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Biomedical subjects

L Fishman

Publications and source records attributed to L Fishman.

At least 19 recordsLinked to original sources
PubMed1992

Oral toxicity to flesh flies of a neurotoxic polypeptide.

An insect selective neurotoxic polypeptide from venom of the scorpion Androctonus australis (AaIT, M(r) 8,000) was shown to cross the midgut of the flesh fly Sarcophaga falculata, using assays of oral toxicity, column chromatography, and microscopic autoradiography of the native and radioiodinated toxin. AaIT induced paralysis of flies within 1-2 h after oral administration, with a lethal dose (LD50) of 10 micrograms/100 mg of body weight. Oral toxicity was about 0.14% of toxicity by injection. Hemolymph collection 70-85 min after feeding flies with [125I]AaIT showed that 5% of ingested radioactivity appeared in hemolymph. Most of this represented degradation products, but included about 0.3% of the chromatographically intact toxin. In contrast, hemolymph of identically treated lepidopterous larvae (Manduca, Helioverpa [= Heliothis]) contained degradation products but no intact toxin. [125I]AaIT was shown to cross the midgut of Sarcophaga through a morphologically distinct segment of the midgut previously shown to be permeable to a cytotoxic, positively charged polypeptide of similar molecular weight. These results suggest that Sarcophaga midgut contains a morphologically and functionally distinct segment that transports small peptides, and that employment of neurotoxic polypeptides for insect control may be feasible. Activity might be greatly improved through modification and metabolic stabilization of active peptides.

Animals↗
PubMed1988

Outdated data.

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Home Care Services↗
PubMed1987

Factors affecting insulin antibody binding in children with insulin-dependent diabetes mellitus.

We measured insulin antibody binding in 2 groups of patients: Study 1, 32 children with newly diagnosed IDDM before onset of insulin therapy, and, in 20 of these, 10 days, 1, 3, and 6 months after beginning therapy; and Study 2, 35 children with long-standing IDDM, 20 of whom had free insulin concentrations measured before, and for 2 hours following subcutaneous injection of 0.25 U/kg regular insulin. Almost 35% of new onset subjects had insulin antibody binding above control levels. In those studied prospectively, binding increased significantly with time. Pre-treatment binding did not correlate with later insulin antibody binding nor metabolic control. In Study 1 we have confirmed previous studies showing abnormally high insulin antibody binding in children with IDDM pre-treatment. We have been unable to demonstrate a relationship between this binding and that found 6 months after initiation of therapy. In Study 2, we have shown that insulin antibody binding is not related to either the level of metabolic control or the rate of rise of free insulin levels in children with IDDM.

Adolescent↗
PubMed1987

Dietary triggers of insulin-dependent diabetes in the BB rat.

Environmental "triggers" (including viruses, toxins and dietary factors) have been implicated in the pathogenesis of insulin-dependent diabetes mellitus. Data have suggested a possible role for cow's milk protein (CMP) as a trigger of diabetes. To study this further, 86 BB rats were divided into 2 groups during the weaning period (days 13-25): Group A received rat chow without CMP; Group B, rat chow with 1% CMP added. Each group was subdivided afterwards into 2: Groups A1 and B1 received chow without CMP; Groups A2 and B2, chow with CMP. Animals weaned with chow containing CMP (B1 and B2) had a higher incidence of diabetes (66%) than those weaned without (A1 and A2; 29%, p less than 0.001). The incidence in both B1 and B2 was significantly greater than in either A1 or A2 (p less than 0.05). The highest incidence of diabetes occurred in male rats weaned on rat chow with CMP (90%), the incidence being significantly higher than female rats weaned with (43%) or without CMP (18%) and males weaned without CMP (39%). Thus, it appears that (a) the presence of cow's milk protein in the diet increases the incidence of diabetes in the BB rat; (b) the critical time for exposure to CMP appears to be the weaning period; and (c) male rats appear to be more susceptible to the development of diabetes than female rats, when exposed to this trigger. This supports the hypothesis that dietary triggers may play an important role in the expression of diabetes in the susceptible host and that its prevalent action occurs early in life.

Animals↗
PubMed1986

Pharmacokinetic characteristics of the gonadotropin-releasing hormone analog D-Ser(TBU)-6EA-10luteinizing hormone-releasing hormone (buserelin) after subcutaneous and intranasal administration in children with central precocious puberty.

A double antibody RIA was developed for the measurement of the long-acting GnRH agonist D-Ser(TBU)6EA10GnRH (buserelin). The antibody, raised in rabbits against a buserelin-hemocyanin conjugate, reacted with the intact molecule and also molecular fragments containing the C6-9 tetrapeptide sequence and permitted the measurement of buserelin activity in serum and urine. Natural GnRH, LH, and FSH did not cross-react in this assay system. The assay was applied to samples obtained from children receiving buserelin for the management of central precocious puberty either by once daily injection of 30 micrograms/kg or by nasal spray (in; 200 micrograms every 8 h). Urine and serum samples, chromatographed on Sephadex G-25, contained immunoreactive material corresponding closely in molecular size to [125I]buserelin. In unextracted serum samples taken at intervals after sc therapy in 11 girls, the peak immunoreactive buserelin levels of 52.2 +/- 14.8 ng/ml (mean +/- SEM) occurred at 30 min. The half-time of elimination was 74.9 +/- 36.9 min. Approximately 30% of the dose was detected in urine collected for 3 h after injection. Similar data were obtained in 3 normal adults given 10 micrograms/kg buserelin, iv. By contrast, after the administration of 200 micrograms buserelin by metered nasal spray, the mean peak serum concentration in 10 girls was 100-fold less (0.65 +/- 0.14 ng/ml), although the halftime of elimination was almost identical. Only 0.73% of the nasal dose was excreted by 3 h. Calculated relative bioavailability data indicated maximal nasal absorption of 6%. However, absorption after nasal administration varied greatly, and in 2 children, serum and urinary concentrations of buserelin after supervised administration were negligible. We conclude that in buserelin therapy, in the dose used in this study, does not represent optimal treatment for the initial management of patients with precocious puberty. The success of in therapy in sustaining initial effects of buserelin given by sc administration presumably reflects changes in receptor sensitivity induced by sc treatment.

