Testicular atrophy in Columbian black-tailed deer in California.

During an 18-year period, 4.1% (34/831) of male deer (Odocoileus hemionus columbianus) killed on a field station during the autumn hunting season had velvet-covered, often misshapen antlers, and at least two deer had testicular atrophy (gonads from most deer were not available for examination). Testes from six similarly affected deer and several normal deer were compared histologically. Lesions ranged from hypocellularity of the semeniferous tubules and relative hyperplasia or degeneration of interstitial cells to complete connective tissue replacement of the testicular parencyma. Chronic vascular changes were present in several testes. The etiology and pathogenesis of the lesions were not determined.


Avian pox in Florida sandhill cranes.

Cutaneous elevations were present on the feet, legs and heads of four Florida sandhill cranes, Grus canadensis pratensis, (one free-living, three penreared birds). As a result of examination of the elevations by light- and electron microscopy, it was determined that the lesions were caused by poxvirus. This is the first record of pox in cranes in North America.


Inclusion body disease (herpesvirus infection) of falcons (IBDF).

Inclusion body disease of falcons (IBDF) is caused by a herpesvirus. The clinical course is short, 24 to 72 hours in duration, and is characterized by mild to severe depression and weakness often accompanied by anorexia. The disease is invariably fatal. The virus has a marked affinity for the reticuloendothelial system and hepatocytes,producing focal to diffuse necrosis of infected tissues accompanied by the formation of intranuclear inclusion bodies. The virus is pathogenic for American kestrels (Falco sparverius) and great horned owls (Bubo virginianus) in which typical lesions of IBDF are reproduced. The lesions of IBDF are similar to those produced by some herpesvirus infections in other avian species.


Inclusion body disease in a great horned owl.

The carcass of a great horned owl (Bubo virginianus), which had been found moribund in southern Ontario, was presented for necropsy. Throughout the liver and spleen were numerous white foci 1-2 mm in diameter; also noted were white plaques in the mucosae of the pharyngeal papillae and intestine. Results of light and electron microscopic studies and experimental transmission to two captive great horned owls suggested that this was a herpvirus disease similar and possibly indentical to the owl disease reported by other workers in Wiconsin and Australia.


Ascorbic acid for the common cold. A prophylactic and therapeutic trial.

Three hundred eleven employees of the National Institutes of Health volunteered to take 1 gm of ascorbic acid or lactose placebo in capsules three times a day for nine months. At the onset of a cold, the volunteers were given an additional 3 gm daily of either a placebo or ascorbic acid. One hundred ninety volunteers completed the study. Dropouts were defined as those who missed at least one month of drug ingestion. They represented 44% of the placebo group and 34% of those taking ascorbic acid. Analysis of these data showed that ascorbic acid had at best only a minor influence on the duration and severity of colds, and that the effects demonstrated might be explained equally well by a break in the double blind.


Renal action of cholera toxin: I. Effects on urinary excretion of electrolytes and cyclic AMP.

The infusion of cholera toxin (CT), 4 mug/min, into one renal artery of normal and thyroparathyroidectomized (T-PTX) dogs produced ipsilateral increments in the excretion of Na, K, Ca, Mg and Cl. Phosphate excretion increased from both kidneys, but more from the infused kidney in intact dogs. Unilateral phosphaturia occurred in T-PTX dogs studied five or more days after T-PTX. The changes in electrolyte excretion appeared 40 to 80 min after initiation of CT infusion and the maximal effects were noted after 100 to 140 min. The effects of CT on electrolyte excretion could not be accounted for by changes in glomerular filtration rate or renal plasma flow. Urinary cyclic adenosine monophosphate (AMP) increased from both kidneys but slightly more from the infused kidney. Adenylate cyclase activity of cortex and outer medulla of the infused kidney was 109 to 142% higher than that of the control kidney. The results indicate that CT decreases the net transport of various electrolytes by the renal tubule. This effect is probably mediated by the activation of renal adenylate cyclase(s) sensitive to the enterotoxin.


The granulovesicular bodies of the arterial wall.

