Search PubMed⌕ Search

Biomedical subjects

M Morris

Publications and source records attributed to M Morris.

At least 253 records · Page 14Linked to original sources
PubMed1993

Analysis of Bacitracin B using fast atom bombardment and tandem mass spectrometry.

Bacitracin is a mixture of polypeptide antibiotics produced by the action of Bacillus subtilis and Bacillus licheniformis. The mixture has previously been shown to contain at least ten components, of which only the major component, Bacitracin A, and its oxidized counterpart, Bacitracin F, have been fully structurally evaluated. Using fast atom bombardment ionization with tandem mass spectrometry, three isobaric components of one of the minor constituents of the mixture, Bacitracin B, have been structurally characterized, delineating the three single substitution sites within Bacitracin A where Ile has been replaced by Val.

Amino Acid Sequence↗
PubMed1993

Microvascular density of the human paraventricular nucleus decreases with aging but not hypertension.

Microvascular density was determined in the supraoptic nuclei (SON) and paraventricular nuclei (PVN) of fixed brain tissue from 19 human subjects ranging in age from 30 to 85 years. Eight of these patients had hypertension. No sex- or hypertension-related differences in microvascular density were found in either the SON or PVN. However, capillary density decreased in the PVN with aging. These results indicate a differential pattern of microvascular loss in the human hypothalamus with aging.

Adult↗
PubMed1993

Stage I cervical adenocarcinoma: prognostic evaluation of surgically treated patients.

In order to evaluate clinicopathologic determinants of recurrence in adenocarcinoma of the uterine cervix, a detailed retrospective chart review and complete pathology analysis were performed for 79 patients who had been treated by Type III radical hysterectomy between 1975 and 1988. All patients had clinical stage I disease; 77 had cervical diameters of 4 cm or less. Eleven patients (14%) developed recurrent disease with a median time to recurrence of 14 months (range, 7-51). Recurrence location was central in 5 patients, pelvic wall in 2, and distant in 4. Seven patients died of disease. Five-year actuarial survival was 89%. None of the clinical features examined as possible prognostic factors was predictive of recurrence, including patient age (P = 0.91), cervical diameter (P = 0.30), presence of pain (P = 0.53), presence of abnormal bleeding (P = 0.19), and history of oral contraceptive use (P = 0.58). However, univariate analysis showed lymph node spread (P = 0.008), lymph-vascular space invasion (P = 0.05), and increasing grade (P = 0.05) to be significant predictors of recurrence. Lymph-vascular space invasion remained significant when patients with positive nodes were excluded (P = 0.026). Depth of invasion > 3 mm was associated with greater recurrence risk than depth < or = 3 mm (P = 0.01). Number of mitoses (P = 0.10) was not significant. Multivariate analysis selected nodal positivity as the major prognostic parameter (P = 0.04). Further studies are needed to more clearly define the role of lymph-vascular space invasion, as an elevated risk ratio of 1.6 suggests an increased risk for recurrence. Patients whose pretreatment biopsies demonstrate obvious lymph-vascular space invasion might be considered for alternate treatment.

Actuarial Analysis↗
PubMed1993

Effect of new investigational drug taxol on oncolytic activity and stimulation of human lymphocytes.

Taxol is a new antineoplastic agent active in the treatment of drug-refractory ovarian and metastatic breast neoplasms. Extensive investigations have been concerned with the effect of taxol on a variety of tumor cells, but there is virtually no information about its effect on human lymphocytes. Since lymphocytes, especially natural killer (NK) cells, have been recognized to play an important role in the body's defense against tumors, we studied the effect of taxol on the cytotoxicity of naive (unstimulated) peripheral blood mononuclear cells (MNCs) and NK cells as well as on these cells' activation and growth in interleukin-2 (IL-2) cultures. We found that taxol impaired the cytotoxicity of naive MNC and NK cells against the NK-sensitive cell line K-562 and against an ovarian cancer cell line, OV-2774, in a concentration-dependent fashion. The highest impairment was observed after incubation of the effector cells with 10 micrograms/ml taxol. In addition, taxol also interfered with the induction of lymphokine-activated cytotoxicity and with lymphocyte growth in IL-2 cultures. However, IL-2 preactivated NK cells displayed substantial levels of cytotoxicity even after taxol treatment. These findings, which indicate that treatment with taxol should follow rather than precede immunotherapeutic intervention, may be important in planning combined chemo- and immunotherapy strategies for cancer patients.

