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Biomedical subjects

M Morris

Publications and source records attributed to M Morris.

At least 343 records · Page 19Linked to original sources

A thermodynamic model for the self-association of human spectrin.

The self-association of human spectrin at 28.8 degrees C in 0.11 M salt (pH 7.5) has been studied by means of sedimentation equilibrium. Coincidence of omega function plots as a function of total spectrin concentration (0-2 g/L) indicated that equilibrium was achieved and that no significant concentration of solute was incapable of participating in the self-association reaction. On the basis of the root-mean-square deviation of the fits and the randomness of the residuals, the behavior can be described equally well, either by a cooperative isodesmic model, in which K12 approximately 2 x 10(6) M-1 and all other K approximately 10(6) M-1, or by an attenuated scheme in which K(i-1)i approximately (3.5 x 10(6)/i M-1. The returned values of the second virial coefficient, B, for both these models fall within the range calculated from the charge and Stokes radius of spectrin. A mechanism for spectrin self-association consistent with both schemes is proposed in which spectrin heterodimers undergo a reversible opening at the self-association interface. These open heterodimers then undergo indefinite self-association to form a series of open-chain oligomers in dynamic equilibrium with closed-loop oligomers.

Chemical Phenomena↗

The influence of Org 10172, an antithrombotic heparinoid, on urinary blood loss after transurethral prostatectomy.

We have measured the effects of Org 10172 (a mixture of naturally occurring glycosaminoglycans derived from hog intestinal mucosa) on blood loss after transurethral prostatectomy (TURP), using doses which are likely to prevent postoperative venous thrombosis (VT). 48 patients entered a double-blind randomised pilot study: 18 were given subcutaneous (sc) injections of a placebo and 30 received sc Org 10172 (750 anti-Xa units/day, 500 units twice daily (bid), or 750 units bid, starting just before TURP and continued until discharge; 10 patients per group). No Org 10172 regimen increased peroperative blood loss but all caused a similar trend towards increased urinary bleeding after surgery. Since there was no apparent dose effect gradient, it was decided to pool the data from all three dosing blocks: this analysis showed that Org 10172 increased geometric mean blood loss during the first 2 days after surgery from 10.4 gm hemoglobin (Hgb; range = 3.2-71) to 20.5 gm Hgb (range = 1.9-147) (p = .005), an effect which retained its significance after allowing for two other major determinants of postoperative bleeding, the weight of prostate resected and the length of surgery, and also when pooling was restricted to the twice daily Org 10172 injection groups and their corresponding controls. Bleeding was not severe, but our results indicate a need for caution when considering the use of Org 10172 in this setting.

Aged↗

An immunochemical and biochemical study of catecholaminergic activity in dissociated hypothalamic cultures.

Dopamine (DA)-containing cells of the medial basal hypothalamus (MBH) were dissociated and maintained in culture for up to 9 days. Cultures were evaluated both biochemically and immunochemically for DA activity. DA biosynthesis was determined using incorporation of [3H]tyrosine and was analyzed by HPLC with electrochemical detection. Immunochemical studies were performed to identify tyrosine hydroxylase (TH)-positive and neuron-specific enolase (NSE)-positive cells. Morphometric analyses determined the cell size, density, process length and the percent of neurons which were catecholaminergic. TH-positive neurons ranged from 6 to 8% of the total neuronal population when examined over days 3-9 of culture and the length of TH-positive neurites was significantly greater than that of NSE-positive cells. There was incorporation of [3H]tyrosine into DA as evidenced by the presence of [3H]DA in both the media and tissue and the inhibition of synthesis with alpha-methyl-p-tyrosine. There was a greater amount of labeled DA in the media than in the tissue at every time point examined. On the other hand, biosynthesis of DA in fresh brain tissue revealed approximately equal levels of DA in the media and tissue. These studies indicate that DA continues to be synthesized in dissociated cultures of MBH as evidenced by both the biochemical and immunochemical analyses and that there appears to be some alteration in the ability of these neurons to store the newly synthesized amine.

Animals↗

Differential regulation of calcitonin gene-related peptide and substance P in cultured neonatal rat vagal sensory neurons.