Small, round, membrane-bound electron-dense bodies were observed in the smooth muscle cells and the intimal and medial intercellular spaces of arteries in the dog, rat, and pig under normal and various experimental conditions. These structures, referred to as granulovesicular bodies (GVB), measured from 0.2 to 0.5 mum. in diameter and contained an inner core of granular and vesicular subunits. The intercellular and extracellular forms of the GVB were structurally similar, and in the interstitial spaces they appeared to have a definite spatial relation to the elements of elastic tissue. The GVB were more numerous under experimental than under normal conditions. It is speculated that the GVB are secretory in nature, originating from the smooth muscle cells, and may play a role in the remodeling of arterial elastic fibers.


Cytoplasmic inclusions in pulmonary macrophages of cigarette smokers.

Alveolar and bronchiolar spaces in the lungs of cigarette smokers usually contain numerous macrophages with pigmented cytoplasmic granules. By electron microscopy the pigmentation appears to be due, at least in part, to increased numbers of lysosomes and phagolysosomes. Within these cytoplasmic organelles, structures are found which we designate "smokers' inclusions", since they are observed exclusively in the interstitial and alveolar macrophages of cigarette users. The inclusions have been referred to by other investigators as "needle-shaped" and "fiber-like". Since cross-sections of the structures are never seen in electron micrographs, a fiber or needle shape seems unlikely. On the other hand, thin sectioning techniques impart varying lengths to the inclusions, suggesting that they have a disc, or platelet, configuration. Surgically resected lung tissue from smokers and nonsmokers was digested in hot potassium hydroxide. Digestates contained varying numbers of hexagonal platelike particles which had features consistent with those of the aluminum silicate kaolinite, and energy-dispersive x-ray spectrometry confirmed the presence of these two elements. The origin of aluminum silicate inclusions in pulmonary macrophages has yet to be determined, although preliminary evidence strongly suggests that they are derived from inhaled tobacco smoke. The cytotoxicity of kaolinite in vitro and the possible role of aluminum silicate crystals in the pathogenesis of pulmonary fibrosis are discussed.


Lead-induced inclusion bodies: results of ethylenediaminetetraacetic acid treatment.

Earlier studies have shown that lead-induced nuclear inclusion bodies are composed of a lead-protein complex. Twenty-four hours after treatment of a lead-poisoned rat with a single dose of ethylenediaminetetraacetic acid (EDTA), urinary excretion of lead is maximally increased and the lead content of the kidneys is significantly decreased. Inclusion bodies in renal cell nuclei at this time are found in various stages of dissolution and migration out of the nucleus. The outer fibrillary margin becomes loosened, and slight disruption occurs at the periphery of the inclusion. Some inclusion bodies appear to be moving through the nuclear membrane. There is an invagination of both inner and outer nuclear membranes. Numerous cytoplasmic vacuoles occur which contain fibrillar material resembling portions of intact nuclear inclusions. Kidney nuclei of rats 24 hours after three daily injections of EDTA have no inclusion bodies. Whether the nuclear-cytoplasmic exchange occurs by dilation of a nuclear pore or by another mode of separation of nuclear membranes cannot be determined. This experiment demonstrates that nuclear inclusion bodies formed in lead poisoning are disrupted and removed from the nuclei by the administration of EDTA. This change corresponds with peak urinary excretion of lead. The sharp increase in urinary lead following EDTA therapy must reflect, at least in part, chelation and excretion of sequestered lead bound to nuclear protein.


A plasma inhibitor of the renin-antirenin reaction and the in vitro generation of angiotensin I.

In the course of studies designed to develop a radioimmunoassay system for the detection of renin, we have identified in human plasma a potent inhibitor that interferes with the renin-antirenin reaction. Utilizing gel filtration, this renin-antirenin inhibitory activity was found to have the same molecular size as renin substrate. However, it could be separated from renin substrate by ion-exchange chromatography. When fractions containing this activity were tested in an in vitro system containing renin and renin substrate, they were found to inhibit the generation of angiotensin I.


Transfusion-associated hepatitis not due to viral hepatitis type A or B.

