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Biomedical subjects

D J Morris

Publications and source records attributed to D J Morris.

At least 37 records · Page 2Linked to original sources
PubMed1998

Skin-sparing mastectomy and immediate reconstruction: oncologic risks and aesthetic results in patients with early-stage breast cancer.

Skin-sparing mastectomy has been advocated as an oncologically safe approach for the management of patients with early-stage breast cancer that minimizes deformity and improves cosmesis through preservation of the skin envelope of the breast. Because chest wall skin is the most frequent site of local failure after mastectomy, concerns have been raised that inadequate skin excision could result in an increased risk of local recurrence. Precise borders of the skin resection have not been well established, and long-term local recurrence rates after skin-sparing mastectomy are not known. The purpose of this study was to evaluate the oncologic safety and aesthetic results for skin-sparing mastectomy and immediate breast reconstruction with a latissimus dorsi myocutaneous flap and saline breast prosthesis. Fifty-one patients with early-stage breast cancer (26 with ductal carcinoma in situ and 25 with invasive carcinoma) undergoing primary mastectomy and immediate reconstruction with a latissimus flap were studied from 1991 through 1994. For 32 consecutive patients, skin-sparing mastectomy was defined as a 5-mm margin of skin designed around the border of the nipple-areolar complex. After the mastectomy, biopsies were obtained from the remaining native skin flap edges. Patients were followed for 44.8 months. Histologic examination of 114 native skin flap biopsy specimens failed to demonstrate breast ducts in the dermis of any of the 32 consecutive patients studied. One of 26 patients with ductal carcinoma in situ had metastases to the skin of the lateral chest wall and back. Four other patients, one with stage I disease and three with stage II-B disease, had recurrent breast carcinoma. The stage I patient had a local recurrence in the subcutaneous tissues near the mastectomy specimen. Two patients suffered axillary relapse, and one had distant metastases to the spine. The findings of this study support the technique of skin-sparing mastectomy as an oncologically safe one, based on an absence of breast ductal epithelium at the margins of the native skin flaps and a local recurrence rate of 2 percent after 45 months of follow-up. Although these results need to be confirmed with greater numbers of patients and longer follow-up, skin-sparing mastectomy and immediate breast reconstruction may be considered an excellent alternative treatment to breast conservation for patients with ductal carcinoma in situ and early-stage invasive breast cancer.

Adult↗
PubMed1998

Dermal autografts for fascial repair after TRAM flap harvest.

To find an alternative to synthetic mesh closure of abdominal fascial defects after transverse rectus abdominis musculocutaneous (TRAM) flap harvest, dermal autografts were removed from tissue to be discarded and used for fascial closure. Dermal grafts have been used for herniorrhaphy and fascial repair after TRAM harvest previously, but have never been systematically studied. The dermal autograft technique was used in 24 patients to repair or reinforce anterior rectus sheath or external oblique fascia after TRAM harvest for breast reconstruction. During the same period, 25 other patients underwent TRAM breast reconstruction with abdominal wall closure by other methods. All patients were followed by serial physical examinations given by the operating surgeon. Average follow-up in the dermal autograft group was 12.6 versus 12.0 months in the second group. In the dermal autograft group, two patients complained of bulging of the anterior abdominal wall; one developed a true hernia, away from the location of the dermal autograft. In the second group, two patients experienced bulging. Wounds and infectious complications were similar in both groups. Dermal autografts are a useful alternative to mesh repair or direct closure of fascial defects after TRAM flap harvest.

Adult↗
PubMed1998

A second enzyme protecting mineralocorticoid receptors from glucocorticoid occupancy.