Nodose (inferior vagal sensory) ganglia were removed from neonatal rats, enzymatically dispersed using neutral protease, and maintained on previously dispersed rat atriacytes. After 7-10 days in culture, calcitonin gene-related peptide (CGRP) was present in 1-3 times the molar amount of substance P (SP). The content of SP was doubled by the addition of nerve growth factor (NGF) whereas CGRP was significantly less increased by 50% or less. The addition of forskolin increased SP and CGRP levels in cultures with or without NGF by 60-80 percent. Phorbol ester (PMA) did not alter SP content but significantly raised CGRP content by 40% in NGF supplemented cultures (P less than 0.001). Corticosterone, 0.01-0.1 microM, reduced SP content by 30% independently of NGF but had no effect on CGRP. These studies demonstrate that SP in vagal sensory neurons is more sensitive than CGRP to the effects of NGF or corticosterone. Both peptides are up-regulated by presumed increases in intracellular cyclic AMP, while CGRP (or CGRP neurons) may be independently regulated by protein kinase C.

Animals↗

Nipple aspirate fluids in adult nonlactating women--lactose content, cationic Na+, K+, Na+/K+ ratio, and coloration.

The presence of lactose in nipple secretions is considered biochemical evidence of breast secretory activity, and has been reported to occur more frequently in white compared to brownish or green colored breast fluid. We studied lactose, Na+, and K+ concentrations, the Na+/K+ ratio, and the coloration of nipple aspirate fluid (NAF) from 49 nonpregnant women. A significant relationship was found between the concentrations of lactose, Na+, and K+, and age and the coloration of NAF. Lactose was present in 22/49 (44.8%) of the NAF samples and declined with age from 100% positivity in women less than or equal to 29 years to 29% in those less than or equal to 35 years. In NAF of deep yellow, brown and green colorations, only traces of lactose were found. Na+ and K+ increased with age and with darker colorations compared to white, pale yellow, or colorless NAF. Lactose was present in NAF samples from both parous and nulliparous younger women, indicating that the breasts of many nonpregnant women respond to prolactin stimulation; hence, lactose may provide a simple marker indicating active physiologic secretory activity of the breast. As reported previously, NAF of darker coloration, containing elevated levels of cholesterol, cholesterol oxidation products, and other substances, suggests retention and impaired reabsorption of these and other products of secretion. Because of the secretion and temporary retention by the breast glands of chemical substances of exogenous and endogenous origin, including mutagens and carcinogens, lactose concentration and coloration of NAF may be useful as markers of secretion and reabsorption in future physiologically based clinical and epidemiologic studies of the pathogenesis of breast disease.

Adult↗

Effects of a gastric implant on body weight and gastrointestinal hormones in cafeteria diet obese rats.

In order to evaluate the effectiveness of a gastric implant in an animal model of dietary obesity, silicone implants (2.5 ml) were inserted into the stomachs of male rats maintained on a chow or "cafeteria" diet. At the time of implantation, the cafeteria fed rats weighed 14% more than chow fed controls. Overweight cafeteria fed animals lost weight in response to the gastric implant, whereas control chow fed animals did not. Both implant groups had significant increases in stomach weights in contrast to sham implant groups, but the increase was much less in the cafeteria diet group. The fasting plasma levels of the gastrointestinal hormones, gastrin and pancreatic polypeptide, and oxytocin (a marker of vagal afferent function) were measured by radioimmunoassay. Cafeteria fed sham or implanted animals had significantly higher fasting levels of plasma oxytocin and gastrin, and significantly lower plasma levels of pancreatic polypeptide than the chow fed groups. These studies demonstrate that the gastric implant has more effect on weight in overweight animals on a palatable mixed diet, perhaps related to both mechanical and neural factors.

Animals↗

High-risk metastatic gestational trophoblastic disease: further stratification into two clinical entities.

Forty-two of sixty-seven patients (62.7%) treated for high-risk metastatic trophoblastic disease achieved and maintained complete remissions. The survival rate was significantly improved in those patients with scores lower than 8 according to a modification of the World Health Organization (WHO) prognostic scoring system. A low score was associated with a higher probability of response to single-agent therapy, although the difference was not statistically significant. The score, however, was significantly associated with response to multiagent chemotherapy with methotrexate, actinomycin D, and cyclophosphamide (P = 0.0004). Therefore, future trials of new combinations of chemotherapy in high-risk patients should be stratified according to the patients' prognostic scores.

Female↗

Secondary cytoreductive surgery for recurrent epithelial ovarian cancer.

