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Biomedical subjects

M M Kaplan

Publications and source records attributed to M M Kaplan.

At least 163 records · Page 9Linked to original sources

Prevalence of abnormal thyroid function test results in patients with acute medical illnesses.

We measured serum total and free thyroxine (T4) and triiodothyronine (T3) concentrations, free T4 and T3 indexes, thyroid-stimulating hormone (TSH), thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA) concentrations in 98 patients hospitalized for acute medical illnesses. The free thyroxine index (FT4I) or TSH level was abnormal in 16 percent, but only 3 percent had thyroid disease. Serum fre T4 measurements by equilibrium dialysis were abnormal in 25 percent, but no additional patients who initially had abnormal concentrations of serum free T4 were subsequently proved to have thyroid disease. Patients with supranormal serum free T4 concentrations (21 percent) ahd higher serum T4, lower serum T3, and higher serum reverse T3 (rT3) concentrations than other patients, but the measured changes in serum T4, TBG and TBPA levels could only partly account for the magnitude of the free T4 elevation. In these acutely ill patients, an accurate diagnosis of thyroid disease could be achieved by determination of FT4I and TSH level and a history of medication usage. We conclude that other tests are rarely necessary for this purpose in a patient population such as this.

Acute Disease↗

Bioavailability of thyroid hormones from oral replacement preparations.

We evaluated gastrointestinal absorption in normal subjects of T4 and T3 from synthetic T3 tablets (Cytomel, SKF), desiccated thyroid tablets (Armour), thyroglobulin tablets (Proloid, Warner-Chilcott) and synthetic L-T4 tablets (Synthroid, Flint and Levothroid, Armour). Measurements of serum T4 and T3 concentrations and free hormone indices were made at multiple times after tablet ingestion, and T3 content in tablets was measured by radioimmunoassay. The time to peak serum T3, and the 26 hr intergrated increment in serum T3, Corrected for the amount if T3 ingested, were not significantly different for 75 micrograms of synthetic T3, 6 grains of desiccated thyroid (containing 99 micrograms T3) and 5 grains of thyroglobulin (containing 90 micrograms T3), the mean integrated increment values for the biological preparations being within 12% of those for synthetic T3. The peak serum T4 concentration, the time to peak T4, and 48 hr integrated increments in serum T4 and T3 were similar after 3 mg of Synthroid and Levothroid. The mean peak serum Free T3 Index after 75 micrograms T3, 500, was much higher than the mean peak Free T3 Index after 3 mg T4, 290. The time to peak Free T3 Index was much less after 75 micrograms T3, 2 hr, than the time to peak after 3 mg T4, 2 days. These results indicate that the time course and extent of T3 absorption do not differ, whether the T3 is given as the synthetic iodothyronine or as part of the thyroid protein, thyroglobulin. This approach appears to be useful in determining bioavailability of thyroid hormones from oral preparations and to assess the possibility of thyroid hormone malabsorption.

Biological Availability↗

Kinetic evidence suggesting two mechanisms for iodothyronine 5'-deiodination in rat cerebral cortex.

Enzymatic 5'-deiodination of 3,3',5'-triiodothyronine (rT3) and 3,3',5,5'-tetraiodothyronine (thyroxine, T4) was studied in microsomal preparations of rat cerebral cortex. Evidence was obtained for the existence of two thiol-dependent 5'-deiodinase entities. One of these predominates in tissue from euthyroid and long-term hypothyroid rats, is specific for rT3, follows "ping-pong" kinetics with dithiothreitol as the cosubstrate, and is inhibited by propylthiouracil (PrSUra) and iodoacetate. Inhibition by PrSUra is uncompetitive with rT3 and competitive with dithiothreitol. These properties are shared with the 5'-deiodinase activity of liver and kidney. The activity of a second type of 5'-deiodinase is highest in cerebral cortex from short-term hypothyroid rats, prefers T4 to rT3 as the substrate, is insensitive to PrSUra and iodoacetate, and follows "sequential" reaction kinetics. A similar PrSUra-insensitive 5'-deiodinase activity is also found in pituitary but is not detectable in liver and kidney; it seems, therefore, characteristic of tissues in which local T4 to 3,3',5-triiodothyronine (T3) conversion supplies a major portion of the total intracellular T3.

Animals↗

The biology of SAA: identification of the inducer, in vitro synthesis, and heterogeneity demonstrated with monoclonal antibodies.

