[The effect of duodenum-preserving pancreatic head resection on the endocrine pancreas function in patients with chronic head pancreatitis]. In a prospective clinical-experimental study, 15 patients with chronic pancreatitis operated consecutively due to severe pain were examined for the effects of a duodenum-preserving resection of the pancreas head on endocrine pancreas function. This was done by means of oral and intravenous glucose tolerance testing before the operation, on the 10th or 11th postoperative day, and three months after the operation. In addition to glucose levels in the peripheral venous blood, levels of insulin, C-peptide, glucagon, somatostatin, and pancreatic polypeptide were determined. As indicated by the k-value, glucose tolerance improved postoperatively in 11 patients; two patients showed no change, and one patient was worse. Only one patient developed evident diabetes mellitus immediately postoperatively. The pre- and postoperative levels of insulin and C-peptide showed no significant differences. The fasting levels of glucagon were significantly lower postoperatively than before the operation (2p less than 0.01). Duodenum-preserving pancreas head resection led to improvement of the glucose tolerance in the majority of patients; a deterioration was observed only in two cases.


[Smith's fracture. A radiological and functional follow-up study of 62 primary and post-primary surgically treated fractures]. The reversed Barton fracture of the distal radius is rare. In the literature there is a rate of 3 to 20.5% of all distal radius fractures. Whereas the reposition is simple, the reduction is difficult. This retrospective report about the treatment by osteosynthesis in the years between 1977 to 1987 in the "Berufsgenossenschaftliche Unfallklinik" Tübingen demonstrates a direct correlation between radiological and functional results. That means in consequence that internal fixation by using a small palmar T-plate is the favorable therapy.


[Dorsal compression fractures of the distal radius metaphysis. Long-term follow-up with conservative therapy]. Conservatively treated compressed fractures of the distal radius dorsal metaphysis healed despite primarily good reduction and consequent treatment with a decrease in dorsal length. The amount of this decline depends on the primary loss of dorsal length. If the fracture showed a loss of dorsal length at the time of the accident of up to 2 mm, the long-term results were almost anatomical. If there was primarily a larger loss of dorsal length, a decline of the distal fragment into the dorsal cave resulted. Most of the dorsal length regained after reduction was lost when the cast was removed. The long-term follow-up examinations were made after about 9 years.


[The value of external fixation in the treatment of radius fractures of the distal end]. 40 distal radial fractures were treated using either and external fixator alone or in combination with other osteosynthetic methods. 31 fractures were available for review with an average follow up 30.3 months. They were assessed according to Pfeiffer's criteria. The functional result was very good or good in 19, moderate in 5 and poor in 7 of these fractures. The functional outcome was related to the degree of articular damage, quality of joint reconstruction and the presence of algodystrophy.


[The treatment of distal radius fractures using the external fixator]. This is a report on the stabilisation of fractures of the distal end of the radius type C2 and C3 and open fractures by external fixator. Between 1982 and 1989 38 patients with 43 fractures were treated. A follow-up was done 8 to 80 months after operation including 35 patients. 14 patients were polytraumatised. Especially in this group of patients, the advantages of this procedure can be seen. This advantages are a small stress for the patient, involving only a short time of assembling of the external fixator besides a high stability of the system. Our results show, as well as the results of the literature, that the external fixator has its place in a differentiated therapeutic concept of intraarticular fractures, open fractures and fractures with a defect of the distal radius.


[Biomechanical aspects of the over-the-top reconstruction of the anterior cruciate ligament]. Strain characteristics of anterior cruciate ligament grafts inserted in the over-the-top technique were studied in an in-vitro model. A cruciate ligament attached at the center of the anatomical insertion sites provides a constant preload and accomplishes the principle of isometry during the whole range of motion. In contrast, the over-the-top reconstructed ligament shows an increasing laxity proportional to the degree of joint flexion due to an approach of the attachment areas. These observations indicate that a sufficient ligament function is not provided so that the over-the-top reconstruction cannot be recommended as method of choice.


[Ocular hypotensive effect of alpha-adrenoceptor agonist and antagonist in the conscious pigmented rabbit]. It has been reported that some of the topically-used antiglaucomatics have a central ocular hypotensive effect. In this study, the influence of topical and intracerebroventricular (i.c.v.) administration of phenylephrine, clonidine, guanfacine, prazosin, yohimbine on the intraocular pressure (IOP) was investigated in the rabbit. Male pigmented rabbits were used throughout the experiments. For measurement of IOP, an applanation pneumatonograph was used. By unilateral topical administration of phenylephrine, an increase in IOP in the eye in which instillation was performed was observed. On the other hand, a slight decrease in IOP was observed by similar treatment of prazosin and yohimbine. No significant change of IOP in the contralateral eye was observed with these drugs. On the contrary, unilateral topical administration of clonidine or guanfacine decreased the IOP of both eyes. Furthermore, the decrease of IOP was more remarkable in the contralateral eye compared to the eye which received instillation. The IOP of both eyes was decreased in a dose-related fashion by i.c.v. administration of clonidine or guanfacine. The ocular hypotensive effects of clonidine were diminished by the pretreatment by i.c.v. administration with yohimbine. These results suggest that the ocular hypotensive effect of clonidine and guanfacine is due to their alpha 2-adrenoceptor stimulation in the central nervous system.


T-lymphocyte activation in adult-onset idiopathic hypoparathyroidism. Patients with adult-onset idiopathic hypoparathyroidism (AOIH) often have antibodies against the parathyroid glands and other tissues, suggestive of immune activation. The purpose of this study was to determine whether T-cell activation is also a component of the endocrine disease. We identified eight patients with idiopathic hypoparathyroidism diagnosed after the age of 30 years at two tertiary care centers and evaluated peripheral blood lymphocyte subset phenotype frequencies using monoclonal antibodies and flow cytometry. Control subjects were 13 patients with Graves' disease (five thyrotoxic and eight euthyroid) and 110 healthy volunteers. In two of the patients with AOIH, we also determined the mitogenic response to parathyroid cell membranes in peripheral lymphocytes. Patients with AOIH had higher than normal frequencies of the following phenotypes (p less than 0.05 versus controls, one-way analysis of variance): CD4, helper T cells; CD29/CD4, inducer of helper T cells; CD16 and CD56, natural killer cells; and CD3/DR, activated T cells coexpressing DR. Patients with Graves' disease had significantly higher than control frequencies of CD25 (T cells bearing the interleukin-2 receptor), CD3/DR, and CD26 (also a marker of T-cell activation); whereas the frequency of CD29/CD4 was significantly less than the control frequency. Neither of the two AOIH patients tested showed lymphocyte proliferation in response to parathyroid or thyroid cell membrane fractions. Generalized T-cell activation represents a novel feature associated with AOIH. Although we could not demonstrate parathyroid-specific lymphocyte clonal expansion, these data are suggestive of a generalized immune disturbance possibly related to autoimmunity, in which one of the manifestations is hypoparathyroidism.


Prophylactic use of apraclonidine for intraocular pressure increase after Nd:YAG capsulotomies. We evaluated the prophylactic effect of 1% apraclonidine HCl in controlling the increase in intraocular pressure after Nd:YAG posterior capsulotomy in a large, multicenter double-masked clinical trial. One hundred sixty-four patients were enrolled into the apraclonidine-treated group, and 165 into the vehicle-treated group. The incidence of increase in intraocular pressure (greater than 5 mm Hg) in the apraclonidine-treated group (7%, 11 of 163 patients) was significantly less than that in the vehicle-treated group (39%, 64 of 164 patients). Similarly, the mean maximal change in intraocular pressure in the apraclonidine-treated group (1.3-mm Hg decrease) was significantly different from the increase in the vehicle-treated group (5.3-mm Hg increase). Few adverse reactions were observed. The risk for significant loss of visual function after Nd:YAG laser posterior capsulotomy, combined with the efficacy and relative safety of prophylactic apraclonidine, suggest its addition to the treatment armamentarium.


Effect of mesangiolysis on autoregulation of renal blood flow and glomerular filtration rate in rats. Interlobular arteries and afferent arterioles are involved in autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR). The question of whether the contractile mesangial cells are also involved in autoregulation was investigated in Wistar rats. Autoregulation of RBF was examined before and 1 h after infusion of antithymocyte (anti-Thy 1-1) antibodies, and both RBF and GFR autoregulation were examined 30 h after the infusion of antibodies. Mesangial cell destruction was present 30 h after the infusion of antibodies. The angiotensin II-induced contraction of isolated glomeruli (70% of control volume, P less than 0.001) was abolished after the glomeruli had been exposed to anti-Thy 1-1 in vitro. RBF, as well as the lower limit of RBF autoregulation, were not different from control 30 h after the infusion (82 +/- 5 vs. 79 +/- 4 mmHg, P greater than 0.10). Autoregulation of GFR was maintained in the control group but was restricted in the experimental group (autoregulatory index: 0.71 +/- 0.42 for left kidney, 0.02 +/- 0.35 for control; P less than 0.05). The afferent arteriolar diameter was unchanged 30 h after the infusion of antibodies (17.8 +/- 0.8 vs. 17.6 +/- 0.4 microns, P greater than 0.10). One hour after infusion of the antibodies, RBF autoregulation was normal. It is concluded that mesangial cells do not seem to be involved in RBF autoregulation, but may in part influence autoregulation of GFR during pressure reduction.


Comparison of responses to sarafotoxins 6a and 6c in pulmonary and systemic vascular beds. Cardiovascular and pulmonary responses to sarafotoxin (S) 6a and S6c were investigated in the anesthetized cat. Intravenous injections of the peptides in doses of 0.1-1.0 nmol/kg caused decreases or biphasic changes in arterial pressure (AP) and increases in central venous pressure, pulmonary arterial pressure (PAP), and cardiac output (CO). Secondary decreases in CO were observed in response to higher doses, and biphasic changes in systemic (SVR) and pulmonary (PVR) vascular resistances were observed. Under constant-flow conditions, the peptides only increased pulmonary lobar arterial perfusion pressure and lobar vascular resistance. AP responses to S6a, S6c, endothelin (ET)-1, ET-2, vasoactive intestinal contractor (VIC), and Lys7-ET-1 were similar, whereas AP responses to S6b and ET-3 were similar. S6a, S6b, S6c, ET-1, ET-2, ET-3, VIC, Lys7-ET-1, and big ET-1 increased PAP. S6a and S6c increased distal aortic and superior mesenteric arterial (SMA) blood flow and caused biphasic changes at the highest doses. Under constant-flow conditions, S6a and S6c produced dose-dependent biphasic changes in hindquarters perfusion pressure. Changes in SVR and PVR in response to the peptide were not affected by hexamethonium, glyburide, or meclofenamate, indicating that responses are independent of autonomic reflexes, activation of ATP-regulated K+ channels, or release of cyclooxygenase products. In contrast, N-nitro-L-arginine methyl ester decreased hindquarters vasodilator response to S6a and S6c. The present data show that S6a and S6c produce both vasodilation and vasoconstriction in the systemic vascular bed and increase lobar vascular resistance and that hindquarters vasodilator responses are mediated, in part, by the release of endothelium-derived relaxing factor.


