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Biomedical subjects

J D Morris

Publications and source records attributed to J D Morris.

At least 37 records · Page 2Linked to original sources
PubMed1989

Scrape-loading of Swiss 3T3 cells with ras protein rapidly activates protein kinase C in the absence of phosphoinositide hydrolysis.

Scrape-loading has been used to analyse the biochemical function of purified p21ras protein. We have shown that scrape-loading oncogenic p21ras into quiescent Swiss 3T3 cells causes morphological transformation of 90% of the cell population within 15 h. Since large numbers of cells can be loaded with p21ras, early induced biochemical changes can be analysed. In this way we have shown that oncogenic p21ras causes rapid activation of protein kinase C five minutes after introduction of protein, but that ras protein fails to stimulate measurable inositol phosphate formation. It appears, therefore, that the stimulation of protein kinase C activity is due to a ras induced increase in diacylglycerol from a source other than inositol phospholipids. Efficient stimulation of DNA synthesis by oncogenic p21ras only occurs in the presence of insulin. This stimulation of DNA synthesis by ras is absolutely dependent on functional protein kinase C activity.

Cycloheximide↗
PubMed1988

Ca2+ and pH responses to sequential additions of mitogens in single 3T3 fibroblasts: correlations with DNA synthesis.

The progression of Swiss 3T3 fibroblasts from the quiescent state (G0) through G1 to DNA synthesis in S phase generally requires the synergistic action of two mitogens. The main aim of this study was to compare systematically the early Ca2+ and pH responses in quiescent cells to all of the pair combinations of eight mitogens (bombesin, platelet-derived growth factor, vasopressin, prostaglandin F2 alpha, epidermal growth factor, 12-O-tetradecanoyl phorbol-13-acetate, insulin, 8-bromo-cAMP) with their subsequent effects on DNA synthesis. Each of the mitogens which caused inositol phosphate accumulation (bombesin, platelet-derived growth factor, vasopressin, prostaglandin F2 alpha) also activated Ca2+- and phospholipid-dependent protein kinase (protein kinase C) and generated both the Ca2+ and pH responses, although epidermal growth factor also generated the ionic responses without causing release of inositol phosphates or activation of protein kinase C. For sequential mitogen additions the ionic signals were measured in single cells as well as in cell populations to avoid ambiguities due to heterogeneity in the responses of the cells to the various mitogens. The modulating effects of the mitogens on the [Ca2+]i responses to subsequent mitogen additions varied widely, but detailed comparisons showed that the pattern of blocking effects could not be attributed solely to the effect of the first mitogen causing either maximal breakdown of phosphatidylinositol 4,5-bisphosphate or complete depletion of the intracellular Ca2+ pool or activation of protein kinase C. From these analyses it was concluded that the requirement for two mitogens for effective DNA synthesis could not be attributed to the summation to a critical threshold of either the ionic signals or phosphatidylinositol 4,5-bisphosphate breakdown, and that these responses are insufficient by themselves to cause the cells to progress to DNA synthesis in S phase.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Contributions of the pulvinar to visual spatial attention.

Neurons in a subdivision of the pulvinar resemble those in parietal cortex: many respond to visual stimuli, some of these have a spatial selection mechanism, and some have signals about the occurrence of eye movements. These properties suggest a role in visual spatial attention. Injection of GABA-related drugs into this part of the pulvinar alters animals' performance on an attentional task. These data support our hypothesis that the pulvinar contributes to visual spatial attention.

Animals↗
PubMed1987

Eight drugs in one day chemotherapy for brain tumors: experience in 107 children and rationale for preradiation chemotherapy.

The development of a new multidrug chemotherapy regimen for primary brain tumors was based upon the cellular heterogeneity within individual tumors, the Goldie-Coldman and Price-Goldie-Hill hypotheses, and known agonistic effects of certain drug combinations and sequences. Eight drugs (vincristine [VCR], hydroxyurea, procarbazine, CCNU, cisplatin, cytosine arabinoside [Ara-C] high-dose methylprednisolone, and either cyclophosphamide or dacarbazine) were administered within 12 hours in an attempt to minimize myelosuppression. Courses were repeated at 2- to 4-week intervals. The regimen was devised to include lipid and water soluble drugs, polar and nonpolar agents, phase-specific and cell-cycle independent agents, and antineoplastics with different mechanisms of action. More than 330 courses of the regimen were administered to 107 children with brain tumors whose tumor had recurred or had been incompletely resected at diagnosis. Tumor response according to protocol-specified criteria and independent review was evaluable in 78% of the patients. After just two cycles of chemotherapy and within a 4- to 6-week interval, 50% had an objective tumor response including 15.5% who had a complete response (CR). Nephrotoxicity and high-frequency hearing losses were noted after three to five courses of therapy in approximately half of the patients. Transfusions with red cells or platelets and use of antibiotics for fever and neutropenia were required in 10% to 25% of patients. The regimen appears satisfactory for preradiation chemotherapy in newly diagnosed patients with residual tumor after surgery, but it must be compared with standard therapeutic approaches in prospective controlled trials before its relative value can be established.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

The efficacy and timing of operative intervention for spontaneous pneumothorax.

