Search

Eight dogs and five cats with histopathologically confirmed fibrosarcomas were treated with Acemannan Immunostimulanta in combination with surgery and radiation therapy. These animals had recurring disease that had failed previous treatment, a poor prognosis for survival, or both. Following four to seven weekly acemannan treatments, tumor shrinkage occurred in four (greater than 50%; n = 2) of 12 animals, with tumors accessible to measurement. A notable increase in necrosis and inflammation was observed. Complete surgical excision was performed on all animals between the fourth and seventh week following initiation of acemannan therapy. Radiation therapy was instituted immediately after surgery. Acemannan treatments were continued monthly for one year. Seven of the 13 animals remain alive and tumor-free (range, 440+ to 603+ days) with a median survival time of 372 days. The data suggests that Acemannan Immunostimulant may be an effective adjunct to surgery and radiation therapy in the treatment of canine and feline fibrosarcomas.

We studied the relevance of the ventrolateral medulla for the cardiovascular and respiratory effects of endothelin-1 in urethane-anesthetized rats. Microinjection of endothelin-1 into the rostral ventrolateral medulla (RVLM) evoked pressor and bradycardic effects followed by sustained decreases in blood pressure, bradycardia, and respiratory depression. These effects were inhibited by endothelin-A receptor antagonists (BQ-123 and BQ-610) but not by endothelin-B antagonists. In the caudal ventrolateral medulla (CVLM) endothelin-1 decreased blood pressure, renal sympathetic nerve activity, respiratory frequency, and phrenic nerve activity, whereas heart rate increased. Pretreatment with BQ-123 in the CVLM increased respiratory frequency by 15 +/- 6 breaths per minute and prevented the effects of intra-CVLM administration of endothelin-1. In separate experiments, the intracisternal administration of endothelin-1 (20 pmol) to rats pretreated with saline in both RVLM and CVLM resulted in a hypotensive and bradycardic phase that was followed by hypertension (50 +/- 15 mm Hg), bradycardia, and 100% mortality. In a separate group, pretreatment with BQ-123 in the RVLM and CVLM completely inhibited the hypotensive phase and reduced by 83% the subsequent rise in blood pressure evoked by endothelin-1. Cardiorespiratory arrest was prevented in all the rats in this group. Selective endothelin receptor blockade in the RVLM attenuated the hypertensive period of intracisternal administration of endothelin-1 and prevented mortality by 33%, whereas in the CVLM the endothelin receptor antagonist inhibited the initial hypotension and reduced mortality by 25%. Our results support the concept that in the ventral medulla, endothelin-1 can modulate cardiovascular and respiratory function.

FES is a non-receptor protein tyrosine kinase expressed in hematopoietic progenitors and differentiated myeloid cells. It has recently been implicated in granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3) and erythropoietin signal transduction. To better understand the role played by FES in normal and neoplastic hematopoiesis, we used cell fractionation techniques to examine the subcellular localization of FES in myeloid cells and cell lines. FES was observed in the nuclear, granular and plasma membrane fractions of primary human neutrophils and the myeloid leukemia cell line, HL-60. The nuclear localization was confirmed by immunocytochemistry of neutrophils.

The purpose of this research was to determine which caregiver-training program (CTP) was most beneficial to caregivers. Two types of CTPs, a behavior management program and a social skills program, were implemented. The effects of the CTPs on attitude toward asking for help, attitude about using adult day care, are caregiving burden were explored. Thirty-three caregivers volunteered to participate. Of the caregivers, the majority were female spouses (n = 22), 76% were over age 60, and 68% had some college education. Subjects were randomly assigned to one of two CTPs or a control group. Pretest was completed during the first phase of the training program. Both CTPs met for six sessions. The control group received no training. The posttest was conducted 1 month after completion of the CTPs. Differences between the three groups were analyzed by using ANOVA. No differences were observed between groups. Six of the subjects chose the alternate training program when given the opportunity for further training. Caregivers who participated in both CTPs experienced a decrease in objective burden and a more positive attitude toward asking for help and using adult day care.

Acemannan, a complex carbohydrate shown to stimulate interleukin-1, tumor necrosis factor alpha and prostaglandin E2 production by macrophages, has also demonstrated antiviral activity in vitro against human immunodeficiency virus, Newcastle disease virus and influenza virus. A pilot study was undertaken to determine acemannan's effect in 49 feline immunodeficiency virus (FIV) infected cats with clinical signs of disease (Stage 3, 4 or 5), 23 of which had severe lymphopenia. Cats received acemannan either by intravenous (Group 1) or subcutaneous (Group 2) injection once weekly for 12 weeks, or by daily oral (Group 3) administration for 12 weeks. Upon entry into the study, cats were randomly assigned to one of the three groups. Laboratory analyses were performed at the beginning of the study and at Weeks 6 and 12. Cats were allowed to continue with a predetermined maintenance regimen of acemannan after completing the 12-week study. Thirteen cats died during the course of treatment. Upon necropsy, the most frequent histopathologic findings were neoplastic, kidney and pancreatic disease. Friedman's two-way ANOVA test showed no significant differences in efficacy among groups administered acemannan by the different routes. Therefore, groups were combined and a signed-ranks test was used to determine changes over time. A significant increase was seen in lymphocyte counts (P < 0.001). Neutrophil counts decreased significantly (P = 0.007), as did incidence of sepsis (P = 0.008). When cats entering with lymphopenia were analyzed separately, a much greater increase in lymphocyte counts was noted (235%) compared with non-lymphopenic cats (42%). A survival rate of 75% was found for all three groups. Thirty-six of 49 animals are alive 5-19 months post-entry. These results suggest that acemannan therapy may be of significant benefit in FIV-infected cats exhibiting clinical signs of disease.

