Neutralization of a transmissible gastroenteritis virus of swine by colostral antibodies elicited by intestine and cell culture-propagated virus.

Cross-protection studies of gilts exposed to 4 transmissible gastroenteritis viruses--Ilinois (field strain), Miller-3, Miller low passage (M-LP), and Miller high passage (M-HP) tissue culture-adapted--indicated that only the gilt vaccinated with Illinois strain was protected, along with its newborn pigs, against challenge exposure with field virus. Similar results were obtained when the 4 viruses were incubated in vitro with colostrum from each of the 4 vaccinated gilts and subsequently used to orally inoculate newborn pigs. However, when the colostrums were used to neutralize M-HP virus in cell cultures, the neutralization titers were similar, indicating that a close antigenic relationship existed among the viruses. Neutralization studies in cell cultures, using immunoglobulin (Ig) fractions derived from colostrums of sows exposed to Illinois and M-HP virus, indicated that Illinois virus elicited more neutralizing activity in IgA than in the IgG fraction and that M-HP virus elicited more IgG than IgA antibody activity. In another study, Illinois virus was treated with these Ig-enriched fractions and then inoculated into the lumen of the jejunum of 3-day-old pigs. Anti-Illinois IgA was the only class of antibody which prevented replication of the Illinois virus in the intestine. Similar intraintestinal inoculations were used to test invasiveness of untreated Illinois and M-HP viruses. It was demonstrated that Illinois virus caused marked effect on the intestine: shortening of the villi, intestinal distension, edema, and presence of accumulated intestinal fluid within 60 hours after inoculation. The M-HP virus grew in the intestinal cells without affecting the length of the villi. The degree of invasiveness of Illinois or M-HP virus may account for the difference in the antibody class elicited in the colostrums.


Apparent propagation of the equine infectious anemia virus in a mosquito (Culex pipiens quinquefasciatus Say) ovarian cell line.

A tissue culture of Culex pipiens quinquefasciatus Say ovarian cells appeared to support the growth of equine infectious anemia (EIA) virus. Shetland ponies inoculated with 2nd, 7th, 9th, and 11th passages of mediums harvested from infected tissue culture had clinical signs of the disease and became EIA positive on 11, 19, 23, and 43 days after inoculation, respectively.


Development of a cell culture line of bovine fetal endometrial cells.

Monolayers of bovine fetal endometrial cells were established as primary culture cells within 1 to 2 weeks. After the 2nd passage, these cells were inoculated with bovine viral diarrhea virus. Effects of the virus were observed each day with a light microscope. Specific cytopathic effects consisting of degeneration and sloughing of the cells and a well-defined pattern of cytoplasmic vacuolation were observed at 5 days after inoculation.


Cholestyramine: an effective, twice-daily dosage regimen.

Nine patients with familial hypercholesterolemia (type II hyperlipoproteinemia) and two normal volunteers were studied to ascertain the effectiveness of cholestyramine in lowering plasma cholesterol when a twice-a-day dosage regimen was compared with the same total dosage administered four times a day. The study showed that in these subjects the two regimens were equally effective. The ability to administer cholestyramine twice daily in working adults and school children should greatly enhance adherence to this agent.


Adriamycin and enhanced radiation reaction in normal esophagus and skin.

Clinical evaluation of 10 patients with small cell carcinoma of the lung treated with radiotherapy and periodic cycles of combination chemotherapy with cyclophosphamide, vincristine, and adriamycin showed frequent and occasionally severe esophageal and skin reactions. Eight of the 10 patients had esophagitis, four required supportive intravenous fluids, and two subsequently developed esophageal narrowing and stricture formation. Recurrent esophagitis with augmentation of injury in the recently irradiated esophagus was observed 11 times in eight of the 10 patients after cycles of chemotherapy, and contributed to the sustained toxicity seen in two patients. Dermatitis in the form of moist desquamation was observed in five of the patients at very low doses of supervoltage radiation therapy. Acute pulmonary reactions was notably absent. This combination of chemotherapy, particularly adriamycin, potentiates the effect of radiotherapy on the normal esophagus and skin, and further implicates the radiosensitizing property of adriamycin.


Defective lung macrophages in pulmonary alveolar proteinosis.

Lung macrophages obtained by segmental lavage from three patients with pulmonary alveolar proteinosis were studied in vitro. The macrophages exhibited morphologic abnormalities including excessive lipid accumulation and giant secondary lysosome formation. These cells survived poorly in tissue culture, showed impaired chemotactic activity, and had decreased adhesiveness to glass. They phagocytized normally but had substantially decreased capacity to kill ingested Candida pseudotropicalis. Evidence was obtained that the macrophage defect was acquired and probably related to ingestion of the proteinaceous alveolar fluid. Peripheral blood monocyte function was normal in one patient and morphologic abnormalities were produced in normal monocyte-derived macrophages cultured with proteinaceous lavage material. These studies suggest that the lung macrophage in alveolar proteinosis is a defective cell as a consequence of an abnormal pulmonary environment.


Vitamin D endocrinology.

Current status of our understanding of the metabolism of vitamin D and its implications in metabolic bone disease is reviewed. The details of metabolism of vitamin D3 to 25-hydroxyvitamin D3 in the liver and its further conversion in the kidneys to either 1,25-dihydroxyvitamin D3 or 24,25-dihydroxyvitamin D3 are presented. The latter conversions are regulated by the vitamin D status, serum calcium through the parathyroid gland system, and serum inorganic phosphorus concentration. The 1,25-dihydroxyvitamin D3 can now be regarded as a calcium- and a phosphate-mobilizing hormone and must be considered as one of the most important serum calcium-regulating hormones. Disruption of the vitamin D metabolic sequence or the signal system for 1,25-dihydroxyvitamin D3 results in several bone and calcium metabolism disorders such as renal osteodystrophy, hypoparathyroidism, pseudohypoparathyroidism, and vitamin D-dependency rickets. The use of the synthetic analogs of 1,25-dihydroxyvitamin D3 as well as 1,25-dihydroxyvitamin D3 itself in the management of these disease states is discussed.


[Sex hormones in the male].

The measurement of androgen hormones in reduced times using small samples of blood is nowadays possible by using  the radioimmunological techniques. The level of testosterone in plasma is directly correlated with glandular secretion, though several different factors may provoke variations of such level. The measurement of testosterone in plasma is used for evaluation of testicular function. The main applications of testosterone determination in clinical practice are reported; special stress is laid on diagnosis on male hypogonadisms and on the study of testicular function in male sexual impotence.


[Evaluation and standardization of radioimmunoassays].