Twenty-two patients who had an episode of transfusion-associated hepatitis not positive for hepatitis B antigen were examined for development of antibody to heaptitis A and B antigens, cytomegalovirus and Epstein-Barr virus. Antibody response to the 27-nm virus-like hepatitis A antigen was measured by immune electron microscopy. In none of the 22 patients studied did serologic evidence of infection with hepatitis A virus develop during the study period. Nine of the 22 patients had antibody responses to cytomegalovirus, but it was difficult to relate these seroconversions to their hepatitis. In addition, all 22 patients had pre-existing antibody to the Epstein-Barr virus. It seems likely that at least a proportion of such antigen-negative transfusion-associated hepatitis is caused by other infectious agents, not yet identified.


Computerized axial tomography: clinicopathologic correlation.

Between August 1973 and April 1974 more than 750 patients had computerized axial tomography (CT) scans at the Massachusetts General Hospital. Ten brains from previously CT-scanned patients in this group were sectioned in the plane of the scan. Nearly exact correlation was found between the anatomic location and extent of intracranial lesions demonstrated by CT scan and the findings on gross and microscopic pathologic examination in cases of primary intracranial tumors, obstructive hydrocephalus, intracerebral hemorrhage, ischemic and hemorrhagic infarctions, pineal tumor, and thermal-burn encephalopathy. Determination of absorption values (mu) of 47 pathologically verified processes showed that high-absorption intracerebral hemorrhage and calcium-containing tumors are readily separable from other processes on the basis of mu values alone. However, the abnormal mu values of primary brain tumor, edema, and infarction are difficult to distinguish from those of normal spinal fluid and white matter.


Biochemical mapping of the noradrenergic projection from the locus coeruleus. A model for studies of brain neuronal pathways.

Mapping of the noradrenergic projection from neurons in the rat locus coeruleus has been examined by combining a sensitive radioisotopic assay for catecholamines with a microdissection technique to remove multiple separate brain nuclei. The effect of a unilateral locus coeruleus lesion on norepinephrine concentration in 19 brain regions ipsilateral and contralateral to the lesion was determined. Evidence for ipsilateral and bilateral innervation to specific regions is presented, and many regions appear to receive combined innervation from other noradrenergic loci, in addition to that from the locus coeruleus. Fluorescence rating was correlated with biochemical measurement of amine content with these techniques and proportionality was observed over a narrow range. With this proportionality taken into consideration, mapping results obtained by biochemical and fluorescence methods are compared.


Peripheral neuropathy in classic Niemann-Pick disease: ultrastructure of nerves and skeletal muscles.

A patient with classic (type A) Niemann-Pick disease had the usual clinical signs of failure to thrive, hepatosplenomegaly, and intellectual deterioration in the first year of life. In addition, there was striking hypotonia, areflexia, and abnormal nerve conduction velocities. Pathologically, the Schwann cells were filled with numerous cytoplasmic bodies. These bodies measured 1 mu in diameter and appeared to be dense, round masses with poorly defined internal structure but with occasional slightly curved parallel lines and small radiolucent areas. Peripheral nerve involvement may be a frequent finding in patients with classic Niemann-Pick disease.


Myopathy associated with linear scleroderma. A histochemical and electron microscopic study.

Pathologic findings in biopsied rectus femoris muscle underlying an area of linear scleroderma are described. The affected muscle was weak and atrophic. On electromyography it showed motor unit potentials of decreased amplitude and duration. Light microscopic changes were minimal. There was atrophy of some histochemical type I fibers. More prominent changes were found at the ultrastructural level, where many of the capillary basal laminae were thickened and reduplicated. Most striking was the presence of two types of electron-dense, rounded inclusions within the mitochondria, one ranging from 29 to 47nm in diameter and the other from 54 to 131 nm in diameter.


Human muscle fiber fine structure: morphometric data on controls.

Muscle fiber fine structure was quantitatively analyzed in 70 longitudinally and 65 transversely sectioned fibers from 10 control subjects without weakness. The average mitochondrial fraction of the fiber volume is close to 4 percent and the mean size of a mitochondrion is about 0.1 mum2. The sarcotubular surface area per unit fiber volume is close to 1.5 mum2/mum3 in transverse sections and 0.65 times this value in longitudinal sections. Only one-third of all fibers contain lipid droplets in the sectioned plane, and for all fibers the droplets account for approximately 0.12 percent of the fiber volume. Variations with the age and sex of the subjects and with different muscles were analyzed and the feasibility of typing human muscle fibers at the ultrastructural level was evaluated.


