Retrograde transport of horseradish peroxidase in sciatic nerve of rats and dystrophy mice.

The relationship between nerve or muscle activity and retrograde HRP transport was studied in rat Sciatic nerve and in dystrophy mice. sciatic nerve stimulation facilitated transport to 250% of control level, while colchicine decrease transport depending on dosage. Tendonectomy as well as colchicine treatment ultimately decreased HRP transport, but before the decrease, there was a transient facilitatory phase in both colchicine treated and tendonectomized rats. In dystrophy mice, almost twice as much nerve trunk injected HRP was transported as in control mice. This suggests that retrograde transport level increases in some stage of dystrophy.


Gastric afferents to the nucleus of the solitary tract in the cat.

Afferent projections of the vagus nerve (X) were investigated following nodose ganglion injections of [3H]leucine or horseradish peroxidase (HRP) and stomach wall injections of HRP. Ganglionic injections demonstrated a projection to the solitary nucleus (SN) including the part designated as the area subpostrema (ASP). A projection to the area postrema was also seen following [3H]leucine injections. Stomach wall injections of HRP labelled fibres and terminals bilaterally in the ASP and more ventral parts of the SN. These results provide the first morphological evidence of gastric afferents of X projecting to an area of the SN previously implicated in gastric functions.


Are histamine H2-receptor depressions of neuronal activity in tissue cultures from rat hypothalamus mediated through cyclic adenosine monophosphate?

Iontophoretic application of histamine H2-agonists depressed spontaneous firing of tuberal hypothalamic neurons in tissue culture. Perfusion with inhibitors of cyclic nucleotide phosphodiesterase increased the strength of these depressions, which persisted during perfusion with Ca2+-free medium. These results support a role of cyclic AMP as a mediator of histamine H2-elicited depressions of neuronal activity.


Immunohistochemical evidence for an intracellular localization of plasma proteins in human foetal choroid plexus and brain.

The intracellular distribution of plasma proteins in human foetal choroid plexus and brain was investigated by immunohistochemistry. Small groups of cells or single scattered cells in the epithelial layer of the choroid plexus exhibited positive staining for alpha-fetoprotein, albumin and transferrin, whereas prealbumin was found in the majority of the epithelial cells. Numerous nerve cells in the cerebral wall and in various brain stem nuclei were positively stained for alpha-fetoprotein, albumin and prealbumin. All appropriate controls were negative. The presence of plasma proteins within choroid plexus epithelial cells suggest that these proteins are transported from blood to CSF by a transcellular route across the choroid plexus epithelium. The intracellular distribution of plasma proteins in developing neurons may indicate that these proteins play some important role in neuronal differentiation or development.


Staining of the dorsal root primary afferent fibers by anterograde movement of horseradish peroxidase and retrograde labelling of motoneurons and preganglionic autonomic cells in the turtle spinal cord.

The enzyme horseradish peroxidase (HRP) has been applied to the proximal stumps of severed thoracic and lumbar dorsal roots in the turtles Pseudemys scripta elegans and Testudo hermanni. The results obtained confirm the distribution pattern observed with anterograde degeneration techniques. Primary afferent terminal structures, however, could be demonstrated in more detail. Commonly, ventral roots were also more or less damaged which resulted in the presence of retrogradely labeled motoneurons and small cells in area X. This group of retrogradely labeled small neurons probably represents cells of origin of preganglionic autonomic fibers.


A horseradish peroxidase study of primary afferent projections to the medullary cuneate nucleus in the rat.

HRP was used to label first order afferent cells of the dorsal root ganglia which synapse at the cuneate nucleus. The results show that it is a population of predominantly large cells that project monosynaptically to the medullary cuneate nucleus and thus support anatomical and physiological studies showing that directly projecting axons to the dorsal column nuclei are larger, faster and conduct information from a select class of sensitive cutaneous mechanoreceptors. The finding, that approximately 20% of DRG neurons can be labeled from the dorsal column nuclei, is consistent with previous estimates of dorsal root fiber projections in the dorsal column based on Marchi degeneration.


Distribution of carotid sinus nerve afferent fibers to solitary tract nuclei of the cat using transganglionic transport of horseradish peroxidase.

The distribution of carotid sinus nerve (CSN) afferent fibers to the solitary tract and its various nuclei has been determined using transganglionic transport of horseradish peroxidase (HRP). The ipsilateral solitary tract was labeled and, in addition, the heaviest labeling was seen dorsomedial within the medial solitary nucleus, as well as just lateral to the tractus solitarius in the lateral solitary nucleus. Bilateral labeling was present caudal to the obex in both the medial and commissural nuclei. The paucity of reaction product within the ventrolateral solitary nucleus supports previous neurophysiological studies suggesting carotid chemoreceptors do not make monosynaptic contacts with respiratory neurons within that nucleus.


Somatotopy in the phrenic motor nucleus of the cat as revealed by retrograde transport of horseradish peroxidase.

Cats received unilateral or bilateral horseradish peroxidase (HRP) injections into various portions of the diaphragm. In two experiments one of the cut cervical roots of the phrenic nerve was immersed in HRP. The phrenic motoneurons located in the fifth and occasionally the fourth cervical segment send their axons, via the upper phrenic root, to pars sternalis and pars costalis of the diaphragmatic dome whereas the neurons of the sixth segment innervate preferentially the dorsal portion both crura and dome. No evidence of contralateral innervation of the diaphragm was obtained.


The presynaptic stimulating effect of acetylcholine on dopamine release is suppressed during activation of nigro-striatal dopaminergic neurons in the cat.

Acetylcholine (ACh) (10(-5) M) in the presence of eserine (2 . 10(-4) M) stimulated the release of [3H]dopamine (DA) continuously formed from [3H]tyrosine, when delivered to a push-pull cannula implanted in the left caudate nucleus of halothane anaesthetized cats. This effect was transient and followed by a second increase in [3H]DA release after removal of ACh and eserine. These changes in [3H]DA release during and after ACh application were no longer seen during activation of the dopaminergic neurons by continuous delivery of substance P to the ipsilateral substantia nigra (SN). These results indicate that the presynaptic regulation of DA release by ACh is dependent on the rate of firing of nigro-striatal dopaminergic neurons.


Location of bladder preganglionic neurons within the sacral parasympathetic nucleus of the cat.

Sacral parasympathetic preganglionic neurons innervating the urinary bladder were labelled by applying horseradish peroxidase (HRP) to branches of the pelvic nerve at the neck of the bladder. Bladder preganglionic cells were located primarily in the intermediolateral grey matter of sacral cord segments 1, 2 and 3 and extended from the ventral end of the central canal to the inferior margin of the dorsal horn. Dendrites extended into the dorsolateral funiculus, toward the lateral edge of the dorsal horn, medially beneath the dorsal horn and ventrally within the nucleus. Although a small number of cells were found medially beneath the dorsal horn, it is concluded that the majority of bladder preganglionic neurons occupy a lateral position within the sacral parasympathetic nucleus.


Superior colliculus efferents to the hypothalamus.

The projection of the superior colliculus to the hypothalamus was studied in the rabbit and rat with light and electron microscopic techniques. This projection system, as demonstrated with the anterograde transport of tritiated leucine, proline, adenosine or horseradish peroxidase, is primarily to dendrites located in the ipsilateral optic and supraoptic tracts. The dendrites originate from cells located in the lateral and anterior hypothalamic areas, retrochiasmatic area and supraoptic nucleus. Thus, the ventral tier of the hypothalamus appears to receive both separate and overlapping visual and multimodal sensory-motor inputs from the retina, ventral lateral geniculate nucleus and superior colliculus.


A unique population of uranaffin-positive intrinsic nerve endings in the small intestine.

A positive uranaffin reaction was observed in the small (40-60 nm) diameter vesicles of some intestinal axons. There was no change in the number of reactive axons or the intensity of reaction after reserpine (5 mg/kg) or after interruption of axons reaching the intestine through the mesentery. The axons were found in the myenteric, submucous and deep muscular plexuses and in the circular muscle. Some uranaffin-positive axons formed synapses with neurons of the myenteric and submucous plexuses. It is concluded that these axons are not noradrenergic. The axons must represent one of the several nerve types which are known to be intrinsic to the intestine, but are as yet unidentified at an ultrastructural level. If, as has been postulated, the reaction localizes amine storage vesicles, the uranaffin-positive axons are probably the intrinsic amine-handling axons previously demonstrated histochemically.


Double labelling of blanched neurons in the central nervous system of the rat by retrograde axonal transport of horseradish peroxidase and iron dextran complex.

The retrograde axonal transport of an iron-dextran complex leads to a labelling of neural cell bodies in the central nervous system (CNS) of the rat. This tracer and horseradish peroxidase (HRP) can both be demonstrated histochemically in same cell bodies of intralaminar thalamic neurons in the central lateral nucleus, after injection of iron-dextran in the striatum and injection of HRP in the motor cortex. This is made possible by processing the sections first for HRP and then for ferric ions by Perl's reaction. This method allows an accurate demonstration of divergent axonal projections and is compatible with cytoarchitectonic studies on the same sections.


In vivo release of substance P in the cat substantia nigra.

Push-pull cannuale were implanted into the substantia nigra (SN) and the caudate nucleus (CN) of the cat to study the in vivo release of substance P (SP), using a radioimmunoassay and high pressure liquid chromatography (HPLC) analysis. The spontaneous release of SP could be detected in the SN and the CN. Potassium (50 mM) locally applied stimulated SP release in both structures. Furthermore an important evoked release of SP was observed in the SN during depolarization of striato-nigral SP fibers with potassium (50 mM) applied in the CN.


Presynaptic localization of substance P degradative enzymes(s) in rat substantia nigra.

Intrastriatal injections of kainic acid in rat brain, which destroyed striatal nerve cell bodies and their axons projecting to the substantia nigra (s. nigra) decreased the rate of breakdown of exogenuously added substance P by washed slice preparations of s. nigra. Injection of 6-hydroxydopamine (6-OHDA) into the s. nigra, which destroys the dopamine nerve cell bodies in this region, did not significantly affect the rate of degradation of substance P by nigral slices. Part of the peptidase activity responsible for breakdown of substance P in the s. nigra may thus be located on the terminals of striatal afferents to the s. nigra.


Mechanisms in the pathogenesis of post-infectious vaccinia virus encephalomyelitis in the mouse.