Analysis of Variance↗
PubMed1993

Aborted exenterative procedures in recurrent cervical cancer.

Preparation for pelvic exenteration is a traumatic experience for every patient, especially so when the procedure has to be aborted because of advanced disease. This occurred in 111 of 394 patients who underwent exploration for possible pelvic exenteration for recurrent cervical cancer at the University of Texas M. D. Anderson Cancer Center between 1970 and 1990. We reviewed these cases to better delineate preoperative factors predictive of unresectability. Distributions of initial stages and pathological diagnoses were similar to those for all cases of primary cervical cancer. The median time from primary therapy to recurrence was 12 months. The reasons for aborting the procedure included the presence of peritoneal disease in 49 patients (44%), for which the only preoperative finding with significant correlation was the presence of a pelvic mass (P = 0.03). Other reasons for aborting the procedure included nodal disease in 45 patients (40%), related to a short interval from primary therapy (P = 0.008) and the notation of fibrosis on preoperative exam (P = 0.01), parametrial fixation in 15 patients (13%), and hepatic lesions or bowel involvement in 5 patients (4.5%). Peritoneal cytology was negative in 61 of 79 patients (77.2%) and was of predictive value only in patients with adenocarcinoma. In conclusion, disseminated disease can seldom be detected during preoperative work-up. Evaluation of nodal status with computed tomography, lymphangiogram and directed fine-needle aspiration, and examination of peritoneal cytology in cases with adenocarcinoma, are the best available means of reducing the number of aborted procedures.

Adult↗
PubMed1993

Prognostic factors for patients undergoing simple hysterectomy in the presence of invasive cancer of the cervix.

To identify significant prognostic factors and sites of treatment failure in patients undergoing simple hysterectomy in the presence of invasive cervical cancer, the records of 122 women referred following such a procedure were reviewed retrospectively. All but 2 patients received postoperative megavoltage irradiation. Patients with and without gross disease at the start of posthysterectomy treatment had 5-year survival rates of 39 and 75%, respectively. Factors found to be significantly related to survival were the presence of gross disease (P = 0.0001), retrospectively determined tumor stage (P = 0.0001), and lymphangiogram status (P = 0.007). Patients with adenocarcinoma did not fare worse than those with squamous carcinoma (P = 0.6). By multivariate analysis, factors emerging as significantly detrimental to survival were the presence of gross disease (P = 0.0001) and aortic adenopathy on lymphangiogram (P = 0.004). The most common site of treatment failure was the pelvis. The radiotherapy complication rate was 18%; 7% of patients experienced major morbidity. While survival for patients with no residual cancer after simple hysterectomy is favorable, the treatment complication rate may be higher than that reported for patients undergoing primary irradiation. Survival for patients with gross disease at the start of posthysterectomy treatment is poor.

Adenocarcinoma↗
PubMed1993

Cervical conization as definitive therapy for early invasive squamous carcinoma of the cervix.

Young women who present with stage Ia carcinoma of the uterine cervix may strongly desire preservation of fertility. There is little published information on the outcome of patients treated for early invasive cervical cancer with cervical conization. Patients were considered eligible for conservative management if they had a squamous lesion invading to a depth less than or equal to 3 mm with no lymphatic or vascular space involvement and negative margins. We identified 14 patients who had been treated by cervical conization alone for early invasive carcinoma of the cervix. Pathologic variables were reviewed for all patients. Patient records were retrospectively reviewed for demographic, pathologic, and follow-up information. The mean depth of invasion was 1.6 mm (range, 0.5-2.8 mm). The mean number of cone sections evaluated was nine (range, 6-13 sections). The median follow-up period following conization was 26.5 months (range, 1-170 months). One patient underwent subsequent hysterectomy and was found to have mild dysplasia. Thirteen patients have retained their uteri and none has developed recurrent invasive or preinvasive lesions. We conclude that cervical conization is an acceptable therapy for selected cases of microinvasive squamous carcinoma of the uterine cervix. Larger studies of this patient group are indicated to confirm the safety of conization as definitive therapy in selected cases of early invasive cervical carcinoma.

Adult↗
PubMed1993

Intraoperative radiographs to confirm the adequacy of lymph node resection in patients with suspicious lymphangiograms.

