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Biomedical subjects

J Meyerhoff

Publications and source records attributed to J Meyerhoff.

At least 19 recordsLinked to original sources

Segregated mathematical model for the fed-batch cultivation of a high-producing strain of Penicillium chrysogenum.

A new segregated mathematical model for the penicillin fed-batch process is presented and applied to the growth of the pellet-forming, industrially used high-producing strain Penicillium chrysogenum S2. The model comprises two kinds of biomass (growing and producing, nongrowing and still producing), cell lysis, and complex medium as an important substrate for primary growth. In accordance with our experimental observation, product formation is not inhibited by glucose, but related to the growth rate. Maintenance metabolism is cell age-dependent. The model was verified with two sets of experimental data including exhaust gas measurements while keeping the estimated parameters almost constant. The presented model derived from that of Bajpai and Reuss (1980, 1981) does not describe our data properly. The particular influence of the pellet structure on the model is discussed. The necessity of new model assumptions (e.g., different kinds of biomass, non-constant maintenance coefficient) is explained by cell damage by lysis and shear forces, and the succeeding repair processes.

Biotechnology

The role of the T cell costimulator B7-1 in autoimmunity and the induction and maintenance of tolerance to peripheral antigen.

T cell tolerance to peripheral antigens is believed to result mainly from the inability of parenchymal cells to present antigens in an immunogenic form due to the lack of expression of T cell costimulator. We found, however, that transgenic expression of the T cell costimulator B7-1 on the islets of Langerhans is not sufficient to abolish the in vivo tolerance to islets antigen. Here, we present evidence indicating that the level of major histocompatibility complex (MHC) antigen expressed by islet cells plays a critical role. Mice coexpressing the B7-1 transgene and high levels of the class II MHC antigen I-E on the islets develop an autoimmune destruction of the beta cells of the pancreas. By contrast, expression of the I-E molecule by islets, in the absence of T cell costimulator, leads to specific tolerance of these autoreactive T cells that cannot be reversed by costimulation with B7-1.

Animals

Conditioned defeat in the Syrian golden hamster (Mesocricetus auratus).

When singly housed under laboratory conditions, male Syrian golden hamsters routinely attack novel conspecific intruders introduced into their home cages. As we report here, after being repeatedly defeated by a larger, more aggressive intruder, such normal territorial aggression on the part of the resident hamsters is replaced by defensive behavior and flight. We have found that such conditioned defeat (CD) can be reliably induced by a series of 5-min trials with an aggressive intruder whether these trials are spread over 4 days or are all given on the same day. A useful behavioral criterion for the appearance of CD during acquisition is the first occurrence of anticipatory flight (AF), i.e., the first time the resident flees from the next aggressive intruder before being attacked. CD shows generalization: Animals trained to the AF criterion (AF Group) subsequently show defensive behavior toward, and even flee from, intruders which show absolutely no sign of aggressiveness. Animals in the AF Group persisted in such defense behavior for two test sessions; animals given three additional defeat trials beyond the appearance of AF (AF + 3 Group) showed a greater magnitude and persistence of defense and flight. A comparison of CD-trained animals which met a non-aggressive intruder (NAI) every day for 5 days to similarly trained animals which met the intruder only on the fifth day after acquisition suggests that CD diminishes passively as a function of time and not as the consequence of repeated encounters with a nonaggressive stimulus animal. We also found that near ideal NAIs could be prepared by treating nonaggressive hamsters with high doses of diazepam: animals so treated locomote more or less continuously around the cage virtually ignoring the subject. An unexpected observation was that subjects in the AF Group tended to closely follow these diazepam-treated, rapidly locomoting NAIs around the cage. Following may be an example of the "risk assessment" activities directed toward a potential threat. The development of a rapid and reliable technique for inducing CD in hamsters sets the stage for further physiological and pharmacological work on this interesting phenomenon.

Aggression

Chronic polyarthralgia in adults.