After intracranial replication of a neurotropic strain of vaccinia in mouse brain, analysis of the purified virus preparation reveals the presence of at least one host protein on the virus which was identified as the myelin basic protein. Vaccinia virus Elstree, a dermotropic virus may substitute for complete Freund's adjuvant (CFA) in inducing experimental allergic encephalomyelitis (EAE). Guinea pigs challenged with virus-myelin emulsions without CFA developed clinical and histological signs of EAE.


Infrequency of retinal neovascularization following central retinal vein occlusion.

Forty-eight patients with the clinical diagnosis of central retinal vein occlusion and ten surgically enulceated eyes with central retinal vein  occlusion documented by histopathologic examination were studied and reviewed. Retinal neovascularization developed in only one of the ten eyes. Rubeosis iridis occurred in 14% (7) of the clinical cases and in all of the histopathologic cases. Ten eyes with neovascular glaucoma, enucleated following central retinal vein occlusion, showed absence of retinal endothelial cells. The absence of retinal capillary endothelial cells is significant in explaining the rare occurrence of retinal neovascularization following central retinal vein  occlusion. However, the small number of cases may reflect a biased result. Further studies of more cases over a longer period are required to reach the final conclusion.


An objective analysis of proliferative diabetic retinopathy before and after pars plana vitrectomy.

Nineteen eyes on which pars plana vitrectomy was performed were studied with fluorescein angiography. The degree of background diabetic retinopathy before and after surgical treatment appeared unchanged. The degree of proliferative retinopathy not only was less after surgical treatment, but continued to show regression with time.


Choriovitreal and subretinal proliferations: complications of photocoagulation.

Ten choriovitreal and three subretinal fibrovascular proliferations were seen after heavy focal photocoagulation of diabetic retinopathy. These complications were believed to be caused by the use of a small spot size with high energy.


Problems associated with prolonged wear soft contact lenses.

Complications of prolonged wearing of soft contact lenses are corneal infection, peripheral vascularization, giant papillary conjunctivitis and allergy, sterile ulcers, corneal warping, lens infection, protein and calcium deposits, lens fragility, and problems with disinfecting solutions. Further long-term studies are needed to compare the safety of prolonged wear soft contact lenses with the safety of intraocular lenses, on which long-term studies are currently being done.


Cell kinetic aspects of chemoradiotherapy in laryngeal and pharyngeal carcinomas.

Chemoradiotherapy is an established method in the therapeutic management of incurable laryngeal and pharyngeal carcinomas or recurrences. On principle two different schedules of chemoradiotherapy are available: (1) the synchronization therapy (irradiation subsequent to a subtoxic dose of 5-fluorouracil) and (2) the combined treatment with bleomycine and X-rays. The results of cell kinetic studies which have fundamentally contributed to our knowledge and understanding of these therapeutic schedules are discussed and the clinical results are demonstrated. The conclusion is drawn that the chemoradiotherapy cannot and shall not substitute the proved methods of surgery and radiotherapy. But in hopeless cases it lengthens the survival time and diminishes the excruciating pain of the tumor patient.


Observations on fast axoplasmic transport in peripheral nerve following repetitive electrical stimulation.

In a series of 13 cats the effect of electrical stimulation of peripheral nerve on the mechanism of fast axoplasmic transport was studied. Electrical stimulation was used for varying time periods at parameters reported in the range of those used to produce electroanalgesia in man. Our results indicate that at these parameters, electrical stimulation produced no effect on this important aspect of nerve function, and, therefore, our work lends support to the safety of these devices in pain states.


Amyloidosis in Malaysian aborigines (Orang Asli).

Material from 334 consecutive autopsies on Orang Asli subjects performed in the University Hospital, Kuala Lumpur between May 1967 and June 1978 was examined for amyloidosis. Nine positive cases were found, all in patients above 40 years of age, giving an age-corrected incidence of about 9%. In 6 cases, amyloidosis was probably secondary to tuberculosis. The remaining 3 cases exhibited a pericollagenous distribution characteristic of primary amyloidosis. Involvement of the heart and lungs was prominent. However, there were considerable similarities in the distribution and staining properties of the amyloid in the 2 groups. Though both the heart and kidney were frequently affected, the kidney was the most common organ to give rise to clinical symptoms. Infection probably plays a major contributory role in amyloidosis in the Orang Asli.


[Scintigraphic follow-up of patients with liver and spleen metastases undergoing cytotoxic therapy (author's transl)].

The importance of scintigrpahy in the diagnosis of liver and spleen tumors is well known. There is, however, up to this time only poor information regarding the use of scintigraphy in follow up studies in patients with liver and spleen metastases undergoing cytostatic therapy. We had the opportunity to investigate 30 patients in whom Hodgkin's disease, Zollinger-Ellison syndrome, ovarian, breast or bronchial and GI malignancy was confirmed by histology. The scintigraphic examinations were performed by means of a scintillation camera using 99mTc sulfur colloid as radiotracer. In each case, three views of the organ were recorded firstly prior to therapy and (at least) once again during or after therapy respectively. The results of liver and spleen scintigraphy were compared with clinical findings, laboratory tests, laparoscopy and histopathology. In 13 of our patients, diminution of metastases was detected. In one patient an increase of the size of the tumors was seen after temporary improvement. In 8 patients, there was no change of the metastatic pattern after cytostatic therapy. 6 patients showed an increase of liver metastases under therapy. Two patients with normal liver scintigraphy in whom clinical and laboratory findings indicated liver involvement yielded no evidence of metastasis at autopsy. In 13 cases, the diagnosis of liver metastasis was detected earlier by scintigraphy than by laboratory tests.


Rotational diffusion of band 3 in the red cell membrane: measurements using triplet probes.

Rotational diffusion of band 3 in the human erythrocyte membrane has been investigated using the technique of flash photolysis. Membranes are labeled with the triplet probe eosin isothiocyanate; most of the label is found to be associated with band 3. Rotation is measured by observing the decay of dichroism of flash-induced absorbance changes arising from the eosin probe. The results indicate that band 3 rotates about an axis normal to the plane of the membrane with a diffusion coefficient in the order of 1,000 sec-1. Removal of spectrin has no observable effect on the rotation of band 3 at pH 7.6. Essentially similar results are obtained with a different probe, iodoacetamidoeosin. Both eosin derivatives are strong inhibitors of anion transport. Illumination of eosin-labeled ghosts causes a rapid loss of acetylcholinesterase activity but this can be prevented by prior displacement of oxygen in the sample by argon.


16, 16 dimethyl prostaglandin E2 reduces histamine release from the stomach and protects the gastric mucosal barrier altered by ethanol in neutral solution.

Damage to the gastric mucosal barrier results in histamine release from intramucosal stores. Previous reports have shown that 16, 16 dimethyl prostaglandin E2 (dm PGE2) protects the stomach from injury by various damaging agents in either acidic or neutral solution. Furthermore histamine released in response to a damaging drug in an acidic medium was reduced by dm PGE2. Using the Heidenhain pouch dog preparation, the present study examined the action of dm PGE2 on ethanol-induced barrier breaking and histamine release in neutral solution. Topical ethanol treatment (15% w/v) damaged the gastric mucosal barrier as evidenced by increased net fluxes of Na+ and K+ and an increase in the histamine content of the fluid irrigating the histamine content of the fluid irrigating the Heidenhain pouch. Intravenous injection of dm PGE2 in the doses of 0.01, 0.10 and 1.00 microgram/kg one-half hour before ethanol administration significantly reduced the appearance of Na+, K+ and histamine. It is concluded that dm PGE2 effectively protects the canine gastric mucosa from damaging agents in neutral solution as evidenced by a reduction in the luminal appearance of Na+, K+ and histamine.


[Clinical and biochemical contributions on the action of maprotiline and clomipramine in depressive states (preliminary observation)].

This study has been conducted on 17 patients suffering from neurotic and psychotic depressions, who had not received a pharmacological antidepressive therapy since at least 1 month. 6 patients suffering from psychotic depression were treated with 100 mg clomipramine i.v. daily for 20 days; 11 patients, 7 of whom suffered from psychotic depression and 4 from neurotic depression, were treated with 150 mg maprotiline i.v. daily for 20 days. In both groups the therapy has been continued orally. In 17 patients a remarkable improvement and even in some cases complete recovery has been obtained. The two psychotropic antidepressive drugs are, furthermore, both active in the same symptoms. The determination of serotonin in human platelets confirms the strong inhibition of its re-uptake by clomipramine and the absence of re-uptake of 5-HT with maprotiline. A constant and progressive increase of 5-HIAA was noted in patients treated with clomipramine. This increase may be considered as a consequence of the increased metabolism of the larger quantity of 5-HT used by the central synapses. The interpretation of the increased levels of 5-HIAA in patients treated with maprotiline is more difficult. Further trials, for instance on the plasmatic tryptophan level, will perhaps solve the problem.


[Rare hemoglobinopathies in Costa Rica].

Among the rare hemoglobinopathies found in Cost Rica are those of the Alfa, Beta, and Delta chains. Among these, Hb Cubujuquí, an undescribed variant, is of special interest. There was an association between the different thalassemic syndromes and their combinations with abnormal hemoglobins.


The secretory component of the interdigestive migrating motor complex in man.

Intraduodenal pH, bicarbonate and amylase secretion, and gastric acid and pepsin output were studied in relation to the migrating motor complex in man. The occurrence of a motor complex in the duodenum was preceded by an increase in gastric acid and pepsin output and followed by a peak in bicarbonate and amylase secretion. It is concluded that the interdigestive phase in man is characterized by periodic activity complexes comprising both motor and secretory components. These observations may have important implications for the interpretation of currently used functional tests of gastrointestinal secretion.


Effects of intestinal amylase and trypsin on pancreatic secretion in the pig.

Pigs were surgically prepared with external pancreatic fistulae and duodenal cannulae in order to elucidate whether the proposed intestinal feedback control of pancreatic secretion in the pig--as in rat and man--is exerted by trypsin. Furthermore, the effect of intraluminal amylase on pancreatic secretion was studied. Reintroduction of pancreatic juice into the duodenum or infusion of trypsin into the duodenum depressed the volume of the pancreatic flow and the protein output markedly. Introduction of amylase into the duodenum did not significantly affect the pancreatic secretion. Thus, it seemed as it trypsin but not amylase was involved in the suppression exerted by pancreatic juice on exocrine pancreatic secretion in the pig.


T helper lymphocytes recognize the VL domain of the isologous mouse myeloma protein 315.

