Outlook for impaired physicians with appropriate treatment.
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Biomedical subjects
Publications and source records attributed to G R Jacobson.
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The overall stereochemical course of the reactions leading to the phosphorylation of methyl alpha-D-glucopyranoside by the glucose-specific enzyme II (enzyme IIGlc) of the Escherichia coli phosphotransferase system has been investigated. With [(R)-16O,17O,18O]phosphoenolpyruvate as the phosphoryl donor and in the presence of enzyme I, HPr, and enzyme IIIGlc of the phosphotransferase system, membranes from E. coli containing enzyme IIGlc catalyzed the formation of methyl alpha-D-glucopyranoside 6-phosphate with overall inversion of the configuration at phosphorus (with respect to phosphoenolpyruvate). It has previously been shown that sequential covalent transfer of the phosphoryl group of phosphoenolpyruvate to enzyme I, to HPr, and to enzyme IIIGlc occurs before the final transfer from phospho-enzyme IIIGlc to the sugar, catalyzed by enzyme IIGlc. Because overall inversion of the configuration of the chiral phospho group of phosphoenolpyruvate implies an odd number of transfer steps, the phospho group has been transferred at least five times, and transfer from phospho-enzyme IIIGlc to the sugar must occur in two steps (or a multiple thereof). On the basis that no membrane protein other than enzyme IIGlc is directly involved in the final phospho transfer steps, our results imply that a covalent phospho-enzyme IIGlc is an intermediate during transport and phosphorylation of glucose by the E. coli phosphotransferase system.
Of 40 participants of a two-year program for rehabilitating alcohol- and other-drug-dependent physicians, 15 have completed 24 months of treatment and monitoring, eight have completed 12 to 23 months, ten have completed one to 11 months, and seven discontinued treatment before completion. Of the 33 treated physicians, 31 have returned to full practice and 22 have experienced no relapse. The prognosis is quite favorable for most impaired physicians in appropriate treatment, monitoring, and follow-up are provided.
Physicians recovering from substance-use disorders face many reintegration problems when they attempt to resume professional activities. Armed with state-of-the-art information, hospital medical staffs and administrators can ensure that the process is as smooth as possible and that the recovering physician's, the patient's, and the hospital's rights are protected.
A transformant Escherichia coli colony bank [Clarke, L. & Carbon, J. (1976) Cell 9, 91-99] has been screened for hybrid ColE1 plasmids carrying the genes for D-mannitol utilization. Two of the plasmids, pLC11-7 and pLC15-48, were shown to contain the mannitol operon, which includes the structural genes for the mannitol-specific enzyme II of the phosphotransferase system and mannitol-1-phosphate dehydrogenase. One E. coli strain harboring plasmid pLC15-48 overproduced mannitol-1-phosphate dehydrogenase activity 4- to 5-fold. However, there was no corresponding increase in mannitol enzyme II activity. Plasmid pLC15-48 was shown to direct the synthesis of two polypeptides in E. coli minicells in the presence of cyclic AMP and mannitol. The larger (Mr = 60,000) was membrane bound and was specifically precipitated by antibody directed against purified mannitol-specific enzyme II. The smaller (Mr = 40,000) was soluble and had an electrophoretic mobility indistinguishable from that of the major component in a partially purified mannitol-1-phosphate dehydrogenase preparation. These data are consistent with previous genetic studies of the mannitol locus and confirm an independent conclusion [Jacobson, G. R., Lee, C. A. & Saier, M. H., Jr. (1979) J. Biol. Chem. 254, 249-252] that mannitol enzyme II consists of a single type of polypeptide chain that has a Mr of 60,000. The plasmid pLC15-48 DNA was characterized by mapping of restriction endonuclease cleavage sites.
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Authors predicted that adult alcoholics with relatively higher scores on obsessive-compulsive drinking subscale of Alcohol Use Inventory (AUI-4) and psychasthenia scale of Minnesota Multiphasic Personality Inventory (MMPI-7) would be better candidates for successful completion of traditional outpatient treatment. Both tests were administered to 89 successively admitted outpatients who were tracked through treatment and later classified as dropouts (premature unilateral termination of treatment, N = 57), mutuals (patient-therapist agreement on appropriate termination, N = 22), or open cases (patients still in treatment at end of 6 months, N = 10). AUI-4, but not MMPI-7, successfully identified dropouts, mutuals, and open cases, and significantly differentiated between dropouts and all other patients. AUI-4 and MMPI-7 were significantly and positively correlated, and AUI-4, but not MMPI-7, was significantly and positively related to number of therapy sessions.
