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Biomedical subjects

B Koch

Publications and source records attributed to B Koch.

At least 145 records · Page 8Linked to original sources

Indirect evidence that protein kinase C plays a critical role in signal transduction of both vasopressin and corticotropin-releasing factor on pituitary cells in culture.

The possible role of protein kinase C (PKC) in the cyclic AMP-dependent mechanism of action of corticotropin-releasing factor (CRF) on proopiomelanocortin cells of anterior and intermediate pituitary glands was examined after pretreatment of cells in culture with the PKC inhibitor retinal or the phorbol ester PMA, which depletes cell stores of the kinase. We found that these drugs not only abolished ACTH response to PMA and vasopressin, which both activate PKC, but unexpectably also dampened by 80-90% the stimulatory effect of CRF. Cell treatment with retinal failed to prevent CRF-induced accumulation of cyclic AMP. Retinal and PMA pretreatments of intermediate pituitary cells likewise inhibited alpha-MSH secretion stimulated by CRF. These data provide evidence to suggest that the mechanism of action of CRF on pituitary cells involves both cyclic AMP and PKC messenger systems.

Animals↗

Indirect relationship between vasopressin-induced secretion of ACTH and cyclic nucleotides in cultured anterior pituitary cells.

The present study examines whether a correlation exists between cyclic nucleotides and the mechanism of action of arginine vasopressin (AVP) on adrenocorticotropin hormone (ACTH) secretion from pituitary corticotrophs. Incubation of cultured anterior pituitary cells with 3-isobutyl-1-methylxanthine (IBMX) or Rolipram elevated the basal intracellular content of both adenosine 3':5'-cyclic monophosphate (cAMP) and guanosine 3':5'-cyclic monophosphate (cGMP) or cAMP alone, respectively. Both IBMX and Rolipram enhanced the AVP-stimulated secretion of ACTH in cultured anterior pituitary cells, but not in AtT-20 corticotrophs which lack functional AVP receptors. Rolipram was less potent than IBMX in this regard, which suggests a possible involvement of cGMP. In contrast, both drugs showed similar potency to stimulate CRF-induced ACTH secretion. Incubation of pituitary cells with atrial natriuretic factor elevated tissue cGMP levels and increased the ACTH response to AVP. The results of this study show that, although AVP fails to directly affect the levels of cAMP and cGMP in anterior pituitary cells, the stimulatory effect of AVP on ACTH secretion was modulated by the cellular cAMP content.

1-Methyl-3-isobutylxanthine↗

Stimulation by atrial natriuretic factor of cyclic GMP production in cultured anterior and intermediate pituitary tissues: evidence for a major contribution of proliferating nonendocrine cells.

Primary cultures of anterior and intermediate pituitary tissues were monitored immunocytochemically for the presence of endocrine and nonendocrine cells and simultaneously tested for their ability to produce cyclic GMP in response to atrial natriuretic factor (ANF). Cells cultured for 3 days and 6 days, in which nonendocrine (vimentin-positive) cells were found to rapidly overgrow the endocrine cells, showed a dramatic elevation in cyclic GMP production stimulated by ANF, with maximum stimulation 300-700% that seen in 1-day cultured cells. Also, ANF-induced accumulation of cyclic GMP in an enriched population of vimentin-positive cells appeared to closely match that triggered in a 3-day culture of anterior pituitary cells, emphasizing the major role played by nonendocrine cells and their ability to synthesize cyclic GMP. In contrast, in the homogeneous population of tumor corticotrophs AtT-20, there was a close relationship between cyclic GMP formation and cell density. It thus appears that contamination of primary cultures of anterior and intermediate pituitary tissues by proliferating nonendocrine cells (mainly fibroblasts), in which ANF-induced accumulation of cyclic GMP may be confused with that of the very secretory cells, leads to overestimation and masking of guanylate cyclase activity of endocrine cells.

Adrenocorticotropic Hormone↗

[Clinico-pathology of salivary gland tumors of the head in children and adolescents].

Tumours of salivary glands are rare in childhood and adolescence. Our material consists of 10 observations. The principles of classification of these tumours and the differences to the adults are reviewed. Nonepithelial tumours are diagnosed in a higher percentage in the first two decades of life. Epithelial neoplasms are often connected with doubtful or malignant behaviour.

Adolescent↗

[Sensitivity of Argas (Persicargas) walkerae to optic irradiation and localization and organization of light perceiving or permeability areas of the integument].