Influence of opioids on CSF vasopressin concentration in newborn pigs. This study was designed to determine the influence of opioids on periarachnoid cortical cerebrospinal fluid (CSF) vasopressin concentration in newborn pigs equipped with closed cranial windows. Topical dynorphin-(1-13) produced tone-dependent pial arterial responses (dilation during normotension, constriction when cerebrovascular tone was decreased by hypotension). Dynorphin-(1-13) increased periarachnoid cortical CSF vasopressin concentrations in both normotensive and hypotensive piglets (5 +/- 1, 11 +/- 1, and 233 +/- 27 microU/ml for control, 10(-10), and 10(-6) M dynorphin-(1-13) during normotension, respectively). Dynorphin-(1-8) and U 50488H, a purported selective kappa-opioid receptor agonist, produced similar tone-dependent responses associated with smaller increases in CSF vasopressin concentration. beta-Endorphin caused only cerebral vasoconstriction associated with modest increases in CSF vasopressin (3 +/- 1, 5 +/- 1, 9 +/- 2 microU/ml for control, 10(-10), and 10(-6) M beta-endorphin, respectively). In contrast, methionine enkephalin- and leucine enkephalin-induced dilations were not associated with changes in CSF vasopressin concentration. Naloxone (1 mg/kg i.v.) blocked both the opioid-induced vascular effects and associated changes in CSF vasopressin concentration. Naloxone also attenuated the increase in CSF vasopressin concentration in response to hemorrhagic hypotension. These data show that dynorphin- and beta-endorphin-induced cerebrovascular effects are associated with increased CSF vasopressin concentration. Furthermore, these data indicate that opioids could contribute to the increase in CSF vasopressin concentration observed in response to hemorrhagic hypotension.


Mechanisms of signal transduction for adenosine and ATP in pulmonary vascular bed. The purpose of the present study was to investigate the contribution of pertussis toxin (PTX)-sensitive guanine nucleotide (G) proteins in the pulmonary vascular response to adenosine and ATP in the intact cat under conditions of controlled pulmonary blood flow and left atrial pressure. Adenosine, ATP, and beta-tau-ATP increased lobar arterial pressure in a dose-dependent manner. The pulmonary vasoconstrictor response to adenosine was abolished by BW 1433U, a specific purinergic receptor (P1) inhibitor, PTX pretreatment, indomethacin, and ONO 3708, a thromboxane A2 (TxA2) receptor antagonist. These data suggest that the pulmonary vasoconstrictor response to adenosine depends on activation of P1 purinergic receptors coupled to PTX-sensitive G proteins and subsequent metabolism of liberated arachidonic acid to form TxA2. Because each blocking agent studied produced similar reductions in the pulmonary vasoconstrictor response to ATP without altering the pulmonary vasoconstrictor response to beta-tau-ATP, the present data suggest that ATP constricts the pulmonary vascular bed, in part, by hydrolysis to adenosine. Moreover, the present study suggests that both A1 purinoceptors that are linked to PTX-sensitive G proteins as well as P2x purinoceptors receptors that are independent of PTX-insensitive G proteins mediate the pulmonary vasoconstrictor response to ATP in vivo.


Neuroendocrine evidence for reduced dopamine receptor sensitivity in alcoholism. Postsynaptic dopamine (DA) receptor sensitivity was assessed during abstinence in 15 male patients with alcohol dependence. The DA receptor sensitivity was evaluated using growth hormone (GH) responses to the DA receptor agonist apomorphine (0.18-0.24 mg intravenously). The patients were cared for in an alcoholism treatment unit for the 2 months prior to the investigation. They were carefully controlled for sobriety during this period. Thirteen healthy men were used as controls. The maximum GH responses to apomorphine were significantly reduced in patients compared with those in the control group. The patients had a significantly higher proportion of blunted GH responses. The findings suggest reduced postsynaptic DA, possibly D2, receptor sensitivity in abstinent alcoholics. The question whether this abnormal DA receptor status is genetically determined or acquired after long-term alcohol consumption remains to be addressed.


New alcohol markers--how useful are they in population studies: the Svalbard Study 1988-89. Regular high consumption of alcohol in selected populations have, with high precision, been identified by two new alcohol markers; carbohydrate-deficient transferrin and mitochondrial aspartate aminotransferase. To test these markers in an unselected population, gamma-glutamyltransferase (GGT), carbohydrate-deficient transferrin (CDT), and mitochondrial aspartate aminotransferase (mAST) were measured in the Norwegian population, 310 males and 171 females, aged 18 to 60 years, living at Svalbard. Using self-reported alcohol intake as gold standard, sensitivity, specificity, positive predictive value, and likelihood-ratio were estimated according to different cutoff-points for alcohol intake and for the tests. In contrast to earlier studies, the sensitivity was in general low. With a specificity of 90% or higher, the sensitivity did not exceed 26% for any of the tests. Whereas CDT showed its best discriminatory power at lower intake of alcohol, GGT discriminated best at higher levels. Parallel and serial analysis of CDT and GGT indicated a conditional independence between the tests, as well as at higher and at lower levels of alcohol consumption. mAST was judged as not suitable in population studies.


Comparative effects of digoxin and xamoterol on arrhythmias in patients with mild to moderate heart failure. The prognosis of heart failure patients is poor and as many as half of the deaths are sudden and thereby presumably attributable to arrhythmias. In the present study the effect of traditional therapy of mild heart failure with digoxin on arrhythmias was compared with the effect of xamoterol, a cardioselective beta 1 partial agonist, which has in addition beta-blocking properties at higher levels of sympathetic tone. Fifteen patients (NYHA class II-III) were included in the study. After a two-week baseline period they were randomized to digoxin or xamoterol for four weeks followed by a two-week washout and another four weeks of crossover therapy. Heart rate, blood pressure, and the number of complex ventricular premature beats remained essentially unchanged with digoxin. With xamoterol heart rate increased from 86 to 93 (ns) but was significantly higher during the night in comparison with digoxin. The number of ventricular premature beats decreased from 186 +/- 317 to 110 +/- 137 and increased to 130 +/- 175 after treatment. The number of runs decreased from 11 +/- 35 to 2.7 +/- 5 and increased to 5.6 +/- 9 after therapy. In conclusion, no significant effect of digoxin or xamoterol on ventricular arrhythmias was found. However, xamoterol showed a tendency to reduce simple and complex ventricular arrhythmias in patients with mild to moderate heart failure.


Premenstrual asthma with seasonal variation. A 19-year-old woman had premenstrual asthma (PMA) usually from April through October each year with normal and regular menstrual cycles. When the monthly variation in the patient's PMA between 1984 and 1990 was compared with the monthly admissions of children for acute asthma in a hospital in this region, there was a great similarity in pattern between the two. Although she had high sensitivity to house-dust mites, the monthly pattern of her PMA did not coincide with monthly variations in the number of mites in house-dust in her home.


Efficacy and safety of cetirizine therapy in perennial allergic rhinitis. A double-blind, placebo-controlled trial was undertaken to assess the safety and efficacy of once daily cetirizine in alleviating the symptoms of perennial allergic rhinitis. Subjects were adults with perennial allergic rhinitis, characterized by nasal congestion, postnasal discharge, sneezing, rhinorrhea, nasal itching, lacrimation, ocular itching, and itching of the roof of the mouth, and a total pretreatment symptom severity score of greater than or equal to 8. Patients were randomized to treatment with 10 mg cetirizine, 20 mg cetirizine, or placebo for 4 weeks. Efficacy was assessed in 215 patients and safety in 216. Cetirizine in once daily dosages of 10 or 20 mg proved to be effective in relieving the overall symptoms of perennial allergic rhinitis and particularly postnasal discharge and sneezing. The 10-mg dose afforded optimal symptomatic relief, and the 20-mg dose provided little or no additional benefit. Cetirizine was well tolerated, and the frequency of somnolence was not significantly greater in patients receiving this drug than in those given placebo.


Coexpression of CD4 and CD8 on mitogen-activated peripheral blood T cells from children with asthma: possible involvement of interleukin 4. Mononuclear cells were isolated from the peripheral blood of 28 asthmatic and 18 healthy children aged 3 to 16 years. The cells were stimulated with phytohemagglutinin for 96 hours. Activated cells were detected microscopically by MTT staining. Expression of cell surface antigens was detected by indirect immune fluorescence using CD4-specific and CD8-specific monoclonal antibodies. Results indicate an enhanced expression of CD8 on mitogen-activated T cells from asthmatic children compared with cells from healthy controls (median 43% versus 27%). Further experiments revealed that CD8 is coexpressed with CD4 on activated lymphocytes. Coexpression is significantly enhanced with lymphocytes from asthmatic patients compared with normal controls. In addition, interleukin 4 is able to enhance this coexpression with lymphocytes from healthy but not asthmatic children suggesting an in vivo preactivation of lymphocytes from asthmatic patients with interleukin 4.


Effects of simulated Fowler-Stephens orchiopexy on testicular structure and function in rats. To determine the effects of the Fowler-Stephens orchiopexy (FSO) on testicular structure and function, young rats underwent simulated FSO and concurrent contralateral orchiectomy, unilateral orchiectomy, or no operation. Rats were killed at 1, 2, 4, 6, 8, and 10 weeks postoperation, and serum testosterone, as well as testicular concentrations of the enzymes LDH & SDH, protein markers of testicular germinal cell development, were measured at the time of death. Although LDH and SDH concentrations decreased by 45 per cent in testes after simulated FSO at 4 weeks, control testes showed a 5 per cent increase in these enzymes. Serum testosterone decreased to one-fourth the initial value in rats after FSO, whereas control rats showed a slight increase. Within 2 weeks after simulated FSO, spermatocytes and sperm were sparse and there was marked disruption of tubular morphology; after 4 weeks interstitial fibrosis became prominent. Only a rare testis with good collateral vessels and resultant good histologic appearance and enzyme profile survived the FSO procedure, and these testes were considerably smaller than the controls.


