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Biomedical subjects

J Phillips

Publications and source records attributed to J Phillips.

At least 235 records · Page 13Linked to original sources
PubMed1988

Phase I clinical and pharmacokinetic investigation of didemnin B, a cyclic depsipeptide.

Didemnin B (NSC-325319), a cyclic depsipeptide isolated from a marine tunicate, has been evaluated in a Phase I trial. The drug was administered in a single intravenous infusion in 150 cm3 of normal saline every 30 min given every 28 days. Forty-three patients received 80 courses of the drug at doses ranging from 0.14 to 4.51 mg/m2. The dose-limiting toxicity was nausea and vomiting which began during or shortly after the infusion and was of variable duration. This toxicity was somewhat ameliorated by pretreatment with an aggressive antiemetic regimen. Mild hepatic toxicity also occurred with mild elevations of transaminases and bilirubin. One patient experienced an allergic reaction during his second infusion, characterized by chills, diaphoresis, flushing and hypotension. No objective anti-tumor response was seen during this trial. The recommended dose for Phase II studies on a single-dose schedule is 2.67 mg/m2 without prophylactic antiemetics and 3.47 mg/m2 if an antiemetic regimen is used. Preliminary pharmacokinetics suggest that didemnin B is sequestered or rapidly converted to a metabolite not identified by the antibody used in the radioimmunoassay. Further evaluation will be performed during Phase II studies.

Adult↗
PubMed1988

Anomalous branches of the cervical internal carotid artery: two cases of clinical importance.

Anomalous branches of the cervical portion of the internal carotid artery are rare. Reports in which these anomalous branches are of any clinical importance are even more rare. We are reporting two cases in which the anomalous branch maintained patency of the cervical portion of the proximally occluded internal carotid artery. Both patients initially had hemispheric symptoms appropriate to the affected internal carotid artery. This article details angiographic methods to demonstrate the unusual anatomic and pathologic aspects of these cases and the successful operative approach.

Aged↗
PubMed1988

Studies of prototype live hepatitis A virus vaccines in primate models.

We have prepared two prototype live hepatitis A virus (HAV) vaccines by serial passage of the HM-175 strain of HAV in African green monkey kidney cells. Passage 21 (P-21) HM-175 virus shows evidence of attenuation for chimpanzees but not for marmosets; passage 32 (P-32) HM-175 virus shows evidence of attenuation for both species. Animals that received P-32 HAV had fewer elevations in levels of liver enzyme activity and evidence of less virus replication in the liver and excretion of virus in stool than did those that received wild-type virus. The P-21 and P-32 viruses were highly immunogenic in both species. The information provided by this study will aid in the development of a live HAV vaccine.

Alanine Transaminase↗
PubMed1988

Long-term survival in small cell lung carcinoma.

We assessed outcome in 208 patients with small cell lung carcinoma two to seven years after treatment with combination chemotherapy, with or without chest and cranial radiotherapy. Fourteen patients (6.7%) survived cancer free for 30 months or longer. Nine of these (64%) had limited disease at diagnosis and four others had extensive disease with only one metastatic site. Two patients remain alive and disease free more than five years after diagnosis but median survival is still only 3.2 years. One patient died from intercurrent causes at 5.4 years but was free from small cell lung carcinoma at autopsy. Six patients are alive and disease free at intervals greater than 30 months but less than five years from diagnosis. All surviving patients are fully active with lifestyles similar to that prior to diagnosis. Five patients died from small cell lung carcinoma which relapsed more than 30 months after diagnosis. A few patients with small cell lung carcinoma are cured but 30-month survival is insufficient to show cure as late relapses do occur. Late toxicity from aggressive therapy does not appear to outweigh the benefits of long-term survival and potential cure in small cell lung carcinoma.

Adult↗
PubMed1988

Microdysgenesis in resected temporal neocortex: incidence and clinical significance in focal epilepsy.

