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Biomedical subjects

M Berger

Publications and source records attributed to M Berger.

At least 757 records · Page 42Linked to original sources

The tumor-inhibiting effect of isomeric dichloro(diphenylethylenediamine)platinum(II) complexes.

Ring unsubstituted dichloro(diphenylethylenediamine)platinum(II) complexes show a dependence of their antitumor activity on the configuration and position of phenyl rings in ethylenediamine ligand. Dichloro(1,1-diphenylethylenediamine)platinum(II) (1d) and meso-dichloro(1,2-diphenylethylenediamine)-platinum(II) (meso-2d) have a weaker effect on the human breast-cancer cell line MDA-MB 231 and on rat leukemia L 5222 than (+/-)-dichloro(1,2-diphenylethylenediamine)platinum(II)((+)-2d) and its enantiomers (+)-2d and (-)-2d which cause marked and comparable inhibition of both tumors; (+/-)-2d is also active on ADJ/PC 6 plasmacytoma of the mouse and on cisplatin-, daunomycin-, and cisplatin/daunomycin-resistant Ehrlich ascites tumors of the mouse. The differences in activity of the diastereomers (+/-)-2d and meso-2d, for which distinct influences on the DNA secondary structure can be demonstrated CD spectroscopically may be explained by a steric hindrance of the drug-DNA interaction.

Animals↗

Long-term variations in plasma gonadotropins in early castrated male rabbits.

LH and FSH levels were determined by RIA in plasma samples collected every 10 days from 30 to 90 days and at 4, 5 and 6 months in control male rabbits and in rabbits castrated at 30 days of age. At all stages studied gonadotropin levels were significantly increased in castrates. Mean LH levels were not influenced by age in controls or in castrates. Mean FSH levels were age dependent and increased during sexual maturation in both groups. The results showed that the secretion of FSH, but not that of LH, may be stimulated during prepubertal and pubertal stages in males where steroidal inhibition is absent.

Age Factors↗

Immunoregulatory effects of C3 and its major cleavage fragments.

The immunoregulatory effects of highly purified C3 and its major cleavage fragments on in vitro responses of human peripheral blood mononuclear cells (PBMC) were examined. Polyclonal immunoglobulin production induced by PWM and T-cell proliferation stimulated by tetanus toxoid in human PBMC were inhibited by human C3b. This effect occurred in a dose range of 10(-6) to 10(-8) M and was observed in cultures containing human serum but not under serum-free conditions. This noncytotoxic suppression did not appear to be mediated by prostaglandin release nor by interference with antigen uptake and presentation by monocytes. In contrast, the addition of C3a resulted in a mild enhancement of immunoglobulin production and T-cell proliferation. This effect, however, was observed only under serum-free conditions and, thus, may not have physiologic importance. The native C3, from which the above fragments were generated, had no effect on these lymphocyte responses. These results suggest that regulation of immune responses may be one consequence of C3 cleavage during complement activation in vivo.

Antibody Formation↗

Kainic acid seizure syndrome and binding sites in developing rats.

In rats up to 16 days after birth, parenteral kainic acid (KA) produced tonico-clonic convulsions, metabolic activation limited to the hippocampus, and no brain damage. Starting with the 19th day after birth, KA produced limbic seizures associated with metabolic activation and subsequent damage in the hippocampus, the amygdala, and other limbic structures. Membranes prepared from hippocampi 10 days after birth bound [3H]KA with a high affinity component, which was localized in the mossy fiber region by slice autoradiography. In contrast, on amygdaloid membranes this component appeared only 17-19 days after birth. Our results further stress the crucial role of the amygdala in the KA seizure syndrome.

Amygdala↗

Cardiopulmonary resuscitation in a hospitalized population: prospective study of factors associated with outcome.

A prospective study of advanced cardiopulmonary resuscitation (CPR) was carried out on 226 patients in order to examine factors predicting successful resuscitation and 6 month survival. The mean age of all patients was 70 years and median age was 74. Cardiopulmonary resuscitation was successful in 40.5% (137) of all arrests and in 48.7% (110) of the first arrests. Thirty of 207 patients with one or more cardiac arrests were discharged alive (14%). Twenty-one of our patients were alive at 6 months (10.3%). Patients in ventricular fibrillation and/or ventricular tachycardia at the time of arrest were more likely to have successful outcomes. When the patient required Isuprel or bicarbonate, cardiopulmonary resuscitation was significantly less successful. We found no correlation of immediate outcome with the following variables: location of arrest; time of day; pre-existence of shock; coma; stroke; malignancy. Uremia and/or chronic obstructive pulmonary disease was not significantly associated with failed resuscitation. Most notable in our results of specific treatments was the evidence for the need to improve the initial pH, particularly when it was less than 7.2. Failure to do so by the time the second blood gas was drawn was associated with failure of cardiopulmonary resuscitation. Our results also suggest that the adequate treatment of metabolic acidosis, and improved ventilatory management with improved PO2 and optimization of PCO2, play a role in the better outcome of cardiopulmonary resuscitation.