Surviving gastrointestinal infarction due to polyarteritis nodosa: a rare event. Poly arteritis nodosa (PAN) is a systemic vasculitis with a male: female ratio of 2:1 and a peak incidence in the fifth decade. Small to medium-sized arteries are involved by focal transmural inflammatory necrosis. Aneurysms with inflammatory destruction of the media also occur. The most frequently involved organs are the kidney, heart, lung, liver, and gastrointestinal tract. There are few reported cases of ischemic necrosis of the intestine and even fewer survivors. A 22-year-old woman was transferred to St. Thomas Hospital (Nashville, TN) after resection of 80 per cent of the small bowel for ischemic necrosis. She had a history of juvenile onset diabetes mellitus, recurrent abdominal pain, and splinter hemorrhages. Emergency aortogram and selective mesenteric arteriogram were performed. The celiac artery was not visualized and small aneurysms were present in the mesenteric and renal arteries. The patient was successfully resuscitated from a cardiac arrest in x ray from a cardiac tamponade. Laparotomy was performed to determine the viability of the bowel. The celiac, hepatic, and splenic arteries were found to be chronically occluded. Pathology of these arteries revealed a nonspecific arteritis. At a third operation, several more inches of small bowel were removed. Characteristic changes of PAN were present on all small bowel specimens. She was treated with high-dose cyclophosphamide and steroids for 6 months and has continued on low-dose cyclophosphamide. She is now 36 months from her original operation and is doing well on oral nutrition. Intestinal hemorrhage from aneurysm rupture or gangrene with perforation are gastrointestinal complications of PAN that the surgeon may be called upon to treat.(ABSTRACT TRUNCATED AT 250 WORDS)


Prognostic value of serum CA 19-9 levels in pancreatic adenocarcinoma. Thirty-eight patients with histologically proven pancreatic adenocarcinoma were investigated to establish the utility of serum CA 19-9 as a prognostic indicator. CA 19-9 assays were performed serially during the course of the disease. In four patients with negative Lewis blood type, the CA 19-9 levels remained essentially normal throughout the disease course. In the remaining 34 patients, (1) CA 19-9 levels were significantly lower in patients with tumor size no larger than 5 cm in diameter, and in patients with resectable tumors than in those with tumor size larger than 5 cm or with unresectable tumors (p less than 0.01). 2) CA 19-9 levels dropped sharply after resection in all 11 resectable patients, whereas no significant change was found after laparotomy without resection. (3) The average survival time in seven patients whose CA 19-9 levels returned to normal after resection was significantly longer than in those four patients with postoperative CA 19-9 levels that decreased but did not return to normal (21.9 versus 8.7 months, p less than 0.05). (4) In 6 of 11 patients who underwent resection, recurrent elevation of CA 19-9 preceded changes detectable by computed tomography or clinical examination by 2 to 9 months. (5) In 23 patients who died of pancreatic carcinoma, 15 (65%) had an obvious rise in CA 19-9 level before death. There was a correlation between the doubling time of the CA 19-9 serum level and survival time (r = 0.5, p less than 0.05). Because it can be demonstrated that the reduction of tumor burden by resection lowers serum CA 19-9 levels, serum CA 19-9 levels may be a useful indicator of whether other forms of treatment such as radiation therapy or chemotherapy also reduce the tumor burden.


Angiotensin and adrenoceptors in the hemodynamic response to aortic cross-clamping. This study was designed to test the hypothesis that activation of adrenoceptors and/or the renin-angiotensin system plays an important role in the overall hemodynamic response to aortic cross-clamping. The experiments were performed on anesthetized rats pretreated with either saline (control group), an angiotensin-converting enzyme inhibitor (enalapril maleate, 2 mg/kg), an alpha 1-adrenergic antagonist (prazosin hydrochloride, 0.5 mg/kg), a beta-adrenergic antagonist (propranolol hydrochloride, 5 mg/kg), or an alpha 2-adrenergic antagonist (atipamezole, 5 mg/kg). Cross-clamping of the thoracic aorta was associated with an expected increase in mean arterial pressure and systemic vascular resistance in all animals. During the period of cross-clamping, cardiac output gradually decreased in all groups. Animals pretreated with the alpha 1-adrenergic antagonist or the angiotensin-converting enzyme inhibitor developed hypertension of a lesser degree than the control animals, while rats pretreated with the beta-adrenergic or alpha 2-adrenergic antagonist demonstrated a greater arterial hypertension than the control animals. The possible mechanisms underlying the observed differences are discussed. In conclusion, the present study confirms the posed hypothesis that the reninangiotensin and sympathetic nervous systems play an important role in hemodynamic response to cross-clamping of the thoracic aorta.


Inflammatory mediators, infection, sepsis, and multiple organ failure after severe trauma. The relation of (multiple) organ failure (OF) to the release of inflammatory mediators and the incidence of infection and sepsis was studied prospectively in 100 patients with multiple trauma (injury severity score = 37). Sixteen patients died of OF, 47 patients survived OF, and 37 patients had no OF. Fifteen (24%) of the patients with OF showed no signs of infection. In patients with early onset of OF (n=45), infection followed with a lag of 2 or more days. In 16 (44%) of these patients, infection led to a deterioration in organ function. With late onset of OF (n=18), infection preceded OF in nine patients. Polymorphonuclear leukocyte-elastase, neopterin, C-reactive protein, lactate, antithrombin III, and phospholipase A discriminated significantly among the three outcome groups. Of all factors, only polymorphonuclear leukocyte-elastase showed a difference between patients with and without infection or sepsis, respectively. These data indicate that infection might not play a crucial role in the pathogenesis of posttraumatic OF in a substantial portion of patients with trauma. Early OF, especially, seems to be mainly influenced by the direct sequelae of tissue damage and shock (eg, the release of inflammatory mediators). Since infection and sepsis did not lead to an augmented release of mediators in patients with trauma, the role of both entities remains unclear.


Expression of intercellular adhesion molecule-1 in thyroid follicular cells in autoimmune, non-autoimmune and neoplastic diseases of the thyroid gland: discordance with HLA. The presence of intercellular adhesion molecule-1 (ICAM-1) on epithelial cells facilitates their recognition by specific T lymphocytes. To assess the possible role of ICAM-1 in the recognition of thyroid follicular cells by T cells in thyroid autoimmune disease, we investigated the expression of ICAM-1 in thyrocytes from thyroid glands affected by Graves' disease, in glands with non-autoimmune pathology and normal glands using immunofluorescence staining on cryostat sections and on dispersed cell preparations. Sequential tissue sections from glands affected by Graves' disease (n = 15), multinodular goitre (MNG, n = 26), benign nodules (n = 11), primary carcinomas (n = 12) and control thyroid glands (n = 5) were stained for ICAM-1, HLA class I, HLA class II, CD3 and thyroid peroxidase (TPO). Weak and patchy ICAM-1 expression was found in the thyrocytes of 4/15 (27%) Graves' disease and of 1/26 (4%) multinodular goitre glands. In contrast, ICAM-1 expression was detected in the thyrocytes of 5/11 (45%) benign nodules and of 8/12 (67%) thyroid carcinomas in which it was sometimes strong. Thyrocytes in the five control glands were negative. These results correlated well with flow cytometry data from 23 of these glands which showed that ICAM-1 expression in thyrocytes from Graves' patients was, when present, 'dull', while in some malignant thyrocytes it was 'bright'. In preparations of thyrocytes from Graves' disease glands we found a striking discordance between the high levels of expression of HLA class I and HLA class II and the low expression of ICAM-1. This is surprising since in vitro the expression of these three molecules is equally induced by IFN-gamma and TNF-alpha. These results suggest that additional factors are involved in the induction of the inappropriate HLA class II expression observed in the thyrocytes of glands affected by Graves' disease.


Bacteriuria in men infected with HIV-1 is related to their immune status (CD4+ cell count). Reports from the United States that urinary tract infections (UTI) are more common in homosexual than in heterosexual men have not been confirmed in Europe. The occurrence of several UTI in men infected with HIV-1 has been recorded in The Netherlands. We therefore analysed the relationship between the presence of bacteriuria and the immune status (CD4+ cell count) in these HIV-1-infected patients. Urinary cultures were obtained prospectively for 2 years, during the first visit and every 6 months thereafter, when signs and symptoms of UTI occurred and when patients had fever of unknown origin. CD4+ cell counts were measured at the same time. The study was performed at the University Hospital, Utrecht, The Netherlands. One hundred and thirty HIV-1-infected men attended our hospital. Data from 98 were analysed. Eighty-nine (91%) of these men were either homo- or bisexual. Positive urinary culture. Group 1 (CD4+ cell count less than 200 x 10(6)/l) consisted of 47 patients; 30% had at least one period of bacteriuria, with 21 episodes. Group 2 (CD4+ cell count 200-500 x 10(6)/l) consisted of 27 patients; 11% had at least one period of bacteriuria, with five episodes. We did not find bacteriuria in the 24 patients in group 3 (CD4+ cell count greater than 500 x 10(6)/l). The rate of bacteriuria per patient-month, 4 (group 1) versus 2 (group 2), differed significantly (P less than 0.001). A significant relationship between CD4+ cell count and bacteriuria was found (P = 0.00003); no relationship, however, was found with anal intercourse, hospitalization, Karnofsky score, follow-up, or age. We conclude that men infected with HIV and presenting with a CD4+ cell count less than 200 x 10(6)/l are at increased risk for bacteriuria.


Primary prophylaxis with fluconazole against systemic fungal infections in HIV-positive patients. To investigate the efficacy of fluconazole prophylaxis against systemic fungal infections in HIV-positive patients. Open label treatment compared with historical controls. Patients were seen at the Parkland Memorial Hospital HIV Clinic, Dallas, Texas, USA between 1 March 1990 and 28 February 1991. Three hundred and thirty-seven historical controls were followed for 157 patient-years, and 329 fluconazole-treated patients for 145 patient-years. Fluconazole (100 mg daily) was administered to all patients with CD4 lymphocyte counts less than 68 x 10(6)/l seen at our HIV clinic after 1 March 1990. Lysis-centrifugation blood cultures were recorded monthly for all patients during both study periods. Twenty infections (16 cryptococcosis, four histoplasmosis) occurred in 337 historical reference control patients (product-limit 1-year incidence, 7.5 +/- 2.0/year). Four infections (one cryptococcosis, three histoplasmosis) occurred in the treated patient group (product-limit 1-year incidence, 1.8 +/- 0.9/year). Fluconazole warrants further evaluation for prophylaxis against systemic fungal infections in HIV-positive patients.


Use of monitored CD4 cell counts: predictions of the AIDS epidemic in Scotland: CD4 Collaborative Group. We describe the CD4 database of the Scottish Immunology Laboratories, and its uses and limitations for making short-term predictions of a CD4 cell count less than or equal to 200 x 10(6)/l (CD4(200)) and of adult AIDS cases in Scotland. The date of the earlier of two consecutive samples (typically 3 months apart) both with CD4 cell counts less than or equal to 200 x 10(6)/l was taken to define when a patient had passed the CD4(200) threshold (referred to as a CD4(200) case). The CD4 database comprises HIV-1-seropositive adults in the four main risk groups [homosexual/bisexual (1), injecting drug users (IDU; 2), heterosexual contact (3), and undetermined (9)] from Scotland's three principal areas of population (Lothian, Tayside and Strathclyde) who have had a CD4 cell count of less than or equal to 500 x 10(6)/l. Three hospitals in Scotland, the Communicable Diseases (Scotland Unit) and the Medical Research Council Biostatistics Unit, Cambridge, UK. The CD4 database at 31 December 1990 listed 813 patients (of whom 52% were IDU): 390 were CD4(200)/AIDS cases (of whom 44% were IDU) and 192 were AIDS cases (of whom 32% were IDU). Individuals in risk groups 1, 2 and 3 were nearly equally represented among newly diagnosed HIV-1 infections in 1990. However, among patients with moderate immunodeficiency, IDU accounted for 50% of the total number. Co-incidence of first CD4 cell count with CD4(200) diagnosis was recorded for only 28% of IDU, but in over 50% of cases for each of the other exposure groups (57%). There was a highly significant decrease of around 80 x 10(6)/l per calendar-year-of-referral in first CD4 cell counts for patients on the CD4 database; and decreases of around 40 x 10(6)/lper decade of age at referral. Since 1988, median time from CD4(200) to AIDS diagnosis in Scotland has been approximately 2 years. Back-projection was applied to annual CD4(200)/AIDS diagnoses before 31 December 1990 and to AIDS diagnoses. From AIDS diagnoses, the central epidemic scenario underestimated past HIV-1-antibody-positive reports (up to the end of 1985). More dramatic underestimation was occasioned by back-projection from CD4(200)/AIDS diagnoses [319 inferred HIV infections compared with 445 HIV-1-antibody-positive reports to Communicable Diseases (Scotland) Unit]. First CD4 cell counts should complement new HIV-1 diagnoses. Past referrals for immunological monitoring were not uniform between risk groups in Scotland. Underascertainment of CD4(200) cases is a problem when CD4(200) cases are used as a basis for back-projection. More information concerning the incubation distribution from HIV seroconversion to CD4(200) diagnosis is required. It is likely that there are twice as many CD4(200)/AIDS as there are diagnosed cases of AIDS.


