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Biomedical subjects

T L Smith

Publications and source records attributed to T L Smith.

At least 181 records · Page 10Linked to original sources
PubMed1995

Prolonged survival in chronic myelogenous leukemia after cytogenetic response to interferon-alpha therapy. The Leukemia Service.

OBJECTIVE: To determine whether a cytogenetic response after interferon-alpha therapy in patients with chronic myelogenous leukemia is independently associated with improved survival. DESIGN: Retrospective analysis. PATIENTS: 274 patients with a diagnosis of Philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase who were treated with interferon-alpha-based programs between 1982 and 1990. INTERVENTION: Therapy with daily subcutaneous interferon-alpha given at 5 x 10(6) U/m2 body surface area (highest dose schedule allowed on studies) or the maximally tolerated lower-dose schedule. RESULTS: Overall, 219 (80%) patients achieved a complete hematologic response and 104 (38%) achieved a major cytogenetic response (< 35% Philadelphia chromosome-positive cells). Estimated median survival was 89 months. Several pretreatment factors were associated with failure to achieve a major cytogenetic response and with worse survival. The existing prognostic models were generally predictive of which patients were likely to achieve a major cytogenetic response (P < or = 0.01) and of survival outcomes (P < or = 0.01). Multivariate analysis identified bone marrow basophilia (P < 0.01) and splenomegaly (P < 0.01) as independent poor prognostic factors for survival. Achievement of a major cytogenetic response, entered as a time-dependent variable while accounting for the other independent factors, was associated with improved survival (P < 0.001). Comparison of survival (dated from 12 months into therapy) with cytogenetic response at 12 months showed that a cytogenetic response was associated with longer survival (P < 0.001). CONCLUSION: Achieving a cytogenetic response with interferon-alpha therapy in patients with chronic myelogenous leukemia was independently associated with improved survival when tested as a time-dependent variable in a multivariate analysis, and this association was confirmed by landmark analysis at 12 months.

Adolescent↗
PubMed1995

Morphology of complex lymphoepithelial organs of the anal canal ("anal tonsil") in the bottlenose dolphin, Tursiops truncatus.

A complex of lymphoepithelial organs, the "anal tonsils," is a consistent structure in the anal canal of the bottlenose dolphin, Tursiops truncatus. This complex occurs as a circumferential cluster of discrete tonsil-like aggregations of lymphoid tissues, together with epithelial ducts ("crypts") and occasional mucus secretory units in the extreme lower portion of the intestinal tract. These structures are concentrated in the segment lined by stratified squamous epithelium and extend for a variable distance cephalad from the anal aperture. The tonsils appear to be most active, judged by the amount of lymphoid tissue present, in young animals. Depletion of lymphocytes and cystic enlargement of the crypts, probably representing functional as well as morphological involution, is a consistent feature of older animals.

Age Factors↗
PubMed1995

Adenocarcinoma as an independent risk factor for disease recurrence in patients with stage IB cervical carcinoma.

Between 1960 and 1989 1538 patients were treated with initial radiation therapy for FIGO Stage IB squamous cell carcinoma (SCC) of the cervix and 229 patients were treated for Stage IB adenocarcinoma (AC). The overall 5-year survival rates for patients with SCC and AC were 81 and 72%, respectively (P < 0.01). Patients with AC more often had a maximum cervical diameter < 4 cm than those with SCC (53% versus 47%). For 903 patients with tumors > or = 4 cm, 73% of those with SCC survived > or = 5 years compared with only 59% of those with AC (P < 0.01). Although there was no significant difference in the rate of pelvic disease recurrence for patients with AC or SCC tumors > or = 4 cm (17% versus 13%, P = 0.16), the rate of distant metastases was greater for patients with AC (37% vs 21%, P < 0.01). For patients with tumors > or = 4 cm, prognosis was strongly correlated with tumor size (P < 0.01) and lymphangiogram findings (P < 0.01) but not with age (P = 0.58) or tumor morphology (exophytic versus endocervical) (P = 0.33); a trend toward better survival in 165 patients who underwent adjuvant hysterectomy (78% versus 71%) was not significant (P = 0.09). Multivariate analysis confirmed a highly significant independent association between histology and survival; patients with tumors > or = 4 cm in diameter that were AC had an estimated risk of death 1.9 times that of patients with SCC (P < 0.01). These results provide strong evidence that patients with AC of the cervix have a poorer prognosis than those with SCC of similar stage and tumor diameter, reflecting primarily a higher rate of distant metastases in patients with AC.