Rheumatologists often see patients with musculoskeletal complaints who do not always have symptoms and findings that fit into recognized syndromes. Twenty-two such patients with chronic polyarthralgias, including eight with a positive test for ANA (anti-nuclear antibodies), seen over a seven-year period, did not meet criteria for classification or diagnosis of any recognized rheumatologic syndromes. The mean follow-up since onset of symptoms was 77.5 months (range, 13-276 months). During this time, none of the patients' conditions evolved into any previously recognized syndromes. This report on the study of these 22 patients emphasizes the existence of such patients and comments on their prognosis and treatment.

Adult

Stroke in the young. (Part I).

We have discussed some of the more common etiologic categories found in young patients with stroke. Though many of the causes are rare, in the aggregate they account for many of the conditions leading to stroke. In Part II of this series (July 1991), we will explore some of the less common causes of stroke in the young and outline an approach to the patient.

Adolescent

Stroke in the young. Part II.

Evaluation of the young stroke patient often requires an interdisciplinary approach because of the complexity of the problems encountered. We discuss some of the less common causes of stroke and present an approach to the patient.

Adolescent

Hemorrhagic hypotension increases plasma beta-endorphin concentrations in the nonhuman primate.

The role which beta-endorphin plays in the pathogenesis of hemorrhagic hypotension is controversial. In the present experiment, 20 ml/kg of blood was bled from ten healthy male baboons (Papio anubis) over 60 min and then retransfused over the next 30 min. We found that the mean plasma beta-endorphin level increased 109% above baseline (p less than .05) within 15 min after starting hemorrhage, and rapidly returned to a baseline concentration with retransfusion. We conclude that in a primate species, circulating endogenous opioid peptide concentrations increase rapidly in response to sublethal hemorrhagic hypotension and normalize with restoration of the baseline intravascular volume. These findings support the concept that endogenous opioid peptides may mediate the hypotension of shock states.

Animals

Glucagon: endocrine effects and calcium involvement in cardiovascular actions in dogs.

Although the cardiovascular effects of glucagon are understood, its mechanism(s) of action remains unclear. We studied the effects of increasing doses of glucagon (0.001, 0.01, 0.1 mg/kg) on cardiovascular responses in dogs relative to concurrent measurements of circulating glucagon, cyclic AMP, glucose, norepinephrine, epinephrine, triiodothyronine, thyroxine, and cortisol levels. Glucagon-induced increases in plasma cyclic AMP, glucose, and catecholamine concentrations paralleled the heart rate response to glucagon administration. Further studies were conducted to evaluate the role of beta-adrenergic function as well as calcium in mediating glucagon's actions. The tachycardic effects of glucagon (0.01 mg/kg) were unaltered by prior beta-adrenergic receptor blockade with propranolol (3.5 mg/kg total dose). The calcium antagonist verapamil (0.2 mg/kg bolus then 7.5 micrograms/kg/min/infusion) prevented glucagon-induced increases in heart rate. However, the coadministration of glucagon (0.01 mg/kg) with calcium (1.0, 5.0, 10.0, or 50.0 mg/kg) did not alter glucagon's cardiovascular effects. These data indicate that glucagon is a potent tachycardiac agent that also elevates circulating endocrine-related substances. The antagonism of glucagon's tachycardiac effects by verapamil suggests that glucagon's action may be via glucagon-induced calcium movement through calcium channels, although extracellular calcium changes do not alter glucagon's effect. Furthermore, the persistence of glucagon's cardiovascular actions following beta-adrenergic blockade indicates the potential clinical utility of glucagon in reversing the adverse effects of beta-blocker overdoses, and its potential usefulness in treating circulatory shock in "beta-blocked" patients.

Animals

Lyme disease.

Lyme disease is a recently described disease of unknown cause that may involve the skin, joints, heart, or nervous system with characteristic symptoms. The disease follows a bite from an Ixodes tick. Symptoms are generally self-limited and despite the varied and sometimes protracted manifestations, the outcome of the disease is favorable. The epidemiologic, clinical, and laboratory features and treatment of Lyme disease are reviewed.

Antigen-Antibody Complex

Mechanisms of abnormal platelet aggregation in systemic lupus erythematosus.