Excitatory amino acids in cerebrospinal fluid in neonatal asphyxia. Of the excitatory amino acids, glutamic and aspartic acid were studied in the cerebrospinal fluid of six infants 4-32 hours after a documented episode of severe neonatal asphyxia. Aspartic acid concentration was definitely increased in the cerebrospinal fluid of these patients, whereas glutamic acid concentration varied considerably. Aspartic acid was always increased, even hours after the period of asphyxia, but values were greater in samples taken less than 12 hours after the asphyxial event. The patients with the highest cerebrospinal fluid aspartic acid concentrations had more severe outcomes.


Neurotransmitter-mediated inhibition of post-mortem human brain adenylyl cyclase. The effects of a range of neurotransmitter agonists showing selectivity for receptor types inhibitorily coupled to adenylyl cyclase were compared in membrane preparations of hippocampus, frontal cortex and caudate nucleus/striatum from previously frozen post-mortem human and rat brain. Agonists were tested against basal and forskolin stimulated activities, forskolin being a potent activator of the catalytic sub-unit of the enzyme. Of those agonists tested, only somatostatin (100 microM) and neuropeptide Y (10 microM) gave consistent inhibitions of basal and forskolin stimulated enzyme activities in all three regions of both human and rat brain. Somatostatin-mediated inhibition of human brain adenylyl cyclase was reduced in the absence of GTP and in the presence of the guanine nucleotide partial agonist, guanosine 5'-O-thiodiposphate, consistent with a G-protein-linked receptor. No such GTP-dependence was found for the neuropeptide Y-mediated adenylyl cyclase inhibition. GTP-dependent somatostatin mediated inhibitions of human brain adenylyl cyclase activity were of highest magnitude in the thalamus, intermediate magnitude in the hippocampus and caudate nucleus and lowest magnitude in the frontal cortex. It is concluded that of a range of neurotransmitter receptor agonists tested, only somatostatin gives robust, GTP-dependent responses that are reproducible enough to be used with post-mortem tissue for the comparison of receptor function in human brain disorders.


A rapid assay for neurotransmitter amino acids, aspartate, glutamate, glycine, taurine and gamma-aminobutyric acid in the brain by high-performance liquid chromatography with electrochemical detection. For simultaneous assay of the five neurotransmitter amino acids, Asp, Glu, Gly, Tau, and GABA in brain tissues, a very rapid and simple chromatographic method using high-performance liquid chromatography with electrochemical detection in combination with o-phthalaldehyde derivatization is described. Because the present method permits the determination of these five amino acids within less than five minutes in one chromatographic run, up to 100 samples a working day can be analyzed using an autosampler. Within-run coefficients of variation for these five amino acids were less than 2% (n = 20). The quantitative detection limit was 2.5 pmol for the 5 amino acids. The present method has been applied to the measurement of the five amino acid neurotransmitter levels in several discrete brain regions of mice treated with and without electroconvulsive shock.


Involvement of 5-HT1B receptors in the anticonflict effect of m-CPP in rats. The anticonflict activity of m-CPP, a non-selective agonist of 5-HT receptors, was studied in the drinking conflict test in rats. m-CPP administered in doses of 0.125-0.5 mg/kg increased the number of punished licks, the maximum effect having been observed after a dose of 0.25 mg/kg. The anticonflict effect of m-CPP (0.25 mg/kg) was antagonized by the non-selective 5-HT antagonist metergoline (1-4 mg/kg) and by the beta-adrenoceptor blocker SDZ 21009 (2 and 4 mg/kg) with affinity for 5-HT1A and 5-HT1B receptors. On the other hand, the 5-HT1A receptor antagonist NAN-190 (0.5 and 1 mg/kg), the 5-HT2 receptor antagonist ritanserin (0.25 and 0.5 mg/kg), and the beta-blockers betaxolol (8 mg/kg) and ICI 118,551 (8 mg/kg) with no affinity for 5-HT receptors did not affect the effect of m-CPP. The effect of m-CPP was not modified, either, in animals with the 5-HT lesion produced by p-chloroamphetamine. These results suggest that the anticonflict effect of m-CPP described above results from stimulation of 5-HT1B receptors--most probably these which are located postsynaptically.


Genetic evidence that placental site trophoblastic tumours can originate from a hydatidiform mole or a normal conceptus. The genetic origin of two placental site trophoblastic tumours was established using a Y chromosome-specific and locus-specific minisatellite probes. A gestational origin was confirmed for both tumours. In one case the origin of the tumour was consistent with derivation from a normal female conceptus while the other was shown to arise from a homozygous complete hydatidiform mole, an abnormal conceptus more usually associated with the development of choriocarcinoma.


Predicting outcome for patients with node negative breast cancer: a comparative study of the value of flow cytometry and cell image analysis for determination of DNA ploidy. This study was aimed at determining whether tumour DNA content measured by cell image analysis could provide additional prognostic information when compared to that provided by flow cytometry. Sections cut from paraffin blocks of tumours from 101 patients with node negative breast cancer were analysed by both methods and the results related to other prognostic variables and to patient relapse and overall survival. DNA ploidy measured by flow cytometry classified 46 tumours as diploid and 55 as aneuploid, whereas by cell image analysis 30 were diploid and 71 aneuploid (P less than 0.002). There were 20 tumours with discrepancies between the two methods; 18 of these were tumours with only one peak in flow analysis, but determined to be aneuploid with image analysis. DNA content as measured by both methods was significant for predicting relapse and survival by log-rank test, as were tumour histological grade, c-erbB-2 expression and tumour size. Multivariate analysis showed DNA ploidy measured by flow cytometry to be the only variable of independent significance (P less than 0.02) for both relapse and overall survival. Compared with cell image analysis, flow cytometry demonstrated a significantly higher proportion of diploid tumours, which may be related to differences in the internal standards applied to each method. We suggest that cell image analysis techniques can provide more sensitive information on the DNA content of tumour cells by direct measurement of nuclear DNA density of both normal lymphocytes and tumour cells in the same section. However, although image analysis appears to be more sensitive than flow cytometry in detecting DNA aneuploidy, the image technique appears to lack the specificity of flow cytometry in correlation with clinical outcome.


Levels of expression of the mdr1 gene and glutathione S-transferase genes 2 and 3 and response to chemotherapy in multiple myeloma. We have quantitated the levels of mRNAs in bone marrow samples from patients with multiple myeloma of the mdr1 gene (responsible for the Multidrug Resistance phenotype) and for two of the glutathione S-transferase gene, GST-2 and GST-3 (which can also inactivate a wide variety of cytotoxic drugs) and examined the relationship between the levels of expression of these genes and response to subsequent chemotherapy. From a total of 47 patients, 37 were treated with chemotherapy with 34 evaluable for response. Twenty-nine of the patients treated had not received any treatment prior to the marrow sampling while eight had previously received chemotherapy. Patients who failed to respond to initial chemotherapy had significantly higher levels of mdr1 than patients who responded (P = 0.01). In the total myeloma patient data set, mRNA levels for mdr1 and GST-2 were significantly correlated (Spearman rank correlation coefficient (r) = 0.54, P = 0.0004) as were expression levels of GST-2 with GST-3 (r = 0.43, P = 0.017). GST-3 and mdr1 levels were more weekly associated (r = 0.16, P = 0.4). These data would suggest a significant relationship between failure of chemotherapy in multiple myeloma patients and increases in expression of the mdr1 gene together with other genes whose products will generate additional mechanisms of resistance to chemotherapeutic agents.


GABA inhibits ACh release from the rabbit retina: a direct effect or feedback to bipolar cells? The cholinergic amacrine cells of the rabbit retina may be labeled with [3H]-Ch and the activity of the cholinergic population monitored by following the release of [3H]-ACh. We have tested the effect of muscimol, a potent GABAA agonist, on (1) the light-evoked release of ACh, presumably mediated via bipolar cells, which are known to have a direct input to the cholinergic amacrine cells and (2) ACh release produced by exogenous glutamate analogs that probably have a direct effect on cholinergic amacrine cells. Muscimol blocked the light-evoked release of ACh with an IC50 of 1.0 microM. In contrast, ACh release produced by nonsaturating doses of kainate or NMDA was not reduced even by 100 microM muscimol. Thus, we have been unable to demonstrate a direct effect of GABA on the cholinergic amacrine cells. GABA antagonists, such as picrotoxin, caused a large increase in the base release and potentiated the light-evoked release of ACh. Both these effects were abolished by DNQX, a kainate antagonist that blocks the input to cholinergic amacine cells from bipolar cells. DNQX blocked the effects of picrotoxin even when controls showed that the mechanism of ACh release was still functional. Together, these results imply that the dominant site for the GABA-mediated inhibition of ACh release is on the bipolar cell input to the cholinergic amacrine cells. This is consistent with previous anatomical and physiological evidence that bipolar cells receive negative feedback from GABA amacrine cells.


Structure of the murine tissue factor gene. Chromosome location and conservation of regulatory elements in the promoter. Tissue factor (TF) is a transmembrane glycoprotein that mediates cellular initiation of the coagulation serine protease cascades. Moreover, expression of TF in human atherosclerotic plaques is likely to play a significant role in the thrombotic complications associated with plaque rupture. In this study the complete murine TF gene, Cf-3, was isolated from mouse NIH 3T3 cells and was found to consist of six exons spanning about 11 kilobase pairs (kbp) of DNA. A major transcriptional start site was located 24 bp downstream of a TATA box. Cf-3 was mapped to chromosome 3 by analysis of an intersubspecies test cross. Conserved transcription factor-binding sites were identified by comparison of 5' flanking regions of the murine and human TF genes. A region of the TF promoter required for constitutive expression exhibited 85% identity in DNA sequence and included two conserved binding sites for Sp1. Furthermore, two AP-1 sites and an NF-kappa B site were conserved in a 56-bp region necessary for transcriptional activation in response to bacterial lipopolysaccharide. These highly conserved regions of the TF promoter, which contain several binding sites for well-characterized transcription factors, are likely to be functionally important in the complex pattern of TF gene expression observed in a variety of cell types.


