Establishment of a C3Hf mammary tumor cell line expressing endogenous mouse mammary tumor virus: antigenic and genetic relationships of this virus with highly oncogenic mouse mammary tumor viruses.

A single-cell clone of C3Hf mammary tumor cells (clone 14) was developed into a continuous cell line expressing high levels of endogenous mouse mammary tumor virus (MMTV) with less than 0.1% murine leukemia virus expression. Comparison of the C3Hf MMTV protein profile on sodium dodecyl sulfatepolyacrylamide gel electrophoresis with that of C3H MMTV revealed that the protein content of the two viruses was quite similar. However, oligonucleotide fingerprints obtained of MMTV 70S RNA revealed that approximately 20% of the large oligonucleotides examined were unique to each virus. The oligonucleotide fingerprint indicated that although the viruses were similar, they differed in their genetic content. The differences in the two viruses extended to immunological differences in the major envelope glycoprotein, gp52. C3Hf MMTV competed only partially in a homologous radioimmunoassay for gp52 of C3H MMTV, whereas C3H MMTV gave complete competition, indicating that gp52 of C3H MMTV contained type-specific determinants not present on gp52 of C3Hf MMTV. Comparison of C3Hf MMTV with highly oncogenic C3H, GR, and RIII MMTVs in a homologous C3H MMTV gp52 assay gave two patterns of reactivity: complete competition by GR and C3H MMTV and incomplete competition by C3Hf and RIII MMTV. Absorption of anti-C3H MMTV serum by either C3Hf MMTV or RIII MMTV removed all antibodies against both viruses but not against GR and C3H MMTVs. These results indicate that C3H and GR MMTVs are more closely related to each other than to RIII and C3Hf MMTVs.


Correlation between Epstein-Barr virus membrane antigen and three large cell surface glycoproteins.

A correlation between Epstein-Barr virus membrane antigen (MA) and three surface glycoproteins has been established on the basis of radio-immunoprecipitation and immunoabsorption experiments. For radio-immunoprecipitation, Epstein-Barr virus-infected cells were radiolabeled either with neuraminidase-galactose oxidase tritiated borohydride, a procedure highly specific for surface glycoproteins, or with a general tritiated amino acid mixture. Intact cells were incubated with MA(-) or MA(+) human sera, washed free of unbound immunoglobulins, and then lysed with Nonidet P-40. The antigen-antibody complexes were bound to protein A-Sepharose and after elution with sodium dodecyl sulfate were analyzed by acrylamide gel electrophoresis in sodium dodecyl sulfate. MA(+) sera specifically precipitated three glycoproteins with molecular weights of 236,000, 212,000, and 141,000 from B95-8 cells induced with 12-O-tetradecanoylphorbal-13-acetate (TPA) and from Raji cells superinfected with P3HR-1 virus. These glycoproteins were not detected on Epstein-Barr virus-negative Ramos cells treated with TPA or on B95-8 cells treated simultaneously with TPA and phosphonoacetic acid. Soybean lectin-Sepharose bound all three glycoproteins, and lectin-Sepharose-bound glycoproteins from TPA-induced P95-8 cells absorbed MA-specific antibody from MA(+) human sera. The data strongly suggest that either all three glycoproteins have MA determinants or they are part of a complex in which one or more of the components constitute the reactive antigen.


Single dose whole pelvis megavoltage irradiation for palliative control of hematuria or ureteral obstruction.

Of 7 patients with bladder carcinoma whose medical condition or disease status prevented an operation 5 had intractable vesical hemorrhage and 2 had progressive azotemia caused by ureteral obstruction. These patients were treated with pelvic irradiation of 1,000 rad single doses. Four patients received 3 doses 3 to 4 weeks apart and 1 patient received 2 doses at a 4-week interval. Prompt cessation of bleeding occurred in all patients and renal function improved in the 2 patients with ureteral obstruction.


Search for specificity in natural cell-mediated cytotoxicity.

Differences in antigenicity between the human osteosarcoma cell line TE 85/B and its feline sarcoma virus-infected subline NIH E1041 were detected by competitive inhibition of natural cell-mediated cytotoxicity (NCMC). Whether the differences could be attributed to the viral infection was investigated by absorption and elution studies of antibodies that determine the specificity of NCMC against the cell lines. Antibodies from the serum of healthy individuals were first absorbed onto target cells against which they were to be tested and then eluted to provide antibodies putatively specific for the target cells. Trypsin-treated effector cells were restored with the absorbed serum or eluted antibodies and tested against TE 85/B and its intentionally infected sublines. The differences observed previously between TE 85/B and NIH E1041 were extended to the detection of small differences in antigenicity among all sublines. Separately maintained sublines from the same culture became antigenically different with continuous passage. The causes for these specific changes were unknown, but a role for the control of these antigens by NCMC was suggested. Differences in antigenicity between virus-infected sublines cultured separately need not be related to the virus infection.


Species cross-reacting epithelial and urothelial specific antigens in human fetal, adult, and neoplastic bladder epithelium.

Antiserum from a New Zealand White rabbit was raised against the saline-soluble fraction of homogenates of calf urinary bladder epithelium. After absorption, with human red blood cells, human, calf, and mouse sera, and nonepithelial organs, this antiserum was specific for all human epithelia tested. Further absorptions with nonurinary tract epithelia rendered the antiserum specific for urothelium. Species cross-reactivity was seen between the superficial cell layers of calf, human fetal, and adult bladder epithelia. The antigen appeared to be cytoplasmic and was also present (although to a lesser extent) in human bladder tumor biopsy specimens and human bladder tumor cell lines.


Primary human breast carcinomas transplantable in the nude mouse.

Of 19 primary human breast carcinomas implanted into noninbred female nude mice, 3 produced transplantable tumors. Membrane components specific for human mammary epithelial cells were demonstrated in the cells from heterotransplants even after four or five passages in nude mice.


Isolation of polyomavirus-induced surface antigens of mouse cells: affinity chromatography and biologic activities.

Tumor-specific transplantation antigen (TSTA) and polyomavirus-induced tumor-associated surface antigen (TASA) were isolated from polyomavirus-transformed BALB/c mouse cells with the use of 3-M KCl solubilization and affinity chromatography on antibody-coated Sepharose 4B. Particular conditions were chosen for removal of the nonspecifically bound proteins from the gel. Under these conditions, the ratio between the amounts of crude extract and specifically bound proteins giving the same TASA activity was about 5,000. Mice inoculated with this material were protected against tumor challenge. We therefore assume that TSTA is a part of TASA. Furthermore, these antigens can be dissociated from the major histocompatibility antigens.


Transplantable argyrophilic gastric carcinoid of Mastomys natalensis secreting both histamine and serotonin.

A transplantable strain of gastric carcinoids of Mastomys (Praomys) natalensis secreted not only histamine but also serotonin [5-hydroxytryptamine (5-HT)]. Mastomys bearing growing transplants excreted 11.3 times more histamine and 4.4 times more 5-hydroxyindole-3-acetic acid (5-HIAA) in the urine than did Mastomys in which transplanted tumors did not grow. Mastomys that developed primary gastric carcinoids also excreted 3.9 times more histamine than did those free from primary tumors, but the difference in urinary excretion of 5-HIAA was not significant in both groups. All transplantable carcinoids contained definite amounts of both histamine and serotonin, whereas the primary gastric carcinoids contained only histamine. We also confirmed that the histamine and 5-HIAA excreted in urine increased as the size of transplanted tumors enlarged. 5-HT was histochemically demonstrated in a small number of carcinoid cells of the transplanted tumors but not in primary carcinoids.


[Sudden death in myocardial infarct, its precursors and the problems of prevention].

Continuous magnetic tape recording of the ECG made it possible to reveal ventricular extrasystoles in 99% of patients with uncomplicated myocardial infarction and extrasystoles, regarded as the precursors of ventricular fibrillation, in 95%. Treatment with lipocaine or trimecaine (103 persons) reduced the frequency of the development of complex gradation of ventricular extrasystoles as compared to a random control group (106 persons). A considerable decrease was also noted in the number of cases with primary ventricular fibrillation in the group of patients treated with antiarrhythmic drugs. Ventricular fibrillation occurred in 3 patients of the experimental group and in 8 patients in the comparison group.


[Preliminary clinical experiences with adenine arabinoside monophosphate (ARA-AMP) in encephalitis due to viruses of the herpes group and varicella/zoster infections (author's transl)].

Adenine arabinoside monophosphate (ARA-AMP) is a new antiviral agent with significant activity against DNA viruses of the herpes group. It appears to be superior to cytosine arabinoside and iodoxuridine in severe herpes simplex infections. Unlike cytosine arabinoside and idoxuridine ARA-AMP has only minimal myelosuppressive and immunosuppressive properties. The original compound, adenine arabinoside (ARA-A) which has been used in the United States in the last years had the disadvantage of poor solubility and tissue penetrance. Compared to adenine arabinoside the monophosphate ester of this compound has the advantage of better solubility and is more slowly metabolized in humans. In eight children with virus induced encephalitis ARA-AMP was well tolerated, we could not observe any severe side effects. A case of herpes simplex encephalitis showed a complete recovery. However it has to be pointed out that in herpes simplex encephalitis ARA-AMP should be given early in the course of infection to have a beneficial effect, therefore an early diagnosis is of utmost importance. A case of generalized herpes zoster healed up within about a week. Of course these are very preliminary results which must be confirmed by further experiences.


Solid-phase radioimmunoassay for hepatitis Be antigen (HBeAg).

A solid-phase radioimmunoassay was developed for the detection of HBeAg and anti-HBe in sera or serum fractions. HBe/sAg positive sera, partially purified HBeAg, partially purified HBsAg, and HBe/sAg negative sera were polymerized in polyacrylamide and compared for their ability to bind 125I-IgG (anti-HBe). Only gels containing HBeAg reacted specifically with the iodinated antibody. The specificity of the binding was confirmed by blocking and inhibition tests using anti-HBe, HBeAg, HBsAg, and negative control sera. The radioimmunoassay allows the specific and quantitative detection of HBeAg and anti-HBe even in the presence of detergents and high salt concentrations.


Serum electrophoretic patterns of karyotypically defined owl monkeys (Aotus trivirgatus).

Sera were electrophoretically separated and examined from 238 karyotyped Aotus trivirgatus and 29 unkaryotyped offspring. Albumin polymorphism was observed with high frequency and found to conform to a codominant allele mode of transmission. A unique alpha globulin was identified in Karyotypes I, VII and unkaryotyped offspring, of which one parent was a Karyotype I. This alpha globulin phenotype appears to be a dominant characteristic.