Thirty patients with recurrent epithelial ovarian carcinoma who underwent secondary tumor-reductive surgery at M. D. Anderson Cancer Center were studied retrospectively. All had been initially treated by primary reductive surgery and postoperative chemotherapy and had a period of clinical remission of at least 6 months thereafter. Ninety percent of patients had grade 2 or 3 tumors. In 17 (57%), residual tumor volume was reduced to less than 2 cm. There were no postoperative deaths, but 40% of patients suffered postoperative morbidity, mostly prolonged ileus. Median survival after second surgery was 16.3-18 months for patients with residual tumor volume less than 2 cm and 13.3 months for those with residual volume greater than 2 cm (nonsignificant). When the second surgery followed the first by less than 18 months, survival was a median of 13.5 months after the second operation as compared with 19 months when the interval was 18 months or longer (nonsignificant). Twenty-two patients received postsurgical chemotherapy; only 11% of those who were evaluable responded. Although secondary tumor-reductive surgery for recurrent ovarian cancer is technically feasible, in the absence of an efficacious second-line medical therapy, its value is limited.

Adult↗

Secondary cytoreductive surgery in epithelial ovarian cancer: nonresponders to first-line therapy.

Thirty-three patients with progressive or stable epithelial ovarian cancer who underwent secondary tumor-reductive surgery at the University of Texas M. D. Anderson Cancer Center were retrospectively studied. All patients had primary cytoreductive surgery followed by chemotherapy. Lack of response to chemotherapy was clinically documented preoperatively. The tumors of 55% of the patients were secondarily cytoreduced to a greatest diameter of less than 2 cm. Sixty-six percent of the patients required bowel resection. Operative morbidity occurred in 24% of patients, mostly in those with bowel resection. Overall, median survival after secondary surgery was 9.4 months. For patients with residual tumor less than 1 cm, median survival after secondary surgery was 19.5 months, compared with 8.3 months for patients with residual tumor of 1 cm or more (P less than 0.004). Patients with an interval between primary cytoreductive effort and secondary surgery of less than 12 months survived a median of 7.3 months, compared with an 18.3-month median survival for patients with an interval of 12 months or more (P less than 0.004). The present study provided no evidence that secondary surgery is of significant benefit in most patients who have progressive disease during chemotherapeutic treatment of epithelial ovarian cancer.

Adolescent↗

The serology of delta hepatitis and the detection of IgM anti-HD by EIA using serum derived delta antigen.

A sensitive and specific capture assay for IgM antibody to hepatitis D virus (HDV) was developed employing serum-derived delta antigen (HDAg). In a retrospective and prospective study of an outbreak of hepatitis B (HB), 135 hepatitis B surface antigen (HBsAg) positive drug-abusers with acute hepatitis and 18 HBsAg carriers, attending various hospitals and clinics in Dublin, were found to be infected with HDV. Serological follow-up was available from 24 of those with acute hepatitis allowing a comparison of the duration and level of IgM anti-HD with the more commonly used markers, HDAg and anti-delta (anti-HD), and an assessment of the usefulness of each. HDV and HB serology was grossly altered by human immunodeficiency virus (HIV) in two patients, with severe clinical manifestation in one. All 135 patients with HDV co-infection had delta antigenaemia. In co-infections with optimum sampling times, the mean duration of delta antigenaemia was 21 days. IgM anti-HD was always found between HDAg and sero-conversion to anti-delta and was the only 'window' marker present in five cases. The mean duration of IgM anti-HD was four weeks (optimum at 2.8 weeks) and was of moderate or low titre and occurred simultaneously with HDAg in 78%. In HDV-infected HBsAg carriers, high-titre IgM anti-HD (greater than 1/10,000) persisted for the duration of the study and is a useful indicator of chronic HDV infection. IgM anti-HD was not found in 202 random blood donors nor in 205 patients with non-B hepatitis or other disorders.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Specificity↗

Immunohistochemical differentiation of clear-cell carcinoma of the female genital tract and endodermal sinus tumor with the use of alpha-fetoprotein and Leu-M1.

The morphologic differentiation between clear-cell carcinoma and endodermal sinus tumors is difficult at times. To improve the accuracy of the diagnosis, the authors studied nine ovarian and eight vaginal clear-cell carcinomas and seven endodermal sinus tumors of the ovary by immunohistochemical methods with the use of antibodies to alpha-fetoprotein and Leu-M1. Sixteen (94.1%) of the 17 clear-cell carcinomas and two (28.5%) of the seven endodermal sinus tumors reacted for Leu-M1, whereas six (85.7%) of the seven endodermal sinus tumors and three (17.6%) of the 17 clear-cell carcinomas stained for alpha-fetoprotein. Three clear-cell carcinomas and two endodermal sinus tumors showed immunoreactivity for both markers. No reactivity for either of these markers was present in one endodermal sinus tumor and one clear-cell carcinoma. All 13 tumors that stained only for Leu-M1 proved to be clear-cell carcinomas, and the four that reacted exclusively for alpha-fetoprotein were endodermal sinus tumors. Therefore, the authors concluded that positive immunostaining for Leu-M1 and negative immunostaining for alpha-fetoprotein support the differential diagnosis of clear-cell carcinoma, whereas a positive reaction for alpha-fetoprotein and a negative reaction for Leu-M1 favor a diagnosis of endodermal sinus tumor. However, positive or negative staining for both markers appears to have no diagnostic value.