Continued studies of the macrophage-derived mediator of SAA synthesis (SAA Stimulating Factor) confirm our previous observations that SAASF copurified with leukocytic pyrogen (LP) and lymphocyte activating factor (LAF). Moreover, new data demonstrate three separate isoelectric points for human LP-LAF-SAASF each of which possess the three biological activities. During the purification of 15,000 MW LP from crude stimulated mononuclear cell supernatants, only those fractions with pyrogenic activity in rabbits caused augmented stimulation of lymphocytes (LAF) and induced SAA synthesis in mice. Purified human LP stimulated isolated mouse hepatocytes in vitro to synthesize SAA in a dose-responsive manner. Colchicine treatment of hepatocytes led to decreased secretion of SAA into the medium and to an intracellular accumulation of SAA. Messenger RNA was isolated from the livers of endotoxin-stimulated mice and translated in a wheat-germ cell-free system. A major product was identified at 13-14,000 MW. Immunoprecipitation with anti-mouse AA identified several bands on autoradiography of polyacrylamide gels. These larger SAA precursors may account for the previously noted heterogeneity of human SAA, comprising at least 6 SAA isomers, of similar molecular weight but different solubility and electrophoretic charge characteristics. Two monoclonal antibodies (IgM-K and IgG1-K) have been prepared using standard cell hybridization techniques. They are directed at the variable COOH terminal region of SAA since they detect differences between the 6 human SAAs but do not react with human, monkey, dog or mouse AA proteins, human AP, C-reactive protein, IgG nor albumin. These antibodies will be useful in examining the origin, structure and function of SAA.

Amyloid↗

Chronic erosive gastritis--clinical and radiological features.

Chronic erosive gastritis has been regarded as an unusual, ill-defined condition of unknown etiology. We report a retrospective study of 40 patients in whom this diagnosis was made relating radiologic findings to patients' age, symptomatology and possible etiologic factors. The condition is more common than previously suspected and requires careful technique combining double contrast and graded compression to demonstrate fine mucosal abnormalities. The radiologic appearance is of mucosal mounds measuring 3-11 mm in diameter with central barium collections and numbering from 3-27 per examination. Antral involvement occurred in 90% of patients, with diffuse involvement of both antrum and body in 58%. Several linear erosions measuring up to 15 mm in length were also demonstrated. Chronic erosive gastritis is most severe and symptomatic between 40 and 60 years, becoming sub-clinical in the elderly. Symptoms mimic those of a peptic ulcer or gastric neoplasm and are more severe the more extensive the disease. Gastric irritants, virus infection and Crohn's disease were possible etiologic factors in some patients in this study.

Adult↗

Chronic intestinal ischemia associated with oral contraceptive use.

A 48-yr-old woman with chronic intestinal ischemia and a long history of oral contraceptive use is reported. She presented with a 6-month history of severe diarrhea, abdominal pain, and weight loss. Abdominal arteriography revealed occlusion of the celiac axis at its origin and 90% stenosis of the superior mesenteric artery. This chronic arterial lesion has not been previously noted in association with the use of oral contraceptive agents in otherwise healthy women. The patient's isolated arterial lesions proved amenable to successful surgical bypass. Postoperatively she became completely asymptomatic and has remained so on long-term follow-up.

Adult↗

Osteoporosis in primary biliary cirrhosis: effects of 25-hydroxyvitamin D3 treatment.

Bone histology, bone mineral content, and calcium absorption were evaluated in 10 patients with primary biliary cirrhosis and osteopenia, before and after 1 yr of treatment with oral 25-hydroxycholecalciferol. Before treatment, quantitative histomorphometric analysis of full-thickness iliac crest bone biopsy specimens with double-tetracycline labeling demonstrated that 9 of 10 patients had osteoporosis. None had osteomalacia. Fasting intestinal calcium absorption correlated well with trabecular bone volume (r = 0.85). Bone mineral content measured by 125I-photon absorption was low in 6 of 10 patients, and it correlated poorly with iliac crest trabecular bone volume. After 1 yr of treatment with oral 25-hydroxyvitamin D3, bone mineral content fell in all 8 patients who were restudied. Iliac crest trabecular bone volume increased in 3 patients, 2 of whom had the greatest pretreatment impairment in calcium absorption, but fell in 5. Bone fractures continued to occur in 3 of 5 patients who were alive after 1 yr and developed for the first time in a sixth patient. We conclude that 25-hydroxyvitamin D3 is ineffective in reversing the bone thinning in the majority of primary biliary cirrhosis patients, but it may be helpful in a few selected patients.

Adult↗

Cerebral cortex responds rapidly to thyroid hormones.

In rats subjected to thyroidectomy there was a two- to fourfold increase in cerebral cortex iodothyronine 5'-deiodinase activity within 24 hours. This increase was prevented by thyroxine replacement. The increased cortical 5'-deiodinase in chronically hypothyroid rats was normalized within 4 hours by a single intravenous injection of triiodothyronine. These results indicate that the adult central nervous system can give a very rapid biochemical response to thyroid hormone.