The term "standardization" may be applied to RIA methods to indicate the "definition of quality characteristics" the level of which must be defined on the basis of the evaluation of the "analytical procedure/specific reagents" system. Each laboratory, by applying a suitable long-term quality control system, must assure the consistent maintenance of the "standardization status" established for all mehtods it uses. As a matter of fact, in the case of RIA, materials are used that have a limited stability, that cannot be produced in large quantities, and that possess a complex composition not always well defined chemically. However, a remarkable role in the standardization process belongs to the producers of special reagents intended for RIA. In order to help the standardization of RIA methods, some programs of inter-laborator cooperation have been worked out in recent years. Among them mention is specifically made of three studies regarding the dosage of insulin: the most recent of them is devised and coordinated by the Instituto Superiore di Santià in cooperation with the Laboratory of Clinical Physiology of the National Research Council of Pisa. The availability of standardized materials is estremely important: for antigens, some materials are already in existence, but it is desirable that the various manufacturers shall follow more uniform criteria in their standardization. As far as the application of the RIA methods in the diagnostic field is concerned, the need exists for the use of standardized basic schemes that would include and unambiguously express all the useful information available in order to define better the clinical significance of the analytical data obtained.


Characteristics and mechanism of neuromuscular block in myasthenia gravis.

The neuromuscular block of myasthenia gravis has the characteristics of an antidepolarizing (competitive block), similar to that produced by d-tubocurarine in normal subjects: progressive decrease in muscle action potentials evoked by two or more nerve stimuli, posttetanic facilitation, posttetanic fatigue, inhibition of the depolarizing action of acetylcholine (ACh) or anticholinesterase compounds, and reversal of the block by ACh or anticholinesterase compounds. In myasthenic patients spontaneously recurring negative discharges were more difficult to locate in the end-plate zone than in normal subjects, suggesting that the number or density of functioning end plates may be reduced. The threshold dose of intra-arterial ACh that increased electrical activity was higher than in normal subjects; the duration of the increased electrical activity was briefer, and was followed by more depression of negative discharges than in normal subjects and by a greater increase in the threshold dose of ACh. These results indicate that the end-plate zone of myasthenic patients is less responsive than that of normal subjects to the excitatory action of ACh, and may be more readily desensitized by ACh. In both myasthenic patients and normal subjects the intra-arterial injection of ACh produced a prompt transient decrease in evoked potentials, attributable to depolarization of the end plates, followed by recovery (and in myasthenic patients by repair), and then by a more prolonged late decrease in evoked potentials, attributable to desensitization of the end plates to transmitter. This prompt depressant effect of ACh on evoked potentials was less in myasthenic patients than in normal subjects, and the late depressant effect of ACh was greater. In myasthenic patients the late block produced by ACh had the characteristics of an antidepolarizing (competitive) type of block, including inhibition of the depolarizing action of ACh and reversibility by ACh or neostigmine, while in normal subjects the characteristics were those of a depolarizing (noncompetitive) type of block, including little or no inhibition of the depolarizing action of ACh and lack of reversal by ACh or neostigmine. The differences between the late depressant action of ACh in myasthenic patients and normal subjects resembled differences in the effect of other depolarizing compounds, such as choline, succinylcholine, and decamethonium, and are best explained by differences in behavior of the postsynaptic receptor. The disease appears to be due to the presence of abnormal forms of receptor or to abnormal responses of receptor to the transmitter. The predominance of one or other form of receptor may determine the clinical state of the myasthenic patient and his response to anticholinesterase medication.


Effect of benomyl and thiophanate-methyl on metabolic activities of Rhizoctonia solani Kühn.

Effect of benomyl and thiophanate-methyl on various metabolic activities of Rhizoctonia solani was investigated. Both fungitoxicants strongly reduced endogenous whole cell and mitochondrial respiration by inhibiting one or the other key enzymes of electron transport chain; the activity of cytochrome oxidase being most markedly inhibited. Incorporation of 3II-thymidine was reduced by both while there was little or no inhibition in the rate of incorporation of 14C-uracil and 14C-leucine. Cell permeability was not affected to any appreciable extent and there was a little release of cellular components from the treated cells only at prolonged incubation. It is concluded that benomyl and thiophanate-methyl have a similar mode of action which primarily involves inhibition of respiratory activities, and as a consequence the biosynthesis of DNA is reduced.


Corticotropin and corticosteroids in generalized myasthenia gravis: comparative studies and role in management.

The effect of 310 courses of corticotropin, methylprednisolone, prednisone, and dexamethasone were studied in 62 patients with generalized myasthenia gravis who were poorly responsive to anticholinesterase medication and most of whom required assisted respiration.  Improvement in strength and response to anticholinesterase medication occurred in 91%  of the courses, and was moderate or marked in 63%. The incidence, degree, and duration of improvement appeared to be dose related. High doses of dexamethasone (20 mg orally each day for 10 days, repeated if necessary), which had 75% more glucocorticoid effect than any other regimen studied, produced the highest incidence of both improvement (100%) and moderate-to-marked improvement (75%), and the greatest duration of improvement (more than 3 months after 40% of the courses). The duration of improvement following intensive courses of any of the corticosteroids was approximately doubled by the subsequent administration of smaller doses of dexamethasone or prednisone on alternate days. Most patients with severe disease relapsed after 3 to 6 months of corticosteroid treatment, but increase in the dose of corticosteroid, and daily administration, which was more effective than alternate-day administratin, almost always again resulted in improvement. Corticotropin and corticosteroids were equally effective before and after thymectomy. High  doses of corticotropin and corticosteroid produced an initial exacerbation of the disease in 80% of the courses, which was moderate or marked in 57%. Reduction in dose reduced the incidence of severe exacerbation, but did not prevent it, and also resulted in slower and less marked improvement. Withholding anticholinesterase medication did not prevent exacerbation or increase improvement, and afforded no advantage, though it was usually helpful to reduce the dose of this medication. Because of the hazard of initial exacerbation and the occurrence of other serious side effects in 15% of the patients. (bleeding ulcer, vertebral compression, aseptic necrosis of the femoral head or tibia, and subcapsular cataracts), it is recommended that corticosteroid treatment be limited to myasthenic patients who are not responding satifactorily to anticholinesterase medication, that smaller  doses be employed in patients whose disease is not life threatening, and that higher doses be reserved for patients who are critically ill and are being managed, at least initially, in an intensive care unit.


Alternate-day prednisone: preliminary report of a double-blind controlled study.

Thirteen patients with moderately severe myasthenia gravis participated in a double-blind study using either 100 mg of prednisone or an equivalen numbder of placebo tablets on alternate days. Anticholinesterase therapy was continued on a demand basis. At the end of 6 months the code was broken.  Seven patients were on placebo and three of these had improved to such a degree that steroid therapy was not indicated. Four of these patients ultimately were started on prednisone and improved. Of the six patients on prednisone, three showed no improvement and three were improved. At the end of 2 years, the seven patients still taking prednisone were on maintenance dosage of this drug. Three of this group had experienced relapses when the dosage was cut to 15 to 25 mg on alternate days, and they again improved when the prednisone dosage was increased. No statistical evaluation is possible because of the small number of patients. It can be stated that seven patients improved with steroid therapy. Conversely, not all patients treated with alternate-day prednisone improved. Finally, any evaluation of treatment of myasthenia gravis must take into consideration the potential for spontaneous improvement, as demonstrated by three of the patients treated with placebo.


