Endocrine control of plasma protein and volume. The loss of blood volume initiates a sequence of events that begin with detection of the volume loss by cardiovascular receptors and the transmission of the signals of that loss to the central nervous system. Central neural processing leads to the release of multiple hormones that act together to induce an increase in extracellular osmolality. In response to the increase in extracellular osmolality, fluid shifts from cells to the interstitium, increasing intersititial volume and pressure. The increase in interstitial pressure leads to increased capillary and lymphatic return of fluid and to increased lymphatic return of preformed albumon. These events combine to form the second definitive phase of the restitution of blood volume, which is crucial both for the support of critical cardiovascular function and for the inhibition of the initial neuroendocrine response. If left unabated, this response may lead to the detrimental features of the metabolic response to injury. The degree of hyperosmolality following volume loss in injury may serve as an index of severity of that injury. The presence of the mechanism outlined provides a further rationale arguing in favor of prompt and adequate fluid therapy of the injuried and volume-depleted patient.


A new technique for hemipelvectomy.

A new technique for hemipelvectomy. A new technique for hemipelvectomy has been developed in which a large anterior well vascularized flap is used. The preservation of an anterior flap is essential if the posterior flap cannot be preserved because of tumor involvement. The vascularized anterior flap may be superior to the posterior flap because of less dermal necrosis. Use of the anterior flap may increase the ease of hemipelvectomy and reduce blood loss at operation.


Oculogenital transmission of type 2 herpes simplex virus in adults. Type 2 (genital) herpes simplex virus (HSV-2) was isolated from three patients (two adults and an 11-year-old girl) with acute ocular infections. Two of these patients had acute blepharoconjunctivitis and one had acute keratoconjunctivitis. Genital herpes infections had preceded the eye infections in the two adults. This was not the case in the 11-year-old, but she had been in close contact with her sister who had apparently had the genital disease. The study strongly suggests transmission of HSV-2 from the genital site to the eye.


Observed relationship between herpetic lesions and antigenic type of Herpesvirus hominis. Of 171 available strains of Herpesvirus hominis isolated in this laboratory during the period 1950 to 1975, 166 could be readily typed as HV-1 or HV-2 by indirect immunofluorescence, while 5 have so far been untypable. Of 72 typable isolates from genitalia and nearby skin, all were HV-2. Of 81 typable isolates from mouth, eye or skin above the waist, 68(84%) were HV-1 and 13(16%) were HV-2. Of isolates from the eye only, 46 of 54(87%) were HV-1, 7(13%) were HV-2, and 1 could not be typed. When sera were available for herpesvirus antibody titrations, the pattern of antibody response tended to match the type of isolate. Clinical findings of 5 of the individuals with ocular herpes caused by HV-2 have been reviewed. The HV-2 infections appeared to be severe, typical herpetic keratoconjunctivitis, sometimes with deep infiltrates and stromal involvement.


Type 1 and type 2 herpes simplex virus in corneal cell cultures. The pathogenicity of herpes simplex virus (HSV) in primary cultures of epithelia, stromal, and endothelial cells of rabbit corneas was studied at various incubation temperatures (30 degrees, 36 degrees, and 40 degrees C). We tested three strains each of type 1 (HSV-1) and type 2 (HSV-2). At all three temperatures, the epithelial cells appeared to be more susceptible to both HSV-1 and HSV-2 than the stromal and endothelial cells. In general, less HSV-1 was requered than HSV-2 to infect the same type of corneal cell at the same incubation temperature. At 40 degrees C, however, there was far less cell destruction by either HSV-1 or HSV-2 than at 30 degrees or 36 degrees C. This inhibition at 40 degrees C was more pronounced in the cells infected with HSV-2 than in those infected with HSV-1, and the inhibition was accompanied consistently by significant suppression of virus multiplication in the cells.


Recurrent herpes simplex uveitis in humans. Herpetic uveitis in man is generally, although not always, a complication of chronic stromal disease of the cornea. It is characterized by pain, photophobia, and redness, and may be abrupt in onset, particularly in recurrent cases. It is often accompanied by a severe secondary glaucoma. Various theories of the pathogenesis are discussed. The weight of experimental evidence favors the proliferation of living virus in the uveal tissues as the cause of the inflammation, although the virus has been isolated only rarely from aspirated aqueous humor. Autoimmune factors must be considered. Cyclopegia is the most important element of treatment, most cases being self-limited and non-destructive. Secondary glaucoma sometimes poses a serious problem that must be treated by radical measures. Antiviral medications such as adenine arabinoside may play an important role in the treatment of resistant cases. Corticosteroid therapy is to be avoided, if possible.


The ocular manifestations of herpes zoster, varicella, infectious mononucleosis, and cytomegalovirus disease. Herpes zoster, caused by varicella-zoster (V-Z) virus which also causes varicella (chickenpox), is usually a benign self-limited disease. However, when the ophthalmic division of the trigeminal nerve is affected, the ocular disease (ophthalmic zoster), although also usually mild and self-limited, may have severe complications (corneal scarring, glaucoma, iris atrophy, posterior synechiae, scleritis, motor disturbances, optic neuritis, retinitis, anterior segment necrosis, and phthisis bulbi and servere postherpetic neuralgia). Varicella affects the eye rarely (except for the typical lid lesions), but associated conjunctival and corneal lesions, iridocyclitis, glaucoma, chorioretinitis, and optic nerve lesions have been described. Infectious mononucleosis may involve the eye either by direct involvement or from a remote focus such as the central nervous system. Ocular manifestations of cytomegalovirus disease is usually limited to the choroid and retina unless involvement of the developing embryo occurs prior to the development of the eye.


The biology of herpes simplex virus infection in humans. Herpes simplex virus is a frequent cause of recurrent ocular, oral, genital or cutaneous eruptions in man. Lesions are highly localized and tend to recur at the same site. Among the most consistent factors provoking recurrence is root section of the trigeminal nerve. Clinical and experimental data suggest that herpes simplex virus is commonly resident within the trigeminal ganglia of man, where it may be responsible for recurrent oral or lip lesions, and is less frequently a resident of the second or third sacral ganglia where it might be responsible for genital eruptions. Generally, the trigeminal virus is type 1 and the sacral virus is type 2; the virus is only rarely recoverable from other sensory ganglia. Factors provoking the reactivation from the virus' latent site and the mechanism for reactivation remain largely unknown. Further study is needed to understand the behavior of HSV and other viruses in nervous system tissue.


Latent infections by herpes simplex virus in experimental animals. Studies in experimental animals, initially the rabbit and more recently the mouse, have been a great importance in establishing present day concepts concerning the phenomenon of herpesvirus latency. These early observations coupled with more recent knowledge of virological consequences following surgical manipulation of the trigeminal tract have led to a general hypothesis for the natural history of herpetic infections: The infection follows a circuit from skin, mucous membrane, or eye (the primary infection) to the corresponding sensory ganglia via associated nerves. Virus becomes latent in the ganglia and later, as a result of one of the many provocations known to be associated with recurrence of herpetic lesions, is reactivated and travels via the nerve to the surface and again produces lesions. Current research investigating this hypothesis is reviewed.


Experimental reactivation of ocular herpes simplex in rabbits. Latent herpes simplex virus (HSV) is known to reside in the trigeminal ganglia. Our studies show that the temporary retrobulbar disruption of trigeminal nerve function in chronically infected animals caused a striking decrease in the number of positive HSV cultures obtained during the 20 weeks immediately following surgery. We found that the stereotaxic interruption of intracranial trigeminal nerve function prior to initial HSV infection dramatically reduced the incidence of peripheral recurrence of HSV. Stereotaxic stimulation of the trigeminal ganglion in chronically infected animals produced a significant increase in positive cultures within two days. But, direct neurosurgical stimulation of the trigeminal ganglion proved strikingly effective, producing 83% positive cultures at the eye within 48 hours of operation. These studies further substantiate the premise that the trigeminal ganglion serves as a reservoir for latent HSV from the trigeminal ganglion to its infectious form in the peripheral ocular tissues somehow involves the trigeminal nerve.


Primary and secondary herpes simplex uveitis in rabbits. Primary and secondary (recurrent) herpes simplex uveitis were studied in the rabbit eye. Intravitreal injection of live herpes simplex virus (HSV) produced primary uveitis, and reinjection of HSV intravitreally in an eye that had completely recovered from the primary disease produced secondary uveitis. The onset of primary herpes simplex uveitis was gradual, but the secondary disease developed immediately after the intravitreal reinjection. Only live HSV would produce primary uveitis, whereas both inactivated and live HSV could produce secondary uveitis. Infectious HSV could be isolated from the eye with primary uveitis, but not from the eye with secondary uveitis, a failure that appeared to be due in part to the persistence of anti-HSV neutralizing antibody in the eye after the primary uveitis. The results suggest that primary uveitis is caused by infection of the uveal tissue by live HSV, and that secondary uveitis is caused by HSV-induced immunological mechanisms.


Morphometric comparison of the midgut epithelial cells in male and female Aedes aegypti L. (Insecta, Diptera). Midgut epithelial cells of male and female Aedes aegypti, 3 days after emergence, were compared morphometrically. The results of the present investigation concerning the female, are in good agreement with those of a previous study (Hecker et al., 1974), demonstrating that morphometric investigation of midgut epithelia in A. aegypti can successfully be reproduced, and that the mosquito strain used did not show quantitative morphological changes due to laboratory rearing. In males, the cells of the anterior (A) and posterior part (P, 'stomach') of the midgut differ in their quantitative composition. Higher values are found for the microvilli and for the basal labyrinth in the A-part. On the other hand a higher volume density of the mitochondria is present in the P-part. No significant differences are found in the A-part between males and females. Significant differences, however, are present in the P-part. Distinctly more rer in the female stomach can be correlated with the synthesis of enzymes for blood digestion, which are absent in the male. In addition, the more complex functions of the female P-part are also reflected by higher values for other organelles and membrane systems (e.g. mitochondria, basal labyrinth).


