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Biomedical subjects

L Klein

Publications and source records attributed to L Klein.

At least 181 records · Page 10Linked to original sources

Increased rate of E-rosette formation by T lymphocytes of pregnant women who drink ethanol.

Ethanol use by pregnant women increased, in a dose-dependent manner, the rate of sheep erythrocyte rosette (E-rosette) formation with T lymphocytes. The time curve for E-rosette formation by T cells from nondrinking subjects was biphasic, with a rapid formation of half the E-rosettes within the first 16 min, followed by a much slower rate for E-rosette formation until the maximal T-cell percentage was reached overnight. For pregnant drinkers, greater than 85% of the E-rosettes formed during the initial rate period, with a concomitant smaller number forming during the overnight incubation. Despite the faster initial rate of E-rosette formation in the drinking subjects, the total percentage T cells was the same for both groups. Other demographic factors, like tobacco or marijuana use, or trimester, did not significantly contribute to the observed differences. An increase in the rate of E rosetting was also obtained by incubating lymphocytes from nondrinkers overnight in physiologically attainable concentrations of ethanol (less than or equal to 0.1%). These results demonstrate that drinking by pregnant women, even at relatively moderate levels (2 oz/week absolute ethanol), causes alterations in their cellular immune systems. With the ability of ethanol to cross the placental barrier and persist in utero, it is apparent that these levels of ethanol have the potential to affect the developing fetal immune system.

Alcohol Drinking↗

Adolescent smokers and nonsmokers: profiles and their changing structure.

The status of smoking among tenth-graders in Jerusalem high schools as part of a smoking prevention program was examined. Two consecutive cohorts of 792 and 771 subjects were given questionnaires on two occasions: at the onset of the study (fall 1980 for the first cohort and fall 1981 for the second), and either 2 years (first cohort) or 1 year (second cohort) later. Based on the theory that smoking relates to counterconformity entailing rebelliousness and conformity to a nonconformist peer culture, subjects were asked about their behaviors and cognitions concerning school, home, peers, drinking, and smoking. It was reasoned that no single variable can predict, let alone explain, the onset and continuation of smoking and that the various factors that relate to smoking and distinguish between smokers and nonsmokers (a) constitute a systematic and coherent syndrome of counterconformity variables, which (b) reinforce each other, and (c) that over time, smoking and counterconformity come to affect each other reciprocally. These hypotheses were supported by the data. Smokers were found to differ from nonsmokers in a number of ways that were all related to counterconformity. Truancy and an inability to resist peer pressure to smoke, manifestations of two aspects of this syndrome, were the best predictors of smoking for both sexes, both cohorts, and both measuring occasions. With time, personal rebelliousness tended to become a weaker predictor, while social interaction variables became relatively stronger. The intercorrelations among the nonsmokers who became smokers were the highest, as predicted. The nature of the syndrome, its changing structure, and implications for prevention are discussed.

Achievement↗

Circadian variations in contributions of bone and intestine to plasma calcium in dogs.

Young euparathyroid dogs, prelabeled with radiocalcium and fed a normal-calcium diet exhibited circadian variations in the amount of bone calcium contributed to the plasma calcium pool, as evaluated by changes in plasma calcium-45 radioactivity. When these dogs were fed a low-calcium diet or fasted, the contribution of bone calcium to plasma calcium rose to the point where bone constituted nearly the sole source of plasma calcium, and plasma calcium-45 no longer varied. In thyroparathyroidectomized (TPTX) dogs fed a normal diet, the fraction of plasma calcium due to bone contribution was reduced and plasma calcium-45 did not vary. When dietary calcium in TPTX dogs was increased by supplementation with calcium lactate pills, total plasma calcium rose, but the contribution of bone calcium to the plasma calcium pool remained unchanged. Thus the ability of normal young dogs to modulate bone calcium mobilization in response to dietary calcium intake appears to be hormonally regulated in a circadian manner.

Animals↗

Effects of amphotericin B with combination chemotherapy on response rates and on survival in non-small cell carcinoma of the lung.

Thirty-seven patients with non-small cell carcinoma of the lung were randomized to receive doxorubicin, lomustine, hexamethylmelamine, and methotrexate (ACHM) or ACHM plus amphotericin B (AMB). The complete plus partial response rate was 39% for ACHM plus AMB, compared to 23% for ACHM alone. However, the median duration of complete or partial response was only 3.0 months with ACHM plus AMB, compared to 7.0 months with ACHM. Most importantly, median survival was only 4.0 months with ACHM plus AMB, compared to 8.0 months with ACHM (P = 0.08; two-tail test). Myelosuppression was enhanced by the addition of AMB. Although AMB has biological and antitumor activity in certain clinical circumstances, it does not appear to have a meaningful role in palliative therapy of patients with non-small cell bronchogenic carcinoma.

Altretamine↗

Comparison of growth-induced resorption and denervation-induced resorption on the release of [3H]tetracycline, 45calcium, and [3H]collagen from whole bones of growing rats.

