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Biomedical subjects

C Hofmann

Publications and source records attributed to C Hofmann.

At least 127 records · Page 7Linked to original sources
PubMed1985

Cellular responses elicited by insulin mimickers in cells lacking detectable plasma membrane insulin receptors.

Madin-Darby canine kidney (MDCK) cells were previously shown to have few or no plasma membrane insulin binding sites (Hofmann et al: J Biol Chem 258:11774, 1983]. Accordingly, neither insulin-stimulated incorporation of [14C]glucose into glycogen, nor insulin-induced uptake of radiolabeled alpha-aminoisobutyrate ([3H]AIB) could be demonstrated. To probe for receptors, MDCK cultures were surface-labeled with Na125I or were labeled with [35S]methionine. When solubilized cells were immunoprecipitated with sera containing antibodies to the insulin receptor, and immunoprecipitates were analyzed on SDS-gel electrophoresis, no evidence for insulin receptor components was found. Also, when intact MDCK cells wee incubated first with serum containing antibodies to the insulin receptor and then with 125I-protein A, no radiolabeling of insulin receptors occurred. Various agents reported to have insulin-like activity were tested on MDCK cells. The insulinomimetic lectins concanavalin A and wheat germ agglutinin as well as hydrogen peroxide enhanced incorporation of [14C]glucose into glycogen and induced stimulated [3H]AIB uptake, whereas trypsin, vanadate, and serum containing antibodies to the insulin receptor were without effects. Altogether, these results showed that MDCK cells had few or no insulin receptors and were correspondingly insulin-insensitive. However, since insulin-associated responses could be elicited by some insulin mimickers, the post-receptor limb of response in MDCK cells was apparently intact.

Animals↗
PubMed1985

Impairment to viability of neutrophils and lymphocytes by angular psoralens and UV-radiation.

The angular psoralen derivative, 4,5'-dimethylangelicin (Dm Agn), both without and with UV-radiation induces under adequate conditions a higher percentage of lethally damaged cultured human polymorphonuclear neutrophils (PMN) as compared with angelicin (Agn). In general, PMN photosensitized with Dm Agn are less resistant than similarly photosensitized lymphocytes. These results suggest that Dm Agn might be used to improve the photochemo (PUVA-)therapy of skin diseases where PMN are of pathogenic importance.

Cell Survival↗
PubMed1983

Subtotal parathyroidectomy for primary hyperparathyroidism. Long-term results in 292 patients.

Subtotal parathyroidectomy was performed in a consecutive series of 292 patients with primary hyperparathyroidism. We evaluated the long-term postoperative results during a period of 16 years. Patients ranged in age from 14 to 83 years and included 176 women and 116 men. Of these, 16% had a history of exposure to radiation in childhood or adolescence, while thyroid disease requiring some form of thyroidectomy coexisted in 91 (31%) of the patients. Histologic information on three or more parathyroid glands was obtained in 73% of the cases. We considered 285 patients (97.6%) cured after their first operation. The remaining seven patients (2.4%) had persistent hyperparathyroidism. However, five were cured after a sternum-splitting mediastinal exploration and one after a second neck exploration. The seventh remains hypercalcemic despite a subsequent mediastinal exploration. Temporary postoperative hypoparathyroidism occurred in 10% of our cases and permanent hypoparathyroidism in 1%. There have been no instances of recurrent hyperparathyroidism.

Adenocarcinoma↗
PubMed1983

Parathyroid cysts: a report of eleven cases including two associated with hyperparathyroid crisis.

