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Biomedical subjects

H Cramer

Publications and source records attributed to H Cramer.

At least 37 records · Page 2Linked to original sources

Somatostatin acts through G-proteins on dopaminergic adenylate cyclase in the caudate-putamen of the rat.

Somatostatin was incubated in an adenylate cyclase assay of a particulate fraction of caudate-putamen tissue of the rat in order to examine the effect of the peptide on D-1 receptor coupled adenylate cyclase in vitro. Somatostatin was able to enhance cyclic AMP formation in the presence of guanylylimidodiphosphate and guanosine-triphosphate. In contrast to this, somatostatin inhibited both dopamine and forskolin-stimulated cyclic AMP accumulation. Pertussis toxin and cholera toxin also depressed forskolin-induced stimulation. Somatostatin was found to antagonize these inhibitory effects of pertussis toxin and cholera toxin. The results suggest that somatostatin acts through a stimulatory as well as an inhibitory guanine nucleotide regulatory protein subtype to affect dopaminergic adenylate cyclase activity.

Adenylate Cyclase Toxin

Ventricular fluid neuropeptides in Parkinson's disease. I. Levels and distribution of somatostatin-like immunoreactivity.

We have measured somatostatin-like immunoreactivity SLI in cerebroventricular fluid of patients with Parkinson's disease (PD) and other extrapyramidal disorders with hyperkinesia. Patients with PD showed a significantly lower concentration of SLI when compared with levels in control patients with chronic stable multiple sclerosis or temporal lobe epilepsy. Less markedly decreased levels of SLI were also noted in patients with torsion dystonia. Of two patients with Huntington's disease one showed a high and one a medium concentration of SLI. According to the site of the stereotactic cannula, verified by ventriculopathy, SLI concentrations in CSF specimen obtained from the foramen Monro tended to be higher than in specimen from a supraforaminal level. Of 5 other patients with lateral and third ventricle being accessible during the passage of the stereotactic cannula, 4 showed higher SLI concentrations in the third ventricle compared to the lateral ventricle. High performance liquid chromatographic analysis combined with radioimmunoassay showed molecular heterogeneity of SLI in CSF. The ratio of SST-14 to SST-28 was higher in the third ventricle than in the lateral ventricle.

Adult

Somatostatin-like immunoreactivity in the cerebrospinal fluid of aged patients with Parkinson's disease. The effect of dopatherapy.

Cerebrospinal fluid (CSF) somatostatin concentrations were measured in 35 aged patients with Parkinson's disease (mean age, 79.5 years) and 11 control subjects (mean age, 82.3 years). In patients with Parkinson's disease the levels of somatostatin-like immunoreactivity were lower than in controls (P less than .02); these values were lowest in the untreated group. Somatostatin-like immunoreactivity levels in the CSF tended to increase with treatment but not significantly (P = .11). Somatostatin values were not correlated to age, sex, or duration of the disease. Somatostatin concentrations tended to be lower in more severely affected patients with higher scores on the Hoehn and Yahr (P = .13) and Webster staging scales (P = .13) and lower scores on Mini-Mental State (P = .10), but without statistical significance for these correlations.

Aged

Whole cell preparation of squamous cell carcinoma for cytometric analysis of DNA.

To date, analysis of the DNA content of head and neck squamous cell carcinomas has relied on the homogenation of the entire tissue specimen and subsequent staining and quantitation of the naked nuclei. This methodology does not make allowance for the extremely variable nature of these tumors with respect to their cellular composition. Further, by destroying the cytoplasm and cell membranes, this methodology makes it impossible to distinguish the DNA content of the tumor cells from that of the background stromal and inflammatory cells. The authors present a methodology for the selective exclusion of inflammatory cell infiltrates from the DNA analysis of these tumors. Using this technique, it has been found that exclusion of the inflammatory cells allows the investigator to look more specifically at the malignant cell population. This has been most helpful in those samples in which the tumor cells have been diploid or near-diploid. With this technical refinement, the relationship between DNA ploidy and clinical prognosis may be more accurately assessed.

Aged

[Hyperthermia in cancer research. Historical development, current status of research, future perspectives and differentiation from alternative medical procedures].