Administration, Intranasal↗
PubMed1985

Ketoconazole in the management of precocious puberty not responsive to LHRH-analogue therapy.

Three boys 3.3 to 3.9 years old, who had precocious puberty that was unresponsive to an analogue of gonadotropin-releasing hormone, were treated with the antifungal agent ketoconazole for up to 12 months. Within 48 hours the serum testosterone concentration fell to normal in two boys and was significantly reduced in the third, paralleling major improvements in behavior. Reciprocal changes in serum levels of 17-hydroxyprogesterone suggested that C17-20 lyase was the principal site of drug action. Although there was evidence of a blunted cortisol reserve during the first week of treatment, the cortisol response to ACTH1-24 had returned to normal by one month of continuous treatment, and normal diurnal cortisol rhythm was preserved. No adverse clinical or biochemical side effects were noted during 9 to 12 months of continuing treatment. During that time, growth velocity was significantly reduced in all three boys, from a mean rate of 1.5 +/- 2.0 cm per year before treatment to 5.9 +/- 0.6 cm per year after ketoconazole therapy. There was a simultaneous retardation of the rate of skeletal maturation. The striking improvements in behavior were sustained for the duration of treatment. These preliminary data suggest that administration of ketoconazole may be a satisfactory treatment for precocious puberty in boys and possibly for other conditions characterized by androgen excess.

17-alpha-Hydroxyprogesterone↗
PubMed1976

Antinuclear antibodies and lupus-like syndromes in children receiving anticonvulsants.

Drug-induced systemic lupus erythematosus (SLE)-like syndromes in children are most commonly associated with the administration of ethosuximide, diphenylhydantoin, and trimethadione. Five children receiving ethosuximide who presented with syndromes suggestive of SLE were studied. Each and fever, malar rash, arthritis, and lymphadenopathy. Two children had pleural effusions and another developed myocarditis and pericarditis. Three patients had anti-DNA antibodies associated with low serum C3. In four of five children symptoms disappeared with the discontinuation of ethosuximide; two of these continue to have antinuclear antibodies (ANA). One child continues to have active SLE with nephritis. A group of 101 children from a seizure clinic were tested for the presence of ANA. ANA were found in 14 of 70 children receiving ethosuximide and/or diphenylhydantoin; 2 of 14 had anti-DNA antibodies. Serum ANA titers in the drug-induced SLE group did not differ significantly from those of the asymptomatic seizure patients. ANA were also present in 5 of 23 children receiving phenobarbital only. The induction of ANA by phenobarbital is a possible hypothesis. Quantitative immunoglobulins and C3 were not significantly altered in the asymptomatic children with ANA. Follow-up studies at ten months showed no asymptomatic child with ANA to have developed clinical with ANA to have developed clinical evidence of SLE. This study suggests that asymptomatic children who develop ANA should have careful observation, but need not have their anticonvulsants discontinued.

Adolescent↗
PubMed1976

Developmental phase-specific alkaline phosphatase isoenzymes of human placenta and their occurrence in human cancer.

Alkaline phosphatase electrophoretic patterns characteristic of three phases in early human trophoblast development are described in this preliminary communication. Phase 1 (6 to 10 weeks) consists entirely of two heat-sensitive, L-homoarginine-inhibited bands, the slower one of which possesses antigenic determinants of live-bone-type alkaline phosphatase, whereas the fast band lacks any of the known alkaline phosphatase antigenic determinants. Phase 2 pattern (11 to 13 weeks) is that of a mixture of Phase 1 and Phase 3 isozyme components, the latter exhibiting two isozyme bands with the characteristics of term placental alkaline phosphatases correspond in order to non-Regan isoenzyme, a mixture of Regan and non-Regan isoenzymes and Regan isoenzyme in a variety of human cancer tissues. The biochemical profile characteristic of trophoblast developmental Phase 1 alkaline phosphatase is expressed as 78.5% heat-sensitive inhibition (5 min at 65 degrees), 66.3% L-homoarginine inhibition, and 17.3% L-phenylalanine inhibition where n = 12. It is hypothesized that the alkaline phosphatase of human tumor tissues reflects the expression of placental genes corresponding to one or more phases of trophoblastic development.

Alkaline Phosphatase↗
PubMed1975

Mineralization of elastin extracted from human aortic tissues.

Elastin was isolated from human aortic tissues by extraction with formic acid. The aortas came from individuals of both sexes with ages ranging from 18 to 67 years. The elastin was treated to remove pre-existing nuclei for hydroxyapatite and mineralized in vitro by incubation in a solution metastable to hydroxyapatite. The results showed an increased rate of mineralization in vitro as the age of the individual from whom the aorta was obtained increased. The lag period in mineral formation seen with elastin samples obtained from individuals below the age 40, disappeared with older elastin. Amino-acid analysis of the elastin samples confirmed earlier results by indicating an increase in the more polar amino acids in the older elastin samples. Exposure of the extracted elastin samples to several proteolytic enzymes including elastase confirmed the identity of the material as elastin.

Aging↗