The fine structure of the digestive system of Daphnia pulex (Crustacea: Cladocera). The alimentary canal of Daphnia pulex consists of a tube-shaped foregut, a midgut (mesenteron) with an anterior pair of small diverticula, and a short hindgut. The foregut and hindgut are structurally similar. Each is formed by a low cuboidal epithelium 5 mum tall and lined with a chitinous intima. The midgut wall consists of a simple epithelium resting on a thick beaded basal lamina which is surrounded by a spiraling muscularis. Anteriorly the midgut cells are columnar in shape being 30 mum in height each having a basal nucleus, anteriorly concentrated mitochondria and in apical border of long thin microvilli. Posteriorly the midgut cells become progressively shorter so that in the posteriormost region of the midgut the cells are 5 mum tall and cuboidal in shape. The microvilli concomitantly become shorter and thicker. All mesenteron cells contain the usual cytoplasmic organelles. The paired digestive diverticula are simple evaginations of the midgut. The wall of each consists of a simple epithelium of cuboidal cells 25 mum in height, each with a brushed border of long thin microvilli. Enzyme secretion appears to be holocrine in mode and not confined to any one region of the mesenteron though definitely polarized anteriorly. The thin gut muscularis encircles the entire length of the midgut and caeca. Thick and thin filaments appear to be in a 6:1 ratio.


Evolution of the glycogen content and of glucose-6-phosphatase activity in the liver of Salmo gairdneri during development. The evolution of the liver's glycogenic content, cytochemical characterization of the glycogen and glucose-6-phosphatase activity enable us to define three successive phases up to stage 36, just before the first feed. The grade which was low up to stage 24 is then due to beta-particles of ovule origin. Then, up to stage 27, there is a storage phase: alpha-particles appear and accumulate while the enzymatic activity remains non-existent. From the stage 28 to 36 the grade is progressively increasing, the enzymatic activity appears and increases. When the phase ends the liver is able to ensure glycemic regulation and to deal with exogenous nutritional contributions.


Immunology of herpesvirus infection: immunity to herpes simplex virus in eye infections. A gereral, overall pattern of the temporal relationship and interaction between cell and antibody-mediated immune responses following herpes simplex virus infection of the rabbit cornea can be synthesized from our studies. Cell-mediated immunity (CMI) appears early following infection, at a time when mononuclear and lymphocytic cellular proliferation occur at the limbus. Interaction between specifically immune lymphocytes with virus antigens are detected by lymphocyte blastogenesis and migration inhabiting factor. During stromal keratitis, a second phase of CMI involves transient virus-specific cytotoxic lymphocytes, which destroy cells that display viral-induced antigens on their surface. Chemotatic factors generated by viral antigens alone or with antiviral antibody or by virus-sensitized lymphocytes play a role in attracting polymorphonuclear leukocytes to the cornea during stromal keratitis. Soluble mediators of CMI secreated by activated lymphocytes act both specifically and nonspecifically on virus-infected cells, allowing cell destruction and making intracellular virus available for neutralization by antiviral antibody. Cell-mediated immunity in the acute infection, diminishes with the appearance of significant antiviral antibody titers. The late phase of the corneal immune response results from a local antigen-antibody interaction and is characterized by cells predominantly of the plasmacytic type. The presence of complement-dependent cytotoxic antibodies capable of destroying virus-infected cells provide an additional factor in restriction of infection.


Venous plasma cyclic AMP in acute cerebrovascular disease. Antecubital venous blood was sampled from stroke patients in the presence of disodium ethylenediamine tetraacetate. Plasma was analyzed for cyclic AMP applying a competitive protein binding method without any special pretreatment. In mild hemispheric infarction as manifested by moderate hemiparesis and/or dysarthria, plasma cyclic AMP remained in the normal range (8-18 picomoles/ml). In most of the cases with moderate infarction, the cyclic AMP level was distinctly below the normal range several days after the onset of symptoms. However, cyclic AMP remained in the normal range in severe infarction with signs of brain edema, and in two cases with moderately severe symptoms. One of the two cases suffered from later development of brain edema, and the other revealed a large lesion in brain scintigrams. The sizes of the lesion revealed in brain scintigrams were smaller in the moderate cases and larger in the severe cases, except in one of the cases mentioned above. It appeared that with plasma cyclic AMP levels we could predict the extent of the lesion, and perhaps the subsequent development of impending brain edema in a few days after the onset of cerebral infarction. In moderate cases of cerebral hemorrhage, judged from the consciousness, cyclic AMP decreased to a subnormal level 2-4 days after the onset. In severe cases it remained in the normal range. Subarachnoid hemorrhage showed significantly elevated cyclic AMP levels in the early stage.


Effect of dibutyryl cyclic AMP on neuromuscular transmission in myasthenia gravis. The effect of dibutyryl 3',5'-cyclic monophosphate (D-cAMP) on the neuromuscular transmission was studied in a patient with myasthenia gravis during anesthesia. D-cAMP caused a slight increase in single twitch tension, and an initial transient decrease in tension which resulted from the trains of 2 Hz stimuli disappeared after D-cAMP. The finding of the present study suggests that D-cAMP has an anti-fatigue effect in patients with myasthenia gravis.


[Cytophotometric determination of DNA concentration in the cells of experimental brain tumors. II. Primary tumors of rat cerebellum induced by 9, 10-dimethyl-1, 2-benzanthracene]. The Feulgen-DNA cytophotometry was applied for studies of 31 rat cerebellum tumors induced by 9, 10-dimetyl-1,2-bensantracene. Most of these gliomas (22) were astrocytomas of different grades of malignancy. The histological diagnosis of other tumors was: glioblastoma -- 4, oligoastrocytoma -- 2, oligodendroglioma -- 1, gliosarcoma 1. The majority cells of 26 tumors had diploid or paradiploid DNA quantity, 4 tumors (1 astrocytoma, 3 dedifferentiated astroyctomas) had triploid modal classes. The tetraploid modal class and a large number of polyploid cells were found only once for glioblastoma multiforme. A supposition was made that drastic changes of ploidy could arise for the second time during the process of tumor evolution. The authors failed to show any exact differences in the ploidy of gliomas in rats with athyreosis or hyperthyreosis, and in the ploidy of somatic cells in control animals.


[Ultrastructural changes in the livers of rats following multiple injections of corticotropin and sodium ribonucleinate]. The mechanism of the corticotropin (ACTH) action was studied. It was found that daily injections of ACTH-zinc-phosphate (5 un./100 g) to intact albino rats for 14 days result in a disturbance of the hepatocytes ultrastructure. When the hormone was injected in combination with sodium ribonucleate (5 mg/100 g), the deviations were less pronounced, injections of the hormones to adrenalectomized rats did not change the ultrastructure of hepatocytes.


[Hormonal and vitamin regulation of glucose-6-phosphatases activity in the liver]. Glucose-6-phosphatase (G-6-Phase) activity in the rat liver is established to correlate directly with the content of corticosteroids in blood: it lowers with hypocorticoidism (adrenalectomy) and rises with hypercorticoidism (stress). The highest G-6-Phase activity in the liver of the intact animals is observed in autumn, the lowest one in spring, i.e. in the periods when the adrenals function has minimal and maximal values, respectively. Thiamin (0.4 g/kg) is shown to cause a decrease in the G-6-Phase activity in the liver of the intact rats and adrenalectomized or hypophysectomized animals. An assumption is advanced that the found in the experiment a pronounced insulin-like effect of vitamin B with respect to the G-6-Phase activity is connected with an intensified synthesis of the corresponding hormone in the pancreas.


[Stability of lysosomal membranes with different protocols of freezing--thawing]. The non-sedimentary activity of the liver hydrolases (acid RNase, DNase, phosphatase and cathepsins) of albino rats was studied at different freezing-thawing programmes (rapid and two-staged). It is found that the non-sedimentary activity of hydrolases increases in case of all freezing-thawing programmes. The lowest activity is observed at two-staged programmes, and after rapid freezing and rapid hawing of lysosomes.


[Adrenaline and cyclic AMP stimulation of ketopentose and sedoheptulose formation in rat liver homogenates]. Formation of sedoheptulose-7-phosphate and ketopentose phosphate was studied in vitro as affected by epinephrine and cAMP. No effect of epinephrine on the activity of transketolase was found with ribose-5-phosphate as a substrate of the nonoxidative reactions of the pentose phosphate ccyle. Epinephrine and cAMP enhance the formation of ketopentoses and sedoheptulose with glycogen as a main carbohydrate source, which is most pronounced in the experiments with cold preincubation. The phosphorylase system mediate influence of epinephrine and cAMP on the nonoxidative reactions products may be assumed.


[Effect of thiol-oxidizing agents on several enzymes in rat liver mitochondria]. The sulphydryl groups of nonprotein thiols and proteins of mitochondria, activity of enzymes, oxidative phosphorylation and swelling of these organellas were studied as affected by the thiol-oxidizing agents. Diamide and azoester are shown to oxidize SH-groups of mitochondria, inhibit isocytrate dehydrogenase and succinate: cytochrome oxidation and inhibits energy-dependent swelling of mitochondria. Under the effect of azoester the rate of oxygen consumption by mitochondria increases and there occurs their sharp swelling.


[Concentration of cyclic adenosine-3',5'-monophosphate in the tissues and its excretion in the urine of rats during ontogenesis]. The intracellular content of cyclic adenosine 3',5'-monophosphate (cAMP) in the liver and epididymal fat as well as excretion of cAMP with urea were studied in rats at the age of 1, 3, 12 and 24 months. No statistically significant age changes were found in the intracellular content of cAMP in the tissues. A decreases in the intensity of cAMP excretion with urea in the 12-month rats as compared to the one-month ones is statistically significant.


Canine cutaneous histiocytoma: ultrastructural and cytochemical observations. Five canine cutaneous histiocytomas were studied by electron microscopy and esterase cytochemistry. The tumor cells contained irregular nuclei, characteristic lysosomal granules, and perinuclear microfilaments. The cells showed activity with alpha-naphthyl acetate esterase stains. These characteristics are evidence that this tumor originates from the mononuclear phagocyte system.


Studies on rotavirus infection and diarrhoea in young calves. The occurrence of diarrhoea in calves was monitored during the first three weeks of life. Calves fed amounts of colostrum sufficient to produce serum Ig levels in excess of 30 mg per ml did not develop diarrhoea, whereas calves fed less colostrum did. Rotaviruses and mycoplasma-like particles were observed in the faeces of calves with and without diarrhoea. The epidemiology of rotavirus infection in calves is discussed.


