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Biomedical subjects

D M Larson

Publications and source records attributed to D M Larson.

At least 55 records · Page 3Linked to original sources
PubMed1989

Human arterial smooth muscle cells in culture: inverse relationship between proliferation and expression of contractile proteins.

Human arterial smooth muscle cells (hASMC) from explants of the inner media of uterine arteries were studied in secondary culture. We had previously found that these cells depend on exogenous platelet-derived growth factor (PDGF) for proliferation in vitro. Deprivation of the serum mitogen(s) by culture in plasma-derived serum or bovine serum albumin (BSA) caused a true growth arrest that was reversible upon reexposure to the mitogen(s). When added to serum-containing medium, heparin caused a reversible growth arrest which could be competed for by increasing concentrations of serum. In the current study we used a set of smooth muscle-specific actin and myosin antibodies to study the expression of contractile proteins in stress fibers under indirect immunofluorescence on hASMC in culture. Even in sparse culture, growth-arrested hASMC expressed stress fibers containing these actin and myosin epitopes. This was true irrespective of whether growth arrest was achieved by culture in media containing only BSA or a combination of heparin and whole blood serum. hASMC proliferating in whole blood serum in sparse culture did not express such stress fibers, as judged by immunofluorescent staining. This was true also for cells that were restimulated to proliferate in serum after a growth arrest. Utilizing a monoclonal antibody against a nuclear antigen expressed in proliferating human cells, we were able to demonstrate an inverse relationship between the expression of this antigen and the SMC-specific contractile proteins, respectively. Under these culture conditions, the reversible transition between dedifferentiated and differentiated hASMC was almost complete and terminated about 1 wk after the change in culture condition. We conclude that hASMC in vitro respond to exogenous PDGF by proliferation and dedifferentiation as a single population of cells. We also conclude that this modulation is reversible, because the cells become uniformly quiescent and differentiated when the mitogenic stimulus is blocked or removed.

Actins↗
PubMed1989

Regional cerebral incorporation of plasma [14C]palmitate, and cerebral glucose utilization, in water-deprived Long-Evans and Brattleboro rats.

Regional rates of incorporation into brain of intravenously administered [14C]palmitate and regional cerebral metabolic rates for glucose (rCMRglc) were measured in water-provided (WP) and water-deprived (WD) homozygous (DI) and heterozygous (HZ) Brattleboro rats, a mutant strain unable to synthesize vasopressin, and in the parent Long-Evans (LE) strain. Following 15 h or 4 days of water deprivation, rCMRglc was elevated threefold in the pituitary neural lobe of LE-WD and DI-WD as compared with LE-WP rats, and in the paraventricular nucleus of LE-WD, and the supraoptic nucleus of DI-WD rats. However, incorporation of [14C]palmitate into these regions was not specifically altered. The results indicate that water deprivation for up to 4 days increases rCMRglc in some brain regions involved with vasopressin, but does not alter [14C]palmitate incorporation into these regions. Incorporation of plasma [14C]palmitate is independent of unlabeled plasma palmitate at brain regions which have an intact blood-brain barrier, but at nonbarrier regions falls according to saturation kinetics as cold plasma concentration rises, with a mean half-saturation constant (Km) equal to 0.136 mumol.ml-1.

Animals↗
PubMed1988

Stage II endometrial carcinoma. Results and complications of a combined radiotherapeutic-surgical approach.

Since one third of the patients with Stage II endometrial carcinoma have occult extrauterine pelvic metastases at diagnosis, adequate treatment must include the pelvic lymph nodes and parametria. Eighty-three patients with Stage II endometrial carcinoma were treated between January 1964 and December 1983. Sixty-nine patients (83%) received combined whole-pelvic irradiation and surgery, five (6%) had surgery alone and nine (11%) had radiotherapy alone. Five-year actuarial survival rates were 67%, 60%, and 38%, respectively. No pelvic recurrence occurred in the 69 patients who received the combined therapy, and there was no vaginal recurrence in the 80 patients treated with intracavity radium. There was a significantly lower incidence of pelvic lymph node metastases (P = 0.03) in patients treated with preoperative irradiation. The median time to recurrence was 17 months, with 67% of the recurrences diagnosed before 2 years, and 88% within 5 years. Ten patients (12%) incurred severe complications and three died as a result. Whole-pelvic irradiation, intracavity radium, and hysterectomy are effective treatment for occult pelvic and vaginal disease.