Alterations in acetyl coenzyme A carboxylase activities in voles and mice treated with monosodium aspartate. Changes of body weights and hepatic acetyl-CoA carboxylase activities were measured in voles and mice treated with monosodium-L-aspartate (MSA). MSA was administrated subcutaneously to neonates at 4 mg/g. The MSA-treated mice showed remarkable obesity, associated with the increase in the plasma insulin concentrations and acetyl-CoA carboxylase activities. The activity of acetyl-CoA carboxylase of control voles was very low; under half that of mice. In the MSA-treated voles, although the plasma insulin concentrations also increased, acetyl-CoA carboxylase activities were not elevated and signs of obesity were not observed.


Does modulation of glutamatergic function represent a viable therapeutic strategy in Alzheimer's disease? Although glutamate dysfunction has been implicated in the pathogenesis of Alzheimer's disease (AD), it is unclear which direction a glutamatergic strategy should take in this illness. Increasing glutamate function may enhance excitotoxicity and neuronal death, whereas decreasing activity in this excitatory amino acid pathway may impair memory processes. Pharmacological modulation of the different NMDA and nonNMDA receptor sites, together with the concept of an agonist versus antagonist approach, are discussed in this review. It would appear that a glutamatergic approach may represent a new and exciting option to pursue in the experimental pharmacotherapeutics of AD.


Plasma homovanillic acid, plasma anti-D1 and -D2 dopamine-receptor activity, and negative symptoms in chronically mediated schizophrenia. We have investigated the relationship between the concentration of homovanillic acid in human plasma (pHVA) and plasma anti-D1 and anti-D2 dopamine receptor activity in chronic schizophrenic patients whose neuroleptic dosage was changed. The change in pHVA level correlated with that in anti-D1, not anti-D2 activity, thus suggesting that the neuroleptic-induced changes in pHVA concentration may be associated with the blocking of D1- as well as D2- receptors. The change of scores on the Scale for the Assessment of Negative Symptoms did not significantly correlate with changes in anti-D1 or anti-D2 activity, but did so correlated with the change in pHVA level.


Electroconvulsive therapy for persistent neuroleptic-induced akathisia and parkinsonism: a case report. Neuroleptic-induced akathisia (NIA) and parkinsonism (NIP) continued for 3 months, despite two courses of anticholinergic treatments, a shift to low-potent neuroleptic (NL) and a NL-free period. The two adverse effects responded dramatically to electroconvulsive therapy (ECT) to reemerge 3 months after termination of ECT. The case supports the idea that ECT is effective for both NIA and NIP even when they are resistant.


Integrin expression profiles during erythroid differentiation. To study the expression of integrins at the erythroid progenitor level we isolated selected populations of cells from human fetal liver after immunoadherence to anti-beta 2 integrin (CD18) coated plates. These CD18 adherent cells (CD18-Ad), in contrast to CD18 nonadherent cells (CD18-NAd), have a blastlike cell morphology and are highly enriched in all progenitor types (14% to 37% progenitors). By several criteria progenitor cells present in CD18-Ad cells appear to have a higher proliferative potential and diversity than the ones found in CD18-NAd, which were mostly later erythroid progenitors. Positivity of CD18-Ad cells with the common beta 2 integrin (CD18) is largely attributable to expression of alpha L (CD11a) chain, rather than alpha M (CD11b). CD11a is present in all types of progenitors, but it is selectively lost at later stages of erythroid differentiation/maturation. By contrast, CD11b appears to be virtually absent from all progenitors but it has an enhanced expression during granulomonocytic differentiation/maturation. In addition to beta 2 integrins, CD18-Ad cells express several other cytoadhesion molecules (VLA-4, VLA-5, I-CAM, H-CAM) as well as other progenitor cell antigens (CD34, HLA-DR, CD38). Cells expressing all these antigens were selectively enriched in CD18-Ad cells. Our data add new information on the regulation of CD11a and CD11b molecules in hematopoiesis and on the composite profile of integrin expression at several stages of erythroid differentiation.


Different molecular consequences of the 1;19 chromosomal translocation in childhood B-cell precursor acute lymphoblastic leukemia. The prognostically important 1;19 chromosomal translocation can alter the E2A gene on chromosome 19p13 in childhood B-cell precursor acute lymphoblastic leukemia (ALL), leading to formation of a fusion gene (E2A-PBX1) that encodes a hybrid transcription factor with oncogenic potential. It is not known whether this molecular alteration is a uniform consequence of the t(1;19) or is restricted to translocation events within specific immunologic subtypes of the disease. Therefore, we studied leukemic cells from 25 cases of B-cell precursor ALL, with or without evidence of cytoplasmic Ig mu heavy chains (cIg); 17 cases had the t(1;19) by cytogenetic analysis. Leukemic cell DNA samples were analyzed by Southern blotting to detect alterations within the E2A genomic locus; a polymerase chain reaction assay was used to identify expression of chimeric E2A-pbx1 transcripts in leukemic cell RNA; and immunoblotting with anti-Pbx1 antibodies was used to detect hybrid E2A-Pbx1 proteins. Of 11 cases of cIg+ ALL with the t(1;19), 10 had E2A-pbx1 chimeric transcripts with identical junctions and a characteristic set of E2A-Pbx1 hybrid proteins. Each of these cases had E2A gene rearrangements, including the one in which fusion transcripts were not detected. By contrast, none of the six cases of t(1;19)-positive, cIg- ALL had evidence of rearranged E2A genomic restriction fragments, detectable E2A-pbx1 chimeric transcripts, or hybrid E2A-Pbx1 proteins. Typical chimeric E2A-pbx1 transcripts and proteins were detected in one of eight cIg+ leukemias in which the t(1;19) was not identified by cytogenetic analysis, emphasizing the increased sensitivity of molecular analysis for detection of this abnormality. We conclude that the molecular breakpoints in cases of cIg- B-cell precursor ALL with the t(1;19) differ from those in cIg+ cases with this translocation. Leukemias that express hybrid oncoproteins such as E2A-Pbx1 or Bcr-Abl have had a poor prognosis in most studies. Thus, molecular techniques to detect fusion genes and their aberrant products should allow more timely and appropriate treatment of these aggressive subtypes of the disease.


Transplantation of umbilical cord blood after myeloablative therapy: analysis of engraftment. The possibility that umbilical cord and placental blood from an HLA-identical sibling might produce stable donor-derived lymphohematopoietic engraftment was tested in a patient with juvenile chronic myelogenous leukemia (JCML). After conditioning with high-dose busulfan and cyclophosphamide, cryopreserved umbilical cord blood, containing 0.5 x 10(8) nucleated cells/kg and 2.7 x 10(4) colony forming units-granulocyte, macrophage (CFU-GM)/kg, was infused. A leukocyte count greater than 1,000/microL, absolute neutrophil count (ANC) greater than 500/microL, and platelet count greater than 20,000/microL (untransfused) were observed on days 39, 39, and 47 after transplantation, respectively. Donor cell engraftment was documented in the peripheral blood and bone marrow by cytogenetic analysis, restriction fragment length polymorphism (RFLP), and polymerase chain reaction (PCR) as early as day 21. Furthermore, the donor origin of each lymphohematopoietic lineage (ie, CD5+ T cells, CD19/20+ B cells, CFU-GM, and burst-forming unit-erythrocyte [BFU-E]) was confirmed. On day 200, assays of the peripheral blood and bone marrow showed an abnormal proliferation of CFU-GM at low seeding densities in the absence of exogenous growth factors, as well as a hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), both pathophysiologic characteristics of JCML. Recurrent disease was confirmed histologically on day 225. Together, these results demonstrate that umbilical cord blood contains sufficient numbers of hematopoietic stem cells necessary for the engraftment of leukemia patients treated with myeloablative therapy and that the detection of "spontaneous" CFU-GM and hypersensitivity to GM-CSF after treatment is a marker of residual or recurrent disease in patients with JCML.


Dendrocytes in verruga peruana and bacillary angiomatosis. Verruga peruana and bacillary angiomatosis are two cutaneous diseases characterized by angiomatous growths linked to the presence of rickettsia-like organisms. These lesions are currently considered to be endothelial hyperplasias and to share many features. By immunohistochemistry and computerized image analysis, we studied the presence of factor-XIIIa-positive dendrocytes in these lesions and compared our data with similar research in capillary angiomas and normal skin. Other cell lines were studied by Ulex europaeus and by antibodies to the L1 antigen and to the von Willebrand factor. Dendrocytes were identified in the three types of angiomatous growth. They were numerous and appeared plump, but no more dendritic than in normal skin. Verruga peruana and bacillary angiomatosis should therefore be viewed as combined growths of endothelial cells and dendrocytes. The biological link between these two types of cells is emphasized.


Restriction fragment length polymorphisms associated with alpha-hemolysin determinants are correlating with the expression of alpha-hemolysin in strains of Escherichia coli. Three different phenotypes of hemolysis on blood-agar were detected when 58 isolates of Escherichia coli were investigated for alpha-hemolysin synthesis. In strains with chromosomally encoded alpha-hly genes, phenotype I (large and clear hemolysis zones) corresponded with high hemolytic activity and with a 17.2 kb size BamHI restriction fragment hybridizing with an alpha-hly-specific gene probe. Phenotype II (small and turbid hemolysis zones) was associated with low hemolytic activity and generally with a 12.8 kb size hybridizing BamHI restriction fragment. An intermediate phenotype (type I/II) was found in a few strains with moderate hemolytic activity. This correlation between hemolytic phenotype and activity was not found in E. coli carrying alpha-hly plasmids. Type I strains differed from all others in the promotor region of their 17.2 kb size BamHI fragment associated chromosomal alpha-hly determinant. The relation between hemolytic phenotype and DNA hybridization pattern was found in unrelated E. coli isolates of human and animal origin. An association of alpha-hemolysin with other virulence factors was found in most strains of all three phenotypes.


Adhesion of fimbriated and non-fimbriated Klebsiella strains to synthetic polymers. Adherence of three fimbriated and non-fimbriated Klebsiella strains to polyetherurethane was investigated in order to assess the possible role of fimbriae in the adhesion of Klebsiella to synthetic polymers. Fimbriated strains with type 1 and type 1.3 fimbriae adhere significantly stronger to polyurethane than the same strains lacking fimbriae, whereas a strain with type 3 fimbriae shows no different adherence compared with the non-fimbriated variant. Analysis of adhesion kinetics and isotherms reveals that adherence of fimbriated Klebsiella strains is proceeded by the formation of multicellular bacterial layers on the polymer surface. Measurements of the relative hydrophobicity of the strains and adherence experiments under exclusion of unspecific interactions point out that fimbriae obviously play a more important role in adhesion than relative hydrophobicity. The demonstration of reduction of bacterial adherence to polyetherurethane by blocking fimbrial action with fimbriae-specific sugars supports this further.