Already at the beginning of the 19th century first clinical trials with systemically induced fever were performed on malignant tumors. An intensified research in thermobiology in the sixties of this century gave the rationale for using this modality for cancer treatment. Clinical use of hyperthermia in combination with radiation or chemotherapy begun in the mid of the seventies when a better technique for selective heating of the tumor was used. In the technical development the problem of heating deep-seated tumors was mainly solved. Temperature measurements of the tumor and surrounding tissues are performed with specialized thermometry systems using thin implanted catheters to measure inside the body. 1986 a pilot study was initiated at the Medical Clinic III of the Klinikum Grosshadern to study the effects of regional hyperthermia combined with systemic chemotherapy. This study is aimed on feasibility, toxicity, and tumor response.

Abdominal Neoplasms

Immunoreactive substance P and somatostatin in the cerebrospinal fluid of senile parkinsonian patients.

The concentration of substance-P-like immunoreactivity (SPLI) and somatostatin-like immunoreactivity (SLI) in the lumbar spinal fluid of senile parkinsonian patients (mean age 77.6 +/- 6.7 years) and senile control patients (mean age 83.5 +/- 5.6 years) were determined by specific radioimmunoassays. Mean SPLI and SLI levels in the control group were 8.1 +/- 2.0 (SD) and 32.5 +/- 12.0 fmol/ml, respectively. The mean SPLI levels were not significantly different in the groups. The mean SLI level was significantly lower in the group of patients with Parkinson's disease (19.8 +/- 9.0 fmol/ml). A comparison with results in patients with senile dementia of Alzheimer type (SDAT) shows that, in addition to clinical and pathological correlations, Parkinson's disease of late onset may share a deficit in somatostatinergic neuromodulation with SDAT.

Age Factors

Parathyroid cysts.

Parathyroid cysts are relatively uncommon lesions. Approximately 200 cases have been reported. Despite their location in the region of the thyroid gland, they have not previously been discussed in the otolaryngologic literature. They arise from remnants of the pharyngeal pouch or as a result of cystic degeneration of a parathyroid adenoma. A case of a parathyroid cyst occurring in a 13-year-old female is presented. This is the youngest case ever reported. Fine needle aspiration of an anterior neck mass yielded clear fluid, a finding highly suggestive of a parathyroid cyst. Radioimmunoassay of the fluid demonstrated a high level of parathormone and low level of thyroglobulin concentration, thereby confirming the diagnosis. In this case, which was diagnosed by FNA, the need for a trial of thyroid hormone suppression or hemithyroidectomy was obviated.

Adolescent

Fine-needle aspiration in the management of breast masses.

The exact role of FNA in the diagnosis of palpable breast lesions is still uncertain. False-positive and false-negative cytological diagnoses occur and raise questions regarding the diagnostic utility of FNA as a replacement for open biopsy in many clinical situations. False-positive diagnoses may result from atypical epithelial proliferations, fibroadenomas, or inflammatory lesions. False-negative aspirates may occur because of technical errors, cystic lesions, and underdiagnosis of low grade neoplasms. The triple diagnosis protocol has been suggested as a replacement for open biopsy of palpable breast masses in many clinical situations. Following this algorithm, the results of palpation, mammography, and cytology are combined to guide management. Mammography should precede FNA or follow the cytologic procedure by 2 or more weeks. Patients with a positive triple diagnosis should undergo open biopsy or confirmatory intraoperative frozen section. Positive FNA results would be useful for preoperative counselling as well as serving as a diagnostic procedure for clinically suspicious lesions in patients wishing a confirmatory test before open biopsy is performed. Patients with discordant triplet results should be referred for open biopsy. The management of patients with negative triplet results is less clear. From the available data, it appears that approximately 2 percent of patients with negative triplet results have carcinoma. Based on these results, we cannot recommend replacing open biopsy by the triple diagnosis method in most patients with a persistent dominant mass. In most cases, a biopsy is indicated. Surgeons, who plan to follow a breast mass with clinical examination, may be able to reduce their false-negative rate by performing FNA. Further study is necessary to establish the best way to use FNA in the diagnosis of breast carcinoma, to determine the cost effectiveness of the triple diagnosis method as a substitute for open biopsy, and to assess the utility of aspiration cytology in the mammographically directed diagnosis of nonpalpable breast lesions.

Adenofibroma

Cerebrospinal fluid immunoreactive substance P and somatostatin in neurological patients with peripheral and spinal cord disease.

