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Biomedical subjects

M Mitchell

Publications and source records attributed to M Mitchell.

At least 55 records · Page 3Linked to original sources

Size and physical map of the chromosome of Haemophilus influenzae.

A variation of pulse-field electrophoresis, field-inversion gel electrophoresis, was used to determine the size and physical map of the chromosome of Haemophilus influenzae. The DNA of H. influenzae had a low G + C content (39%) and no restriction sites for the enzymes NotI or SfiI. However, a number of restriction enzymes (SmaI, ApaI, NaeI, and SacII) that recognized 6-base-pair sequences containing only G and C nucleotides were found to generate a reasonable number of DNA fragments that were separable in agarose gels by field-inversion gel electrophoresis. The sizes of the DNA fragments were calibrated with a lambda DNA ladder and lambda DNA restriction fragments. The sum of fragment sizes obtained with restriction digests yielded a value for the chromosome of 1,980 kilobase pairs. Hybridization of a labeled fragment with two or more fragments from a digest with a different restriction enzyme provided the information needed to construct a circular map of the H. influenzae chromosome.

Chromosomes, Bacterial

A team approach to prevocational services.

This paper presents a chronology of legislative mandates for vocational rehabilitation, discusses their impact on occupational therapy, and describes relationships between special educators and vocational agencies. The Career Training Workshop, a prevocational program developed and used successfully by a North Carolina school district, is described here as an example of one effort to prepare students with disabilities for employment.

Activities of Daily Living

Selective inhibition of glycoprotein-processing enzymes. Differential inhibition of glucosidases I and II in cell culture.

In this study, we compared the effects of 2,6-dideoxy-2,6-imino-7-O-(beta-D-glucopyranosyl)-D-glycero-L-gulohep titol (MDL) to those of the glucosidase I inhibitor, castanospermine, on the purified processing enzymes glucosidases I and II. WE also compared the effects of these two inhibitors on glycoprotein processing in cell culture using influenza virus-infected Madin-Darby canine kidney cells as a model system. With the purified processing enzymes, castanospermine was a better inhibitor of glucosidase I than of glucosidase II, whereas MDL is more effective against glucosidase II than glucosidase I. In cell culture at the appropriate dose, MDL also preferentially affected glucosidase II. Thus, at 250 micrograms/ml MDL, the major [3H]glucose-labeled (or [3H]mannose-labeled) glycopeptide from the viral hemagglutinin was susceptible to endoglucosaminidase H, and the oligosaccharide liberated by this treatment was characterized as a Glc2Man7-9GlcNAc on the basis of size, resistance to digestion by glucosidase I (but sensitivity to glucosidase II), methylation analysis, and Smith degradation studies. These data indicate that at appropriate concentrations of MDL (250 micrograms/ml), one can selectively inhibit glucosidase II in Madin-Darby canine kidney cells. However, at higher concentrations of inhibitor (500 micrograms/ml), both enzymes are apparently affected. Since MDL did not greatly inhibit the synthesis of lipid-linked saccharides or the synthesis of protein or RNA, it should be a useful tool for studies on the biosynthesis and role of N-linked oligosaccharides in glycoprotein function.

Alkaloids

Generation of different nucleosome spacing periodicities in vitro. Possible origin of cell type specificity.