Restriction fragment length polymorphism and virulence pattern of the veterinary pathogen Escherichia coli O139:K82:H1. Escherichia coli O139:K82:H1 strains originating from outbreaks and single cases of oedema disease in pigs were characterized by their genomic restriction fragment length polymorphism (RFLP), their virulence pattern, and by the occurrence as well as the genomic distribution of the determinants for hemolysin (hly) and verotoxins (shiga-like toxins; sltI, sltII). Whereas the RFLPs revealed considerable variation among the E. coli O139:K82:H1 isolates depending the origin and epidemic source of the strains, the virulence gene slt II was found to be present in nearly all strains in a particular chromosomal region. Similar to RFLPs, the plasmid profiles are useful for epidemiological analysis.


Determination of S fimbriae among Escherichia coli strains from extraintestinal infections by colony hybridization and dot enzyme immunoassay. 449 E. coli strains obtained from septic infections (124 isolates), urinary tract infections (246) and water (79) were surveyed for S/F1C fimbrial DNA by DNA hybridization and for expression of S fimbriae by enzyme immunoassay. S/F1C fimbrial DNA was detected with greater frequency in septic (35%) and urinary (43%) isolates than in water isolates and was often associated with the O2, O4, O6, O18, O83, and O156 serogroups. Most O45 strains did not possess such sequences. Only 12% and 28%, respectively, of the septic and urinary strains possessing S/F1C fimbrial DNA expressed S fimbriae.


A search for contrast effects with fear evoking stimuli. The occurrence of fear contrast effects was investigated in a laboratory study of fearful people. A total of 65 university students were exposed on separate occasions to two fearful stimuli (spiders and snakes). The first exposure session was manipulated so that experimental groups differed in the amount of fear evoked by the stimulus (high fear, moderate fear and low fear). Exposure to the second animal was designed to produce a moderate level of fear in all subjects. During exposure to the animals, measures of subjective fear and heart rate were taken. Compared to a control group of subjects who experienced moderate fear on two occasions, a prior high fear experience led to a decrease in fear of the second stimulus, and a prior low fear experience led to an increase in fear of the second stimulus. The increase in fear in the latter group was evident in both subjective and physiological indices of fear, but in the high fear group the contrast was evident only in subjective fear.


Endothelial-dependent sexual dimorphism in vascular smooth muscle: role of Mg2+ and Na+. 1. In isolated aortae of the male rat [Mg2+]o withdrawal and concomitant reduction in [Na+]o (to 84 mM) induced significant increases of basal tone, but, surprisingly, this did not occur in intact aortae removed from female rats. Such tension development, however, was observed in endothelium-denuded aortic preparations from both sexes. These observed gender-related differences were not dependent on animal strain or types of tissue preparations. 2. No tension development was observed in aortae obtained from castrated males treated with oestradiol. Aortic tissues of sexually-immature male and female rats exhibited marked tension development when exposed to 0 mM [Mg2+]o and low [Na+]o. 3. Tension development in Mg(2+)-free, low-Na+ media was not tachyphylactic and completely dependent on extracellular Ca2+; addition of 1.2 mM Mg2+ to the Mg2+ and Na(+)-deficient incubation media relaxed the increase in tension to a normal basal level. 4. Two known endothelial-derived relaxant factor (EDRF) inhibitors, methylene blue and haemoglobin, induced tension development in female aortae with intact endothelium exposed to Mg(2+)-Na+ deficient media, while use of a specific inhibitor of EDRF-derived nitric oxide, viz., NG-monomethyl-L-arginine (L-NMMA), resulted in potentiation of tension development in male, but not in female, aortae. This effect of L-NMMA was antagonized by L-arginine. 5. The Ca ionophore, A23187, partially relaxed contractile responses in male aortae (with intact endothelium) which were followed by potentiated contractions. Endothelium-dependent vasodilator responses to A23187 (10(-10)-10(-6) M) of aortic rings from male or female rats in normal Krebs-Ringer bicarbonate solution were not different.6. These results suggest that: (a) as in vascular smooth muscle cells, Mg2+ plays an important role in Ca2 + homeostasis in endothelial cells, probably via Na+-Ca2+ exchange; and (b) sex steroid hormones, probably the female sex hormone, 17-beta-oestradiol, may regulate contractile responses of intact vascular smooth muscle by modifying endothelium functions through such Mg2 '-regulated internal Natdependent Ca2+ entry. These data may help to explain why female subjects, despite Mg deficiency, unlike male subjects, are protected against ischaemic heart disease and cerebrovascular disease until menopause.


The electrical and mechanical responses of the rabbit saphenous artery to nerve stimulation and drugs. 1. Electrical and mechanical responses to field stimulation (1-64 Hz, 0.5 ms supramaximal voltage) were recorded simultaneously in the rabbit saphenous artery. The electrical response consisted entirely of excitatory junction potentials (e.j.ps) which were abolished by alpha, beta methylene ATP (alpha, beta MeATP, 10(-6) M) and by tetrodotoxin (TTX, 10(-6) M) but were unaffected by the alpha 1-adrenoceptor antagonist, prazosin (10(-6) M). No additional electrical response was evoked by field stimulation, even in the presence of normetanephrine (NMN) and desmethylimipramine (DMI, each 10(-6) M), which block neuronal and extraneuronal uptake of noradrenaline (NA) respectively. Action potentials to field stimulation were produced only in the presence of tetraethylammonium (10(-3) M) which also enhanced the contraction. 2. Contractions to field stimulation were reduced (by some 50%) by prazosin (10(-6) M) and abolished by the additional presence of alpha, beta MeATP (10(-6) M), which blocks purinoceptors by desensitization, suggesting the involvement of both NA and an ATP-like substance in the contractile response. 3. Idazoxan (10(-6) M) which blocks prejunctional alpha 2-adrenoceptors, significantly increased the amplitude of both e.j.ps and the contraction to field stimulation (10 pulses, 1-4 Hz, 0.5 ms, supramaximal voltage). 4. NA (10(-2) M by pressure ejection) did not alter membrane potential even in the presence of NMN and DMI (each 10(-6) M). ATP (10(-2) M by pressure ejection) produced a concentration-dependent, alpha, beta MeATP-sensitive depolarization. 5. In tissues desensitized by constant infusion of alpha, beta MeATP (10(-6) M contractions to NA (10(-7) - 3 x 10(-5) M), histamine (10(-7) - 3 x 10(-5) M) and KCl (1-1.6 x 10(-2) M) were unaffected.6. Following restoration of the membrane potential, after an initial depolarization, alpha,beta MeATP (4 x 10-6M) did not change the amplitude of electrotonic hyperpolarizing current pulses significantly but abolished evoked ej.ps. The rates of recovery of evoked ej.ps and the depolarization to ATP (10-2M by pressure ejection) following desensitization to alpha,beta MeATP (10- 6 M) were comparable. These results suggest that the effects of a,fl MeATP are mediated selectively via receptors (purinoceptors).7. Suramin (10-3M) abolished ej.ps and the prazosin (10-6M), insenstive component of the contractile response and antagonized contractions to xfl MeATP (10-7_1i-5M), ATP (10-5_1i-3M), histamine (10- 7-3 x 10-SM) and 5-hydroxytryptamine (10-7-10-SM) but those to NA (10-7-10-SM) and KCI (1-1.6 x 10-2 M) were unaffected. Suramin is insufficiently selective, under these conditions, as a purinoceptor antagonist.


Characterization of postsynaptic alpha-adrenoceptors in the arteries supplying the oviduct. 1. In vitro experiments were designed to characterize postjunctional alpha-adrenoceptor subtypes in ring segments (1 mm length; outer diameter 300-500 microns) from arteries supplying the oviduct of the heifer. 2. Noradrenaline, adrenaline and phenylephrine evoked concentration-dependent contractile responses. The pD2 values were 5.67, 5.89 and 5.93, respectively. Medetomidine clonidine and B-HT 920 (2-amino-6-allyl-5,6,7,8-tetra-hydro-4H-(thiazo)-4,5-d-azepoine ) were ineffective. 3. The alpha-adrenoceptor selective antagonists, prazosin (1 nM-0.1 microM) and rauwolscine (0.1-10 microM) competitively antagonized the response to noradrenaline. The pA2 values were 9.38 and 6.83, respectively. 4. The dissociation constant (KD) for noradrenaline calculated by use of the irreversible antagonist, dibenamine, was 3.95 (2.09-5.81) microM. The occupancy-response relationship was non-linear. Half-maximal response to noradrenaline was obtained with 22% receptor occupancy while maximal response required 100% occupancy. 5. B-HT 920 evoked a biphasic contractile concentration-dependent response in preparations incubated in a physiological solution containing 20 mM K+, 0.1 microM prazosin and 1 microM propranolol. Rauwolscine 0.1 microM significantly (P less than 0.01) blocked the first component of the B-HT 920 concentration-response curve with an apparent pA2 value of 8.52 (7.86-9.18). 6. These results strongly suggest that alpha-adrenoceptors in oviductal arteries are mainly of the alpha 1 subtype, although a possible role for alpha 2-adrenoceptors cannot be excluded.


Reduced alpha 1- and beta 2-adrenoceptor-mediated positive inotropic effects in human end-stage heart failure. 1. alpha 1-Adrenoceptor (phenylephrine in the presence of propranolol) and beta 2-adrenoceptor (fenoterol)-mediated positive inotropic effects were investigated in human ventricular preparations isolated from five non-failing (prospective organ donors) and from eight explanted failing hearts with end-stage idiopathic dilative cardiomyopathy (NYHA IV). 2. For comparison, the nonselective beta-adrenoceptor agonist isoprenaline, the phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine (IBMX), the cardiac glycoside dihydroouabain, and calcium were studied. 3. Furthermore, the influence of IBMX on adenosine 3':5'-cyclic monophosphate (cyclic AMP) PDE activity as well as total beta-adrenoceptor density, beta 1- and beta 2-adrenoceptor subtype distribution, and alpha 1-adrenoceptor density were compared in nonfailing and failing human heart preparations. The radioligands (-)-[125I]-iodocyanopindolol for beta-adrenoceptor binding and [3H]-prazosin for alpha 1-adrenoceptor binding were used. 4. The inotropic responses to calcium and dihydroouabain in failing human hearts were unchanged, whereas the maximal alpha 1- and beta 2-adrenoceptor-mediated positive inotropic effects were greatly reduced. The inotropic effects of the other cyclic AMP increasing compounds, i.e. isoprenaline and IBMX, were also reduced to about 60% of the effects observed in nonfailing controls. The potency of these compounds was decreased by factors 4-10. 5. The basal PDE activity and the PDE inhibition by IBMX were similar in nonfailing and failing preparations. 6. The total beta-adrenoceptor density in nonfailing hearts was about 70 fmol mg-1 protein. In failing hearts the total number of beta-adrenoceptors was markedly reduced by about 60%. The betal/beta2-adrenoceptor ratio was shifted from about 80/20% in nonfailing to approximately 60/40% in failing hearts which was due to a selective reduction of beta1-adrenoceptors. The beta2-adrenoceptor population remaining unchanged. alpha-Adrenoceptor density was increased from about 4 fmol mg-' protein in nonfailing to 10 fmol mgprotein in failing hearts.7. Changes in PDE activity and adrenoceptor downregulation cannot completely explain the reduced positive inotropic effects of alpha 1- and beta 2-adrenoceptor agonists in failing human hearts. This supports the hypothesis that impairment of other processes such as the coupling between receptor and effector system, i.e. the respective G-proteins, are equally important in end-stage heart failure.