The pathology of the Mongolian Gerbil (Meriones unguiculatus): a review.

Both naturally occurring disease processes and experimental models of human disease in the Mongolian gerbil were reviewed. The gerbil was highly susceptible to cerebral infarction following unilateral ligation of one common carotid artery and was useful in studies of the pathogenesis of stroke. Spontaneous epileptiform seizures mimicked those of human idiopathic epilepsy, and both seizure-sensitive and resistant strains have been bred. Perhaps because of its more efficient nephron, the gerbil accumulated four to six times as much renal lead as the rat, and the gerbil has been proposed as an experimental model of lead nephropathy. On standard diets, about 10% of the animals became obese, and some showed decreased glucose tolerance, elevated serum immunoreactive insulin and diabetic changes in the pancreas and other organs. Some breeders exhibited hyperactivity of the adrenal cortex associated with hyperglycemia, hyperlipidemia and degenerative vascular disease. Although dietary supplements of cholesterol were toxic and did not induce atherosclerosis, the gerbil was useful in other studies of cholesterol absorption and metabolism. Spontaneous, insidious periodontal disease became evident after about 6 months on standard diets, and dental caries were induced by cariogenic diets or by pathodontic streptococci. Spontaneous neoplasia occurred in 8.4--24% of gerbils, usually after 2 years of life. Adrenal cortical, ovarian and cutaneous tumors were the most consistently reported neoplasms.


Benign prostatic hyperplasia in a squirrel monkey (Saimiri sciureus).

Benign prostatic hyperplasia was diagnosed at necropsy in a middle-aged squirrel monkey (Saimiri sciureus). Grossly, the prostate gland was asymmetrically enlarged and had an irregular surface. Microscopically, both cystic glandular hyperplasia and fibromuscular, nodular hyperplasia were identified.


The effects of early auditory deprivation on temporal perceptions: a comparison of hearing and hearing-impaired children on temporal pattern matching tasks.

This study was designed to test the hypothesis that hearing children, but not children deprived of early auditory experiences, would use an auditory frame of reference, or auditory encoding, for temporal perceptions. Two age groups (8 and 11 years of age) of hearing and hearing-impaired children were tested in two sessions; tasks required each child to decide whether two temporal patterns (sequences of lights, sounds or both) were the same or different. Specific trial-types were designed to reveal different patterns of performances (across trial-types) for children who differed in terms of whether an auditory frame of reference was used. The results suggested that all children used similar temporal frames of reference, but that hearing-impaired children demonstrated developmental lags.


The accessibility of antigenic determinants of ribosomal protein S4 in situ.

Antibodies to Escherichia coli ribosomal protein S4 react with S4 in subribosomal particles, eg, the complex of 16S RNA with S4, S7, S8, S15, S16, S17, and S19 and the RI reconstitution intermediate, but they do not react with intact 30S subunits. Antibodies were isolated by three different methods from antisera obtained during the immunization of eight rabbits. Some of these antibody preparations, which contained contaminant antibodies directed against other ribosomal proteins, reacted with subunits, but this reaction was not affected by removal of the anti-S4 antibody population. Other antibody preparations did not react with subunits. It is concluded that the antigenic determinants of S4 are accessible in some protein deficient subribosomal particles but not in intact 30S subunits.


Instability of cerebral blood-flow in insulin-dependent diabetics.

Cerebral blood-flow (CBF) was measured in 23 insulin-dependent diabetics before and 2--3 h after insulin/breakfast. In 10 of these patients CBF changed significantly during the day, with a significant fall in 9. In 3 patients who had the greatest falls in CBF there was a concomitant sensation of an impending faint. Thus CBF is unstable in insulin-dependent diabetics in contrast to control subjects in who there is little or no variation. Sudden falls in CBF in insulin-dependent diabetics may explain the symptoms of impending faint without hypoglycaemia; such falls would also be relevant to the pathogenesis of strokes in these patients.


Emergence of trimethoprim-resistant enterobacteria in patients receiving long-term co-trimoxazole for the control of intractable urinary-tract infection.

In patients with previously intractable urinary-tract infection treated with low-dose co-trimoxazole for 6--58 (mean 32.7) months, the percentage of infected urines fell from 41.4 before treatment to 6.3 during treatment. Only 6 episodes of infection were due to trimethoprim-resistant bacteria. Results in a small group of patients in whom treatment was continued with trimethoprim alone were similar. Under the conditions of this study, long-term control of urinary-tract infection was not materially compromised by breakthrough infections due to trimethoprim-resistant organisms.


Oral rehydration of neonates with dehydrating diarrhoeas.

Thirty-nine of forty neonates with mean dehydration equivalent to 6.7% of body-weight were orally rehydrated with a glucose/electrolyte solution. Only one patient required any intravenous fluids for rehydration. Hypernatraemia and acidosis present at admission were corrected within a few hours without complications. It seems that oral rehydration, is suitable for neonates as well as for children and adults.


Raised maternal serum-alpha-fetoprotein levels and spontaneous fetomaternal transfusion.

Study of blood smears showed that spontaneous fetomaternal transfusions were significantly more common among 42 pregnant women with raised serum-alpha-fetoprotein (AFP) levels than among 45 pregnant women with normal serum-AFP levels. Raised serum-AFP was associated with a spontaneous fetomaternal transfusion of greater than or equal to 0.1 ml in at least 21 of the 42 women in the study group.


Efficacy of immune plasma in treatment of Argentine haemorrhagic fever and association between treatment and a late neurological syndrome.

In a double-blind trial patients with Argentine haemorrhagic fever treated with immune plasma within 8 days of the onset of the disease had a much lower mortality than those given normal plasma. Some patients treated with immune plasma developed late neurological complications.


Sensitive trypsin assay for dried-blood specimens as a screening procedure for early detection of cystic fibrosis.

An immunoreactive-trypsin assay uses small dried-blood spots (diameter 1.25 mm) and is therefore suitable for incorporation in established neonatal screening schemes. Blood specimens from neonates with cystic fibrosis had trypsin levels greater than those in control subjects, thus confirming earlier findings. Trypsin levels were below normal in several older patients with cystic fibrosis.


Prematurity.

Perinatal epidemiologists no longer speak much of "prematurity". Instead the World Health Organization recommends that infants born before 37 completed weeks of gestation should be designated "preterm" and those of birthweight less than 2500 g "low birthweight". Both definitions have obvious drawbacks--the former because menstrual dates are often unknown or unreliable, the latter because it does not separate preterm from small-for-gestational-age infants. Whatever the classification of these small infants there is no dispute about their high mortality and morbidity; in the United Kingdom they account for over two-thirds of first-week deaths.


Aspirin and secondary mortality after myocardial infarction.

A randomised controlled double-blind trial of aspirin in the prevention of death was conducted in 1682 patients (including 248 women) who had had a confirmed myocardial infarct (MI). 25% of the patients were admitted to the trial within 3 days of the infarction and 50% within 7 days. Aspirin, 300 mg three times daily, was given for 1 yr. Total mortality was 12.3% in patients given aspirin and 14.8% in those given placebo, a reduction by aspirin of 17%, which was not statistically significant at p less than 0.05. The reduction in specific ischaemic-heart-disease (IHD) mortality was 22% and in total mortality plus IHD morbidity (readmission to hospital for MI in survivors) was 28%.


Paroxysmal nocturnal dyspnoea and periodic respiration.

Patterns of breathing at night were recorded in 4 patients with heart-failure. 2 had periodic breathing while awake and in 2 it developed after they fell asleep. In all 4 the phase of hyperventilation disturbed sleep. These cases also illustrate other problems caused by periodic respiration in heart-failure, which range from tiredness during the day to an inability to sleep for more than a few minutes. Nocturnal waking in the hyperventilation phase of Cheyne-Stokes breathing should be differentiated from paroxysmal nocturnal dyspnoea caused by episodes of pulmonary oedema at night.


Comparison of hormonal and metabolic effects of salbutamol infusion in normal subjects and insulin-requiring diabetics.

A comparison of the metabolic effects of salbutamol in diabetic patients and normal subjects showed that salbutamol infused at 5 and 2 microgram/min (a) stimulated hepatic glucose production to a greater extent in diabetic patients than in normal subjects despite prior restoration of the diabetic patients' fasting blood glucose to normal by an overnight infusion of insulin; (b) caused a greater rise in plasma glucose, free fatty acids, glycerol, and ketone-body concentrations in the diabetic patients; and (c) produced a marked fall in plasma-potassium concentrations. The differences between the diabetic and normal groups were accounted for by an immediate (six-fold) stimulation of insulin secretion in the normal subjects.


Abnormal small-bowel motility demonstrated by radiotelemetry in a patient with irritable colon.

Jejunal motility was recorded for 47 h by telemetry from a tethered ingested radio-pill in a patient with irritable colon. In fasted controls, motor complexes are as frequent at night as during the day; the patient with irritable colon had a pronounced reduction in complexes when awake. Two prolonged episodes of pain were associated with irregular contractile activity, and ended when cyclical interdigestive activity resumed. This study suggests that irritable colon may be a disorder affecting the upper digestive tract.


Endogenous cell-mediated immunity, blood transfusion, and outcome of renal transplantation.

The cell-mediated immunity (CMI) of a group of patients on regular dialysis was measured by a quantitative dinitrochlorobenzene (DNCB) skin test, the reaction being graded 0--15. The score in these patients varied widely, although the mean was much lower than that occurring in a group of 15 healthy subjects. 55 cadaveric renal allografts were subsequently done in 51 of these patients, and graft survival was assessed at 6 months. The 39 patients with weak DNCB skin reactions had a much higher graft survival (71%) than did the 12 with strong reaction (15%) (p less than 0.01). The weak DNCB reactors also had more pre-transplant blood transfusions. The findings suggest that the CMI of the recipient as measured by the DNCB test has an important influence on subsequent graft survival. This influence may partly be related to pre-transplant blood transfusion.


Bone density in ageing Caucasian and African populations.

Fracture surveys in the Johannesburg metropolitan area showed that the rate of femoral-neck fractures rose sharply after the climacteric in Caucasians, whereas the incidence of such fractures in African Negroes of the same age was almost negligible. However, a parallel epidemiological survey of metacarpal bone density in random samples of the same populations showed that absolute values for skeletal mass and bone density were greater in the Caucasians through most of the age-range from 5 to 75 years. Also, although bone density increased more rapidly and reached higher maximum values in young Caucasians than in Africans, it fell more rapidly in the former from the fourth decade onwards. The differences in the pattern of bone density alone are unlikely to account for the large difference in the fracture rates in the two populations. Perhaps quantitative changes in bone mass associated with ageing are accompanied by qualitative changes which may be critical in determining the liability to fracture.


