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Biomedical subjects

C A Baker

Publications and source records attributed to C A Baker.

At least 19 recordsLinked to original sources
PubMed1995

Conversion of a bovine UDP-GalNAc:polypeptide, N-acetylgalactosaminyltransferase to a soluble, secreted enzyme, and expression in Sf9 cells.

A soluble, secreted UDP-GalNAc:polypeptide, N-acetylgalactosaminyltransferase, was prepared by substituting the honeybee melittin leader sequence for the sequences coding for the cytoplasmic and membrane spanning domains of a cloned, bovine full-length cDNA (F. L. Homa et al., 1993, J. Biol. Chem. 268, 12609-12616). When this construct was expressed in insect cells using a recombinant baculovirus, a fully active soluble enzyme was recovered from the culture medium. In large-scale preparations, approximately 2-3 mg of enzyme protein was produced per liter of medium. A one-step purification of the soluble molecule on apomucin-Sepharose yielded an essentially homogeneous enzyme preparation. The purified soluble enzyme has a molecular mass of approximately 61 kDa and appears to contain both N- an O-linked oligosaccharides. NH2-terminal sequencing demonstrated that the melittin leader sequence is cleaved at the predicted site and amino acid analysis gave results in close agreement with the composition predicted by the nucleic acid sequence. The enzymatic properties of the soluble, recombinant molecule are similar to those of the enzymes isolated from bovine colostrum and porcine submaxillary gland: the specific activity is approximately 2160 U/mg protein and the Kms for UDP-GalNAc and the synthetic acceptor peptides PPASTSAPG and PPDAASAAPLR are approximately 1.7 microM, 6.5 mM, and 3.6 mM, respectively.

Amino Acid Sequence↗
PubMed1994

Minoxidil sulfation in the hair follicle.

The in vivo model which may be the most accurate for the ability to predict hair growth in humans, and which was utilized in the preclinical development of minoxidil, is the adult stumptailed macaque. Previous reports have suggested that the enzyme activity which accounts for the activation of minoxidil, i.e., minoxidil sulfotransferase, is present in skin. We have demonstrated that scalp skin from the stumptailed macaque contains minoxidil sulfotransferase activity, and further with dissection of that scalp skin into epidermis, dermis and hair follicle, most of sulfotransferase activity was present in the follicle. Sulfotransferase activity in the hair follicle in freeze-dried scalp skin sections from 9 stumptailed macaques ranged from 47 to 84% of the total (mean 61 +/- 12%). Much less minoxidil sulfotransferase activity was measured in the epidermis (mean 18 +/- 11%, with a range of 2-37%) and the dermis (mean 21 +/- 8%, with a range of 4-35%) of these scalp sections. These results indicate that the scalp skin from the stumptailed macaque contains minoxidil sulfotransferase activity and this activity is largely localized in the hair follicle which may account for its ability to stimulate hair growth in this animal model.

Animals↗
PubMed1994

Human islet amyloid polypeptide accumulates at similar sites in islets of transgenic mice and humans.

The cellular mechanisms responsible for conversion of islet amyloid polypeptide (IAPP) into insoluble amyloid deposits in non-insulin-dependent diabetes mellitus (NIDDM) are not clear. Overexpression of IAPP and the amino acid sequence of human IAPP (hIAPP) have both been implicated. To examine factors involved in amyloid formation, transgenic mice expressing the hIAPP or rat IAPP (rIAPP) gene were generated. These mice had elevated plasma IAPP concentrations, and they were normoglycemic and normoinsulinemic. No amyloid deposits were detected by light microscopy. To examine the ultrastructure of islets, pancreatic tissue was studied from hIAPP and rIAPP transgenic mice and from age-matched control mice by immunoelectron microscopy. IAPP was immunolocalized in beta-cell secretory granules of all mice, and the COOH- and NH2-terminal flanking peptides of hIAPP were localized in beta-cell granules of hIAPP mice. Accumulations of nonfibrillar perivascular IAPP-immunoreactive material were found between capillaries and beta-cells in hIAPP transgenic mice but not in rIAPP transgenic or control mice. Similar nonfibrillar masses were identified in islets of an NIDDM patient. Secondary lysosomes in beta-cells and macrophages of hIAPP transgenic mice showed dense labeling for IAPP. We suggest that hIAPP is degraded more slowly than rIAPP or mouse IAPP by beta-cell lysosomes. Accumulations of IAPP in islet perivascular spaces may represent the early stages of islet amyloid formation.

