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Biomedical subjects

J Sack

Publications and source records attributed to J Sack.

At least 73 records · Page 4Linked to original sources
PubMed1988

In utero thyroxine therapy for the induction of fetal lung maturity: long term effects.

Intra-amniotic thyroxine has been used for the induction of fetal lung maturity. The long term effects of this therapy was evaluated in a group of eighteen preschool children, 5 to 6 years of age, whose mothers received intra-amniotic thyroxine during the last trimester of their gestation. Eleven children born during the same time period were selected as controls. The children were all clinically well with no evidence of growth or endocrine abnormalities. Neurological assessment was normal and psychomotor development was in the normal range for our population and did not differ from the control subjects. Intra-amniotic thyroxine administered during the last trimester of gestation did not appear to have any significant long term detrimental effects in the treated patients.

Amnion↗
PubMed1987

Thyrocyte specific killer cell activity is decreased in patients with thyroid carcinoma.

Natural killer cells (NK) are important in immune surveillance, and they have found to be decreased in the serum of patients with various types of malignancies. In patients with thyroid carcinoma, we investigated NK activity of peripheral lymphocytes directed against either a standard tumor cell target, K562, or against the clinically relevant target cell, the thyrocyte. Although NK-cell activity was normal when directed against K562 cell targets, NK-cell activity was reduced when labeled thyrocytes were used as target cells. At effector to target cell ratios of 100:1 and 20:1, there was 43 +/- 3% (n = 7) and 29 +/- 3% (n = 7) lyses of thyrocytes using normal lymphocytes, and 17 +/- 4% (n = 5) and 13 +/- 2% (n = 3) using lymphocytes from patients with thyroid carcinoma. These findings suggest that NK-cells have distinct subpopulations and that immune surveillance against specific thyrocyte target cells may be important in thyroid cancer.

Adult↗
PubMed1987

Oral administration of vanadate normalizes blood glucose levels in streptozotocin-treated rats. Characterization and mode of action.

The effect of oral administration of vanadate, in normalizing blood glucose levels of streptozotocin-treated rats (ST-rats), is further characterized and its mode of action is determined. We have examined the effects of two orally administered doses of sodium metavanadate. High concentrations of orally administered vanadate (0.8 mg/ml in drinking water) reduced blood glucose levels within 2-4 days of application and led to the appearance of hypoglycemia in test animals. Lower concentrations of vanadate (0.2 mg/ml in drinking water) also lowered blood glucose levels within 4 days, but did not lead to hypoglycemia for at least 3 weeks. These effects of vanadate were found to be reversible; hyperglycemia recurred within 2 days after removal of vanadate from the drinking water. In streptozotocin-treated rats receiving low vanadate treatment, circulating levels of vanadate were about 0.8 microgram/ml after 3 weeks of treatment. These rats became anabolic, while rats receiving high vanadate treatment remained catabolic. Subsequent to vanadate treatment, adipocytes derived from ST-rats responded to lower insulin concentrations. In addition, vanadate treatment lowered the increased insulin binding capacity of liver plasma membranes derived from ST-rats. Insulin binding capacity under these conditions approached that of control non-ST-rats. Basal rates of hexose uptake in muscle and liver tissues were doubled in vanadate-treated ST-rats. It is concluded that the oral administration of vanadate leads to normoglycemia by stimulating glucose uptake. Treatment with "low vanadate" leads to the formation of a stable anabolic and normoglycemic state in ST-rats and appears to restore insulin responsiveness of target tissues, without apparent signs of toxicity. Vanadate treatment did not impair either kidney or liver function, as assayed by the measurement of serum urea, creatinine, and glutamic-oxaloacetic transaminase.

Adipose Tissue↗
PubMed1986

Killer cell activity and antibody-dependent cell-mediated cytotoxicity are normal in Hashimoto's disease.