Eleven parathyroid cysts were found in 325 patients who underwent parathyroid operations. Ten cysts were located in the neck and one was located in the mediastinum. The cysts ranged in size from 1.6 to 10 cm with a mean of 3.9 cm. The patients who had cysts included six women and five men, and their ages ranged from 28 to 72 years with a mean of 51 years. In contrast to other reports that have suggested that most parathyroid cysts are nonfunctional, all but one of our patients had hyperparathyroidism, as evidenced by hypercalcemia, hypophosphatemia, and elevated parathyroid hormone level, which was corrected by cyst removal. The nonfunctional cyst first appeared to be an asymptomatic neck mass. Two patients had acute hyperparathyroid crises, which required emergency operations. It is postulated that the crises may have been the result of spontaneous necrosis of preexisting parathyroid adenomas. This is supported by the pathologic findings of degeneration and early organization as well as by the presence within the cyst of sanguineous fluid that contained a parathormone concentration greater than 100 times normal serum levels.

Acute Disease↗
PubMed1983

Effects of radiation on parafollicular C cells of the thyroid gland.

While radiation has well-recognized effects on follicular cells of the thyroid gland, those on parafollicular C cells are not yet established. Low-dose radiation that has been proved to be nonablative and carcinogenic to follicular cells was administered to 8-week-old Long-Evans rats to study the changes in C cell number and function. Circulating calcitonin levels were significantly reduced in animals that had undergone radiation at age 24 months. Mean calcitonin values were 0.66 (+/- 0.20) ng/ml and 1.64 (+/- 0.59) ng/ml for control males and females compared with 0.14 (+/- 0.06) ng/ml and 0.11 (+/- 0.01) ng/ml for males (P less than 0.05) and females (P less than 0.001) that had undergone radiation, respectively. These levels correlated well with C cell population density in thyroid glands in the control group and in the group that had undergone radiation as evidenced by light microscopy. Routine hematoxylin and eosin staining showed C cell hyperplasia in 77% of control animals of both sexes compared with 4% in animals that had undergone radiation (P less than 0.005). Immunoperoxidase staining with an anticalcitonin antibody showed virtual absence of C cells in most animals that had undergone radiation compared with diffusely scattered cells in animals in the control group. Medullary carcinomas occurred in 14% of animals in the control group compared with 3% of animals that had undergone radiation (P less than 0.05). These data indicate that the radiation dosage that is carcinogenic to the follicular epithelium causes lethal injury to C cells and thus suggest that C cells are more sensitive to radiation than are follicular cells. This increased sensitivity could explain the virtual absence of C cells, decrease in calcitonin levels, and reduced numbers of medullary carcinomas in the animals that had undergone radiation.

Animals↗
PubMed1983

Successful autotransplantation of parathyroid adenomas in seven patients.

The autotransplantation of normal as well as adenomatous parathyroid tissue is currently being used with increasing frequency. In the present report, we describe our experiences with the successful transplantation of adenomatous or hyperplastic parathyroid tissue in seven patients. Prior to transplant surgery, six of these patients had recurrent or persistent primary hyperparathyroidism. The last patient was on hemodialysis for chronic renal failure and was presumed to have tertiary hyperparathyroidism. A large superior mediastinal parathyroid adenoma was found at a second neck exploration. In all patients, the only remaining parathyroid tissue was either adenomatous or hyperplastic. A total of 30 to 75 mg of this parathyroid tissue was diced and transplanted into single subfascial pockets of the forearm muscles (6) or sternocleidomastoid muscle (1). Following transplantation, all patients required transient calcium and vitamin D supplements for six to 12 weeks. In follow-up studies of ten months to 12 years, all patients have remained eucalcemic with normal parathyroid hormone levels. The use of a single subfascial pocket (versus the popular method of multiple implants) may explain the lack of recurrent hyperparathyroidism in our small population.

Adenoma↗
PubMed1982

Polymorphous light eruption. Experimental reproduction of skin lesions.