The localization of a major determinant on an isologous myeloma protein (M315) which stimulates BALB/c helper T cells was investigated. Augmentation of the adoptive secondary antibody response to NIP-M315 and the idiotype of M315 (Id315) was used as an indicator of helper effects. Spleen cells primed with the light chain of M315 (L315) and its V-domain (VL315) were highly efficient helpers; priming with the fragment containing the two V-domains of M315 (FV315) induced a somewhat weaker helper effect than L315 or VL315. The helper effect was abolished or markedly reduced by treating the primed cells with rabbit anti-brain theta + C. Cells primed with the heavy chain of M315 (H315) effected weak but significant help. The V-domain of H315 (VH315) was incapable of eliciting cells with detectable helper effect. The data indicate that the VL315 embodies a major determinant for T helper lymphocytes. This determinant is expressed on the free VL315 as well as on the complete M315. In contrast, previous studies have shown that BALB/c antibodies produced against Id315 recognize antigenic sites that are only displayed on associated (VL315 + VH315) domains.


I-region-coded products expressed on both macrophages and thymus epithelium influence T-cell activities.

I-region-coded products expressed on the surface of both macrophages (Mph) and thymus epithelium were shown to restrict T-cell activities at the level of antigen recognition and determination of the T-cell repertoire. Thus keyhole limpet haemocyanin (KLH) -pulsed Mph could elicit a delayed-type hypersensitivity response in a KLH-sensitized mouse only when the Mph and the sensitized mouse were compatible at the I-A region of the major histocompatibility complex. Also, experiments with thymus-grafted chimaeras showed that I-region compatibility between the thymus of the cell donor and the reticuloendothelial system of the recipient was essential for successful transfer of the DTH reaction. Thus, F1 T cells derived from stem cells differentiating in a P1 thymus graft, where F1 parents (P1 and P2) differed only at defined regions of the H-2 complex, could always transfer sensitivity to P1 mice. However, successful transfer to P2 mice was possible only if P1 and P2 were H-21-compatible.


The availability for recognition of normal H-2 antigens by cytotoxic T lymphocytes on a Rauscher-virus-transformed cell, RBL-5A.

The availability for recognition of cell surface H-2Db antigenic determinants on RBL-5A cells in comparison to normal C57BL/L cells was investigated by an in vitro immunological assay. No differences in the immunological recognition of the H-2Db antigens on RBL-5A cells compared to normal C57BL/L cells were detected. This assay system, however, readily detected changes in the H-2Kb determinant profile on target cells from the C57BL/L H-2Kb region mutant strains H(zl) and H(zl70) when compared to normal C57BL/6 mice. The result obtained with RBL-5A target cells therefore suggests that Rauscher murine leukaemia virus transformation does not induce, either genotypically or phenotypically, an immunologically recognizable alteration of the H-2Db antigen profile on this cell.


Relative opsonic and protective activities of antibodies against K1, O and lipid A antigens of Escherichia coli.

The K1 Escherichia coli capsular antigen has been implicated as a virulence factor because of the frequency of isolation of K1 containing strains from certain invasive human infections. In the study of the interaction between K1 strains, normal human polymorphonuclear cells (PMNs) and fresh human serum, we have found varying susceptibility to phagocytosis and killing; thus, the in vitro opsonophagocytic and in vivo protective role of K1, somatic O and core glycolipid antibodies remain unclear. We have therefore examined strains of E. coli with defined susceptibility to phagocytosis by normal PMNs and sera and compared the effect of K1, somatic O and lipid A antibodies in opsonophagocytic tests and mouse protection experiments. K1 E. coli strains demonstrating relative resistance to phagocytosis and killing were effectively opsonized only with specific K1 capsular antisera. Similarly, K1 capsular antisera, but not anti-O or lipid A antisera, also provided protection in mice challenged with a LD100 of K1 E. coli that were "resistant" to phagocytosis. The ability of purified capsular antigens from Neisseria meningitidis group B and K1 "resistant" E. coli to inhibit the phagocytosis of a "sensitive" non-K1 and a K1 E. coli strain of "intermediate" susceptibility to opsonophagocytosis was also investigated. Purified K1 and group B capsular antigens were able to block specific capsular-antibody mediated opsonophagocytosis, yet these capsular antigens failed to inhibit the phagocytosis of non-K1 "sensitive" or K1 "intermediate" E. coli. These studies suggest that K1 antibodies are obligatory for the in vitro and in vivo opsonophagocytosis of "resistant" K1 E. coli and that the K1 antigen must remain in situ on the bacterial surface to exert an anti-phagocytic effect.


The weight of the dorsal, lateral and medial prostatic lobes in man.

The weight of the prostatic lobes in man was determined in an atuopsy series comprising 158 cases. In children the medial pair of lobes formed half of the prostate gland. The "normal" mean weights in adult men of the dorsal, lateral and medial pair of lobes were 3.6, 3.4 and 4.3 g, respectively. In adult men there was no change in lobe weight with increasing age. In subjects who died after protracted disease all of the prostatic lobes had decreased in weight. In subjects with periurethral adenomas the greater weight of the total prostate was due to higher weights of the dorsal and medial prostatic lobes. The observation that the separate prostatic lobes in man can react differently to growth promoting factors indicates that the lobation of the human prostate is not only of anatomical but also of physiological significance.


Prostatism. I. The correlation between symptoms, cystometric and urodynamic findings.

One hundred and seven consecutive patients referred with symptoms of bladder outlet obstruction were studied using cystometry and combined pressure-flow-electromyographic investigation. The symptoms of infravesical obstruction were not statistically significantly correlated to the hydrodynamic documentation of increased bladder outlet resistance as judged by maximum flow rate and the calculated urethral resistance. Irritative symptoms such as frequency, nocturia, urgency and urgeincontinence were statistically significantly correlated to the presence of detrusor hyperreflexia. The functional disorder bladder neck dyssynergia was encounterd in 5% of the patients (95% confidence limits 1-10%). This diagnosis cannot be made by conventional urological investigations. It is concluded that objective demonstration of infravesical obstruction is mandatory in the selection of patients with symptoms of lower urinary tract dysfunction for surgery on the prostate or the bladder neck.


[Method for long-term pacemaker treatment of refractory reentry tachycardias].

A new method for pacemaker treatment of refractory reentry tachycardias has been developed which in 5 patients proved effective over a period of up to ten months. The system consists of a modified QRS-synchronous pacemaker and an external trigger unit. During tachycardia the external unit senses pacemaker spikes and by timed skin stimulation activates the implanted pacemaker to provoke the ventricular premature beats necessary for interruption of the tachycardia. The system also allows repetitive non-invasive programmed stimulation of the heart.


[High spontaneous variability of ventricular arrhythmias limits the evidence gained by long-term ECG studies].

The spontaneous variability of ventricular arrhythmias was investigated in 8 patients with chronic coronary heart disease. In each patient 6 eight-hour long-term ambulatory ECG recordings were made. During the first three periods patients were without medication and during the following three periods they received a placebo b.i.d. Hour to hour variability was high in all patients. When compared with the first hour of an eight-hour period the number of ventricular premature beats (VPB) per hour in four patients declined by more than 90%, in two patients by more than 70% and in only two by less than 50%. On the other hand, increments of several hundred percent were often observed. Day to day variability of VPBs was also high. When compared with the first documented eight-hour period VPBs either decreased or increased substantially (-84% to +940%). A spontaneous reduction of VPB's for several hours may simulate an antiarrhythmic drug effect. For the group as a whole placebo had a significant effect on the number of VPBs (p less than 0.001). Beside variations of quantity, the complexity of ventricular arrhythmias (Lown classification) spontaneously changed several classes in one patient. Therefore, high spontaneous variability renders it very difficult to estimate the behaviour of ventricular arrhythmias in the individual patient with the Holter-ECG.


[Action of feeding lindane or/and zineb on aflatoxin B1-induced toxic effects in rat and mouse liver (author's transl)].

The action of the ingestion of balanced diets containing pesticides [lindane (125 ppm) or/and zineb (5200 ppm)] on aflatoxin B1-induced toxic effects (inhibition of RNA and protein syntheses in liver) has been determined in two animal species. In the rat, the ingestion of these diets for 4 weeks before aflatoxin B1 treatment (0,7 mg/kg for 3 h), strongly decreased the toxic effects on both transcription and translation. By contrast, in the mouse, the above-mentioned diets did not modify the extent of the inhibition produced by aflatoxin B1 (60 mg/kg for 3 hr) on RNA and protein syntheses. These results were discussed.


Predictive value of HLA-DR matching for nonreactivity in mixed lymphocyte culture (MLC) depends on matching for HLA-D.

In white members of our panel who have been repeatedly typed, close association between the HLA-D and DR specificities was observed. The typings were concordant with both haplotypes in 71% of the North American white panel. In American Indians concordance was observed in 47%, and in American black panel members in only 24%. One-way MLC reactions between individuals matched for both HLA-DR and D were very low (15.8%). MLC reactions between individuals who were DR matched but D mismatched were found to be generally strong, with a mean DNV of 72.3%. It was concluded that the HLA-DR matching predicted the outcome of mixed lymphocyte culture reactions only when the individuals tested were matched also for HLA-D.


Phase and amplitude contrast in electron microscopy of stained biological objects.

For biological objects negatively stained with heavy atom material, electron microscope images show best contrast for image detail on the scale of 10--20 A when a small objective aperture is used. In images taken under the optimum phase contrast imaging conditions of Scherzer, the required image detail is lost in unwanted noise. Both of these conditions may be described in terms of phase contrast imaging for a thin phase object. Calculations of image intensities and noise are reported for a model object consisting of heavy and light atoms randomly distributed to simulate a negatively stained protein molecule. The results are consistent with experimental observations.


Recent advances in applied malaria immunology.

Our present knowledge of cellular and humoral factors which are involved in immunity to plasmodial infections are discussed. Immunization against plasmodial infection has been achieved in birds, rodents, simians, and humans. Avian hosts have been immunized against gametocytes which resulted in inhibition of gametocytes within the mosquito vector. Immunization of humans against plasmodial gametocytes would indirectly protect them against malaria by blocking mosquito transmission to other susceptible individuals. Immunization by sporozoites provides short-lived protection against sporozoite challenge, but gives no protection against erythrocytic forms. Some success has been obtained in immunizing avian and mammalian hosts with exoerythrocytic forms obtained from cultured avian cells. The most significant advances have occurred in immunizing simian hosts against simian or human malaria by vaccinating with fresh erythrocytic merozoites or a nonviable lyophilized antigen obtained from intraerythrocytic forms. The development of an antigen preparation suitable for use as a human malaria vaccine is dependent upon prior development of an in vitro system which would provide adequate amounts of parasite material. Efforts to cultivate the sporogonic, exoerythrocytic, and erythrocytic, and erythrocytic phases of plasmodia as well as the feasibility of using these forms for vaccination are discussed.