Effects of some immunosuppressive procedures on myasthenia gravis.

Clinical  Observations. A total of 53 MG patients have been treated with different immunosuppressive methods (alone or combined) with the following effects: Thymectomy was performed in 38 patients. The improvement was excellent in 15, and moderate or uncertain in 20. In three patients severe long-lasting deterioration followed the operation. ACTH treatment (n=32): Initial deterioration during the 5-7 days of heavy ACTH treatment (1000 IU) was followed by an improvement lasting on an average 4 months. The improvement was good or moderate in 78% of the patients. Betamethazone treatment has been tried in six patients where ACTH and azathioprine was ineffective. In four of these patients the results were excellent. Azathioprine treatment has been given to 26 patients for periods up to 7 years. An improvement is measurable after 6-12 weeks and it seems maximal after about 1 year. Of the 26, 80% responded favorable with reduction in the need for cholinesterase inhibitors. Severe complications were seen in three patients with one death. Drainage of thoracic duct lymph was initiated in 14 patients up to 4 weeks with rapid improvement lasting as long as drainage was performed. Long-termed effects of the drainage may be present, however. Retransfusion of homologous cell-free lymph precipitated a return of the myasthenic symptoms. Biochemical Studies on Myasthenic Lymph. Using a membrane preparation from the electric organ from Torpedo marmorata and tritiated Naja naja siamensis neurotoxin we demonstrated a decreasing binding of toxin to the receptor in the presence of MG lymph gamma-globulin fraction. Gammaglobulins from controls showed almost no inhibition of the neurotoxin binding. Immunological Studies. An increased frequency of HL-A1 and 8 was found in female patients. LD typing was also performed. During a period of three weeks of thoracic duct drainage 130X10(9)  or about 10% of total number of lymphocytes in the body were removed. In the lymph an initial decrease in the proportion of thymus-derived lymphocytes (T cells) occurred, which was accompanied by a sequent increase in the proportion of bone-marrow-derived lymphocytes (B cells). Towards the end of drainage this effect was reverted. Mitogenic stimulation using lymphocytes from thoracic duct drainage revealed no differences as compared to normal cells. The proportions of T and B cells was studied in the peripheral blood in nine patients treated with ACTH. During treatment there was an initial decrease in the proportion of T cells accompanied by a subsequent rise in the proportion of B cells, which was maximal after 3-10 days. These proportions were reverted to normal 1-5 days after the maximal change. The effect of azathioprine on T and B cells has also been studied.


The specificity and nature of serum-angiotensin-converting enzyme (serum ACE) elevations in sarcoidosis.

Elevation of serum-angiotensin-converting enzyme (serum ACE) in patients with active sarcoidosis was confirmed in a total of 64 subjects with a mean serum ACE of 15.76+/-7.4 units compared with 6.05+/-2.0 units in 194 patients with other types of respiratory disease. Resolution of the sarcoidosis disease state or therapeutic control with adequate doses of corticosteroids (15 mg prednisone daily) brought the elevated serum ACE levels down into the normal range. A longitudinal study of serum ACE activity was found to be an effective way of judging the therapeutic efficacy of various steroid dosage levels. No other disease state involved in the differential diagnosis of sarcoidosis was found to have elevations of serum ACE activity. However, 6 patients with Gaucher's disease did have elevated serum ACE activity that ranged well above the usual level seen even in patients with sarcoidosis. The two diseases could be readily distinguished in the laboratory by elevated serum acid phosphatase activity in most cases of Gaucher's disease. It would appear that detection of elevated serum ACE levels can be a useful procedure for confirming a diagnosis of active sarcoidosis and for judging the therapeutic response.


Elevation of angiotensin-converting enzyme in granulomatous lymph nodes and serum in sarcoidosis: clinical and possible pathogenic significance.

A statistically highly significant elevation of serum ACE was found in a group of 58 patients with sarcoidosis (serum ACE was elevated in 34% of patients), as compared with normal controls and patients with tuberculosis and various other common diseases. The results suggest that serum ACE is a useful aid for the diagnosis of sarcoidosis when elevated, but that a normal value does not rule out the condition and may occur in more than one-half of monitored patients. There is a trend to diminution of serum ACE with increasing duration of disease with or without steroid therapy, perhaps correlating with the total body mass of active granulomas, as indirectly suggested in preliminary data by correlation of serum ACE with  serum globulin in 16 sarcoidosis patients. It is not yet clear whether there is any significant steroid effect on serum ACE, but a significant number of patients on steroid therapy for more than 2-4 yr have elevated serum ACE values, which in some instances are extremely high. There was a 12-fold elevation in ACE to specific activities generally exceeding those of normal lung in granulomatous lymph nodes of 14 patients with sarcoidosis, suggesting that sarcoid granulomas may be actively synthesizing ACE and resulting in elevation of serum ACE. Extensively fibrotic sarcoid lymph nodes had normal or slightly elevated ACE, suggesting that obliteration of granulomas in sarcoid lymph nodes diminishes their ACE content and that this obliteration may be related to the tendency to diminution of serum ACE with time. ACE was not elevated in one tuberculous lymph node or in experimental granulomas, suggesting that elevation of ACE may have some specificity for the granuloma of sarcoidosis rather than being a characteristic of all granulomas. The catalytic and physical properties of ACE in serum and lymph nodes in sarcoidosis were generally similar to normal ACE with respect to pH activity, modulators, polyacrylamide-gel electrophoresis, and Sephadex G-200 gel filtration. However, sarcoid lymph node ACE appeared to be more heat labile than normal lung or lymph node ACE, suggesting the possibility that an abnormal ACE may be present in sarcoidosis. If an abnormal enzyme is indeed present, it might be coded for by a host gene that is not normally expressed or a nonhost gene or it might be a normal ACE that has been altered. No ACE activity was found in circulating white blood cells in sarcoidosis or in control subjects, suggesting that circulating white blood cells may not contain the epithelioid cell precursor or that ACE synthesis (or less likely, uptake) may be turned on at a later stage in the transformation. Lysozyme activity was also elevated in sarcoid lymph nodes. Serum ACE and serum lysozyme were significantly positively correlated in 16 sarcoidosis patients, suggesting a relationship between the two...


Estimation of T- and K-cell activity in the peripheral blood of sarcoidosis patients.