Isolation of herpes simplex virus from the cerebrospinal fluid in viral meningitis.

Two cases of meningitis are reported in which the etiologic diagnosis was established by isolation of herpes simplex virus from the cerebrospinal fluid. Both patients were afebrile and had bradycardia when the cultures were obtained, and one patient had been thought to have leukemic meningitis. This experience added to that of others in the literature indicates the value of culture for herpes simplex virus in the cerebrospinal fluid.


[Study of the action of tolbutamide on the hypothalamo-hypophyseal-adrenocortical system in normal and obese subjects].

Changes in plasma cortisol during the tolbutamide test were evaluated in normal subjects and in obese patients with a normal (D = 60,1 plus or minus 8,3) or reduced (D = 23,2 plus or minus 9,5) blood sugar decrease coefficient. Increases were noted in normal subjects (from 14,0 plus or minus plus or minus 2,9 mug/100 ml to 25,5 plus or minus 11,5 mug/100 ml) or in obese patients with normal D (from 15,7 plus or minus 5,1 mug/100 ml to 25,9 plus or minus 9,2 mug/100 ml), while no significant variations were observed in patients with depressed D. Though a direct corticosteroidogenetic effect and/or interference with liver metabolisation of cortisol (and increased clearance) cannot be excluded, the data suggest that increased blood cortisol following tolbutamide is secondary to the lowering blood sugar action of the drug.


Effect of exogenous estrogen on serum pregnenolone, cortisol, and androgens in postmenopausal women.

Previous studies from this laboratory have included reports on the serum concentrations of the following steroids in premenopausal and postmenopausal women: pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, cortisol, corticosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, testosterone, dihydrotestosterone, estone, and estradiol 17-beta. In general the steroid levels were lower in postmenopausal subjects, and this difference was significant at P smaller than 0.05 for 8 of the steroids. The significantly decreased peripheral level of steroids in the postmenopausal state can be explained by decreases either in ovarian secretion of steroids or in ovarian stimulation of the adrenal cortex. Since the contribution of the adrenal cortex to the peripheral levels of dehydroepiandrosterone sulfate (DHEA-S) is greater than 95% in premenopausal women, a plausible explanation for the marked drop observed in peripheral DHEA-S levels after menopause is that the ovary influences the steroidogenic activity of the adrenal cortex. In such cases a decrease in the stimulation of the adrenal cortex by some ovarian steroids would be expected. Estrogen therapy in 10 postmenopausal women resulted in significant increases in the serum levels of 3 of the steroids compared to those in untreated subjects, confirming the postulate that ovarian estrogens stimulate the secretion of adrenal androgens.


Bell's palsy associated with acute herpetic gingivostomatitis.

One of the most recent hypotheses relative to the cause of Bell's palsy is that involving the latent herpes simplex virus. A case is presented in which the primary infection of the facial nerve by the herpes simplex virus could have been a factor in the unilateral facial paralysis.


The odontogenic adenomatoid tumor. A comprehensive study of twenty new cases.

Twenty new cases of odontogenic adenomatoid tumor are added to the literature, bringing the total number of reported cases to 152. The clinical, radiographic, and microscopic findings in these cases support the previously reported data for this lesion. The odontogenic adenomatoid tumor is a benign lesion which arises from residual odontogenic epithelium. It should be treated conservatively, as there is no indication that this lesion will recur. The histogenesis of this lesion, as well as the origin of the esinophilic droplet material, is discussed.


Metastatic malignancy in the submandibular gland.

Metastatic disease in the major salivary glands has been observed and reported in the literature. Often the site of origin of the primary tumor is the skin or mucosal lining of the head and neck structures, and the primary tumors most commonly are melanomas or squamous-cell carcinomas. The most frequently involved salivary gland is the parotid. The submandibular and sublingual glands are rarely involved by mestastatic disease. Secondary lesions arising from distant primary tumors may occasionally involve the parotid gland, but they are extremely rare in the other major salivary glands. The second reported case of metastatic carcinoma in the submandibular gland is presented here. Our case and the previously reported case are similar in that both primary tumors originated in the breast. The clinical and morphologic features are reviewed.


Multiple unit activity study of brain stem and limbic structures during environmental habituation and circadian rhythm.