Argyrophil cell carcinoma (apudoma) of the esophagus. A histopathologic entity. In a series of 79 cases of primary esophageal carcinoma resected at The Center for Adult Diseases, Osaka, there were six tumors with specific histopathologic features valid for the diagnosis of argyrophil cell carcinoma. Of the 6 tumors, 3 were studied electron microscopically and assay for ACTH content was performed on 4 tumors. Clinically, the ages of the 6 patients ranged from 56 to 71 years; two were women and four men. Four of the 6 patients died with widespread tumor recurrences within 9 months of operation. Microscopically, the 6 tumors were composed largely or almost entirely of small, spindle-shaped cells resembling those of oat cell carcinoma of the lung, and were characterized by the arrangement of tumor cells in solid sheets or anastomosing cords, the presence of argyrophil tumor cells, and the deposits of amyloid. Electron microscopically, the three tumors contained neurosecretory-type granules. Using bioassay or radioimmunoassay ACTH activity in the tumor tissues was detected in 3 out of the 4 tumors determined. From the light and electron microscopic characteristics and the assay evidence, it seems reasonable to conclude that the 6 tumors are endocrine polypeptide producing tumors (apudomas) that arise from argyrophil cells normally found among the basal cells of the esophageal mucosa, and that they represent a distinct histopathologic entity clearly distinguishable from other types of esophageal carcinomas.


The appearance and degradation of specific hepatocellular cytoplasmic inclusion bodies in rat liver due to D-galactosamine. I. The relation between the amount of liver glycogen and the appearance of the atypical dense bodies in the liver cell. One of the most sensitive and specific signs of the galactosamine effect upon the rat liver cell is the appearance of PAS-positive and diastase-resistant granules within the cytoplasm of hepatocytes. Light-microscopic, histochemical, biochemical, and electron-microscopic findings reveal that the appearance of these ADB (= atypical dense bodies) depends upon a working glycogen metabolism at the time of GalN treatment. The ADB are composed of particles resembling, due to shape and size, ribosomes and beta particles of glycogen. Most of them are surrounded by the rER, but they are never enclosed by a limiting membrane. Due to sequential changes they can be generally classified into three types; the early, the intermediate, and the late type. In seven experiments it can be shown, that the appearance of the ADB depends upon the time and dosage after GalN treatment. They occur even if an additional treatment with galactose or uridine prevents the liver from the features of a hepatitis, as also shown in the livers of newborn animals up to 3 weeks of age. The histochemical response against various glucosidases, hexosaminidases, pronase, and RNAse as well as against various fixatives indicates that ADB are composed of, at least, two different constituents, the former RNAse-sensitive and visible with routine light-microscopic staining procedures, the latter RNA-resistant, PAS-positive, and invisible after staining with H & E or toluidine blue. The latter is diastase-resistant, suggesting that this portion of ADB does not represent the usual glycoproteins but some abnormal metabolite of glycogen. The ADB can be detected with maximal accumulation in the cytoplasm of hepatocytes at that time when the glycogen content determined in the liver homogenate by biochemical methods is greatly reduced.


[Effect of a reduced diet on hyperlipoproteinemia in metabolic-alimentary obesity]. The effect of calorifically reduced diet No 8e on the lipoproteinic composition of the blood serum in patients with metabolic-alimentary adiposity was studied. Most of the patients examined demonstrated hyperlipoproteinemia, basically of the IIb type, more seldom of the IIa and IV types. Following a course of the reduced diet the frequency of hyperlipoproteinemia of the II, III and IV types declines and the content of atherogenid lipoprotein fractions in the serum goes down. In young patients the effect of a reduced diet on the lipoprotein composition of the blood serum proved most effective.


[Mechanism of resistance of a clone isolated from L cells chronically infected with the virus of vesicular stomatitis]. The results of the study on antiviral immunity acquired by L cells to vesicular stomatitis virus are presented. We failed to detect the presence of the indicator virus in the resistant culture by means of virological, electron microscopic or cytochemical methods. Molecular hybrization experiments demonstrated the lack in the nuclear DNA of sequences homologous to vesicular stomatitis virus RNA.


[Aetiological studies on viral pneumonia (author's transl)]. 401 cases of viral pneumonia diagnosed between January 1973 and August 1975 were investigated serologically by the complement-fixation test. The percentage distribution of the responsible pathogenic organism in this series of cases was as follows: influenza virus A 45.9%, Mycoplasma pneumoniae 19.5%, Coxsackie B viruses 9.2%, cytomegalovirus 7.5% and Chlamydia psittaci 8.5%. The remaining 9.4% cases were caused by adeno, parainfluenza, measles, influenza B, herpes simplex and respiratory syncytial viruses. Influenza virus was found mainly in elderly people (mean age 58.4 years), whilst pneumonia due to Mycoplasma occurred mainly in young adults (mean age 24.4 years). Infections with Coxsackie B viruses were almost entirely restriced to the warmer months; by contrast, the influenza virus was usually found in epidemic form and only during a few weeks in winter.


[Current concepts in the physiology of fat absorption (author's transl)]. Current concepts of intestinal fat absorption are reviewed and the aspects of intraluminal formation and the role of the mixed lipid micelle, the concept of the unstirred water layer and the role of the fatty acid-binding protein in the intracellular transport of long-chain fatty acids are particularly emphasized. In addition, several aspects of intestinal lipoprotein production, secretion and metabolism are discussed.


[Development of cellular immunity in patients with viral hepatitis]. The development of cell-mediated immunity (CMI) to the surface antigen of hepatitis B virus (HBSAg) and Botevgrad antigen (BA) was traced in 50 hepatitis patients. Migration inhibition test (MIT) was performed with purified HBSg and AB. Blood samples from every hepatitis patient were obtained at the beginning of the icteric phase, 10 days later and during convalescence. There was correlation between the two types of viral hepatitis and the type of cellular immune response. The development of CMI is associated with disappearance of HBSAg from the serum of hepatitis patients. CMI to HBSAg develops within 9-12 days after the onset of icterus and to BA during the first two days of icterus. There is a relationship between the persistence of HBSAg and CMI.


[Experimental study of the influence of reovirus infection on the course and outcome of pregnancy]. The possibility of intrauterine infection of fetuses of random-bred white mice with reovirus type 3 at various periods of pregnancy has been demonstrated. The unfavourable effect of reovirus infection on the course and outcome of pregnancy in some cases was manifested by impairment of embryogenesis, stillbirths and subsequent death of defective offsprings. Morphological examinations revealed marked pathological alterations in the lungs, brain, liver, and kidneys of suckling mice infected in utero.


[Partial trisomy 9 with partial retention of the long arm (author's transl)]. A new case of partial trisomy 9 is reported. The characteristic clinical features consist of: 1. Microcephaly, enophthalmos, antimongloid slant of the eyes, hypertelorism, protruding ears, large nose, downward slant of the mouth corners, hypoplasia of phalanges. 2. Abnormal dermal ridge system and crease picture: irregularities of the ridge pattern of finger prints, palms and soles, a much reduced total ridge count (TRC), transverse palmar crease on both palms, underdevelopment of the C line. 3 Severe mental retardation. However, this case represents a variation of the chromosomal anomaly described so far, in as much as an important part of the long arm of the additional chromosome 9 is present.


[The secretory function of the pancreas and the ageing progress (author's transl)]. A short literature survey is followed by an exposition of the methods of research (pancreozymin and secretin stimulation) and the results and their valuation. There is proved an decrease of the secretory pancreatic function.


[Effect of gestagen therapy upon estradiol- and progesterone-receptor-level and 17beta-hydroxysteroid dehydrogenase in human endometrial adenocarcinoma (author's transl)]. Oestradiol was converted to oestrone about ten time more rapidly by subcellular fractions of normal human endometrium of the secretory phase than by tissue of the proliferative phase. In subcellular fractions of endometrial carcinoma the 17beta-hydroxysteroid dehydrogenase (17beta-HSD) activity decreased with decreasing differentiation of the tumour. Most of the 17beta-HSD activity was located in mitochondrial and microsomal fractions of both normal and neoplastic endometrium. After treatment of patients with gestagens only the well differentiated carcinomata significantly increased in 17beta-HSD activity demonstrating that the hormonal stimulus leads to similar effects on the 17beta-HSD activity as in normal endometrium. Furthermore quantitative aspects of the in vitro binding of 3H-oestradiol and 3H-progesterone to receptor components from normal endometrium and endometrial carcinoma cytoplasmic fractions have been studied. In normal tissue the number of cytoplasmic binding sites for both oestradiol and progesterone varied dramatically during the menstrual cycle: number of oestradiol binding sites were highest during the proliferative phase and fell during the secretory phase; for progesterone site the contrary was the case. In all endometrial carcinomata high oestradiol binding activity was observed. In contrast the number of progesterone sites in the tumours was related to the state of differentiation, which paralled the progestional sensitivity of these tumours.


[Differing carcinogenic activity in BD-rats of 1-phenyl- and 1-(pyridyl-3)-3,3-diethyltriazene after single doses on 1., 10. or 30. day of life (author's transl)]. 1-Phenyl- and 1-(pyridyl-3)-3,3-diethyltriazene have been investigated for carcinogenic effects in BD-rats after subcutaneous injection of a single dose of 50 mg of the compounds on day 1, 10, or 30 of life. The phenyl derivative showed a lower carcinogenic activity in comparison with the pyridyltriazene. Predominantly neurogenic tumors were observed. These were seen much more on treatment on day 1 or 10 of life than on treatment on day 30. The results confirm that the nervous system of rats is a target organ predominantly during early postnatal life.


Histochemical correlation between glycogen, nucleic acids and nucleases in pre-neoplastic and neoplastic lesions of rat liver after short-term administration of N-nitrosomorpholine. After 7 weeks of oral administration of the carcinogen N-nitrosomorpholine (12 mg NNM ad 100 ml of drinking water) to male rats, marked hepatocellular changes were found predominantly in the centers of the lobules. These were loss of glycogen, disorganisation of the basophilic bodies and, sometimes, loss of cytoplasmic basophilia or pyroninophilia, necrotic cells and increase in the activity of acid DNAse and RNAse. These centrilobular alterations were reversible after withdrawal of the carcinogen. They are, therefore, attributed to the nonspecific-toxic effect of the carcinogen. In peripheral and midzonal regions of the lobules basically different cellular changes appeared which were unimportant during the phase of intoxication, but became prominent after cessation of the carcinogenic treatment. These lesions were: excessive storage of glycogen, displacement of basophilic bodies and an increase in cytoplasmic acidophilia. The hepatocytes showing these cytoplasmic changes initially formed foci. Neoplastic nodules and frank hepatocellular carcinomas developed later. During these later stages of the experiment both the foci and the nodules consisted of 4 main types of altered hepatocytes: 1) "clear" glycogen storage cells, 2) acidophilic cells, 3) vacuolated (fat storing) cells, 4) basophilic (pyroninophilic) cells poor in, or free from, glycogen. The larger nodules and carcinomas contained predominantly basophilic cells. The activity of nucleases, especially that of acid DNAse, decreased in small foci which as a rule developed later than the foci of glycogen storage. In most cells of neoplastic nodules and carcinomas the activity of these enzymes disappeared, but it reappeared in necrotic cells. The progressive alterations in the activity of the nucleases seemed to be related to the phenotypic expression of malignancy and could be a sign of a fundamental metabolic change taking place during a relatively late step in the malignant transformation.


