Biomedical subjects

John B Miller

Publications and source records attributed to John B Miller.

5 recordsLinked to original sources

PubMed2005

Tumor predisposition in mice mutant for p63 and p73: evidence for broader tumor suppressor functions for the p53 family.

p63 and p73 are functionally and structurally related to the tumor suppressor p53. However, their own role in tumor suppression is unclear. Given the p53-like properties of p63 and p73, we tested whether they are involved in tumor suppression by aging mice heterozygous for mutations in all p53 family genes and scored for spontaneous tumors. We show here that p63+/-;p73+/- mice develop spontaneous tumors. Loss of p63 and p73 can also cooperate with loss of p53 in tumor development. Mice heterozygous for mutations in both p53 and p63 or p53 and p73 displayed higher tumor burden and metastasis compared to p53+/- mice. These findings provide evidence for a broader role for the p53 family than has been previously reported.

Adenocarcinoma↗

PubMed2004

An unusual zwitterionic, diradical intermediate in photochemical electron-transfer substitution reactions.

An unusual zwitterionic diradical intermediate complex R*...X-...HR'B*+ is generated during the photoinduced electron-transfer substitution reaction between alkyl halides (RX) and Lewis bases (HR'B). This reaction intermediate was observed for the 1-chloroadamantane and tert-butylamine system in a hydrocarbon glass at 25 K by electron spin resonance spectroscopy. Ab initio density functional calculations were carried out to examine the physical and electronic structure of the intermediate.

Journal Article↗

PubMed2003

Alkyl halide charge transfer complexes with hard Lewis bases.

The unusual charge transfer complexes formed between alkyl halide acceptors and hard Lewis base donors (amines and alcohols) in low dielectric solvent were examined using ultraviolet spectroscopy. The lambda(max) of the complex decreases with increasing ionization potential of the donor. The complex formation equilibria were probed by thermodynamic analysis and concentration variation. At ambient temperatures complex formation is generally slightly exergonic with a negative complexation entropy. The complex extinction coefficients are much lower (<10 l mol(-1) cm(-1)) than for typical charge transfer complexes. These complexes are extraordinary within a classical context since the halide acceptors have a negative electron affinity. They exhibited an atypical hypsochromic shift with increasing solvent dielectric constant.

Chemistry↗

PubMed2002

Photoinduced electron-transfer substitution reactions via unusual charge-transfer intermediates.

The photoinduced substitution reactions of halogenated alkanes (1-haloadamantanes, 1-haloronorbornanes, menthyl chloride) with a homologous series of amines or alcohols (methylamine, 2-methyl-2-aminopropane, methanol, or 2-methyl-2-propanol) to form the corresponding alkane-substituted amines or ethers and HCl were investigated. The geometry of the bridgehead carbons made S(N)2 reactions impossible. Nonpolar reaction conditions were employed which made classical and nonclassical carbocation S(N)1 reaction pathways unlikely. The reaction rates were measured. Trapping experiments indicated that free radical reactions were uninvolved in the substitution product formation. A novel, photoinduced electron-transfer reaction mechanism involving a charge-transfer intermediate is proposed to explain the observed production of secondary amines and ethers. The excitation wavelength dependence (action spectrum) was measured and found to be comparable to the ultraviolet absorption spectra of the charge-transfer complexes. The stereochemical implications of the reaction mechanism were investigated. The formation of the methyl ether of (1R,2S,5R)-menthol was the only organic reaction product observed in the photoreaction between (1R,2S,5R)-menthyl chloride and methanol.

Journal Article↗

PubMed2002

The increase in international medical graduates in family practice residency programs.

BACKGROUND AND OBJECTIVES: The number of filled positions in family practice residency programs decreased by 18.6% from 1997-2001. This study sought to determine the degree of reliance on international medical graduates (IMGs) to fill family practice residency positions and the relative proportion of US citizen IMGs. METHODS: We analyzed the 1992-2001 National Resident Matching Program results, the 2000 American Medical Association Masterfile, and the 1992-2001 American Academy of Family Physicians Annual Survey of Family Practice Residency Programs. RESULTS: The percentage of IMGs matching in family practice remained stable between the years of 1992-1996 (10.0%-11.8%) but since 1997 has increased to a high of 21.4% in 2001. This rise in IMGs corresponds with a drop in the total percentage of family practice residency positions filled in the Match from 90.5% in 1996 to 76.3% in 2001. Despite the drop in Match numbers, the percentage of first-year family practice positions filled in July has remained in the range of 95.5%-97.8% since 1996. IMGs account for an increasing percentage of post-Match fills from 16.7% in 1996 to 47.9% in 2001. In 1999, a majority of family practice programs (279 [55.6%]), had at least one IMG. Of these, 48 programs (9.6%) had at least 50% of residents who were IMGs, and eight programs (1.6%) were entirely composed of IMGs. In five states (Connecticut, Illinois, Michigan, New Jersey, and New York), more than 25% of family practice residents were IMGs. CONCLUSIONS: Family practice is becoming increasingly reliant on IMGs to fill residency positions.

Career Mobility↗