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Biomedical subjects

J Singer

Publications and source records attributed to J Singer.

At least 91 records · Page 5Linked to original sources

The concentration of IgG in the serum is a major determinant of Fc-dependent reticuloendothelial function.

Defective Fc receptor-specific reticuloendothelial (RE) function has been reported in certain patients with a variety of immunologic and nonimmunologic diseases. The mechanism responsible for the impaired RE function is uncertain, but it could be caused by immune complexes that are present in many of these disorders. Alternatively, the impaired RE function could be a secondary effect of the high concentrations of monomeric IgG in the serum of these patients, since monomeric IgG can compete with complexed IgG for macrophage receptors in vitro. We studied the Fc-dependent RE function in 30 healthy control subjects and 27 patients using IgG-coated radiolabeled autologous red cells. There was a significant relationship between the concentration of IgG in the serum and the rate of clearance of antibody-sensitized cells (r = 0.51, P less than .01). Patients with hypergammaglobulinemia had the slowest Fc-dependent clearance, whereas those with hypogammaglobulinemia had the most rapid clearance. Immune complexes (Raji or polyethylene glycol) could not be shown to contribute to Fc-dependent RE clearance above the effect of the IgG in the serum. The unusually rapid clearance in a patient with hypogammaglobulinemia could be returned to normal by raising the concentration of IgG in the serum. This study supports the concept that serum (monomeric) IgG competes with immune complexed IgG for macrophage Fc receptors in vivo. The competition for Fc receptors determines the level of competence of Fc-dependent RE function. Based on the results of this study, one can predict that a number of disorders characterized by hypergammaglobulinemia also will have impaired Fc-dependent RE function.

Agammaglobulinemia

Methylation of DNA in mouse early embryos, teratocarcinoma cells and adult tissues of mouse and rabbit.

The distribution and amount of 5-methylcytosine (5-MeCyt) in DNA was measured for early embryos of mouse strain CF1 (2 to 4 cell stage to blastocyst) and mouse teratocarcinoma cells. In each case, the pattern of methylation was examined by use of the restriction enzymes Hha I and HPA II HPA II, which cut DNA at the sites 5'GCGC and 5'CCGG respectively, when the cytosines at these sites are not methylated. Mouse embryo DNA was found to have the same level of methylation as adult mouse tissues, and no changes in methylation were seen during differentiation of the teratocarcinoma cells. The ratio of 5-MeCyt/Cyt in DNA was measured by high performance liquid chromatography for the differentiating teratocarcinoma cells and for several adult mouse and rabbit tissues. The variation between tissues or between teratocarcinoma cells at different stages of differentiation was less than 10 percent. These results are discussed in view of proposals that 5-MeCyt plays a role in differentiation.

Animals

Methylation of mouse liver DNA studied by means of the restriction enzymes msp I and hpa II.

The restriction enzymes Hpa II and Msp I both recognize the sequence 5'-CCGG (C, cytosine; G, guanine). However, Hpa II cuts mouse liver DNA to fragments four times larger than does Msp I. The size of DNA cut by Msp I is close to that predicted from base composition and nearest neighbor analysis. The most probable explanation of these results is that in mouse the site 5'-CCGG is highly methylated.

Animals

Antepartum determination of pre-ejection period of fetal cardiac cycle: its relation to newborn body weight.

Simultaneous recordings of the fetal electrocardiogram and ultrasound Doppler-cardiogram were used for the determination of the pre-ejection period (PEP) of the fetal cardiac cycles. All 50 fetuses selected for the present study experienced uneventful perinatal lives despite maternal antepartum complications which required hospitalization. A significant positive correlation between the PEP and gestational age of the fetuses was again demonstrated. The PEP of the fetus measured within one week prior to delivery was also found to be significantly correlated with the newborn body weights at birth. Statistical analysis demonstrates that fetal body weight was more closely related to the physiologic lengthening of the PEP.

Birth Weight

Avoiding patient relation stress in an orthodontic practice.

1. Consumer rights apply to the practice of orthodontics as well as other areas of health care. 2. To avoid consumer complaints, the orthodontist must be prepared to deal with personality problems as well as treatment complications in his practice. 3. Only by careful questioning of the patient before treatment will the orthodontist be able to detect possible future problems. 4. An explanation of informed consent by the orthodontist and an acknowledgement of it in writing, signed by the parent or responsible party, is now regarded as essential to avoid misunderstandings and complaints. 5. An informed patient leads to a better relationship with the orthodontist as well as a healthier atmosphere in which to practice.