[Localization of two neurotropic molecules in cultured glial cells by ion microscopy]. The intracellular localization of two families of neurotropic drugs: flunitrazepam and flurazepam (benzodiazepine), triflupromazine and trifluoperazine (phenothiazine) has been studied by ion microscopy. The molecules have been incubated with C6 glioblastoma cells from rat origin and with astroglial primary cultures. The images of the intracellular distributions of the two drugs are easily obtained by selecting the fluorine atom of the molecules. The images obtained show that flunitrazepam and flurazepam, two drugs of the benzodiazepine group are mainly located to the nuclei, whereas triflupromazine and trifluoperazine, two phenothiazines are exclusively located inside the cytoplasm.


Effect of P-glycoprotein expression on the accumulation and cytotoxicity of topotecan (SK&F 104864), a new camptothecin analogue. Topotecan (TPT, 9-dimethylaminomethyl-10-hydroxycamptothecin) is the first topoisomerase I-directed cytotoxic agent to enter clinical trials in the United States in two decades. The effect of P-glycoprotein (Pgp) overexpression on TPT cytotoxicity was examined in CHRC5 (colchicine-resistant) and AuxB1 (parental) Chinese hamster ovary cells. Examination of the IC50 values observed in colony-forming assays revealed that the CHRC5 cells were 15-fold (SD, +/- 3; n = 3) resistant to TPT after a 1-h exposure and 3.2-fold (SD, +/- 1.4; n = 4) resistant in continuous exposure experiments. Band depletion immunoblotting revealed that 4-fold higher concentrations of extracellular TPT were required to induce the formation of topo I-DNA complexes in CHRC5 cells as compared to AuxB1 cells. To assess the role of Pgp in this resistance, drug accumulation and cytotoxicity assays were repeated in the absence and presence of quinidine. Addition of quinidine enhanced TPT accumulation (measured by high-performance liquid chromatography) and diminished the IC50 for TPT to a greater extent in CHRC5 cells than in AuxB1 cells. To examine whether similar effects could be detected in Pgp-expressing human cells, MCF-7/Adriar breast cancer cells and KG1a human acute myelogenous leukemia cells were examined. Quinidine or verapamil enhanced TPT accumulation in both of these cell lines but had no effect in parental MCF-7 cells or a variety of human leukemia cell lines that do not overexpress Pgp. Cytotoxicity measurements performed by counting the number of surviving cells (MCF-7/Adriar) or employing a modified, highly stable tetrazolium dye reduction assay (leukemia cell lines) revealed that quinidine diminished the IC50 for TPT in the Pgp-overexpressing cell lines but not in the control lines. These results suggest that Pgp overexpression diminishes TPT accumulation and TPT cytotoxicity in hamster and human cells. It should be stressed, however, that these effects were substantially smaller than the effects of Pgp overexpression on the accumulation and cytotoxicity of the anthracycline daunorubicin and the epipodophyllotoxin etoposide in the same cell lines.


Differences in breast cancer risk factors to neu (c-erbB-2) protein overexpression of the breast tumor. To investigate whether overexpression of the neu protein in breast tumors differentiates risk factor patterns for breast cancer, neu protein overexpression was determined in 296 breast carcinomas of patients participating in an ongoing population-based case-control study. Risk factor information on these patients and 737 controls was obtained during home interviews. Most breast cancer risk factors showed similar associations with neu-positive and neu-negative tumors, but remarkable differences were found for breast-feeding and age at first full-term pregnancy. In contrast to the slightly protective effect of breast-feeding in the neu-negative group, the risk of neu-positive breast cancer was 4.2-fold increased in women who ever breast-fed. Increasing age at first full-term pregnancy was positively associated with both neu-positive and neu-negative breast cancer, but the association was about 2 times stronger for neu-positive tumors. We conclude that neu oncogene overexpression of the breast tumor seems to be associated with a distinct risk factor pattern.


Molecular analysis of the chromosome 11p region in renal cell carcinomas. Comparative histological data suggest that papillary renal cell tumors in adults and Wilms' tumors in children develop from maturation-arrested cells of similar origin. Wilms' tumor is characterized by genetic changes at the chromosome 11p region. In the present study, we have analyzed 10 papillary and 10 non-papillary renal cell tumors and determined the allelic status of 6 loci on the short arm of chromosome 11. Only one papillary renal cell carcinoma among the 20 tumors showed a loss of constitutional heterozygosity for the chromosome 11p region. These data suggest that separate molecular events occur in the development of Wilms' tumor and papillary renal cell tumors, subsequent to the proliferation of maturation-arrested cells of the kidney.


The role of thyroid stimulating antibody (TSAb) in the thyroid function of patients with post-partum hypothyroidism. We investigated the association between thyroid function and the biological activities of thyroid stimulating antibodies (TSAb) and thyroid stimulation blocking antibodies (TSBAb) in patients with post-partum hypothyroidism. A prospective study. We studied 25 patients with post-partum hypothyroidism who visited our thyroid clinic during the period from 1985 to 1990. We measured TSH binding inhibitory immunoglobulin (TBII) and TSAb activity at the initial presentation of each of the 25 patients. Women found to have elevated TSAb activity were followed up. Upon finding negative TSAb activity along with positive TBII activity in the serum at the initial presentation, we measured TSBAb activity. Women found to have elevated levels of TSBAb at the initial presentation were also followed up. Elevated TBII activity was found in six of the 25 patients, as was high TSAb activity (205-2651%, normal 55.0-145.0%) in five of these six and in one other patient at the initial presentation. Markedly elevated TSBAb activity (89%) was found in one TBII positive patient. We were able to follow up serially five TSAb positive patients and the TSBAb positive patient over periods ranging from 11.5 to 26.5 months post-partum. The maximal value of TSAb activity was observed at the initial presentation in all TSAb positive patients, following which the activities gradually decreased. One of these patients developed Graves' hyperthyroidism associated with high TSAb activity (1223%) at 10.5 months post-partum. One of the other patients was restored to euthyroid with elevated TSAb activity (279%), but thereafter developed hypothyroidism in conjunction with the disappearance of TSAb activity at 26.5 months post-partum. In the other two patients, normalization of thyroid function was observed with elevated TSAb activity. Thereafter, thyroid function remained within the normal range even with the disappearance of TSAb activity. In the other patient, normalization of thyroid function was observed at 11.5 months post-partum, 3 months after the disappearance of TSAb activity. In the TSBAb positive patient, TSBAb activity decreased to 21% by 17.5 months post-partum associated with normalization of thyroid function. The present study demonstrates the presence of elevated levels of TSAb activity in some patients with post-partum hypothyroidism. In these patients, Graves' hyperthyroidism may be induced by TSAb activity, and hypothyroidism may reoccur with the disappearance of the TSAb activity. Furthermore, post-partum hypothyroidism may be due to increased TSBAb activity in some patients.


Pharmacokinetics and dose proportionality of D2-agonist MK-458 (HPMC) in parkinsonism. To investigate the pharmacokinetic profile, bioavailability, and dose proportionality of the D2-agonist MK-458 (hydroxypropylmethylcellulose tablet, a sustained release formulation), a 4-period crossover study was conducted in 10 patients with mild to moderate Parkinson's disease (mean age = 63 y; 1 woman, 9 men). Following a titration phase to induce tolerance, each patient was given single oral doses of 6, 12 and 18 mg and a single intravenous 40 micrograms dose (5 micrograms/h over 8h). The maximum concentrations of MK-458 observed in plasma after oral administration were 139, 240 and 344 ng/L for the 6, 12 and 18 mg doses, respectively, and occurred after 8.0, 9.0 and 5.5 h, respectively. Mean areas under the plasma concentration-time curves were 1728, 2849 and 5484 ng/L.h, respectively. The mean plasma half-life was 3.8 h and mean plasma clearance was 3390 ml/min (203.4 L/h). The bioavailability (approximately 5%) was very similar for the 3 tablet formulations tested. The disposition of MK-458 was independent of the dose over the range of doses studied.


Selective brain cooling in desert animals: the camel (Camelus dromedarius). 1. Animals living in the Arabian desert are subjected to extremely high temperatures during the day in summer and very cold nights in winter. They have developed various adaptive mechanisms in order to cope with these severe heat conditions. 2. The camel (Camelus dromedarius), like many other land animals, resorts to selective brain cooling when it is subjected to heat stress. 3. This mechanism protects the heat-sensitive brain tissue from heat stress and at the same time increases the animals' tolerance to high temperatures. 4. The blood cooled in the nasal cavity by evaporative heat loss is diverted to the brain sinuses via the nasal and angular veins. 5. In the cavernous sinus, the arterial blood in the carotid rete is cooled by the cold venous blood before entering the brain. This will lead to significant cooling of the brain tissue. 6. Active myogenic tone was mainly observed in the facial, nasal and angular oculi veins of the camels head. This tone was found to be sensitive to small changes in temperature in the range 33-45 degrees C. 7. The facial veins constricted, while the nasal and angular oculi veins relaxed to increasing temperatures. This leads to a coursing of cold venous return to the brain's sinuses for selective brain cooling. 8. It is concluded that this myogenic vasoactive mechanism is a major factor in the control of blood flow in the facial area of the camel during heat stress.


Na-transport during long-term incubation of the hen lower intestine: no aldosterone effect. 1. In order to test the aldosterone effect in vitro, Na-transport of the coprodeal epithelium from hens on low-NaCl diet was measured in the Ussing chamber for up to 8 hr. Short-circuit current (SCC, near equal to the amiloride inhibitable Na-transport) was recorded. 2. Incubation media were either Krebs-phosphate or bicarbonate buffer with and without addition of beta-hydroxybutyrate, glutamine and mannose as "metabolic fuels". The media were replaced every hour. The Krebs-phosphate buffer was further tested with and without indomethacin and media replacement. Na-transport was best maintained in this buffer with replacement: SCC at 4 hr: 156 +/- 21 microA/cm2, 8 hr: 73 +/- 14 microA/cm2. 3. The aldosterone experiments were carried out on tissues from hens resalinated for 24 hr. No effects were demonstrated at concentrations up to 10(-5) M. The SCC showed an unexpected raise within 2-4 hr to a very high level (4 hr: 221 +/- 61 microA/cm2) both in the control and in all aldosterone-treated tissues. This SCC decreased slowly to 210 +/- 29 microA/cm2 at 8 hr. It was abolished by amiloride. 4. No increase in SCC was observed in tissues from hens after 48 and 72 hr of resalination either after aldosterone or on chronic high-NaCl diet.