Seasonal variations of rat thyroid C cell population.

With the aid of argyrophilic and metachromatic reactions male rats' thyroid C cells were investigated in spring and autumn. Autumn C cells were found to be more swollen and richer in granules and showed a more pronounced metachromasia and argyrophilia than spring C cells. The area occupied by C cells in the central part of the thyroid lobe was large in autumn and reduced in spring. A study into the proportions of C cell: follicular cell: colloid: stroma indicated a significantly higher number of C cells in autumn than in spring.


[Structuro-functional analysis of identified grape snail neurons].

The study of microanatomy of central neurons in Helix pomatia showed that each identified neurone has a constant number of definitely directed processes. The branching pattern of the processes is also specific for each neurone, but in the same cell the number of the branches may vary. It is concluded, that the general morphology of the neurone is its sufficiently stable characteristic and may serve as a criterion for its identification. The possible functional role of different types of the neurone's branchings is discussed. It is suggested that the processes and branches of RPa3 neurone are axones whereas the branches in the form of fine threads are dendrites. It is shown that the neurone with such organization of process branchings play integrative and command functions.


Further study on HLA-A, B, C, D, DR and haplotype antigen frequencies in psoriasis vulgaris.

HLA-A, B, C, D, and DR antigens in 40 Japanese patients with psoriasis vulgaris were analysed using the antisera obtained from the Seventh International Histocompatibility Workshop. The most deviant HLA antigens in psoriasis were found to be HLA-Cw6 and DRw7. by observing the HLA-A, B, C and DR antigens en bloc in psoriasis, it is shown that the statistically significantly associated haplotype antigens were HLA-A1, B13, Cw6 and DRw7, and A1, B37, Cw6 and DRw6 respectively. No HLA-Dw11 (LD17) antigen was associated with the disease.


Acid mucopolysaccharides of the dermis in incipient psoriasis.

Acid mucopolysaccharides have been studied in the dermis of 40 cases of incipient psoriasis. In the upper dermis a marked reduction of the material stained with colloidal iron and with Alcian blue solutions containing 0.1 and 0.2 M MgCl2 was observed; enzymatic controls with hyaluronidase support the idea that this material consists mainly of hyaluronic acid. The intensity and the extension of this dermal alteration far beyond the limits of the above-mentioned epidermal alteration give credence to the hypothesis that in the pathogenesis of psoriasis, dermal alterations are of a primitive character.


Formation of the horny layer in psoriasis--primarily defective or secondarily affected.

It is our belief that any abnormality in keratinization is secondary to an increased rate of epidermal cell production and decreased transit time and research into the underlying nature of psoriasis should concentrate on the issue of whether the stimulus to increased epidermopoietic activity is dermally or epidermally derived.


Cytologic investigations in Chlamydia infection.

Chlamydia is an extremely common genital infection. It can cause serious disseminated disease and can infect the neonate and the sexual partner. Morphologically, Chlamydia infection was identified in routine Fast smears obtained from 160 women. Chlamydia infection manifests as intracytoplasmic coccoid and inclusion bodies in the metaplastic cells. Infected cells also reveal cytomegaly and multinucleation. Immunofluorescence studies, electron microscopy, tissue studies, histochemical techniques and tissue cultures were undertaken to establish the diagnosis of Chlamydia infection as observed in Papanicolaou-stained material. Detailed cytomorphology of Chlamydia infection is described. Clinical implications of such a diagnosis are discussed.


Elevated plasma beta-thromboglobulin levels in multiple myeloma and in polycythaemia vera.

Plasma beta-thromboglobulin levels were determined in 22 multiple myeloma patients, in 15 patients with polycythaemia vera and in 70 healthy controls. In both multiple myeloma and polycythaemia vera significantly increased plasma concentrations of this platelet-specific protein were found.


Serum enzymes after hip joint surgery.

The effect of hip joint surgery on routine serum enzyme values was studied. The increase in creatine kinase was most marked and normal levels were restored again after approximately 1 week. Asparatate aminotransferase was slightly elevated throughout the first two postoperative weeks. Alanine aminotransferase was essentially unchanged during the first three postoperative days in contrast to lactate dehydrogenase which reached preoperative values again after only 2--3 days. Alkaline phosphatase showed an increase after 1 week whereas S-amylase was essentially normal throughout the 2 weeks studied.


Hyperparathyroidism associated with distal tubular dysfunction but intact reabsorption of protein in the proximal tubules.

The urinary output of beta 2-microglobulin was measured in ten hypercalcemic patients undergoing surgery because of hyperparathyroidism. In three subjects the beta 2-microglobulin excretion was abnormally increased and in seven patients it was normal before surgery. Three of these seven patients displayed markedly impaired distal tubular function with a reduced urinary concentration capacity. After surgery all patients became normocalcemic and the urinary concentrating capacities improved. The beta 2-microglobulin excretion, on the other hand, remained unchanged. Thus, hypercalcemia per se does not readily affect the proximal tubular function of reabsorbing low molecular weight proteins. "Tubular proteinuria", if found in patients with hypercalcemia, should be suspected to reflect damage to the kidney by additional mechanisms.


The surface structure of the completely and incompletely orthokeratinized oral epithelium in the rat: a light, scanning and transmission electron microscope study.

Mucosa from the hard and soft palates, molar gingiva, cheek and dorsal surface of the tongue of the rat was examined in the light microscope, following Mallory's triple connective tissue stain, and in the scanning and transmission electron microscopes. The epithelium covering the hard palate, gingiva, the smooth band of mucosa at the junction of the hard and soft palates, intermediate zones of the soft palate, fungiform papilla-like structures in the central zone of the soft palate, the fungiform papillae, and the more superficial part and posterior surfaces of the filiform papillae of the tongue all exhibited complete orthokeratinization. The oral surfaces of the epithelial cells in all these areas had a honeycomb pattern of interconnecting ridges surrounding depressions. Imprints of the overlying cells that had been desquamated were apparent, and the lateral boundaries between the cells were formed by two raised ridges separated by a gap. The epithelium covering the cheek, central zone of the soft palate apart from the fungiform papilla-like structures, lateral zones of the soft palate, gingival crevice, and the mucosa between the fungiform and filiform papillae of the tongue all exhibited incomplete orthokeratinization. The oral surfaces of the epithelial cells in all these areas were relatively smooth and did not exhibit a honeycomb pattern of interconnecting ridges. Imprints of the overlying cells that had been desquamated and the lateral boundaries between the cells were only very occasionally found. In the transmission electron microscope the outlines of the cells were compatible with the surface patterns seen in the scanning electron microscope. The possible relationships between the degree of orthokeratinization and ultrastructure of the various epithelia are discussed.


Intra-operative frozen section technique for pituitary adenomas.

Orange G-hematoxylin stains performed on frozen sections from the sella turcica had a diagnostic accuracy of over 90% when compared to permanent sections on the same tissue. This technique allows the pathologist to make an intra-operative contribution to the establishment of tumor margins in the selective removal of pituitary adenomas.


Role of serotoninergic and adrenergic mechanisms in the action of prominal.

The aim of this work was determination of the interrelations between the metabolism of biogenic amines in the brain and the action of Prominal. The power of the anticonvulsive action of Prominal was decreased by p-chlorphenylalanine (PCPA). The influence of the tested anticonvulsant on the levels of noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and on serotonin turnover was investigated and a correlation was found between the anticonvulsive action of Prominal and its effect on the serotonin level. Prominal increased serotonin synthesis and turnover in the brain. It may be supposed that the anticonvulsive action of Prominal is connected with its effect of serotonin metabolism in the central nervous system.


Haematological changes in hyperimmunized rabbits treated with hydrazinophthalazines for long time periods.

Haematological investigations of peripheral blood and bone marrow were performed in rabbits receiving hydrazinophthalazines (hydralazine or binazin) with or without simultaneous hyperimmunization by means of repeated injections of bovine albumin. It was found that long-term administration of hydralazine caused appearance of LE factor in the serum and LE cells in blood. Less evident changes were caused by Binazin administration. Hyperimmunization caused weaknening of the effects of hydralazinophthalazines. Haematological investigations demonstrated hypochromic anaemia.


Diagnostic value of histochemistry in embryonal rhabdomyosarcoma.

Embryonal rhabdomyosarcomas from the nasopharynx of two children were examined by histochemical methods commonly applied to muscle biopsies. These stains included nicotinamide adenine dinucleotide-tetrazolium reductase (NADH-TR), succinate dehydrogenase (SDH), PAS, PAS-diastase, myophosphorylase, calcium-mediated adenosine triphosphatase (ATPase) preincubated at high and low pH, and oil red O. Myofibrils were easily identified with ATPase and blood vessel walls were also stained. NADH-TR clearly showed longitudinal and cross-striations that were not seen with H&E or PTAH stains. The modified Gomori trichrome stain additionally contributed to the recognition of myofibrils. Some techniques of muscle histochemistry applied to fresh frozen sections of tumor tissue may provide evidence of muscular differentiation in otherwise poorly differentiated sarcomas for a more accurate diagnosis of rhabdomyosarcoma.


The association of pyloric antral tissue levels of 5-hydroxytryptamine and restraint stress ulceration in the rat.

To determine the possible role of 5-hydroxytryptamine (5-HT) in the formation of restraint ulcerations, we investigated the relationship among mucosal tissue levels of 5-HT, vagotomy, and restraint ulcerations. Three murine experimental groups and one control group were used to compare the ulcerogenic effects of restraint with and without prior vagotomy. Ulcers were graded as to frequency, size, and hemorrhage on a 0-4+ scale. 5HT was measured in the gastric mucosa of each animal. Restraint caused significant ulcerations. The mean tissue level of 5-HT was significantly higher in the group with marked ulcerations (p less than 0.001). Our data suggest an increased cellular production of 5-HT during the development of the restraint ulcers. Vagotomy protected the animals against restraint ulcerations without depleting the baseline levels of 5-HT. Previous experiments have shown that urine levels of 5-hydroxyindoleacetic acid (5-HIAA) increase during the restraint period. Thus, increased tissue and urine levels of 5-HT appear to coincide with the development of restraint stress ulcers in the rat. Accordingly, if the coincidence occurs in humans, the measurement of urinary levels of 5-HIAA may be an indirect means of determining those patients at high risk for the development of stress ulcers.