Lamellar structures in rat ova and their chemical composition. The paper represents a study of the chemical composition of lamellar structures in rat ova during cleavage based on the morphology of their submicroscopic structure after the action of various fixatives and various methods of contrasting ultrathin sections and on the employment of cytochemical methods. Reactions to RNA, polysaccharides, acid and alkaline phosphatase, non-specific esterase, glucoso-6-phosphatase and succinate dehydrogenase were tested on a submicroscopic level; lipids were tested on a light-microscopic level. The results have shown that the lamellae are composed of proteins. No RNA, polysaccharides, lipids or any of the investigated enzymes were detected in lamellar structures. Lamellar structures, therefore, are considered to be storage material chiefly used in the second half of the cleavage for developmental processes in the rat ovum.


Histochemical studies on the distribution of alkaline phosphatase, acid phosphatase, 5-nucleotidase and ATPase in various reproductive tissues of certain digenetic trematodes. Out of other functions performed by vitellaria in digenetic trematodes, their role in the formation of shell globules and shell membrane of the capsule, as well as in the excretion of iron with the help of vitamin C is very important. The present histochemical work shows the localization of certain enzymes in different parts of the reproductive system of ten species of trematodes viz.: Neopronocephalus triangularis Mehra, 1932; Glossimetra orientalis Mehra, 1937; Orientodiscus lobatus Srivastava, 1938; Eumegacetes artemii Mehra, 1935; Ganeo tigrinus mehra et Negi, 1928; Encyclometra caudata Dollfus, 1928; Thapariella udaipurensis Gupta and Sharma, 1970; Paradistomoides indicum Narain et Das, 1929; Patagifer wesleyi Verma, 1936; Proalarioides tropidonotus Vidyarthi, 1937 and indicates their functional significance. The hydrolytic enzymes (alkaline phosphatase, acid phosphatase, 5-nucleotidase and ATPase) are suggestive of their involvement in the uptake of certain nutrients, glycogen and lipoprotein being very significant among others. The four enzymes could also be detected in testes, ovary, uterus, cirrus sac and egg shell. The possible functional significance of each enzyme has been discussed.


Conformation-controlled trans-effect of the proximal histidine in haemoglobins. An electron spin resonance study of monomeric nitrosyl-57Fe-haemoglobins. A monomeric allosteric haemoglobin from Chironomus thummi thummi was reconstituted with 57Fe-haem. This reconstituted haemoglobin was found to be identical to the non-reconstituted material with regard to the O2-binding properties and the visible spectra. The 270 MHz proton magnetic resonance of the bis (cyano)-57Fe-haemin shows that the reconstituted haem is identical with the non-reconstituted haem. Furthermore it has been proved by proton magnetic resonance that in Chironomus haemoglobins the prosthetic group is proto-haem IX. The ESR spectrum of the native nitrosyl haemoglobin demonstrates rhombic symmetry of the haem iron (gxx=2.086, gyy=1.981, gzz=2.005) and hyperfine structures at gyy (aNepsilon=1.35 mT) and at gzz (a15NO=3.05 MT, a14NO=2.19 mT, aNepsilon=0.715 mT, a57Fe=0.38 mT). The spectrum is independent of pH and can be classified as a type II spectrum following the classification of ref. 2. NO-binding obviously stabilizes the tertiary structure of this haemoglobin in a "tense" conformation with a relatively strong sigma bond of the 5th ligand (Nepsilon of imidazole) and a relatively weak sigma bond of the 6th ligand (NO). Reaction of this haemoglobin with anionic, cationic and non-ionic detergents, respectively, leads to a transformation of the NO-ligated form into a "relaxed" conformation with a stretched or broken sigma bond of the 5th ligand (Nepsilon of imidazole) and a strong sigma bond of the 6th ligand (NO). The ESR spectrum of this modified NO-haemoglobin shows again a rhombic symmetry of the haem iron (gxx=2.10, gyy=2.06, gzz=2.010), but dramatically changes in the g tensors (low field shift), hyperfine structures and hyperfine splitting constants (a15NO=2.32 MT, a14NO=1.66 mT, a57Fe=0.48 mT). The hyperfine splitting is isotropic. Transition from the "tense" conformation to the "relaxed" conformation corresponds with an increase of the spin density at the iron atom by 26% and a decrease of the spin density at the NO ligand by 25%. The spin density at the Nepsilon of imidazole strongly decreases in the "relaxed" conformation, so that a hyperfine splitting of this ligand is not any more resolved. These results demonstrate the trans-effect of the proximal imidazole which in haemoglobins controls of the binding properties of the external ligand in trans-position.


Regulation of intracellular pyrophosphatase-activity and conservation of the phosphoanhydride-energy of inorganic pyrophosphate in microbial metabolism. The conservation of the phosphoanhydride-energy of inorganic pyrophosphate (PP) in microbial metabolism requires a stringent metabolic control of the intracellular pyrophosphatases (PPases, EC 3.6.1.1). In this article, the rate of intracellular PP-liberation during biosynthesis of cellular constituents is calculated from the specific growth rate and the macromolecular composition of the respective microorganism. This rate is compared with the maximal specific activity of PPase in cell free extracts or purified enzyme preparations in order to investigate the possibility of the limitation of biosynthesis through PPase-activity. The catalytic and regulatory properties of microbial PPases are discussed in respect to the occurrence of PP-dependent ransphosphorylases. The evidence showing that certain anaerobic microorganisms including photosynthetic bacteria, can use PP instead of ATP as phosphate donor for transphosphorylation reactions will be discussed.


Photosynthetic electron carriers at a heptane-water interface. Surface properties of monomolecular films of chlorophyll (Chl), plastocyanin (Pc), cytochrome c (Cyt) and ferridoxin (Fd) were measured at a heptane-water interface. Mixed films of Chl and the other components were examined in darkness and in light. The area/molecule, A, for Fd (from Cl. pasteurianum) is much larger at a heptane-water than Fd (from spinach) at an air-water interface. This difference in A may be the source of the Fd or the extent of denaturation at the different interfaces. There appears to be a photoreaction between Chl and Fd in the presence of ascorbate. The A for Cyt is much larger at a heptane-water than at an air-water interface. In mixed films there is a strong interaction between Chl and reduced Cyt in the dark. No such interaction is observed between Chl and oxidized Cyt. With mixed films of Chl and reduced Pc there is a significant, reversible, light induced change in deltaV.


Chirality of the hydrogen transfer to NAD catalyzed by myo-inositol dehydrogenase from Klebsiella pneumoniae. Chirality, Hydrogen Transfer, myo-Inositol Dehydrogenase. The chirality of the hydrogen transfer to NAD catalyzed by myo-inositol dehydrogenase (myo-Inositol: NAD 2-oxydoreductase, EC 1.1.1.18) from Klebsiella pneumoniae (formerly classified taxonomically as Aerobacter aerogenes or Kleb siella aerogenes) was investigated. [4-3H] NAD was enzymatically reduced to [4-3H] NADH with non-labeled myoinositol and myo-inositol dehydrogenase. The stereochemistry of the prochiral center at C4 of the NADH produced was determined. It was found that the label was exclusively located at the (4S) position of the produced NADH. Since the hydrogen transferred from non-labeled myo-inositol to [4-3H] NAD must have entered the opposite of (R) position, myo-inositol dehydrogenase from K. pneumoniae should be classified as an (R) or A-type enzyme with respect to the stereochemistry of the hydrogen transfer to NAD.


[Histochemistry of proteins and their functionally active groups in the skin of the neck and mucous membrane of the oral cavity of white rats in the zone exposed to a helium-neon laser]. The author made experiments on 49 white rats exposing their cervical skin ano oral cavity mucous membrane to the irradiation beam of a 40 mvt helium-neon laser (lambda 6328A) during 10-15 minutes. The reactive capacity of proteins was found to have intensified and the content of functionally active groups, especially SH. to have increased as well as well as the activity of the cytochromozydase. When the exposition to laser irradiation was raised to 30 minutes pronounced morphohistochemical lesions were noted in the cervical skin and oral cavity mucous membrane. The data received may be useful in clinical practice for the application of low-power laser irradiation of 6328A wave length for stimulation of metabolic processes.


Cystinosis with crystal-induced synovitis and arthropathy. A clinically and experimentally verified intermediary form of cystinosis is described. A 30-year old patient has been examined initially for eye complications confined to the frontal segment of the eye on the cornea and conjunctiva. The joint disease received no attention despite the fact that the motor apparatus of the patient was involved from her childhood. As regards the arthrology, the disease can be classed among crystal-induced synovitis and arthropathy. The lesion of the tubular apparatus of the kidney, which cannot transform vitamin D into its active form, represents an important factor in the genesis of osteoporosis. A description of the intermediary from of cystinosis with eye, kidney and joint symptoms was not found in the literature.


[Effiency in surgery (author's transl)]. Increase in the cost of medical care force us to adopt "medical rationalisation" instead of as previously "hospital rationalisation". This medical rationalisation constitutes a new, well-thought out way of putting questions about diagnosis, therapy and after-care. We must abandon the opinion that the prestige of a surgical department rests in the number of beds. Instead we must use other yardsticks such as the greater use of ambulant care, the shortest hospital stay for routine operations, the shortest preoperative waiting times and an increased operation frequency. Moreover, we need a diagnosis fixed from the start, a large enough operation capacity and sufficient possibilities for postoperative care, stringency in keeping agreed admittances and discharges as regards elective routine surgery and intimate co-operation between doctors, hospital economists, nursing staff and other experts.


Ultrastructure of lipopolysaccharides of Yersinia enterocolitica, Salmonella typhimurium and Escherichia coli. The fine structure of isolated lipopolysaccharides (LPS) from the rough and smooth form of an Yersinia enterocolitica strain (Ye 75 R/Ye 75 S) and from smooth forms of Salmonella typhimurium (S 1010) and Escherichia coli (Essen) were examined electron-microscopically by negative staining. Partial denaturation of LPS in Tris-buffer with acid and/or polymyxin B treatment revealed a common structure of strandlike LPS. Electron-microscopically, LPS-strands were found to consist of two identical sub-strands which form a double helix. High resolution electron microscopy permitted the identification of a total of four longitudinal fibrils (diameter approximately 20 A); therefore, each sub-strand consists of two longitudinal fibrils. These results were correlated with those obtained with positive staining procedure and chemical fixation technique. The development of the "double-track"-profile of the outer membrane was interpreted to result from the projection of the helical longitudinal fibrils into the image plane.