Brachytherapy↗
PubMed1988

Recurrent cervical carcinoma after radical hysterectomy.

The characteristics of recurrent carcinoma following radical hysterectomy and pelvic lymphadenectomy for cervical carcinoma are not well known. Disease recurrence was noted in 27 of 249 patients (11%) with stage IB cervical carcinoma who were treated with a primary surgical approach between January 1962 and December 1984. Fourteen recurrences (52%) occurred within 1 year of surgery, and 24 (89%) within 2 years. Patients with pelvic node metastases or adenocarcinoma had a significantly higher recurrence rate than did patients with negative nodes (33% vs 8%) or with squamous carcinoma (22% vs 8%). Seventeen patients (63%) had disease recurrence in the pelvis or vulva and 12 of these patients had recurrences within 1 year. Eight patients developed asymptomatic pelvic or vulvar recurrences, and all were diagnosed within 1 year. Ten patients (37%) developed recurrences outside the pelvis and 8 of these experienced recurrence after 1 year. Successful treatment after recurrence was independent of clinical or histopathologic parameters except site of recurrence. Eight of 15 patients (53%) who were treated with irradiation for a recurrence in the pelvis or vulva are free of disease 10 to 126 months (median, 48 months) after recurrence. Since irradiation can aid in salvaging patients with recurrent cervical carcinoma confined to the pelvis following radical surgery, clinical vigilance for this site of recurrence is emphasized.

Adenocarcinoma↗
PubMed1988

Characterization of a mammalian smooth muscle myosin heavy chain cDNA clone and its expression in various smooth muscle types.

A cDNA clone, SMHC-29, encoding the light meromyosin of smooth muscle myosin heavy chain (MHC), was isolated from a rabbit uterus cDNA library constructed in phage lambda gt11. This smooth muscle MHC cDNA demonstrates significant nucleotide and amino acid sequence homologies with known sarcomeric MHC genes from rabbit, rat skeletal, and nematode body wall myosin, and even with nonmuscle MHC gene from a slime mold (Dictyostelium discoideum), suggesting that smooth muscle, striated muscle, and nonmuscle MHC genes diverged from a common ancestor. The deduced amino acid sequences of the smooth muscle light meromyosin show very similar periodic distributions of hydrophobic and charged residues as found for the light meromyosin of striated muscle MHCs together with a high potential for alpha-helical formation, indicating an alpha-helical coiled-coil structure for the smooth muscle light meromyosin sequences. Furthermore, S1 nuclease mapping has revealed that this smooth muscle MHC gene for SMHC-29 is specifically expressed in smooth muscles of vascular and nonvascular types but not in the striated muscles or nonmuscle cells.

Amino Acid Sequence↗
PubMed1988

Activation of smooth muscle cell outgrowth from BB/Wor rat aortas.

An essential event in atherogenesis is the migration and proliferation of vascular smooth muscle cells (VSMCs), which contributes to the fibrocellular component of the atherosclerotic intimal thickening. We have been modeling this process by studying the outgrowth of VSMC from aortic explants onto tissue-culture plastic substrate. Our hypothesis is that certain risk factors for atherosclerosis favor increases in subpopulations of cells with enhanced responsiveness to a variety of migratory and proliferative stimuli, in vivo and in vitro. As a known risk factor for atherosclerosis, diabetes might be reasonably postulated to induce such cell populations with altered susceptibility to additional noxious stimuli. We have tested this hypothesis with aortic explants from rats of the spontaneous autoimmune diabetic BB/Wor group, including diabetes-resistant, diabetes-prone, and treated acutely (less than 2 wk after onset of hyperglycemia) and chronically (greater than 2 wk) diabetic strains. As a group, the VSMCs from BB/Wor animals showed enhanced outgrowth in 0.1% serum (23-48%) compared with VSMCs from ordinary Wistar rats (less than 10%). Within the BB/Wor group, however, the rank order of enhanced outgrowth was diabetes-resistant greater than chronically diabetic greater than acutely diabetic subjects. When the outgrowth assay was performed in the presence of supplemental insulin (10 mU/ml), outgrowth was increased, especially for the diabetes-prone animals, giving a new rank order of diabetes-prone greater than acutely diabetic greater than diabetes-resistant greater than chronically diabetic subjects. These data suggest a genetic predilection in the entire BB/Wor rat group for increased VSMC responsiveness to migratory and proliferative stimuli, a sensitivity of these VSMCs to insulin, and the dissociation of this vascular cell effect from other manifestations of diabetes, e.g., hyperglycemia.