Considering a negative phototaxis as a stimulus reaction to narrow - or wideband monochromatic radiance of varying ranges of wavelengths and different irradiance it was established that both unfed and engorged I. and II. nymphs, as well as male and female adult ticks of Argas (Persicargas) walkerae, responded almost to the whole spectrum of the investigated wavelengths from 246-809nm, however, depending on the irradiance. Peaks of sensitivity with 50-100% of phototactically negative reacting ticks, however, were only registered in the range of 415 nm to 604 nm at moderate and high irradiance. Interstadially unfed and fed ticks showed no or only slight differences of reaction. Engorged ticks responded analogously to the unfed ticks but usually with smaller percentages. The lower readiness of reaction of the engorged stages was also established by the comparison of the temporal threshold values, which were ca. 1 min shorter for unfed ticks. Ablation tests for localizing light perception in or through the integument by means of covering the integumental areas in various combinations and simultaneously confronting them with the highly sensitive range of wavelengths from 446-568 nm revealed that unfed female adults probably perceived the light stimuli primarily through the dorsum. Covering the entire dorsum with white or black paint caused a phototactically negative response in 10-30% of the ticks. Untreated control ticks reacted to the light stimuli with a proportion of 50-75%. Scanning electron microscopical examinations of the dorsum, ventral surface and supracoxal folds of unfed female ticks gave no evidence of morphologically recognizable, superficially organized or integument-integrated photoreceptor areas or optical organs similar to lenses.

Animals↗

Binding and effect of atrial natriuretic factor on cyclic GMP formation and alpha-MSH secretion of intermediate pituitary cells.

The present study shows for the first time that in proopiomelanocortin cells of the rat intermediate pituitary gland ANF binds to two receptor forms, with apparent molecular weights of 150K and 70K. Scatchard plots revealed specific and high affinity non-interacting sites, with a KD value of about 3 nM and a density of 7,000 sites/cell. The presence of these binding sites was further confirmed by autoradiographic studies. Activation of these receptors led to an increase in cellular content of cGMP, with half-maximal effect being elicited with about 5 nM ANF, while cAMP formation was unaltered. Alpha-MSH secretion of intermediate pituitary cells was unaffected by ANF, whether the cells were incubated in the absence or presence of corticotropin-releasing factor or bromocryptine. These data thus indicate the presence of multiple ANF receptor sites in the intermediate pituitary which are coupled to cell production of cGMP, but independent of alpha-MSH secretion.

Animals↗

Characterization of high affinity receptor sites for atrial natriuretic factor in anterior pituitary gland: evidence for the existence of two receptor forms.

The present study shows that in rat anterior pituitary tissue atrial natriuretic factor (ANF) binds to two distinct receptor forms, with apparent molecular weights of about 166K and 58K. Binding assays carried out with (125I)-ANF revealed specific and high affinity non-interacting binding sites, with Ko values of 1-1.7 nM and a density of 10-15,000 sites/cell. rANF fragments (5-25), (5-27) and (5-28) exhibited apparent equipotency in displacing tracer binding, while fragment (13-28) and various other peptides were ineffective. ANF (5-25) was about 100-times less potent than ANF (8-33) in stimulating half-maximum pituitary cGMP production. These data indicate the presence of multiple binding sites for ANF in the pituitary gland and suggest that only part of these sites may be coupled to activation of guanylate cyclase.

Animals↗

Antibody prevalence to HBLV (human herpesvirus-6, HHV-6) and suggestive pathogenicity in the general population and in patients with immune deficiency syndromes.

Detailed serologic screening showed an antibody prevalence to HBLV (HHV-6) in the general population of 26% if very strict criteria for antibody positivity were applied. Lower and borderline antibody titers yet may be found in up to 63% of the population. Only 17% of these persons have clinical symptoms; in the majority infection remains silent. HHV-6 infection apparently occurs already quite early in life, and initial symptoms can occur, such as short-term high fever, sore throat, local lymphadenopathy and skin rash. Lesions disappear without specific treatment. The frequency of positive antibody tests at higher titers rises in patients with immune deficiency and with atypical lymphoproliferative diseases to 60 and 75%. The rise in antibody titers is associated in patients with immune deficiency by characteristic shifts of blood lymphocyte populations, essentially by increase in immature T-lymphocytes. Highest titers are found in patients with lymphoproliferative syndromes, yet the percentage of atypical lymphoid cells harboring the viral genome is low (about 2% of seropositive patients). Thus it appears, that HBLV, similar to other herpesviruses such as Epstein-Barr virus, usually causes a silent seroconversion, yet may be associated with variable clinical pathology when persisting in an active state. Its pathogenic effect might be rather a cofactor contributing to immune disturbance than overt oncogenicity.