The clinical features of polymorphous light eruption (PLE) are reviewed from the literature with special emphasis on the experimental reproduction of skin lesions. Our clinical experience with 180 patients is reported. In forty-three patients a newly developed UVA provocation test was performed. UVA, free of sunburn radiation (50-100 J/cm2), was administered, sometimes repeatedly up to four times, to large sites of previously involved skin. With this technic the reproduction of PLE lesions under laboratory conditions was possible in 90% of this group of forty-three patients. The diagnosis was substantiated by microscopic examination of genuine and experimentally induced lesions. Characteristic histologic features of PLE are described. Phototesting with large doses of UVA aids in confirming the diagnosis of PLE. Hitherto, this diagnosis depended often on exclusion of other dermatoses. Eusolex 8021, a UVA-effective sunscreen, blocked eruptions of PLE lesions under laboratory conditions. An effective means of treatment is offered by PUVA therapy.

Adolescent↗
PubMed1982

[Growth of finger nails in psoriasis patients undergoing PUVA therapy].

In 78 persons aged 13-78 years with and without psoriasis the daily growth rate of fingernails was measured on three nails each of the right and left hand. Untreated patients with psoriasis had an increased growth rate (112.7 +/- 25.5 micrometers) compared to control subjects (102.5 +/- 18.5 micrometers) without psoriasis (p less than or equal to 0.001). In patients with psoriatic nail involvement the growth rate was significantly increased (113.9 +/- 29.2 micrometers). Photochemotherapy (PUVA) slowed down the nail growth rate in patients without nail involvement (92.8 +/- 21.8 micrometers) vs. untreated psoriatics without nail involvement (p less than or equal to 0.05). In psoriatics with nail involvement, PUVA therapy had no measurable effect on the growth rate of fingernails.

Adolescent↗
PubMed1982

Castration induces a marked reduction in the incidence of thyroid cancers.

Although thyroid disease in humans predominates in females, the prognosis of thyroid cancer in males is much less favorable. To further explore the role of male sex hormones, we utilized the experimental model of radiation-induced follicular cancer in the rat, studying the effects of castration on tumor development. Microscopic evidence of tumor formation was correlated with the biochemical parameters serum thyroxine (T4), thyrotropin (TSH), and thyrocalcitonin (TC) at 24 months. The incidence of follicular carcinomas in intact males ws 58%, compared to 28% in comparable females. Castration of males caused a reduction in the incidence to 22%. Mean circulating levels of TSH were markedly elevated in all three irradiated groups. Mean T4 levels were reduced significantly only in irradiated castrated animals. TC levels were reduced in all irradiated groups. We conclude that although elevated levels of TSH probably play a significant role in the development of radioactive iodine-triggered follicular thyroid neoplasms in the rat, male sex hormone may also play an important role beyond their known effect on basal and thyrotropin-releasing hormone-stimulated TSH.

Adenocarcinoma↗
PubMed1981

Photoaffinity labeling of the insulin receptor in H4 hepatoma cells: lack of cellular receptor processing.

Photoaffinity labeling techniques were used to identify insulin-binding components of the plasma membrane in insulin-responsive, monolayer-cultured hepatoma cells. The activated, photosensitive reagent, an n-hydroxysuccinimide ester of 4-azidobenzoic acid, was coupled with highly purified insulin, and the hormone derivative was subsequently iodinated, bound to cell surface receptors of intact H4 cells, and photoactivated. Ater dissolution of the cells, labeled proteins were analyzed by SDS/polyacrylamide gel electrophoresis under reducing conditions. The main labeled band exhibited an apparent molecular weight of 130,000. Two minor components of apparent mol wt 95,000 and 40,000 were also identified. Specific labeling of all 3 bands was inhibited by simultaneous incubation of the cells with native insulin, but not by the heterologous hormone, glucagon, prior to photoactivation. Binding of azidobenzoyl insulin to H4 cells was time-dependent, as was the correlated labeling of receptor components. Band-labeling by the photosensitive insulin derivative was totally light-dependent; spontaneous covalent linking of insulin and receptor was not observed. The labeled receptor-related proteins were not degraded by the cells under our experimental conditions.

Affinity Labels↗