Forty-three dogs and cats with spontaneous tumors were treated with the immunostimulating polysaccharide acemannan by intraperitoneal and intralesional routes of administration. Tumors from 26 of these animals showed histopathological evidence of immunological attack as shown by marked necrosis or lymphocytic infiltration. Thirteen showed moderate to marked tumor necrosis or liquefaction. Twenty-one demonstrated lymphoid infiltration, and seven demonstrated encapsulation. Twelve animals showed obvious clinical improvement as assessed by tumor shrinkage, tumor necrosis, or prolonged survival; these included five of seven animals with fibrosarcomas. It is believed that acemannan exerts its antitumor activity through macrophage activation and the release of tumor necrosis factor, interleukin-1, and interferon.

EGR-1/TIS8 is a primary response gene that encodes a zinc finger containing protein and is induced in a number of cell types by a variety of ligands. We have isolated and mapped the human EGR-1/TIS8 gene and sequenced the 5' upstream flanking region. A 'TATA' homology and several putative regulatory elements, including two Sp1 sites, five serum response-like elements, two cAMP response-like elements, an EGR-1 binding site (EBS), and a tetra-decanoyl phorbol acetate (TPA)-responsive element have been identified within 700 nucleotides of the upstream region. We demonstrated that a 500-base pair fragment, which includes several of these possible regulatory sequences, is functional and responsive to TPA in transient transfection assays. A further understanding of the regulation and function of human EGR-1/TIS8 gene expression may provide insight into the mechanisms that control normal and neoplastic proliferation of human cells.

Over a 54-month period 6,142 patients were consecutively admitted to our Level I trauma center. Ninety-two blunt trauma patients required massive transfusion (MT) of 20 or more units of packed red blood cells (range, 20-126). Eighty-two per cent of all transfused blood was given within 24 hours of admission. Forty-eight patients (52%) were long-term survivors. Twenty-six patients died (28%) within 24 hours and 21 of these exsanguinated. Eighteen patients died greater than 24 hours: nine (50%) died from multiple organ failure, and nine (50%) died from severe closed head injury (CHI). Clinical predictors of increased mortality were: shock on admission, closed head injury, and age. Forty-three survivors were followed for a mean of 2.5 years (range, 1-5 years). No patient died during followup. All patients were home at 1 year; only four patients required continued medical assistance. Thirty-two patients (74%) returned to work. We conclude that: 1) blunt and penetrating trauma patients receiving MT have similar survival rates of 50%; 2) shock, closed head injury, and age predict increased mortality but do not preclude survival; 3) long-term outcome in blunt patients requiring MT is excellent. Post-discharge death is rare and 3/4 of the survivors return to work, justifying the high cost of acute care.

Urinary kallikrein is increased by restriction of dietary sodium and by administration of fludrocortisone, a sodium-retaining steroid. In order to determine whether salivary kallikrein responds similarly, we studied 16 normal volunteers after 1-week periods of daily intake of 9, 109, and 259 mEQ of sodium; 10 subjects were studied after addition of 0.6 mg/day fludrocortisone for a week to a regimen of 109 mEq/day sodium. During sodium restriction, parotid saliva had a significantly higher mean concentration of kallikrein ad potassium and a significantly lower concentration of sodium than during periods of intake of 109 or 259 mEq/day sodium. Sodium restriction also caused significantly higher urinary excretion of kallikrein and aldosterone. Salivary amylase remained unchanged during the three sodium periods. Administration of fludrocortisone significantly increased the mean concentration of parotid kallikrein and excretion of urinary kallikrein in comparison with control levels, however the concentrations of parotid sodium and potassium did not change significantly. Four patients studied before and after removal of aldosterone-producing adenomas each showed decreased concentrations of parotid kallikrein and potassium and increased concentrations of parotid sodium after surgery. It is concluded that both salivary and urinary kallikrein increased in response to restriction of sodium and that these increases were mediated by levels of sodium-retaining steroid. Increased output of kallikrein in response to increased levels of sodium-retaining steroid may be a generalized response of organs that contain glandular kallikrein and can conserve sodium.