Bronchial provocation studies in farmers allergic to storage mites.

In an investigation of the relationship between storage mites and symptoms of allergic respiratory disease in farmers exposed to hay and grain dust, the clinical responses suggested an immediate type-I hypersensitivity. This study confirmed that farmers are exposed to large numbers of mites, particularly while feeding cattle. Storage mites may be an important cause of asthma in the farming community and should also be considered in the differential diagnosis of farmers lung.


Significance in neonatal myasthenia gravis of inhibitory effect of amniotic fluid on binding of antibodies to acetylcholine receptor.

The effect of amniotic fluid on the binding of anti-acetylcholine receptor (anti-AChR) antibodies from myasthenia gravis (MG) patients to AChR preparations was examined by radioimmunoassay using 125I-labelled alpha-bungarotoxin. Human amniotic fluid from healthy women in their second trimester inhibited the in-vitro interaction between antibody and antigen. This finding suggests that during pregnancy there is a similar inhibitory effect in MG on the in-vivo binding of maternal anti-AChR antibodies, transferred through the placenta, to AChR at the fetal neuromuscular junction. The presence of feto-placental inhibitory factors may explain the development of transitory muscular weakness only after birth and only in the minority of the babies born to myasthenic mothers.


1,25-dihydroxyvitamin-D-receptor in breast cancer cells.

A specific receptor for 1,25-dihydroxyvitamin D has been demonstrated in a cultured human breast cancer cell line. This is the first such demonstration in any cancer cell. It may explain the high incidence of metastatic bone destruction and hypercalcaemia in this common malignancy, and the limited success of other steroid-receptor assays in predicting the response of breast cancer to therapy.


Dietary fats and coronary heart disease: unfinished business.

In the scientific and lay press, dietary recommendations that are aimed at prevention of coronary heart disease in the general public are appearing more and more frequently. The dietary pattern that is now most widely advocated is a low-fat, low cholesterol diet with a polyunsaturated/saturated ratio of 1. The argument for such a dietary change is supported mainly by extrapolations from epidemiological data and from animal experimentation. Reasons are given for concluding that the recommendations are unwise, impractical, and unlikely to lead to a reduced incidence of arteriosclerotic disease. Sinc complacency is equally inappropriate, a few practical questions are outlined that should be settled before the public is assured that a low-fat diet will lead to a reduced risk of coronary heart disease.


Reliability of assessment of alcohol intake based on personal interviews in a liver clinic.

In 37 patients with alcoholic liver disease urinary alcohol was measured daily for up to 6 months. Every week the patients were asked about their drinking during the past week. Those who convinced the physicians of their abstinence were recorded as not drinking. Patients with alcohol in their urines convincingly denied alcohol intake 52% of the times that they were questioned. 25% of them denied drinking every time. Only 17% of all patients admitted it at all times. Patients who always admitted to drinking had an average urinary alcohol value of 1420 +/- 66 mg/l, compared to 81 +/- 5 mg/l in those who denied drinking every time. Those who admitted drinking intermittently had significantly higher urinary alcohol values (1001 +/- 57 mg/l) when admitting than when denying (538 +/- mg/l). The personal interview should not be used to separate populations of abstainers and non-abstainers in the follow-up of alcoholic patients. On the other hand, deniers appear to consume less alcohol than those who admit their drinking.


Sequential combination chemotherapy for advanced squamous cell carcinoma of the head and neck.

Thirty-four patients with advanced squamous cell carcinoma of the head and neck have been treated with sequential combination chemotherapy consisting of Cytoxan, methotrexate, oncovin, bleomycin and adriamycin, followed by Leucovorin (COMBAL). All patients had undergone extensive prior radiation and/or surgery. All the patients had recurrent cancer. Toxicity included two deaths from drug induced pancytophenia and one from sepsis. Treatment was well tolerated and could be given in the outpatient clinic. No bleomycin pulmonary or adriamycin cardiac toxicity was seen. Results include 4 patients who achieved complete remission, objective improvement in measurable lesions in 6 others, stabilization of disease for 1 to 3 mo. in 5, and progression of disease in 13. Survival has ranged from 1 to 19+ months with a median of 10.7 mo. for patients that were evaluated. We conclude that COMBAL produces objective evidence of improvement in approximately 45% of patients with far advanced, previously treated squamous cell carcinoma of the head and neck.


Ultrastructure and partial characterization of a regular array in the cell wall of Lactobacillus brevis.

The cell wall of Lactobacillus brevis was revealed by electron microscopy to have an outer layer composed of a regular array. The morphological unit of the regular array appeared to consist of four spherical subunits, each about 2 nm in diameter, which were arranged in a tetragonal pattern about 4.5 by 7.0 nm in dimension. The regular array was composed of the tetragonal units in rows in two directions at an angle of about 75 degrees to each other. The average spacing between the rows was about 10 nm in one direction and about 7 nm in the other. The tetragonally arranged subunits were removed from the cell wall by treatment with guanidine hydrochloride, urea, or sodium dodecyl sulfate (SDS) but not by the action of ethylenediaminetetraacetate, nonionic detergents, or proteolytic enzymes except pepsin. The regular subunits were shown to be composed of a protein with a molecular weight of about 51,000 by SDS-polyacrylamide gel electrophoresis.


The pathogenesis of osteoarthrosis.

Recent investigations on protease inhibitors in articular cartilage have provided new insights into the possible initial lesions of osteoarthrosis. A hypothesis has been formulated based upon an impaired ability of chondrocytes to synthesize protease inhibitors, which leads to loss of matrix integrity and vascular invasion from subchondral bone and the joint margins.


Oleander poisoning.

The two common oleanders, Thevetia peruviana and Nerium oleander, contain a mixture of poisons including cardiac glycosides, and are extremely toxic. They are cultivated universally throughout Australia, and rank equally with mushrooms as the major cause of children's admission to hospital after accidental plant ingestions. A seven-year total population survey from south-east Queensland has revealed that, in practice, the rate of clinical poisoning due to oleander is inconsequential, and mortality is negligible. The annual age-specific admission rate for children (aged from birth to 12 years of age), for all plant ingestions is 2.33 per 100 000, and 0.62 per 100 000 specifically for oleander. Oleander ingestion causes a syndrome of combine cardiac and gastrointestinal symptoms and signs. A case series of 13 children is described, and the clinical features summarized. After accidental oleander ingestion, current experience indicates that the prognosis is excellent.


The repair of bleomycin-induced DNA damage and its relationship to chromosome aberration repair.

Previous studies using the technique of premature chromosome condensation indicated that nearly one-half of the bleomycin-induced chromatid breaks and gaps in CHO cells could be repaired within 1 h (repair starting at 30 min) after treatment. Cycloheximide and streptovitacin A (but not hydroxyurea or hycanthone) inhibited chromosome repair. The purpose of this study was to measure the kinetics of DNA repair after bleomycin treatment using the alkaline elution technique and to determine whether various inhibitors could block this repair. After bleomycin treatment, the major proportion of the repair of DNA damage occurred within 15 min, with significant repair evident by 2 min. This fast repair component was inhibited by 0.2% EDTA. A slower repair component was observed to occur up to 60 min after bleomycin treatment. None of the inhibitors tested were found to have a significant effect on the repair of bleomycin damage at the DNA level. Since chromosome breaks were observed not to begin repair until after 30 min while over 50% of the DNA was repaired by 15 min, these results suggest that the DNA lesions that are repaired quickly are not important in the formation of chromosome aberrations. Further, since cycloheximide and streptovitacin A blocked chromosome repair but had little measurable effect on DNA repair, these results suggest that the DNA lesions responsible for chromosome damage represent only a small proportion of the total DNA lesions produced by bleomycin.


Non-mutagenicity for Salmonella of the chlorinated hydrocarbons aroclor 1254, 1,2,4-trichlorobenzene, mirex and kepone.

A polychlorinated biphenyl mixture, Aroclor 1254, two commercial grade insecticides, mirex and kepone, and a pesticide breakdown product, 1,2,4-trichlorobenzene were evaluated for mutagenicity and hepatic enzyme induction potential in the Salmonella/microsomal assay. None was found to revert strains TA1535, TA1537, TA98 or TA100 when tested with or without metabolic activation. Liver microsomal extracts (S9) from rats induced with 1,2,4-trichlorobenzene were shown to differ from S9 of either control or Aroclor 1254-induced rats in the capacity to activate 2-aminoanthracene mutagenesis.


Ionomycin stimulates mast cell histamine secretion by forming a lipid-soluble calcium complex.

The activation of cellular function following the direct introduction of Ca2+ into the cytosol by the use of a Ca2+-transporting ionophore has served to confirm the widely held idea that Ca2+ has the status of a second messenger in many cell types. However, this evidence has been obtained largely from the use of a single ionophore, the antibiotic A23187; experiments with X537A, which is another ionophorous antibiotic capable of transporting Ca2+ (ref. 3), have failed to show the expected characteristics. For example, histamine release from rat mast cells mediated by X537A is neither dependent on extracellular Ca2+ nor prevented by metabolic inhibitors. Ionomycin is a recently described polyether antibiotic produced by Streptomyces conglobatus ATCC 31005, and is active against Gram-positive bacteria. The antibiotic action is presumably due to its ionophorous properties, as it extracts Ca2+ from an aqueous phase into an organic phase with a stoichiometry of 1:1 (ref. 6). The ionophore is also capable of transporting 45Ca2+ across biological membranes (our unpublished results). Here we report the application of ionomycin to rat mast cells. We show that ionomycin stimulates mast cell secretion solely through its ability to form a lipid-soluble calcium complex, and thus to convey Ca2+ across the hydrocarbon region of the cell membrane.


[Levels of complement and its various fractions in the blood of patients with Horton's headache. Preliminary report].

The pathogenesis of cluster headache remains unexplained and the immunological mechanisms have not been studied in this disease. Suspecting a possible allergic character of headache attacks it was decided to determine the haemolytic activity of the complement system and the levels of its C3 and C4 components. The investigations were carried out in 11 patients with cluster headache and in 10 patients with neurotic symptoms who served as controls. It was found that the levels of complement and its C4 fraction were not different in both groups but the level of C3 fraction showed a statistically significant difference. The authors discuss the obtained results and postulate continuation of investigations.


Uptake and retrograde axonal transport of horseradish peroxidase in normal and axotomized motor neurons during postnatal development.