To reassess the role and timing of operative intervention for spontaneous pneumothorax, 119 patients were retrospectively reviewed to compare recurrences, complications, and hospital stay between a nonoperative group (Group 1) and an operative group (Group 2). Total hospital days were greater in Group 2, but excluding the length of preoperative stay, the number of hospital days were similar in both groups. Group 1 patients more than 40 years old had a longer postoperative hospitalization, but not a higher rate of complication. Overall, morbidity was not different between the two groups, and there were no immediate or perioperative deaths in either group. There were no recurrences in Group 2. At least 11 of the 49 patients in Group 1 had a recurrence (p = .012). Considering the excellent results achieved with operative pleurodesis and the total hospital days accrued with nonoperative therapy, operative pleurodesis should be considered if an active leak persists more than three days after the initial episode of spontaneous pneumothorax or at the time of the first recurrence in the hospitalized patient.

Adolescent↗
PubMed1985

Modified methods for preparation of cryostat sections of skeletal muscle.

We developed two modified methods for the preparation of cryostat sections of skeletal muscle: one using solid carbon dioxide and the other using the ultra-low freezer to prepare 2-methylbutane (isopentane) for freezing of skeletal muscle. The results were quite satisfactory, with good preservation of cellular details and histochemical properties. Freezing artifacts were minimal when compared with the standard liquid nitrogen method.

Adenosine Triphosphatases↗
PubMed1985

Early response pattern analysis of the mitogenic pathway in lymphocytes and fibroblasts.

The early biochemical responses stimulated by the action of mitogens and growth factors on mouse thymocytes and 3T3 fibroblasts are analysed as part of a systematic attempt to define the mitogenic pathways from G0 to S phase in these cells. Although the primary response to each mitogen can be distinguished by the pattern of secondary responses they initiate, there is substantial overlap in these responses. The aim is therefore to determine whether there is early convergence on a common mitogenic pathway, defined by a sequence of responses obligatory for progression from G0 to S phase for different mitogens and cell types. The 'dual-signal' hypothesis for the mitogenic stimulation of thymocytes is a simple version of a common mitogenic pathway. It proposes that the T-cell receptor initiates the pathway via the breakdown of phosphatidylinositol (4,5)-bisphosphate to generate a Ca signal (from the release of inositol (1,4,5)-trisphosphate) and to activate protein kinase C (from the release of diacylglycerol). The rationale for this hypothesis lies in the co-mitogenic action of the Ca2+-ionophore, A23187, and the phorbol ester, 12-o-tetradecanoyl phorbol 13-acetate, which is assumed to activate specifically protein kinase C. However, detailed analysis of the coupling between some of the early responses, including the Ca and pH signals, phosphatidylinositol (4,5)-bisphosphate metabolism, c-myc gene activation and general metabolic stimulation, indicates clearly that the hypothesis is inadequate to account for the initiation of the normal mitogenic pathway in thymocytes.

Animals↗
PubMed1985

Ulnar neuropathy at the wrist: case report and review of literature.

We present a case of pure motor ulnar neuropathy with sparing of the hypothenar muscles and a review of 55 published cases of ulnar neuropathy at the wrist in which the clinicoanatomic correlation was clearly delineated. We propose a classification of ulnar neuropathies at the wrist divided into five types based on clinical findings, electrophysiologic studies, and clinicoanatomic correlations. Type I: a mixed motor and sensory neuropathy, occurring just outside or within the proximal end of Guyon's canal. II: a pure sensory neuropathy, where the lesion involves the superficial branch of the ulnar nerve (UN) at the wrist but distal to the branch to the m. palmaris brevis. III: a pure motor neuropathy due to a lesion of the deep branch of the UN just distal to the superficial branch but proximal to the branch to the hypothenars. IV: a pure motor ulnar neuropathy with sparing of hypothenars; this lesion occurs on the deep branch of the UN distal to the origin of the superficial branch and distal to the branch going to the hypothenars. V: a distal motor neuropathy in which the lesion occurs just proximal to the branches going to the first dorsal interosseus and adductor pollicis muscles.

Adult↗
PubMed1984

Some mitogens cause rapid increases in free calcium in fibroblasts.