Antibody-dependent cell-mediated cytotoxicity (ADCC) is the process by which antibodies interact with killer cells to effect cell lysis, whereas natural killing (NK) refers to the ability of peripheral blood killer cells to lyse target cells in the absence of specific antibody. The purpose of the present study was to determine if either NK cells or ADCC might play a role in the development of Hashimoto's thyroiditis (HD) by testing the ability of killer cells to cause lysis of K562 erythroleukemia tumor cells and human thyrocytes in the presence and absence of serum from normal and HD patients. Using K562 target cells, NK activity was 70 +/- 4% (mean +/- SEM) for HD effector cells and 66 +/- 5% for normal effector cells at an effector to target ratio of 100:1. Similarly, with thyrocytes as targets, effector cells from HD patients (38 +/- 3%) and normal subjects (34 +/- 5%) caused comparable lysis (at an effector to target ratio of 100:1). Using K562 target cells, ADCC was 35% when effector cells from HD or normal subjects were coincubated with either normal or HD sera. Using thyrocyte target cells, lysis was about 25-30%, but, again, no differences were found between HD and normal effector cells or serum. There was a significant correlation between lysis for K562 and thyrocyte target cells, but there was no significant correlation between the titer of serum antithyroid microsomal antibodies and specific lysis. Intrathyroidal lymphocytes and peripheral lymphocytes from one patient with HD caused comparable lysis of labeled thyrocyte targets, as did normal peripheral lymphocytes. We conclude that ADCC and NK activities in peripheral lymphocytes were normal in HD patients and, therefore, may not have a primary role in mediating thyrocyte destruction in Hashimoto's thyroiditis.

Adult↗
PubMed1986

A human monoclonal antibody to insulin.

To elucidate the immune aspects of insulin-dependent diabetes mellitus (IDDM), we attempted to generate human monoclonal anti-insulin antibodies by fusing peripheral blood lymphocytes obtained from 10 insulin-treated IDDM patients with cells from a human lymphoblastoid cell line. Hybridomas that secreted immunoglobulins appeared in 9 of 400 wells. One of these hybridomas secreted anti-insulin antibody of the IgM class. The lymphocytic partner of this hybridoma was obtained from an IDDM patient who had undetectable levels of antibodies to insulin in his serum. Thus, by employing the hybridoma technique, it was possible to reveal the presence of insulin-sensitized B-lymphocytes in a patient who was serologically negative for anti-insulin antibodies. The monoclonal antibody recognized intact human insulin and insulins of other species, but not isolated A- and B-chains. This indicates that the antibody was functionally an autoantibody directed to an epitope formed by the native conformation of a highly conserved portion of the insulin molecule. This is the first report of a human hybridoma antibody to insulin.

Animals↗
PubMed1986

The Cohen syndrome in Israel.

Thirty-nine patients of 32 families affected by the Cohen syndrome are described with regard to clinical features, ethnic distribution and mode of presentation. Associated diseases, mode of inheritance and the apparent high prevalence of the syndrome among Jewish children are discussed.

Abnormalities, Multiple↗
PubMed1986

Influence on psychological development of early treatment of congenital hypothyroidism detected by neonatal screening: a controlled study.

It has been shown that early diagnosis and treatment of congenital hypothyroidism based on neonatal screening will improve outcome. To test this hypothesis, we performed standard psychological tests (Gesell, Stanford-Binet, or Wechsler) in three groups of children with treated hypothyroidism: 14 were discovered by neonatal screening and 24 (15 with thyroid agenesis and 9 with ectopic thyroid) were diagnosed prior to institution of screening. Age (weeks) at initial treatment differed among the three groups (mean values +/- SE: screened 4.6 +/- 0.8, thyroid agenesis 19.3 +/- 4.0, ectopic thyroid 46.4 +/- 8.0). Age at testing averaged 3.3 years in all three groups. The global developmental quotient (DQ) or IQ score was lowest in the thyroid agenesis group (82 +/- 6, range 52 to 142), intermediate in the ectopic thyroid group (93 +/- 10, range 56 to 141) and highest in the screening group (104 +/- 4, range 75 to 127). Neonatal screening for congenital hypothyroidism results in earlier diagnosis than does use of the clinical criteria, and the consequent early treatment results in improved psychomental development.

Child Development↗
PubMed1985

Thyroid-stimulating hormone, prolactin, and growth hormone response to thyrotropin-releasing hormone in treated children with congenital hypothyroidism.

The purpose of the present study was to assess thyroid-stimulating hormone (TSH), prolactin, and growth hormone responses to TRH stimulation in 12 congenitally hypothyroid children adequately treated with L-thyroxine from the first weeks of life. Although clinically euthyroid, six of these children were found to have abnormally high basal serum TSH concentrations despite clinical euthyroidism. Serum triiodothyroxine and L-thyroxine concentrations were normal and did not differ whether the children had elevated or normal basal serum TSH. All six of the children with high basal TSH had an exaggerated TSH response to TRH and 4 of them also had an augmented prolactin response to TRH. The children with normal basal TSH concentrations had normal TSH and prolactin responses to TRH. An abnormal ("paradoxical") elevation of growth hormone concentration in response to TRH was found in four of seven children in a separate group of patients who had prolonged, untreated primary hypothyroidism, but such responses were not found in any of the adequately treated children. These findings suggest the following conclusions: 1) the phenomenon of high serum concentrations of TSH in conjunction with normal L-thyroxine and triiodothyronine levels (and clinical euthyroidism), is prevalent in congenital hypothyroid patients. 2) These patients have an exaggerated response of their pituitary thyrotroph and lactotroph cells to TRH, presumably caused by selective and relative resistance of these cells to the inhibitory effects of thyroid hormones. 3) Congenital hypothyroidism is not associated with abnormal somatotroph cell responses to TRH.