Adenocarcinoma↗
PubMed1995

Lack of involvement of protein kinase C in ethanol-induced inhibition of metabotropic-glutamate receptor function in primary cultures of astrocytes.

The stimulation of [3H] inositol phosphate (InP) formation by the selective metabotropic-glutamate receptor agonist, 1S, 3R-ACPD, was significantly reduced in rat cortical astrocytes chronically exposed to 100 mM ethanol for 4 days. Under the same conditions, chronic ethanol either increased or did not affect the InP responses to norepinephrine and carbachol, respectively. The InP responses to all three agonists were sensitive to phorbol 12-myristate 13-acetate. Although the protein kinase C inhibitors, calphostin C and staurosporine, significantly relieved the ethanol induced inhibtion of the InP response to 1S, 3R-ACPD, these responses were still significantly less than corresponding values obtained from control cells treated with these inhibitors. The data suggests that mechanisms in addition to protein kinase C are responsible for the ethanol induced inhibition of metabotropic-glutamate function.

Alkaloids↗
PubMed1995

The microcirculatory effects of peripheral sympathectomy.

Microvascular physiology following peripheral artery sympathectomy was evaluated in seven hands with refractory pain (n = 7) and ulceration (n = 7) by serial isolated cold stress testing, which measures digital temperature and cutaneous perfusion (laser Doppler fluxmetry). All patients (n = 6) had vasospasm (secondary Raynaud's phenomenon) and arteriographically proven digital and palmar occlusive disease. Microcirculatory flow responses were correlated with symptoms and signs (including ulcer healing) before and after (2-8 weeks, 12-15 weeks, and 24 weeks) peripheral sympathectomy. Baseline data were compared with those of controls (n = 7 extremities). Following surgery, all seven hands had diminished pain; six had ulcer healing and one had ulcer reduction. Isolated cold stress testing demonstrated abnormalities in temperature and laser Doppler fluxmetry response between patients and controls. Although total flow (reflected by temperature) was not significantly increased after surgery, peripheral sympathectomy increased nutritional flow in these patients with combined vasospastic vessels and occlusive injury. The clinical changes observed following peripheral sympathectomy appear to be related to postsurgical correction of abnormal arteriovenous shunting and to improved nutritional blood flow to ischemic areas. This accounts for the resultant diminution of pain and healing of ulcers observed in these patients after surgery.

Adult↗
PubMed1995

An evaluation of type A and B alcoholics.

Evaluations of 1539 alcohol-dependent subjects (including 512 women) were carried out in an attempt to replicate the Type A/B dichotomy suggested by Babor et al. (1992). The subjects are participants in the Collaborative Study on the Genetics of Alcoholism (COGA), and each was evaluated using a face-to-face structured interview. Following the procedure of Babor et al. (1992), data were used to create 17 domains, and a k-means clustering method was invoked to generate a two-cluster solution. Thirty-one per cent of the males and 25% of the females fell into the Type B group, with overall R2 of 0.22 and 0.24 for males and females, respectively. The scores in each of the 17 domains and the analyses of the clinical characteristics for Type A and B subjects were, in general, consistent with the earlier onset and more severe course for Type B men and women. The ability of the domains to identify subgroups of alcoholics remained robust even after the exclusion of alcohol dependent subjects with antisocial personality disorder (ASPD) and those with an onset of alcohol dependence before age 25 years. The present analyses suggest that five of the 17 domains might be especially useful in identifying Type A and B groups.

Adult↗
PubMed1995

Interleukin-15 and the growth of tumor derived activated T-cells.