Multiple unit activity (MUA) of brain stem, hypothalamic and limbic structures was studied during habituation to a novel environment and circadian rhythm in chronically implanted freely moving rats. MUA was analysed in the mesencephalic reticular formation (MRF), area hypothalami posterior (PH), basal nuclear group of amygdala (AMY), area septalis (SEPT), dorsal hippocampus (HIPP) and area hypothalami anterior (AH). It was found that in the novel environment MUA of all subcortical structures increased to a high level. During habituation MUA in each phase of wakefulness--sleep cycle decreased to stable low level both in brain stem and forebrain structures. Gradual decrease in MUA was characteristic to MRF, and a sharp decrease occured in AH and AMY. The environmental habituation proved to be a long lasting process in rat. During all phases of wakefulness--sleep cycle activity was significantly higher in the light period than in the dark, and MUA base level showed circadian variation both in brainstem and limbic structures. Close correlation was found between the actual MUA level and responsiveness to various sensory modalities both during habituation and circadian rhythm. The higher the MUA level, the higher the responsiveness, and a fall in activity was accompanied by decreased neuronal responsiveness.


Antagonism between parathyroid hormone and norepinephrine on cyclic adenosine-3':5'-monophosphate (cAMP) levels in isolated tubules from rat kidney cortex.

Isolated rat kidney cortex tubules were used as a model system to study the hormonal regulation of cyclic adenosine-3':5'-monophosphate (cAMP) levels in vitro. When incubated over 15 min, parathyroid hormone increased cAMP levels 4-fold in the absence of inhibitors of cAMP phosphodiesterase. Norepinephrine in a concentration of 5-10-7 M which had itself no effect on cAMP levels under this condition, inhibited the effect of parathyroid hormone by 50%. This effect of the catecholamines could be completely abolished by the addition of an alpha-receptor blocking agent, phentolamine. The addition of an inhibitor of cAMP phosphodiesterase, in a concentration sufficient to prevent the breakdown of extratubular cAMP, potentiated hormone effects on cAMP levels. The antagonism between catecholamines and parathyroid hormone on cAMP levels was however not abolished by this treatment. This indicated that catecholamines probably inhibited parathyroid hormone stimulated cAMP formation. Since most of the cAMP was found to be intratubular, it can be assumed that norepinephrine and parathyroid hormone interact in the same cell. Proximal tubular sodium reabsorption and renal gluconeogenesis are discussed as possible events of this hormone interaction.


Adenylate cyclase activity along the rabbit nephron as measured in single isolated segments.

A method is described, which allows adenylate cyclase activity measurement in single pieces of various nephron segments. Tubular samples of 0.5 to 2 mm length were isolated by microdissection from collagenase treated slices of rabbit kidney. A photograph of each piece was taken in order to measure its length. After a permeabilisation treatment involving preincubation in a hypoosmotic medium and a freezing step, each sample was incubated for 30 mm at 30 degrees C in a medium containing high specific (alpha-32-P)-ATP 3-10-4 M, final volume 2.5 mu 1. The (32P)-cAMP formed was separated from the other labelled nucleotides by filtering the incubate on a dry aluminium oxide microcolumn, 3H cAMP was added as a tracer for measuring cAMP recovery. The sensitivity of the method was found to be a few fentomoles (10-15 M) cAMP. cAMP generation increased linearly as a function of the incubation time up to more than 30 min, and as a function of the length of the segment used. Control and fluoride (5 mM) stimulated adenvlate cyclase activities were measured in the following segments of the nephron: early proximal convoluted tubule (PCT), pars recta of the proximal tubule (PR), thin descending limb of the loop (TDL), cortical portion of the thick ascending limb (CAL), distal convoluted tubule (dct), first branched portion of the collecting tubule (BCT), further cortical (CCT) and medullary (MCT) portions of the collecting tubule. Mean control adenylate cyclase activity varied from 7 (PR) to 75 (BCT) fmoles/mm/30 min. Flouride addition resulted in a 10 (BCT) to 50 (PR) fold increase in enzyme activity. Series of replicates gave a scatter equal to plus or minus 20% (S.D. as a per cent of the mean). The method described appears to be suitable to determine which nephron segments contain hormone-dependent adenylate cyclase.