The axonal uptake and somatopetal transport of horseradish peroxidase (HRP) was studied during early postnatal development of facial neurons in mice and rats. HRP injected systemically or locally into the muscles of the vibrissae, diffused into the region of the immature neuromuscular junction and was incorporated into vesicles in the axon terminals on the first and third postnatal days, at a time when synaptic vesicles were already present. HRP later was found in the nerve cell bodies of the facial nucleus in the brain stem indicating a somatopetal transport of the tracer in axons. The response of facial neurons to nerve transection changed from rapid neuronal death to prolonged survival between the 6th and 10th postnatal day. HRP was transferred to nerve cell bodies after topical application to the proximal stump of transected facial nerves in rats 3 days-of-age. In the perikaryon it was localized to vesicles and vacuoles with no signs of leakage into the cytoplasm. In the light of our findings different hypotheses for the mechanism of the neuronal death in the immature animals are discussed.


Influence of cholinergic agents on dopamine release from medial basal hypothalamus.

The ability of acetylcholine to influence the stimulation-induced release of [3H]dopamine in medial basal hypothalamus was evaluated. A muscarinic facilitation of electrical field-stimulated but not potassium-stimulated release was observed. These data suggest a muscarinic enhancement of dopamine release perhaps via an action at the level of the cell body. These data suggest that observed effects of cholinergic agents on prolactin release may be mediated in part through such a cholinergic-dopaminergic interaction.


Myelin basic protein depolarizes neuronal membranes.

Bath application of 10(-5) M myelin basic protein (MBP) to various types of cultured nerve cells resulted in a membrane depolarization amounting to a change of 41 +/- 15 mV. Excitability could be restored by repolarizing the membrane by means of current injection through the recording electrode. The action of MBP persisted in the presence of tetrodotoxin (TTX), Co2+ or D-600 as well as in low Na+ and low Cl- solutions, whereas it was abolished by increasing extracellular Ca2+ concentrations. The action MBP was mimicked by ouabain. We propose that the effect of the protein might be generated by blockade of an ion pump. It is speculated that MBP may exert a direct effect on neuronal membranes in demyelinating diseases.


Cytomegalovirus strain differentiation by DNA restriction analysis.

The heterogeneity of CMV DNA obtained from standard strains and new isolates, including a vaccination strain (Towne 125), was investigated. The cleavage patterns produced by the restriction endonucleases Eco RI and Bam 1 revealed stable strain specificities of CMV. On the other hand, a remarkable homology of sequence-specific CMV DNA fragmentation was demonstrated. A CMV subtyping relevant to clinical questions seems to be improbable.


Oncornavirus-like particles released by human prostatic explant cultures.

Explant cultures from several human prostatic tissues have been examined for oncornavirus production. Some of these explants, epithelial in morphology, appear to release oncornavirus-like particles. The extracellular particulate material, obtained from the culture medium of these explants display the following characteristics: (1) It contains particles that band at a density of 1.1-1.2 g/cm3 in a sucrose density gradient. (2) The particles contain RNA-directed DNA polymerase. This polymerase utilizes poly(Cm) as a template and shows preference for poly(A) over poly(dA) and manganese over magnesium. (3) Apparently, the particles also contain RNA that directs the synthesis of DNA in vitro. The DNA thus synthesized is associated with RNA, some of it with high molecular weight RNA. Such particles are not observed in the culture medium from monolayers of monkey kidney CV-1 cells. We have found that explant cultures from 5 out of 15 tissue specimens with prostatic hyperplasia and 3 out of 4 with prostatic adenocarcinoma release particles that band at a density of 1.1-1.2 g/cm3 and contain RNA-directed DNA polymerase. Explant cultures of two normal prostates examined did not release such particles.


The antigen-specific signal in T-lymphocyte activation by alloantigen.

Current concepts of the mechanism of alloactivation of cytotoxic lymphocytes and the identity of the target cell determinants with which they interact are reviewed. The results of a quantitative analysis of the stimulatory activity of different forms of antigen and the role of a costimulator factor are presented. These lead to the conclusions that SD antigens are not the target cell antigens and that existing theories of cytotoxic T cell activation are inadequate. A new theory of activation of alloareactive cytotoxic lymphocytes is proposed.


Terminal care: evaluation of in-patient service at St Christopher's Hospice. Part I. Views of surviving spouse on effects of the service on the patient.

The surviving spouses of 34 patients who died of cancer at St Christopher's Hospice have been interviewed about 13 months after the patient's death. The information given is compared with that obtained from 34 spouses of patients dying from cancer in other hospitals and matched with the St Christopher's group. Patients at St Christopher's were less often thought to have suffered severe pain and other distress than at other hospitals, but pain relief was not bought at the cost of drug-induced confusion and patients at St Christopher's remained more mobile than at other hospitals. Hospice patients were more aware of chapel services and prayers than at other hospitals. None was said to have been upset by these and 66% were glad of them. Despite the frequency of deaths in the Hospice, patients at St Christopher's were no more likely to be thought to have been 'upset' by such events than patients elsewhere or to have found their interactions with other patients anything but helpful.


Assessment of the quality of sitting and gait patterns in children with Down's syndrome.

Clinical work with children with Down's syndrome resulted in a suggestion of a relationship between the external rotation and abduction of their hips, their excessive hip mobility in sitting, and their wide-based gait. This relationship was examined using data from 104 questionnaires completed by the parents of children with Down's syndrome. The clinical and demographic findings consistently documented the unusual sitting patterns of these children. How children were placed in the sitting position significantly influenced subsequent come-to-sit patterns but did not appear to influence subsequent walking patterns. Longitudinal studies of sitting patterns, hip mobility and gait are recommended. Therapeutic implications are that body rotation should be incorporated into motor intervention programs for children with Down's syndrome.


Correlation of the macrogram and the microgram of the penicillin focus in turtle (Testudo) cerebral cortex. Localization of the capillary microelectrode tip with Pontamine Sky Blue 6BX.

Localization of the tip of the recording microelectrode with Pontamine Sky Blue 6BX introduced into the tissue iontophoretically was used to study the relationship of the morphological type of the neurone to a given type of elecrographic activity during the epileptic focal discharge. Paroxysmal depolarization shifts (PDSs) and short bursts of spikes in the negative phase of the focal discharge were found to be related to cells of the pyramidal type. Conversely, ovoid cells were active only in quiescent intervals and were inhibited throughout the whole duration of the focal discharge.


Is schizophrenia an HLA-associated disease?

Certain specificities of the human leukocyte antigen (HLA) system have been shown to be associated with particular diseases. A review of recent studies in schizophrenia shows inconsistent results for schizophrenia as a whole, although a significant increase in HLA A28 remains on combining the data. There are more consistent findings for disease subtypes. In particular, HLA A9 and HLA CW4 are increased in paranoid schizophrenics, while HLA A1 and the A1-B8 haplotype are increased in nuclear forms. It is postulated that the relationship between the schizophrenias and certain HLA types could be due to an influence of the latter upon neuronal post-synaptic membrane sensitivity to central neurotransmitters such as dopamine.


Osmiophilic reagents in electronmicroscopic histocytochemistry.

Direct histocytochemical staining methods on undisrupted tissues, stabilized by chemical fixation, potentially offer perhaps the most reliable approach to the study of the enzymes of the cell with relation to its ultrastructure. The atoms which, for the most part, comprise the biomacromolecules and enzymes of cells and tissues contribute little to their inherent electron opacity or ability to scatter electrons differentially. The latter property of a substance is responsible for its observation with the electron microscope. Since the introduction of osmiophilic reagents into cytochemistry (HANKER et al. 1964), the selective deposition of relatively large amounts of polymeric osmium black reaction products at the subcellular sites of insoluble or immobilized enzymes or biomacromolecules has facilitated their demonstration with the light and electron microscopes. Perhaps the most widely employed osmiophilic reagent in histocytochemistry has been DAB which was introduced by GRAHAM and KARNOVSKY (1966a, b). Although it receives its widest use for demonstrating the sites to which the exogenous ultrastructural tracer horseradish peroxidase (HRP) is transported in vertebrate tissues, it is also widely employed for the demonstration of catalase in peroxisomes with the media of FAHIMI (1969) or of NOVIKOFF and GOLDFISCHER (1969), and for the demonstration of cytochrome oxidase with the medium of SELIGMAN et al. (1968a). The importance of this reagent lies in its ability to undergo oxidative polymerization forming an insoluble osmiophilic melanin-like product (HANKER et al. 1972a) which comforms well to ultrastructure, at the sites of enzymic or nonenzyme proteins which catalyze its oxidation. In the past few years, studies in our laboratory have shown that a rational approach to the histocytochemical demonstration of enzymes could be devised. It is based on the selective deposition of transition metal compounds at the sites of enzymes that resemble hemoproteins in their ability to catalyze the oxidative polymerization of DAB. The most useful of these compounds, cupric ferrocyanide (Hatchett's brown) was also introduced into cytochemistry by Karnovsky's laboratory (KARNOVSKY 1964; KARNOVSKY and ROOTS 1974). By the use of natural substrates, when available, or synthetic substrates which liberate or form a reducing agent at the sites of the enzymatic activity, many diverse types of enzymes have been demonstrated by methods depending on this principle known as catalytic osmiophilic polymer generation. DAB has probably been the most useful histocytochemical reagent of the past decade. Yet its borderline carcinogenicity and the frequent interruption of a supply of good quality DAB have encouraged research into a substitute reagent. A new substitute for DAB has resulted from the study of artificial melanins in our laboratory for several years. It consists of a mixture of p-phenylenediamine and pyrocatechol and is much better than DAB for the demonstration of HRP used as a cytochemical tracer...


Antigens of Hyostrongylus rubidus, the red stomach worm of pigs. Analyses by means of passive haemagglutination and immediate hypersensitivity tests.

Antigens were prepared from different stages of worm development and adult worm antigens were fractionated by ion exchange and exclusion chromatography. The antigens, or fractions of them, were assessed for their activity in passive haemagglutination reactions or intradermal tests. The results of the passive haemagglutination reactions indicated that circulating agglutinins were more readily detected when adult stage specific antigens were used. Antigen prepared from worms isolated when the population was declining was less sensitive. Fractions of adult worm antigen did not confer greater sensitivity than the whole worm extract.


Immunological release of histamine from human lung. I. Studies on the beta 2-sympathomimetic stimulator fenoterol.