Platelet aggregation was measured in 14 patients with systemic lupus erythematosus (SLE) and 13 normal controls. Ten SLE patients (group I) showed decreased responsiveness to collagen, while aggregation was normal in 4 (group II). Group I patients also responded poorly to epinephrine. Platelets from SLE patients did not differ from controls in the production of malondialdehyde in response to N-ethylmaleimide, suggesting intact prostaglandin synthetic pathways. However, a significant decrease (P less than 0.005) in platelet levels of the dense granule constituent, serotonin, was noted in group I SLE patients. Treatment of SLE platelet-rich plasma with deoxyribonuclease (DNase) resulted in enhancement of collagen-induced aggregation in 4 group I SLE patients, but not in 1 group II or 8 normal individuals. These results suggest that defective aggregation in SLE platelets may be partially related to a storage pool deficiency state. However, the ability to restore aggregation to collagen by digestion of platelet-rich plasma with DNase indicates that the defect is reversible and that it is perhaps mediated by plasma or platelet-associated DNA.

Blood Platelet Disorders

Decreased platelet serotonin levels in systemic lupus erythematosus.

Platelet serotonin levels were measured in 41 patients with systemic lupus erythematosus (SLE) and 36 normal controls. SLE patients had significantly lower mean serotonin levels (243 +/- 131 versus 414 +/- 175 ng/10(9) platelets, P less than 0.001); the lowest levels occurred in those patients with active disease. No differences in mean platelet serotonin levels were found when we compared patients with or without a history of renal disease, thrombocytopenia, or neuropsychiatric involvement. Decreased release of platelet granule constituents, as measured by plasma levels of the alpha-granule protein, beta-thromboglobulin.

Adrenal Cortex Hormones

Familial Mediterranean fever: report of a large family, review of the literature, and discussion of the frequency of amyloidosis.

Familial Mediterranean Fever is a rare disease which usually begins in childhood and occurs primarily among persons of Mediterranean ancestry. It is characterized by short, self-limited, febrile episodes that may occur alone or with inflammation of serosal surfaces. Some individuals may exhibit an erysipilas-like erythema, almost always on the lower extremities. These attacks are associated with considerable morbidity and may lead to unnecessary surgery, but this disease does not appear to be associated with an increased mortality, except in those individuals who develop amyloid nephropathy. For those patients death usually occurs below the age of 40 years although longer survival has been reported. This complication occurs frequently in Turks and Sephardic Jews, but only rarely in individuals of other ethnic origins. A rare patient may develop destructive changes in a joint that has been subjected to a protracted attack. Recent data indicate that either daily or intermittent colchicine will effectively reduce the severity and frequency of attacks; in some individuals these regimens have induced a complete remission. Preliminary data suggest that colchicine may also reduce the degree of nephropathy associated with amyloidosis. Diagnosis of this disease depends, in the absence of any objective markers, on the recognition of the symptoms in a susceptible individual. Despite the name of the disease, it may occur without a family history and in non-Mediterranean individuals. Most of the attacks, however, are associated with a rise in temperature although the fever spike may be more transient than the associated symptoms. Any individual with suggestive symptoms who is significantly disabled by the attacks should have a therapeutic trial of colchicine.

Adolescent

Temporal changes in growth hormone, cortisol, and glucose: relation to light onset and behavior.

Plasma growth hormone (GH), cortisol, and glucose were measured every 20 min in the last 2 h of a 12-h dark cycle and the first 4 h of a 12-h light cycle in eight environmentally limited rhesus monkeys; additionally, ongoing behavior was scored every 20 min in the last 4 h when the lights in the booths housing the monkeys were on. Episodic fluctuations in levels of GH, cortisol, and glucose occurred. Onset of booth illumination was associated with a significant number of GH secretory bursts (6 of 18), and more than twice as many bursts per hour occurred in the light than in the dark (L:D = 0.44:0.19). The onset of illumination was also associated with significant increases in glucose for the eight animals. In addition, plasma glucose increased concurrently with the onset of 13 of 18 bursts of GH secretion. Monkeys were rated as significantly more alert or aroused when plasma levels of GH and glucose were increasing than when they were decreasing. In contrast plasma cortisol showed small, rhythmic fluctuations over time that did not correlate with booth illumination or degree of behavioral arousal. This latter finding challenges the traditional assumption that cortisol is a sensitive index of behavioral arousal.

Animals