[Studies on virus inactivation by chlorine during water disinfection (author's transl)]. The studies described indicate a potential for water-borne transmission of viral diseases and the problems involved in virus inactivation by means of water chlorination. In contrast to the amount of free chlorine, the value of the oxidation-reduction potential (ORP) was found to be a criterion of virus inactivation. For virus inactivation, higher ORP values and longer periods of contact than for the killing of bacteria, respectively, were found to be necessary. To ensure the inactivation of poliovirus in water contaminated with organic substances, an ORP of + 780 mV (0.3-0.6 mg/l free chlorine) should be maintained for 15-30 min. Adenovirus has shown an almost identical resistance to inactivation. Possibilities for utilizing the mechanism of virus inactivation by the action of chemical disinfectants are discussed.


[Results of animal experiments concerning the carcinogenic effect of fibrous dusts and their interpretation with regard to the carcinogenesis in humans (author's transl)]. After reviewing the hypotheses about the pathogenesis of asbestos-induced malignant tumours we report about experimental data on animals. A high incidence of tumours (most of them mesotheliomas) was induced in rats by intraperitoneal injection of fibrous dusts (chrysotile, palygorscite, crocidolite, glass fibres, nemalite). Treatment with 8 types of granular dusts led though applicating a high dosage (50--100 mg) to neoplasms in only a small percentage of animals. After intraperitoneal application of 2 mg of chrysotile, crocidolite or glass fibres a tumour incidence in a range from 16% to 38% was observed and fibrous reaction was slight. 100 mg of milled chrysotile with relative short fibres (99.8% less than 5 mum, 99.5% less than 3 mum) caused no asbestosis, nevertheless tumours developed in 32% of the rats. Intraperitoneal injection of fibrous dusts also induced mesotheliomas in mice, however not in Syrian hamsters and guinea pigs. Our results point out that the fibrous shape of asbestos dust causes its carcinogenic effect and that furthermore other fibrous dusts can also lead to tumours. Prerequisites are an adequate measure of the fibres and their constancy in the tissue. For these two parameters no exact dates exist. It is estimated that a fibre with a diameter less than 1 mum and a length less than 3 mum exert a cancerogenic effect. Furthermore, a sequence of other factors has an importance for the dose-effect relationship of fibrous dusts. Material of the fibres plays a role in so far it defines the effect producing amount of fibres. The relevance of the results of animal experiments to man is discussed especially with regard to the cancerogenic effect of glass fibres.


[Effect of the site of microbial aerosol application on the pathogenesis and clinical picture of aerosol infection]. On the basis of experimental and clinical study of infections with the aerosol mechanism of infection there was revealed a relationship between the fractional-dispersive composition of the microbial aerosol, the porta of infection and the clinico-pathogenetic peculiarities of the course of the disease. On the example of tularemia, plague and other nosological forms it was demonstrated that coarse-dispersive aerosol caused development of oculo-bubonic and anginous-bubonic form of the disease, whereas the high-dispersive aerosol led to the appearance of primary pneumonia. In experimental aerosol infection with the causative agents in which the infection under natural conditions is not air-borne (botulism, American horse encephalo-myelitis, etc.) specific disease as a rule develops without any primary affection of the respiratory organs.


[The coxsackievirus-infected mouse: an animal model for the study of virus myocarditis]. Basing on the experimental infection of adult mice with coxsackie virus A9 reported by Lerner in 1965 and the successful cultivation of the virus from the hearts of experimental animals, a model for studying virus myocarditis is proposed. By a combination of factors favouring the infection (age of the animals above 1 year, physical load prior to infection by repeated swimming) a high virus re-isolation rate was achieved. Cultivation of the virus from the mouse heart was possible on the 3rd day p.i. in 81%, on the 6th day in 71%, on the 9th day in 31%, and on the 12th day in 12% of the cases. In 66% of the animals towards the end of the period of observation a significant increase in few cases is the virus isolated on the 3rd and 6th day p.i. also from the skeletal muscles. The model can be used both for pathogenetic studies on myocardites elicited by cardiotropic viruses and for in vivo testing of antiviral substances.


[Glycogen synthetase and fructose diphosphatase activity in the tussues of mollusks (Mytilus galloprovincialis) and crustacenas (Balanus improvisus, Carcinus maenas)]. The level of the activity of the enzymes studied is rather similar in all the species investigated, being the highest in muscles and gills. Seasonal changes in the activity of the enzymes in mussel tissues are closely related to reproductive periods and reflect changes in the level of glycogen synthesis.


Effect of arecoline on synaptosomal K+-phosphatase and (Na+ + K+)-ATPase. Synaptosomal fractions and synaptosomal membranes from rat brain tissue were prepared and characterized enzymatically. Arecoline increased both the activity of K+-phosphatase in incubated synaptosomal fractions and the (Na+ + K+)-ATPase activity of synaptosomal membranes by 40% and 78%, respectively. This activation of ion transport processes is believed to be associated with increased ACh synthesis produced by arecoline.


[Seasonal changes in the reaction of the hypophyseal-adrenal system to adrenomimetics in the suslik Citellus erythrogenys]. Studies have been made on the reaction of the hypophysial-adrenal system to the injection of adrenalin and novodrin to the ground squirrel C. erythrogenys at various seasons of year and at different functional conditions of the animals. Together with seasonal variations in the basal level of corticosteroids in the peripheral blood, seasonal changes in the reaction of non-hibernating animals to adrenomimetics were found. Stimulating effect of the adrenomimetics was higher at spring, immediately after awakening, being significantly lower in summer and being absent before the onset of hibernation. At the same time, the sensivity of the adrenal cortex to ACTH was relatively high. Presumably, seasonal changes in the reaction of the hypophysial-adrenal system in the ground squirrels to adrenomimetics are associated either with changes in the sensitivity of the adrenoreceptors, or with changes in the reactivity of the central part of the hypothalamo-hypophysial-adrenal system.


[Discriminant-analytic structure-effect relationship of qualitative biological data. Virostatic effect of isatin-beta-isothiosemicarbazones]. "Yes/No" results from the plaque-diffusion inhibition test concerning the virostatic activity of substituted isatin-beta-isothiosemicarbazones against mengo- and vaccinia-viruses can be described discriminant analytically by means of simple substituent constants. The discriminant analysis permits quantitative structure-activity analysis of qualitative and semi-quantitative test data, thus offering a chance for theoretical synthesis optimization already at the level of rough screening.


[The effect of diisopropylfluorphosphate on the adenylate cyclase activity and the 3',5'-AMP content of myocardium and brain]. Adenylate cyclase [ATP-pyrophosphatelyase (cyclizing) EC 4.6.1.1.] from ventricular muscles and the cerebrum of rats can be inhibited by diisopropylphosphofluoridate (DFP) and paraxone in concentrations from 10(-7) - 10(-9)M, and by dimethoate in concentrations from 10(-5) - 10(-7)M. The cAMP content in the heart diminished after i.p. 1.44 mg/kg DFP by 59.9%, and in the cerebrum by 68.2%. The depletion of cAMP caused by double LD50 DFP in the rat heart can be influenced neither by atropine alone, nor in combination with TMB-4. The results are discussed with regard to a possible action mechanism.


Stimulation of Ca2+ uptake by cyclic AMP and protein kinase in sarcoplasmic reticulum-rich and sarcolemma-rich microsomal fractions from rabbit heart. The effect of cyclic AMP on Ca2+ uptake by rabbit heart microsomal vesicular fractions representing mainly fragments of either sarcoplasmic reticulum or sarcolemma was investigated in the presence and absence of soluble cardiac protein kinase and with microsomes prephosphorylated by cyclic AMP-dependent protein kinase. The acceleration of oxalate-promoted Ca2+ uptake by fragmented sarcoplasmic reticulum following cyclic AMP-dependent membrane protein phosphorylation, observed by other authors, was confirmed. In addition it was found that the acceleration was greatest at pH 7.2 and almost negligible at pH 6.0 and pH 7.8. A very marked increase in Ca2+ uptake by cyclic AMP-dependent membrane protein phosphorylation was observed in the presence of boric acid, a reversible inhibitor of Ca2+ uptake. In addition to the microsomal fraction thought to represent mainly fragments of the sarcoplasmic reticulum, the effect of protein kinase and cyclic AMP on Ca2+ uptake was investigated in a cardiac sarcolemma-enriched membrane fraction. Ca2+ uptake by sarcolemmal vesicles, unlike Ca2+ uptake by sarcoplasmic reticulum vesicles, was inhibited by low doses of digitoxin. The acceleration of oxalate-promoted Ca2+ uptake by cyclic AMP and soluble cardiac protein kinase, however, was quite similar to what was seen in preparations of fragmented sarcoplasmic reticulum, which suggests that it may reflect an acceleration of active Ca2+ transport across the myocardial cell surface membrane.


An improved protein binding assay for guanosine-3',5'-monophosphate using a binding protein from the pupa of the silkmoth, Bombyx mori L. A modification of the protein binding assay for cyclic guanosine-3',5'-monophosphate (cyclic GMP) is described that is more sensitive and less subject to interference by cyclic AMP than are previously published protein binding methods. The assay employs a purified binding protein from the fat body of the pupa of the common silkmoth, Bombyx mori. The dissociation constant of the binding protein for cyclic GMP is 4.3 nM. A protein kinase modulator protein isolated from the same species increases the binding affinity and capacity of the cyclic GMP binding protein and can be used to advantage in the assay for cyclic GMP. As little as 0.1 pmoles of cyclic GMP can be detected by this procedure. Changes in the level of cyclic GMP in the frog heart during the cardiac cycle were determined by means of the new assay.


[The systemic fungicide tridermorph as an inhibitor of the respiratory chain of electron transfer particles from beef heart mitochondria]. Tridemorph (N-tridecyl-2,6-dimethylmorpholine) inhibits both the NADH-oxidase and the succinate-cytochrome c oxydoreductase system of non-phosphorylating electron transfer particles from beef heart. The concentration required for half-inhibition amounted to 3,4 muM and 24 muM respectively. Two different sites of action in the respiratory chain could be localized by means of difference spectroscopy and measurements of enzymic activities in various partial systems. The inhibition of the NADH-ubiquinone oxydoreductase activity as well as the suppression of the NADH-induced reduction of all cytochromes on the one hand and the insensitivity of the NADH-ferricyanide oxydoreductase system on the other argue in favour of a site of action similar to rotenone. The partial suppression of the succinate-induced reduction of cytochrome b with simultaneous complete inhibition of the reduction of the other cytochromes indicate an additional site of action analogous to antimycin A. Both inhibitory actions appeared instantaneously after the addition of tridemorph and were counteracted by serum albumin. Furthermore, tridemorph inhibited the oxydation of external ferrocytochrome c but not that of ascorbate/tetra-methyl-p-phenylene-diamine-HCI (TMPID) showing that it is not a true inhibitor of the cytochrome oxidase. The TMPD-induced bypass of the succinate oxidation was inhibited as well. The possible role of the inhibition of the main pathway of the respiratory chain for the fungicidal action of tridemorph is discussed.


