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Biomedical subjects

M Newman

Publications and source records attributed to M Newman.

At least 127 records · Page 7Linked to original sources
PubMed1986

Interstrain correlation between behavioural effects of lithium and effects on cortical cyclic AMP.

Six inbred mouse strains were studied to explore possible correlations between lithium effects on behaviour and on cortical cyclic AMP. The strains were fed lithium in ground food for 3 weeks before behavioural tests and ex vivo evaluation of cyclic AMP accumulation. Replicating previous reports, there was a significant inverse correlation (r = 0.73, n = 6) between spontaneous activity and noradrenaline-induced cyclic AMP, and an almost significant correlation (r = 0.67, n = 6) between spontaneous activity and adenosine-induced cyclic AMP accumulation. The effect of lithium to depress spontaneous activity correlated with its effect to inhibit adenosine-induced rises in cyclic AMP (r = 0.716, n = 6). There were significant strain differences in the behavioural responses to amphetamine. In two strains where amphetamine raised activity and lithium inhibited the amphetamine-induced rise, lithium also significantly inhibited the adenosine-induced rise in cyclic AMP. Two other strains showed amphetamine-induced rises in activity that were not inhibitable by lithium, and these strains showed no significant inhibition by lithium of adenosine-induced cyclic AMP accumulation. The remaining two strains showed no behavioural activity increase with amphetamine.

Amphetamine↗
PubMed1986

Does testosterone affect the normal menstrual cycle?

In order to throw further light on the role of androgens in the aetiology of the polycystic ovary syndrome (PCO) we have examined the effect of artificially increasing serum testosterone levels on menstrual function in a group of ovulating women. Six women were studied who had either severe premenstrual syndrome or loss of libido for which they were treated with 100 mg testosterone by s.c. implantation. All had regular menstrual cycles. For 1 month before implantation serum LH, FSH, oestradiol (E2), progesterone and testosterone were measured three times per week. All women showed normal cyclical variation of LH, FSH, E2 and progesterone. Following implantation, three times weekly blood samples were taken during the first and third cycles. No patient had any disturbance of menstrual pattern. All continued to show cyclical changes of LH, FSH, E2 and progesterone. Serum E2 and progesterone were lower but not significantly so in the luteal phase of the treated cycles. This was despite a mean serum testosterone which rose from 1.3 to 7.1 nmol/l at the end of the third week following implantation and to 4.1 nmol/l at the end of the third month. Sex hormone binding globulin levels fell as expected by 18.5% during the first cycle. The lack of significant effect of a markedly elevated serum testosterone level on cyclical hormone changes is indirect evidence that in PCO the primary cause of the menstrual disturbance is not excessive production of ovarian or adrenal testosterone.

Adult↗
PubMed1986

Spontaneous early preterm labour associated with abnormal genital bacterial colonization.

The association between infection and preterm labour was studied in 72 women in spontaneous preterm labour between 26 and 34 weeks gestation and in 26 control subjects having an elective caesarean section at the same gestational age. The genital microbial flora of each group was studied comprehensively and included mycoplasmas, chlamydiae, ureaplasmas and anaerobes. Subsequent neonatal infection and chorioamnionitis was also studied. Abnormal bacterial colonization, the presence of ureaplasmas, heavy growth of mycoplasmas and chorioamnionitis were all found significantly more often in the study group. This supports the premise that a significant proportion of idiopathic preterm labour is associated with infection and this may permit better prediction and prevention of preterm birth. The continued use of tocolytics should depend upon the identification of the presence or absence of infection. Infection appeared to be the result rather than the cause of ruptured membranes. A recommendation with respect to the classification of abnormal or normal bacterial colonization between 26 and 34 weeks is suggested on the basis of strict criteria.

Bacteria↗
PubMed1986

Equine T lymphocytes express MHC class II antigens.

Six anti-HLA class II mouse monoclonal antibodies (mAbs) were used in conjunction with a rat monoclonal antibody raised against horse lymphocytes to define class II major histocompatibility complex (MHC) molecules in the horse. By utilizing an ELISA assay and complement dependent lymphocytotoxicity assay, five out of the six anti-HLA class II antibodies and the rat anti-horse monoclonal antibody were found to react with a high percentage of peripheral blood lymphocytes. Flow cytometry demonstrated a variable antigen density on peripheral blood lymphocytes and clear evidence for expression by lymphocytes that carried no detectable surface immunoglobulin. None of the antibodies reacted with equine platelets. The mAbs immunoprecipitated an antigenic complex of Mr 29,000-33,000 from horse lymphocytes. It appears that the distribution of MHC class II antigens in the horse is different from that in man but is similar to that in the dog, since MHC class II antigens are expressed on resting peripheral blood lymphocytes which lack membrane-bound immunoglobulins. Correlations between the distribution of MHC class II antigens on lymphocyte subpopulations and their role in immunological phenomena may contribute to our understanding of the functional properties of these molecules.

