Derepressed alloantigen in transplacentally induced lung tumor coded for by H-2 linked gene

A transplacentally induced lung tumor of strain C3Hf mice grows progressively when transplanted to (C3Hf X A)F1 hybrid mice but not when transplanted to C3Hf recipients. Progressive tumor growth occurs in [(C3Hf X A)F1 X C3Hf] backcross mice inheriting the H-2a haplotype from the F1 parent. Furthermore, radioresistant immunity to the lung tumor can be induced in C3Hf mice by immunization with normal tissue of B10.A and B10.A(2R) but not of B10 or B10.A(5R) strain mice.     

Energetics of triosephosphate isomerase: deuterium isotope effects in the enzyme-catalyzed reaction

The effect of isotopic substitution of the specifically labilized hydrogen in the substrates of triosephosphate isomerase on the steady-state rates of the enzyme-catalyzed reaction has been examined. The k cat value for the enzyme-catalyzed transformation of [1(R)-2H] dihydroxyacetone phosphate is 2.9 times smaller than that for the 1(R)-1H compound. Because of the rapid loss of 2H to solvent from the enzyme-enediol complex, this factor represents the full kinetic isotope effect of the proton abstraction step. The values of k cat and of Km for D-[2-2H]glyceraldehyde 3-phosphate are indistinguishable from those of the 2-1H material. This arises from the rapid loss of 2H from the enzyme-enediol intermediate, which results in 1H rather than 2H transfer in the rate-limiting step. The steady-state kinetic results reported in this paper qualitatively confirm and quantitatively extend the results from the previous papers on the variation of the free energy along the reaction path.     

Comparative structural and immunochemical properties of leghaemoglobins

Circular dichroism studies on leghaemoglobins from snake bean, lupin, serradella and other plants show that, in common with soybean (reported earlier) they have a similar overall polypeptide chain conformation and haem environment and orientation. Immunochemical studies, on the other hand, suggest that the antigenic determinants on the surface of the leghaemoglobins vary considerably. Thus, firstly the alpha-helix content of the leghaemoglobins as a class is very similar (60-65%) and approaches that of the myoglobins, secondly, the sign, magnitude and shape of their circular dichroism spectra in the near ultraviolet, Soret and visible regions suggest close similarities in the environment and orientation of a structurally important tryptophan residue and of the haem moiety, and thirdly, there is comparatively weak haem-protein interaction. The extent of immuno cross-reactivity was found to be best deomonstrated using the Farr radioimmunoassay procedure. The results were (a) 5 leghaemoglobins from one plant (soybean) crossreacted completely but with varying affinities. (b) The extent of cross reactivity between leghaemoglobins from different plants was compared to that within a single plant; the reaction of antiserum to a soybean leghaemoglobin with a serradella leghaemoglobin was weak, with a snake bean leghaemoglobin still weaker (and incomplete) while lupin leghaemoglobins showed no cross reactivity at all. (c) The "rapid" attenuation of cross reactivity among different plant leghaemoglobins is explicable in terms of the extensive amino acid substitutions which have been demonstrated in the literature and in the present studies. (d) In view of this rapid divergence it is not surprising that sperm whale and horse heart myoglobins showed no cross reactivity with soybean leghaemoglobins. In summary, amino acid substitutions in the leghaemoglobin family are conformationally but not immunochemically conservative.     

Cerebral ischemic events associated with prolapsing mitral valve

Twelve patients who had no evidence of arteriosclerotic cerebral vascular disease, lacked hypertension or coagulation defect, and had not been receiving contraceptive therapy had recurrent transient cerebral ischemic attacks (TIAs) and partial nonprogressive strokes. All had prolapsing mitral valve proved by angiocardiography. The average age was 38 years, compared with 62 years in a larger series of patients with TIA associated with arteriosclerosis. We propose that the ischemic events are related to emboli emanating from the abnormal mitral valve with or without an associated paroxysmal cardiac arrhythmia.     

Engineered Neutral Phosphorous Dendrimers Protect Mouse Cortical Neurons and Brain Organoids from Excitotoxic Death

Nanoparticles are playing an increasing role in biomedical applications. Excitotoxicity plays a significant role in the pathophysiology of neurodegenerative diseases, such as Alzheimer’s or Parkinson’s disease. Glutamate ionotropic receptors, mainly those activated by N-methyl-D-aspartate (NMDA), play a key role in excitotoxic death by increasing intraneuronal calcium levels; triggering mitochondrial potential collapse; increasing free radicals; activating caspases 3, 9, and 12; and inducing endoplasmic reticulum stress. Neutral phosphorous dendrimers, acting intracellularly, have neuroprotective actions by interfering with NMDA-mediated excitotoxic mechanisms in rat cortical neurons. In addition, phosphorous dendrimers can access neurons inside human brain organoids, complex tridimensional structures that replicate a significant number of properties of the human brain, to interfere with NMDA-induced mechanisms of neuronal death. Phosphorous dendrimers are one of the few nanoparticles able to gain access to the inside of neurons, both in primary cultures and in brain organoids, and to exert pharmacological actions by themselves.     

A computer model of intracranial dynamics integrated to a full-scale patient simulator

The ability to visualize intracranial dynamics during simulated clinical scenarios is a valuable tool for teaching brain physiology and the consequences of different medical interventions on the brain. Studies have isolated physiologic variables and shown their effects on brain dynamics. However, no studies have shown the combined effects of these variables on intracranial dynamics. This brain model offers one approach that brings all these relationships together and shows how they affect the dynamics of the brain. The brain model obtains its physiologic inputs from a full-scale patient simulator which responds to clinical interventions. This integration allows individuals working on the patient simulator to see the effects of their actions on brain dynamics. The brain model gives a real-time display of intracranial events (cerebral metabolic rate, cerebral blood flow, cerebral blood volume, cerebral perfusion pressure, and intracranial pressure) and responds to changes in the pulmonary and cardiovascular condition of the patient simulator.     

Rupture recurrence after surgical repair of postinfarction ventricular septal rupture. Influence of early thrombolysis

OBJECTIVES: The aim of this study was to identify factors causing rupture recurrence after surgical repair of postinfarction ventricular septal rupture and to evaluate the indication for reoperation. PATIENTS: Recurrence of rupture was analysed in 25 out of a series of 109 patients who underwent surgical repair for postinfarction ventricular septal rupture between 1980 and 1992 in our institution. RESULTS: The mean interval between initial operation and recurrence was 3.6 days with a median of 2 days. Multivariate logistic regression analysis identified early thrombolysis after infarction (P = 0.0085) as a risk factor for recurrence of the rupture. Rupture recurrence occurred more in the anterior then in the posterior infarction site, although non-significant. Reoperation was indicated in 15 patients, in 13 for postrecurrent cardiac failure. The main determinant of cardiac failure was a large postrecurrent shunt (P = 0.05). The mean interval between initial operation and reoperation was 136 days with a median of 101 days. In 6 patients a combined apical ventricular septal rupture recurrence and anterior ventricular aneurysm was found, in 9 patients the recurrent rupture was proximally located, without concomitant aneurysm formation. Of 15 patients who were reoperated, one died in hospital and three after the in-hospital period. Of 10 patients treated conservatively, one died in hospital and two after the in-hospital period. One residual ventricular septal rupture closed spontaneously. CONCLUSIONS: Rupture recurrence is mainly determined by early thrombolysis. Postrecurrent cardiac failure, as the main indication for reoperation, is dependent on postrecurrent shunt size.