We have confirmed that A6 cells (derived from kidney of Xenopus laevis), which contain both mineralocorticoid and glucocorticoid receptors, do not normally possess 11 beta-hydroxysteroid dehydroxgenase (11 beta-HSD1 or 11 beta-HSD2) enzymatic activity and so are without apparent "protective" enzymes. A6 cells do not convert the glucocorticoid corticosterone to 11-dehydrocorticosterone but do, however, possess steroid 6 beta-hydroxylase that transforms corticosterone to 6 beta-hydroxycorticosterone. This hydroxylase is cytochrome P-450 3A (CYP3A). We have now determined the effects of 3 alpha,5 beta-tetrahydroprogesterone and chenodeoxycholic acid (both inhibitors of 11 beta-HSD1) and 11-dehydrocorticosterone and 11 beta-hydroxy-3 alpha,5 beta-tetrahydroprogesterone (inhibitors of 11 beta-HSD2) and carbenoxalone, which inhibits both 11 beta-HSD1 and 11 beta-HSD2, on the actions and metabolism of corticosterone and active Na+ transport [short-circuit current (Isc)] in A6 cells. All of these 11 beta-HSD inhibitory substances induced a significant increment in corticosterone-induced Isc, which was detectable within 2 h. However, none of these agents caused an increase in Isc when incubated by themselves with A6 cells. In all cases, the additional Isc was inhibited by the mineralocorticoid receptor (MR) antagonist, RU-28318, whereas the original Isc elicited by corticosterone alone was inhibited by the glucocorticoid receptor antagonist, RU-38486. In separate experiments, each agent was shown to significantly inhibit metabolism of corticosterone to 6 beta-hydroxycorticosterone in A6 cells, and a linear relationship existed between 6 beta-hydroxylase inhibition and the MR-mediated increase in Isc in the one inhibitor tested. Troleandomycin, a selective inhibitor of CYP3A, inhibited 6 beta-hydroxylase and also significantly enhanced corticosterone-induced Isc at 2 h. These experiments indicate that the enhanced MR-mediated Isc in A6 cells may be related to inhibition of 6 beta-hydroxylase activity in these cells and that this 6 beta-hydroxylase (CYP3A) may be protecting the expression of corticosterone-induced active Na+ transport in A6 cells by MR-mediated mechanism(s).

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

Localization of 2 11beta-OH steroid dehydrogenase isoforms in aortic endothelial cells.

11Beta-hydroxysteroid dehydrogenase (11beta-HSD) is expressed in vascular smooth muscle cells (VSMC) but has not been reported to be present in vascular endothelial cells. This enzyme assists in regulating the cellular concentration of active endogenous glucocorticoids (GCs). We have observed that endothelium intact rat aortic rings express message for both Type 1 and Type 2 11beta-HSD whereas primary cultures of VSMC express only mRNA for the Type I isoform. Since GCs diminish prostacyclin synthesis in endothelial cells, we hypothesized that 11beta-HSD is present in vascular endothelial cells. In primary cultures of rat aortic endothelial (RAE) cells, mRNA from both isoforms of 11beta-HSD could be detected by RT-PCR with higher levels of the Type 1 isoform. The oxo-reductase reaction "activating" 11-dehydro metabolites back to the parent steroid is the preferred enzyme direction (12:1 after a 120 minutes steroid incubation) in intact RAE cells. When RAE cells are grown in the presence of antisense oligonucleotides specific for Type 1 11beta-HSD, oxo-reductase activity is decreased by approximately 50% but the dehydrogenase reaction, which inactivates endogenous GCs and is characteristic of the Type 2 isoform, is unaffected. Thus endothelial cells appear to express both isoforms of 11beta-HSD; the Type 1 isoform dominates functioning in the oxo-reductase mode. Inhibition of the oxo-reductase reaction may lower the local concentrations of GC and indirectly allow for increased production of prostacyclin in endothelial cells.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

Impact of dietary Na+ on glycyrrhetinic acid-like factors (kidney 11beta-(HSD2)-GALFs) in human essential hypertension.

Our previous studies have shown that human urine contains glycyrrhetinic acid-like factors (GALFs) that possess inhibitory activity against kidney 11beta-hydroxysteroid dehydrogenase isoform 2 (HSD2). The present studies were undertaken to determine the impact of dietary Na+ intake on the levels of kidney 11beta(HSD2)-GALFs. The excretion of kidney 11beta(HSD2)-GALFs in 24-hour urine samples of 30 unmedicated subjects (10 normotensive and 10 high/normal-renin and 10 low-renin essential hypertensive subjects) on both 200- and 10-mmol Na+ diets was studied. No differences in the urinary levels of kidney 11beta(HSD2)-GALFs were observed among the three groups on the high-Na+ diet. However, with a low-Na+ diet, the levels of kidney 11beta(HSD2)-GALFs were significantly increased in hypertensive subjects but not in normal subjects. Levels increased from 8.3+/-1.4 to 17.3+/-2.9 and 6.7+/-1.3 to 10.6+/-1.4 carbenoxolone sodium units/d in high/normal-renin (P=.01) and low-renin hypertensive subjects (P=.07), respectively; normal subjects changed from 8.0+/-1.9 to 10.6+/-2.4. The levels of kidney 11beta(HSD2)-GALFs were significantly higher in the high/normal-renin hypertensive subjects than in either the control normotensive subjects or the low-renin hypertensive subjects when challenged with the low-Na+ diet (P<.05 by Wilcoxon rank-sum test). The greater response of the high/normal-renin essential hypertensive subjects indicated that they may utilize kidney 11beta(HSD2)-GALFs when challenged with a low-Na+ diet, whereas the low-renin essential hypertensive subjects do not.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Breast infarction after internal mammary artery harvest in a patient with calciphylaxis.