Between June 1991 and October 1992, we used presurgery lymphangiograms and intraoperative radiographs to identify and remove suspicious nodes in the pelvic and para-aortic chains of 19 patients with bulky pelvic cancers. Surgery comprised extraperitoneal exploration using a midline vertical or paramedian "J" incision. After grossly enlarged nodes were removed, an intraoperative anterior-posterior (AP) abdominal radiograph was obtained. The exposure field approximated the 24-hr delay AP LAG radiograph. Both films were compared in the operating room to confirm removal of abnormal nodes. Initial resection removed all suspicious nodes in 16 of 19 cases. Additional dissection resulted in successful node excision in the other 3 patients. Most of these "missed" nodes were behind or between vessels. The median number of nodes sampled was 15 (range 2-47). Bilateral sampling was performed in 15 cases. Metastatic tumor was present in 14 patients (74%) who had from 1 to 8 positive nodes. Of the 5 negative specimens, all contained lipogranulomata; two had extensive fatty replacement, 2 contained Müllerian inclusions, and 1 had reactive follicular hyperplasia which could be accountable for the radiographic abnormalities. Extracapsular extension was noted in 12 of 14 metastatic samplings. Radiotherapeutic treatment planning was then tailored to lymph node status and the location of positive nodes. Combined use of preoperative LAG and intraoperative films is useful in ensuring that complete resection of abnormal nodes has been accomplished. Whether removal of gross lymph node metastases enhances survival requires further study.

Adult↗
PubMed1993

Treatment of advanced or recurrent endometrial carcinoma with single-agent carboplatin.

Cisplatin and the combination of cisplatin, doxorubicin, and cyclophosphamide have documented activity in women with advanced or recurrent endometrial adenocarcinoma. However, response duration has been short and toxicity is substantial. To determine if similar activity could be obtained with less morbidity, we prospectively treated 33 patients with 360 mg/m2 carboplatin given intravenously every 28 days. Mean patient age was 69 years (range 40-86); all had a Zubrod functional status of 2 or less. Seventeen patients had advanced primary tumors, and 16 had recurrent disease. Prior treatment included surgical resection in 29 cases, hormonal agents in 7, and radiotherapy in 22. No patient had received prior chemotherapy. Mean treatment was 5.7 cycles. Nine of 27 patients (33%) with measurable disease had objective responses, including three complete and six partial responses. Nonresponders included 10 patients with stable disease and 8 whose disease progressed while on treatment. Median time to response was 3 months. Median progression-free survival for responders and nonresponders was 5 and 4 months, respectively. At analysis, 20 patients had died of disease, 7 were alive with disease, and 6 were clinically free of disease. Disease-free patients include 1 with a complete response and 5 who began treatment without measurable disease. Median follow-up for surviving patients was 18 months (range 4-32). Treatment toxic effects were minimal and largely limited to myelosuppression; 3 patients had grade 3 thrombocytopenia, 1 had grade 3 neutropenia, and 5 had grade 3 anemia. Carboplatin has define activity in endometrial carcinoma and offers a well-tolerated palliative therapeutic alternative.

Adenocarcinoma↗
PubMed1993

Evidence that suppression of insulin secretion by insulin itself is neurally mediated.

We examined the mechanism by which an increase in blood insulin concentration inhibits insulin secretion by the pancreas. To this end, we determined plasma C-peptide concentrations during euglycemic-hyperinsulinemic (approximately 500 pmol/L) clamps in five patients with insulin-dependent diabetes mellitus (IDDM) after combined pancreas and kidney (P/K) transplantation, in five nondiabetic patients after kidney transplantation (K), and in six normal control subjects. Hyperinsulinemia decreased C-peptide concentrations in K patients (by 60%, P < .01) and controls (by 35%, P < .05), but not in P/K patients (653 +/- 115 v 702 +/- 197 pmol/L before and after 4 hours of hyperinsulinemia, respectively). The main difference between K patients and controls and P/K patients was that the pancreas in K patients and controls was innervated, whereas the transplanted pancreas of K/P patients was denervated. The data therefore suggested that the inhibition of pancreatic insulin secretion by hyperinsulinemia was neurally mediated.

Adult↗
PubMed1993

High incidence of ectopic nucleolar organizer regions in human testicular tumors.