Fifty patients underwent superficial temporal lobectomy for intractable temporal lobe epilepsy. Total cure rate was 52%, and significant improvement was achieved in 88%. Cytoarchitectural changes in gray and white tissue were analyzed under light microscopy. Neuronal dysgenesis was correlated with the duration of seizure disorder, age of onset, and other etiologic factors, and with clinical outcome. Temporal lobes from 33 neurologically normal autopsy brains which were age- and sex-matched with patients were examined as controls. Severe neuronal ectopia (greater than 8 neurons/2 mm2 white matter) was present in 42% of patients with epilepsy and in none of controls. There was neuronal clustering in 28% of those with epilepsy, and Chaslin's (subpial) gliosis in 38%. Controls did not have these changes. The presence of severe neuronal ectopia and clustering was predictive of a favorable clinical outcome following surgery (p less than 0.05). No correlation was found between microdysgenesis and other factors. These findings suggest that the presence of neuronal dysgenesis may be of significance in the clinical outcome following surgery, and that the abnormal tissue may be important as a morphologic substrate for seizures in some patients.

Adolescent↗
PubMed1988

Selective generation of erythroid burst-promoting activity by recombinant interleukin 2-stimulated human T lymphocytes and natural killer cells.

Because T lymphocytes and natural killer (NK) cells produce a variety of growth factors and interleukin 2 (IL2) modulates the activity of both, we assessed the ability of IL2 to stimulate human T cells and NK cells to produce hematopoietic growth factors detectable in clonogenic marrow culture. Human recombinant interleukin 2 (rIL2) added directly to cultures of human bone marrow that had been depleted of monocytes or depleted of both monocytes and T cells caused no significant alteration of myeloid (CFU-GM) or erythroid colony formation. Conditioned media harvested from rIL2-stimulated (greater than 100 U/mL) peripheral blood mononuclear cells, T cells, Leu-2 cells, and Leu-3 cells all had erythroid burst-promoting activity (BPA) but lacked myeloid colony-stimulating factor (GM-CSF) or CFU-GM-inhibitory activity. These T cells were IL2 receptor-negative, and the addition of anti-IL2 receptor monoclonal antibody (anti-Tac) to T cell cultures did not abrogate this IL2-stimulated BPA production. In addition, Percoll gradient-enriched, large granular lymphocytes (LGL) were separated by fluorescence-activated cell sorting into Leu-11+ (NK) cells and Leu-11- (low-density Leu-4+ T) cell fractions. rIL2 stimulated LGL, Leu-11+ and Leu-11- cells to produce BPA but not detectable GM-CSF or CFU-GM-inhibitory activity. Leu-11+ (NK) cells were Tac-negative from days 0 through 14 of culture. We conclude that rIL2 at high concentrations stimulated T cells, Leu-2 and Leu-3 cell subsets, LGL, and NK cells to produce BPA but not GM-CSF and that this stimulation may be mediated by an IL2 receptor distinct from Tac or by an epitope of the IL2 receptor not recognized by the anti-Tac antibody.

Antibodies, Monoclonal↗
PubMed1987

A novel missense mutation in the factor VIII gene identified by analysis of amplified hemophilia DNA sequences.

To date the only point mutations demonstrated to cause hemophilia are C to T transitions in TaqI sites. These were detected by screening Southern blots with cloned factor VIII probes. During the development of improved methods for detecting and analyzing mutations in genomic DNA, a novel G to C transversion mutation has been identified. This rare transversion results in a missense mutation, with proline being substituted for arginine in one of the active domains of the factor VIII molecule. The results suggest that the improved methods will be useful for detecting mutations in hemophilia as well as in other genetic disorders. In this method, specific DNA sequences in genomic DNA are amplified using oligonucleotide primers and a heat-resistant DNA polymerase. Mutations are detected and localized in the amplified samples by RNase A cleavage, and the altered region is then sequenced.

Base Sequence↗
PubMed1987

Comparison of T cell receptor gene rearrangements in patients with large granular T cell leukemia and Felty's syndrome.

