William Bosworth Castle: Pioneer of Haematological Clinical Investigation

Elrod, Jeffrey M.; Karnad, Anand B.

doi:10.1046/j.1365-2141.2003.04242.x

Cited by 2 publications

(2 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 1927, Castle, a 30-year-old resident physician at the Thorndike Memorial Laboratory, performed his first set of original experiments that demonstrated the existence of the gastric intrinsic factor for the first time (Castle, 1929;Elrod & Karnad, 2003). Normal human gastric juice alone and nearly raw hamburger meat alone did not stimulate a reticulocyte response when fed to patients with pernicious anaemia.…”

Section: Pernicious Anaemiamentioning

confidence: 99%

Boston city hospital and the thorndike memorial laboratory: the birth of modern haematology

Elrod

Karnad

2003

Br J Haematol

Self Cite

View full text Add to dashboard Cite

SUMMARYEstablished in 1923, the Thorndike Memorial Laboratory at Boston City Hospital was the first clinical research laboratory in a municipal hospital in the United States of America. Minot and Castle, who were the second and third directors of the Laboratory, were pioneer haematologists and clinical investigators of the highest calibre who created an atmosphere at the Laboratory that would foster patient-centred research and attract the best physician-scientists to work and train there. The haematology research division of the Laboratory made important original contributions to the understanding of the pathophysiology of anaemia, the mechanisms of red cell and platelet destruction and the phagocytic role of the spleen, the nature of haemoglobin (normal and sickle cell), the nature of haemophilia and its therapy and the early classification of lymphoma. It contributed to the Thorndike Memorial Laboratory's worldwide reputation as a model research laboratory and established its reputation as the birthplace of modern haematology.It is not merely a question of permitting universities to carry on research within the hospital walls, but of actually providing laboratories, equipment, technicians, and salaries for professional workers -it is, in fact, a question of realizing that the fostering of medical research is one of the most important means of enabling a hospital to perform its full function of giving the best medical care to the sick. Francis Weld Peabody (1923)

show abstract

Section: Pernicious Anaemiamentioning

confidence: 99%

Boston city hospital and the thorndike memorial laboratory: the birth of modern haematology

Elrod

Karnad

2003

Br J Haematol

Self Cite

View full text Add to dashboard Cite

show abstract

“…These conditions were later determined to be associated with vitamin B12 deficiency. In the early 20th century, effective treatment of pernicious anemia was established by using quantities of liver concentrate (later determined to contain vitamin B12) along with an intrinsic factor contained in gastric juice, with contributions by George Whipple, Edwin Cohn, William Castle, William P. Murphy, and George Minot [2][3][4][5]. Whipple, Murphy, and Minot shared the 1934 Nobel Prize in Physiology or Medicine for their work [5].…”

Section: Introductionmentioning

confidence: 99%

The Miracle of Vitamin B12 Biochemistry

Spataru

2024

Reactions

View full text Add to dashboard Cite

For decades, the comparison of experimental data with theoretical results in studying the biochemistry of vitamin B12 has been very confusing. While the methylcobalamin cofactor-dependent Methionine Synthase process can undergo unlimited turnovers, and some of the adenosylcobalamin-dependent processes run with close-to-unity equilibrium constants (e.g., with close-to-zero energy barriers), the DFT and QM/MM based on density functional theory, the most used and appreciated methods for calculating the electronic structure of molecules, have been showing a much shorter than experimental-determined Co-N distances in the vitamin B12 cofactors of Co+2 and the inadequate large energetic barriers of their enzymology bioprocesses. The confusion was even larger since some in vitro experimental data showed large barriers to the vitamin B12 cofactor reactions (which in fact play a destructive role in the Methionine Synthase process and which barriers were caused mostly by the influence of the solvents in which the reaction took place). It reached the point where solid contributions to the study of the biochemical processes of vitamin B12 were almost officially questioning the correctness of the experimental determination of the Co-N chemical bond distances in the cobalt(II) cofactors of vitamin B12. Unexpectedly, all the theoretical biochemistry of the vitamin B12 cofactors began to agree with all in vivo experimental data only when they were treated with the MCSCF method, the method that considers the orbital mixing, or in other words, the Pseudo-Jahn–Teller Effect. MCSCF data establish unknown mechanistic details of the methyl radical and hydrogen transfers, the origin of the electronic transfers between bioreagents, and the nature and the relationship between the bioreactions. The Pseudo-Jahn–Teller Effect, e.g., orbital mixing, governs vitamin B12 chemistry in general and provides insight into particular details of vitamin B12-dependent reactions in the human body. It turns out that the DFT or QM/MM based on DFT method theoretical data are incongruent with the experimental data due to their limitations, e.g., the unaccounted-for effects of orbital mixing.

show abstract

William Bosworth Castle: Pioneer of Haematological Clinical Investigation

Cited by 2 publications

References 21 publications

Boston city hospital and the thorndike memorial laboratory: the birth of modern haematology

Boston city hospital and the thorndike memorial laboratory: the birth of modern haematology

The Miracle of Vitamin B12 Biochemistry

Contact Info

Product

Resources

About