Animals↗
PubMed1985

The treatment of hirsutism with a combination of desogestrel and ethinyl oestradiol.

Some available oral contraceptive agents are unsuitable for the treatment of hirsutism since, although they suppress endogenous gonadotrophins and so ovarian androgen production, they contain a progestogen which is itself androgenic. The combination of 30 micrograms ethinyl oestradiol (EE2) and 150 micrograms desogestrel (Marvelon) does not suffer from this drawback. We have therefore assessed its value in 15 hirsute women treated for one year. Mean +/- SE androgen-dependent hair growth, assessed photographically fell from 0.31 +/- 0.01 to 0.23 +/- 0.01 mm/d at 1 year (P less than 0.001). Ten of the fifteen patients reported definite subjective improvement. Treatment was associated with a marked rise in SHBG concentration identical to that seen with 30 micrograms EE2 alone. By four months there were significant falls in serum levels of androstenedione and LH throughout the cycle, but not for testosterone, dihydrotestosterone or 5 alpha-androstane 3 alpha, beta 17 -diol. Calculated free testosterone levels were significantly suppressed. All the biochemical changes were maintained after seven months of treatment. We conclude that this preparation is a suitable oral contraceptive for the treatment of hirsute women.

Adolescent↗
PubMed1985

A comparison of lithium effects on human brain and rat brain noradrenaline-sensitive adenylate cyclase.

Lithium (Li) is a drug with numerous biochemical effects. Many of these biochemical effects occur only at high Li concentrations, or disappear after chronic Li treatment. Such effects are probably not related to Li's mechanism of therapeutic action. Inhibition of noradrenaline (NE)-sensitive adenylate cyclase has been proposed as a possible therapeutic mechanism of action for Li. Tolerance does not develop to this effect, which has been reported to occur reliably beginning at 2mM Li in rat cortex. Since 2mM Li is at the upper limit of therapeutic levels in humans, controversy has continued as to whether Li inhibition of NE-sensitive adenylate cyclase is a mechanism of Li's therapeutic action or a mechanism of Li toxicity. We hypothesized that human brain NE-sensitive adenylate cyclase may be more sensitive to Li inhibition than rat brain NE-sensitive adenylate cyclase. Fresh cortical human grey matter was obtained from the edges of surgically removed brain tumors in seven patients. Results showed significant inhibition of NE-sensitive adenylate cyclase at 1mM Li. These results support the possibility that inhibition of NE-sensitive adenylate cyclase is a mechanism of Li's therapeutic action.

Adenylyl Cyclase Inhibitors↗
PubMed1985

Type 1 human T-cell leukemia virus small envelope protein expressed in mouse cells by using a bovine papilloma virus-derived shuttle vector.

In an attempt to express the small (transmembrane) envelope protein p21e of type 1 human T-cell leukemia (lymphotrophic) virus (HTLV-1) exclusive of other viral gene products, we have constructed a recombinant plasmid clone (pMBE-1) in a bovine papillomavirus-derived mammalian expression vector. Mouse C127 cells transfected with the pMBE-1 plasmid expressed the introduced HTLV-1 viral gene(s) as demonstrated by Northern blot and indirect immunofluorescence with natural human antisera. The transfected mouse cells were injected into BALB/c mice, and a monoclonal antibody was recovered which specifically recognizes a 21-kilodalton protein present in HTLV-1 virions, indicating that the pMBE-1 plasmid encodes the small envelope protein.

Animals↗
PubMed1984

The effects of chronic lithium and ECT on A1 and A2 adenosine receptor systems in rat brain.

The influence of chronic dietary lithium administration and electroconvulsive therapy on adenosine A1 and A2 receptors in rat brain were determined. A2 receptor activity was measured by accumulation of cyclic AMP in a cerebral cortical slice preparation after in vitro addition of 2-chloro-adenosine, and was unchanged in animals which received chronic Li but reduced following chronic ECT. A similar reduction was found in the response to noradrenaline and a combination of the two agents. A1 receptors were measured by binding of [3H]cyclohexyladenosine. Both Kd and Bmax values were unchanged after chronic Li or a single ECS, but chronic ECT led to a 70% increase in Bmax. It is proposed that this effect may mediate the reduced locomotor activity seen after chronic ECT in rats, and that it may also be related to the increase in seizure thresholds seen during a course of ECS treatment in humans.

Adenosine↗
PubMed1984

Effect of cyclo(Leu-Gly) on reserpine-induced hypomotility and increases in cortical beta-adrenergic receptors.