Thermogenic, thermolytic and body temperature effects of fenfluramine, a 5-hydroxytryptamine agonist, in the domestic fowl (Gallus domesticus). 1. Intramuscular injection of the 5-HT agonist DL-fenfluramine increased the metabolic rate of mature cockerels by about 25% over the following 22 hr. The acute effect, over the 3 hr following injection, attained 40% at 10 degrees C, 35% at 20 degrees C and 25% at 32 degrees C. 2. Heat loss mechanisms (peripheral vasodilatation, postural change and panting) were also stimulated, to an extent which varied with ambient temperature. 3. Food intake, respiratory quotient and locomotor activity were significantly reduced by fenfluramine injection. 4. The opposing effects on heat production and heat loss had an influence on deep-body temperature which varied from a reduction of 0.5 degrees C at 10 degrees C ambient to an increase of about 0.5 degrees C at 32 degrees C. 5. The 5-HT blocker, methysergide, prevented the effects of fenfluramine on both heat production and heat loss for about 5 hr after injection. 6. The autonomic ganglion blocker, hexamethonium chloride, reduced the thermogenic but not the heat-loss effects of fenfluramine. 7. The results suggest that DL-fenfluramine has centrally-occurring but independent effects on heat production and a number of heat loss effectors, and that the heat production effect is mediated by the autonomic nervous system. The effect of fenfluramine on deep-body temperature appears to result from an altered equilibrium between heat production and heat loss.


The kinetics of homosynaptic short-term depression in cell RPa3 of Helix pomatia depends upon the level of activity prior to depression. 1. Following synaptic rest periods of 2 min, recovery from EPSP depression was dominated by a monoexponential phase completed within 2 min. After rest periods of 6 min, a two-phased recovery occurred: a transient phase followed by a slow phase lasting 10 min. 2. The shift of recovery kinetics was associated with a change of the time course of depression: following rest periods of 2, 6 and 12 min, EPSP trains of 1/10 Hz gave three different depressions. 3. The change of recovery inverted a logarithmic proportionality between frequency of EPSPs and degree of depression to an inverse relation.


Ureotelism as the prevailing mode of nitrogen excretion in larvae of the marsupial frog Gastrotheca riobambae (Fowler) (Anura, Hylidae). 1. Embryos from the pouch of the marsupial hylid frog Gastrotheca riobambae excrete urea. 2. Free-living tadpoles of G. riobambae excrete mainly urea, in comparison with tadpoles of other hylid frogs. 3. The activity of arginase is high in embryos from the pouch, and in tadpoles of G. riobambae. 4. The ureotelism of G. riobambae larvae is an adaptation for prolonged incubation in the pouch of the mother, and for development in limited amounts of water.


The response of statocyst receptors of the lobster, Homarus americanus, to movements of statolith hairs. 1. While recording from the statocyst nerve of Homarus americanus, we deflected the statolith hairs from the "rest" position they assumed after the lith was removed. 2. Each of the smaller statocyst hairs apparently drove three sensory receptors; all receptors were sensitive to hair position, hair movement velocity, and hair movement direction. 3. Two of the receptors, types A and C, only responded when the hair was lifted up and away from rest; the third, type B, only responded vigorously when a hair was moved back toward rest from such a deflexion. 4. Type A and B receptors were phasic-tonic; type C receptors were phasic.


Statolith hair movements and the regulation of tonic gravity reflexes in the lobster, Homarus americanus. 1. The irregularity of the statolith of the lobster, Homarus americanus, probably causes a large and haphazard variation in the response of the individual statocyst receptors to body rotation. 2. Lobster gravity reflexes are regulated by the summed responses of the statocyst receptors; this probably compensates for the haphazard variation in the sensory input.


Distribution and vasomotor effects of neuropeptides in angular oculi and facial veins of reindeer. 1. The vasomotor responses to neuropeptides of the angular oculi and facial veins of reindeer were examined in vitro and correlated with the neuropeptide distribution in the perivascular nerves, as demonstrated by immunohistochemistry. 2. Nerves displaying calcitonin gene related peptide (CGRP)- or neuropeptide Y (NPY)-like immunoreactivity (-LI) were observed in the media of both veins, while very few fibers were immunoreactive to vasoactive intestinal polypeptide (VIP) or substance P (SP) in either vein. 3. The staining pattern for NPY-LI was largely identical to that of dopamine-beta-hydroxylase, a marker for noradrenaline (NA) producing fibers, indicating coexistence of NPY and NA. 4. Administration of NPY in vitro elicited contractions in both veins in the presence of propranolol, though more conspicuously in the angular oculi vein. 5. The peptide was without any modulating effect on NA-stimulated contractions in the angular oculi vein, whereas a small enhancement of the NA-induced tone was seen in the facial vein. 6. CGRP caused partial relaxation of both veins, whereas atrial natriuretic polypeptide caused relaxation only in the facial vein. VIP and SP had no effect on either vein. 7. The results suggest that in reindeer the sympathetic nerve fibres to both facial and angular oculi veins contain the vasoconstrictor neuropeptide NPY besides NA, even though these fibres exert a vasodilator action on the myogenically active facial vein. 8. The vasodilator neuropeptide CGRP, which is present in other more sparse perivascular nerve fibres mainly in angular oculi vein, is perhaps of afferent nature in which case CGRP might subserve axon reflex functions. 9. If, however, also the CGRP fibres are truly efferent in nature, chances for a central reciprocal control of flow through angular oculi vein might be at hand.


Localization, cellular morphology and respiratory capacity of "brown" adipose tissue in newborn reindeer. 1. The localization and cellular morphology of adipose tissue was studied by light, fluorescence and electron microscopy in reindeer between 2 weeks pre partum and 4.5 months post partum during calving, and the subsequent growth period. The respiratory capacity of the adipose tissue was examined in terms of morphometric mitochondrial volume and cytochrome-c oxidase or succinate dehydrogenase activity. 2. Adipose tissue was located at specific anatomical sites in the newborn reindeer (from 0 to 2 days of age). The perirenal-abdominal depot was the largest location (32%) followed by the inter(pre)scapular (18%) and sternal (12%) depots. Internal depot dominated over external or peripheral depots (66-34%). The locations of adipose tissue were largely similar in foetal, newborn and young reindeer. 3. The adipose tissue of the newborn reindeer had all the typical cell morphological characteristics of brown adipose tissue: abundant mitochondria, multilocular fat, high vascularization and a dense spot-like sympathetic innervation between the adipocytes. In the young reindeer, however, it resembled white adipose tissue, being almost totally unilocular with few mitochondria. 4. There was a significant correlation between morphometric mitochondrial volume and cytochrome-c oxidase activity (r = 0.848) in the adipose tissue. Mitochondrial volume, cytochrome-c oxidase and succinate dehydrogenase activity were highest after birth and decreased to almost an undetectable level during the first month. A parallel decrease occurred in the amount of brown adipose tissue from birth (1-2%) to the age of about one month (0.3%). 5. It is concluded that the distinct cell morphological features and high respiratory capacity of the adipose tissue indicate the presence of brown adipose tissue at specific anatomical locations in newborn reindeer. A marked progression towards the characteristics of white adipose tissue then takes place at the same locations during the first month. The results suggest the fundamental significance of brown adipose tissue for non-shivering thermogenesis in newborn reindeer.


Dependence of the sympatho-adrenal activity on the nutritional status in corticosterone treated rats. 1. An integrated sympatho-adrenal (SA) activity, expressed in terms of urinary catecholamines (CA) excretion, and direct sympathetic activity in the interscapular brown adipose tissue (IBAT), expressed in terms of noradrenaline (NA) turnover, were studied in corticosterone treated stock fed and sucrose overfed rats. 2. Corticosterone in stock fed rats significantly decreased both the rate of IBAT NA turnover and its mass as well as urinary NA excretion but did not change either IBAT NA content, urinary adrenaline excretion or adrenal CA content. 3. Sucrose overfeeding significantly increased SA activity, i.e. the rate of NA turnover in the IBAT and urinary excretion of CA. However, corticosterone did not inhibit the sucrose-induced sympathetic nervous system activation but potentiated the activity of adrenal medulla. 4. The results suggest that the effect of corticosterone treatment on the SA activity in rats is dependent, in addition to other factors, on the nutritional status of the animals.


Miracidium of Schistosoma mansoni: a macromolecular glycoconjugate as signal for the behaviour after contact with the snail host. 1. The behaviour of the miracidium of Schistosoma mansoni after contact with agar blocks containing Biomphalaria glabrata snail conditioned water (SCW) or its components, was studied. 2. "Repeated investigation" was the most specific response at contact with the snail host. 3. Fractionation and specific chemical treatment of SCW revealed that this response was stimulated by a lysozyme sensitive glycoconjugate with a mol. wt greater than 300,000. 4. Low molecular weight components of SCW had no stimulatory effect on the miracidia, although MgCl2 offered as pure chemical did so.


Seasonal changes in the tolerance of osmotic stress in natterjack toads (Bufo calamita). 1. Bufo calamita were exposed to tap water to solutions of urea (up to 1000 mM) and NaCl (up to 250 mM). 2. The effects of season and nutrition on the adaptation to osmotic stress were studied by monitoring body mass, moulting rate, hematocrit, plasma osmolality and the plasma concentrations of urea, chloride and glucose. 3. There were marked seasonal changes in the time of survival in tap water as well as in the ability to acclimate to high concentrations of urea and NaCl. 4. The maximal concentration of urea in the plasma of starving toads was greater in winter (650 mM) than in summer (410 mM), but fed toads also reached winter levels (653 mM) during summer. 5. Salt acclimation was accompanied by urea accumulation in plasma up to 175 mM. 6. Salinities exceeding 454 mOsmol/l of NaCl were lethal.


A time course study of the isometric contractile properties of rat extensor digitorum longus muscle injected with bupivacaine. 1. The effect of intramuscular injections of the myotoxin bupivacaine on the isometric contractile properties of rat extensor digitorum longus (EDL) muscle was studied. 2. Immediately after injection the EDL muscle did not contract when stimulated. The absolute (mN) and normalized (N/g) peak twitch (Pt) and tetanic (PO) tensions gradually returned to normal by 21 days after injection. 3. Thereafter, the injected muscles grew at an accelerated rate and by 80 days were 70% heavier than controls. 4. The hypertrophy was not paralleled by a proportional increase in absolute Pt and Po and consequently the normalized Pt and Po were 30% less than controls.


The use of purified condensed tannin as a reference in determining its influence on rumen fermentation. 1. Tannins were purified from the leaves of trees forming part of giraffe's diet in the Kruger National Park. 2. In general, hydrolysable tannin formed less than 10% of the total purified crystal complexes, condensed tannin and possibly some non tannin phenols forming the balance. 3. Each tree species condensed tannin gave a different calibration curve and these were used in the assay. 4. Volatile fatty acid production during in vitro fermentation was greatly reduced when the substrate contained more than 6% condensed tannin.


Differences in fatty acid composition of various tissues of the marmoset monkey (Callithrix jacchus) after different lipid supplemented diets. 1. The fatty acid composition of different muscles, organs and blood components of the marmoset monkey were examined after long-term feeding of several well defined lipid supplemented diets. 2. Similarities between the fatty acid composition of cardiac and skeletal muscles which persisted after all diets suggest that biopsy of skeletal muscle may have an important diagnostic value in this and other primate species. 3. The relationship between the dietary intake of individual fatty acids and their proportions in different tissues is both complex and variable. 4. However, the lipid metabolism of Callithrix jacchus recommends this small non-human primate as a most suitable species for the study of lipid nutrition.