[Dynamic and plastic expression as a method of accident prevention during infancy (author's transl)].

Authors review the importance of fostering suitable methods at infancy, as a prophylaxis of accidents at such stage in life. They propose the use of plastic expression handed-out as a sequence of pictures, ordered in the form of a story or tale, rigorously studied from the psychological point of view and which limelights the most frequent risks. Likewise they value the importance of dynamic methods of expression and summarise their experience with puppet theatres. A prototype show is described and psychological result evaluation analized.


Enhancement of retrovirus production by anti-interferon serum.

In order to investigate the role of endogenous interferon in retrovirus production by infected or induced cells, the effect of two sera raised against mouse interferon has been tested on various C-type murine viruses. Addition of a highly potent anti-interferon serum to 3T3/IC cells chronically infected by the Moloney strain of MLV results in a considerable increase of virus production, as tested by reverse transcriptase assay. This effect is neutralized by an excess of exogenous interferon. The greatest effect of anti-interferon sera was obtained in the derepression of endogenous retroviruses: in K. BALB/c cells treated by IUDR, anti-interferon serum increases up to 50-fold the expression of the endogenous virus. The extinction of virus production which secondarily occurs after its induction by IUdR is likely to be caused by cellular endogenous interferon. The biological parameters of the viral agent produced in the presence of anti-interferon serum are those of the xenotropic endogenous virus.


Characterization of clones derived from an attenuated strain of Rauscher murine leukaemia virus.

With a view to defining its subpopulations, an attenuated strain of Rauscher leukaemia virus, which comprises a majority of fragile virions, was closed by end-point dilution. The presence in the obtained clones of markers (analyzed by radioimmunoassay and isoelectric focusing) associated with Rauscher virus, together with persistent infectivity and leukaemogenicity, excluded the hypothesis that endogenous virus might have replaced the original Rauscher population. Due to the closing method employed, non fragile virions were obtained. Moreover, despite its selectivity for the lymphatic leukaemia virus component, sporadic cases of atypical erythroblastogenic leukaemia were observed.


The generation of an allospecific suppressor factor in culture.

When mouse spleen cells were stimulated by irradiated allogeneic cells in a mixed lymphocyte culture for 96 hours, allospecific suppressor cells were generated that could inhibit the replicative processes when transferred to another MLR. When the primed cells were purified on Ficoll and incubated alone for another 24 hours, they released into the medium a subcellular factor which could also suppress MLR allospecifically. Evidence is provided that the cells which generate this factor arise by cooperation of at least two types of T-lymphocytes, one of which is the progenitor of the suppressor cell and the other an essential accessory cell. Adherent cells were shown to be also essential for the priming of suppressor lymphocytes.


Comparison of antigen-specific I-region-associated cell interaction factors.

Two basic types of factors reacting with anti-I region (anti-Ia) antisera are compared, those derived from macrophage-like antigen presenting cells and others derived from T-lymphocytes, of either the suppressor or helper type. Despite the common property of reacting with anti-Ia antisera, the two sets of factors differ by many criteria. Macrophages, upon culture with antigen, release complexes of Ia antigen and a fragment of the original immunogen. This material is only produced by responder macrophages and thus appears to be a soluble Ir gene product. The genetic restriction of the T-macrophage interaction was investigated in chimeras, and it was found that the host environment as well as the donor genotype was of importance in determining restrictions, which were thus not really directed to "self." There was no evidence for intrinsic T-cell Ir genes, as nonresponder stem cells developed into responder T-cells in a (responder X nonresponder) F1 environment. However, these cells only responded in the presence of responder macrophages. Specific T-cell factors are different in nature. These all react with anti-Ia antisera, but the nature or function of the T-cell Ia is unknown. The basic structure involves a VARIAble region" responsible for antigen binding which, as it reacts with anti-idiotype antisera and anti-variable region framework antisera is an immunoglobulin variable region. There is also a "constant region," defined by its biological properties as well as by specific rabbit antisera. This two-region nature of specific factors is reminiscent of immunoglobulin structure and it is a reasonable hypothesis that the constant region is linked to the Ig cluster of genes.


Has myelin basic protein received a fair trial in the treatment of multiple sclerosis?

Autosensitization to some central nervous system antigen still remains one of the best hypotheses for the continuing pathogenesis of multiple sclerosis (MS). Enough is now known about the cause, pathogenesis, and treatment of experimental allergic encephalomyelitis (EAE) to test this hypothesis. Reports of therapeutic failure of the encephalitogen myelin basic protein (BP) in the treatment of MS have their counterparts in similar therapeutic failures in EAE. Only highly inbred strain 13 guinea pigs respond consistently to BP therapy, and this only when BP is administered in relatively high doses. Noninbred guinea pigs respond much less well to simple BP therapy, and monkeys hardly at all. In both strains of monkeys so far studied, a nonspecific adjunctive factor--an antibiotic in Macaca mulatta and a steroid in Macaca fascicularis--is also required. Accordingly, human trials of the therapeutic efficacy of BP in MS should include its administration in large concentrations together with an adjunctive agent.


Myelin basic protein treatment of experimental allergic encephalomyelitis in monkeys.

Treatment of experimental allergic encephalomyelitis (EAE) in two strains of monkeys with large amounts of myelin basic basic protein (BP) fails unless an adjunct is also used. In both strains the adjunct by itself is more effective than BP by itself, but in the one strain which could be investigated sufficiently, the combination can be made almost totally effective in reversing EAE. The adjunct varies with the strain of monkey, an antibiotic in Macaca mulatta and a steroid in Macaca fascicularis. Similar adjunctive treatments should be considered in the management of multiple sclerosis, for EAE remains one of the best studied models.


Degradation of myelin basic protein by cerebrospinal fluid: preservation of antigenic determinants under physiological conditions.

Cerebrospinal fluid contains several proteolytic enzymes that can degrade myelin basic protein (BP) under physiological conditions into peptide fragments of various sizes which still contain antigenic determinants capable of binding antibodies to BP. These enzymes are optimally active in either acid (pH 4) or nuetral (pH 7 to 8) conditions and can be characterized by the nature of the BP peptide fragments produced. Proteinases resembling cathepsin D, thrombin, plasmin (fibrinolysin), or kallikrein are present in variable amounts in CSF. No relationship to any particular disease has yet been established.


Rapid enzymatic determination of amylase in serum and urine using a centrifugal analyzer.

A convenient, totally enzymatic procedure for amylase assay using a centrifugal analyzer is described. The reaction scheme is examined using both starch and maltotetroase as substrates. Data for the reaction kinetics, linearity and sensitivity are presented. The proposed method exhibits linear reaction kinetics between three and five minutes after the initiation of the reaction and is linear to 1200 U per liter of amylase. The determination is rapid, (five minutes analysis time), convenient, (only one reagent), and precise, (1.2% within-day C.V. and 4.6% day-to-day C.V.), at a level of 62 U per liter. The proposed method compares favorably with chromogenic procedures; (r = 0.979, n = 84).


Characterization and mode of action of a bacteriocin produced by a Bacteroides fragilis strain.

A Bacteroides fragilis strain produces a low-molecular-weight (13,500 to 18,700), proteinaceous bacteriocin during the stationary growth phase. The extracellular bacteriocin is not inducible by ultraviolet light or mitomycin C and is stable between pH 7.5 and 8.2. The majority of the bacteriocin is thermolabile, but a small proportion (3%) of the bacteriocin is stable after autoclaving at 121 degrees C for 15 min. Killing of sensitive bacteroides cells follows single-hit kinetics, and the interaction of a single molecule of bacteriocin with a target cell occurs in two stages. The killing of susceptible cells is affected by temperature and the growth state of the susceptible cells. The bacteriocin is unusual in that the primary event in its mode of action is the inhibition of RNA synthesis. The bacteriocin inhibits RNA synthesis immediately but has no effect on DNA synthesis or intracellular ATP levels. Protein synthesis is inhibited after a delay of 20 min, presumably as a result of the initial inhibition of RNA synthesis.


Triggering of autolytic cell wall degradation in Escherichia coli by beta-lactam antibiotics.

A biochemical method was developed to quantitatively compare the effectiveness of beta-lactams in triggering murein degradation (autolysin activity) in Escherichia coli. Bacteria prelabeled in their cell walls with radioactive diaminopimelic acid in growth medium were exposed for 10 min to the antibiotics at the appropriate minimal growth inhibitory concentrations and at multiples of these values, and the rate of cell wall degradation was followed during subsequent penicillin-binding protein (PBP)-1 were the most effective triggers of autolytic wall degradation; beta-lactams selective for PBP-2 were the poorest; and antibiotics preferentially binding to PBP-3 showed intermediate activities. The relative effectiveness of beta-lactams in autolysin triggering was found to parallel the effectiveness of the same drugs in causing rapid loss of viability, culture lysis, and spheroplast formation. Autolysin triggering was suppressed by inhibitors of protein and ribonucleic acid biosynthesis but not by inhibitors of deoxyribonucleic acid synthesis. The beta-lactam-induced cell wall degradation did not seem to involve a direct stimulation of enzyme activity or synthesis of new enzyme molecules, and murein sacculi isolated from cells that had been preexposed to a triggering dose of beta-lactam treatment exhibited the same sensitivity to crude, homologous autolysins as sacculi prepared from untreated control bacteria. On the basis of these observations, mechanisms are considered for the triggering of E. coli autolysins and for the role of autolytic activity in bacterial spheroplast formation, lysis, and death.


Microbial conversion of ethylbenzene to 1-phenethanol and acetophenone by Nocardia tartaricans ATCC 31190.

A culture of Nocardia tartaricans ATCC 31190 was capable of catalyzing the conversion of ethylbenzene to 1-phenethanol and acetophenone while growing in a shake flask culture with hexadecane as the source of carbon and energy. This subterminal oxidative reaction with ethylbenzene appears not to have been previously reported for Nocardia species. When N. tartaricans was grown on glucose as its source of carbon and energy and ethylbenzene was added, no subsequent production of 1-phenethanol or acetophenone was observed. The mechanisms of 1-phenethanol and acetophenone production from ethylbenzene are thought to involve a subterminal oxidation of the alpha-carbon of the alkyl group to 1-phenethanol followed by biological oxidation of the latter to acetophenone.