Acquired Immunodeficiency Syndrome↗

[Facial granuloma. On the clinic-histologic extent of variations of finding in 5 patients].

The clinical and histopathological findings are presented in five patients with granuloma faciale. The lesions most often occur on the face and are characterized by single or multiple soft, elevated, well-circumscribed nodules or plaques ranging in color from reddish purple to brown. The sites most commonly affected are the nose, temple, checks and forehead. The etiology of granuloma faciale is unknown. The condition is extremely persistent and may last for many years. Histologically, a narrow zone of uninvolved dermis is usually observed between the epidermis and the dermal, dense, polymorphous infiltrate at all levels of the corium. The infiltrate is usually diffuse or shows a nodular perivascular pattern, consisting of lymphocytes, plasma cells, neutrophils and histiocytes together with a varying number of eosinophils. In older lesions the formation of the fibrous tissue may be seen, accompanied by capillary proliferation. Differential diagnosis includes sarcoidosis, discoid lupus erythematosus, erythema elevatum et diutinum, angiolymphoid hyperplasia with eosinophilia and histiocytosis X. The diagnosis of granuloma faciale requires a synopsis of clinical and histological findings.

Adult↗

[The CREST syndrome].

If a patient has peri- and intra-articular calcinosis, as well as acro-osteolysis and esophageal hypomotility, and rheumatic symptoms, Crest syndrome should be considered as a manifestation of progressive systemic sclerosis. In connection with relevant symptoms on the skin and visceral involvement, radiological studies offer the possibility of classifying progressive systemic sclerosis more accurately.

Calcinosis↗

Evidence that AVP receptors in AtT-20 corticotrophs are not coupled to secretion of POMC-derived peptides.

This study reports the presence in AtT-20 corticotrophs of high affinity-low capacity receptors for arginine-vasopressin (AVP), whose binding capacity was considerably enhanced by the divalent metal ion nickel. These binding sites, when analyzed in the presence of nickel, showed high affinity for AVP, vasotocin and oxytocin, but recognized to a lesser extent the V2-agonist 1-deamino-AVP, as well as V1-antagonists. Surprisingly, AVP failed to alter secretion of proopiomelanocortin (POMC)-derived peptides from the cells or corticotropin-releasing factor (CRF)-induced cAMP synthesis, as reported in normal corticotrophs. Exposure of cells to CRF elicited an increase in mRNAPOMC levels, while, in contrast, AVP was without significant effect. It thus appears that in AtT-20 tumor cells, the AVP receptors are not coupled to either the biochemical or biological cellular response.

Adrenocorticotropic Hormone↗

Characterization and modulation of corticotropin-releasing factor in the neurointermediate pituitary gland.

The present study attempts to determine whether part of the corticotropin-releasing factor (CRF)-like materials present in the 'posterior pituitary' is composed of authentic CRF and examines whether the concentration of that peptide may be modulated by circulating glucocorticoids. Analysis of crude extracts of neurointermediate lobes (NIL) of rat pituitaries by reverse-phase HPLC, coupled with a specific radioimmunoassay (RIA), revealed the presence of a major component eluting with the same retention time as rat CRF (rCRF) and, importantly, which was indistinguishable by RIA from the synthetic peptide. Also, two minor forms eluted earlier than rCRF upon HPLC; one of these forms matched the elution position of r[Met(O)21,38]CRF. All three species did show biological activity and stimulated ACTH release from pituitary cells. Essentially the same elution profile was generated by median eminence (ME) extracts. Immunoreactive CRF (CRFi) content of the NIL was about 3% of that of the ME and was found to undergo a significant increase as a result of long-term adrenalectomy while, in contrast, CRFi content of the ME was decreased. This effect of adrenalectomy was completely antagonized by dexamethasone treatment. This study thus provides strong evidence for the presence of authentic CRF within the NIL of the rat pituitary and also shows that tissue concentration of that peptide was modulated by glucocorticoids.

Adrenalectomy↗

Congenital muscular torticollis: results of conservative management with long-term follow-up in 85 cases.