Acid-Base Equilibrium↗

A multidisciplinary study of folic acid neurotoxicity: interactions with kainate binding sites and relevance to the aetiology of epilepsy.

Folic acid has been injected unilaterally into the amygdaloid complex of awake chronically implanted rats, or in rats under anaesthesia. Clinical, electrographic, and metabolic changes (estimated by means of the 2-deoxyglucose method) have been studied in relation to subsequently demonstrated neuropathology using Fink-Heimer and Nissl stains. The observations are compared to the corresponding effects of intra-amygdaloid application of kainic acid. Major differences were noted between the folate and the kainate induced seizure/brain damage syndrome. Thus: folate produced essentially stereotypies, alternating with myoclonic unilateral jerks of head and limbs. In contrast, limbic motor seizures which are characteristically produced by kainic acid, were extremely rare. Folate did not produce the preferential and sequential electrographic activation of limbic structures as observed after kainate. 2-Deoxyglucose autoradiography revealed an enhanced metabolic activity in the injected amygdala and in the overlying piriform and entorhinal cortices. The most conspicuous rise in labelling, however, occurred in the entire fronto-parietal cortex (ipsilaterally) up to the cingulate region, as well as in the ventral thalamic complex and the globus pallidus, i.e. in structures which are not labelled after kainate treatment. Some extent of local damage was observed 1-8 days after the injection; distant from the injection site, we found massive anoxic-ischemic type of damage in the superficial layers of the fronto-parietal cortex, a complete necrosis of the piriform lobe, and neuronal cell loss in the ventral thalamus and several extrapyramidal structures. The full range of limbic damage associated with kainate was never produced by folate. The CA3 region of the hippocampus, most susceptible to kainate, was only mildly affected by folate. These differences between kainate and folate prompted us to re-evaluate the recently reported high affinity of folates for kainic acid membrane binding sites. We found that folic acid competed only very weakly with [3H]kainic acid for binding sites on striatal, cortical, hippocampal, amygdaloid, and cerebellar membranes. It is thus concluded, that folate is not a good candidate for an endogenous kainate-like substance. We propose intracerebral injections of folic acid as a useful tool to study the vulnerability of brain structures to anoxic-ischemic conditions.

Amygdala↗

Right to left intracardiac shunt: a unique presentation of metastatic cardiac disease.

A 54 year old man presented with signs and symptoms of severe hypoxemia. He had a history of a nasopharyngeal epidermoid carcinoma that was thought to have been totally eradicated 2 years earlier. He was found to have a right to left interatrial shunt through a patent foramen ovale due to tricuspid valve obstruction by a solitary cardiac metastasis. No other such reported case of a metastatic cardiac lesion could be found.

Carcinoma, Squamous Cell↗

Evaluation of aortic stenosis by continuous wave Doppler ultrasound.

Twenty-four patients with suspected aortic stenosis (Group I) were evaluated noninvasively by continuous wave Doppler ultrasound before undergoing cardiac catheterization. Twenty normal subjects served as the control group (Group II). Maximal velocity measurements in the ascending aorta ranged from 3.0 to 5.8 m/s (mean 4.34 +/- 0.65) in Group I versus 1.0 to 1.6 m/s (mean 1.28 +/- 0.16) in Group II (p less than 0.001). Using the Bernoulli equation, the peak pressure gradient across the aortic valve was calculated from the maximal velocity in the Group I patients. The results correlated well with the peak aortic valve gradient obtained at cardiac catheterization (r = 0.79). In 20 of these 24 patients, the peak Doppler gradient was within 25% of the gradient found at cardiac catheterization. In three patients, the Doppler study under-estimated the gradient by slightly more than 25% but still detected the presence of significant aortic stenosis. The Doppler technique failed to detect critical aortic stenosis in only one patient. Significant overestimation of the gradient by Doppler measurement did not occur in any patient. The technique was particularly helpful in older patients in whom other noninvasive tests often yield inconclusive results. An important but infrequent limitation of the technique is underestimation of the gradient that occurs when the angle of incidence between the ultrasound beam and aortic blood flow is too large. The findings indicate that continuous wave Doppler ultrasound provides a reliable estimate of the valvular gradient in most patients with aortic stenosis.

Adult↗

Dichloro[1,2-bis(4-hydroxyphenyl)ethylenediamine]platinum(II) complexes: an approach to develop compounds with a specific effect on the hormone-dependent mammary carcinoma.