Effect of vitamin A acid on the growth of keratinocytes in culture.

The effect of vitamin A acid on the culture of guinea pig ear keratinocytes was investigated. Use of this agent and treatment of the plastic dishes with collagen solution facilitated attachment and growth. Vitamin A acid elicited a wave of DNA synthesis which was studied by incorporation of tritiated thymidine and quantitation of cellular DNA, particularly during the period 24--45 h after plating. During this period, thymidine incorporation into DNA was increased ten-fold by vitamin A acid and showed a complex pattern of peaks and shoulders which may represent the S phase of synchronous keratinocytes.


[Viral acanthomas and specialized forms of keratinosome "membrane coating granules" (author's transl)].

In the case of viral acanthomas, the stratum spinosum and granulosum presents ballooned cells which contain all transitional stages from multivesicular bodies (MVB) to keratinosomes. A particularity in condylomata acuminata are the "wagon-wheel" bodies. These structures are typical for the non keratinazed squamous epithelium. The participation of intercellular extruded "wagon-wheel" bodies, MVB and atypical keratinosomes on an irregular baso-apical diffusion-barrier in the epidermis of cases with viral acanthomas has been discussed. On the basis of the relation seen between MVB and the Golgi-apparatus, their transition to partially atypical keratinosomes in cases of viral acanthomas and their "expulsion" into the intercellular space could indicate that in keratinozytes the enzymatically regulated feed-back between the cellular surface and the capability to synthesize is changed by viral agents. The interference appears to manifest itself in the Golgi-apparatus and also appears to be "specified" by the terrain present.


Experiments on the accumulation of lindane (gamma-BHC) by the primary producers Chlorella spec. and Chlorella pyrenoidosa.

Experiments were performed on the accumulation of the pesticide lindane (gamma-isomer of BHC) by two algae with different surfaces. An analytical procedure was developed for the gas chromatographic determinnation of lindane. At room temperature, lindane had a water solubility of 7.8 mg/L in distilled water and 6.7 mg/L in tap water. Under the experimental conditions of 10 to 100 microgram/L, 2.3% of the dissolved lindane was lost through adsorption on the glass walls of the equipment and 0.2% through evaporation. The recovery rate of lindane was 98% for the water samples and more than 90% for Chlorella spec. The tolerance in the gas chromatographic measurements amounted to 1.2%. Investigations on the effect of lindane on the growth of Chlorella spec. revealed irreparable damage to the algae cells through loss of chlorophyll, coagulation, and complete sedimentation at concentrations greater than 300 microgram/L. The experiments on sublethal accumulation showed the development of a state of equilibrium between the amount of lindane per cell and in the surrounding water with lindane concentrations of 10 to 100 microgram/L. The lindane was adsorptively attached to the algal cells within a few hr, and after three days lindane stabilized in the cells. The gelatinous surface of the algae increases the accumulation of lindane.


Molecular adaptability of carp myosin: a study of some physico-chemical properties and their comparison with those of rabbit myosin.

During thermal inactivation, the addition of as low as M urea resulted in the reduction of delta G identical to barrier of the inactivation of carp myosin Ca2+-ATPase, whereas that of rabbit myosin remained unaffected. In the absence of urea, a four-hour incubation of carp myosin was accompanied by the release of light chains at 30 degrees C, a value 10 degrees C lower than that for rabbit myosin. Electron micrographs revealed that carp myosin forms artificial thick filaments, which were uniform in size and may differ in a few details from those of rabbit. Not only that helical content of carp myosin was about 4% less than those of rabbit myosin, but it showed more sensitivity to thermal and urea denaturation; and its reversibility upon subsequent cooling or removal of urea was rather poor. The loss in helicity of myosins by urea was a concentration- and temperature-dependent biphasic reaction, with the most obvious effect observed on carp myosin. That carp myosin has increased tendency of unfolding in urea solutions was confirmed by viscosity data and the exposure of thiols also. Even in the absence of urea more SH groups of carp myosin were incorporated by DTNB, and more epsilon-amino groups reacted with NQS. Carp myosin remained in solution till the modification of about 52 surface myosin remained in solution till the modification of about 52 surface amino groups, whereas no precipitation effect was noted in case of rabbit myosin. Neither amino-acid composition nor some parameters derived from it, such as average hydrophobicity polarity index and number of polar side chains, revealed any difference pertinent to the relative stability of the two myosins. On the contrary, the contractile efficiency of carp myosin in the near physiological range was high and thus inversely related with the thermostability. This relationship along with the above evidence has been regarded to demonstrate the adaptability of carp myosin through a loose molecular conformation, which has probably been achieved by the addition of weak interactions in the course of evolution.


Reinvestigation of denervation diuresis and natriuresis in conscious dogs.

The function of innervated and denervated kidney was compared in clearance studies with conscious dogs. The animals were prepared for experiments by unilateral renal denervation and surgical division of the bladder to form two hemibladders enabling separate urine collection from two kidneys. The mean urine flow was 6% higher for the denervated kidney (not significant) while mean differences for osmolar clearance (+ 13%), sodium excretion (+21%) and GFT (+5%) were all significant (P less than 0.05). When corrected to 100 ml GFR, sodium excretion was not significantly higher for the denervated kidney. In most experiments higher sodium excretion on the denefvated side was associated with higher GFR. Thus, contrary to some earlier views, a slight increase in the excretory function which follows denervation of the kidney is demonstrable also in conscious undisturbed animals. The data suggest that increased haemodynamics of the denervated kidney are responsible for higher excretion, but do not exclude a contribution of inhibited tubular reabsorption.


Thirst and renal excretion of water and electrolytes during pyrogen fever in dogs.

Body temperature, water intake, urine output, sodium and potassium excretion, osmolal and free water clearance, plasma osmolality, sodium and potassium concentrations and osmotic thirst were examined in conscious dogs during pyrogen fever and compared to those found under control conditions. Arterial blood pressure and central venous pressure were also measured in some experiments. Administration of pyrogen produced transient but significant decreases in urine output and striking increases in the spontaneous water intake in some of the experiments in the phase of increasing fever. Arterial blood pressure decreased, whetreas central venous pressure increased at this stage of fever. No significant changes in renal excretion of solutes and free water as well as sodium and potassium were found. Plasma osmolality and sodium concentration increased and potassium concentration decreased unsignificantly both in control and pyrogen experiments. The main finding was that the thirst threshold to osmotic stimuli increased markedly during the phase of stabilized fever may be caused by significant increase in internal body temperature.


Purification of prophenoloxidase in the haemolymph of Calliphora vicina (R. & D.).

An improved method for the purification of prophenoloxidase is described. The proenzyme was purified 400 fold in homogenous form. The purity was tested by disc-electrophoresis and the molecular weight was found to be 87 000 in comparison to the mobility of marker enzymes, which were run simultaneously in SDS-gel electrophoresis. The proenzyme was denatured at 80 degrees C and maximum conversion into active state was found between 40 and 50 degrees C.


A comparative study in Porcellio laevis (Lat.) and Armadillidium vulgare (Lat.): response to temperature, photoperiod and oxygen concentration.

Relationship of body weight, imposed fasting, temperature, light intensity, and oxygen concentration to oxygen consumption in Porcellio laevis and Armadillidium vulgare has been investigated in a series of laboratory experiments. It was observed that (1) the metabolic response in the two species to temperature change was a uniform increase of oxygen consumption with increasing temperature from 15 degrees C to 60 degrees C. Beyond 30 degrees C, the oxygen consumption in each species fell, and the thermal death point was reached at about 40 degrees C. (2) The response  to decreasing oxygen concentrations was a corresponding decrease in oxygen consumption. Armadillidium vulgare was a partial regulator while Porcellio laevis was able to conform its internal state to the changing oxygen levels. (3) In each species there was a decrease in metabolic rate with increasing body weight. (4) On the basis of their general activity level and oxygen consumption rate, Porcellio appeared to be a nocturnal species, while Armadillidium had a day active metabolism.


Studies on the cholinesterase forms present in the ascitic fluid of Ehrlich tumour.

Cholinesterase activity was detected in the ascitic fluid of Ehrlich tumour and studied in a comparative manner in relation to that found in mice plasma. Enzymes from both sources were characterized with respect to optimum pH, substrate concentration and quinidine inhibition. After gel filtration by Sephadex G-200 and Sepharose 6B, two enzyme forms were observed in ascitic fluid as well as in mice plasma: a large form (L) and a small form (S) presenting molecular weights of 191 000, and 224 000 daltons for L forms and 71 000 and 69 000 daltons for S forms respectively. Concanavalin A interacts with both molecular forms, suggesting a glycoprotein nature for these enzymes.


Occurrence and subcellular localization of glucose 6-phosphatase in bovine thyroid.

In bovine thyroid tissue the glucose 6-phosphatase activity is not entirely due to the presence of an unspecific acid phenylphosphatase nor to beta-glycerophosphatase. This glucose 6-phosphatase is very probably localized within endoplasmic reticulum membranes. It is not a good marker for distribution patterns obtained after differential pelleting. However it can be used as a marker for endoplasmic reticulum membranes after centrifugation in a zonal rotor.


Effects of exogenous gonadotropic and steroid hormones on the social behaviour and gonadal maturation of male domestic ducklings Anas platyrhynchos L.

Male domestic ducklings were injected during their first month of life with mammalian gonadotrophins (ovine LH or FSH, HMG) or gonadal steroids (testosterone or oestradiol). LH and testosterone stimulated sexual behaviour while oestradiol inhibited the increase of aggression observed in control birds during the experiment. The mammalian gonadotrophins did not increase plasma testosterone but nevertheless they all stimulated the testis growth. Several hypotheses which could explain this finding (stimulation of spermatogenesis without any apparent effect on testosterone) are discussed and the possibility of a direct action of LH on the sexual behaviour is analysed. Social displays were only moderately stimulated by testosterone and not at all by gonadotrophins. The hormonal controls of these behaviour patterns remains thus largely unknown.


[Deoxyribonucleic acids from Pasteurella multocida and Pasteurella haemolytica].