Adolescent↗
PubMed1985

Screening for neonatal hypothyroidism in Israel during a 4-year period.

The neonatal hypothyroidism (NH) screening program in Israel was initiated in May 1978, and by the end of April 1984, 538,565 infants had been screened. One hundred sixty-six newborns were found to have NH; 7 of these exhibited only transient hypothyroidism. During the screening period the average age for initiation of treatment decreased from 6 to 4.8 weeks. A thyroid scan was performed on 51 of the neonates with NH; 41% had agenesis of the thyroid, 24% ectopic thyroid tissue, 29% dyshormonogenesis, and 6% secondary or tertiary hypothyroidism. This high incidence of dyshormonogenesis in Israel is probably due to a high rate of consanguinity among the Arab population and also within some of the Jewish ethnic groups. No blood sample was received from four infants with NH, and one infant with NH was not notified. This study indicates that a neonatal screening program can effectively detect infants with NH, resulting in earlier treatment.

Congenital Hypothyroidism↗
PubMed1984

Growth and puberty arrest due to prolactinoma.

A 13-year-old male with prolactin secreting pituitary tumor is described. The unusual features were arrested puberty and growth. Previously reported pediatric patients with prolactinoma are reviewed. The importance of serum prolactin measurement and bromocriptine therapy is emphasized.

Adenoma, Chromophobe↗
PubMed1984

Correlation between HbA1c, purified insulins, diabetic control, and insulin antibodies in diabetic children.

Insulin antibodies were determined in sera from 38 children diagnosed as having juvenile diabetes for a duration of 0.7-15.2 years (median = 4.9 years). 8 children were treated with purified porcine insulins from the beginning of their disease, 16 children with bovine insulin NPH alone, and 14 children with non-purified, of whom 9 were later transferred to purified insulins. Serum insulin antibodies were measured by non-specific and specific methods using beef (B) and pork (P) antigens as described by Welborne and Sebriakova, respectively. 12/38 children had insulin binding levels similar to those of normal children, irrespective of the type of insulin used. The concentration of antibodies using radiolabelled B or P insulins as antigens were strongly correlated, by both the non-specific (p less than 0.01) and the specific (p less than 0.01) methods. Children with better score for diabetic control had significantly lower levels of insulin antibodies against B (p less than 0.05) and P (p less than 0.05) than those with poor diabetic control. There was also a significant positive correlation between mean HbA1c concentration and both B and P mean insulin antibody concentration (p less than 0.01). Finally, patients treated with purified porcine insulin had significantly lower levels of antibodies than patients with non-purified bovine insulin (p less than 0.05).

Adolescent↗
PubMed1984

Sex reassignment in a girl with 11 beta-hydroxylase deficiency.

A two-month-old infant was referred to our department because of a short penis (2 X 1.2 cm). No testes were palpable. Acceleration of growth and bone age were observed. Laboratory results showed that serum urea, nitrogen, electrolytes and urinary sodium excretion were all normal. However, levels of serum testosterone (2.1 ng/ml), 17-OH-progesterone (1.8 ng/ml), and 11-deoxycortisol (33 ng/ml) were all high. Urinary excretion of 17-ketosteroids and tetrahydro-s (tetrahydro-pregnane-3 alpha, 17 alpha, 21-triol-20-one) were also very high. Analysis revealed a 46 XX chromosome; laparoscopy revealed normal internal female genitalia. The abnormal concentrations of metabolites were corrected by cortisol acetate treatment. Thus, the diagnosis of virilizing congenital adrenal hyperplasia (11 beta-hydroxylase deficiency) was confirmed. Under our guidance the parents raised the infant as a girl. Reduction clitoroplasty and reconstruction of female external genitalia were performed at the age of 22 months. Early medical, psychological and surgical treatment of children with virilizing congenital adrenal hyperplasia should enable them to become normal adults.

Adrenal Hyperplasia, Congenital↗