Depressed ADCC activity was found in sarcoidosis patients in clinical Stage II when whole blood was used as the effector cell pool. Whole blood in Stage I patients as well as purified peripheral lymphocytes of sarcoidosis patients did not reveal a diminished cytotoxic activity. Stimulation experiments with PHA, Con A, and PPD in two different concentrations resulted in a normal PHA response, a significantly decreased Con A response (regardless of the clinical stage of the patients), and a significantly decreased PPD responsiveness of peripheral lymphocytes in Stage II patients, respectively. Regarding the distribution of peripheral B and T lymphocytes, only a significantly depressed T-cell number in Stage I sarcoidosis patients was observed. Peripheral cells forming EA and EAC rosettes and staining for membrane-bound immunoglobulins were within normal ranges. Serum antibody titers to different herpes viruses, including Epstein-Barr virus, were found not to be elevated. Twenty percent of sarcoidosis patients showed anti-immunoglobulins in their sera specific for the Fc and Fab fragment.


Isozymes of glyceraldehyde-3-phosphate dehydrogenase in man and other mammals.

Multiple electrophoretically distinct forms of glyceraldehyde-3-phosphate dehydrogenase have been observed in human and other mammalian tissues. The human isozymes appear to have essentially the same structural and kinetic properties. An apparent correlation between red-cell age and the relative intensities of the isozymes supports the idea that the isozymes arise as a result of post-translational modification of the polypeptide chain. The possibility that a second locus is involved in the determination of these isozymes is discussed.


The control of glycogen metabolism in the liver.

The major factor that controls glycogen metabolism in the liver is the concentration of phorphorylase alpha. Indeed, this enzyme catalyzes the limiting step of glycogen breakdown and, by controlling the activity of synthetase phosphatase, also regulates glycogen synthesis. The formation of phosphorylase alpha is stimulated by cAMP, by glycogen, and presumably also by some still ill-defined ionic changes. The ininactivation of phosphorylase is greatly stimulated by glucose and inhibited by AMP and glycogen. Glycogen synthesis is proportional to the concentration of synthetase alpha, which in normally fed animals is formed only when most of the phosphorylase is in the beta form. The inactivation of glycogen synthetase is stimulated by cAMP, an elevated concentration of which puts a double lock on glycogen synthetase by activating phosphorylase alpha (and thereby preventing synthetase activation) and by inactivating glycogen synthetase. The effect of cAMP, 5'-AMP, glucose, and glycogen can presently be explained in molecular terms. The main missing link is in the ionic effect whose elucidation might lead to the understanding of the mode of action of insulin.


[Histochemistry and electron microscopy of the embryonal development of the golden hamster kidney: study of the interstitial cells].

The structure and the origin of the interstitial cells in the kidney of the golden Hamster during its embryonic development was studied. For this purpose kidneys from 11, 13, 15 and 17 day-old embryos were used. The histochemical observations as well as the electron microscopy demonstrated that the interstitial cells have a metanephric origin and are embryonically similar to the cellular elements that differentiate the primordial renal vesicles and later organise the epithelial portion of the nephrons. These cells seem to take part in the formation of the basal membranes during tubular genesis.


BCG immunoprophylaxis of recurrent herpes progenitalis.

Thirty-eight patients with severe, recurrent herpes progenitalis were treated by immunoprophylaxis with repeated BCG inoculations. Results of the study demonstrated no significant prophylactic benefit of BCG when contrasted to other homologous or heterologous antigens or to control patients receiving placebos. Caution is warranted in the use of homologous vaccines from Germany because theoretically, tumor growth might be enhanced by immunologic means, although the vaccine apparently has no intrinsic oncogenic qualities.


Angiokeratoma corporis diffusum (Fabry disease). A lysosomal disease.

Angiokeratoma corporis diffusum (Fabry disease) is an X-linked recessive disease. We had an opportunity to examine a heterozygous female patient with angiokeratoma and cornea verticillata. The patient's serum alpha-galactosidase activity was reported to be about 50% of normal. Skin lesion biopsy specimens were stained with electron microscopic acid phsophatase (ACP), with proper controls. Acid phosphatase activity was demonstrable within membrane-bound inclusions of cutaneous vascular endothelial cells. This suggested that the accumulation of abnormal glycolipids in the vascular cells occurs in the lysosomes.


Nevus sebaceous and syringocystadenoma papilliferum.

A 52-year-old patient was admitted to the hosptial for evaluation of hypertension. He had two skin lesions, one on the forehead and one in the postauricular area, which had been present since birth. The forehead lesion was a nevus sebaceous and the postauricular lesion was a syringocystadenoma papilliferum. Except for a few patients with widespread nevus sebaceous and syringocystadenoma papilliferum associated with neurologic abnormalities, most of the previously reported patients with these nevi have had solitary lesions of one or the other. An association of nevus sebaceous and syringocystadenoma papilliferum in the same lesion is not uncommon. Despite bleeding and crusting in one of the lesions and despite informing the patient that a malignant neoplasm may develop in these nevi, he refused excision of either of the lesions.


Idiopathic hypoglycaemia in sibs with morphological evidence of nesidioblastosis of the pancreas.

Two sibs who sustained severe hypoglycaemia in the neonatal period are reported. In spite of treatment with frequent feeds intravenous glucose, glucagon, hydrocortisone, and diazoxide, hypoglycaemia persisted, and both infants eventually required subtotal pancreatectomy. Tests for leucine toleranct were normal though the second case showed some protein sensitivity. Histological and immunohistochemical studies indicated nesidioblastosis in both specimens of pancreata. The children are presently performing at mildly retarded levels, and required diazoxide and anticonvulsant medication for some time postoperatively. Because both sexes are represetned, an autosomal recessive inheritance pattern is suggested. The theory of a gut hormone stimulating insulin production is briefly discussed.


Response in the newborn to raised upper airway resistance.

The effect of raising the airways resistance of 56 normal newborn babies by blocking alternate nostrils was studied by means of oesophageal intubation and the trunk plethysmograph. Increased resistance was associated with reduced respiratory rate and ventilation. A comparison was made of the response in different sleep states. In rapid eye movement (REM) sleep respiratory tidal volume decreased on blocking, there was no increase in the work of breathing and the fall in minute volume was greater than in non-REM sleep where tidal volume and minute work increased on blocking. These responses may be relevant to the sudden unexpected death syndrome in infancy, and to the management of normal newborns.


Langerhans cells at the sites of vaccinia virus inoculation.

Langerhans cells in the epidermis at the sites of vaccina virus inoculation were studied with the electron microscope. The cells contained unusually increased numbers of the Langerhans cell granules. Such abnormal Langerhans cells have not been described except for in histiocytosis X. Vaccinia virus particles were found in the Langerhans cells, where they were located individually or embedded in the granular matrix or in lysosomes.