Animals↗
PubMed1988

Junctional transfer in wounded cultures of bovine aortic endothelial cells.

Both in vivo and in vitro, endothelial cells form continuous monolayers displaying growth control by cell density as well as cell contact. Several functions of endothelium are dependent upon maintenance of an intact monolayer. When such a monolayer is injured, endothelial cells migrate out from the wound edges and proliferate to cover the area of denudation. The response of endothelium to wounding is therefore a matter of both growth control and cellular motility. Since intercellular gap junctions have been postulated to have a role in growth control, we set out to determine whether junctional communication was altered in the activated, migrating cells. We found extensive transfer of microinjected fluorescent dye molecules (Lucifer yellow CH) in cells at or near the wound edge at various times after wounding (1 minute to 48 hours). However, cells near a wound edge transferred dye at a frequency significantly diminished from that observed in undisturbed monolayers (81.1 +/- 1.5 (SE) versus 92.7 +/- 0.8% of adjacent cells received dye). There was a significant positive correlation between transfer frequency and distance from the wound (expressed as intervening cells) but not between transfer frequency and time after wounding. These results suggest that endothelial cells in a wounded monolayer retain junctional communication at a slightly but significantly reduced level and that increased motility and the wound healing response do not necessarily correlate with total loss of communication.

Animals↗
PubMed1988

Diagnosis of recurrent cervical carcinoma after radical hysterectomy.

A standard surveillance program for cervical carcinoma patients treated with radical hysterectomy is reviewed. Between 1962-1984, 249 patients with stage IB cervical carcinoma treated with radical hysterectomy and pelvic lymphadenectomy were entered in the surveillance program. Of the 27 patients (11%) diagnosed with recurrent carcinoma, 17 (63%) were identified by clinical history, 22 (81%) by physical examination, five (18%) by vaginal cytology, six (22%) by chest radiography, and eight (30%) by renal contrast imaging. Combined clinical history and physical examination identified 24 patients (89%) with recurrent carcinoma. Disease recurrence was detected by vaginal cytology in one asymptomatic patient with a normal examination. The recommended surveillance procedures for patients with cervical carcinoma after radical hysterectomy include clinical history, physical examination, and vaginal cytology. Chest radiography and renal contrast imaging should be reserved for symptomatic patients.

Cytodiagnosis↗
PubMed1987

Prognostic factors in stage II endometrial carcinoma.

The rarity of Stage II endometrial carcinoma and variable treatment modalities have made the evaluation of prognostic factors difficult. Clinical, surgical, and pathologic characteristics were evaluated in 64 patients treated with whole pelvic irradiation and intracavitary radium followed by hysterectomy at The University of Texas M.D. Anderson Hospital and Tumor Institute from January 1965 to December 1983. Comparison of 5-year actuarial survival rates revealed the following statistically significant categories: age, grade, depth of myometrial invasion, disease extent at surgery including lymph node metastases, and pelvic cytology. Race, weight, and cell type were not significant prognostic factors. Evaluation of prognostic factors at surgery includes pelvic and para-aortic lymph node biopsies, omental biopsy, pelvic cytologic washings, and biopsy of any suspicious tissues. Patients with adverse prognostic factors are candidates for trials with adjuvant therapy.

Actuarial Analysis↗
PubMed1987

Intrahepatic infusional therapy for metastatic ovarian carcinoma.