Adenocarcinoma↗

Cultured hypothalamic explants from spontaneously hypertensive rats have decreased vasopressin and oxytocin content and release.

To investigate the central nervous system (CNS) changes in the spontaneously hypertensive rat (SHR), a tissue culture model was used to examine the content and release (24 hour) of the peptide hormones, vasopressin (VP) and oxytocin (OT), from brain explants. Nuclear regions consisting of the paraventricular (PVN) or supraoptic (SON) nuclei were microdissected from prehypertensive SHR and Wistar-Kyoto (WKY) rats. Media levels of VP and OT were measured at 1, 3, 4, and 7 days of culture. After three days of culture, the PVN explants from SHR secreted significantly less VP and OT (both reduced 80%) than did those from WKY. Release of both VP and OT in the SON explants was significantly lower (approximately 50% lower) in the SHR only at seven days of culture. Additionally, tissue content of the peptides was measured after 0, 1, 4, and 7 days of culture. Tissue content of VP and OT was decreased (40% or more) in the SHR in both nuclear regions after four and seven days of culture. In addition, nicotine was found to stimulate the release of VP from SON, but not PVN, cultures in both SHR and WKY explants. Immunohistochemical data showed that there was not a preferential loss of VP or OT neurons in explants from the SHR. Therefore, this in vitro model would indicate that there is a difference in the ability of cultured explants of PVN and SON from SHR and WKY (four-week-old) to synthesize and/or release the peptide hormones VP and OT.

Animals↗

Baroreceptor influences on oxytocin and vasopressin secretion.

The objective of these studies was to investigate the role of arterial baroreceptors in the control of neurohypophyseal secretion. The effect of sinoaortic denervation on basal and osmotic-induced release of oxytocin and vasopressin and on blood pressure was determined. Hypertonic or isotonic saline was infused intravenously into sham-operated or denervated rats 3 days after surgery. Plasma oxytocin and vasopressin were measured at 5 and 15 minutes after the infusion. The control levels of oxytocin were increased in the denervated rats, but vasopressin levels were not significantly altered. The vasopressin and oxytocin responses to hypertonic saline were greater after baroreceptor denervation. Plasma oxytocin was increased from 4.7 +/- 0.9 to 72.2 +/- 8.7 pg/ml in the denervated rats and from 1.8 +/- 0.3 to 39.9 +/- 6.7 pg/ml in the sham-operated control group at 5 minutes after the infusion (p less than 0.01). The plasma vasopressin response to hypertonic saline was 7.1 +/- 0.6 pg/ml in the sham-operated versus 11.1 +/- 1.6 pg/ml in the denervated rats (p less than 0.05). There was no difference between sham-operated and denervated rats in the effect of hypertonic saline on plasma sodium and hematocrit. Mean arterial blood pressure was increased after sinoaortic denervation (116.3 +/- 4.2 mm Hg in the sham-operated vs. 138.2 +/- 8.3 mm Hg in the denervated rats, p less than 0.05); however, there was no difference in the pressor response to hypertonic saline. These results show that the baroreceptor system influences the secretion of both oxytocin and vasopressin, with effects on basal secretion as well as the response to an osmotic stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Neuropeptide Y in the sympathetic control of blood pressure in hypertensive subjects.

Neuropeptide Y (NPY) coexists with noradrenaline in postganglionic sympathetic neurons and with noradrenaline and adrenaline in the central nervous system. The possibility that NPY is released into the circulation during activation of the sympathoadrenal system was investigated in ten moderately hypertensive volunteers using three different stimuli. In healthy moderately hypertensive volunteers cold pressor test, head up tilt and graded bicycle exercise resulted in increased blood pressure, heart rate and plasma catecholamine concentrations. While there was a trend for plasma NPY-like immunoreactivity (NPY-LI) to increase during cold pressor test and head up tilt, NPY-LI concentration only increased significantly during bicycle exercise, the stimulus of greatest duration. These results suggest that plasma NPY-LI can be released into the circulation on sympathoadrenal activation in moderately hypertensive subjects and demonstrate that the pattern of release is similar to that previously observed in normotensive subjects.

Adrenal Glands↗