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Biomedical subjects

J Lindner

Publications and source records attributed to J Lindner.

At least 19 recordsLinked to original sources
PubMed1992

Low incidence of antibody formation due to long-term interferon-alpha 2c treatment of cancer patients.

In order to study the long-term immunogenicity of interferon-alpha 2c (Berofor) in cancer patients, serum was collected starting in 1983 from study patients with various proliferative diseases who received interferon-alpha 2c at different doses, according to different schedules, and via different routes. A total of 1992 samples were tested for the presence of anti-interferon-alpha 2c antibodies. Due to long-term interferon-alpha 2c treatment, 346 patients were eligible for induction of neutralizing anti-interferon antibodies over a treatment period of 2-52 months. Most patients were treated for longer than 6 months. Of the 346 patients, three patients (0.87%) exhibited measurable titers of neutralizing antibodies following therapy with interferon-alpha 2c. One hundred and sixty-three patients suffered from non-Hodgkin lymphomas, leukemias, and preleukemias. One patient with chronic myeloid leukemia experienced antibody induction under therapy. The other 183 patients had solid tumors. Two of them reacted with antibody production. All titers were very low (1:12, 1:8, and 1:64). Compared with figures reported for other interferon-alpha preparations, the propensity of interferon-alpha 2c to induce neutralizing antibodies seems to be very low. This property might be related to arginines occurring as critical residues in positions 23 and 34 of the interferon-alpha 2c molecule.

Antibody Formation↗
PubMed1992

[Coronary heart disease and insulin concentration in type II diabetic patients--results of a diabetes intervention study].

There is experimental, clinical and epidemiological evidence that elevated insulin levels are associated with development of atherosclerosis. Early results came from studies in non-diabetics, but the situation with respect to diabetes is more complex and not so clear. The Diabetes Intervention Study is a population-based follow-up study in newly detected type II diabetics (30- to 55-yr-old). After 5 years 431 men and 320 women received a complex check up with oral glucose tolerance tests and measurements of plasma insulin and glucose levels, fasting and 2h post-load. Regarding the metabolic parameters, the fasting and postprandial insulin levels were higher among the patients having coronary heart disease (15% of men, 36% of women), as compared to patients without this disease. In multivariate analysis sex, age, antihypertensive treatment, blood pressure, body mass index, and fasting insulin levels were independently associated with the prevalence of coronary heart disease in patients with non-insulin dependent diabetes mellitus (NIDDM) treated with diet and/or oral antidiabetics. Body mass index and triglycerides were the only variables that independently correlated to insulin: fasting insulin = 0.4 (body mass index) + 0.1 (triglycerides) - 4,2. In future prospective studies of diabetics relating insulin concentrations to the development of vascular disease are of particular interest and necessity. Because hyperinsulinemia may contribute to accelerated atherosclerosis in NIDDM-patients, the aim of the treatment of type II-diabetes should be to correct hyperglycemia without aggravating insulin levels and other cardiovascular risk factors.

Adult↗
PubMed1991

Combined administration of a gonadotropin-releasing hormone antagonist and testosterone in men induces reversible azoospermia without loss of libido.

GnRH antagonists suppress pituitary and gonadal function by competing with endogenous GnRH for binding to receptors on pituitary gonadotrophs. We studied the effects of GnRH antagonist administration to men in a protocol simulating a likely male contraceptive regimen combined with a low dose of testosterone. The GnRH antagonist Nal-Glu was given daily (10 mg, sc) for 20 weeks to eight normal men, and a low dose of testosterone enanthate (25 mg, sc) was given every week. Sperm counts started declining during week 4, and complete azoospermia was reached within 6-12 weeks in six of the eight subjects. Subjects 7 and 8, whose sperm counts and serum gonadotropin levels were not suppressed after 10 weeks, were given 20 mg Nal-Glu starting at week 10. One became azoospermic at week 16, while the other's total sperm counts continued declining and reached a nadir of 1.4 million by week 20. Sperm motility and viability in this subject were completely suppressed after week 14. Sperm counts returned to baseline levels 12-14 weeks after the end of Nal-Glu administration. The mean serum LH level of the first six subjects decreased from 3 +/- 03. U/L at baseline to less than 0.1 U/L until week 20, and then levels returned to baseline. FSH levels similarly decreased from a combined mean of 3.6 +/- 0.9 U/L at baseline to below 0.3 U/L after 4 weeks of Nal-Glu administration. Serum mean testosterone levels between weekly injections of testosterone enanthate ranged from 27.4 +/- 5.9 to 4.8 +/- 1.4 nmol/L, but remained in the hypogonadal range (less than 10 nmol/L) for 4 of the 7 days. None of the subjects, however, complained of decreased libido or potency, as assessed by a questionnaire. No systemic or significant local side-effects were observed, other than a minimal reaction at the injection site. These data suggest that complete sustained azoospermia can be achieved in man, without loss of libido, by chronic administration of a GnRH antagonist plus testosterone.

Adult↗
PubMed1990

Regulation of pituitary glycoprotein alpha-subunit secretion after administration of a luteinizing hormone-releasing hormone antagonist in normal men.