Twenty-four women with ovarian carcinoma that had metastasized to the liver were treated with intrahepatic infusional therapy. No consistent drug regimen was used. There were no complete responders; however, 33% had a partial response. All responses were noticed after the first course of therapy. The median length of response was 6.3 months. The median survival from the time of the first hepatic infusion was 7.5 months for all patients. In this series, there were two treatment-related deaths, one secondary to the chemotherapy, the other to improper catheter placement. Because of the multiplicity of chemotherapy regimens employed, no definite conclusions can be made concerning the efficacy of intrahepatic infusional therapy for metastatic ovarian carcinoma. It is suggested that its future use be restricted to patients with disease limited to the liver and who are being treated according to a study protocol.

Adolescent↗
PubMed1987

Nature of cervical involvement in endometrial carcinoma.

In patients with endometrial carcinoma the prognostic significance of clinical and histopathologic variants of cervical involvement is unknown. Fifty-eight patients with endometrial carcinoma and cervical involvement diagnosed by gross examination or endocervical curettage are reviewed. Three clinicopathologic groups were identified: gross cervical involvement (10 patients), occult stromal invasion (25), and no evidence of stromal invasion (23). There were no differences in clinical, pathologic, surgical, or therapeutic characteristics. There was no significant difference in actuarial 5-year survival rates between patients with gross cervical involvement (70%) and occult disease (65%). There was also no significant difference in survival rates among patients with occult cervical stromal invasion (67%). The presence of cervical involvement in endometrial carcinoma is an important prognostic factor. However, the extent of cervical involvement does not appear to be of significant prognostic value.

Adult↗
PubMed1987

Junctional transfer of small molecules in cultured bovine brain microvascular endothelial cells and pericytes.

We have utilized cultures of bovine brain microvascular endothelial cells (MEC) and pericytes to study two aspects of intercellular relations in the microvasculature. First, the apparent contradiction between the reported demonstration of dye transfer between endothelial cells in capillaries and venules in rat omentum and the lack of ultrastructurally demonstrable interendothelial gap junctions in the same vessels in omentum, brain, and other tissues led us to examine this problem in vitro. MEC showed extensive transfer of both fluorescent dye (Lucifer yellow CH, 96% transfer incidence in primary culture) and radiolabeled uridine nucleotides (97%). Freeze-fracture replicas of MEC revealed both gap and tight junctions. These results demonstrate that MEC are capable of producing gap junctions and engaging in junctional communication in vitro. Second, we have examined the interaction of pericytes with MEC. Cultured pericytes showed gap junctions in freeze-fracture replicas, variable dye transfer (cell density dependent, 19-91%), and extensive nucleotide transfer (94%). While the incidence of dye transfer between MEC and pericytes was low (10-31%), nucleotide transfer between these cells was extensive (86-96%). The demonstration of junctional transfer between MEC and pericytes in vitro may be particularly significant considering the high frequency of junctional contact between these cells in vivo. These cultured cell models should help us to better understand the complex interactions of vessel wall cells in microvascular physiology and pathophysiology.

Animals↗
PubMed1987

Stimulatory effect of the D2 antagonist sulpiride on glucose utilization in dopaminergic regions of rat brain.

Local cerebral glucose utilization (LCGU) was measured, using the quantitative autoradiographic [14C]2-deoxy-D-glucose method, in 56 brain regions of 3-month-old, awake Fischer-344 rats, after intraperitoneal administration of sulpiride (SULP) 100 mg/kg. SULP, an "atypical" neuroleptic, is a selective antagonist of D2 dopamine receptors. LCGU was reduced in a few nondopaminergic regions at 1 h after drug administration. Thereafter, SULP progressively elevated LCGU in many other regions. At 3 h, LCGU was elevated in 23% of the regions examined, most of which are related to the CNS dopaminergic system (caudate-putamen, nucleus accumbens, olfactory tubercle, lateral habenula, median eminence, paraventricular hypothalamic nucleus). Increases of LCGU were observed also in the suprachiasmatic nucleus, lateral geniculate, and inferior olive. These effects of SULP on LCGU differ from the effects of the "typical" neuroleptic haloperidol, which produces widespread decreases in LCGU in the rat brain. Selective actions on different subpopulations of dopamine receptors may explain the different effects of the two neuroleptics on brain metabolism, which correspond to their different clinical and behavioral actions.