Stereoisomeric dichloro [1,2-bis(4-hydroxyphenyl)ethylenediamine]platinum(II) complexes (meso-3a, (+/-)-3b, (+)-3c, (-)-3d) and their N,N'-dibutyl derivatives (meso-4a, (+/-)-4b, (+)-4c, (-)-4d) were synthesized and tested on antitumor activity. The most active compound, 3d, shows a modest inhibition of the [3H]estradiol receptor interaction and causes a marked effect on the growth of the hormone-dependent human MCF 7 breast cancer cell line. It is also active on the hormone-independent human MDA-MB 231 breast cancer cell line, on the ADJ/PC6 plasmacytoma of the Balb/C mouse, and on the L 5222 leukemia of the BD IX rat. Apparently the inhibition of the MCF 7 cell line is not mediated by the estrogen receptor system. Histopathological studies on 3d revealed very low toxicity.

Animals↗

Human neutrophils increase expression of C3bi as well as C3b receptors upon activation.

We used monoclonal antibodies and flow cytometry to study the expression of the receptors for the complement fragments C3bi (CR3) and C3b (CR1) on human polymorphonuclear neutrophil leukocytes (PMN). Expression of both receptors was minimal on cells stained in anticoagulated whole blood incubated at 0 degree or 37 degrees C. PMN isolated with Percoll density gradients and held at 0 degree C also had only minimal expression of both receptors. With the isolated cells, however, a spontaneous increase in expression of both receptors occurred upon warming to 37 degrees C. This did not represent complete expression of either receptor since additional increments in surface expression could be induced upon stimulation with N-formyl-methionyl-leucyl-phenylalanine or Raji cell supernatant. The increases in complement receptor (CR) expression appeared to be specific since there were no changes in expression of the Fc gamma receptor or beta-2-microglobulin under any of these conditions. The increased CR expression seems to involve translocation from an intracellular pool since it is complete within minutes and is not blocked by puromycin or cycloheximide. These results demonstrate that both CR3 and CR1 expression increase rapidly upon activation of PMN and that isolated cells can be used to study this phenomenon, which may be a critical part of neutrophil function in vivo.

Antibodies, Monoclonal↗

Intrapericardial instillation of sodium hydroxide: failure to produce pericardial symphysis.

Previously reported clinical studies have suggested sodium hydroxide as an effective agent in causing pleural symphysis. To explore the sclerosing potential of this agent, we instilled 0.5% sodium hydroxide into the pericardium of four dogs. Normal saline was instilled into the pericardium of one control dog. Echocardiograms, 24 hour EKG monitoring and intracardiac pressures were recorded. One dog was sacrificed at the end of 24 hours, another at the end of seven days and three other dogs were sacrificed at the end of 28 days. ST elevations and prolonged episodes of supra-ventricular and ventricular tachycardia were noted during and within 24 hours after the intrapericardial instillation of sodium hydroxide in all the dogs. No arrhythmias were noted in the control dog. None of the dogs showed pericardial symphysis. These results suggest that sodium hydroxide causes serious cardiac arrhythmias when instilled intrapericardially and is of limited value in causing pericardial symphysis.

Animals↗

The limited utility of the dexamethasone suppression test for the diagnostic process in psychiatry.

In 231 psychiatric in-patients, the 1 mg or 1.5 mg DST with blood samples at 0900 h, 1600 h and 2300 h and a post-dexamethasone plasma cortisol threshold of greater than or equal to 5 micrograms/dl were tested for their differential diagnostic utility in clinical psychiatry. Neither test significantly separated endogenous depressed patients from patients with other depressive or non-depressive psychiatric disorders. Studies of the 1 mg or 1.5 mg DST in 75 healthy subjects revealed about 12% of cortisol non-suppressors, when a post-dexamethasone cortisol threshold of greater than or equal to 5 micrograms/dl was used. This seemed to be an unacceptably low specificity of the test in normal subjects. A threshold criterion of greater than or equal to 8 micrograms/dl, however, yielded only 2.7% of non-suppressed normal subjects. Analyses of the DST data of the psychiatric patients, using a cortisol threshold of greater than or equal to 8 micrograms/dl, also failed to reveal a significantly higher specificity of the DST for endogenous depression. However, it was demonstrated that intervening variables such as stress due to hospital admission, drug withdrawal, suicidal turmoil, weight loss, as well as a low dexamethasone plasma level, enhance the rate of abnormal DST results in psychiatric in-patients, regardless of their diagnostic classification.

Adult↗

Pituitary and gonadal function in pubertal and adult male rabbits with pseudohermaphroditism secondary to immunization of mothers against testosterone.

Pituitary and testicular function was studied in pubertal and adult rabbits with pseudohermaphroditism secondary to immunization of mothers against testosterone. Circulating testosterone, LH and FSH levels showed a developmental pattern during sexual maturation, similar to that observed in controls. Plasma FSH levels were elevated in male pseudohermaphrodites despite normal plasma testosterone concentrations. Fighting, male sexual behaviour and coitus occurred normally as in controls. The testicular response to endogenous elevated LH levels and the pituitary LH and FSH responses to LRH injection and to castration were similar in affected males and in controls. These observations suggest that inhibition of the central effects of androgens during the embryonic and perinatal period has little or no effect on the differentiation and maturation of the hypothalamo-pituitary-testicular axis in rabbit.

Animals↗