Human lung tissue passively sensitized with anti-grass pollen IgE antibodies release histamine upon exposure to specific grass pollen antigen. Fenoterol, a beta 2-sympathomimetic stimulator drug, is shown to be a potent inhibitor of antigen-induced release of histamine. This inhibitory effect occurred with fenoterol concentrations of 2 x 10(-8) to 1 x 10(-7) M, and was determined by 67 and 95%, respectively. Thus, the beta 2-receptor stimulator fenoterol is a valuable drug for treating allergic bronchial asthma since it exhibits a combination of prophylactic and direct therapeutic properties.


Alpha-fetoprotein in intracranial malignant teratoma.

Serum alpha-fetoprotein was identified in five patients with histologically verified teratomas and in one patient with a suspected malignant teratoma. Detection of serum alpha-fetoprotein is specifically indicative of malignant teratoma, as no other known type of intracranial tumor produces it.


Initial therapy of suspected microbial corneal ulcers. I. Broad antibiotic therapy based on prevalence of organisms.

The initial treatment of bacterial ulcers of the cornea should consist of a combination of antibiotics that are effective against the major pathogens in the community. A gram stain may be misleading and therefore may suggest inappropriate therapy. Antibiotic therapy should include subconjunctival injections and concentrated eye drops, but not systemic administration except following perforation. Initially, we use cefazolin and tobramycin or gentamicin. Bacitracin may be substituted as a topical medication. Antibiotic therapy should be changed only if the pathogen is reported to be resistant to initial therapy and if the corneal ulcer continues to worsen.


Initial therapy of suspected microbial corneal ulcers. II. Specific antibiotic therapy based on corneal smears.

The encounter of the microorganism with the cornea is a complex event which generates tissue destruction through multiple host and organism-derived mediators. Suspicion of microbial invasion, proper utilization of the microbiology laboratory, and initiation of effective antimicrobial agents are the crucial measures in controlling the replicating organism and preserving visual function.


Inhibition of idiosyncratic reactions to aspirin in asthmatic patients by clemastine.

An H1-receptor blocking antihistamine, clemastine, taken before aspirin gave complete or partial protection against flushing, rhinorrhea, cough, and headache in ten asthmatic patients with idiosyncrasy to aspirin. In five of the ten patients aspirin-precipitated bronchoconstriction was also reduced or prevented after pretreatment with clemastine. Thus histamine appears to play a part in the production of most non-respiratory symptoms occurring after aspirin ingestion in intolerant patients with asthma. Bronchial reactions might depend partly on histamine and partly on the action of other spasmogens. It is suggested that inhibition of prostaglandins of the E series by aspirin-like drugs plays a crucial part in the release of histamine from tissue stores in aspirin-sensitive asthmatic patients. Clemastine might be of use in the treatment of acute reactions to aspirin.


Effects of single and repeated exposures to abate on rat behavior and cholinesterase activity.

Rats were injected i.p. with the organophosphate insecticide ABATE and tested over the next 16 days. Animals given 1000 mg/kg showed impaired performance of a previously conditioned avoidance response 6 days after injection but not 2, 8, 10, or 16 days after injection. No behavioral changes were observed in animals given 316 or 562 mg/kg. A subsequent experiment showed that the avoidance impairment in animals given 1000 mg/kg was accompanied by significant erythrocyte, plasma, and brain cholinesterase activity inhibition and decreased spontaneous motor activity. If administration of the same ABATE dose was distributed over 6 days (167 mg/kg/day), cholinesterase and motor activity depression was still evident but conditioned avoidance performance was unimpaired. The results were interpreted as differential behavioral adaption to repeated injections of ABATE.


A comparative light microscopic evaluation of oxytalan fiber staining with a variety of dye substances.

Staining of oxytalan fibers in marsupial, eutherian and human periodontal ligaments was surveyed with 65 different dyes. Using the criteria of response to preoxidation, distribution, and morphologic appearance, 27 dye preparations in addition to the Gomori aldehyde-fuchsin, Taenzer-Unna orcein, and Weigert resorcin-fuchsin techniques displayed oxytalan fibers. With two exceptions all dyes were cationic and reacted with varying degrees of excellence with different animals. Most dyes produced their best staining results as concentrated solutions in 3% acetic acid, suggesting involvement of oxidatively engendered polyanions predominantly associated with an acid mucopolysaccharide component of the oxytalan fiber. The significance of carboxyl and sulfur-containing groups should not be overlooked in further studies aiming to elucidate oxytalan fiber chemistry and microstructure. This study supported the view that oxytalan fibers belong to the family of elastic tissues and represent a biologically important system within the periodontal ligament.


An improved silver stain for developing nervous tissue.

A reduced silver technique using physical development to stain embryonic nervous tissue is described. Brains are fixed in Bodian's fixative. Paraffin sections are pretreated with 1% chromic acid or 5% formol. They are impregnated with 0.01% silver nitrate dissolved in 0.1 M boric acid/sodium tetraborate buffer of pH 8 or with silver proteinate. Finally they are developed in a special physical developer which contains 0.1% silver nitrate, 0.01-0.1% formol as reducing agent, 2.5% sodium carbonate to buffer the solution at pH 10.3, 0.1% ammonium nitrate to prevent precipitation of silver hydroxide, and 5% tungstosilicic acid as a protective colloid. The development takes several minutes in this solution, thus the intensity of staining can be controlled easily. The method yields uniform, complete and reproducible staining of axons at all developmental stages of the nervous tissue and is easy to handle.


Feulgen cytophotometry of pine nuclei. II. Effect of pectinase used in cell separation.

Pectinase used for cell separation prior to cytophotometry contains a DNase that is able to penetrate the cells of pine root tips and attack nuclear DNA. When pine root tips were exposed to 1% pectinase (pH 6.0), there was a decrease in nuclear DNA content at every sample point and a sharp drop between 16 and 20 hr. The effect of the DNase was eliminated by preparing the enzyme solution in 0.01 M sodium citrate or 0.001 M EDTA. It is suggested that heat denaturation of the DNase should also be effective and might be used in combination with the magnesium chelators.


[Preliminary results of the pilot phase of neutron treatment in Essen (author's transl)].

In agreement with the EORTC Charged Particle Therapy Project Group, a pilot phase of neutron treatment was performed on 59 patients in 1978. All patients suffered from far-advanced tumours. Sixteen were treated with neutrons exclusively, while all the others had recurrences after chemotherapy, surgery, or combined surgery and photon- or electron therapy. 29 of them received reduced doses (10 to 14 Gy), thirty patients got a full neutron course of 16 Gy (Total Effective Dose). The observation time varied from 2 to 11 months. Serious side effects occurred in 11 cases. A complete tumour regression was achieved in 35 patients, and a partial regression in 17. Recurrences developed in 5 cases, no tumour regression was seen in 2 cases. These preliminary results encouraged us to start a randomized trial of head and neck tumours according to the protocols of the EORTC Charged Particle Therapy Project Group.


[Influence of radiotherapy upon tumor accumulation and organ distribution of 57Co-bleomycin in mice with chemically induced squamous cell carcinoma (author's transl)].

Squamous cell carcinoma was induced in male 6 to 8-week old NMRI-mice by application of 9,10-dimethyl-1,2-benzanthracene on the skin. 15 weeks later macroscopically visible skin tumors are developed. Then organ distribution and tumor accumulation of 57Co-Bleomycin (spec. activity 1 mCi/3.3 mg) were studied 1 to 48 hours after injection. In squamous cell carcinoma a high uptake of this tumor-seeking agent can be demonstrated (n = 46). After radiotherapy (100 kV; 1.7 mm Al-filter; 18.8 Gy) (n = 26), however, a significantly reduced uptake of 57Co-Bleomycin in tumor tissue is observed. Possible consequences from these animal studies for tumor scintigraphy with this radiopharmaceutical in man are discussed.


Characterization of estrogen binding in the developing rat testis. Ontogeny of the testicular cytoplasmic estrogen receptor.

The properties and physical characteristics of a steroid binding component present in the immature (7 to 35 day) rat were investigated and found to be different from those of the 17 beta-estradiol receptor in the mature rat testis. These properties include a binding capacity of 483 fmol estradiol/mg protein, a Ka at equilibrium of 4.23 x 10(7)M-1, and broad steroid specificity as shown by interaction with several steroids; no binding was observed with diethylstilbestrol. The component, found in blood and several tissues including the testis, migrated as a 4.6S peak on sucrose gradients. This 4.6S component, which interacted with an anti-alphafetoprotein antiserum, decreased with age and was not detectable in the testis after day 21 or in the serum after day 25. These data suggest that this component is alphafetoprotein. Ontogenic appearance of the testicular cytoplasmic 17 beta-estradiol receptor in the developing rat was further elucidated. Sucrose gradient sedimentation analysis of cytosols revealed an 8S binding component that was first detectable at 23 days. Specific binding (fmol [3H]-estradiol/testis) was relatively low in neonates, rose to 59 fmol during the third week, and increased dramatically to 333 fmol at 7 weeks; binding rose only gradually after maturity. The receptor was tissue specific and steroid specificity studies demonstrated that only diethylstilbestrol and other estrogens were effective in competing with 17 beta-estradiol for binding sites. The Ka at equilibrium was determined as 3 x 10(10)M-1 and the binding sites were saturable in an in vitro system. The receptor did not interact with anti-alphafetoprotein antiserum as indicated by sucrose gradient studies. These data demonstrate the developmental appearance of the testicular cytoplasmic estradiol receptor in the immature rat.


[The use of audiovisual teaching and learning aids in dentistry].

In order to intensify university teaching (mastering of the ever increasing advance of knowledge and realization of the specified curriculum with its increased requirements in the teaching and learning process), it will be necessary to use audio-visual teaching aids to a greater extent. The audio-visual tools are used in combination, with due regard to the specificity of each of them. The specificity and the use of diapositives, synchronized slide audiotype series, fragmental films, survey films, folding foils, natural models, drawings on the blackboard, and closed-circuit television are dealt with.


Peripelvic urinoma associated with benign prostatic hypertrophy.

A case report of a large peripelvic urinoma which disappeared after decompression of a distended obstructed bladder is presented. The etiology of this rare complication of bladder outlet obstruction is reviewed and discussed.


Abnormal seminiferous tubule cells associated with choriocarcinoma: immunoperoxidase study.

A case is presented of widely metastatic choriocarinoma, associated with an intratubular proliferation of atypical germ cells in the testis and a minute adult cystic teratoma. Immunoperoxidase study of the intratubular germ cells did not confirm their trophoblastic origin. Intratubular proliferation of undifferentiated germ cells may be associated with choriocarcinoma.


Urodynamics studies in benign prostatic hypertrophy.