The use of the internal mammary artery during coronary artery bypass grafting is commonplace. Complications associated with the harvest of the internal mammary artery have predominantly been wound related. These range from skin dehiscence to complete avascular necrosis of the sternum. This report documents complete ischemic necrosis of a breast in a patient with end-stage renal disease and a history of calciphylaxis, after the harvest of an internal mammary artery.

Breast↗
PubMed1997

Effects of licorice derivatives on vascular smooth muscle function.

Vascular smooth muscle contains a bidirectional form of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) which can inactivate (dehydrogenase) endogenous circulating glucocorticoids (GCs) or activate (oxo-reductase) 11-dehydro-metabolites by their conversion back to the parent steroid. Enzyme direction in vascular smooth muscle (VSM) has potential physiological consequences since GCs may enhance the response to known vasoconstrictors. We determined that carbenoxolone is a competitive inhibitor of 11beta-HSD contained in VSM cells with a lower Ki for forward dehydrogenase reaction (0.02 microM) compared to the oxo-reductase reaction (0.41 microM). To test whether changes in enzyme directional activity can affect the contractile response, aortae from adrenally intact Sprague Dawley rats were removed and sectioned into 2.5 mm rings. Rings were incubated with corticosterone 10 nM plus carbenoxolone (CBX) 10 microM (a concentration well above the Ki for both the dehydrogenase and oxo-reductase reaction) for 24 hrs. These rings showed an enhanced dose dependent contractile response to phenylephrine (PE) 0.01 microM(-1) microM and to angiotensin II 1 microM compared to rings incubated with corticosterone alone, CBX alone, or controls: [e.g. response to PE 1 microM in mg of contractile force, mean +/- SE: corticosterone plus CBX 1495 +/- 162 (n=10) vs corticosterone 1039 +/- 64 (n=9), p<0.05]. Aortic rings preincubated with 11-dehydrocorticosterone 10(-7)M and CBX 10 microM displayed a decreased contractile response compared to 11-dehydrocorticosterone alone. Thus in situ glucocorticoid metabolism is important in mediating the constrictor responses of vascular tissue.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Selective inhibition of sheep kidney 11 beta-hydroxysteroid dehydrogenase isoform 2 activity by 5 alpha-reduced (but not 5 beta) derivatives of adrenocorticosteroids.

We have previously reported that 5 alpha and 5 beta pathways of steroid metabolism are controlled in vivo by dietary Na+ and glycyrrhetinic acid, see Gorsline et al. 1988; Latif et al. 1990. The present investigations provide evidence supporting the suggestion that endogenous substances may regulate the glucocorticoid inactivating isoenzymes, 11 beta-HSD (hydroxysteroid dehydrogenase) 1 (liver) and 11 beta-HSD2 (kidney). The activity of 11 beta-HSD is impaired in essential hypertension, following licorice ingestion, and in patients with apparent mineralocorticoid excess where 11 beta-HSD2 is particularly affected. In all three conditions, excretion of the less common 5 alpha metabolites is elevated in urine. We now report on the differential abilities of a series of Ring A reduced (5 alpha and 5 beta) adrenocorticosteroid and progesterone metabolites to inhibit these isoenzymes. Using liver microsomes with NADP+ as co-factor (11 beta-HSD1), and sheep kidney microsomes with NAD+ as co-factor (11 beta-HSD2), we have systematically investigated the abilities of a number of adrenocorticosteroids and their derivatives to inhibit the individual isoforms of 11 beta-HSD. A striking feature is the differential sensitivity of the two isoenzymes to inhibition by 5 alpha and 5 beta derivatives. 11 beta-HSD1 is inhibited by both 5 alpha and certain 5 beta derivatives. 11 beta-HSD-2 was selectively inhibited only by 5 alpha derivatives: 5 beta derivatives were without inhibitory activity toward this isoform of 11 beta-HSD. These results indicate the importance of the structural conformation of the A and B Rings in conferring specific inhibitory properties on these compounds. In addition, we discuss the effects of additions or substitutions of other functional groups on the inhibitory potency of these steroid molecules against 11 beta-HSD1 and 11 beta-HSD2.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Successful diagnosis and management of cytomegalovirus carditis.

