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Biomedical subjects

J J Franks

Publications and source records attributed to J J Franks.

At least 55 records · Page 3Linked to original sources

Inhibitory effect of quinidine on plasma pseudocholinesterase activity in pregnant women.

The effect of quinidine at therapeutic and subtherapeutic concentrations on pseudocholinesterase activity in the plasma of 16 normal pregnant women was studied. The mean plasma pseudocholinesterase activity in the absence of quinidine (control) was 0.67 +/- 0.11 U/ml. The mean pseudocholinesterase activity in the presence of quinidine at concentrations of 0.5, 1.0, 2.0, and 5.0 micrograms/ml 0.48 +/- 0.09, 0.38 +/- 0.09, 0.29 +/- 0.10, and 0.19 +/- 0.09 U/ml, respectively. At therapeutic concentrations needed to treat cardiac arrhythmias (2 to 5 micrograms/ml), quinidine inhibited pseudocholinesterase activity by 60% to 70%. All the plasma samples had a normal dibucaine number (78 to 85). We recommend caution when succinylcholine and/or ester-type local anesthetics are used in pregnant women receiving quinidine.

Adolescent↗

Fibrin(ogen)olysis in polymyalgia rheumatica and temporal arteritis: preliminary findings on association with disease activity.

Postulating an increased production of fibrin(ogen)olytic degradation products (FDP) and an abnormality of fibrinogen metabolism in polymyalgia rheumatica (PMR) and temporal arteritis (TA), we studied 16 PMR/TA patients and 10 control subjects using a sensitive radioimmunoassay for a specific type of FDP, namely, fibrin(ogen)-related D-antigen. Median serum D-antigen levels were increased five-fold in those 11 PMR/TA patients who were untreated compared with control subjects. In the five PMR/TA patients who were treated with prednisone the median D-antigen levels were not significantly different from those of the healthy controls. D-antigen concentration correlated significantly (r = 0.83) with ESR in the seven untreated PMR patients. In PMR patients prednisone therapy was followed by a reduction of serum D-antigen levels.

Aged↗

Marrow biopsy and survival in multiple myeloma.

Pretreatment posterior iliac crest bone marrow biopsies were obtained from 26 multiple myeloma patients. Biopsies were processed in methacrylate. The percentage of myeloma tissue, myeloid tissue, and fat was estimated in each biopsy. In 20 patients who died there was a positive correlation between the percent of myeloid tissue in posterior iliac crest biopsies and survival time (r = 0.47, P less than 0.025), but no correlation could be demonstrated between percentage of myeloma tissue and survival time. The ratio of percentage of myeloid tissue to percentage of myeloma tissue also was related to survival. Six deceased patients with ratios greater than one had a median survival of 4.4 years, compared with 1.8 years in 12 deceased patients with ratios less than one. These medians differ significantly (P less than 0.05). Seven patients also had simultaneous biopsies of the posterior iliac crest and either or both the greater trochanter and the proximal tibia. All five greater trochanter biopsies showed extension of both myeloma tissue and myeloid tissue into the proximal appendicular skeleton.

Adipose Tissue↗

Differences in judgments of learning difficulty.

Academically successful and less successful fifth graders were asked to make judgments about the ease of understanding and remembering various sentences and were given the opportunity to attempt to remember some of them before being asked to judge new sets of sentences. The results of the first experiment indicate that, at the beginning of the experiment, the successful students were much more likely than their less successful peers to realize that sentences expressing arbitrary relationships were more difficult to remember. These differences became even greater after students were given the opportunity to attempt to remember some of the sentences they had judged initially. The memory performance of the successful students also improved as they became more familiar with the experimental task, but the performance of the less successful students did not. The results of the second experiment showed that less successful students who had received appropriate training were able to use information about the arbitrariness of relationships as the basis for their judgments of learning difficulty. The training also facilitated their ability to remember. Implications of these findings are discussed.

Child↗

Effect of fibrinogenolytic products D and E on fibrinogen and albumin synthesis in the rat.

Previous studies are in conflict over the effect of infusing mixed fibrinogen-fibrin degradation products on fibrinogen synthesis, as determined by changes in fibrinogen concentration or by incorporation of labeled amino acids into fibrinogen. We have injected purified homologous fragments D1 and E into rats and measured their fibrinogen and albumin synthetic rates by the [14C]carbonate technique, a method that provides quantitative estimates of hepatic secretory protein synthesis. Fibrinogen fractional synthetic rates were increased 2.5 times in animals injected with fragment D1, compared with saline-injected controls. No increase were observed in fragment E-injected animals. Neither fragment produced changes in albumin synthesis. Fragment D increased plasma fibrinogen concentration, but did not raise plasma haptoglobin levels. These results suggest that fragment D is a regulator of fibrinogen synthesis.

Albumins↗

Sites of D-domain interaction in fibrin-derived D dimer.