PTH sensitive adenyl cyclase activity in different segments of the rabbit nephron.

PTH sensitive adenylate cyclase activity was measured in 9 different segments of the nephron, isolated by microdissection from collagenase-treated rabbit kidney slices. The enzyme of the following segments was stimulated by PTH, 1 U/ml: PCT. (proximal convoluted tubule); PR (pars recta); CAL (cortical portion of the thick ascending limb); DCT (distal convoluted tubule); BCT (first, branched portion of the collecting tubule); the segments which did not respond to PTH were: TDL (thin descending limb): MAL (medullary portion of the thick ascending limb); CCT (cortical portion of the collecting tubule distally adjacent to BCT); MCT (collecting tubule from the outer medulla). PTH sensitive adenylate cyclase per mm tubule in PR was half that measured in PCT. Half maximal stimulation corresponded to 50-100mm U/ml PTH (1-2 times 10-8M) in both PCT and PR, and to about 350 mm U/ml in CAL. PTH (1 U/ml) stimulation factors ranged from 5 to 60 depending on the structures. It is concluded that in addition to PCT and PR, CAL and BCT might be target structures involved in the physiological actions of PTH on the kidney.


[Dose-time effects of competitive displacement of radiopertechnetate by sodium perchlorate following oral and intravenous administration].

The effect of various doses of sodium perchlorate in several dose fractions on the extent and the time scale of displacement of radiopertechnetate, in dependence on application mode, was studied. An intravenous dose of 50 mg perchlorate was in respect of competitive suppression of organs actively concentrating pertechnetate as effective as intravenous 1000 mg ClO-4- simultaneously or 1000 mg orally 30 min before the injection of radiopertechnetate. An intravenous injection of perchlorate given later also produces a complete and immediately beginning depletion of pertechnetate already accumulated in the thyroid, within a period of 195 min after 99m-TcO-4-injection with a corresponding increase in blood levels. 20 mg result in incomplete depletion which becomes complete after a second additional dose. The intravenous application of perchlorate offers advantages in clinical use.


The discharge crisis: the experience of families of psychiatric patients.

Families of 16 psychiatric patients were interviewed immediately prior to discharge regarding the impending discharge of their relative, events prior to admission, and the families' impression of the hospitalization. Despite wide variation sample families' descriptors and differences in exposure to the treatment settings, there was a marked uniformity in responses. The families were not prepared for the discharge of their relative. In spite of their experiences and exposure to treatment, families continued to demonstrate tremendous uncertainty and lack of direction about the future with the patient. Families did not view the patient as ready to be discharged. They had not experienced an opportunity to express their views or participate in decision making. They did not consider the staff as a resource for themselves.


Cadmium-its in vivo detection in man.

Neutron capture gamma-ray analysis has been applied to the in vivo detection of Cd in man. The technique was designed for the screening of industrial workers at risk. The limit of sensitivity in a liver-sized phantom is 0-5 ppm for a dose of 0-4 rad. Reproducibility and the effects of positional uncertainties have been investigated. A number of cadavers were studied to establish normal limits prior to commencement of a programme of clinical investigation. A patient with known Cd poisoning was estimated to contain 65-110 ppm of Cd in his liver. A liver dose of 0-05 rad was required.


Infectious diseases in primitive societies.

Incidence of various infectious diseases in several Amazon Indian tribes has been determined serologically. Diseases that infect only man fall into two distinct categories. Those which can persist in an individual for a prolonged period are highly endemic, but those which are infectious only in the acute phase die out quickly after introduction. The suggestion is made that the latter diseases could not perpetuate themselves before the advent of advanced cultures and did not exert selective pressures on the human genetic constitution until relatively recently.


A comparative study of agar overlay and standard tissue culture methods for isolation of enteroviruses.

A study was made of the isolation of enteroviruses from 62 cerebrospinal fluids and 141 autopsy specimens with standard fluid monolayer tissue culture methods and tissue cultures under agar overlay with and without added MgCl2 (0.025M). Sixteen virus isolations were made only by the overlay method, two only by the standard technique, and six by both procedures. Additional studies were carried out on 975 diagnostic specimens of various types with standard tissue culture methods and with primary rhesus kidney cells under agar overlay containing 0.025M MgCl2. Seventeen virus isolations were made only by the overlay procedure, 20 only by the standard tissue culture method, and 75 by both techniques. Since there were instances in which either the agar overlay or the standard method alone succeeded in isolating a virus, use of both types of procedures would be desirable to isolate as many enteroviruses as possible from clinical specimens.