Effect of salicylate and adrenocorticotropin on the hepatic and serum cholesterol in catfish, Heteropneustes fossilis (Bloch). A single injection of salicylate or salicylate plus ACTH was able to lower the hepatic cholesterol content within one hour after the treatment. However, their daily injection for eight days caused significant rise in the hepatic cholesterol. ACTH alone could not significantly alter the liver cholesterol content after similar treatment. A single injection of salicylate produced hypocholesterolemia within one and three hours after the treatment. ACTH or salicylate plus ACTH also brought about 50 per cent reduction in serum cholesterol level from its initial control value within one hour. Similar treatments, however, raised the serum cholesterol after three hours. The rise in the serum cholesterol level was about twofold in animals five hours after salicylate plus ACTH treatment. Daily administration of salicylate, ACTH or salicylate plus ACTH for eight days caused, however, hypocholesterolemia.


Effects of ethosuximide upon psychomotor responses and electromyographic parameters of healthy individuals. The purpose of this paper was to investigate the effects of anticonvulsant ethosuximide upon physiological parameters, psychomotor reactions and electromyographic criteria. Ethosuximide increased the reaction times to flashes and the choice reaction time in most subjects, often provoked a greater amount of errors during choice reactions and decreased the average heart frequency. The functional activation during the tasks was diminished. The EEG showed no marked qualitative or quantitative changes. Ethosuximide reduced the maximum conduction velocity of the motor nerve and changed the action potential duration but not the action potential shape. There is no exact parallelism between the increase in reaction time and decrease of nerve conduction velocity. The drug effect upon psychomotor reactions seems to be caused by reduction of vigilance and an inhibitory effect upon the individual's motor responsiveness. Like other anticonvulsants, ethosuximide may alter the electrical properties of all excitable membranes and, by this ubiquitous site of action, exerts the described effects.


Existence of big and little forms of luteinizing hormone in human serum. Serum fractions from normal subjects obtained by gel chromatography have been investigated using three different assay systems: radioimmunoassay (RIA), radioligand receptor assay (RRA), and testosterone production assay (TPA). The bulk of immunoassayable and "bioassayable" LH-activity was found in two fractions differing widely in their molecular size. The slower moving component, designated as "little" LH, migrated identical to the radioiodinated pituitary hormone (LER 960) with a molecular weight of about 30,000, while "big" LH appeared in an elution volume consistent with a molecular weight range between 140,000 and 180,000. Concordance was seen between the LH-activities measured in all three assay systems. The RRA/RIA ratio varied between 1.6 and 8.9, the RRA/TPA ratio was close to unity. Treatment with 6 M urea and 0.1% mercaptoethanol and also, exposure to different pH values and salt concentrations did not change the elution position of the two LH components. Also, "big" and "little" LH appeared unaltered after re-filtration and no conversion each other could be found. In another experiment injection of gonadotrophin releasing hormone (Gn-RH) into a male induced a profound shift of LH towards the low molecular weight species. Kinetic uptake studies with "big" and "little" LH using RRA showed identical affinities to the receptor preparation. Ion exchange chromatography of serum, however, did not give two LH components, indicating no major differences in charge properties. This finding could be confirmed by preparative gel isoelectric focusing. The RRA potencies following gel filtration were in good agreement with that applied to the column, however, the immunological activities exceeded that of loaded by a factor 3-4. A new aspect of serum LH heterogeneity is the finding of a low molecular substance (mol. weight approximately 1000) in the outer dialysate of serum, which has LH like activity in all three assay systems.


A study of insulin receptors in human mononuclear leucocytes. Insulin binding sites were demonstrated in human mononuclear leucocytes by use of a technique which includes isolation of mononuclear leucocytes from defibrinated blood and separation of cell bound and free [125I]insulin with silicone oil. The binding was time and temperature dependent. At 15 degrees C equilibrium was reached after 90 min and a plateau maintained for at least 50 min. Incubations were carried out at 4 degrees C, 15 degrees C and 37 degrees C. Maximal binding was obtained at 15 degrees C. The optimum pH for insulin receptor interaction occurred at about 8. [125I]insulin binding to mononuclear leucocytes was demonstrated to be a linear function of cell number concentration over a range of 17-70 X 10(6) X ml-1. The binding was a displaceable function of native insulin concentration. In a group of 21 young healthy persons with normal body weight we found a mean specific cell binding fraction of 1.92 +/- 0.58 (s) X 10(-2). Analysis of the equilibrium between insulin and its receptor revealed an apparent heterogeneity of insulin receptors.


The insulin receptor in normal and obese persons. Using [125I]insulin at 172 pmol/1 (1 ng/ml) the binding of insulin to mononuclear leucocytes isolated from peripheral blood was studied. Our present study comprised 21 healthy subjects (22-33 years old, 90-110% of ideal weight) and a comparable group of 22 obese subjects (20-37 years old, minimum 150% of ideal weight). A significant difference in insulin binding was found between the two groups, the mean specific insulin binding fraction in normals being 1.92 +/- 0.58 (s) X 10(-2) and that for the obese 1.19 +/- 0.41 (s) X 10(-2) (P less than 0.01). No correlation was found between body weight and the number of insulin receptors in the obese subjects. However, the number of insulin receptors was negatively correlated to fat cell size (P less than 0.05). Insulin receptors in subjects were also negatively correlated to fasting plasma insulin (P less than 0.05). Insulin receptors were studied in 11 obese subjects before and after 10 days of fasting. A significant increase in the number of insulin receptors was observed with a simultaneous decrease in plasma insulin to normal values. The results indicate that obesity complicated by hyperinsulinism is associated with a decrease in the number of insulin receptors compared with the normal. This finding may in part explain the decreased insulin sensitivity of the hyperinsulinaemic obese.


Cytologic presentation of mammary carcinoma on aspiration biopsy smears. Needle aspirates from 598 histologically verified carcinomas of the female breast were reviewed. Four cytologic types were recognized: duct cell, acinic cell, apocrine cell, and mucous cell carcinoma. Duct cell carcinomas were further subdivided into ductal, ductular-acinar, monolayered and dissociated types. The highest ten-year survival rate was found in mucous cell carcinoma, and the lowest ten-year rates in acinic and dissociated duct cell types. The derivation of the mammary carcinomas is discussed on the basis of comparisons with cellular aspirates from benign mammary lesions. It is suggested that ductular-acinar, monolayered, dissociated and acinic cell carcinomas, which comprised about 50 per cent of the tumors originate in the lobular structures of the mammary gland. The problems involved in distinguishing well differentiated forms of the mammary carcinomas from the corresponding benign structures in needle aspirates are also discussed.


Cortisol effect on collagen biosynthesis in embryonic explants and in vitro hydroxylation of protocollagen. The effect of increasing doses of hydrocortisone acetate, hydrocortisone phosphoric acid complex, and hydrocortisone sodium succinate on collagen biosynthesis was assayed in two different systems. I. Explants of chicken embryo tibiae showed decreased biosynthesis of [14C]hydroxyproline and total and glycosylated [14C]hydroxylysine under the influence of high doses of hydrocortisone. With the lower doses of hydrocortisone acetate, no effect was noticed. The total uptake of the precursor amino acids followed patterns similar to those of collagen biosynthesis. II. Hydroxylation of [14C]proline labelled protocollagen by protocollagen proline hydroxylase was inhibited by high doses of hydrocortisone acetate, hydrocortisone phosphoric acid complex, and hydrocortisone sodium succinate. III. A decreased diffusion of collagen to the medium with increasing doses of hydrocortisone acetate, hydrocortisone phosphoric acid, and hydrocortisone sodium succinate was noticed. IV. No further hydroxylation of new-synthesized collagen was obtained under the influence of hydrocortisone phosphoric acid and hydrocortisone sodium succinate, when the undialyzable material was used as a substrate for protocollagen proline hydroxylase.


The occurrence of macrophages in the ischaemic rabbit eye. Mature macrophages involved in the removal of outer segment material were found between the visual cells and retinal pigment epithelium of the ischaemic rabbit retina. The mature macrophages were evident after only 15 min of ischaemia and the cells became progressively more numerous with increasing periods of ischaemia. A quantitative study was undertaken into the occurrence of the macrophages. These cells were probably of retinal pigment epithelial origin.


Progressive external ophthalmoplegia. Evidence for a generalised mitochondrial disease with a defect in pyruvate metabolism. Muscle biopsies from four patients with chronic progressive external ophthalmoplegia and pigmentary retinopathy with symptoms and signs from other organs were studied by means of light and electron microscopy. Examination revealed a marked proliferation of abnormal mitochondria with a degeneration of both muscle and nerve tissue. Blood levels of lactate and pyruvate were measured and abnormal values of these metabolites were found in the three patients with the most pronounced ultrastructural changes. On the basis of these findings it is suggested that there is a biochemical defect in pyruvate-lactate metabolism which could be responsible for the marked proliferation of the abnormal mitochondria.


Zonation of the adrenal cortex. III. Distribution of cytochrome P-450 in the zona glomerulosa of the bovine adrenal cortex. A microsomal fraction was obtained from the zona glomerulosa of the bovine adrenal cortex. Glucose-6-phosphate activity of the fraction was found to be much lower than that of the liver. Contents of RNA and phospholipids, besides electron microscopic findings, of the fraction also indicate that it is rich in smooth-surfaced endoplasmic reticulum. Distribution of cytochrome P-450 in the zona glomerulosa was studied using various fractions including the microsomal fraction described above. The amount of cytochrome P-450 in mitochondria and that in microsomes were determined to be 0.73 and 0.32 nmoles/mg protein, respectively. The CO-difference spectrum was affected not only by the concentration of added deoxycholate but also by the incubation time after addition. Approximately 40-50% of cytochrome P-450 in the samples were converted to cytochrome P-420 within 20-30 seconds of incubation with deoxycholate.