A study of patients with benign prostatic hypertrophy indicates that flow rates may well be useful in evaluating the degree of obstruction and the results of therapy. Electromyography and cytometry studies, while demonstrating certain tendencies in benign prostatic hypertrophy, do not give statistically significant data for evaluation and prognostication either by themselves or when correlated with radiographic changes and flow rates.


[Physicochemical properties of neurospecific basic protein (SCP) of the spinal cord].

Basic protein (SCP) known as antiencephalytogenic was isolated from the bull spinal cord and spinal roots. The protein is purified to a molecular homogeneous state, some of its physicochemical properties are studied. Molecular homogeneity of the protein is established by the method of disk electrophoresis in 15% polyacrylamide gel with sodium dodecyl sulphate present and by analytic ultracentrifugation. During electrophoresis in 15% polyacrylamide gel at pH 4.0 the protein movement occurs only in one zone, and at pH 7.0 three closely located zones are formed. The protein molecular weight determined by different methods is about 13500. The protein amino acid composition is determined and it is shown that 9.6 mole of amide nitrogen falls on 1 mole of the protein. The presence of the tertiary structure in the protein is supposed.


[Effect of axoplasmic flow blockade on enzymic activities and components of the rat muscle adenylate system].

Proteolytic aspartate and alanine aminotransferase, beta-D-galactosidase, N-acetyl-beta-D-glucosaminidase activities, contents of phosphocreatine, AMP + IMP, ADP, ATP were studied in the rat musculi gastrocnemius after denervation and blockade of axoplasmic flow, the latter being caused by 0.05 M colchicin solution applied to the sciatic nerve. Two weeks after denervation and the axoflow disturbance all the indices (except the N-acetyl-beta-D-glucoseaminidase activity) showed uniform changes. A month following the colchicin blockade the phosphocreatine and adenylates contents became normal. A conclusion is made on significance of the axoplasmic flow as a factor performing the trophic function of the nervous system.


[Leucosis diagnosis in cattle using the Sudan black B staining method on granulocytes and monocytes].

In the peripheral blood of healthy cattle and cattle suffering from leucosis a positive reaction with Sudan black B was found in neutrophilic and eosinophilic granulocytes: in healthy cattle at an intensity from ++ to ++++, and in cattle suffering from leucosis it was somewhat slighter (++ to +++). This finding can, to a certain extent, help in the distinguishing of reactive lymphocytosis from the leucosis of cattle. Compared with granulocytes the reaction of monocytes is markedly weaker: in healthy cattle at an intensity from 0 to (++), and in diseased cattle from 0 to (+++). In the bone marrow there is a significantly weaker reaction to Sudan black B in the group of large cells (neutrophilic and eosinophilic promyelocytes and myelocytes); in the group of healthy and diseases cattle the reaction is weaker than in neutrophilic and eosinophilic granulocytes of the peripheral blood. The reaction obtained with Sudan black B for lipids can be used as an aid for the distinguishing of cells of the myeloid, monocytic, and lymphoid order of peripheral blood and bone marrow in cattle leucosis.


[Antigenic structure of the L forms of Br. Abortus 544].

The gel precipitation test after Ouchterlony and Mancini was employed to study comparatively the antigenic structures of S and L forms of Brucella abortus 544. Reduction of the antigenic fractions was established with the L-transformed Brucella organisms as compared to the initial cultures. Reduced were mainly fractions of the antigenic structures that took part in cell wall building. Cytoplasmic antigens remained unchanged. Those that participated in the building of cell walls precipitated in compact lines. On the other hand, the cytoplasmic antigens produced diffuse-and-compact precipitation zones. The intact antigenic structures retained their specificity.


[Potentialities of diagnostics and palliative surgery in patients with obstructive jaundice of tumorous origin].

The work deals with the results of treatment of 322 patients with subhepatic jaundice of tumorous origin, who were treated at the clinic of Hospital Surgery of the Kuibyshev Medical Institute during the recent 15 years. In patients subjected to surgery associated with chemotherapy a longer survival was noted as compared with those without chemotherapy.


[alpha-fetoprotein biosynthesis in a human embryonic tissue culture].

Labelled amino acids from 14C-chlorella hydrolysate incorporated into alpha-fetoprotein during "in vitro" cultivation of fetal liver, gastrointestinal tract, lung, kidney and bone tissues, obtained with in 6-12 weeks of pregnancy. alpha-Fetoprotein was apparently synthesized in tissues of entodermal origin.


[The efficiency of cold staining methods at the light microscopical evidence of acid fast bacilli (author's transl)].

Comparing studies has been demonstrated wether or not the cold staining of acid fast bacilli is qualitative and quantitative better than the Ziehl-Neelsen-method. The hot staining was superior to all cold staining methods and their modifications tested. If a cold staining is necessary two methods are recommended, the Kinyoun method and the staining with carbolfuchsin which chloroform is added to. Thin smear and homogeneous material provide better results. Additional investigations concerning decolorizations have shown, that 10% sulfuric acid is as effective as hydrochloric acid-ethanol mixture.


The zinc iodide-osmium (ZIO) reaction in the central nervous system: localization and relations to functional activity.

The fine structural characteristics of ZIO reaction was studied in the cerebral and cerebellar cortex and olfactory bulb of the rat and in synaptosomes prepared from rat cerebellar cortex. It was concluded that: 1. Organelles of different nerve cell types exhibit different ZIO reactions provided that the impregnation was carried out under standardized conditions. 2. 6...10 times more synaptic vesicles were stained by ZIO in the inhibitory terminals than in the excitatory ones. 3. ZIO positivity was found in all types of synaptosomes prepared from cerebral cortex. Following electrical or chemical (KCl) depolarization there was a decrease in the number of ZIO positive synaptic vesicles, which decrease was directly proportional to the parameters of stimulation. 4. By x-ray microanalysis Os, Zn and Ca were consistently detected in the ZIO precipitates. Iodine, however, could not always be found. After stimulation the presence of Ca was observed even in those synaptosomes in which the ZIO reaction product was absent. 5. On the basis of the staining characteristics the reaction, under standard conditions, can reflect certain functional states of the nerve terminals.


[Use of Drăgan's high-speed PBT staining method in oral cytology examinations (author's transl)].

Drăgan's high-speed PBT (polychrome blue tannin) staining method enables cellular elements to be detected in oral smears in one minute at most. The basic dyes in the polychrome blue solution allow the acid-group-containing substrate to be detected in the nucleus, in the cytoplasm of epithelial cells and leukocytes, as well as in the elements of the flora. The chromatin shows a distinct basophilic, orthochromatic reaction. The fine, reddish-violet metachromatic granules in the cytoplasm are of a glycolipid nature and occur with the tonofibrils. The keratohyalin granules show a basophilic orthochromatic or metachromatic, homogeneous or granular reaction in relation to the chemically acid portions of their structure.


[Light microscopic findings on globular hyalin bodies in the human liver and its electron microscopic equivalents (author's transl)].

According to electron microscopic investigations, there is no uniform substratum and no uniform formal pathogenesis in the light microscopic appearance of globular hyalin bodies in the liver. This paper presents a survey on the different electron microscopic equivalents of the light microscopic findings of globular hyalin bodies in human liver biopsies. These electron microscopic equivalents, their occurrence, their different pathogenesis and, resulting from this, their different diagnostic and prognostic significance are described and demonstrated in detail.


[Determination of the internal association constant as a measure of the affinity of erythocyte-fixed antibodies that interact with mono- and multivalent antigens].

The fraction of antibody-bound determinants of a polyvalent antigen is determined by the fraction of free antigen molecules and the valence of the antigen. The internal association constant for antibodies fixed onto erythrocytes can be found by the suspension method, the index obtained in this process being similar when both monovalent and polyvalent antigens are used. The sensitivity of the antibody-erythrocyte diagnostic preparation in the passive hemagglutinin test depends on the affinity of the active centers of antibodies.


[Modified method of obtaining washings of the large intestine for determining coproantibodies and immunoglobulins in the dynamics of acute dysentery].

The study of the washings obtained during rectoscopy from the mucous membrane of the large intestine with the use of a special attachment for a rectoscope revealed that this method had a number of advantages when compared with the study of coprofiltrates; in particular, this method allowed to obtain pure secretions of the mucous membrane free of fecal admixtures and to concentrate the gamma globulin fraction. The study of the dynamics of coproantibody secretion in acute dysentery revealed that coproantibodies were most frequently detected on the second week of the disease (reaching 85.7%), while immunoglobulins occurred in the protein fraction of the washings with almost the same frequency during the whole period of the disease.


The effect of gramicidin A on the K+ conductance of the membrane of isolated frog skeletal muscle fibres.

Gramicidin A effects a drastic decrease of the membrane resistance of frog skeletal muscle fibres in isotonic K2SO4 solution. In detubulated fibres the effect is not so pronounced. The reduction of the membrane resistance is caused by an increase in the K+ conductance of the surface and T-system membranes of the muscle cell.


Studies on the inactivation of encephalitogenic myelin basic protein by serum.

This study confirms previous reports that myelin basic protein loses its encephalitogenic activity when incubated in normal serum at 37 degrees C. The mechanisms for this was studied. 125I-labelled human myelin basic protein was rapidly degraded by normal guinea pig serum to low molecular weight products as shown by polyacrylamide gel electrophoresis. An intermediate product of molecular weight about 6000 daltons was seen. Plasma had a much lower degradative activity than serum; the half life of myelin basic protein was 3.8 hours in plasma compared with 12 minutes in serum. Serum degraded myelin basic protein was no longer capable of suppressing experimental allergic encephalomyelitis in the guinea pig nor of eliciting delayed-type hypersensitivity in guinea pigs sensitized to myelin basic protein.


Proteolytic enzyme activity in patients with severe head injury and the effect of a proteinase inhibitor.

A study was performed to detect the inhibitory effect of intravenously administered aprotinin (Trasylol) on brain and CSF protease activity in 25 patients with severe head injury. The data presented include measurements of CSF protease activity, alpha-1-antitrypsin, alpha-2-macroglobulin, haptoglobulin, polyacrylamidgel-electrophoresis pattern, total protein and hemoglobin content. The results indicate that increased protease activity is present and that this induces autolytic processes which can be inhibited by aprotinin treatment. The survival rate was higher after aprotinin treatment. Total CSF protein content was significantly higher in nonsurvivors than in survivors.


Human kininogen from Cohns Fraction IV: comparisons of antigenicity and multiple forms.