Interleukin-15 was tested to determine whether this recently discovered cytokine was capable of stimulating the growth of tumor derived activated T cells in culture (TDAC, also referred to as tumor infiltrating lymphocytes). When established cultures of IL-2 induced, IL-2 dependent TDAC were tested, IL-15 stimulated growth in a dose dependent manner, alone or in the presence of IL-2. One established TDAC was cultured with IL-15 alone for 18 passages over a 10 week period. Comparing IL-2 and IL-15 treated cultures, growth rate with IL-15 was slower. IL-15 doubled the secreted interferon alpha and granulocyte-macrophage colony stimulating factor. IL-15 and IL-2 were compared in primary TDAC cultures. IL-15 induced TDAC outgrowth in 3 of 6 cultures. IL-2 induced outgrowth in all 6. Tumor cells were eliminated as TDAC grew out in both IL-2 and IL-15 treated cultures. These results suggested that IL-15 like IL-2, is capable of stimulating the growth of TDAC with antitumor activity, but with certain distinct effects which may be of interest therapeutically.

Humans↗
PubMed1995

The relationship among stress, depression, locus of control, irrational beliefs, social support, and health in Alzheimer's disease caregivers.

This study evaluated the hypothesis that Alzheimer's disease caregivers and control subjects who experienced stressful life events, held the belief that external factors control one's destiny, endorsed irrational beliefs, and had decreased social support would experience more depression and poor health than less stressed individuals who were more internal, had less rigid cognitive beliefs, and had better support. A battery of psychosocial and health measures were administered at baseline and 6 months later. The results suggest that, overall, the experience of marked adversity, increased externality, and the endorsement of irrational beliefs were related to depression and poor health. While diminished social support was not associated with poor health in this study, satisfaction with social support and diminished adherence to irrational beliefs were related to improved ratings of subjective health over time. These findings indicate that psychosocial interventions designed to modify cognitive reactions to stress might improve the quality of life and the physical well being of a population at risk for poor health as a result of their age and life circumstances.

Adaptation, Psychological↗
PubMed1995

Comparative antibody responses and protection in mice immunised by oral or parenteral routes with influenza virus subunit antigens in aqueous form or incorporated into ISCOMs.

The total and subclass antibody responses of mice and protection of these animals against live influenza A/Sichuan/2/87 virus challenge infection were determined after immunisation with homologous A/Sichuan/87 aqueous or ISCOM-formulated surface glycoprotein subunit antigens administered by either the oral or intramuscular routes. The results show that the greatest systemic and local antibody responses were elicited in mice immunised with A/Sichuan ISCOMs by the intramuscular route; protection against homologous virus challenge was also effective in these animals, particularly after two doses of the vaccine. However, relatively high immune responses and protection were also elicited by the A/Sichuan/87 ISCOM vaccine administered orally. Immunisation of mice by the intramuscular route resulted in levels of serum IgG2a subclass antibody significantly greater than those induced by the same preparation given by the oral route, or by the aqueous A/Sichuan/87 subunit antigen preparation administered by either route. The findings indicate that the ISCOM delivery system can be used for immunisation by the oral route, although in mice, under the conditions used, this strategy compares unfavourably with the intramuscular route in terms of both local and systemic immune responses and protection against homologous challenge virus infection.

Administration, Oral↗
PubMed1995

Prognostic significance of magnetic resonance imaging in patients with asymptomatic multiple myeloma.

PURPOSE: To assess the prognostic significance of magnetic resonance (MR) imaging in patients with newly diagnosed asymptomatic multiple myeloma. PATIENTS AND METHODS: Thirty-eight consecutive patients with asymptomatic myeloma of low tumor mass and negative skeletal surveys underwent MR imaging of the thoracic and lumbosacral spine. The presence and patterns of marrow involvement were correlated with standard laboratory parameters and time to disease progression. RESULTS: Nineteen patients (50%) had evidence of marrow involvement at spinal MR imaging. MR patterns of marrow involvement were classified as diffuse (five patients), variegated (nine), and focal (five). Patients with abnormal MR imaging studies required therapy after a median of 16 months, versus 43 months for those with normal MR studies (P < .01). CONCLUSION: Abnormal marrow patterns were present in half of patients with asymptomatic myeloma. An abnormal MR study of the spine identified asymptomatic patients who were likely to require treatment earlier than those with a normal MR study. A normal MR pattern provided additional justification to defer institution of chemotherapy. However, MR imaging remains an investigational tool to stage patients with multiple myeloma until more data are accumulated.

Adult↗
PubMed1995

Collection of peripheral-blood diploid cells from chronic myelogenous leukemia patients early in the recovery phase from myelosuppression induced by intensive-dose chemotherapy.