We have examined the plasmic digestion products of fibrin formed in the presence of dansylcadaverine, the fluorescent D dimer, to determine whether they are held together not only by the cross-link region on the gamma chain but also by other interactions on the D domain. Antibodies to the D dimer reacted 8X more strongly with sites on the D dimer (purified or in the presence of E) than with sites on fibrinogen or plasmin-digested fibrinogen. The reactivity of this surface site was lost when the gamma chain was cleaved by plasmin after the molecule had been destabilized by the removal of calcium ions, thus breaking the covalent linkage of the homodimer. The noncovalent D dimer retained its dimeric structure by the criteria of molar volume, measured by fluorescence polarization, and molecular sieving. The noncovalently attached, cross-link-containing peptide bound tightly to the parent molecules at higher temperatures but rotated more freely below 15 degrees C, and could be lost from the parent molecules without destroying the dimeric structure. We therefore propose that the forces maintaining the dimeric structure of the noncovalently joined molecule are not solely located at the gamma-chain cross-link region. These other sites on the D domain are therefore candidates for the initial fibrinogen polymerization site and may also have a role in fibrinogen half-molecule assembly.

Animals↗

Enhanced thrombin and plasmin activity with exercise in man.

We measured products of thrombin and plasmin action and of the platelet release reaction during exercise to determine if the well-known effect of exercise on in vitro coagulation and fibrinolytic tests reflects activity of these systems in vivo. Plasma fibrinopeptide A, produced by thrombin-mediated proteolysis of fibrinogen, increased with graded treadmill and cycle exercise to postexercise levels of 20--30 times resting values. Fibrin/fibrinogen-related D antigen increased in a similar fashion with peak levels at maximal O2 uptake. Plasma-activated partial thromboplastin times fell as fibrinopeptide A levels increased. Unheated fibrin plate lysis areas increased as D antigen concentrations rose, indicating increased release of plasminogen activator. In contrast to activation of the soluble coagulation and fibrinolytic systems, platelet counts and plasma levels of beta-thromboglobulin, a platelet release protein, did not change significantly with exercise. The effect of exercise on thrombin and plasmin was not influenced by prior physical training, but appeared to be less with cycle exercise than with treadmill exercise.

Blood Coagulation↗

Elevated fibrin(ogen) degradation products in the adult respiratory distress syndrome.

During a 60-h period after the onset of either the adult respiratory distress syndrome (ARDS) in 14 patients, or similar predisposing conditions without respiratory insufficiency (non-ARDS) in 12 patients, blood was obtained 3 times for assessment of coagulation, fibrinolysis, and complement. Platelet counts decreased progressively in both groups, and a platelet release protein, Beta-thromboglobulin, was similarly increased in both groups. Fibrinopeptide A concentrations were similarly increased in both groups. Hemolytic activity of complement components C3 and C5 was within the normal range in both groups. In contrast, the fibrin/fibrinogen degradation product, D-antigen, was significantly increased in the ARDS group over all time periods (p < 0.01). These findings suggested that higher concentrations of circulating fibrin/fibrinogen degradation products are associated with ARDS itself, either as a marker or more extensive microvascular injury or as a possible mediator of injury.

Adolescent↗

Thoracic duct fistula and renal transplantation.

Thoracic duct drainage (TDD) was established for 21-115 days in 40 kidney recipients with an average removal per patient day of 4.7 1 lymph and 1.88 billion cells. Cellular and humoral immunity were depressed. TDD and immunosuppressive drugs were started at transplantation in 35 recipients of cross-match negative grafts. Although the results were better than in precedent non-TDD controls, eight patients rejected their grafts before a full TDD effect, and three of the eight developed predominantly anti-B lymphocyte cytotoxic antibodies which were probably responsible for positive cross-matches with their next donors. With continuing TDD, all eight patients had good initial function after early retransplantation. In five more "nontransplantable" patients with performed cytotoxic antibodies, TDD was started 30-56 days before transplantation. In these five pretreated patients, antibodies persisted with positive antidonor cross-matches. Hyperacute rejection occurred repeatedly in two patients with high anti-T (and anti-B) titers, but was surmounted in three patients with lower titers. From the clinical and immunologic data, we have concluded that TDD should be used for pretreatment of all cases with or without prior antibodies, and have suggested an adjustable management plan that takes into account new developments in antibody monitoring.

Adolescent↗

Comparison of procoagulant activities in extracts of normal and malignant human tissue.

Cancer procoagulant A (CPA) was originally described in extracts of tumor tissue, but whether this represented a quantitative and/or a qualitative difference from procoagulant activity in normal tissue extracts was not clear. Procoagulant activity was quantitated in extracts of 12 matched normal and malignant human tissue samples from the large intestine, breast, lung, and kidney. The specific activity of procoagulants in the tumor extracts was not greater than that in the extracts of normal tissue. Two enzymatic characteristics of CPA that distinguish it from tissue thromboplastin are its inhibition by diisopropylfluorophosphate (DFP) and its lack of dependence on factor VII. These specific tests were used to evaluate qualitative differences between procoagulants from normal and malignant intestinal tissues. In the paired normal and malignant tissue extracts, all tumor samples were inhibited by DFP and were active in factor VII-depleted bovine plasma (F7D-BP). In contrast, the extracts of normal tissue were insensitive to DFP and, except for one extract, were inactive in F7D-BP. Four of 9 other tumor extracts (44%) were positive for both of these tests for CPA, whereas the other 5 extracts were positive for only one of the two tests. The results suggest that extracts of normal and malignant tissues contained similar levels of procoagulant. However, malignant tissue contained a procoagulant enzymatically different from normal tissue thromboplastin. Furthermore, most of the malignant tissue extracts seemed to contain little or no thromboplastin.

Blood Coagulation Factors↗