Kininogen was isolated from Cohns fraction IV by DEAE-chromatography, gel filtration and ammonium sulphate precipitation. Immunologically pure kininogen was prepared by removal of protein impurities using specific immunoadsorbents with Sepharose-bound antibody. Anti-kininogen serum was raised in rabbits against the pure antigen. Comparison with anti-kininogen sera prepared with the biologically active LMW antigen from whole plasma suggested antigenic identity by double immunodiffusion analysis. The Cohn-kininogen was shown to contain mainly two components (85%) in about equal amounts focusing with peaks at pI 4.2 (42%) and pI 4.3 (43%). These represent apparently structurally altered forms of the native plasma kininogen focusing at pI 4.5-4.6 (54%), which occurred as a minor component (13%).


The isolation of leukokinin-H and leukokininogen from human ascites fluid; their properties and role.

The leukokinin-leukokininogen system is a pathological kinin generating system which is catalyzed by acid proteases present in neoplastic cells, white cells and even normal tissues. The components of the human system including leukokinin-H and leukokininogen have now been isolated and characterized. Very specific protease inhibitors of the system such as pepstatin have been found and are now known to prevent "in vivo" the formation of pathological fluids such as neoplastic ascites. Strong evidence has been previously published and additional evidence has been presented here which indicates that pepstatin's actions are related to the inhibition of cathepsin-D in vivo and the inhibition of leukokinin formation. Both leukokinins and leukokininogens have been clearly defined and shown to differ from bradykinin and human bradykininogens. This clearly demonstrates the presence in pathological systems of a kinin-generating system which is separate and distinct from the bradykinin generating system. The importance of the leukokinin-leukokininogen system in disease would seem to be very great. The finding that pepstatin can inhibit the system in vivo opens the way for studies of pepstatin and related protease inhibitors as therapeutic agents in neoplastic disease and protease mediated inflammatory disorders.


Immunogenicity of guinea-pig submandibular and coagulating gland kininogenases.

The antigenic relationship between submandibular and coagulating gland kininogenases of the guinea-pig has been examined using Ouchterlony double diffusion, crossed and rocket immunoelectrophoresis and immunofluorescent techniques. The evidence suggests a partial immunological identity between submandibular and coagulating gland kininogenases of the guinea-pig. In this respect these enzymes seem to differ from the glandular kallikreins of other species (porcine, human and rat) which apparently share a complete immunological identity.


Relevance of GABA in the nigrostriatal system.

In conclusion, even though the mutual integration of intrastriatal circuits remains an open question, the electrophysiological and neurochemical approaches seem to provide valid support toward understanding the complexity of these systems. Recent findings seem to indicate that, besides a dopaminergic and cholinergic link, interactions between DA and GABA neurons may be operative within the striatum. An understanding of these functional interplays may facilitate future attempts aimed at clarifying the electrophysiological discrepancies concerning the inhibitory or excitatory action of DA on the target cells in this brain structure. Studies on the functional roles of pathways projecting from striatum to substantia nigra have indicated that these may be implicated in the regulation of nigral efferents to other brain nuclei and that they do control striatal DA activity through feedback mechanisms.


Effects of some anti-rheumatic agents on copper-catalyzed thermal aggregation of gamma globulin.

Gerber has shown that specific anti-rheumatics, D-penicillamine and aurothiomalate, inhibit copper(II)-catalyzed thermal aggregation of human gamma globulin. Various anti-rheumatics were tested for the activity. Steroidal and non-steroidal anti-inflammatory agents were almost ineffective, while a new non-steroidal anti-inflammatory agent, TAI-284 (6-chloro-5-cyclohexyl-1-indancarboxylic acid), was found to be one half as active as aurothiomalate. The structure-activity relationship of TAI-284 derivatives and the mode of action of TAI-284 were investigated.


Metastatic neuroblastoma in bone marrow aspirate smears.

The authors observed rosette formation and partially fibrillar, blue-grey, extracellular material in Wright-Giemsa-stained bone marrow aspirate smears in five preparations from three cases of neuroblastoma metastatic to bone marrow. These features are little publicized in the literature and textbooks. These findings in neuroblastoma metastatic to bone marrow should prove helpful in differentiating that entity from acute leukemia and from other metastatic small-cell neoplasms in bone marrow.


A quick and easy method for the staining of reticulocytes.

This report presents a simplification of the conventional method for the staining of reticulocytes that is easier, faster and requires no extraneous equipment. Blood is applied directly to a spot of dried stain on a microscope slide. An identical slide is placed over the first and the blood and stain are mixed for about a minute. The slides are held apart by paper labels at each end. The slides are then slid apart to produce a smear on each slide.


Prostate-specific acid phosphatase: purification and specific antibody production in rabbits.

Demonstration of prostate-specific acid phosphatase by immunologic methods in tissue sections or in plasma necessitates a monospecific antiserum. This is produced by immunizing rabbits with pure prostate-specific acid phosphatase antigen, prepared from seminal fluid. The ejaculate is centrifuged, dialyzed against a citrate buffer, pH 4.8, and centrifuged again. The supernatant is brought onto a Sephacryl S-200 Superfine column and eluted with the same buffer. Prostate-specific acid phosphatase-positive fractions are concentrated, brought onto and stepwise eluted from a Sulphopropyl Sephadex column with citrate buffers at pH 4.8, 5.2, and 5.5. Fractions containing prostate-specific acid phosphatase are concentrated again and purified over a Blue Sepharose CL-6 B column. After elution, a new concentration step yields a protein concentration of 0.5-1.0 mg . ml-1. This sample in polyacrylamide gel electrophoresis shows a single protein band and is used to immunize female rabbits. The purity of the antiserum is then tested by immunoelectrophoresis and an Ouchterlony technic. Besides anti-prostate-specific acid phosphatase, two other antibodies against serum proteins are present, one of which is anti-albumin. Absorption of these impurities results in a monospecific antiserum against prostate-specific acid phosphatase.


Quality assurance of gram-stained direct smears.

Clinical laboratories do not always prepare and examine direct smears. In part, this may be explained by lack of control over the precision and accuracy of the procedure, which has diminished confidence in direct smears among both laboratory scientists and clinicians. Objective criteria were established for enumeration of cells and placement of bacteria in identification categories. Two methods for monitoring the accuracy and reproducibility of their application were studied: (1) examination of previously examined and reported direct smears of clinical specimens by independent observers with subsequent review of discrepancies with decisions by personnel; (2) preparation of suspensions of cells and bacteria that yielded identical smears for subsequent examination as unknowns. Method 1 showed agreement in bacterial identification category in 65%, quality score 74%, enumeration of neutrophils 79%, squamous cells 76%, and erythrocytes 92%. Method 2 showed that conformance of technologists' observations to expected results varied, for neutrophils conformance was 72-78%, squamous cells, 68-78%, bacterial identification category, 100%, and bacterial enumeration, 45-96%.


The inhibition of corneal vascularization with aortic extracts in rabbits.

A low molecular weight fraction of bovine aortic extract inhibited corneal vascularization and edema in rabbits when administered either subconjunctivally or topically as long as 48 hours after injury. The extract also appeared to enhance the regression of newly formed corneal vessels. Topical administration for as long as two months had no deleterious ocular side effects. Tissue culture experiments showed that analagous fractions prepared from bovine vitreous inhibit endothelial cell growth. The major growth inhibitor of corneal neovascularization was not the Kunitz bovine protease inhibitor.


Axoplasmic transport blockage therapy in herpes zoster ophthalmicus.

Three patients with herpes zoster ophthalmicus were treated with an oral administration of colchicine and corticosteroid, while another seven were given systemic corticosteroid, vitamins, and sedatives. Colchicine inhibited the formation of new skin lesions but did not suppress the already grown vesicles. The effect of colchicine was attributed to a blockage of intra-axonal dissemination by neurotrophic virus.


Anti-anaphylactic and bronchodilating action of a beta-adrenoceptor stimulator, KWD 2131, in human lung tissue.

The beta-adrenoceptor stimulating agent KWD 2131 has been studied with regard to inhibitory effect on allergen-induced histamine release from passively sensitized human lung tissue and relaxing effect on contracted small (diameter = 1 mm) and large (diameter greater than 3 mm) isolated human bronchi. The dose for 50% inhibition of the allergen-induced histamine release was 2 x 10(-11) M. The potency of KWD 2131 was approximately 0.15 times that of terbutaline and 0.05 times that of isoprenaline in this respect. The bronchodilating potency of KWD 2131 was 0.02-0.03 times that of terbutaline. The data indicate that KWD 2131 is a compound with preferably anti-anaphylactic potency in the human lung.


Ataxia-telangiectasia and hepatocellular carcinoma.

Ataxia-telangiectasia (AT) is a multi-system disease involving the cerebellum, cutaneous blood vessels and the immune system including both cellular and humoral components. It also involves hematological, endocrine and peripheral nervous systems. This disease is often associated with abnormal liver function tests, such as, raised alkaline phosphatase and various nonspecific histological changes in the liver. High incidence of various malignancies involving lymphoreticular, gastrointestinal and mesenchymal organs have reported in ataxia-telangiectasia. Elevated levels of alpha fetoprotein have been noted commonly in this disorder. In spite of the hepatic histological and biochemical changes associated with elevated alpha fetoprotein, to our knowledge, development of hepatocellular carcinoma has not been reported in patients with ataxia-telangiectasia. A case of a young white female with AT who developed hepatocellular carcinoma along with significantly elevated levels of alpha fetoprotein is presented.


Immunotherapy in spring-time hay fever. A clinical and immunological study comparing two different treatment extract compositions.

In a study of the efficacy of two different treatment schedules for perennial immunotherapy, 47 adult patients with spring-time hay fever due to allergy against birch and other deciduous trees were randomly assigned to three treatment groups: one group received birch, alder and hazel allergen in Allpyral, another group received the same Allpyral mixture and in addition all relevant tree pollens in aqueous extract and a control group received no injections. For determination of antibody titres the radioallergosorbent test (RAST) and the ammonium sulphate precipitation (ASP) technique were used. Cellular responsiveness was studied by measuring birch pollen (BP) induced leucocyte histamine release in peripheral blood. The clinical and immunological response was similar in the two treated groups. Treated patients had less symptoms and a lower consumption of antihistamine tablets during the pollen season than the control group. Non-IgE BP antibodies and IgE antibodies recorded with the ASP technique increased after immunotherapy while RAST values did not change significantly. A decrease of RAST values from postseasonal values during the first year to preseasonal values in the following year was seen in all patient groups but was less pronounced in treated than in untreated patients. The decrease was more pronounced in patients with high RAST values of postseasonal sera than in patients with low RAST values. Cellular reactivity increased slightly during the first phase of therapy but returned to the pre-treatment level later. Clinical improvement was positively correlated to the percentage increase of non-IgE antibody titre and to the pre-treatment non-IgE/IgE antibody ratio. Patients with high preseasonal RAST titres or high cellular sensitivity tended to have more severe symptoms during the pollen season. It is concluded that a mixture of birch, alder and hazel is sufficient for immunotherapy in spring-term hay fever. It is obvious that changes of a single immunological variable do not account for the therapeutic results in immunotherapy.