Felty's syndrome (FS) refers to the occurrence of rheumatoid arthritis, splenomegaly, and neutropenia. A subset of these patients has recently been described with a chronic T cell leukemia of large granular lymphocytes (LGCL). To examine the spectrum of lymphocyte abnormalities in FS and LGCL, we examined phenotypic and genotypic properties of lymphocytes from eight FS patients. In two of these FS patients, we observed an elevated proportion of T cells with an unusual phenotype (CD3+/Leu-7+/Leu-8-/CR3+) (46 +/- 5% of mononuclear cells). The FS lymphocytes had large granular morphology on Wright-Giemsa stain and were active in antibody-dependent cellular cytotoxic activity. This phenotype, morphology, and activity was similar to LGCL patients except that the latter T cells additionally expressed the Fc-IgG receptor recognized by monoclonal antibody Leu-11 (CD 15). In the remaining six FS patients, the proportion of CD3+/Leu-7+/CR 3+ T cells was only 10 +/- 8%, which was not significantly different from age-matched normal subjects (6.6 +/- 2.2%). To determine the clonality of T lymphocytes in FS and LGCL, we examined DNA for rearrangements of the T cell antigen receptor beta-chain (Ti beta) and gamma-chain (Ti gamma) genes by using Southern blotting techniques. We found a clonal rearrangement of the Ti beta 1 and Ti gamma genes in both LGCL patients. In contrast, no clonal rearrangements of Ti beta or Ti gamma genes were detected in lymphocytes from the FS patients. These results indicate that FS patients are heterogeneous in their phenotype and that one subset exhibits polyclonal expansion of an unusual lymphocyte subset.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1987

Characteristics of the homeless mentally disordered population in Fresno County.

A survey of a sample comprising 9.5% of the estimated homeless mentally disordered population of Fresno County was conducted as a needs assessment for a treatment program proposal. Eighty percent of the sample were found to meet the criteria for a psychiatric diagnosis as determined by a standardized interview. Of these, 34% were rated severely impaired and urgently in need of treatment. An additional 33% were rated moderately impaired so that treatment would be of substantial benefit. Survey data are presented of the samples' priorities concerning primary needs, preferred locale for treatment and services, type of personnel with whom they would feel most comfortable, and most important problems.

Adult↗
PubMed1987

Primary intracerebral Hodgkin's lymphoma.

The case is reported of a 51 year old man with primary intracerebral Hodgkin's lymphoma treated by surgical excision, intrathecal chemotherapy and whole-brain irradiation. One year later the patient had no evidence of Hodgkin's lymphoma intracranially or elsewhere. The possible histogenesis of this rare condition is discussed and a brief review of the literature is presented.

Cerebellar Neoplasms↗
PubMed1986

Hormonal and behavioral effects associated with intravenous L-tryptophan administration.

Doses of 5.0, 7.5 and 10.0 g L-tryptophan, the amino acid precursor of serotonin, or saline alone were administered by IV infusion to a group of 11 healthy male subjects, and both hormonal and behavioral responses were monitored. Significant increases were observed in plasma concentrations of growth hormone and prolactin after all three doses of L-tryptophan, but not after saline infusion. No alterations in cortisol or thryotropin were noted at any level. Examination of behavioral effects of L-tryptophan revealed a dose-dependent impairment in performance on the symbol copying test. In addition, L-tryptophan produced significant effects on mental and physical sedation, but did not alter subjective ratings of tranquilization. In agreement with some prior reports, these observations support the ability of L-tryptophan, when administered IV in high doses, to produce pronounced effects on the central nervous system in humans, and suggest the potential utility of this paradigm as a neuroendocrine challenge test.

Adult↗
PubMed1986

Specific transfer factor protects mice against lethal challenge with herpes simplex virus.

Bovine transfer factor (TFd) specific to herpes simplex virus (HSV)1 or to HSV2 was prepared by immunizing calves with the corresponding virus. The TFd preparations were then injected into Swiss mice in an attempt to protect them against a subsequent lethal challenge with HSV1 or HSV2 virus. It was thus shown that injection of anti-HSV TFd protects the mice against the corresponding HSV virus, whereas the injection of a nonspecific TFd (anti-CMV) fails to protect against a challenge with HSV1. Furthermore, a dose-response effect was observed, since potent TFd preparations were ineffective when they were used at one-fifth of the original concentration. It seems, therefore, that animal models may be used to assay the potency of TFd preparations specific for herpes viruses.

Animals↗