMLP may return to the surface or to an intracellular receptor pool. Another finding was that the digestive activity of the lysate of cord blood granulocytes was decreased compared with that of adult blood granulocytes. This decrease may explain in part the impaired chemotaxis of cord blood granulocytes.

Cell Membrane↗
PubMed1984

Hyperimmunoglobulin-E-associated recurrent infection syndrome accompanied by chemotactic inhibition of polymorphonuclear leukocytes and monocytes.

An 8-yr-old girl with a history of severe recurrent infections including perinephritic, pulmonary, and hepatic abscesses had elevated serum IgE levels. Her serum inhibited chemotaxis of polymorphonuclear leukocytes (PMN) and monocytes. Exchange blood transfusion or plasma exchange at the time of severe infection resulted in normalization of chemotactic activity of PMN shown by the skin window method. Although this effect became negative 1 wk after the treatment, the procedures improved her clinical course. The patient's serum, obtained by exchange blood transfusion, 1) inhibited normal PMN chemotaxis toward cultured supernatant of E. coli, zymosan-activated serum, and formyl methionyl-leucyl-phenylalanine (f . Met-Leu-Phe), a synthetic chemotactic peptide; 2) inhibited monocyte chemotaxis, 3) showed an absence of digestive activity of f . Met-Leu-Phe, 4) was heat stable at 56 degrees C for 30 min and 5) showed an absence of antigenicity of IgE in a partial purified inhibitor with a molecular weight of 30,000-40,000. The inhibitory effect seemed to be reversible.

Bacterial Infections↗
PubMed1983

Chemotactic receptor of cord blood granulocytes to the synthesized chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine.

Chemotactic mobility of cord blood granulocytes (CBG) was studied under varying concentrations of synthesized chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (f . Met-Leu-Phe). The maximal chemotactic mobility was found at a concentration of 2 X 10(-7)M in CBG and 1 X 10(-7)M in adult blood granulocytes (ABG) (n = 8). The maximal distance of granulocyte mobility of CBG was significantly shorter than that of ABG (P less than 0.01). The number of chemotactic receptors and the affinity constant were assayed by the competitive inhibition method, using f . Met-Leu-[3H]Phe, and the data were subjected to Scatchard analysis. The number of chemotactic receptors of ABG was 2.5-fold of CBG, as shown by 21,800 +/- 7800 per cell in ABG (n = 3) and 9000 in CBG (n = 1). This figure was confirmed by the one point assay method by increasing the sample numbers of cord blood. It was found that bound chemotactic peptide (X 10(-14) moles/10(7) cells) was 7.9 +/- 0.7 in ABG (n = 4) and 3.4 +/- 0.7 in CBG (n = 5). Affinity constants were similar in CBG and ABG.

Chemotaxis, Leukocyte↗