Heterotransplantation of experimentally induced dog stomach adenocarcinoma to nude mice. Heterotransplantation of gastric adenocarcinoma, induced in dog by N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) has been attempted to nude mouse. Biopsied materials from Borrmann 3 type carcinoma, which showed signet-ring cell carcinoma at the subcardiac region of a beagle dog, were inoculated into the muscles of the hind legs of BALB/c-nu/nu nude mice. Serial transmission was obtained in 2 lives, so far 4-5 passages. The histological findings of the grafts were mainly poorly differentiated adenocarcinomas.


Correlation between serum high density lipoprotein content and liver function during experimental hepatic degeneration and regeneration. Intravenous injection of praseodymium nitrate into female Wistar rats results in liver damage. The aim of this study is to investigate the quality of serum high density lipoprotein content as an index for the severity and time course of liver damage and regeneration following the administration of praseodymium. Serum high density lipoprotein content drastically decreases to a minimum after 24 - 48 h, returning to control values after four days. Liver degeneration is characterized by some intracellular parameters, i.e. the nuclear RNA polymerase reactions, the ribosomal protein synthesis, hepatic spermidine concentration and the activities of serum transaminases (GOT, GPT) and the sorbitdehydrogenase. From the data it is evident that the time course of serum high density lipoprotein content follows the intracellular changes closely. Liver regeneration is represented by the ornithin decarboxylase, the deoxycytidylate deaminase, the thymidine kinase activities and the hepatic putrescine content. The time course of these parameters shows that the regeneration reaches a maximum after 3 - 4 days. In the serum, high density lipoprotein content reflects this process by returning to control values. From our data we conclude that serum high density lipoprotein content after i.v. administration of praseodymium can be considered as an expression of the functional state of the liver.


Ultrastructural features of malignant fibrous histiocytoma of bone. Five cases of malignant fibrous histiocytoma originating in the femur and tibia, sometimes with local recurrences, are reported. Histological and clinical characteristics of this lesion were similar to those in soft tissues with the same disease. The present histiocytomas were observed by electron microscopy and shown to consist of 5 types of neoplastic cells which were regarded as undifferentiated cells, histiocyte-like cells, which were predominating, fibroblast-like cells, multinucleated giant cells and xanthomatous cells. These findings led us to confirm the existence of malignant fibrous histiocytoma originating in bone as well as in soft tissues.


Kidney size and growth in unilateral renal agenesis and in the remaining kidney following nephrectomy for Wilms' tumor. The kidney size and renal growth were determined in unilateral renal agenesis and in the remaining kidney following nephrectomy for Wilms' tumor. The ultimate length of 98 per cent of the functioning kidneys in renal agenesis is expected not to exceed +5.6 SD. In the tumor series the corresponding figure is +4.2 SD.


Changes in the adrenergic control and the rate of lipolysis of isolated human adipose tissue during fasting and after re-feeding. The influence of changes in nutritional state on lipid mobilization has been investigated, using subcutaneous fat portions removed from 8 obese patients submitted to fasting for one week. The maximal rise in the tissue level of cyclic AMP (cAMP) and the rate of glycerol release were determined when adipose tissue was exposed to noradrenaline (6 X 10(-6) mol/1), isopropylnoradrenaline (6 X 10 (-6) mol/1) or none of the agents (basal medium). Fasting resulted in significant increases in the tissue level of cAMP and the rate of lipolysis in adipose tissue unexposed to lipolytic agents. Noradrenaline decreased the level of cAMP, in contrast to isopropylnoradrenaline, and significantly inhibited the rate of lipolysis during fasting. These noradrenaline effects were abolished by the simultaneous presence of phentolamine (13 mmol/1) in the incubation medium. Re-feeding with Meritene for one day resulted in a diminished rate of basal lipolysis, whereas the cAMP level was unaffected. The response of the cAMP accumulation to isopropylnoradrenaline was further augmented by re-feeding. Noradrenaline produced a significant rise in the level of cAMP and significantly stimulated the rate of glycerol production. It is concluded that the nutritional changes are of significance for the adrenergic regulation of lipolysis as indicated by the response of cAMP to the catecholamines. In pharmacological terms, fasting for one week resulted in increased alpha-as well as beta-adrenergic responsiveness. Increased basal lipolysis during fasting may be related to an increased level of cAMP or a direct activation of lipase.


Urethane-induced hyperglycemia in rats.

Urethane-induced hyperglycemia in rats. The occurrence of hyperglycemia and glucosuria was investigated in urethane anesthetized rats. The substance found in urine was chromatographically identified with d-glucose. Marked increase in the arterial blood catecholamine concentration was observed. Hyperglycemia appeared after infusion of catecholamines in concentration comparable to that found in the blood of anaesthetized rats. The results support a hypothesis that the urethane-induced hyperglycemia is caused by an endogenous adrenaline liberation. Some observations in hypophysectomized and adrenalectomized rats indicate that the adrenal steroids may play a role in this reaction.


Studies on the mechanism of PGF2alpha and gonadotropin interactions on LH receptor function in corpora lutea during luteolysis. 1. In the present experiments evidence was shown which demonstrates that PGF2alpha treatment of the rat produces a rapid fall in circulating progesterone in the latter part of pseudopregnancy but not shortly after corpus luteum formation. This refractory period of at least 3 days following ovulation is similar to that which occurs in large animals, such as the cow. 2. Loss of luteal LH receptors was associated with a loss in LH-stimulated progesterone synthesis and an attenuation of LH-stimulated cyclic AMP synthesis in vitro, a finding which supports a functional loss of LH activity in such tissues exposed in vivo to PGF2alpha. Tissue levels of cyclic GMP were generally decreased by both LH, PGF2alpha, and incubation and the relevance of the latter cyclic nucleotide remains obscure in luteolysis and corpus luteum function. 3. The depression of progesterone induced by PGF2alpha precedes a marked drop in corpus luteum LH receptors but no change in reeptor affinity was seen. For example, the first significant drop in LH receptors was observed 8 hr after PGF2alpha treatment whereas serum progesterone was depressed within 2 hr. 4. Prolactin administration to animals simultaneously with PGF2alpha blocked the loss in LH receptors and serum progesterone observed with PGF2alpha treatment alone. In one experiment, but not in the other, prolactin treatment alone produced an elevation in corpus luteum LH receptors. Suppression of endogenous prolactin secretion with ergocryptine mimicked the effect of PGF2alpha on both the LH receptor and serum progesterone and this effect was also blocked with simultaneous prolactin treatment. It is concluded that the mechanism of PGF2alpha-induced luteolysis has several components. The initial event appears to be due to direct gonadotropin antagonism which occurs independently from a change in quantity of luteal LH receptors. This effect has been shown in vitro (10) as well as in vivo (3) and the mechanism appears not to be related to changes in ovarian hemodynamics and not to direct antagonism of LH binding to its receptor (23). Possibly the early effect of PGF2alpha may be due to elevation of cGMP which then antagonizes cyclic AMP action, but our studies to date have been unsuccessful in demonstrating such a response. Eight hours following PGF2alpha administration, the first measurable decrease in LH receptors was seen and this response was correlated with the first sign of functional luteolysis, elevation of serum 20alpha-ol. The latter response is correlated with a loss of prolactin action on the corpus luteum; it was therefore interesting to observe that prolactin blocked, and ergocryptine mimicked, the PGF2alpha effect on the LH receptor and serum progesterone. Thus, one is lead to the conclusion that the mechanism of luteolysis produced by PGF2alpha in the rat is closely associated with a loss in prolactin activity...


Tumors of the islets of Langerhans.

Tumors of the islets of Langerhans. The islet cell tumors of the pancreas are now known to produce a variety of polypeptides in addition to insulin. These include glucagon, serotonin, corticotropin, melanocyte-stimulating hormone, gastrin and a secretinlike hormone that may be VIP or a combination of such polypeptides. The development and wide availability of the newer immunoassays for the various recognized hormones as well as candidate hormones of the gut will simplify the diagnosis of these challenging tumors, which up until this time have produced symptoms that were bizarre and often fatal to the patient.


The detection and diagnosis of early, occult and minimal breast cancer. Radical mastectomy as originally conceived at the turn of the century consisted of complete removal of the breast tissue, the overlying skin, the pectoral muscles, the intervening lymphatics and the axillary lymph nodes. The aim was logical but initially the results were poor. Only 41% of the 76 patients in Halsted's original series were without disease at the end of 3 years. The principal reason for this was the advanced stage of disease in the patients selected for treatment. By contrast, Gilbertsen, using clinical examination alone, surveyed women 45 years of age or older and found that of 32 patients with breast cancers detected by the screening procedure, 24 had no axillary lymph node involvement. The absolute 5-year survival rate of this group was 96%, which approaches the anticipated survival of comparable women free of breast cancer. Those with positive lymph nodes had an absolute survival rate of 75% at 5 years. Further, of 13 patients observed for 10 years, the survival rate for those without node involvement was 90% and for patients with node involvement was 33%. Patients treated at the Barnes Hospital in St. Louis between 1912 and 1933 were contrasted with similarly treated patients at the Barnes Hospital and the Ellis Fischel Cancer Hospital from 1940 to 1955. A poorer survival rate in the earlier series was related primarily to the greater frequency of advanced and larger tumors. That a significant reduction in breast cancer mortality can be achieved is becoming increasingly apparent. Among survey-detected breast cancers in the study conducted by the Health Insurance Plan of Greater New York, the 6-year mortality was half of that of controls. This reduction is even more impressive when one considers that among these patients were many with full invasive, mass-forming carcinomas at the time of initial screening. A recent report by Wanebo, Huvos and Urban discusses the treatment of prognostically favorable forms of breast cancer by modified radical mastectomy. It is possible to select from among their patients those who fit the definition of minimal breast cancer. In this group the 5-year survival rate was 97% and the 10-year survival rate was 95%. Only 1 patient died of breast cancer in 10 years. In another reported group of 65 patients with intraductal carcinoma only, there were no deaths due to breast cancer in 10 years. Should the NCI-ACS demonstration projects show, as now seems probable, that community screening programs can be effective in early breast cnacer detection, it is to be anticipated that widespread public demand for screening facilities will follow. This may present insurmountable logistic and economic problems. The total number of radiologists in the United States is not sufficient to screen annually the total population of women over age 40, or even over age 50. There is great need for the development of criteria for the ready identification of that segment of the population in which most of the cancers would be found...