Aged↗
PubMed1993

Enhanced in vitro hair growth at the air-liquid interface: minoxidil preserves the root sheath in cultured whisker follicles.

Inasmuch as hair follicles are difficult to maintain in culture, the study of hair biology using cultured hair follicles has met with only limited success. In our attempts to solve the problem of follicle degeneration, we cultured follicles at the air-surface interface on a modified collagen matrix (Gelfoam). In follicles cultured at the air-surface or submerged, we examined follicular morphology, hair shaft growth, sulfotransferase levels, cysteine incorporation, an expression of a tissue inhibitor of metalloproteinase (TIMP), and ultra-high sulfur keratin (UHSK). Follicles cultured at the air-liquid interface produced a 2.7-fold increase in hair growth and maintained an anagen-like morphology. Substrates such as nylon mesh seeded with fibroblasts, Full Thickness Skin, or 5-microns polycarbonate filter also supported hair growth, whereas Gelfilm, GF-A glass filter, filter paper, or 1-micron polycarbonate filter did not. The UHSK expression was significantly higher in the air-liquid interface cultures compared to the submerged culture. Several potassium channel openers, including minoxidil, a minoxidil analog, and the pinacidil analog (P-1075), all stimulated significant cysteine incorporation in follicles. Minoxidil and its analog specifically preserved the follicular root sheath, in contrast to P-1075 which did not, indicating a difference in the two drug types. The preservation of the root sheath was measured by increased TIMP expression and sulfotransferase activity and indicates that the root sheath is a target tissue for minoxidil. Our results show that follicles cultured at the air-liquid interface maintain a better morphology and produced greater hair growth than follicles cultured on tissue culture plastic.

Air↗
PubMed1993

Female circumcision: obstetric issues.

Female circumcision is a problem unfamiliar to most Western obstetrician-gynecologists. We present a case illustrative of the unique management problems posed by these patients during labor. A method of releasing the anterior vulvar scar tissue to allow vaginal delivery is described. Sensitivity and a nonjudgmental approach as to what is culturally appropriate care for these women are of paramount importance.

Adult↗
PubMed1993

Tympanic thermometry for recording basal body temperatures.

Evaluation of 12 menstrual cycles using oral, rectal, and TM temperature measuring devices (over 2,000 individual readings) confirmed the ovulatory thermal shift was equally detected with TM thermometry compared with the traditional methods. Although a single TM reading was satisfactory, an average of three successive readings provided a smoother graph (decreased variance). The device appears acceptable, and even preferred, for recording BBT charts, primarily because of its nearly instantaneous readings.

Adolescent↗
PubMed1992

Comparative study of mammography and mammary serum antigen estimation for breast cancer screening.

OBJECTIVE: To compare mammary serum antigen (MSA) levels with mammography as a screening test for breast cancer. To determine the value of MSA testing to decrease the need for women to undergo mammography. DESIGN: A blind prospective comparison of MSA levels and mammography to detect breast cancer. SETTING: Royal Women's Hospital Breast Cancer Screening Clinic. Women were mainly self-referred. RESULTS: MSA levels had a wide range in normal women and women with mammography-detected breast cancer. Mean MSA levels in women with breast cancer reflected tumour volume, but a wide range was again seen. At 60% specificity, the sensitivity of an elevated MSA level for breast cancer was 63% for invasive cancer and zero for in-situ disease. MSA levels were modestly but significantly elevated in smokers over non-smokers. CONCLUSION: The MSA level is an insufficiently sensitive or specific marker to have a role in screening for breast cancer.

Antigens, Neoplasm↗
PubMed1992

Capacitance, short-circuit current and osmotic water flow across different regions of the isolated toad skin.

The amphibian antidiuretic hormone, arginine vasotocin, stimulated osmotic water flow across isolated skin from the pelvic but not the pectoral skin of the toad, Bufo woodhouseii. Changes in the apical membrane capacitance were not observed for either region of the skin following treatment with arginine vasotocin when there was an osmotic gradient across the tissue. In the absence of an osmotic pressure gradient, the apical membrane capacitance of the pelvic skin increased from 2.8 +/- 0.5 to 3.3 +/- 0.6 microF.cm-2 after treatment with 5 x 10(-8) M arginine vasotocin. Under these conditions, apical membrane capacitance of the pectoral skin was 1.8 +/- 0.1 microF.cm-2 and did not change significantly after arginine vasotocin treatment. The amiloride-sensitive short-circuit current across the pelvic skin was stimulated by arginine vasotocin as was the density of channels in the apical membrane as determined by fluctuation analysis. Values for channel density in the pelvic skin also correlated with apical membrane capacitance and increased from 90 to 273 channels per micron2 of estimated membrane area following arginine vasotocin treatment. In the pectoral skin the stimulation of short-circuit current following arginine vasotocin treatment was small and an increase in channel density could not be demonstrated. The current through single Na+ channels in both regions of the skin did not different either before or after arginine vasotocin treatment.

