Biomedical subjects
M E Levin
Publications and source records attributed to M E Levin.
Foot lesions in patients with diabetes mellitus.
Diabetic foot ulcers are common. If treatment is delayed or is inappropriate, the lesions can become infected, resulting in gangrene and amputation. Physicians and clinics that perform aggressive therapy for these ulcers, provide revascularization when indicated, practice a team approach, suggest the use of therapeutic shoes, and repeatedly educate patients in foot care have reduced their amputation rates by 50% or greater. Goals of the United States Department of Health for the year 2000 include a 40% reduction in the amputation rate in patients with diabetes. This should be the goal of everyone providing care for patients with diabetes.
Transcriptional regulation of repressor synthesis in mycobacteriophage L5.
Mycobacteriophage L5 is a temperate phage of the mycobacteria that forms stable lysogens in Mycobacterium smegmatis. Lysogeny is maintained by the putative repressor, the gene 71 product, which also mediates immunity to superinfection. We show here that there are three promoters located upstream of gene 71 which are active in an L5 lysogen but which do not require any phage-encoded proteins. In early lytic growth, gene 71 is also transcribed from a promoter, Pleft, located at the right end of the genome and which appears to be a target of gp71 regulation. A model is given for the regulation of L5 life cycles.
Preventing amputation in the patient with diabetes.
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Additional causes of the blue toe syndrome.
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Otx1 and Otx2 define layers and regions in developing cerebral cortex and cerebellum.
Within the cerebral and cerebellar cortices, neurons are organized in layers that segregate neurons with distinctive morphologies and axonal connections, and areas or regions that correspond to distinct functional domains. To explore the molecular underpinnings of pattern formation in layered regions of the CNS, we have characterized the patterns of expression of two homeodomain genes, Otx1 and Otx2, by in situ hybridization during embryonic and postnatal development in the rat. Otx1 and Otx2 are vertebrate homologs of the Drosophila gap gene orthodenticle, and are expressed during the development of the murine CNS (Simeone et al., 1992). Here we report that Otx1 mRNA is expressed in a subpopulation of neurons within cortical layers 5 and 6 during postnatal and adult life. This gene is also expressed by the precursors of deep-layer neurons within the developing cerebral ventricular zone, but is apparently downregulated by the progenitors of upper-layer neurons; Otx1 is never expressed by the neurons of layers 1-4. The spatial and temporal patterns suggest that Otx1 may play a role in the specification or differentiation of neurons in the deep layers of the cerebral cortex. Within the cerebellum, mRNAs for Otx1 and Otx2 are found within the external granular layer (EGL), but in three spatially distinct domains. During postnatal development, Otx1 is expressed within anterior cerebellar lobules; Otx2 mRNA is localized posteriorly, and a region of overlap in mid-cerebellum defines a third domain in which both genes are expressed. The boundaries of Otx1 and Otx2 expression correspond to the major functional boundaries of the cerebellum, and define the vestibulocerebellum, spinocerebellum, and pontocerebellum, respectively. Spatially restricted patterns of hybridization are observed early in postnatal life, at times that correspond roughly to the invasion of spinal and pontine afferents into the cerebellum (Arsénio-Nunes and Sotelo, 1985; Mason, 1987). These results raise the possibility that Otx1 and Otx2 play a role in cerebellar regionalization during early development.
A programmed translational frameshift is required for the synthesis of a bacteriophage lambda tail assembly protein.
Two proteins, one of 31 kDa and one of 16 kDa, are encoded by a segment of the phage lambda tail gene region that contains two overlapping reading frames, neither of which is long enough to encode the larger protein. We show that the abundant 16-kDa protein (gpG) is encoded by the upstream open reading frame, gene G. The 31-kDa protein, gpG-T, is encoded jointly by gene G and the overlapping downstream T open reading frame. gpG-T is synthesized as the result of a translational frameshift that occurs when a ribosome translating the G gene slips back by one nucleotide at a position six codons from the C terminus of the gene and thereby bypasses the G termination codon to continue on in the T open reading frame. The resulting protein shares 135 residues of N-terminal amino acid sequence with gpG, followed by 144 amino acid residues of unique sequence. The frameshift event occurs with a frequency of approximately 4% at the sequence G GGA AAG, which encodes the dipeptide -Gly-Lys- in both the zero and -1 reading frames. The frameshift frequencies of point mutants in this "slippery sequence" argue that codon-anticodon interactions with both the glycyl and the lysyl-tRNA are important for frameshifting to occur. We find no clear evidence for a pausing mechanism to enhance frameshifting, as is seen in other well-characterized frameshifts. No simple secondary structure has been predicted for the region downstream from the slippery sequence, but this downstream sequence does contribute to the frameshifting rate. Our results together with those of Katsura and Kühl show that the frameshift product, gpG-T, has an essential role in lambda tail assembly, acting prior to tail shaft assembly. The role of gpG in tail assembly is not known. We find that both gpG and the gpG-T are absent from mature virions.