Pasteurella multocida and P. haemolytica strains contain between 1.5 and three per cent phosphorus, between nine and 14 per cent nitrogen, between two and four per cent DNA, and between five and 18 per cent RNA, the precise figures depending on culturing conditions. High-molecular DNA may be isolated by means of bacteriolysis, using deoxycholate or dodecylsulphate and the usual steps of purification, with yield and purity differing by strains. DNA with sufficient purity can be obtained from Sepharose 2 B by gel chromatography. The isolated DNA yields were characterised, base values being between 37 and 38 per cent GC for P. haemolytica and between 41 and 48 per cent GC for P. multocida. Highly suitable precursors to DNA synthesis for tritium labelling are 3H-thymidine, which is incorporated in excess of 3H-thymine by a factor of 255, as well as 3H-uracil, with its activity being recovered also from the pyrimidine bases of DNA via pyrimidine biosynthesis.


[Separation of cellular and viral DNA polymerase from oncornavirus infected chicken cells].

RNA-directed DNA polymerase was isolated from the liver, spleen, and myeloblasts of chickens that had been infected with virus of avian myeloblastosis. The enzyme was chromatographically purified from the myeloblasts and brought to about 1,000-fold concentration. The method consisted in cell fractionation, lysis of the microsomal fraction, chromatography on Sephadex G-200 and phosphocellulose, as well as ultracentrifugation in the glycerol gradient. The cellular DNA polymerases alpha and beta were clearly separated from the DNA polymerase of avian myeloblastosis virus and could be distinguished from one another by template-specific reactions. The viral DNA polymerase activities in the microsomal fractions of liver, spleen, and myeloblasts were compared with one another. The amount of avian myeloblastosis virus and related DNA polymerase recorded from the myeloblasts was about six times that in the liver and four times higher than that in the spleen. The procedure described, together with the use of cell fractionation and gel filtration, is an appropriate method for biochemical detection of avian oncorna viruses in cells.


Purification of antibodies to influenza A virus structural proteins by affinity chromatography, and their participation in haemagglutination-inhibition, neutralization and enzyme-linked immunosorbent assay.

Affinity chromatography was used to purify rabbit antibodies to common and strain-specific antigeneic determinants of haemagglutinin, to neuraminidase, and to a combination of the internal proteins of influenza A viruses. The purity of the antibodies was assessed by haemagglutination-inhibition, enzyme-linked immunosorbent assay (ELISA) and competition ELISA. The antibodies were examined for their participation in neutralization and haemagglutination-inhibition assays, and in ELISA. ELISA was found to be the most sensitive technique for detecting antibodies. Antibodies to the common and strain-specific determinants of haemagglutinin were shown to participate in neutralization assay and ELISA, but only those antibodies to the common determinants were detected by haemagglutination-inhibition.


Human tumour immunology.

Many human cancer cells appear to differ from their normal counterparts in ways that are recognisable by the immune system of the host or patient. The specificities of these differences, however, and the nature, extent and significance of the most responses to them are often not very clear. Disturbances of the immune system generally contribute little to the occurrence, progression and clinical features of common malignant diseases. The present value of immunological monitoring of cancer patients is rather limited. Immunotherapy remains an experimental mode of treatment, the results of which are often disappointing. Current studies of the host-tumour relationship in experimental animals and man suggest, however, that a wholly pessimistic view is not justified.


Repetitive DNA and Feulgen hydrolysis kinetics in three species of Bufo.

Two North American species of the genus Bufo (Bufo cognatus and Bufo boreas, 2n = 22) and one African species (Bufo regularis, 2n = 20) were analyzed with respect to their repetitive DNA fractions and the behaviour of their chromatin to the acid hydrolysis at different times. The mean melting point of the total isolated DNA decreased from 89 degrees C to 87 degrees C with a genome size increase from 4.4 to 7.5 pg. The differences in genome size can only partly be explained on the basis of repetitive DNA fractions (renaturing up to Cot 10 in 0.12 M phosphate buffer). Several fractions in this repetitive range behave independently in the three species and the spectrum of repetitive fractions in the African Bufo regularis differs distinctly from those of the American toads. When fixed chromatin of these species in histochemical preparations is hydrolyzed with 5N HCl during the Feulgen reaction, the kinetics of depurination are equal in all species, while hydrolytic DNA breakdown proceeds distinctly more slowly in Bufo reularis as compared to the other species.


Autoradiographic thymidine-3H activity after successive steps of the Feulgen reaction.

Autoradiographs were prepared of sections of the ovary of Dytiscus marginalis labelled with thymidine-3H after each successive step of the Feulgen reaction and after treatment with each separate component of the Schiff's reagent. Results of grain counts over ovarian nurse cells showed that losses of thymidine-3H activity occur not only during hydrolysis but also during the successive steps of the Feulgen reaction. It is suggested that the latter decrease in radioactivity may depend on the extraction of fragments of apurinic acid from the sections. An emulsion desensitizing effect has also been observed in sections stained with basic fuchsin alone; this effect appears, however, to be strongly counteracted by the metabisulphite present in the Schiff's reagent.


Histochemical and electron microscopical investigations on the calcified keratin in the horn pearls of a glans carcinoma (calcified keratin).

The calcified keratin in the horn pearls of a glans carcinoma has been studied by histochemical and ultrastructural methods. The former have shown that the calcified areas contain glycoproteins and acid proteoglycans and have a concentration of sulphydryl groups greater than that of the surrounding, uncalcified keratin. Electron microscopy has shown the presence of intracellular needle- and filament-like crystals closely related to the keratinocyte filaments and similar to those found in other calcified tissues. Besides the close relationship discovered between crystals and keratinocyte filaments, the other main conclusions are that keratin calcification is an intracellular process and that keratin molecules are responsible for the induction and regulation of the process.


Comedo naevus of the palm--a sweat duct naevus?

A 9-year-old boy is described with keratotic pits on the left palm, present since birth, which clinically resembled those seen in comedo naevus. Histology and scanning electron microscopy of skin surface replicas showed the lesions to be large, abnormal sweat ducts. It is suggested that comedo naevi are not necessarily pilosebaceous in origin and that in our case the term sweat duct naevus may be more appropriate.


DNA-directed cell-free protein-synthesizing system of Bacillus subtilis.

A cell-free coupled system of transcription and translation using cell extracts from Bacillus subtilis and DNA from phage SP82 has been developed. Under optimum conditions, it incorporated approx. 300 pmol methionine during a 1 h incubation. The activity of the system increased linearly as the concentration of S-150 supernatant fraction protein increased from 125 to 325 microgram per assay. The optimum Mg2+ concentration was 12.5-15 mM. Ribosomes required treatment with DNAase in order to reduce endogenous activity, but the S-150 fraction was kept DNAase-free to prevent degradation of exogenously added DNA. The coupled system was sensitive to inhibitors of RNA and protein synthesis. Kinetic studies showed that the number of pmol of nucleotides present in newly synthesized RNA increased linearly for the first 20-min reaction and that the rate of amino acid incorporation increased linearly for the first 30 min. Polyacrylamide gel electrophoresis of the in vitro synthesized products yielded a band pattern that closely resembled the pattern of early phage SP82 proteins produced in vivo.


Immunochemical comparison of histidine-rich protein in keratohyalin granules and cornified cells.

(1) Combination of techniques for extraction and purification of histidine rich protein established by several investigators were employed for comparison of histidine-rich protein in granular cells and cornified cells of newborn rats. (2) Histidine-rich protein extracted from the same cell fraction by two different techniques either in 1 M potassium phosphate buffer (Ugel) or in 4 M urea (Dale) showed identical elution profiles on CM 52 cellulose ion exchange chromatography and the same SDS polyacrylamide gel electrophoretic patterns. (3) Histidine-rich protein from granular cells contained polypeptides of larger molecular sizes than those in histidine-rich protein from cornfield cells, although amino acid composition of the two histidine-rich protein was non-distinguishable (histidine residue was more than 7%). (4) Antibodies raised in rabbits by injection of histidine rich protein from granular cells and that from cornfield cells immunologically cross-reacted. Furthermore, the antisera were found to be reactive over both keratohyalin granules and cornified cells, but not epidermal cells of the lower strata.


Control of albumin and alpha-fetoprotein expression in rat liver and in some transplantable hepatocellular carcinomas.

Albumin and alpha-fetoprotein production by rat liver and by four selected transplantable hepatocellular carcinomas is compared to the messenger RNA present in these tissues. Albumin and alpha-fetoprotein were measured by radioimmunoassay of serum concentration, immunofluorescence, and in vitro incorporation of labeled amino acids into proteins specifically precipitated by antisera. The number of mRNA molecules per cell was calculated from the hybridization of specific cDNA probes to polysomal mRNA and by translational activity of polysomal RNA in a wheat germ system. The amount of albumin and alpha-fetoprotein produced by the different tissues is directly related to the number of functional mRNA molecules per cell for each protein.


The chemical heterogeneity of human hemoglobin F. Direct evidence for the existence of three types of gamma chain, the G gamma I, A gamma I, and A gamma T chains.

Direct evidence is presented for the existence of three types of gamma chain of human hemoglobin F. A modification of a CM-cellulose chromatographic method has allowed the incomplete separation of these gamma chains while high pressure liquid chromatography and fingerprint analyses of tryptic peptides of zones of the isolated gamma chains, and amino acid analyses of isolated peptides were used to identify the chains. These studies have shown that the presence of a glycyl residue in position 136 (G gamma chain) is directly related to that of an isoleucyl residue in position 75 (I gamma chain), thus indicating the existence of an G gamma I chain, and that the presence of an alanyl residue in position 136 (A gamma chain) can be related to that of an isoleucyl residue in position 75, thus suggesting the existence of an A gamma I chain. When the isoleucyl residue at positive 75 is replaced by a threonyl residue, invariably it is related to the alanyl substitution at position 136 (A gamma T chain). These data support indirect evidence from case analyses and family studies which were published before, and indicate that the T gamma chain is an allele of the A gamma which should be renamed the A gamma T chain.


Immunological and serological data concerning human histocompatibility antigens (HLA) and alpha 1-microglobulin co-purified from urine.

Serologically active glycoproteins (HLA) purified from urine contained only about 4% HLA antigens co-purified with alpha 1-microglobulin. The immunization of rabbits with the serologically active product gave rise to an antiserum containing two kinds of antibodies: anti-HLA-A9 and anti-alpha 1-microglobulin. The anti-HLA-A9 antibodies were detected by the lymphocytotoxicity and indirect immunofluorescence techniques against peripheral blood lymphocytes and cultured lymphoid cell lines. Anti-alpha 1-microblobulin antibodies were detected by immunoprecipitation in gel. Pure alpha 1-microglobulin gave rise to an antiserum directed only against alpha 1-microglobulin. This antiserum did not react with peripheral blood lymphocytes and cultured lymphoid cell lines.