On the occurrence of sphaeridia in basalioma cells and the basal cells of the overlying epidermis.

302 nuclear sections of basalioma cells, 145 nuclear sections of the basal cells of the epidermis above the tumor, and 177 nuclear sections of the basal cells of normal epidermis were investigated and statistically evaluated with the aim of determining the presence of sphaeridia occur significantly more frequently in the basal cells of the epidermis above the tumor and in normal epidermis than in the tumor itself. These findings are discussed in connection with the degree of cellular protein synthesis.


[Quantitative histometric investigations on the epidermis and corium of rat paw after experimental inflammation (author's transl)].

The epidermis and corium of rat right hind paw were investigated both histologically and histometrically after a subplantar injection of aerosil, formalin, carrageenin or Freund's complete adjuvant. The thickness of the epidermis and corium was determined on 5 rats respectively at 12 different times between 0.5 and 480 h post-treatment. Paw swelling was measured plethysmometrically on living rats. The left paw of untreated rats as well as the saline-injected and the untreated left paw of carrageenin-treated and adjuvant-treated animals respectively served as controls. Results 1. After the injection of the 4 substances, an acute inflammation developed maximally 4 to 24 h post-treatment in the corium. The thickness of the corium increased simultaneously with paw swelling. 2. Epidermal hyperplasia set in after a lag-phase of 12 h following the injection of formalin, carrageenin and adjuvant. 3. After injection of aerosil a subcutaneous oedema developed but no epidermal hyperplasia occured. 4. The formation of granulation tissue and necroses in the corium was seen only in the adjuvant-treated group 4 to 20 days post-treatment. At the same time, epidermal hyperplasia reached an absolute maximum. 5. The disturbance of nutrition and the lack of oxygen in the inflamed corium is possibly responsible for the initiation and persistence of the hyperplasia.


Actions and interactions of theophylline and imidazole on cardiac contractility, phosphorylase activation and cyclic AMP.

Injection of 1.0 mg theophylline and 1.6 mg imidazole into guinea-pig hearts perfused by the Langendorff technique increased cardiac contractile force by 20.0 +/- 1.0% and 23.3 +/- 1.2% over control and activated phosphorylase without producing significant changes in cyclic AMP levels. When guinea-pig hearts were perfused with theophylline (10(-3) M) or imidazole (20 mM), injection of either imidazole or theophylline did not further increase cardiac contractility or phosphorylase a levels. In all cases there was no change in cycylic AMP levels. Data in the literature indicate that calcium plays a role in the cardiac biochemical and mechanical effects of theophylline and imidazole. Both drugs may thus produce their cardiac effects by a calcium rather than a cyclic AMP mediated mechanism.


Bile duct carcinoma mimicking chronic liver disease.

In a case of cholangiocarcinoma involving the bifurcation of the common duct, the association with striking intermittence of jaundice and with signs of chronic liver disease presented a diagnostic enigma. Disappearance of jaundice does not rule out the diagnosis of bifurcation tumors and may be misleading. Adequate demonstration of the biliary tree, best achieved with percutaneous transhepatic cholangiography, is essential for early diagnosis of this entity.


Ribulose 1,5-diphosphate carboxylase and Cholorobium thiosulfatophilum.

1. Cell-free extracts of the photosynthetic bacterium Cholorobium thiosulfatophilum, strains 8327 and Tassajara, were assayed for ribulose 1,5-diphosphate (RuDP) carboxylase and phosphoribulokinase--the two enzymes peculiar to the reductive pentose phosphate cycle. 2. RuDP carboxylase was consistently absent in strain 8327. The Tassajara strain showed a low RuDP-dependent CO2 fixation activity that was somewhat higher in cells following transatlantic air shipment than in freshly grown cells. The stability and behaviour of this activity in sucrose density gradients were similar to those described by other workers. 3. The radioactive carboxylation products formed in the presence of RuDP by enzyme preparations from the Tassajara strain did not include 3-phosphoglycerate--the known product of the RuDP carboxylase reaction, but instead consisted of the unrelated acids glutamate, aspartate and malate. 4. Phosphoribulokinase was absent in all preparations of the two Chlorobium strains tested. By contrast, phosphoribulokinase as well as RuDP carboxylase were readily demonstrated in preparations from pea chloroplasts and the photosynthetic bacterium Rhodospirillum rubrum. 5. It is concluded that C. thiosulfatophilum appears to lack RuDP carboxylase, phosphoribulokinase, and hence, the reductive pentose phosphate cycle.


Action of polymyxin B on bacterial membranes. Binding capacities for polymyxin B of inner and outer membranes isolated from Salmonella typhimurium G30.

Radioactive mono-N-acetyl-14C-polymyxin B or natural polymyxin B are within 60 s absorbed by isolated inner (cytoplasmic) and outer membranes from Salmonella typhimuriumG30. The sigmoidal binding isotherms indicate saturation of inner and outer membranes with approximately 30 and 60 nmoles polymyxin B bound per mg membrane, respectively. Based on the known content of these membranes in lipopolysaccharide, phosphatidylglycerol, cardiolipin and phosphatidylethanolamine, a calculation of the  theoretical binding capacities yields almost identical values if lipopolysaccharide, phosphatidylglycerol and cardiolipin are assumed to function as the actual binding sites for the antibiotic in the isolated membranes. The excellent agreement between theoretical evaluation and experimental determination of polymyxin B-binding capacities leaves little doubt that the named anionic compounds are the chemoreceptors for the cationic antibiotic. This is further substantiated by very similar binding and killing kinetics of polymyxin B.


[DNA synthesis in spinal ganglia of rabbit after Herpes suis infection. Findings obtained by electron microscopy and autoradiography].

The mulitplication of herpes suis virus in neurons, amphicytes, gliocytes, as well as Schwann's and endothelial cells of the spinal ganglion of rabbit was traced by electron microscopy and autoradiography, using tritium-labelled thymidine. Marking of nuclear zone margin, quite common when it comes to ganglion cells, was observed also in the context of mesenchymal cells beyond expectation on the basis of light microscopy, but in the case under review it had no direct relationship with virus synthesis. Repeated markings were recorded from the nucleoli of apparently unchanged ganglion cells which suggested the suitability of the technique for early detection of infectious attack on intact cells. Exogenous 3H-thymidine was supplied three hours and absorbed with specificity by the DNA-forming centres of the nuclei, but the growing virus drew into itself additional cellular or inactive thymidine. The method proved to be highly significant, as in comparison to the nuclear environment there were ten times as many lemnici in the DNA production centres of neurons and Schwann's cells and about six times as many in the amphicytes and gliocytes. Now, there is definite justification in rejecting as unfounded all doubt expressed repeatedly and more recently in the specificity of herpes-dependent intranuclear inclusions.