Communication

Occult fractures in the production of gait disturbance in childhood.

Trauma to the lower extremities is the principal cause of gait disturbance in early childhood. Three cases are presented to emphasize the relative frequency of children hospitalized for diagnostic evaluation of altered gait who have occult fractures. The cases may refresh the primary physician of the variables that serve as obstacles to accurate diagnosis.

Child

Postvaricella suppurative meningitis. Case reports and review of the literature.

Suppurative meningitis should be recognized as being a complication of varicella. The clinician must assiduously exclude suppurative meningitis that at times may be clinically indistinguishable from the typical postinfectious encephalomyelitis of varicella. Misdiagnosis of the cause of CNS alterations during the course of varicella is possible.

Chickenpox

Chronic lymphocytic leukaemia: Clonal origin in a committed B-lymphocyte progenitor.

The glucose-6-phosphate dehydrogenase (G.-6-P.D.) types of isolated blood-cell populations and normal skin were determined in two patients with chronic lymphocytic leukaemia (C.L.L.) who were heterozygous at the G.-6-P.D. locus. Normal tissues from each patient manifested both A and B G.-6-P.D. types, but the C.L.L. B-lymphocyte preparation from one patient showed only a single enzyme type, and from the other patient it showed 95% activity of one G.-6-P.D. type. These observations confirm the supposition based on immunoglobulin-marker data that at the time of study C.L.L. has a clonal origin. In contrast to the B lymphocytes, granulocytes, erythrocytes, platelets, and T lymphocytes displayed both enzyme types in proportions similar to those found in skin. These findings indicate that C.L.L. involves committed B-lymphocyte progenitors. Thus, the disease stands in contrast to chronic myelocytic leukaemia and other myeloproliferative syndromes, all of which involve multipotent haemopoietic stem cells.

Aged

Ectopic secretion of chorionic gonadotropin by a lung carcinoma. Pituitary gonadotropin and subunit secretion and prolonged chemotherapeutic remission.

The ability of tumor markers to improve cancer therapy is not established. We studied a man with a human chorionic gonadotropin (HCG)-secreting large cell carcinoma of the lung and gynecomastia. Preoperatively, levels of HCG (109 ng/ml), its alpha and beta subunits (3.2 and 21 ng/ml, respectively) and plasma estradiol were elevated. Despite apparently complete tumor resection and total resolution of gynecomastia, HCG titers remained elevated (3.3 ng/ml), heralding tumor recurrence three weeks later. Because the pathophysiologic consequences of the ectopic secretion of HCG on pituitary function are not established, we administered 100 microgram of gonadotropin-releasing hormone (LHRH) and observed a markedly delayed increase in pituitary gonadotropins. Early chemotherapy, guided by persistence of HCG, reduced HCG to undetectable levels, restored to normal the response to LHRH and resulted in a distinctly unusual 30-month complete remission. Use of HCG as a tumor marker levels is more sensitive than the symptom of gynecomastia and may permit detection of small, potentially curable tumor foci.

Carcinoma, Small Cell

5-Methylcytosine content of rat hepatoma DNA substituted with bromodeoxyuridine.

The aim of these experiments was to test whether incorporation of bromodeoxyuridine into DNA affects DNA methylation. Rat hepatoma (HTC) cells in culture were labeled for two generations with [14C]bromodeoxyuridine and [3H]thymidine to yield DNA which was 2.1, 20.6, 52.6, and 95.0% bromodeoxyuridine-substituted in the newly made strands. The DNA then was fractionated into highly repetitive, moderately repetitive, and single copy sequences. As determined by a comparison of 14C and 3H counts per min, the percentage of substitution with bromodeoxyuridine was found to be the same in each repetition class. The 5-methylcytosine content of each fraction was determined using high pressure liquid chromatography. It was found that bromodeoxyuridine, even at a level of substitution into newly mad DNA of 95%, has no effect on the 5-methylcytosine content of DNA. At all levels of bromodeoxyuridine substitution, highly repetitive DNA has slightly more 5-methylcytosine (3.0% of total cytosine) than does single copy DNA or moderately repetitive DNA (2.3%). The 5-methylcytosine content of whole HTC DNA is the same as that of rat liver DNA (2.4%).

Animals