The major effect of immobilization during growth is a smaller bone mass induced by either an increased bone resorption or a decreased bone formation. Using a method of analyzing radioisotopic loss of [3H]tetracycline and [3H]collagen from bone prelabeled in vivo, we compared the amount of bone resorption due to immobilization with bone resorption induced by growth. One hind limb was denervated in growing male rats, 6 weeks of age, that had been chronically prelabeled with [3H]tetracycline, 45calcium, and [3H]proline. The total radioactivity of the whole femur and tibia/fibula from the denervated limb was compared with that from bones of the control limb at 0, 1, 2, 4, and 8 weeks after denervation. The effect of growth on bone formation was measured by net increases in bone length, volume, and mass of matrix and mineral. Experimental bones had a significantly smaller volume and mass. Bone resorption was much greater during growth modeling than during denervation. The additional bone resorption induced by denervation was a small fraction (one-fourth) of the resorption induced by growth. Denervation during growth resulted in less bone being formed due to a smaller gain in matrix and mineral mass as a result of a reduction in bone formation.

Animals↗

Direct measurements of basal bone resorption in microphthalmic mice in vivo.

Microphthalmic mice and their normal littermates were prelabeled extensively in utero with 3H-tetracycline and 3H-proline, or with 45Ca alone. The loss of 3H-tetracycline and 3H-collagen from whole femur was measured from birth to 24 days of age at weekly intervals to determine bone resorption of mineral and matrix in vivo. The ratio of blood 45Ca specific activity to that of bone (blood/bone ratio) was used to reflect the interrelationship between bone, blood, and dietary calcium, as well as bone resorption. There was little, if any, loss of 3H-tetracycline and 3H-collagen from bones of the microphthalmic mutants whereas there was a marked and continuous loss (67 and 51%, respectively) from bones of the normal littermates due to normal bone modeling. Blood/bone ratio was much lower in the mutants (42-70%) compared with the normals, suggesting that blood calcium is maintained by diet. These data provide direct evidence that basal bone resorption in growing microphthalmic mice was almost completely inhibited.

Animals↗

Effects of ethane-1-hydroxy-1,1-diphosphonate (EHDP) upon the kinetics of bone resorption and bone formation at the whole bone level in prelabelled chicks.

Chicks chronically prelabelled with 45Ca, 3H-tetracycline, and 3H-proline were used to measure the weekly effect of EHDP (5 mg P/kg for 28 days) on bone turnover at the whole bone level in vivo. Direct measurements were made of cortical bone resorption (loss of 3H-tetracycline and 3H-collagen from whole femur, blood-bone ratio of 45Ca), skeletal collagen formation and bone mineralization (collagen and calcium mass per whole femur, respectively). Chicks were sacrificed after 5, 14, 21 and 28 days of EHDP administration. By five days of treatment, EHDP caused a greater inhibition of bone mineralization (86%) than bone resorption (30-39%) without affecting skeletal collagen mass. The blood-bone ratio of 45Ca decreased 34%, which was similar in degree to the inhibition of 3H-tetracycline loss (30%) and 3H-collagen loss (39%). Almost complete inhibition of bone resorption and bone mineralization occurred by 14 days of treatment without effects on skeletal collagen mass. No additional effect was seen at 21 and 28 days of EHDP treatment. In chicks, EHDP inhibits almost completely bone mineralization (bone formation) and cortical bone resorption without affecting skeletal collagen mass.

Animals↗

Respiratory illness and hypophosphatemia.

We retrospectively reviewed the charts of 308 admissions to a pulmonary disease ward and 100 admissions to the general medical service over one year to find the prevalence, sequelae, and etiology of hypophosphatemia. The overall prevalence of low serum phosphate levels (less than 2.4 mg/dl) occurring at least once during hospitalization in chest patients was 17 percent, but was higher in patients with respiratory infections (28 percent). Moreover, the prevalence of hypophosphatemia on admission (before institution of intravenous fluid or drug therapy) was ten times higher in patients with respiratory infections than in patients with noninfectious respiratory illness or general medical patients (21 vs 2 percent, p less than 0.001). Serum phosphate less than 2.0 mg/dl occurred in 4 percent of patients. Twenty-seven percent of the patients (including two with ventilatory failure) with abnormally low serum phosphate levels had symptoms or signs of uncertain etiology later explicable by the presence of hypophosphatemia. The most common additional laboratory finding associated with hypophosphatemia was elevation of muscle enzymes. Although mortality was no higher in hypophosphatemic patients, hospital stay was twice as long as that of patients with normal levels of serum phosphate. No correlation was found between simultaneous arterial blood gases and serum phosphate levels. Two patients given antacids had severe hypophosphatemia and worsened ventilatory function; phosphate-binding antacids should be used judiciously in patients with severe respiratory disease, since they may lead to the development or worsening of hypophosphatemia and diminished ventilatory function.

Female↗

Ultrastructural properties of collagen fibrils in rat intestine.