[Superneutralization test--a new virus serology examination procedure].

The serum neutralisation test, based on the antigen-antibody reaction and cytopathic action of a given virus upon certain in-vitro cultured cell systems, was expanded to the dimensions of a super-neutralisation test by including specific control sera with known titre and applying then to all samples positive to serum neutralisation through repeated addition of virus to tubular cell cultures with no CPE in the serum neutralisation test. Another antigen-antibody reaction was introduced by repeated addition of virus. In samples with less antibody (lower titre) due to lacking or partial neutralisation of added virus such reaction gave a CPE of with the intensity was inversely proportional to the titre. The CPE (cytopathic effect) will disappear beyond a certain titre limit owing to complete neutralisation of added virus. The point of disappearance can be controlled to the purpose of the given test by appropriate choice of the virus dose. This approach will entail negligible extra expenses but enable, in addition to qualitative assessment of reagents, quantitative identification of their antibody titres, and this will, no doubt, add to the informative weight of the test result. The advent of the super-neutralisation test has added to laboratory diagnosis in the field of virus serology a conventiently applicable, uninvolved, and highly effective technique.


[General adaptation syndrome (Selye) in the calf. 5. Effect of increased glucocorticosteroid values on the phagocytosis activity of luekocytes, the function of RHS and the morphology of lymphatic organs].

Studies were conducted with the view to elucidating the correlations between increased glucocorticosteroid levels in the blood and the defense potential of calf organism against infectious diseases. The test animals were exposed to several substances (ACTH, cortisol, colibacteria, coliendotoxin), and even one to two days of increased 11-OHKS values were followed by marked decline in phagocytosis activity of leucocytes. In addition, RHS function was considerably reduced, after ten to thirteen days of application had elapsed, since at that point the disappearance of intravenously applied bacteria from circulating blood of test animals took place at rates which were much lower than those recorded from untreated calves. Differentiated length of stress or action (four to thirteen days) was followed by conspicuous changes in the lymphatic tissue of calf organism, with severe involution of thymus and follicular atrophy of intestine-associated lymphatic tissue having been the major findings. The results seem to suggest that rise in adrenocortical hormone level under stress may reduce potential organic defense to infection.


Rapid eye movement sleep density. An objective indicator in severe medical-depressive syndromes.

The electroencephalographic sleep patterns of 12 patients with a final diagnosis of primary depression and those of 12 patients admitted to the Clinical Research Unit with this diagnosis, but subsequently also found to be suffering from severe medical disease, were compared. Patients with depression concurrent with severe medical disease have significantly less phasic conjugate rapid eye movement (REM) activity during REM sleep than subjects with the diagnosis of a primary depression. These findings suggest that quantification of REM density may be used clinically to distinguish between medical-depressive syndromes and primary affective disorders.


Electroencephalographic sleep diagnosis of primary depression.

Studies of severely depressed hospitalized patients suggest a shortened rapid eye movement (REM) latency as a specific biological marker for primary affective disease. To assess the validity of these findings, 40 outpatients referred to our Electroencephalographic Sleep Center for evaluation of depressive symptoms were studied. Concurrent with the all night EEG sleep studies, all patients received a brief clinical interview and a battery of self-rating scales. The entire sample was then subdivided into primary and secondary depressives on the basis of follow-up diagnoses. While there were no significant differences between groups on self-ratings of depressive symptoms, the group of primary depressives had significantly shorter REM latencies and higher measures of phasic REM than the secondary depressives. Furthermore, in this patient group, the delineation of primary vs secondary depression was greater than 80% on the basis of only two nights of EEG sleep. Such objective biological measures, if replicated, could provide a method for increasing the accuracy of differential diagnosis among depressed populations in clinical research.


Poorly differentiated synovial sarcoma. A light and electron microscopic study.

Few studies of the ultrastructural features of synovial sarcoma have appeared in the literature. The case under study represented a poorly differentiated synovial sarcoma with a predominant fibrosarcomatous component and a few areas with epithelioid and pseudoacinar patterns. Ultrastructurally, the cellular elements of the varied histologic patterns were similar. Basement membranes and desmosomes were absent, and the cell surfaces facing the acinar lumen exhibited multiple microvilli. It appears from a comparison of our studies with the previous reports that the fine structure of this tumor varies according to the degree of histologic differentiation.


Nasal polyposis with stromal atypia. Review of follow-up study of 14 cases.

The clinical, microscopical, and gross pathological features of 14 cases of intranasal and paranasal sinus polyposis with unusual stromal cell atypia are described. In gross appearance, the lesions were polypoid, translucent masses, similar to the usual nasal polyp. Although clinically the lesions were indicative of allergic and inflammatory nasal polyposis, microscopical examination showed numerous large, often pleomorphic histiocytes or facultative fibroblasts that were suggestive or sarcomatous, malignant degeneration. Diagnoses by the original contributing pathologists included embryonal rhabdomyosarcoma, stromal neoplasia, and juvenile masopharyngeal angiofibroma. Follow-up data showed no evidence of neoplasia, despite the remarkable cytological changes found in the stroma. The stromal atypia most likely represents a reactive phenomenon secondary to inflammation.


[The neuronal Torres bodies in experimental yellow fever encephalomyelitis. An additional example of the heterogeneous nature of Cowdry type A intranuclear inclusions].

In experimental yellow fever virus encephalomyelitis of adult albino mice, the occurrence of intranuclear inclusions within nerve cells, in particular, within spinal and bulbar motoneurons, is a constant finding. The light microscopic features of these so-called neuronal Torres bodies correspond entirely to the criteria laid down by Cowdry for the type A intranuclear inclusions. At the ultrastructural level, these karyoplasmic formations consist of haphazardly distributed patches of an essentially amorphous material of various density. Unlike the Cowdry type A intranuclear inclusions characteristic of several herpesvirus and paramyxovirus infections, neuronal Torr-s bodies do not contain any viral structures. The frequency with which neuronal Torres bodies, certain nucleolar alterations and severe tigrolytic changes occur together, possibly indicates that this sort of type A intranuclear inclusion developes as a consequence of a virus induced disturbance of the cell nucleic acid and/or protein anabolism.


Purification and characterization of equine infectious anemia virus.

EIA virus was purified from equine fetal kidney cell cultures by PEG-precipitation, two sucrose-gradient sedimentations (5-30 per cent) and (25 to 60 per cent) centrifugation, using the immunodiffusion test to follow the procedure. Purified EIA virus had a density (20 degrees C) of 1.162 and a sedimentation constant of S20w=656. electron microscopy revealed a particle of about 100 nm in diameter with a very flexible but usually spherical shape. The dense core may be at various locations inside the membrane bound particle.


The effect of influenza virus infection on the agglutinability by concanavalin A of polyoma-transformed BHK-21 cells.