Previous studies have indicated that the endogenous peptide, melanotropin release inhibiting factor (MIF) and its analog cyclo(Leu-Gly) ( CLG ) facilitate dopamine (DA) receptor agonist binding and inhibit DA receptor supersensitivity induced by neuroleptics and opiates. The effect of CLG was tested on beta-adrenergic hypersensitivity induced by reserpine to ascertain whether CLG has effects on other neuronal systems besides DA. Administration of reserpine to rats induced hypomotility and enhanced binding of [3H]dihydroalprenolol (DHA) to cortical membranes. Concurrent administration of CLG blocked both the hypomotility and the enhanced [3H]DHA binding to cortical membranes. Lithium has also been shown to prevent reserpine induced hypomotility and increased cortical [3H]DHA binding. These studies suggest that CLG may be producing its effect either like lithium or by an amphetamine like action. If CLG can be shown to have lithium like activity, it could prove to be useful in the treatment of mania.

Animals↗
PubMed1984

Pulling the plug.

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Critical Care↗
PubMed1984

The effect of endogenous progesterone on serum levels of 5 alpha-reduced androgens in hirsute women.

This study was to examine indirectly the effect of endogenous progesterone, a known competitor for 5 alpha-reductase, on androgen metabolism in target organs in hirsute women. Serum levels of progesterone, testosterone (T), androstenedione (A), dihydrotestosterone (DHT) and 5 alpha-androstane 3 alpha 17 beta-diol (3 alpha-diol) and sex hormone binding globulin (SHBG) were assessed serially over a four week period in normal women, six hirsute women with regular menstrual cycles, eight hirsute women with oligomenorrhoea (and presumptive polycystic ovaries) and seven non-hirsute women with oligomenorrhoea. Serum T and A levels were significantly higher than normal in both hirsute and non-hirsute women with oligomenorrhoea, while serum SHBG was significantly lower than normal in the two groups of hirsute women. The calculated free T level was higher than normal in all three groups of patients. DHT levels were not significantly different from normal in any of the three groups of patients. The 3 alpha-diol level showed considerable overlap with normal in all groups of patients and was only significantly higher than normal in hirsute women with oligomenorrhoea (P less than 0.05). There was a small fall in DHT in the late luteal phase of the cycle of those women with a sustained rise in serum progesterone in the second half of the cycle, but no change in serum 3 alpha-diol. These studies suggest that serum 3 alpha-diol may not be as good an indicator of peripheral androgen metabolism in hirsute women as previously reported and that a rise in serum progesterone has only a minimal effect on circulating levels of the active 5 alpha-reduced androgen metabolites. Although in vitro 3 alpha-diol has been shown to be a potent inhibitor of 5 alpha-reductase this casts doubt on its role in this regard in vivo.

Adolescent↗
PubMed1984

Which testosterone replacement therapy?

Three different forms of testosterone (T) replacement therapy were compared; they were the intramuscular injection of mixed testosterone esters 250 mg; the subcutaneous implantation of 6 X 100 mg pellets of fused testosterone; and the oral administration of testosterone undecanoate (TU) 80 mg twice daily. Six hypogonadal males were treated with oral TU for an eight week period, during which time serial serum hormonal estimations were performed over 10 h at the initiation and after four and eight weeks of therapy. Serum T levels showed marked variability both between subjects and within the same subject on different occasions. We attribute this to variability in absorption of TU, which is formulated in oleic acid. The overall mean T level calculated from the areas under the profiles of TU was 12.0 nmol/l. Hormone responses to injected T esters were studied in nine hypogonadal males. Serum T rose to supraphysiological peak concentrations (mean 71 nmol/l) 24-48 h after an injection, followed by an exponential decay to reach baseline concentrations after 2-3 weeks. The overall calculated mean T level in subjects receiving testosterone esters 250 mg every three weeks was 27.7 nmol/l. Subcutaneous implantation of testosterone in six hypogonadal men produced a gradual rise in serum T followed by a slow decline, with T levels remaining within the normal range for 4-5 months. The calculated overall mean T level over 21 weeks after implantation was 17.0 nmol/l. Serum oestradiol (E2) levels remained within the normal male range throughout the study periods on both TU and T implant therapy but showed a supraphysiological peak (mean 347 pmol/l) 24-48 h after a T injection. 5 alpha-dihydrotestosterone (DHT) levels appeared to parallel those of T on the three forms of therapy, with DHT:T ratios being highest for TU therapy. This was also true for the target organ metabolite 5 alpha-androstane-3 alpha,17 beta-diol. At the doses studied drug costs were similar for T implantation (every 5 months) and T ester injections (every 3 weeks), but were 7-8 times higher for TU (80 mg twice a day). We conclude that T implantation remains overall the most physiological form of androgen replacement therapy, is generally well accepted and attended by few side effects; TU may have a useful role in the initial phases of therapy.

Administration, Oral↗
PubMed1984

CPR goes to work.

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Commerce↗