The influence of prostatic anatomy on the differing results of prostatectomy according to the surgical approach.

An anatomical study of cadaver prostates has demonstrated that, in all cases, adenomatous tissue lies inferior to the verumontanum. The proportion of tissue distal to the verumontanum varies from less than 10 to 50%. In a series of 100 patients the post-operative urodynamic studies showed that in the tansurethral resection group the mean urethral length was longer, the flow rate lower and the residual urine higher than in the retropubic prostatectomy group. It is suggested that prostatectomy by the transurethral route is less complete due to residual sub-verumontanal prostatic tissue. However, it is likely that by restricting resection to supra-verumontanal tissue many patients are spared post-operative stress incontinence.


Diagnosis and staging of prostatic cancer by transrectal ultrasonography. A preliminary study.

Sixty men (7 normal, 53 with prostatic disease) underwent transrectal ultrasonic scanning of their prostates in order to assess the technique and evaluate its reliability in the detection and staging of prostatic cancer. The prostatic capsule was clearly seen in 58 men; non-integrity of the capsule occurred only in those with proven cancer (17 cases). An ultrasound diagnosis of cancer was made for 32 of 33 men with proven disease and it was shown that ultrasound demonstrated anterior perforations of the capsule in 6 out of 18 men with tumours that had been judged by rectal palpation to have been confined to the prostate. It is concluded that transrectal ultrasound is a promising technique of imaging the prostate, particularly in relation to selection of patients for biopsy and for checking staging of cancer carried out by digital assessment of the prostate.


Identification of a silver binding protein associated with the cytological silver staining of actively transcribing nucleolar regions.

Nucleoli isolated from Novikoff hepatoma cells were stained with AgNO3 to demonstrate the typical staining of active ribosomal cistrons. Pre-treatment of the nucleoli with 80 mM Tris-HCl (pH 7.5) -- 2.0 M NaCl did not interfere with silver staining. Treatment of the nucleoli with 80 mM Tris-HCl (pH 7.5) -- 0.15 M NaCl did, however, eliminate silver binding. Serial extraction of nucleoli with 2.0 M NaCl buffer followed by 0.15 M NaCl buffer also abolished silver staining. Analysis of the supernatant fraction of these extracts by polyacrylamide gel electrophoresis indicates that, although more than one nucleolar protein can bind silver, only one protein is associated with the staining of active ribosomal cistrons.


Combination chemotherapy trials in metastatic carcinoid tumor and the malignant carcinoid syndrome.

One hundred eighteen patients with metastatic carcinoid tumor were randomized to treatment with streptozotocin combined with cyclophosphamide or with 5-fluorouracil (5-FU). Commonly experienced side effects were nausea, vomiting, leukopenia, thrombocytopenia, and nephrotoxicity. Objective response rates among eligible and evaluable patients treated with the 5-FU combination was 14 of 42 (33%) and with the cyclophosphamide combination, 12 of 47 (26%). Among those patients with carcinoids primary to the small bowel the respective response rates were 44% and 37%. The overall response rates for patients with carcinoids of pulmonary or unknown origin were only 12% and 17%. There was no significant difference in patient survival between the two treatment arms. Among 11 patients who received crossover therapy with 5-FU alone there were two responders. There were no responders among eight patients treated with cyclophosphamide alone. Urinary 5HIAA excretion proved to be a useful biologic marker in these patients that correlated well with the observed measurements of tumor bulk. Median survival times from the diagnosis of unresectable malignant disease related to sites of origin of carcinoid tumor were the following: small bowel, 28.4 months; pancreas, 24.0 months; lung, 15.1 months; and unknown origin, 9.0 months. Metastatic carcinoid tumor is a malignant disease susceptible to chemotherapeutic approaches and continued investigation of the therapy of these neoplasms should be strongly encouraged.


Feasibility and efficacy of 5-azacytidine used early in the therapy of adult acute nonlymphocytic leukemia: an ECOG pilot study.

Ten of 19 adult patients (53%) with acute non-lymphocytic leukemia achieved a complete remission (CR) after receiving combination therapy with daunorubicin and cytosine arabinoside. The early administration of 5-azacytidine to treatment failures did not enhance the CR rate. Patients gaining CR received six monthly cycles of single-agent chemotherapy (5-azacytidine, daunorubicin, and cytosine arabinoside) sequentially as consolidation therapy over the next 7 months and no subsequent maintenance therapy. The median duration of CR is 10 months which is similar to previous studies. The early administration of 4-azacytidine did not increase the duration of remission, but was not associated with significant toxicity.


Prolonged disease-free survival in MOPP-resistant Hodgkin's disease after treatment with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD).

Twenty-one patients with advanced Hodgkin's disease resistant to MOPP (mechlorethamine, vincristine, procarbazine, prednisone) were treated with ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). ABVD induced complete remission in 13 patients (62%) and partial remission in 2 (9.5%). In particular, complete response to ABVD was obtained in 7 of 13 patients who failed to respond to primary MOPP chemotherapy. After six cycles, no further therapy was given to patients in complete remission. At 36 months from starting ABVD, 69.7% of complete responders remain alive and free of disease, with a total survival of 73.4%. In contrast, none of the patients in whom partial response or nonresponse was observed was alive at 18 months. ABVD for six cycles was accompanied by mild and reversible toxicity. The results indicate that there is no cross-resistance between MOPP and ABVD. ABVD appears a simple effective, and tolerable multiple-drug chemotherapy for use in patients who are resistant to MOPP.


Physiologically based pharmacokinetic models for anticancer drugs.

The rationale and history of the development of physiologically based pharmacokinetic models are briefly reviewed in this paper. The methods of model construction and the previous application of this type of model to anticancer drugs are discussed. Future research should be focused on the following areas: (1) interspecies scaling, (2) the effects of disease states on the pharmacokinetics of anticancer drugs, and (3) the applications of pharmocokinetics to the studies of growth behavior of cancer cells. The ultimate goal will be to utilize this basic information to design an optimal dosage regimen and treatment schedule for the safe and effective cancer chemotherapy of each individual patient.


Liposome-incorporated enzymes: studies on amylase.

Alpha-amylase (EC 3.2.1.1) from hog pancreas was incorporated into artificial phosphatidylcholine and phosphatidylserine liposomes. To kinetically follow the enzyme-catalyzed hydrolysis of amylose the liposome-bound amylase was incubated in a medium containing amylose-iodine substrate. The reaction was studied at different concentrations of amylose and at different ionic strengths. Activation of amylase incorporated into liposomes by chloride ions varies with the type of phospholipid utilized to prepare the liposomes. Whe amylase bound to negative charged liposomes was used, a sigmoidal relationship between the reaction velocity and substrate concentration was found. Incorporation into liposomes protects amylase from heat inactivation.


Determination of renal clearances of amylase/creatinine with chromogenic and enzymatic methods.

Urinary amylase was estimated by chromogenic (amylochrome Roche) as well as enzymatic methods (SKI and Beckman: substrate starch and substrate maltotetraose respectively). Random and timed urines (24 hour collections) were analysed. Clearances of amylase gave different results dependent upon the amylase-test used and the glomerular filtration rate. Correlation between chromogenic and enzymatic methods (starch as substrate) was poor. The ratio of amylase and creatinine clearance was used to test different methods. Reference values for this ratio for the amylochrome method (N = 106) were 2.85 +/- 0.99% and for the Beckman-DS method (N = 60) 2.82 +/- 0.87%.


Precocious puberty associated with primary hypothyroidism in a mongol girl.

A mongol child suffereing from hypothyroidism who presented with precocious puberty is described. A presumptive diagnosis of idiopathic precocious puberty was first made and she was treated initially with medroxyprogesterone acetate, and later, with cyproterone acetate. The diagnosis of primary hypothyroidism was made late because of misleading results of protein bound iodine estimations. Subsequently, thyroid medication resulted in a prompt return to the normal range of the previously elevated levels of plasma gonadotrophins, thyroid stimulating hormone and plasma and urinary oestrogens, but the serum prolactin remained elevated for several months after therapy was begun.


Smooth muscle autoantibodies and autoantigens.

Smooth muscle autoantibody (SMA) was first found in the sera of patients with chronic active hepatitis and subsequently in the sera of patients with other autoimmune liver diseases, viral infections, certain cancers, heroin addicts and female infertility. SMA from patients with chronic active hepatitis reacts with many muscle and 'non-muscle' tissues while SMA from patients with other diseases usually reacts only with smooth muscle. These differences in immunofluorescent staining reactions suggest that SMA is a heterogeneous group of autoantibodies reactive with different smooth muscle autoantigens. As further evidence for this are findings that broad-reacting SMA can be absorbed out by actin, whereas autoantibodies reactive only with smooth muscle cannot, and that different SMAs give different immunofluorescent staining patterns using fibroblasts in tissue culture. Such staining patterns correspond to reactivity with either microfilaments, microtubules or intermediate filaments, ubiquitous cytoplasmic structures which make up the 'cytoskeleton'. Autoantibodies to actin-like microfilaments appear specific for chronic active hepatitis, autoantibodies to microtubules occur in infectious mononucleosis whereas autoantibodies to intermediate filaments occur in infectious hepatitis, chickenpox, measles and mumps. Predictably, future studies will show that presence of SMA with specificities for other proteins in the three types of cytoplasmic filaments, and given more information on antigenicity of the proteins and pathogenicity of the corresponding autoantibodies.


Common enterobacterial antigen and ONPG test in the taxonomy of the genus Yersinia.

The detection of the common enterobacterial antigen (Kunin) in strains of Y. pestis, Y. pseudotuberculosis and Y. enterotocolitica has brought an additional reason for separating them from the Pasteurella and for their inclusion in the family Enterobacteriaceae. Yersinia that give a positive ONPG test lack true beta-galactoridase, except when they harbour a lactose plasmid.


Differentiation of antibodies against Brucella abortus and Yersinia enterocolitica by enzyme-linked immunosorbent assay.

The enzyme-linked immunosorbent assay (ELISA) was found to be from ten to hundred-fold more sensitive than commonly used tube agglutination text. The ELISA using both direct and indirect inhibition assays revealed antigenic differences between Brucella abortus and Yersinia enterocolitica O-group V (serotype 9), which are undetected by commonly used serological routine tests. The results point to the possibility that the ELISA assay can be used as a serological method for differentiation between antibodies against different Brucella species and Y. enterocolitica O-group V.