Collagen fibers (bundles of fibrils) of rat small intestine as observed by Nomarski differential interference contrast microscopy were densely packed in parallel undulating arrays. At the electron microscopical level the diameters of intestinal collagen fibrils increased gradually from 50 nm at three weeks of age to 80 nm at 12 months of age. At each age the fibril diameters were fairly uniform in size. At three weeks or six months of age collagen fibrils from stretched, salted samples were somewhat larger in diameter (12-16%) than those from unstretched, unsalted samples. A biaxial orientation existed between bundles of collagen fibrils at angles that varied from 32 degrees to 81 degrees with a mean of 60 degrees. Thus, intestinal collagen at the fibril level is aligned at varying angles to the longitudinal and circular directions of the intestine.

Aging↗

Scanning electron microscopy of collagen fibers in intestine.

Collagen fibers of rat intestine were observed with and without mechanical stress in the scanning electron microscope. Observations were correlated with the previous results obtained by optical polarized microscopy to provide further insight into the organization and morphology of intestinal collagen. Larger fibers, approximately 4 micrometers in diameter, are densely packed in parallel undulating arrays. The initial response to stress is straightening of the original fibers. The extended fibers are biaxially oriented at +30 degrees and -30 degrees to the longitudinal direction. These large fibers appear as assemblies of subfibers. At higher magnifications, the larger fibers appear to be enmeshed in a network of small randomly oriented fibers approximately 0.2 micrometer in diameter. Study of the effect of age on fiber morphology showed that the length of the large fiber undulations increases during maturation but remains constant during aging. The diameters of large and small fibers appear not to change with age, but more of the 4 micrometers fibers are loosely associated into larger fibers which can be observed at both the optical microscope and scanning electron microscope levels. A hierarchical organization of intestinal collagen is proposed.

Aging↗

Isotopic evidence for resorption of soft tissues and bone in immobilized dogs.

UNLABELLED: Various experimental methods for producing bone and ligament atrophy have yielded contradictory results. These methods include denervation, immobilization (both internal and external), and disarticulation. We studied a model of internal skeletal fixation for twelve weeks in dogs that were chronically prelabeled with 3H-tetracycline, 45Ca, and 3H-proline. Bone resorption was analyzed by the loss of 3H-tetracycline, and bone and soft-tissue mass were analyzed by the radiochemical and chemical analysis of calcium and collagen. The strength of the anterior cruciate ligament was studied in tension to failure when a fast rate of deformation was applied. Failure of the femur-ligament-tibia complex occurred through the insertion of the ligament into the tibia for both the experimental and the control limbs. Loss of collagen was greater in the tibia and femur than in the lateral meniscus and anterior cruciate ligament, and correlated with a mechanical failure via bone. No evidence for collagen replacement in atrophied tissues was found, but one-half of the resorbed calcium was conserved. The marked loss of 3H-tetracycline indicated that bone atrophy was the result of increased resorption of bone rather than decreased bone formation. CLINICAL RELEVANCE: We have demonstrated significant atrophy of the soft tissues (lateral meniscus and anterior cruciate ligament) as well as of bone in immobilized joints of dogs. It is likely that the decrease in strength of the bone-ligament-bone complex is related to this atrophy of soft tissues and bone around the joint.

Animals↗

Serum levels of carcinoembryonic antigen and a tumor-extracted carcinoembryonic antigen-related antigen in cancer patients.

Levels of carcinoembryonic antigen (CEA) and a tumor-extracted CEA-related antigen (TEX) were determined in sera from patients with carcinomas of the breast, colon, lung, head and neck, and a number of miscellaneous categories. The purpose of this study was to compare the levels of each antigen at various stages of malignant disease. Competitive radioimmunoassays developed in our laboratory were shown to be sufficiently specific to detect either of these two antigens independent of each other. The results indicate that: (a) with our specific assays, CEA was not significantly elevated in smoker controls, but TEX was elevated in 29% of smoker controls; (b) TEX was equivalent to CEA as a tumor marker for colonic cancer. TEX was better than CEA as a marker for lung cancer and, based on limited data, there is a possibility that TEX is a significantly better tumor marker than is CEA in early lung cancer; (c) TEX was superior to CEA as a tumor marker for breast and head and neck cancers; (d) there is a strong indication that serial determinations of TEX can be used as effectively as CEA in the monitoring of disease progress. These preliminary results must be confirmed by increasing the number of cancer patients and including nonmalignant disease controls.

Antigens↗

Localized healing of small intestinal anastomoses.

Small bowel anastomoses were made in a group of adult Sprague-Dawley rats. In another group of animals, interrupted suture of the terminal ileum was performed without transection. The animals were labeled repeatedly by injections of 3H-proline during the second and third week after surgery. Animals were sacrificed at three weeks after anastomosis or suturing. Ten and two mm segments were precisely excised on either side of the anastomoses or suturing. Total collagen and total radioactivity were measured per length of segment. In the small intestine, a similar increase in collagen (four-fold) and its radioactivity (four-fold) occurs only within a centimeter of the anastomotic site, mostly within 0.4 to 0.6 mm. Some of this increase in secondary to the effects of the suture, but most of the increase is due to the anastomosis. The collagen data indicate that the healing of a small intestinal wounds is a local phenomenon.

Animals↗