Cytomegalovirus (CMV)-associated carditis in the immunosuppressed patient carries a 60% mortality. Underlying pathogenesis is poorly understood but may involve either direct viral invasion or autoimmune cardiac damage triggered in response to the infection. Specific anti-cytomegalovirus therapy and/or anti-inflammatory drugs have been shown to benefit in cases where an early diagnosis was established. We report an unusual case of endo-pericarditis which was temporally related to acute cytomegalovirus infection diagnosed by the immediate early antigen detection in cell culture on whole blood.

Adult↗
PubMed1997

Interactions between pulse separation and pulse polarity order in cochlear implants.

Interactions between pulse separation and pulse polarity order were examined using psychophysical studies of electrical detection thresholds in nonhuman primates. Subjects were trained using acoustic stimuli, then deafened in one ear and implanted with an electrode array for electrical stimulation of the cochlea. Threshold vs pulse separation functions for trains of biphasic electrical pulses were compared for constant and alternating leading phase polarity. When leading phase polarity was held constant, threshold vs pulse separation functions were nonmonotonic (U-shaped). Small polarity-dependent (cathodic vs anodic leading phase) differences in absolute thresholds were observed at long pulse separations, but function shape was independent of leading phase. When leading phase polarity alternated, there was a pronounced reduction in thresholds at short pulse separations (below about 1 ms), resulting in monotonically increasing threshold vs pulse separation functions. At long pulse separations, functions for alternating and constant polarity stimuli were similar. Polarity effects were most apparent for longer duration trains (20 pulses) at long pulse durations (1-2 ms/phase). For stimuli consisting of only two biphasic pulses, alternating polarity effects depended on whether cathodic or anodic phases were adjacent. The neural mechanisms underlying these effects probably include refractory properties and/or residual potentials.

Acoustic Stimulation↗
PubMed1997

11Beta-hydroxysteroid dehydrogenase in the Dahl rat.

Dahl salt sensitive (Dahl-S) rats develop hypertension soon after birth. The cause of the increased salt-sensitivity in the Dahl-S rat is unknown. The mineralocorticoid specificity of the kidney receptor is conferred by the activity of 11beta-hydroxysteroid dehydrogenase (11beta-HSD). There are two isoforms of 11beta-HSD (11beta-HSD1 and 11beta-HSD2). Deficiency or inhibition of 11beta-HSD2 causes sodium retention and hypertension. In the present study we measured the activity of hepatic and kidney 11beta-HSD1 in Dahl-S and R rats before and after the development of hypertension. The activity of 11beta-HSD1 in the liver was lower in the Dahl-S rats at 6 weeks of age (S = 8.01 +/- 0.89 v R = 11.91 +/- 0.84 nmol/mg protein/10 min (P < .02) but there was no difference at 10 weeks. In contrast, 11beta-HSD1 in the kidney was not different at 6 weeks but it was significantly lower in the Dahl-S rats at 10 weeks (S = 0.91 +/- 0.04 v R = 1.12 +/- 0.01 nmol/mg protein/10 min (P < .001). Plasma renin concentration was lower at 6 (6w) and 10 weeks (10w) in the Dahl-S rats: S-6w = 4.2 +/- 0.4 versus R-6W = 6.3 +/- 0.8 ng angiotensin I (AI)/mL/h (P < .04) and S-10w = 6.4 +/- 0.7 versus R-10w = 10 +/- 0.9 ng AI/mL/h (P < .009). Plasma aldosterone and corticosterone were not different between the two strains. Systolic blood pressure (SBP) in the Dahl-S rats was 124 +/- 3 mm Hg at 6 weeks and 241 +/- 6 mm Hg at 10 weeks (P < .001). SBP in the Dahl-R rats was 113 +/- 5 mm Hg at 6 weeks and 143 +/- 4 mm Hg at 10 weeks. In conclusion, Dahl-S rats have lower hepatic 11beta-HSD1 activity at 6 weeks of age and lower kidney 11beta-HSD1 at 10 weeks of age compared with Dahl-R rats of the same age. These findings suggest that diminished activity of both liver and kidney 11beta-HSD1 may play a role in the salt sensitivity and development of hypertension in the Dahl-S rat.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

Chromosome 2 hypersensitivity and clonal development in murine radiation acute myeloid leukaemia.