Quiescent 3T3 fibroblasts grown on microcarrier beads and loaded with the [Ca2+] indicator quin2 had a cytosolic free Ca2+ concentration ( [Ca2+]i) of 154 +/- 11 nM (SE; n = 32). Stimulation with the mitogens vasopressin, epidermal growth factor (EGF) or prostaglandin F2 alpha (PGF2 alpha) caused a very rapid increase in [Ca2+]i to a maximum of 200-500 nM after 60-90 s. [Ca2+]i declined thereafter to a level above that in quiescent cells which was maintained for at least 15 min. In contrast no immediate effects on [Ca2+]i were detected after the addition of the mitogens insulin or 12-O-tetradecanoylphorbol 13-acetate (TPA). These studies indicate that early changes in [Ca2+]i may be involved in the action on fibroblasts of some, but not all, mitogens.

Aminoquinolines↗
PubMed1984

Evacuation of calcific valvular debris using a standard Ellik evacuator.

A simple but effective technique is described for removing calcific and other debris following aortic and mitral valve replacement. This technique uses an Ellik evacuator , which is readily available in most operating rooms. An 11-year experience is presented, documenting the efficacy of this method in several hospitals.

Aortic Valve↗
PubMed1984

Acute reaction to protamine. Its importance to surgeons.

Three open heart surgery patients developed noncardiogenic pulmonary edema after administration of protamine following cardiopulmonary bypass. A catastrophic series of events are characteristic of this reaction: 1) sudden onset; 2) severe bronchoconstriction with early extreme difficulty in ventilation; 3) hyperinflation of the lungs; 4) pulmonary hypertension with normal pulmonary wedge or left atrial pressures; 5) progression to fulminant noncardiogenic pulmonary edema; 6) significant mortality; and 7) ventilatory perfusion abnormalities in survivors. Review of the literature reveals three types of reactions to protamine injection of varying severity: 1) brief hypotension; 2) anaphylactoid generalized reaction; and 3) high protein noncardiogenic pulmonary edema with cardiopulmonary collapse. The severity of the reaction had no relation to the dose of protamine. Previous protamine exposure was documented in 14 of 35 cases. Awareness of this reaction is essential for prompt treatment if fulminant pulmonary edema occurs. Administration of epinephrine, steroids, vasopressors, and potassium replacement may be required. Needless use of protamine sulfate should be discouraged.

Acute Disease↗
PubMed1980

Long-term results of open mitral valvuloplasty.

The long-term results of open mitral valvuloplasty in 51 patients are assessed. At the time of operation, 4 patients were in New York Heart Association Functional Class II, 41 in Functional Class III, and 5 in Functional Class IV. Group I (14 patients) had had previous closed mitral commissurotomy. Three patients died 2 to 4 years after open valvuloplasty. One patient died following valve replacement 7 years after the open valvuloplasty. Five others required mitral valve replacement 1 to 12 years following open valvuloplasty. Only 4 of the 14 patients are in Functional Class I or II 10 to 15 years following valvuloplasty. Group II (36 patients) had never undergone a previous mitral operation. Four of them died of progressive myocardial failure 4 to 6 years following valvuloplasty. One patient died of carcinoma of the lung 2 years postoperatively. Six patients underwent valve replacement 6 to 11 years following initial operation. Twenty-six have survived for at least 10 years without additional operation. Fourteen are in Functional Class I, and 12 are in Funcitonal Class II. Open mitral valvuloplasty allows for (1) accurate commissurotomy and careful subvalvular dissection, (2) direct vision to diagnose clot in the left atrial appendage or left atrium proper, (3) accurate assessment of residual or induced mitral regurgitation and immediate repair, and (4) reasonable operative mortality and morbidity.

Adolescent↗
PubMed1978

Wheel running of kangaroo rats, Dipodomys merriami, as related to food deprivation and body composition.

Kangaroo rats deprived of food ran themselves to death in 48 h in wheel cages. Despite the loss of 14.5% of body weight the ratio of water to protein was the same after the run as it was in control rats. Metabolic measurements at rest and in the running wheel and weight loss in the 48-h run were used to estimate fuels used and water expended. Two-thirds of the initial amount of fat and 9% of the protein were metabolized. The terminal mean percentage of body fat was about twice that observed in rats trapped in the spring of 1967, when seed production was low: death in the 48-h run could not have been due to depletion of body fat alone. The powerful activity drive seen in hungary kangaroo rats presumably is intensified in dry years when food is scarce and may deplete their reserves enough to result in death from starvation.

Animals↗
PubMed1977

Serum and urinary amylase levels following pulsatile and continuous cardiopulmonary bypass.

The incidence of elevated serum and urine amylase values was examined in a prospective clinical study of patients subjected to either continuous or pulsatile extracorporeal perfusion. Mean postoperative values for urine and serum amylase were higher in the continuous group, and the incidence of abnormal values was also greater in the continuous group (70 percent versus 32 percent, p less than 0.01). Clinical pancreatitis was absent in both groups. This study documents a high incidence of elevated amylase values following bypass with either modality and provides evidence for possible improved visceral circulation with pulsatile extracorporeal bypass during routine cardiac operations.

Adult↗