Animals↗
PubMed1987

Stage IB cervical carcinoma treated with radical hysterectomy and pelvic lymphadenectomy: role of adjuvant radiotherapy.

A retrospective review of 194 patients with stage IB cervical carcinoma treated with radical hysterectomy between January 1977 and December 1984 revealed 30 patients (15%) with pelvic node metastases. Twenty patients with pelvic node metastases received postoperative radiotherapy and ten patients did not. Five of 20 patients who received adjuvant radiotherapy had recurrence, compared with five of ten patients who did not receive radiotherapy. No pelvic recurrences occurred in the adjuvant radiotherapy group compared with two in the no radiotherapy group. Only one serious complication occurred in a patient receiving radiotherapy. Adjuvant postoperative radiotherapy may reduce pelvic recurrences and improve survival in patients with pelvic node metastases treated with radical hysterectomy and pelvic lymphadenectomy.

Adenocarcinoma↗
PubMed1987

The significance of residual tumor after preoperative pelvic irradiation for stage II endometrial carcinoma.

The prognostic significance of residual endometrial carcinoma in the hysterectomy specimen after preoperative radiotherapy is controversial. Sixty-two patients with stage II endometrial carcinoma were treated with a standardized program of preoperative radiotherapy, followed in six weeks by an extrafascial hysterectomy. Twenty patients (32%) had no residual carcinoma in their hysterectomy specimens and 42 (68%) had residual carcinoma. There were no significant clinical, surgical, or pathologic differences between patients with or without residual carcinoma. Patients with no residual carcinoma had a 25% recurrence rate and a 53% actuarial five-year survival rate. Patients with residual carcinoma had a 21% recurrence rate and a 78% actuarial five-year survival rate. The presence of residual endometrial carcinoma in the hysterectomy specimen does not imply a compromised prognosis in patients with stage II endometrial carcinoma treated by the described method.

Adult↗
PubMed1987

Ureteral assessment after radical hysterectomy.

Postoperative intravenous pyelography was performed in 233 patients with stage IB cervical carcinoma treated with radical hysterectomy and pelvic lymphadenectomy between January 1962 and December 1985. Four patients developed symptoms of ureteral injury, two (0.8%) ureteral fistulae, and one (0.4%) stricture and obstruction due to recurrent carcinoma. No ureteral injuries were observed in 229 asymptomatic patients. A 5.2% incidence of transient severe ureteral dilatation occurred in asymptomatic patients, but resolved within a median of 94 days. A significant urinary tract anomaly was observed in 3.4% of preoperative pyelograms. All of these anomalies were apparent at surgery and presented no intraoperative difficulties. Three patients (1.3%) sustained intraoperative ureteral transections, which were diagnosed and repaired without sequelae. In patients with early cervical carcinoma having primary operative treatment, the role of routine preoperative and postoperative intravenous pyelography is questionable.

Adult↗
PubMed1986

Chemotherapeutic complete remission in patients with metastatic ovarian dysgerminoma. Potential for cure and preservation of reproductive capacity.

Two patients with metastatic dysgerminoma of the ovary were treated with a combination of etoposide, bleomycin, and cisplatin at The University of Texas M.D. Anderson Hospital and Tumor Institute at Houston. Both patients achieved a complete remission. Patient 1 developed a massive recurrence in the para-aortic lymph nodes 21 months after diagnosis and treatment with right salpingo-oophorectomy alone. She received four cycles of chemotherapy and is free of disease 21 months from the start of chemotherapy. Patient 2 had Stage III dysgerminoma and a lymphangiogram positive for tumor in the para-aortic lymph nodes. After surgery she received three cycles of chemotherapy and is free of disease 20 months from the start of chemotherapy. Both complete remissions were documented with second-look laparotomy. Chemotherapy may be an alternative to radiotherapy for the treatment of metastatic dysgerminoma and should also be considered for selected patients with Stage I disease. A literature review further supports the conclusion that additional clinical trials might expand the indications for chemotherapy in patients with this disease.

Adolescent↗