Polyoma-transformed (Py-transformed) BHK-21 cells are agglutinated more readily by Concanavalin A (Con A) after they are infected with influenza virus; this agglutination was only slightly affected by fixation with glutaraldehyde or colchicine treatment. It is suggest that the mechanism is not dependent on membrane fluidity. The same amounts of 125i-labelled Con A were bound after infection with influenza virus and after glutaraldehyde fixation with or without colchicine treatment: it seems therefore that new receptors for Con A are not expressed between 90 and 600 minutes after these cells are infected with influenza virus.


Envelopment and the envelopes of infectious bovine rhinotracheitis virus in ultrathin sections.

An electron microsopic study of cell cultures and bovine foetal tracheal organ cultures infected with infectious bovine rhinotracheitis (IBR) virus showed the following. a) The difference in the site at which the outer envelope is acquired in the infected cell is responsible for some morphological differences between the virions. Where envelopment of the capsids occurs by budding into cytoplasmic tubules, dense material adjacent to the tubules is often incorporated between the capsid and the outer envelope, giving a pleomorphic appearance to the latter. No dense material is seen in the same position if envelopment occurs in the nucleus. b) Dense material adjacent to the cytoplasmic tubules is not only incorporated in the virions, but may also bud into the cytoplasmic tubules without nucleocapsids, thus giving rise to dense bodies. c) Dense material in the virions is closely adjacent to the inner side of the outer envelope, but is separated from the capsid by a lucent zone. A similar zone can be seen around some nucleocapsids in the nucleus. d) The outer envelope of numerous extracellular virions and of those located in the cytoplasmic tubules shows the unit membrane structure with projections. The outer envelope of intranuclear particles and of those located in the perinuclear cisterna had the appearance of a dense membrane.


Quantitative studies on adsorption, elution, and haemagglutination of vesicular stomatitis virus.

Radioactively-labelled VSV, both Indiana and New Jersey serotypes, were rapidly and efficiently adsorbed onto goose erythrocytes, but only within a narrow range of pH and at low temperatures. Under optimal conditions for adsorption, both infectivity and haemagglutinating activity of VSV were reduced. A basic difference between the two serotypes was identified: adsorption and haemagglutination of the Indiana serotype were stable even at pH 9.0 and at 37 degrees C, whereas New Jersey serotype was eluted slowly at +0 degrees C and at pH 6.4 and rapidly at a higher temperature and pH. The rapid elution offers a useful method for purification of New Jersey serotype. Particle counting of VSV showed that 10 to 50 virus particles were required for one PFU. Haemagglutination was not a sensitive method for assaying small amounts of VSV; 3--20X10(7) virus particles or more than 10(7) PFU corresponded to one HAU.


[Herpesvirus-induced autoantibodies in animals (author's transl)].

After immunization with autologous testicle cells which were infected with herpes virus hominis type 1 or 2, histologically homogeneous, eosinophilie PAS-positive substances could be detected in five out of six rabbits, mainly within the interstitium. These substances have been found by immunofluorescence microscopic techniques to be antibodies against testicle tissue.


Ultrastructure of mouse periventricular and choroid plexus tissues in experimental vesicular stomatitis virus infection.

The ultrastructure of the periventricular and choroid plexus tissues was studied in the three-week-old mouse, infected with the vesicular stomatitis virus (VSV) by the intranasal route. The VSV reached the periventricular ependymal lining late in infection. It was carried within the cytoplasm of myelinated axons and their sheath cells. Inflammatory cells, although few in numbers, may have also contributed to the virus dissemination. Once in the periventricular tissues the VSV entered the cells from the intercellular space. It replicated in both the ependymal and subependymal cells. It matured either directly in the cytoplasm, or by budding from the plasmalemma as well as the cytoplasmic membranes. In numerous cells the cytoplasmic membranes formed the so-called undulating tubules which contained the VSV particles. The infected ependymal cells became necrotic and separated from the ventricular surface. The changes were similar in all three of the cerebral ventricles. At no time during the infection was the VSV observed near or within any of the choroid plexuses. Some ultrastructural changes, however, occurred in the choroidal epithelial cells. These may have developed either as a consequence of viral damage in the periventricular tissues, or due to virus presence in the cerebral ventricles.


Late-infantile neuronal ceroid-lipofuscinosis. An ultrastructural study of lymphocyte inclusions.

Ultrastructural study of peripheral blood from two patients with late-infantile neuronal ceroid-lipofuscinosis with curvilinear bodies, demonstrated in brain biopsies revealed curvilinear bodies in lymphocytes. These findings indicate that ultrastructural investigation of circulating lymphocytes may be useful in the diagnosis of late-infantile neuronal ceroid-lipofuscinosis and may circumvent the need for brain biopsy. Curvilinear bodies were also present in the lymphocytes of a neurologically normal younger female sibling of patient 1, who has had a single seizure, leading to speculation that she may be in the early stages of the same disease. This case suggests the possibility of early detection of this disorder and indicates the importance of screening lymphocytes of siblings of affected patients. Tubular cytoplasm inclusions were present in a high percentage of lymphocytes of the asymptomatic parents and a younger sibling of these patients.


Suspected multiple primary tumors of the lacrimal and parotid glands.

A 63-year-old man had apparent primary tumors of the lacrimal and parotid glands. Initially an adenocarcinoma of ectopic lacrimal gland origin was suspected following biopsy of a mass in the left orbit. The patient received radiation therapy to this area and showed no recurrence of the original lesion or development of other tumors for a period of 27 months. At that time, the patient returned with a mass in the left preauricular area. This was surgically resected and found to be an adenocarcinoma of the left parotid gland. Both tumors were histologically similar, mucin-secreting adenocarcinomas. There has been  no further evidence of tumor growth in an additional three-year period.


Occult tumors of the infratemporal fossa: report of seven cases appearing as preauricular facial pain.

Seven patients had occult malignant neoplasms either originating in or extending to the infratemporal fossa. Common symptoms were facial pain centered over the temporomandibular joint and facial numbness. These symptoms were sometimes associated with middle ear effusion and trismus. Multiple biopsies are often necessary to establish the diagnosis. The average delay in diagnosis from first symptom was 14 months. Infratemporal fossa neoplasia belongs in the differential diagnosis of facial pain.


Hereditary deafness and sensory radicular neuropathy.

We report a case of radicular sensory neuropathy and deafness. The patients appears to be one of a family in whom several members were similarly afflicted. Thus, this case fits the pattern of hereditary deafness and sensory radicular neuropathy, originally described by Hicks in 1922.


Equine herpesviruses. 6. Sequential infection of horses with types 2, 3 and 1.