Nitrosourea derivatives 9--13 which utilize phensuximide (1) as the carrier were synthesized as potential central nervous system antitumor agents. The N-(2-chloroethyl)-N-nitrosourea 13 was active in the mouse ependymoblastoma brain-tumor system, as well as the intraperitoneal L1210 leukemia system.

Kininogen was isolated from human urine by batch adsorption with immobilized antibody to the immunologically identical heavy (H) chains of both high molecular weight (HMW) and low molecular weight (LMW) human plasma kininogens. All releasable kinin in the guanidinium chloride eluate was associated with kininogen antigen in gel filtration fractions. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the eluate gave major stained and antigenic bands corresponding to the major form of plasma LMW kininogen. Also, the staining patterns and antigenic profiles obtained upon alkaline disc gel electrophoresis of the urinary and plasma LMW kininogens were strikingly similar. When antibody to H chain was used in an indirect immunofluorescence technique, cytoplasmic staining was observed in cells of distal tubules and c cortical and medullary collecting ducts of human kidneys. No fluorescence was observed using antibody to the unique light (L) chain of plasma HMW kininogen and no intact HMW kininogen was found in urine by radioimmunoassay. We conclude that the kidney is a source of urinary kininogen, while the L chain antigen in urine probably represents filtered degradation products of plasma HMW kininogen.

Numerous species of Meriones have been incriminated as natural reservoir hosts of Leishmania major in Mongolia, Soviet Asia, Afghanistan, the Middle East, and North Africa. However, little is known about the immunological response or course of infection in these small rodents. In this study, 40 commercially obtained inbred Meriones unguiculatus were divided into equal groups and injected in the right hind footpad with various doses of L. major promastigotes or with medium only. At regular intervals, blood was collected from the animals for subsequent evaluation of the kinetics of anti-L. major serum antibody production. Footpad lesions were measured periodically for 13 wk, beginning just before infection. The humoral response to infection and the course and severity of disease were dose related. However, metastasis lymph nodes, liver, spleen, and secondary cutaneous sites occurred at each of the doses tested.

A 29-year-old woman with an enchondroma that was expanding and eroding the palmar cortex of the middle phalanx was successfully treated by curettage and implantation of bone morphogenetic protein. The metaphysis and cortex were repaired by lamellar bone within 2 months. The medulla was completely filled with trabecular bone by 9 months. The full range of motion and normal functions of finger and hand joints were restored, and there was no recurrence or abnormalities at follow-up visits 2 1/2 years after the operation.

The mesodermal tissue of some amphibian gastrula develops into a dorsal-to-ventral sequence of notochord, somite, pronephros, and lateral plate cell types. The cellular proportions regulate with respect to embryo size. The dorsal blastoporal lip appears to function as an organizer for the embryo. The transplantation of a donor lip to the ventral side of a host causes a second, opposed embryo to form and the system commits similar total proportions of cells as do normally developing embryos. Transplantation of donor somite to the ventral side of a host causes a reduction in the proportion of host somite developed. A modified reaction-diffusion system governing embryo development is proposed. Developmental simulations consistent with experimental observations are presented and analyzed. The results suggest that the degree of somite inhibition is positively correlated with the size of the somite transplant. Further predictions are that sufficiently large somite transplants would induce ectopic, ventral pronephros to form and ventral pronephros transplants would inhibit host pronephros development.

To understand the role of the kallikrein-kinin system in the kidney all components of the system and their localization need to be considered. About half the kallikrein in urine occurs as the proenzyme which arises in the distal tubule. Kinins are formed in the distal tubule and collecting duct from urokinnogen which is found throughout the tubule. Urine contains about twice as much lysyl-brandykinin as bradykinin. A third kinin, methionyl-lysyl-bradykinin, also can occur in urine. It is probably produced by uropepsin as the kinin is largely formed in acidified urine and its formation is inhibited by pepstatin. The significance of the three kinins is unknown. Kinins are normally slowly (few hours) destroyed in urine. The importance of kallikrein, urokinogen and kininases in regulating the level of kinins needs to be determined.

The relationship between elevated serum cholesterol and coronary heart disease, is now generally accepted as being causal. To examine current attitudes and practices regarding the treatment of high serum cholesterol, questionnaires were sent to a randomly selected sample of general practitioners in the Takapuna health district during 1986. The response rate among the 92 doctors in general practice at the time of the study was 80%. The majority of general practitioners (82.5%) believed that there was a casual relationship between high serum cholesterol and coronary heart disease and that reducing levels would help prevent coronary heart disease. Almost all general practitioners (96%) were screening some groups of patients for high serum cholesterol, with most screening those with symptomatic coronary heart disease or associated risk factors, and 15% screening all patients. Although almost 90% of general practitioners had patients on diet therapy and one third had patients on drug treatment, there was wide variation in attitudes regarding the serum cholesterol levels meriting dietary or drug treatment. This suggests that there is still considerable confusion as to when and how to treat high cholesterol levels and that specific national guidelines for the detection and management of high serum cholesterol are required as part of a comprehensive programme to prevent coronary heart disease.