Acute myeloid leukaemias induced by ionizing radiation in mouse are characterized by chromosome (chr) 2 aberrations. While it is known that chr 2 aberrations form early and in abundance post-irradiation, unequivocal evidence for hypersensitivity of chr 2 in the first post-irradiation mitoses is lacking. Here it is established that chromosomal aberrations detected in bone marrow cells by chromosome painting are induced in all mice at an approximately 2-fold greater frequency in chr 2 by comparison with chrs 1 and 3 at 24 and 48 h following in vivo whole-body X-irradiation. Long-term follow up studies (to 15 months post-irradiation) indicated that chromosomal hypersensitivity is accounted for largely by the existence of hot-spots for aberration formation on sensitive chromosomes. Analysis of clonal developments suggested that chr 2 aberrant clones are selected for entry into the proliferating bone marrow cell compartment in preference to cells with other aberrations and that these clones in general have a higher proliferative potential. However, neither the induction of chr 2 aberrations nor the presence of a chr 2 aberrant clone specifically predict the development of AML in an individual irradiated mouse. Nonetheless these events or sub-groups of these events are necessary for AML development.

Acute Disease↗
PubMed1997

Polymerase chain reaction for detection of Chlamydia trachomatis in conjunctival swabs.

AIMS/BACKGROUND: Ocular Chlamydia trachomatis infection in the west occurs as opthalmia neonatorum, acquired from the mother, or adult paratrachoma which is also associated with current genital tract infection. Accurate rapid laboratory diagnosis facilitates management, but the relative merits of antigen detection or DNA amplification tests are unresolved. METHODS: A polymerase chain reaction (PCR) test was developed which amplified part of the plasmid shared by all the serovars of C trachomatis. Conjunctival swabs were tested using an in house immune dot-blot test (IDBT) for chlamydial lipopolysaccharide antigen, a commercial direct fluorescent antibody (DFA) test for chlamydial elementary bodies, and the PCR (DNA extracted using guanidinium lysis buffer). RESULTS: The PCR achieved a detection limit of 100 plasmid copies (10 elementary bodies). In a combined retrospective and prospective clinical evaluation, the PCR and IDBT gave identical results with 21 positive and 57 negative eye swabs. However, interpretation of the DFA test required meticulous examination of the stained smear, sometimes by two microscopists. CONCLUSIONS: The PCR is likely to play an increasing role in the diagnosis of ocular C trachomatis infection because of its excellent sensitivity and specificity.

Adult↗
PubMed1997

Kidney 11 beta-HSD2 is inhibited by glycyrrhetinic acid-like factors in human urine.

We have previously shown that human urine contains substances that, like glycyrrhetinic acid, inhibit 11 beta-HSD1. We have named these substances "glycyrrhetinic acid-like factors" or GALFs. We now have found that human urine contains measurable quantities of both 11 beta(HSD1)- and 11 beta(HSD2)-GALF inhibitory substances. Both are markedly elevated in pregnancy. Their chemical and high-performance liquid chromatography (HPLC) characteristics suggest that several of the GALFs are steroidal. Large quantities of neutral 11 beta(HSD1)- and 11 beta(HSD2)-GALFs can be extracted directly from urine into ethyl acetate, yielding fraction EA1. Hydrolysis of the GALFs remaining in the aqueous phase by beta-glucuronidase markedly increases the total amounts of GALFs, with the majority now being ethyl acetate extractable (fraction EA2). These EA2 post-hydrolysis GALFs can be separated by HPLC resulting in at least six components with inhibitory activity against each isoenzyme. Only two GALF peaks are active against both 11 beta-HSD1 and 11 beta-HSD2. The others are peaks with specific 11 beta(HSD1)- and 11 beta(HSD2)-GALF inhibitory activity. The GALFs in the same posthydrolysis EA2 extract are also inhibitory toward the 11 beta-HSD1 that is present in vascular smooth muscle where they may play a role in the mechanisms controlling blood pressure. We have also found that 11 beta-HSD2 is selectively inhibited by 5 alpha- (but not by 5 beta-) reduced steroids. GC-MS analysis of the 11 beta(HSD2)-GALFs in EA2 is now being performed to determine whether this group includes 3 alpha,5 alpha-ring A-tetrahydro-reduced derivatives of steroids.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1997

11BetaOH-progesterone affects vascular glucocorticoid metabolism and contractile response.