His bundle recordings in a case of complete atrioventricular block combined with pre-excitation syndrome. In  a patient with complete A-V block suffering from attacks of dizziness an intermittent A-V conduction with a short P-R interval and a delta wave of the conducted ventricular complex were observed. After accelerating the sinus rate by atropine and by exercise, one-to-one conduction was established with QRS complexes of WPW type A configuration. His bundle recordings revealed a complete block within the normal conduction system at the level of the A-V node. A slow junctional rhythm with a normal H-V interval was activating the ventricle. During atrial pacing a one-to-one conduction through an accessory pathway could be documented at cycle lengths between 800 and 380 msec. sandwiched in between zones of complete block at smaller or longer cycle lengths. During ventricular stimulation no retrograde V-A conduction could be observed. The findings support the thesis of at least two functionally different A-V pathways in patients with pre-excitation syndrome.


Effects of Rous Sarcoma Virus on the synthetic programs of chondroblasts and retinal melanoblasts. Chondroblasts and retinal melanoblasts have been transformed with a temperature-sensitive Rous Sarcoma Virus. At permissive temperature the transformed cells do not display their unique phenotypic properties. When such transformed cells are shifted to non-permissive temperature they do display their unique phenotypic properties.


An outbreak of infectious mononucleosis among the personnel of an outpatient clinic. During a four-week period, nine current or recent primary Epstein-Barr virus (EBV) infections were identified among 29 staff members of an obstetrics and gynecology outpatient clinic of an air force base hospital by EBV-specific serologic tests; i.e., early detection of IgM antibodies to EB viral capsid antigen (VCA), high titers of IgG antibodies to VCA, presence of antibodies to the D (diffuse) component of the EBV-induced early antigen (EA) complex and initial absence and later development of antibodies to the EBV-associated nuclear antigen (EBNA). Five of these individuals showed classical signs and symptoms of infectious mononucleosis (IM) so that the ratio between overt and silent infections was 1.25:1. All but one of these nine individuals gave positive monospot reactions. Three additional staff members were reported to be monospot-positive, of whom two, with prior histories of IM, had IM-like illnesses during the study period but the results of EBV-specific serologic tests were indicative of infections in the past. The EBV infections were limited to the nurses, corpsmen and administrative personnel, of whom none remained susceptible (antibody negative). The virus did not spread to the medical staff although two of the residents had no antibodies to EBV. The data indicate that under some circumstances IM may be more contagious than usually observed.


Herpesvirus hominis type 2 meningoencephalitis following renal transplantation. Herpesvirus hominis (HVH) type 2 meningoencephalitis, confirmed by isolation of the virus from cerebrospinal fluid and brain biopsy specimens, is described in a 44 year old man following renal transplantation. An HVH type 2 genital infection developed two weeks after renal transplantation, which was followed by meningoencephalitis 10 days later. Subsequently an intracerebral hemorrhage developed with evidence of diffuse vasculitis on arteriography. In a second transplant patient a similar clinical syndrome also developed after an HVH type 2 genital infection, but viral studies were not made to confirm the etiology of the meningoencephalitis. HVH has been recognized as a cause ot mucocutaneous diseases in  recipients of renal transplants, but involvement of the central nervous system has not been reported.


Angiotensin receptors in vascular tissue. The biologic effect of angiotensin II is triggered by its interaction with components of target organs, which specifically recognize the hormone. These receptors have been studied with the use of radioactive angiotensin and, as for other peptidic hormones, have been localized in the plasma membrane of target cells. Such angiotensin  receptors have been characterized in three target organs: vascular tissue, uterus and adrenal cortex. The binding characteristics differ in contractile tissue and in adrenal glands, the N and C terminal ends of angiotensin being involved in the former, whereas the N terminus does not appear to have the same importance in the latter. Numerous factors, including ionic composition, seem to be able to modify angiotensin-receptor interaction in vascular smooth muscle. However, the molecular mechanisms responsible for angiotensin binding and for the transmission of the signal determined by receptor-angiotensin interaction are not yet understood. As observed with other peptidic hormones, the number of angiotensin receptors seems to be susceptible to variation under certain conditions. In uterine smooth muscle, it was shown that the number of receptors increased after nephrectomy, a phenomenon which was prevented by the prolonged infusion of angiotensin. The significance of such a variation remains unknown, but it may be partially responsible for the inverse relationship that exists between the endogenous angiotensin level and the pressor effect of exogenous angiotensin. In the near future, investigation of the angiotensin-receptor mechanism will probably answer whether the variation in angiotensin receptors is similar in all target tissues and whether an angiotensin-receptor mechanism is involved in the pathogenesis of certain varieties of hypertension. In addition, a precise understanding of the angiotensin-receptor interaction with help the development of new angiotensin antagonists.


Vascular angiotensin receptors and their role in blood pressure control. The renin angiotensin system has an important role in regulating arterial blood pressure in homeostasis and disease. A reciprocal relationship exists between sodium balance and the circulating levels of renin and angiotensin II. The vascular responsiveness to angiotensin II, the major vasconstrictor component of the renal pressor system, can be impaired by numerous factors including sodium depletion or a reduction in effective plasma volume. In situations in which the renin-angiotensin system is activated, a negative relationship between the angiotensin II pressor response and the circulating angiotensin II level is observed. This effect seems to involve a change of the angiotensin II receptor interaction in the vascular smooth muscle. The prevention of angiotensin II generation by the inhibition of converting enzyme causes an immediate increase in the pressor response to angiotensin; after bilateral nephrectomy, it takes much longer to develop. In addition, the depressor response to angiotensin antagnoists and converting enzyme inhibitor is preserved after bilateral nephrectomy for much longer periods than can be accounted for by the disappearance of circulating renin. These observations support the view that the decrease in vascular response to angiotensin II during sodium deprivation or when body fluid volumes are reduced is the result of prior occupancy of the receptor sites by endogenous hormone generated both in the plasma and locally within blood vessel walls. Therefore, a change in the number or affinity of receptors consequent to a change in sodium balance or as a modulating function of the renin-angiotensin system need not be postulated to explain changes in angiotensin vascular responsiveness.


Estimating renin participation in hypertension: superiority of converting enzyme inhibitor over saralasin. This study was designed to examine more closely the differences in blood pressure responses in hypertensive patients to two agents which block the renin-angiotensin system. Accordingly, 39 seated patients received under the same conditions both saralasin, an octapeptide competitive antagonist of angiotensin II, and the nonapeptide converting enzyme inhibitor, SQ20881, which blocks the generation of angiotensin II from angiotensin I. A second component of the study involved administration of these agents in 10 addtional studies in anephric subjects. Although both agents produced maximal responses in blood pressure that correlated well with each other (p less than 0.001) and with the pretreatment plasma renin levels (p less than 0.001), analysis of the results by renin subgroups revealed significant differences. Thus, both drugs lowered the diastolic pressures of patients with high renin levels, but but converting enzyme inhibitor produced changes of greater amplitude (p less than 0.05). In contrast, saralasin was consistently pressor in both patients with low renin levels and anephric patients in whom converting enzyme blockade preduced no significant changes in blood pressure. Another impressive disparity in the responses to the two agents occurred in the group with normal renin levels in whom saralasin produced either neutral or pressor responses (mean change was +2.0 +/- 1.5 standard error of the mean (SEM) per cent control diastolic pressure) whereas the converting enzyme inhibitor consistently induced depressor responses (mean change was -10.2 +/- 1.2 per cent, p less than 0.001). Altogether, the results suggest that converting enzyme inhibitor tests for angiotensin II-dependent blood pressure with more sensitivity than the partial agonist saralasin. Moreover, it is unlikely that the differences between the responses to the two agents were due to bradykinin accumulation, since depressor responses to converting enzyme inhibitor were not observed in the patients with low renin levels and the anephric patients.


Observations on the human corpus luteum: histochemical changes during development and involution. Morphologic studies of the developing, gestational, and involuting corpus luteum show that rapid structural changes occur and that involution is not associated with an appropriate inflammatory response. Histochemical techniques were used to demonstrate several patterns of enzyme activity. The luteunized granulosa cells stained with increasing intensity for lactic dehydrogenase, succinic dehydrogenase, cytochrome oxidase, glucose-6-phosphatase, and 3 beta-hydroxysteroid dehydrogenase, but reactivity for these enzymes dropped markedly with early involution, and staining was never conspicuous in the organizing cavity. Reactions for acid phosphatase, glucosaminidase, galactosidase, glucuronidase, and nonspecific esterase were also present in the developing corpus luteum, but staining decreased more slowly during involution and was prominent in the occasional macrophages in the granulosa and the granulation tissue in the cavity. Staining was moderately intense for all of the enzymes in the corpus luteum of pregnancy. The decrease in activity for these metabolic enzymes confirms the histologic impression of degeneration, but the loss of staining for lysosomal enzymes was more rapid than expected. The latter finding complicates the hypothesis of involution of involution of the corpus luteum as an example of programmed cell death.


Blood as a potential vehicle for the cytomegaloviruses. This study analyzed transfused blood as a potential vehicle for infectious cytomegalovirus (CMV) particles. A total of 207 patients who received a total number of 897 units of blood were monitored. A complement-fixing antibody titer of 1:8, as determined by micro-titer technique, was observed in 14.8 per cent of the blood units. A total of 140 individuals in this study were serosusceptible. Eighty-six serosusceptible individuals did not receive blood containing complement-fixing CMV antibodies. In this patient population three instances of seroconversion were identified. Among the 54 serosusceptible individuals who received at least one unit of blood whose complement-fixing titer to the AD-169 strain of CMV was 1:8 or greater, 13 seroconversions were observed.


Immunologic studies in patients with trophoblastic neoplasia. Histocompatibility antigen was analyzed in 1,104 patients with trophoblastic neoplasia and in their husbands. Furthermore, the patients were examined for cell-mediated immunity. (1) There was no significant difference in the frequency of the ABO blood groups between patients with hydatidiform or destructive mole or choriocarcinoma and healthy persons. (2) The incidence of appearance of anti-HL-A antibody was more frequent in the patients with destructive mole than in those with hydatidiform mole or choriocarcinoma. (3) Patients with choriocarcinoma were frequently incompatible at HL-A9, HL-A10, and HL-AW5. (4) The mixed lymphocyte culture (MLC) showed lower values in patients with choriocarcinoma than in those with destructive mole. Histocompatibility between the patients and their husbands was more remarkable in the patients with chriocarcinoma than in those with destructive mole. (5) In patients with choriocarcinoma, incompatibility was detected at HL-A10, HL-A11, HL-AW5, and HL-A13 in the group with good prognosis and at HL-A5, HL-AW15, and HL-A12 in the poor prognosis group. The MLC value was lower in the poor prognosis group.