PURPOSE: To evaluate whether intensive chemotherapy followed by peripheral stem-cell (PSC) collections during early hematopoietic recovery results in a higher percentage of diploid cell collections in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML). PATIENTS AND METHODS: Fifty-five adults with Ph-positive CML received intensive chemotherapy with daunorubicin and high-dose cytarabine (ara-C) (DAUNO-HDAC; 26 patients) or fludarabine, high-dose ara-C, and mitoxantrone (FAM; 29 patients). Collections of the peripheral mononuclear cells were initiated when the WBC count was > or = 0.8 x 10(3)/microL. Simultaneous peripheral and marrow samples were subjected to cytogenetic studies. RESULTS: Thirty-eight of 55 patients (69%) were able to undergo the PSC collections. The rate of collection was higher in chronic phase (26 of 30 patients; 87%) than in accelerated (11 of 17; 65%) and blastic phases (1 of 8; 12%). Among the 30 patients in chronic phase, cytogenetic analyses of PSC showed cytogenetic responses (Ph-positive < 95%) in 60%, which were major (Ph < 35%) in 43% and complete (Ph = 0%) in 27%. Seven of 19 patients with simultaneous studies (37%; 23% of total) had a significantly lower percentage of Ph-positive cells in the peripheral collection compared with the marrow collection; one had the reverse phenomenon (5%; 3% of total). Cytogenetic responses were modest in both peripheral and marrow collections in CML accelerated and blastic phases. Myelosuppression-associated complications were frequent, resulting in febrile episodes in 76% of patients. CONCLUSION: PSC collection during early hematopoietic recovery from intensive chemotherapy allowed the collection of diploid-rich stem cells, mostly in chronic-phase CML. The approach could be used for in vivo purging before autologous stem-cell transplantation (ASCT).

Adolescent↗
PubMed1995

Insulin-dependent diabetic microangiopathy in the inner ear.

Thickening of the basement membrane in capillaries is implicated in the microangiopathic complications of diabetes mellitus. This study was designed to evaluate microangiopathic changes of the inner ear associated with insulin-dependent diabetes mellitus (IDDM) and concurrent moderate-intensity noise exposure. Male Sprague-Dawley rats were injected with streptozotocin (65 mg/kg) to induce IDDM. Half of the control and diabetic animals were exposed to chronic noise of 95 dB over the 6-month study period. Photomicrographs of the capillaries in the stria vascularis were obtained by transmission electron microscopy, and basement-membrane thickness was measured with an image processing system. This study quantitatively demonstrates basement-membrane thickening consistent with diabetic microangiopathy in the inner ear of IDDM rats. Noise exposure did not significantly change basement-membrane thickness in either diabetic or control animals.

Animals↗
PubMed1995

Cognitive recovery with abstinence and its relationship to family history for alcoholism.

OBJECTIVE: The relationship between drinking relapse and family history for alcoholism to cognitive functioning was investigated in alcoholics who completed a 28-day inpatient treatment program. METHOD: The current study examined 144 primary alcoholics who completed a battery of cognitive tests on admission to treatment and at a 3-4 month follow-up visit. Participants were classified as either family history positive (FH+) (n = 86) or family history negative (FH-) (n = 58) based on information on alcohol dependence in first degree relatives. The subjects were further classified as drinkers (n = 56) or abstainers (n = 88) at follow-up, based upon information gathered about their drinking practices during the interval. RESULTS: There were no differences between the groups based on family history status at admission to treatment. Comparisons made at follow-up revealed that the abstainers' (both FH+ and FH-) performance improved. The FH+ drinkers' performance was worse than that of both the FH- drinkers and the FH+ abstainers at follow-up. The poor performance of the FH+ drinkers relative to the FH- drinkers was not attributable to differences in drinking consumption during the test-retest interval. CONCLUSIONS: These results suggest that alcoholics who maintain abstinence following treatment show improvement on cognitive testing at follow-up; both FH+ and FH- abstainers showed improvement, indicating that a positive family history of alcoholism does not impede recovery that occurs with abstinence. The most important finding, however, is that the FH+ drinkers show greater deterioration at follow-up compared to the other groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effect of magnesium on secretion of platelet-derived growth factor by cultured human umbilical arterial endothelial cells.