We have been able to generate ordered nucleosome arrays that span the physiological range of spacing periodicities, using an in vitro system. Our system (a refinement of the procedure previously developed) uses the synthetic polynucleotide poly[d(A-T)], poly[d(A-T)], core histones, purified H1, and polyglutamic acid, a factor that increases nucleohistone solubility and greatly promotes the formation of ordered nucleosome arrays. This system has three useful features, not found in other chromatin assembly systems. First, it allowed us to examine histones from three different cell types/species (sea urchin sperm, chicken erythrocyte, and HeLa) as homologous or heterologous combinations of core and H1 histones. Second, it allowed us to control the average packing density (core histone to polynucleotide weight ratio) of nucleosomes on the polynucleotide; histone H1 is added in a second distinct step in the procedure to induce nucleosome alignment. Third, it permitted us to study nucleosome array formation in the absence of DNA base sequence effects. We show that the value of the spacing periodicity is controlled by the value of the initial average nucleosome packing density. The full range of physiological periodicities appears to be accessible to arrays generated using chicken erythrocyte (or HeLa) core histones in combination with chicken H5. However, chromatin-like structures cannot be assembled for some nucleosome packing densities in reactions involving some histone types, thus limiting the range of periodicities that can be achieved. For example, H1 histone types differ significantly in their ability to recruit disordered nucleosomes into ordered arrays at low packing densities. Sea urchin sperm H1 is more efficient than chicken H5, which is more efficient than H1 from HeLa or chicken erythrocyte. Sea urchin sperm core histones are more efficient in this respect than the other core histone types used. These findings suggest how different repeat lengths arise in different cell types and species, and provide new insights into the problems of nucleosome linker heterogeneity and how different types of chromatin structures could be generated in the same cell.

Animals

Ultrasonic growth parameters in fetuses of mothers with primary addiction to cocaine.

Sixty-seven women with primary addiction to cocaine were evaluated during their pregnancies by multiple ultrasound studies. Ultrasonic parameters included biparietal diameter, femur length, abdominal circumference, and head circumference. These values were compared with ultrasonic growth parameters in nonaddicted fetuses. Head and abdominal circumference data were used to evaluate the fetuses according to growth pattern. With this system of scoring, subtleties of asymmetric versus symmetric intrauterine growth retardation become apparent. In addition, birth weights of addicted infants were compared with birth weights of nonaddicted infants. The results suggest that, although statistically significant differences in birth weights cannot be demonstrated, abnormal growth of the addicted fetuses does occur. Addicted fetuses show a greater proportion of biparietal diameter and abdominal circumference values below the 50th and 25th percentiles than nonaddicted fetuses, and addicted fetuses more frequently exhibit intrauterine growth retardation patterns. These data suggest that it is fruitful to study these infants with near-normal size but with abnormal intrauterine growth patterns.

Birth Weight

Septic arthritis.

Infectious arthritis is a commonly encountered clinical problem which may result from articular contamination by a wide variety of organisms. Involvement of an articulation may occur by one of four mechanisms: hematogenous spread, spread from a contiguous source of infection, direct implantation, or postoperative contamination. Distribution is typically monoarticular with a swollen, erythematous, and painful joint. The radiographic differential diagnosis includes limited rheumatoid arthritis, gout, synovial osteochondromatosis, and pigmented villonodular synovitis. In order to prevent complications, including growth disturbances, articular destruction with ankylosis, osteomyelitis, or soft tissue extension, early diagnostic arthrocentesis is important. Radiographic abnormalities, which include soft tissue swelling, joint space loss, periarticular osteopenia, and central or marginal osseous erosions, may be delayed following clinical onset of infection. Advanced imaging techniques such as scintigraphy, CT, or MRI may allow accurate diagnosis of the infectious process at an earlier stage.

Arthritis, Infectious

Diagnostic imaging of bone tumors in the foot.

Many tumor and tumor-like lesions may involve bone. Bone tumors in the foot are, however, very rare. An accurate diagnosis relies on a cooperative clinical and imaging effort. The patient's age, sex, history, clinical findings, and presentation, in addition to the radiographic features, allow for proper diagnosis. Specialized imaging techniques may be helpful in certain instances. Aside from a biopsy, the radiograph is clearly the most important single approach to the diagnosis of bone tumors affecting the foot.

Bone Cysts

Arthrography, tenography, and bursography of the ankle and foot.

A brief description of normal anatomy and common arthrographic, tenographic, and bursographic procedures is presented. The described procedures are important diagnostic tools and do not carry major risk. Therefore, these procedures can be performed on an outpatient basis.