3H-histamine release from human leukocytes. A new method for detecting type I allergy compared with basophil histamine release technique.

A rapid, simple, and inexpensive method for large scale screening of patients suspected of type I allergy has been developed. The method is based on in vitro incorporation of 3H-histamine in the leukocytes of the patient, whereafter release of labelled histamine is measured after provocation of the cells with the suspected allergen. The new method was compared with the conventional basophil histamine release technique by in vitro provocation of six asthmatic patients under suspicion of type I allergy against animal dander, house dust, and mite, and an almost identical release of histamine was observed in both assays.


Gamma-aminobutyric acid pathways in the cerebellum studied by retrograde and anterograde transport of glutamic acid decarboxylase antibody after in vivo injections.

Injections of characterized antibody against glutamic acid decarboxylase (GAD), the enzyme responsible for the synthesis of gamma-aminobutyric acid (GABA), were made into the cerebellum. Small cortical injections of anti-GAD antibody produced labeled stellate, basket, Purkinje, and Golgi cells and their processes at the injection site. Anterograde transport of GAD antigen-antibody complexes in Purkinje cell axons caused intense labelling of terminals in deep cerebellar and several vestibular nuclei. Small groups of mossy fiber rosettes labeled and produced retrograde labeling and GAD immunoreactivity in a small number of pleomorphic neurons in the deep cerebellar nuclei. Injections into the dentate nucleus produced retrograde labeling in Purkinje cell bodies and anterograde label in a small number of mossy fiber rosettes. All projections conformed to previously reported topographic distributions of corticonuclear and nucleocortical cerebellar pathways. These findings confirm the GABA content of most Purkinje cell-deep nuclei connections and provide new evidence for a GABA component in part of the nucleocortical pathway in the cerebellum. Immunocytochemical controls for specificity were conducted by injections of preimmune rabbit serum as a substitute for GAD antibody. Only nonspecific labeling was obtained in these cases. Colchicine caused a cumulative enhancement of GAD immunoreactivity in all cases. The present studies indicate that the method of in vivo antibody injections can be utilized to study chemically specific connections in nervous tissue.


Penicillin and cephalosporin immunogenicity in man.

Whether cross-allergenicity exists between the penicillin and cephalosporin antibiotics is controversial. A solid-phase radioimmunoassay was adapted to detect drug-specific IgG, IgM and IgE antibodies. Penicillin and cephalothin-specific serum immunoglobulins were determined in patients' serum before and after a therapeutic course of sodium cephalothin. Changes in IgG, IgM and IgE antipenicillin and anticephalothin antibodies, respectively, occurred and were closely correlated to one another (r = 0.80--0.99, p less than 0.0005), indicating that antibody responses to penicillin and cephalothin were linked. This in vitro assay system should prove useful for further study of clinical drug allergies.


The role of mite allergen in chronic urticaria.

Fifty-two patients with chronic urticaria were tested intradermally with mite allergen (Dermatophagoides farinae). None had any past history of any other atopic diseases. Thirty of the 52 patients gave positive skin tests to mite allergen. A good correlation between skin sensitivity to mite allergen and in vitro mite antigen-induced histamine release from leucocytes was observed. These facts suggest that a mite may be an important role in chronic urticaria.


Serologic studies on porcine strains of Haemophilus parahaemolyticus (pleuropneumoniae): extraction of type-specific antigens.

By the use of phenol water extraction it was possible to obtain strictly serotype-specific antigens from mucoid cell cultures of five serotypes of Haemophilus parahaemolyticus (pleuropneumoniae). These serotype-specific antigens did not cross-react with each other in immunodiffusion tests. The type-specific precipitating phenol-water-fractions were composed of two to four antigenic components, presumably of polysaccharide or lipopolysaccharide nature.


Evaluation of pseudorabies viral antigens in the agar gel immunodiffusion test.

Procedures designed to extract pseudorabies viral (PRV) antigens from PRV-infected tissue cultures were investigated to determine whether differences in extraction method had an effect upon the final concentrated antigenic product. All four of the preparations made from PRV-infected tissue culture cells (trypsin extract and disrupted cells) or entire PRV-infected cultures (polysorbate 80 extract and (NH4)2SO4 precipitate) contained relatively large amounts of the same antigen, whereas cell-free PRV-infected tissue culture fluids did not contain significant amounts of this antigen. Specific antibody directed against this antigen was present in all PRV antisera tested. Two other antigens were observed in some of the preparations, but PRV antisera varied in their ability to precipitate with these antigens. Therefore, the number of precipitation lines observed in agar gel immunodiffusion between PRV preparations and PRV-positive antisera depended both upon the extraction method used to obtain the antigen and upon the specificity of the selected antiserum.


Characterization of antigens from Aspergillus fumigatus. III. Comparison of antigenic relationships of clinically important aspergilli.

Antigenic relationships between strains of Aspergillus fumigatus, Aspergillus fumigatus var. elipticus, Aspergillus phialiseptus, Aspergillus flavus, and Aspergillus niger were analyzed by fused rocket immunoelectrophoresis and by skin tests. Seventy-three to 89 % of the numbers of antigens detected between strains and species of the A. fumigatus series were shared. The degree of sharing between antigens of A. flavus, A. fumigatus series, and A. niger was much lower and ranged from 19 to 35 %. In reciprocal skin tests in sensitized guinea pigs, similar relationships were shown. Three fractions of A. fumigatus extract proved to be markedly specific for this species. Cross reactivity was associated primarily with carbohydrate and glycoprotein fractions.


Language deficits after apparent clinical recovery from childhood aphasia.

Twenty-seven children with childhood injury to the left hemisphere were tested for language function and compared with appropriate controls. Eleven children had incurred their lesions before the age of 1 year, 16 afterward. The group with perinatal injury to the left hemisphere did not show a specific aphasic deficit even though they were mildly cognitively impaired. The group of children with later injury to the left hemisphere showed aphasic deficits if the original injury had caused a language defect; otherwise the left hemisphere injury was not associated with specific disturbances in language function. The average age at time of lesion in those children who had recovered from aphasia was 4.7 years. We conclude that even when childhood aphasia results from a unilateral nonprogressive lesion, recovery of language is less complete than has been generally supposed.


Chronic progressive myelopathy: investigation with CSF electrophoresis, evoked potentials, and CT scan.

Chronic progressive myelopathy (CPM) is a difficult clinical problem. Many patients who present with CPM turn out to have a spinal form of multiple sclerosis (MS), but until there is clear lesion dissemination, a definite clinical diagnosis cannot be made. We have looked for MS-related abnormalities in 72 patients with CPM. The mean age of onset was 42 years, mean duration was ten years, and mean Kurtzke disability rating was 4.5. Studies performed were cerebrospinal fluid electrophoresis for oligoclonal banding, pattern-reversal visual evoked responses, blink reflex latencies, and computerized axial tomography. Oligoclonal banding was found in 32 patients (44%), patterned visual evoked responses were abnormal in 32 (44%), and blink latencies were abnormal in 40 (56%). A least one of these studies was abnormal in 61 patients (85%) and at least two in 48 (66%). The CT scan was abnormal in 38 )53%), 36 with atrophy and 3 with low-density or enhancing lesions. These results suggest that at least 44% of patients with CPM may have MS that could be diagnosed by oligoclonal bands. Other physiological tests suggesting diffuse or disseminated disease bring the total to 85%. Only autopsy follow-up will tell us the exact diagnostic accuracy of these studies in this complex syndrome.


Multiple sclerosis: circulating antigen-reactive lymphocytes.

Circulating lymphocyte populations were examined in 85 patients with multiple sclerosis (MS), 26 of whom showed exacerbations; 48 patients with other neurological diseases (OND); 14 patients suffering from psychiatric disorders; and 2 normal subjects. The study involved the assay of early (active, high-affinity rosetting) T-cells, myelin basic protein (MBP)-reactive early T-cells, late (total, 24-hour rosetting) T-cell levels were significantly lower in MS (p less than 0.01) than in OND subjects. Exacerbations in MS were usually accompanied by further decreases in early T-cells. The lower levels of early T-cells in MS and their fluctuations are believed to reflect disease activity. MBP-reactive early T-cells were more frequently increased in MS (75% of cases) than OND (50%), and while this might be indicative of increased sensitization against myelin antigens, it was found not to be an MS-specific phenomenon.


[Role of gramicidin S in the sporulation of the R+ and R- variants of Bacillus brevis var. G.-B].

The effect of gramicidin S added to the cultivation medium on sporulation of the gramicidin S-producing P+ variant and gramicidin S-nonproducing P- variant of Bacillus brevis var. G.-B. was studied. Gramicidin S added to the synthetic medium with glucose in an amount of 30 and 100 microgram/ml 4 and 7 hours after inoculation with the vegetative cells of R- variant had no effect on the growth of the culture but retarded its sporulation. When gramicidin S was added in an amount of 100 microgram/ml 4 hours after inoculation, the sporulation rate of R- variant strongly decreased, rohile sporulation was not suppressed as it was noted before with respect to R+ variant. Active stimulation of Bacillus brevis var. G.-B. sporulation was observed after addition of gramicidin S 13 hours after development of R+ and R- variants without the antibiotic biosynthesis. Synthesis of gramicidin S by R+ strain was suppressed by the specific inhibitor beta-phenyl-beta-alanine. The amount of gramicidin S added to the medium during the sporulation process of R+ and R- variants decreased. On addition of 30 microgram/ml of the antibiotic it was practically not detectable when the culture showed the greatest number of the spores. Therefore, gramicidin S added to the medium is probably adsorbed by the cells of Bac. brevis var. G.-B. and affects sporulation of R- and R+ variants thus accelerating or retarding this process depending on the cultivation conditions.


Diagnostic considerations in ataxia-telangiectasia.

13 children with ataxia-telangiectasia were followed for 6 years. Unlike previously reported cases, these patients had progressive, debilitating neurological disease and slight pulmonary or infectious symptoms. Immunological dysfunction was variable and endocrinological defects were absent. Oculomotor findings, alpha-fetoprotein levels, and the incidence of chromosomal breakage were the most consistent parameters in the diagnosis of the condition. This disease should be considered in any patient with chronic ataxia, regardless of immunological findings or whether he has a history of infections.