Conditioned media were prepared by incubating human cultured umbilical arterial endothelial cells for 48 h in magnesium (Mg) sufficient (900 microM) and deficient (100 microM) conditions. Minimum essential media (MEM) are designated as [900]- and [100]-MEM, respectively. After the incubation, a portion of the [100]-MEM media was adjusted from 100 to 900 microM magnesium ([100-900]-MEM). Smooth muscle cells were incubated with the three media and their growth rates were determined by [3H]-thymidine incorporation and cell counting. The growth rate in [100-900]-MEM was significantly higher than in [900]- or [100]-MEM. When platelet-derived growth factor (PDGF) was neutralized by the addition of a mixture of anti-PDGF-AA and -BB, [3H]-thymidine incorporation in [100-900]-MEM decreased by 12.5 per cent, but only by 4.9 per cent in [900]-MEM. These results indicate that magnesium deficiency increases the secretion of PDGF by endothelial cells. This is also supported by the results of the radioimmunoassay for PDGF-BB; the quantity of PDGF in the magnesium-deficient media was greater than in the magnesium-sufficient media.

Blood Proteins↗
PubMed1995

Effect of apolipoprotein A-I deficiency on lecithin:cholesterol acyltransferase activation in mouse plasma.

Plasma cholesteryl ester (CE) synthesis by lecithin cholesterol acyltransferase (LCAT) is activated by apolipoprotein (apo)A-I. We studied the effect of plasma apoA-I concentration on LCAT activation, using normal, heterozygous or homozygous apoA-I-deficient mice made by gene targeting. Plasma esterified cholesterol concentrations of mice fed chow diets were ordered (mean +/- SEM): 105 +/- 7 (normal) > 70 +/- 5 (heterozygotes) > 26 +/- 2 (homozygotes) mg/dl. Plasma free cholesterol concentrations were similar among the three genotypes. Endogenous LCAT activity, measured as the decrease in plasma free cholesterol after a 1 h incubation at 37 degrees C, was ordered: 44 +/- 3 (normal) > 21 +/- 2 (heterozygotes) > 5 +/- 1 (homozygotes) nmol CE formed/h per ml plasma. Using a recombinant exogenous substrate consisting of egg yolk phospholipid, [14C]cholesterol, and apoA-I, CE formation of normals and heterozygotes was similar (27.4 +/- 0.6 and 28.8 +/- 1.3 nmol/h per ml plasma, respectively), but was significantly less for homozygotes (19.2 +/- 1.7 nmol/h per ml plasma). However, using a small unilamellar vesicle substrate particle containing phospholipid and [14C]cholesterol, CE formation was ordered: 1.6 +/- 0.1 (normal) = 1.6 +/- 0.1 (heterozygotes) > 0.6 +/- 0.1 (homozygotes) nmol/h per ml plasma; addition of apoA-I to the plasma of homozygous animals restored CE formation to normal levels (1.6 +/- 0.1). CE fatty acid analysis demonstrated that plasma from homozygous mice contained significantly more saturated and monounsaturated and fewer polyunsaturated fatty acids compared to normal and heterozygous mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

[N-methylnorleucine-(28,31)]cholecystokinin-(26-33) (SNF 8702) activity at a cloned rat CCKB receptor.

[N-methyl-Nle 28,31)]cholecystokinin-(26-33) (SNF 8702) is a highly selective ligand for the CCKB type of receptor present in the vertebrate central nervous system. Radioligand binding data showing that SNF 8702 binding affinity is reduced by the GTP analog guanylyl-imidodiphosphate suggest that SNF 8702 is an agonist but the ability of SNF 8702 to activate CCKB receptors has not been demonstrated. The present study shows that SNF 8702 is a highly potent agonist at rat CCKB receptors expressed on COS-7 cells and that these receptors are coupled to the mobilization of intracellular calcium. The A50 measured for SNF 8702-induced calcium mobilization (66 pM) is over 6-fold less than that of cholecytstokinin octapeptide (420 pM). Data are also presented showing that SNF 8702 has high binding affinity for these receptors with a Kd value (760 pM) consistent with previous measurements using guinea pig brain tissue preparations.

Animals↗