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The possible use of high density lipoprotein cholesterol (HDLC) as a marker of alcohol abuse was studied in 92 alcoholic patients entering an inpatient treatment program. The average HDLC levels of 68 male patients (66 +/- 23 mg/dl) and 24 female patients (83 +/- 18 mg/dl) were significantly higher than the values for the corresponding control groups of similar ages. Approximately 20% of the male patients had HDLC levels over the mean +/- 2 SD over the control groups. Following 2 wk of alcohol abstinence, the HDLC levels decreased to the control range. HDLC, as a measure of alcohol abuse, may be especially useful in combination with determination of gamma glutamyl transpeptidase (GGT), since these two tests singly or in combination were elevated in 65% of the male and 85% of the female patients.
The inducible, mannitol-specific Enzyme II of the phosphoenolpyruvate:sugar phosphotransferase system has been purified approximately 230-fold from Escherichia coli membranes. The enzyme, initially solubilized with deoxycholate, was first subjected to hydrophobic chromatography on hexyl agarose and then purified by several ion exchange steps in the presence of the nonionic detergent, Lubrol PX. The purified protein appears homogeneous by several criteria and probably consists of a single kind of polypeptide chain with a molecular weight of 60,000 (+/- 5%). In addition to catalyzing phosphoenolpyruvate-dependent phosphorylation of mannitol in the presence of the soluble enzymes of the phosphotransferase system, the purified Enzyme II also catalyzes mannitol 1-phosphate:mannitol transphosphorylation in the absence of these components. A number of other physical and catalytic properties of the enzyme are described. The availability of a stable, homogeneous Enzyme II should be invaluable for studying the mechanism of sugar translocation and phosphorylation catalyzed by the bacterial phosphotransferase system.
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Of 2,996 welfare recipients applying for CETA benefits at the Milwaukee office of Jewish Vocational Service between 3/1/78-9/30/78, a 10% sample (N = 309) was screened for assessment of alcohol problems. After obtaining voluntary informed consent from participants (6% declined), trained interviewers individually administered a 16-item alcoholism At-Risk Questionnaire (ARQ) based on observations by NCA's Criteria Committee; a standard form of the 25-item Michigan Alcoholism Screening Test (MAST); and a 35-item interview structured around a selectively modified version of NCA's Criteria for the Diagnosis of Alcoholism (CRIT). Analyses of data suggested that our ARQ was of little value in discriminating between problem drinkers and other persons, although significantly correlated with MAST and CRIT scores. Using a conventional scoring of the MAST, 53.6% of the sample appeared to have significant alcohol problems, while our CRIT identified only 31.9% as problem drinkers. By combining the MAST + CRIT in a unique scoring system, a more conservative estimate of 36.57% problem drinkers, with an estimated error rate of 1.63% false negatives and 23.45% false positives, was determined. Further modification of MAST + CRIT scoring led to a revised estimate of 25.41% problem drinkers with estimated false-positive and false-negative rates of 7.55% and 6.5% respectively. Implications for research and plans for further modifications of screening procedures are discussed.
Limited proteolysis of native elongation factor Tu (Mr 44 000) by trypsin occurs in at least three distinct steps. The first intermediate arises through cleavage at a site about 65 residues from the amino-terminal end of the protein. It is functionally active [Jacobson, G. R. & Rosenbusch, J. P. (1976) Biochemistry, 15, 5105-5110] and is partially protected from further degradation by the antibiotic kirromycin. The second step converts this intermediate to one of similar size (Mr 37 000) which now is partially inactivated. It is likely to be identical with the intermediate described by Arai et al. [(1976) J. Biochem. Tokyo, 79, 69-83]. In the third step, the partially inactive intermediate is cleaved without any apparent change in the functional properties tested. The resulting two trypsin-resistant fragments have molecular weights of 24 000 and 14 000, and remain associated under nondenaturing conditions. When either of these polypeptides, after isolation in 8 M urea, is allowed to renature, no significant reactivation of GDP binding is observed unless the isolated fragments are mixed before renaturation. These results show that the two fragments are structurally and functionally interdependent.
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Ideas of purpose and meaning in life, religious or spiritual values, belief in a Higher Power, and related constructs often play an important role in traditional alcoholism rehabilitation approaches, but very few data are available. Consequently, 49 males and 8 females in a 30-day inpatient treatment program for alcoholics were given the Purpose in Life (PIL) test and Study of Values (SOV) shortly after admission to the hospital and again just before discharge. Results indicated: (1) significant increases in PIL scores; (2) no significant dissimilarities between alcoholics and normals on the SPV; and (3) significant correlations between PIL and the Aesthetic and Religious scales of the SOV on the second administration only. Results were discussed in terms of future directions for research and implications for treatment.
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