The immunological and virological status of 3 foals in respect of equine herpesviruses (EHV) was established and the foals were sequentially infected with EHV2, EHV3 and EHV1. Following experimental infection with EHV2, no clinical signs of disease were observed in any foal. The inoculation of EHV3 into the genital tract resulted in lesions of the mucous membrane and perineal skin that were considered typical of equine coital exanthema. Following intransal inoculation of EHV3 extensive ulceration and pustule formation on the nasal mucosa was observed by day 5 accompanied at day 7 by a profuse, mucopurulent nasal discharge; on day 8 pustular lesions of the skin about the external nares appeared. Signs of disease after inoculation with EHV1 were milder than expected in 2 of the 3 foals. The possibility that recent, prior infection with EHV2 and/or 3 may protect against EHV1 was considered.


Duck viral enteritis: a comparison of replication by CCL-141 and primary cultures of duck embryo fibroblasts.

Cultures of primary cells and a line of fibroblast-like cells from the Pekin duck were both compared for their replication of the herpesvirus of duck viral enteritis. The two kinds of cells were equally accurate for quantifying virus upon isolation. Also, one-step growth curves showed that in both kinds of cultures new virus appeared by the 18th hour and that infectivity peaked at about 36 hours. Primary cultures yielded about 5.6 times as much virus as did the cell line, though plaques were more easily discerned in the latter. Because of availability, uniformity, and their known health history, CCL-141 cells offer some advantages for work with the agent of duck viral enteritis.


Spleen lesions of hemorrhagic enteritis of turkeys.

Spleens from turkeys were examined at intervals after intravenous inoculation with hemorrhagic enteritis virus. Spleen size increased until the 4th day after inoculation. On the 5th day, spleen size was markedly reduced and continued to approach normal size. Hemorrhagic enteritis antigen reached a peak concentration on the 2nd day, was reduced in concentration on the 3rd day, and was absent by the 4th day. Hemorrhagic enteritis precipitin antibody was present in all serum samples taken after the 10th day. Necrosis of lymphoid cells in the white pulp was prominent in the 1st day. Proliferation of immature-appearing cells on the 2nd, 3rd, and 4th days coincided with a lower virus antigen content in the spleen. Massive disintegration of the white pulp, associated with the appearance of small dense-staining lymphocytes, began on the 4th day. By the 5th day only the splenic arteries and the surrounding reticular cells remained. Restoration of normal-appearing white pulp was completed by the 8th day. No correlation was noted between splenic lesions and intestinal lesions. Many stages in the development of typical intranuclear inclusions were observed.


Role of the bursa of Fabricius in the pathogenicity of inclusion body hepatitis and infectious bursal disease viruses.

Chickens were chemically bursectomized with cyclophosphamide at 3 days old, and studies made of the effects of infection by inclusion body hepatitis virus (IBHV) and infectious bursal disease virus. In another experiment, 3-week-old chickens were infected with infectious bursal disease virus before inoculation with IBHV. Interference with the bursa of Fabricius by cyclophosphamide or by infectious bursal disease virus enhanced the pathogenicity of IBHV. In contrast, cyclophosphamide effects on the bursa protected chickens against infectious bursal disease.


Serologic differences between strains of infectious bronchitis virus from New Zealand, Australia, and the United States.

The antigenic relationships of strains of infectious bronchitis virus from New Zealand, Australia, and the United States were evaluated by a virus-neutralization procedure similar to that used in typing human rhinoviruses. The four previously described New Zealand serotypes were antigenically distinct from all the other strains tested.


Electron-microscope studies on the pathogenesis of infectious bursal disease after intrabursal application of the causal virus.

Intrabursal application of infectious bursal disease virus (IBDV) is of advantage in studying sequential morphological events since the time of infection of the bursa is exactly known. A highly pathogenic strain caused first clinical symptoms 12 hr postinfection (PI) and death 24-30 hr PI. These are respectively 12 and 18 hr earlier than after per-oral infection. Numerous virus particles 53-58 nm in size, arrayed in a crystalline pattern and not surrounded by a membrane, are first found 6 hr PI in the cytoplasm of normal-looking lymphoid cells and macrophages. Some of the particles are less electron-dense and obviously immature; others have no core and therefore are regarded as incomplete. However, there is no evidence for the presence of more than one type of virus particle. Seven hr PI a membrane to segregate the virus clusters is formed, finally leading to autophagic vacuoles containing virus particles and cellular remnants. Within these vacuoles virus degradation takes part, though most of the infected cells, particularly the lymphoid cells, undergo cellular lysis, release the virions, and spread the infection to other cells of the bursa. At 18 hr PI the follicles are almost depleted of lymphoid cells. The findings show that early replication of IBDV is in the lymphoid cells and macrophages. These cells represent the main areas of virus multiplication, but the virions also can replicate in heterophils, reticulum cells, and reticular epithelial cells of the bursa.


Marek's disease vaccine breaks: differences in viremia of vaccinated chickens between those with and without Marek's disease.

Viremia with turkey herpesvirus (HVT) and/or Marek's disease (MD) herpesvirus (MDHV) was examined in chickens from three different commercial flocks experiencing "vaccine breaks" following vaccination with HVT vaccine against MD. In all groups of sample chickens from the flocks, the incidence of detectable HVT viremia was significantly less in the MD-affected than in the healthy penmates, and incidence of MD was significantly higher in the birds without detectable HVT viremia than in the viremic penmates. The results suggest an association between HVT viremia and protection against MD development.


Effect of infectious bursal agent on the response of chickens to Newcastle disease and Marek's disease vaccination.

White Leghorn chickens raised from one day old in an environment contaminated by the infectious bursal agent (IBA) had lower geometric mean titers (GMT) as measured by the hemagglutination-inhibition (HI) test to the Newcastle disease virus (NDV), than control Leghorns reared in an uncontaminated environment. Immunosuppression, defined as a reduction in GMT, was most pronounced at 35-56 days old for Leghorns vaccinated with NDV at 1 and 28 days or at 28 days. In a separate trial with broilers, immunosuppression was similar at 42-56 days old. This study also demonstrated that IBA infection in chickens increased susceptibility to Marek's disease (MD). The unvaccinated control chickens infected with IBA averaged 56.3% MD lesions, whereas unvaccinated controls not exposed to IBA averaged only 18.1% macroscopic lesions. It was also found that 20.7% of the HVT-vaccinated chickens exposed to IBA had gross MD lesions, whereas those HVT-vaccinated chickens reared in an environment free of IBA had 2.99% gross MD lesions.


Isolation of infectious bronchitis virus from broiler chickens in Chile.

An infectious-bronchitis-like virus was isolated from 6-week-old broiler chickens unvaccinated with infectious bronchitis virus (IBV). The isolate produced lesions in embryonating chicken eggs (ECE) and clinical signs in birds characteristic of IBV. Serum-neutralization and agar-gel diffusion tests demonstrated the serological relationship of this isolate to IBV.