Ankle

Research in service settings: Part I--Consortium project outcomes.

As nurse executives in today's cost-conscious environment attempt to meet their professional responsibilities for encouraging and supporting staff involvement in nursing research, they may wish to consider strategies similar to those described here. In this unique 3-year project, a consortium of nine health care agencies shared research expertise and resources, with the overall aim of incorporating nursing research into practice. This article reports the outcomes and the authors' assessment of the experience. Part 2 , which will be published in the March issue of JONA will describe the consortium's current focus and program.

Adult

Research in service settings: Part II--Consortium project.

Part I (February 1988) of this series of two articles described the outcomes of the first 3 years of this project, which is aimed at incorporating nursing research in service settings through a consortium of health care agencies. So that nurse executives interested in employing similar strategies in their own geographic area may have a complete picture of the evolution of this collaborative approach, Part II describes the consortium's current program and its ongoing development.

California

Mapping the testis determinants by an analysis of Y-specific sequences in males with apparent XX and XO karyotypes and females with XY karyotypes.

A number of patients with paradoxical sex chromosome complements (so-called XY females, XX and XO males) have been investigated with a series of 19 Yp and 4 Yq DNA probes to establish which region of the Y is essential for male sexual differentiation. Of the 23 XX males, 18 possessed one or more Yp probe sequences with only 5 lacking such sequences. Of 9 XY females examined, only one showed evidence of a deletion in Yp occurring either as a result of X-Y interchange or interstitial deletion. This suggests that the majority of XY females are not commonly deleted for those Y sequences which are found to be transferred to the X in XX males. The DNA of two XO males both contained different portions of the Y. From a comparison of the patterns of Yp sequences in these patients, it has been possible to elaborate a model of Yp in terms of the order of probe sequences and to suggest a location for the testis determining region in distal Yp.

Chromosome Deletion

Urorectal septum malformation sequence. Report of six cases and embryological analysis.

We encountered six female infants with a specific pattern of developmental abnormalities of the urogenital and lower intestinal tracts. The anomalies included ambiguous genitalia, lack of perineal openings, and müllerian and urinary tract anomalies. Each patient had normal female chromosomes and normal adrenal gland function. We believe that this combination of anomalies represents a recognizable and specific sequence that is due to a failure of migration to and/or fusion of the urorectal septum with the cloacal membrane. This, in turn, we postulate, leads to persistence of the cloaca and cloacal membrane and failure of normal differentiation of the external genitalia. Persistence of the cloacal membrane results in absence of the urethral and vaginal openings and an imperforate anus. We propose calling this entity the urorectal septum malformation sequence.

Anus, Imperforate

Lactic dehydrogenase isozymes, 31P magnetic resonance spectroscopy, and in vitro antimitochondrial tumor toxicity with gossypol and rhodamine-123.

Three compounds that share specific antimitochondrial properties are gossypol, rhodamine-123, and lonidamine. We compare the antiproliferative activities of these drugs against six human cell lines derived from breast (T47-D), pancreas (MiaPaCa, RWP-2), prostate (DU-145), colon (HCT-8), and cervix (HeLa) carcinomas. Tumor cells enriched in cathodal LDH isozymes (LDH4 and LDH5) are significantly more sensitive to gossypol and rhodamine-123. When compared for ability to inhibit growth of human marrow in soft agar, 10 microM gossypol shows little effect on colony formation whereas 10 microM rhodamine-123 completely prevents stem cell growth, suggesting that gossypol may have the most favorable therapeutic index. Within 24 h of drug administration, there is a relative increase in intracellular inorganic phosphate pools and a marked decline in soluble high-energy phosphates in sensitive tumor cells, as measured by 31P magnetic resonance spectroscopy. These studies suggest that specific antimitochondrial agents might be selectively administered on the basis of tumor LDH isozyme content and noninvasively monitored for antiproliferative activity by 31P spectroscopy.

Cell Division