Animals↗

Partial peripheral resistance to thyroid hormone.

A 33 year old partially thyroidectomized woman was euthyroid when ingesting 500 microgram of L-triiodothyronine (T3) daily. Her condition was evaluated during therapy with daily T3 doses between 50 and 500 microgram. She was hypothyroid and had a markedly subnormal oxygen consumption rate when taking 50 to 100 microgram T3 daily, and oxygen consumption did not increase greatly above predicted normal values despite serum T3 concentrations up to 3,200 ng/dl. Her pulse rate, blood pressure, systolic time intervals and exercise tolerance changed minimally and remained within the normal range during the different dosage schedules. Urinary creatine and hydroxyproline, indices of muscle and skeletal protein catabolism, increased normally with higher T3 doses, but serum cholesterol, creatine phosphokinase, calcium and alkaline phosphatase did not change substantially. Basal and thyrotropin-releasing hormone (TRH) stimulated thyrotropin secretion were suppressed during all T3 doses. The prolactin response to TRH was normal at 50 microgram T3/day and was reduced by higher doses of T3. Absorption of T3, serum T3 protein binding and T3 metabolic clearance rates were all within normal limits. The findings in this patient are compared to clinical and biochemical findings in 17 previously described patients. The manifestations of peripheral thyroid hormone resistance are quite variable in the organ systems involved and in the degree of involvement. The molecular basis of the abnormality in our patient remains undefined.

Adolescent↗

Maturational patterns of iodothyronine phenolic and tyrosyl ring deiodinase activities in rat cerebrum, cerebellum, and hypothalamus.

To explore the control of thyroid hormone metabolism in brain during maturation, we have measured iodothyronine deiodination in homogenates of rat cerebrum, cerebellum, and hypothalamus from 1 d postnatally through adulthood. Homogenates were incubated with (125)I-l-thyroxine (T(4)) + [(131)I]3,5,3'-l-triiodothyronine (T(3)) + 100 mM dithiothreitol. Nonradioactive T(4), T(3), and 3,3',5'-triiodothyronine (rT(3)) were included, as appropriate. The net production rate of [(125)I]T(3) from T(4) in 1-d cerebral homogenates was similar to the rate in adult cerebral homogenates (9.9+/-2.5[SEM]% vs. 8.9+/-1.2% T(4) to T(3) conversion in 2 h). Production of T(3) was not detectable in 1-d cerebellar and hypothalamic homogenates. The net T(3) production rate in adult cerebellar homogenates was twice as great as, and that in adult hypothalamic homogenates similar to, the rate in cerebral homogenates. Tyrosyl ring deiodination rates of T(4) and T(3) were more than three times as great in cerebral homogenates from 1-d-old rats as in adult cerebral homogenates. In cerebellar homogenates from 1-d-old rats, tyrosyl ring deiodination rates were much greater than the rates in adult cerebellar homogenates, but less than those in 1-d cerebral homogenates. In 1-d hypothalamic homogenates, tyrosyl ring deiodination rates were the highest of all the tissues tested, whereas rates in adult hypothalamic homogenates were similar to those in adult cerebral homogenates. During maturation, T(4) 5'-deiodination rates increased after 7 d and exceeded adult rates between 14 and 35 d in cerebral and cerebellar homogenates, and at 28 and 35 d in hypothalamic homogenates. In cerebral homogenates, the peak in reaction rate at 28 d reflected an increase in the maximum enzyme activity (V(max)) of the reaction. T(4) and T(3) tyrosyl ring deiodination rates decreased progressively with age down to adult rates, which were attained at 14 d for cerebrum and cerebellum and at 28 d for hypothalamus. These studies demonstrate quantitative differences in T(4) 5'-deiodinase activities in cerebrum, cerebellum, and hypothalamus at all ages, with the overall maturational pattern differing from the developmental patterns of both the pituitary and hepatic T(4) 5'-deiodinases. Iodothyronine tyrosyl ring deiodinase activities also vary quantitatively among these same brain regions and exhibit a pattern and a time-course of maturation different from that of the T(4) 5'-deiodinase. These enzymes could have important roles in the regulation of intracellular T(3) concentrations and, hence, on the expression of thyroid hormone effects.

Animals↗

Evidence for the natural transmission of influenza A virus from wild ducts to swine and its potential importance for man.

In 1979, epidemics of influenza occurred in pigs in Belgium from which were isolated strains of influenza A (Hsw1N1) virus antigenically closely related to Hsw1N1 strains previously isolated from ducks in North America and the Federal Republic of Germany. This finding is considered as the first supportive evidence that an influenza A virus in an avian species might have been transmitted to mammals.

Animals↗