Vascular smooth muscle (VSM) contains a bidirectional isoform of 11beta-hydroxysteroid dehydrogenase (11beta-HSD), the enzyme that can metabolize endogenous glucocorticoids to their respective 11-dehydro derivatives. 11BetaOH-progesterone (11betaOH-P), a compound that can be produced in vivo, is as potent or more potent than licorice derivatives in inhibiting renal and hepatic 11beta-HSD. When studied in homogenates prepared from primary cultures of rat VSM, 11betaOH-P and its derivative, 11-keto-progesterone (11-keto-P), proved to be potent, directionally specific inhibitors of vascular 11beta-HSD. 11BetaOH-P selectively inhibited the forward dehydrogenase reaction (corticosterone-->11-dehydrocorticosterone), whereas 11-keto-P selectively blocked the reverse oxidoreductase reaction. To test the physiological effects, vascular rings were prepared from rat aorta. Rings were incubated in culture media containing either a submaximal concentration of corticosterone (10 nmol/L), 11-dehydrocorticosterone (100 nmol/L), 11betaOH-P (1 micromol/L), 11-keto-P (1 micromol/L), or a combination of glucocorticoid and inhibitor for 24 hours. After the 24-hour incubation, rings were briefly stimulated sequentially with phenylephrine (10 nmol/L to 1 micromol/L) and angiotensin II (1 micromol/L). The immediate contractile response in rings incubated with both corticosterone and 11betaOH-P was greater than in rings previously incubated with either the corticosterone or 11betaOH-P alone (eg, response to 100 nmol/L phenylephrine in milligrams of force, mean+/-SE: corticosterone, 728+/-56, n=9; 11betaOH-P, 325+/-105, n=4; both, 1132+/-122, n=8; corticosterone versus both, P<.01). In contrast, the immediate contractile responses to phenylephrine and to angiotensin II were attenuated in rings exposed previously to both 11-dehydrocorticosterone and 11-keto-P. Thus, 11betaOH-P and 11-keto-P (and possibly structurally similar compounds) alter the vascular effects of glucocorticoids and may play a role in glucocorticoid-induced hypertension.

Animals↗
PubMed1997

Influence of dietary sodium on the renal isoforms of 11 beta-hydroxysteroid dehydrogenase.

Endogenous glucocorticoids are converted to their biologically inert 11-dehydroderivatives by isoforms of the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD). The low-K(m), NAD(+)-dependent renal isoform (Type 2) identified in the distal nephron protects mineralocorticoid receptors from activation by endogenous glucocorticoids. The function of high-K(m), NADP(+)-dependent renal isoform (Type 1) is less well understood. Since glucocorticoids may modulate sodium transport in renal proximal tubules (PT), we hypothesized that Type 1 activity in this segment may be regulated by dietary Na(+)-11 beta-HSD activity was assessed in homogenates of canine PT by the conversion of cortisol to cortisone in the presence of NADP+ 200 microM. A high-Na+ diet for 4 days increased the Vmax 4-fold, with no change in the Type 1 K(m) (40 mEq/day Na+ diet: K(m) 0.959 microM, Vmax 3.40 pmoles/min/mg protein versus 150 mEq/day Na+ diet: K(m) 0.962 microM, Vmax 14.8 pmoles/min/mg protein). Type 1 mRNA also rose in the salt repleted animals. The high-Na+ diet produced no detectable change in the Type 2 isoform enzyme kinetics and mRNA level. No reverse oxo-reductase activity was noted with either renal isoform. Thus, renal Type 1 11 beta-HSD can be regulated by dietary Na+ independent of changes in the renal Type 2 isoform.

11-beta-Hydroxysteroid Dehydrogenases↗