Eight primary testicular germ cell tumors, one teratocarcinoma cell line, and one Leydig cell tumor were studied to determine the importance of modifications of the nucleolar organizer regions (NORs) in human testicular tumors. Cytogenetic analysis after silver staining showed active ectopic NORs in two primary embryonal carcinomas (EC) in the cell line and in single cells of each of two seminomas (S). In one EC, an ectopic NOR was localized to chromosomal region 1q4; the others were on unidentified rearranged chromosomes. All tumors in which ectopic NORs were observed were hyperdiploid and possessed marker chromosomes typical of human germ cell tumors. Quantitative DNA analysis was performed on three tumors: a teratocarcinoma (TC) and the Leydig cell tumor, which had provided no analyzable mitoses, and a seminoma which was cytogenetically diploid. In all three cases, the major populations were hyperdiploid. The results, in combination with those of an earlier study, provide evidence that active ectopic NORs are common in human testicular tumors.

Aneuploidy↗
PubMed1993

Multiple nodules of intermediate trophoblast following hydatidiform moles.

After removal of a complete hydatidiform mole, seven patients developed an unusual complication characterized by a proliferation of intermediate trophoblast-forming nodules in the endometrium or myometrium. The patients were examined because of vaginal bleeding or mildly elevated human chorionic gonadotrophin (HCG) titers. Three patients were cured by hysterectomy, one by endometrial curettage, one by endometrial curettage plus chemotherapy, and one (who also had choriocarcinoma) by multiple doses of chemotherapy after hysterectomy; the seventh patient was lost to follow-up. These nodules probably represent a mild form of postmolar trophoblastic disease.

Adult↗
PubMed1993

Huntington's disease: predictive testing and the molecular genetics laboratory.

We describe the laboratory-related aspects of a series of 40 completed presymptomatic tests for Huntington's disease, using linked DNA markers. Pedigree structure and marker heterozygosity are shown to be important factors, both in the number of laboratory analyses required to give an informative situation and the residual uncertainty of the final estimate. Specific problems encountered by the testing laboratory are described, with possible ways of avoiding them, and the close links required between laboratory and clinical staff are emphasised.

Adult↗
PubMed1993

Sinoaortic denervation alters the molecular and endocrine responses to salt loading.

Neuroanatomical and physiological evidence indicates that baroreceptors influence hypothalamic vasopressin (VP) and oxytocin (OT) neurons. We evaluated the effects of sinoaortic denervation (SAD) on the molecular and endocrine response to salt loading. Sham-operated or SAD rats were given a 2% NaCl solution to drink for 72 h. A group with limited salt water intake was included as a second control because the denervated rats consumed less salt than the controls. Plasma VP, OT and osmolality and posterior pituitary peptide content were measured. Brains were processed for evaluation of VP and OT mRNA expression using in situ hybridization with computer quantitation. Salt loading produced equivalent increases in plasma VP and OT in the control and SAD groups, however, there was a greater depletion of posterior pituitary peptides in the denervated animals. Salt loading produced significant decreases in pituitary VP and OT in the SAD animals, 69.8 +/- 8.4% and 68.3 +/- 4.0%, respectively. In the control groups, there was no decrease in VP content and a decrease in OT only in the control ad lib group. The peptide mRNA response to salt loading was also altered in the denervated rats. There was a significant increase in the area and intensity of the labeling for OT mRNA in the PVN in the SAD salt group. The control salt rats showed an increase in the SON and the salt-limited group showed no changes. For VP mRNA, the only change noted was in the SON of the salt-loaded SAD animals. These results show that chronic denervation of arterial baroreceptors augments the hypothalamic VP and OT response to salt loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Many peptides that are present in the external zone of the median eminence are not secreted into the hypophysial portal blood of sheep.

Apart from the well recognized factors that are produced by the hypothalamus and secreted into hypophysial portal blood to regulate pituitary function, there is a range of neuropeptides that are present in the median eminence and could be secreted to serve a modulatory function. In this study we have collected hypophysial portal blood and jugular venous blood from sheep in an attempt to identify which of these putative modulatory peptides might be secreted from the median eminence. We have measured neuropeptide Y (NPY), substance P (SP), galanin (GAL), neurokinin A (NKA), peptide histidine isoleucine (PHI), vasoactive intestinal peptide (VIP), neurotensin (NT) and cholecystokinin (CCK). We also examined the sheep median eminence using immunohistochemistry for NPY, SP and GAL and determined degradation profiles of NPY, SP, GAL and NKA in portal and jugular plasma. In no instance did we find that levels of the above peptides were consistently higher in portal blood than in peripheral blood. In some cases levels of peptide were lower in portal plasma e.g. for NPY (6/10 sheep). In one experimental series SP levels in portal plasma were significantly (p < 0.05) lower than levels in jugular plasma but this was not found in another experimental series. Galanin levels were significantly (p < 0.01) lower in portal plasma compared to levels in jugular plasma. We conducted in vitro studies to determine whether or not the above peptides are selectively degraded in portal blood but were unable to show any differences between the rates of degradation in portal and jugular plasma. Immunohistochemistry revealed projections into the external zone of the median eminence for NPY, GAL and SP. This study shows that none of the above peptides are secreted into the hypophysial portal blood of sheep. For some peptides e.g. GAL, enzymes from the endothelial cells of the portal vessels may enhance degradation. Projections into the external zone of the median eminence of neuronal systems containing these peptides may serve to modulate the secretion of the well recognized release and inhibiting factors by acting on the neurosecretory terminals.