Mycobacterium smegmatis RNA polymerase: DNA supercoiling, action of rifampicin and mechanism of rifampicin resistance.
We have isolated RNA polymerase from Mycobacterium smegmatis and established conditions for specific transcription initiation in vitro. The M. smegmatis enzyme has a strong dependence on supercoiling of the DNA substrate for transcription from mycobacterial promoters. We also show that RNA polymerase is the target for rifampicin, and that this antibiotic specifically inhibits the transition from synthesis of short oligoribonucleotides to full-length transcripts. RNA polymerase isolated from a rifampicin-resistant mutant of M. smegmatis is less sensitive to rifampicin in vitro, confirming that one mechanism of rifampicin resistance in mycobacteria is through alteration of RNA polymerase. This in vitro transcription system provides a simple method for the characterization of gene expression in mycobacteria including the pathogens Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium leprae. It also provides a system for evaluating potential anti-mycobacterial drugs.
Does crossing the legs decrease arterial pressure in diabetic patients with peripheral vascular disease?
OBJECTIVE: To evaluate the effect of crossing the legs at the knee and the ankle on peripheral arterial pressures. RESEARCH DESIGN AND METHODS: A prospective study of 6 diabetic patients with known peripheral vascular disease and 5 nondiabetic control subjects without peripheral vascular disease was conducted. Peripheral arterial pressures were taken at the ankle and at the great toe before and after crossing the legs at the knees and ankles. Comparisons were made of measurements obtained in the supine and sitting positions. All crossed leg measurements were taken in the sitting position. RESULTS: Ankle arm indexes and digital arm indexes pressures taken in the sitting position were equal to or higher than supine pressures, with the exception of one subject, GB. In this patient, ankle arm indexes and digital arm indexes on the right extremity were lower in the sitting position, but increased with the legs crossed at the knees and ankles compared with the uncrossed sitting position. In all patients, lower extremity pressures that decreased slightly with crossing the legs remained higher than pressures obtained in the supine position. Statistical analyses showed no significant differences. Wave forms did not change even when there was a slight decrease in ankle arm indexes or digital arm indexes. Control subjects without peripheral vascular disease showed no change in pressures with crossing the legs. CONCLUSIONS: Crossing the legs at the knees and ankles does not result in a significant decrease in peripheral arterial pressures in diabetic patients with peripheral vascular disease.
Subtractive processes in light adaptation.
We measured the time course of light adaptation in foveal vision following the onset of an adapting background. Several adaptational steps in the low to mid photopic range were examined. The time course of multiplicative and subtractive components of the adaptation were extracted from the data. Unlike previous findings there were no subtractive changes for several hundred milliseconds following light onset, and the process took 10-15 sec to reach steady state. It seems likely that the fast component previously observed results from effectively instantaneous center-surround antagonism, and that our measurements reflect a second subtractive process involving the slow loss of the d.c. signal over time.
Nodular adrenal hyperplasia--a caveat.
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Thallium stress tests and bank vaults.
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Diabetes mellitus in adults.
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Understanding your diabetic patient.
In 1987, it is quite evident that the diagnosis etiology, complications, and management of diabetes have come a long way since those days 65 years ago when the lifespan of an insulin-requiring diabetic was 1.2 years. There are exciting times ahead. Today, with the number of diabetics increasing and the problems multiplying, anyone caring for diabetics should have a general knowledge of all aspects of the disease and be able to participate in the total care of the diabetic. For example, the podiatrist should not confine diabetic care only to the foot, but should check blood sugars and blood pressures, take brief diabetic histories, suggest yearly eye examinations, and encourage adherence to diet, blood sugar control, exercise programs, and the avoidance of smoking. While great strides have been made in diabetic management particularly in the last decade, the ultimate cure is yet to be achieved and is the goal of the future.
Pregnancy and diabetes. Team approach.
Each year, 10,000 babies are born to diabetic women. Gestational diabetes occurs in 2% of all pregnant women, resulting in 60,000 to 90,000 cases of gestational diabetes yearly. Prior to 1922 and the discovery of insulin, fetal mortality for the pregnant diabetic was almost 100%. Today, total fetal mortality for the pregnant and gestational diabetic is approaching that of the nondiabetic. This has been achieved by extremely tight control of blood glucose levels throughout pregnancy, with blood glucose levels averaging under 100 mg/dL/day and glycosylated hemoglobin levels in the normal range throughout pregnancy. An increased number of malformations in fetuses of pregnant diabetic women is still a problem. However, animal and human studies indicate that a normal level of glycosylated hemoglobin at conception may significantly reduce these malformations.
Diabetes: geriatric complications.
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Diabetes: the geriatric difference.
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The diabetic foot.
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