We have measured substance P-like (SPLI) and somatostatin-like (SLI) immunoreactivities in cerebrospinal fluid of 49 patients with peripheral (polyneuropathy, lumboischialgia) and spinal cord disease and in 16 control patients. The patient groups showed significantly higher CSF SPLI levels than controls while the mean SLI levels were unchanged. Fractionated sampling of CSF (total volume 30 ml) in 20 patients with various neurological diseases showed no significant differences between early and late fractions for SLI. In contrast, lumbar-cisternal concentration gradients were negative for SPLI, total protein and IgG, and positive for the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindolacetic acid. This suggests that SPLI may be released into the lumbar CSF from lower levels of the neuraxis, presumably the spinal cord and spinal ganglia, whereas SLI stems from diffuse CSF secretion without spinal preponderance.

Adult

Dopamine and somatostatin modulated adenylate cyclase activity in the rat caudate-putamen following unilateral cortical ablation.

Dopamine and somatostatin-14 (SRIF) were incubated with a membrane fraction of rat caudate-putamen (CP) tissue in an adenylate cyclase assay in order to examine the D-1-receptor coupled adenylate cyclase activity 5 days and 3 weeks after unilateral ablation of the left frontal and lateral cortex. Five days after decortication the ipsilateral basal and dopamine stimulated adenylate cyclase activity was increased by about 30% compared to that of the contralateral side. Three weeks after decortication no significant difference could be seen. On either side basal and dopamine stimulated adenylate cyclase activity was not significantly decreased compared to sham operated controls. Somatostatin (10(-7) mol/l) reduced basal adenylate cyclase activity of the ipsilateral CP five days following lesioning and reduced the maximal stimulation induced by dopamine. The effects of somatostatin were most marked in the absence and at low concentrations of dopamine (10(-7)-10(-6) mol/l). The effects of somatostatin in the lesioned CP were no longer apparent three weeks following surgery. These results do not favour a presynaptic localization of D-1-receptors on cortico-striate projection fibers and suggest that somatostatin is involved in the interaction of the cortico-striate and nigro-striatal projection systems and may play a role in the regulation of D-1-receptor linked adenylate cyclase.

Adenylyl Cyclases

Comparison of DSIP- (delta sleep-inducing peptide) and P-DSIP-like (phosphorylated) immunoreactivity in cerebrospinal fluid of patients with senile dementia of Alzheimer type, multi-infarct syndrome, communicating hydrocephalus and Parkinson's disease.

The concentrations of delta sleep-inducing peptide (DSIP)-like (DSIP-LI) and P-DSIP-like (phosphorylated, Ser7) immunoreactivity (P-DSIP-LI) were measured by specific radioimmunoassay in the cerebrospinal fluid (CSF) of patients with senile dementia of the Alzheimer type [SDAT, subdivided into early (S1), middle (S2) and late dementia (S3)], multi-infarct dementia (MD), Parkinson's disease (PD), vascular disease (VD) and communicating hydrocephalus (H), as well as in control patients (C1, C2). Mean DSIP-LI and P-DSIP-LI concentrations were found to be significantly higher in the elderly control group (C1, mean age 83 +/- 5 years) than in the middle-aged control group (C2, mean age 40 +/- 16 years). DSIP-LI and P-DSIP-LI were positively correlated with age in both control groups. Significant decreases of DSIP-LI compared with age-matched controls (C1) were observed for S2, S3, MD, PD, VD and H. In contrast, no significant differences corresponding to pathology were found for P-DSIP-LI.

Adult

Molecular size distribution of somatostatin-like immunoreactivity in the cerebroventricular fluid of neurosurgical patients.

The molecular size distribution of somatostatin-like immunoreactivity (SLI) in the cerebroventricular fluid of patients with Parkinson's disease, dystonic syndromes, multiple sclerosis, basal and midline tumors, epilepsy and pain syndromes was investigated by separation with a Sephadex G-50f column and subsequent radioimmunoassay of the eluate. Marked heterogeneity of SLI was observed in most of the pools investigated. The most conspicuous feature of the elution profiles was the preponderance of the peak coeluting with synthetic somatostatin-14, whereas the peaks comigrating with synthetic somatostatin-28 and attributable to precursor-like SLI represented only minor or trace amounts of total immunoreactivity. These findings are consistent with the greater biological activity of somatostatin-14 in the human central nervous system, whereas somatostatin-28 appears to represent the more active form in the pituitary and in the intestinal mucosa. Solely in the case of brain tumor patients, some differences could be seen, resulting in an approximately equal distribution of somatostatin-14 and somatostatin-28 in two pools of ventricular fluid and by the detection of a degradation product of somatostatin-14 in another one. These observations could be explained by a lowered barrier function as a consequence of increased intracranial pressure in case of brain tumors, which is well in accordance with a markedly elevated total protein content being a sign of a lowered barrier function.