Pituitary glycoprotein hormones are composed of two different subunits, the alpha- and beta-subunits. The alpha-subunit is common to all FSH, LH, and TSH, while the beta-subunit is specific for each of these hormones. We studied the effects of a potent LHRH antagonist on alpha-subunit and LH secretion in normal men. The LHRH antagonist Nal-Glu, ([Ac-D2Nal1,D4ClPhe2,D3Pal3,Arg5,DGlu6(AA) ,Ala10]LHRH), was given (10 mg daily) as one injection of 5 mg every 12 h. Blood samples were drawn every 24 h, and on days 1 and 7 a day curve was established by drawing hourly blood samples for 26 h. Mean serum alpha-subunit levels decreased progressively (P less than 0.001) from 2.9 +/- 0.49 micrograms/L at baseline to a nadir of 1.4 +/- 0.27 micrograms/L on day 8. In contrast, mean immunoreactive LH (IR-LH) levels decreased rapidly from 3.2 +/- 0.6 U/L at baseline to 0.9 +/- 0.08 U/L on day 2 and remained suppressed (P less than 0.001) throughout the treatment period. On day 1 after the administration of Nal-Glu mean alpha-subunit levels decreased, although not significantly (P = 0.054), from 3.0 +/- 0.6 micrograms/L at baseline to a nadir of 2.0 +/- 0.3 micrograms/L at 17 h. alpha-Subunit remained at this level for the remainder of day 1. On day 7, however, the baseline serum alpha-subunit level was 1.5 +/- 0.3 micrograms/L, significantly suppressed (P less than 0.01) compared to the level on day 1, and no further decrease was seen after administration of Nal-Glu. IR-LH on day 1 before the first injection of 5 mg Nal-Glu was 3.5 +/- 0.8 U/L. Then, IR-LH levels decreased significantly (P less than 0.001) to a nadir of 0.9 +/- 0.1 U/L and remained at this level throughout day 1. IR-LH levels on day 7 were at or below 1.0 U/L throughout the sampling period. These results indicate that alpha-subunit secretion can be partially suppressed after chronic administration of a LHRH antagonist. Furthermore, LH serum levels dissociate from those of pituitary glycoprotein alpha-subunit after administration of LHRH antagonist analogs.

Adult↗
PubMed1979

[Studies on DNA content of tissues and organs. 1st communication: changes in cell content of some mesenchymal and parenchymatous rat organs during development, maturation, and in part aging (determinations of DNA) (author's transl)].

In this study the cell content was analyzed by means of the DNA content of certain mesenchymal and parenchymal organs of the rat. The main aspects were the postnatal stages of development and maturation. Their correlation to aging was examined only on examples, so was their correlation to the prenatal development (on 2 examples: liver and skin). One important result of this research is that a gradual reduction in the exponential growth takes place with increasing maturation and development. The "growth by production" prevails over the "growth by division" (of cells). This is the explanation for the "relative" (= apparent) decrease in the cell content of the tissues and organs analyzed during the decisive postnatal development and maturation phases. In this period the complete differentiation of the cytoplasmic structures and of the differentiation products of the tissues and organs here analyzed occurs. This leads to a shift in their relative amounts to the disadvantage of the cell nuclei, which prevailed in the total weight of tissues and organs during the early phases of development. This concerns determinations of the DNA content related to wet weight even more than such of the DNA content related to dry weight. As already shown clearly, the different tissues and organs of the mammalian organism (here on the example of the rat) grow, mature and age differently. During growth different phases can be distinguished, too, by analysis of the DNA content which partly correlate with phases of growth which were differentiated morphologically. Determinations of DNA contents are necessary as parameters for determinations of the production metabolism (e.g. activities of enzymes, products of formation and differentiation) of the different tissues and organs during their development, maturation and aging.

Aging↗
PubMed1979

[Studies on DNA content of tissues and organs. 2nd communication: findings on DNA content in various rat organs 1. during maturation and aging and 2. during experimental pathological models and their therapy (author's transl)].

In this paper the DNA content as a quantitative parameter of the cell content was analyzed on selected rat organs. Aging changes in parenchymatous and connective tissue (= mesenchymal) organs were examined. Further, some pilot studies on experimental animal models of human diseases (experimental shock and liver fibrosis) and their therapy were carried out. In these simulations of human diseases only some preliminary indications about changes in cell or DNA content, resp., of the various organs could be obtained. The results show that these pilot studies justify intensified continuation (in larger series).

Aging↗
PubMed1978

[Trends in modern international gerontological research. Morphological aspects].

Ageing develops during the whole life with differences on cells, tissues and organs, and begins if their capacities for adaptations and compensations decrease. Theories about ageing are insufficiently. That results from the further development of ageing research in morphology also. Parenchymal cells are reduced in all organs, in favour of an enhanced connective tissue content, the function of the single parenchymal and mesenchymal cell is not diminished coincidently in ageing. In the most organs are young and old cells in every age stage (but more old cells in senile age). The most cells don't live endless, but they can be regenerated. Their organelles possess own biological half life times, which are very shorter than their cell life times. Ageing-typical increase of the total content of connective tissue, esp. of collagen in many organs is combined with alterations of the proteoglycan and collagen metaoblism rates and patterns (collagen types included), and are thereby connected with age dependent changes of the several functions of the cells, tissues and organs. Everybody, and esp. the physician has to know that the mean age of the population (and of the patients) becomes higher. So we need the morphological research in gerontology also, as demonstrated and summarized in this review.

Adolescent↗