Amiloride↗
PubMed1992

Minoxidil sulfotransferase, a marker of human keratinocyte differentiation.

The sulfation of minoxidil is catalyzed by a sulfotransferase activity in a number of tissues including skin. To investigate further the nature of the minoxidil sulfotransferase activity in epithelial tissue and to compare this activity to that of cholesterol sulfotransferase, which has already been shown to be induced during the differentiation of epithelial cells, we cultured normal human epidermal keratinocytes in a keratinocyte growth medium for 4 d, after which the media were replaced with either the same growth media or media with increasing Ca++ concentrations. Cholesterol sulfotransferase, minoxidil sulfotransferase, and transglutaminase were determined during the differentiation of the cells in the three media. Time-activity curves that suggested two different sulfotransferase activities were induced during the differentiation process. U-77581, a competitive inhibitor of minoxidil sulfotransferase activity, inhibited the sulfation of minoxidil sulfotransferase activity in the keratinocyte homogenates, but it did not inhibit the sulfation of cholesterol. These data indicate that at least two sulfotransferase activities are induced during the differentiation of epithelial keratinocytes and minoxidil sulfotransferase is an early marker of that differentiation.

Biomarkers↗
PubMed1992

Factors associated with rehabilitation in head and neck cancer.

Head and neck cancer patients must adapt to changes in facial structure and dysfunctions associated with breathing, eating, sensing, and movement following treatment. The impact of social support, mode(s) of treatment, and disfigurement and dysfunction on rehabilitation outcomes was studied in a convenience sample of 51 cancer survivors. The Sickness Impact Profile, a 136-item self-report instrument that elicited data in 12 activity of daily living areas was used to measure the dependent variable, rehabilitation outcome. Perceived social support was measured with the Personal Resources Questionnaire (Part 2). Facial disfigurement was measured based on the surgical procedure; nine dysfunctions common to head and neck cancer patients were measured on ladder scales and combined to provide a total dysfunction score. Facial disfigurement was not significantly associated with rehabilitation outcomes, but perceived social support and degree of dysfunction were significantly correlated with rehabilitation. No significant differences in rehabilitation outcomes between modes of treatment were found. Findings suggest a need for further research on rehabilitation strategies which improve outcomes for dysfunctions associated with head and neck cancer.

Activities of Daily Living↗
PubMed1991

The abnormal mammogram--what to do.

When an abnormality is detected in a mammogram the following questions should be answered: 1. Does a significant abnormality exist, that is, is the abnormality present in at least two views? 2. Should special imaging techniques, such as ultrasound, be used? 3. What is the conclusion of the radiologist? 4. Is the radiological abnormality clinically palpable? 5. Is the opinion of a breast specialist required? 6. Can fine needle aspirations cytology of the area be performed accurately and without trauma? 7. Should biopsy be undertaken? By posing these questions in sequence and obtaining firm answers, small cancers should not be missed and the biopsy rate will be kept to an acceptably low level.

Biopsy↗
PubMed1990

Minoxidil sulfate is the active metabolite that stimulates hair follicles.

An important step in understanding minoxidil's mechanism of action on hair follicles was to determine the drug's active form. We used organ-cultured vibrissa follicles to test whether it is minoxidil or its sulfated metabolite, minoxidil sulfate, that stimulates hair growth. Follicles from neonatal mice were cultured with or without drugs and effects were assessed by measuring incorporation of radiolabeled cysteine in hair shafts of the treated follicles. Assays of minoxidil sulfotransferase activity indicated that vibrissae follicles metabolize minoxidil to minoxidil sulfate. Dose-response studies showed that minoxidil sulfate is 14 times more potent than minoxidil in stimulating cysteine incorporation in cultured follicles. Three drugs that block production of intrafollicular minoxidil sulfate were tested for their effects on drug-induced hair growth. Diethylcarbamazine proved to be a noncompetitive inhibitor of sulfotransferase and prevented hair growth stimulation by minoxidil but not by minoxidil sulfate. Inhibiting the formation of intracellular PAPS with chlorate also blocked the action of minoxidil but not of minoxidil sulfate. Acetaminophen, a potent sulfate scavenger blocked cysteine incorporation by minoxidil. It also blocked follicular stimulation by minoxidil sulfate apparently by directly removing the sulfate from the drug. Experiments with U-51,607, a potent minoxidil analog that also forms a sulfated metabolite, showed that its activity was inhibited by both chlorate and diethylcarbamazine. These studies show that sulfation is a critical step for hair-growth effects of minoxidil and that it is the sulfated metabolite that directly affects hair follicles.