Adolescent

Enzymatic determination of red cell creatine as an index of hemolysis.

An enzymatic assay for creatine, depending on the creatine kinase reaction, has been modified for the determination of creatine in packed erythrocytes, using a centrifugal analyzer (COBAS BIO). The method is precise, sensitive and shows excellent accuracy in recovery experiments when compared to the diacetyl-alpha-naphthol method. The enzymatic red cell creatine correlates with the erythrocyte survival time determined with the radioactive chromium method. It can be used as a rapidly available parameter for the quantification of hemolytic processes.

Adult

Somatostatin-like immunoreactivity in cerebroventricular fluid of patients with basal midline tumours.

The concentration of somatostatin-like immunoreactivity (SLI) was determined by specific radioimmunoassay in the cerebroventricular fluid of patients with tumours of the basal midline and compared to findings in patients with multiple sclerosis. Mean SLI levels of the two groups were not significantly different. In patients with basal tumours (astrocytoma, craniopharyngioma, etc.) SLI levels varied widely and tended to increase with increased intracranial pressure. Lateral ventricular SLI levels decreased in patients with blockade of foramen Monro and in patients with communicating hydrocephalus or post-radiation encephalopathy. There was no apparent correlation with dysfunction of the hypothalamohypophyseal axis.

Adolescent

Effects of somatostatin on dopamine sensitive adenylate cyclase activity in the caudate-putamen of the rat.

The effect of somatostatin-14 (SRIF) on dopamine-sensitive adenylate cyclase in caudate-putamen pellets was studied in naive female rats, and in rats with chemical lesions of the nigrostriatal dopaminergic tract produced by injection of 6-hydroxydopamine, or of the caudate-putamen itself produced by injection of kainic acid 3 week earlier. In unlesioned rats somatostatin at a concentration of 10(-7) moles/l inhibited adenylate cyclase activation by submaximal concentrations of dopamine, increasing the apparent Km but not altering Emax. In 6-hydroxydopamine lesioned rats somatostatin no longer influenced adenylate cyclase activity, whereas in kainic acid lesioned rats somatostatin still increased the apparent Km for dopamine activation. The effect of somatostatin in untreated and lesioned rats is compatible with a partial competitive antagonism to dopamine. Although the data from the lesioned rats present preliminary results, the dose response characteristics and the effects in lesioned animals suggest a more complex interaction, possibly by binding of somatostatin to an inhibitory subunit of regulatory adenylate cyclase components.

Adenylyl Cyclases

Effects of haloperidol on somatostatin-like immunoreactivity in the CSF of Schizophrenic patients.

The levels of somatostatin-like immunoreactivity (SLI) were determined in the cerebrospinal fluid (CSF) of 14 schizophrenic patients before and after 3 weeks on haloperidol treatment. Baseline levels of SLI correlated negatively with psychopathological items on the Brief Psychiatric Rating Scale related to psychotic productivity. SLI levels increased after haloperidol treatment, but this increase did not correlate with psychopathological improvement. A difference in the ratio of larger and smaller molecular forms of the peptide was found before and after treatment. The drug-free samples showed a preponderance of the larger molecular forms, resulting in a ratio of 4:1, whereas the haloperidol-treated samples showed an equal distribution of both species.

Adult

Permeability of epidural somatostatin and morphine into the intrathecal space of dogs.

In an in vivo saline perfusate of the intrathecal space of 6 dogs, the concentration of somatostatin was determined by radioimmunoassay before and over 2 h after epidural administration of 3 mg somatostatin. The total recovered amount of somatostatin was negligible, about 0.02%. However, within 50 min after the bolus epidural injection of somatostatin, the concentration per ml perfusate increased from 0.1 +/- 0.02 ng/ml to 138 +/- 102 ng/ml (P less than 0.001) and declined to 4 +/- 1.7 ng/ml after 120 min. This increase of the somatostatin concentration by 3 orders of magnitude might explain why epidurally administered somatostatin is effective in treatment of acute and chronic pain. In a control investigation with epidural morphine in another 6 dogs to prove the feasibility of the method, the total recovered amount of morphine in the intrathecal perfusate over 2 h was about 12%.

Animals