Animals↗
PubMed1993

Glucose metabolism and leg blood flow after pancreas/kidney transplantation.

Patients with insulin-dependent diabetes mellitus (IDDM) who have undergone combined pancreas and kidney (P/K) transplantation, are hyperinsulinemic and have impaired insulin-stimulated whole body glucose uptake. We have investigated whether their reduced glucose uptake was due to insulin resistance at the tissue level or was caused by reduced muscle blood flow, previously reported to be present in patients with IDDM. Leg blood flow (LBF, determined with mercury strain-gauge plethysmography), glucose uptake (GRd, determined with 6,6 D2-glucose), and glucose oxidation (Gox, determined by indirect calorimetry) were obtained during euglycemic-hyperinsulinemic (approximately 500 pM) clamping in five P/K patients, five kidney transplant (K) patients, and six controls. Insulin-stimulated GRd was reduced in P/K patients compared to controls (23 +/- 4 vs. 44 +/- 6 mumol/kg/min, P < 0.05); Gox was comparable but glucose storage was reduced in P/K and K patients compared to controls (9 +/- 3 and 13 +/- 4 vs. 28 +/- 7 mumol/kg/min, P < 0.05). Basal LBF (3.9 +/- 0.3, 4.6 +/- 0.9, and 4.9 +/- 0.6 mL/dL leg tissue/min) and insulin-stimulated LBF (5.6 +/- 0.6, 6.1 +/- 1.1 and 6.1 +/- 0.9 mL/dL leg tissue/min) were similar in P/K, K patients, and controls. We concluded, that P/K patients had normal muscle blood flow but were insulin resistant at the tissue level, and that the insulin resistance was responsible, at least in part, for their hyperinsulinemia.

Adult↗
PubMed1993

Measurement of chromosomal aberrations, sister chromatid exchange, hprt mutations, and DNA adducts in peripheral lymphocytes of human populations at increased risk for cancer.

Using a multidisciplinary approach, we have measured various indicators of DNA damage in peripheral lymphocytes of human populations potentially at increased risk for cancer. Sister chromatid exchanges (SCE) and polycyclic aromatic hydrocarbon (PAH)-DNA adducts were evaluated in a group of firefighters; chromosomal aberrations and hprt mutations were evaluated in a group of cancer patients undergoing radioimmunoglobulin therapy (RIT); SCE and acrolein-modified DNA were measured in cancer chemotherapy patients and in pharmacists preparing chemotherapy prescriptions; and SCE and PAH-DNA adducts are being measured in U.S. army troops stationed in Kuwait. Our results indicate that both SCE and PAH-DNA adduct levels were not elevated in firefighters, but that other factors such as smoking status and race were risk factors for increased SCE and PAH-DNA adducts. RIT was found to increase background rates of chromosome-type aberrations and frequencies of hprt mutations and there was a strong correlation between levels of therapy-induced chromosome damage sustained in vivo and in vitro sensitivity to radiation-induced chromosome damage. Peripheral blood lymphocytes of cancer patients treated with cyclophosphamide showed higher levels of SCE and had a higher incidence of acrolein adducts in DNA. Lymphocytes from pharmacists preparing antineoplastic drugs were found to acquire increased in vitro sensitivity to SCE induction by phosphoramide mustard with increased lifetime duration of drug handling. A prospective, longitudinal study was performed to identify environmental factors that modulate genetic damage in breast cancer patients. Women with benign breast masses and no apparent disease served as controls. Mutant frequency, cloning efficiency, and chromosomal aberration frequency did not differ significantly among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromosome Aberrations↗