Acetaminophen↗
PubMed1990

Changing patterns in the presentation of breast cancer over 25 years.

The clinical stage at presentation of 280 women with histologically proven breast cancer is reviewed over a 25 year time span from 1962 to 1987. The data from 240 unscreened patients, including 87 women from the period 1962 to 1963, 103 women from 1981 to 1982, and 50 women from 1986 to 1987 demonstrate a chronologically based improvement in the stage of disease at presentation over the 25 years. Specifically, over that period, there was a fall in the mean tumour diameter, a reduction in the proportion of patients with involved axillary nodes, and a greater percentage of patients with Stages I and II disease. A reduction in the symptomatic period was also noted over this time, and a direct relationship was found between the duration of symptoms and tumour size, nodal status and overall stage of disease. A subsequent comparison with the staging data from 40 women with breast cancer detected at a breast screening clinic (1985-87) shows that significant further advances in the earlier diagnosis of breast cancer can be achieved. Mammographic breast screening centres represent the best-known means of early breast cancer detection, and thus may hold the key to reducing breast cancer mortality.

Adult↗
PubMed1989

Recovery: a phenomenon extending beyond discharge.

The purpose of this study was to conceptualize and order theoretically the process of recovery. Intensive telephone interviews were carried out at 2, 4, and 6 weeks postoperatively to elicit descriptions of postdischarge experiences from 25 subjects who had experienced uncomplicated hospitalizations for cholecystectomy surgery. Postdischarge recovery was a process of returning to normal as defined by preillness comparative standards of physical, social, and psychological well-being that progressed sequentially in three phases: passivity, activity resumption, and stabilization. Decisions concerning phase progression were made by integrating physiological and health professional cues with self-imposed and situational pressures. Subjects who perceived negative physical symptoms, especially fatigue, and who were unable to respond to pressures expressed frustration with the recovery process. Implications for nursing practice include providing patients with individualized anticipatory guidance and interventions that build endurance.

Activities of Daily Living↗
PubMed1988

Quantitative aspects of growth hormone cell maturation in the normal and little mutant mouse.

Growth hormone (GH) cells were analyzed by means of ultrastructural morphometry in the pars distalis of pituitary glands from male adult and immature normal (C57BL) and homozygous little (lit/lit) mutant mice. Thin sections were exposed to anti-GH serum and processed immunocytochemically with the colloidal-gold technique. In the pars distalis of adult lit/lit mice, the mean volume density of GH cells/total tissue was 24% of the normal value, granules/GH cells was 58% of normal, and granules/total tissue was only 12% of normal. Deficits in all of these parameters likewise occurred in immature glands, though to a lesser extent than in the adults. The results indicate that the GH deficiency in this mutant reflects quantitative deficits in both the secretory granule content of GH cells, as well as the GH cell content of the gland, with the latter being the more severely affected.

Animals↗
PubMed1987

Sulfation of minoxidil by human platelet sulfotransferase.

In an attempt to determine whether (1) sulfotransferase activity in human platelets would convert minoxidil to minoxidil sulfate and (2) inter-subject variations in this sulfotransferase activity could be noted, platelet homogenates were incubated with minoxidil and 35S-PAPS in HEPES buffer at 37 degrees C for 30 min. Radioactivity which was extracted into ethyl acetate and shown by HPLC to elute with authentic minoxidil sulfate was counted by scintillation counting. Aliquots of the platelet homogenates were also preincubated at 43 degrees C for 15 min to determine the thermal stability of the sulfotransferase activity. Sulfotransferase activity in platelets from 48 adult males ranged from 0.9-13.2 pmol minoxidil sulfate produced/10(7) platelets per 30 min (mean 4.91 +/- 2.84 pmol/10(7) platelets per 30 min +/- SD). Thermal stable sulfotransferase activity ranged from 0.2-7.6 pmol minoxidil produced/10(7) platelets per 30 min and varied from 15 to 57% of the total sulfotransferase activity. Thus, the results indicate that human platelets can effect the sulfation of minoxidil and that sulfotransferase activity does show inter-subject variation.

Adolescent↗