A retrospective review of 277 patients with congenital muscular torticollis seen between 1970 and 1982 was conducted. In 85 cases this was supplemented by questionnaires and recent photographs, permitting a two- to 13-year follow-up. The first visit for 81.6% of patients was before six months of age. All were enrolled in a specific physical therapy program at the time of the first visit, unless they presented with severe torticollis after 12 months of age. Torticollis was mild to moderately severe in 90.6% of cases. Sternomastoid fibrotic nodules were present in 38.6%, more frequently in the more severe cases. Hip dysplasia increased in direct relation to severity and occurred in 10.5% of cases. At 12 months the torticollis had been conservatively resolved in nearly 70% of patients regardless of severity and presence or absence of focal fibrosis. Tenotomies were indicated in only ten children, eight of whom had first been seen after 12 months of age. Long-term sequelae were mild and consisted of craniofacial asymmetry, intermittent head tilt, and mild scoliosis. Developmental asymmetry or high tone due to limited mobility in the cervical spine were noted in 25.3% of infants initially and tended to subside with appropriate therapy. However, 11.8% of patients with long-term follow-up showed persistent functional asymmetry of the involved body side despite mild or moderate severity, early diagnosis, and complete resolution of the torticollis. Long-term observations indicate that congenital torticollis rarely requires surgical treatment.

Female↗

Modulation by Leu-enkephalin of peptide release from perifused neurointermediate pituitary. II. Inhibition of calcium-mediated secretion of alpha-MSH and beta-endorphin.

The present study examines the effect of opiates on alpha-MSH and beta-endorphin release from perifused neurointermediate rat pituitaries, as stimulated by various secretagogues for which Ca ions and/or cAMP serve as messengers. alpha-MSH release stimulated by high K+ concentrations (5-min pulses) and veratridine depolarization, which is closely dependent on Ca2+ fluxes, was abolished by both Leu-enkephalin and beta-endorphin. A dose-response relationship between inhibition of alpha-MSH secretion and the concentration of Leu-enkephalin, with ED50 approximately 10(-9) M, was observed. High K+-induced release of beta-endorphin was likewise blunted by Leu-enkephalin. The stimulatory effect of the Ca2+ ionophore A 23187 was inhibited in a similar way as was that of CRF, which requires both Ca2+ fluxes and cAMP formation. The antagonist naloxone not only reversed the action of opiates, but also enhanced spontaneous hormonal output. In contrast, the effects of l-isoproterenol and forskolin, for which cAMP serves as a primary messenger, were unaffected in the absence of extracellular Ca ions and, also, in the presence of Leu-enkephalin. We conclude that opioid peptides may exert a direct inhibitory influence on the release of both alpha-MSH and beta-endorphin and do so by interfering with the Ca2+ messenger system. In addition, these data also suggest the existence of an opiate-opiate negative feedback mechanism.

Animals↗

Central nervous system control of pituitary vasopressin receptors: evidence for involvement of multiple factors.

The regulation of pituitary vasopressin (VP) receptor concentration was investigated in rats with antero-lateral cuts (ALC) placed around the hypothalamus, as well as in Brattleboro homozygotes (HO) that genetically suffer from a lack of AVP. Hypothalamic ALCs caused a reduction in (3H)-AVP binding, while counteracting the dramatic fall in binding that normally occurs after adrenalectomy. Surprisingly, in HO rats, long-term adrenalectomy did cause pituitary AVP receptor number to decrease to an extent similar to that seen in normal rats. However, the receptor disappeared twice as rapidly in heterozygote controls than in HO animals, with calculated half-lives of 1.1 and 2.0 days, respectively. In HO, chronic administration of VP reduced receptor concentration by about 80%, while the same dose of oxytocin (OT) produced only a 20-30% reduction. Whereas dexamethasone injections did reverse the depressing effect of adrenalectomy on pituitary AVP receptors, they failed to enhance binding in sham-operated controls, treated or not with VP; thereby suggesting a central site of action of the steroid. In contrast, in rats with hypothalamic ALCs (i.e. with the pituitary lacking central control), corticosterone implants did antagonize the reduction in receptor density caused by adrenalectomy. We conclude that the pituitary AVP receptor system lies mainly under control of the central nervous system, through a mechanism of action that not only seems to imply AVP and OT, but probably also some other hypothalamic factor(s). Glucocorticoids appear to exert a dual effect, acting indirectly through negative feedback control of neuropeptide release and, possibly, also directly on the pituitary to regulate binding sites.

Adrenalectomy↗