Sleep and cardiac rhythm in the gray seal.

Telemetric studies of electroencephalograms, electrocardiograms, and electroculograms and concurrent observations of behavior revealed that seals can sleep underwater, on the surface, or while hauled out. Rapid eye movement preceded slow wave sleep and was accompanied by increased respiratory rate and rhythmic tachycardia. While slow wave sleep occurred under all sleep conditions, rapid eye movement occurred only when a seal was hanging at the water surface or hauled out, never underwater.


Ornithine decarboxylase activity: control by cyclic nucleotides.

Both exposure to cold and administration of aminophylline result in rapid increases in cyclic adenosine monophosphate (cyclic AMP) in the adrenal medulla and adrenal cortex. These increases are followed by dramatic increases in ornithine decarboxylase activity is due to new enzyme systhesis. The data suggest that the decarboxylase activity is regulated by an increase in cyclic AMP.


Selection of a variant lymphoma cell deficient in adenylate cyclase.

Isoproterenol, a stimulator of adenylate cyclase, was used to select a stable variant clone of mouse lymphosarcoma cells deficient in the enzyme. The inability of four different stimulators to activate cyclic adenosine monophosphate synthesis in the variant, in contrast to its wild-type parent, implies that in normal cells one type of adenylate cyclase molecular can respond to different activators.


Cyclic AMP and cyclic GMP may mediate opposite neuronal responses in the rat cerebral cortex.

Electrophysiologically identified pyramidal tract neurons in the rat cerebral cortex were tested with norepinephrine, acetylcholine, adenosine 3',5'-monophosphate (cyclic AMP), and guanosine 3',5'-monophosphate (cyclic GMP) applied by microiontophoresis. The neurons were usually inhibited by norepinephrine and cyclic AMP, but excited by acetylcholine and cyclic GMP. These opposing responses of pyramidal tract neurons to cyclic AMP and cyclic GMP suggests that these two nucleotides could function as reciprocal intracellular second messengers for norepinephrine and acetylcholine, respectively.


Primate type C virus p30 antigen in cells from humans with acute leukemia.

Antigens related to the major structural protein (p30) of type C viruses isolated from a woolly monkey and a gibbon ape were found in peripheral white blood cells from five patients with acute leukemia.


Phosphorylation of lymphocyte nuclear acidic proteins: regulation by cyclic nucleotides.

Guanosine 3',5'-monophosphate (cyclic GMP) and cholinergic agents stimulate incorporation of phosphate into specific nuclear acidic proteins of horse peripheral blood lymphocytes. Agents that raise intracellular adenosine 3',5'-monophosphate (cyclic AMP) inhibit nuclear acidic protein phosphorylation. The opposing effects of cyclic GMP and cyclic AMP upon nuclear protein phosphorylation parallel the effects of the cyclic nucleotides upon induction of lymphocyte proliferation.


Insulin-induced augmentation of lymphocyte-mediated cytotoxicity.

Physiologic concentrations of insulin enhance the ability of cytotoxic lymphocytes to injure target cells. The effect of insulin closely resembles the action of cholinomimetics and guanosine 3',5'-monophosphate upon this system. Since both insulin and cholinomimetics elevate intracellular concentrations of guanosine 3',5'-monophosphate, a common mode of action is suggested.


Prolactin receptors in rat liver: possible induction by prolactin.

A prolactin receptor, present in adult female rat liver, can be induced in males by estrogen. Hypophysectomy diminished receptor levels in the female and rendered males unresponsive to estrogen. A renal pituitary implant blunted the decrease in hypophysectomized females and induced the receptor in hyophysectomized males. The increased receptor level in hypophysectomized males with a renal pituitary implant was preceded by a sustained elevation of circulating prolactin. Our observations suggest that prolactin induces its own receptor.


Butylated hydroxytoluene inactivated lipid-containing viruses.

Butylated hydroxytoluene (BHT) is widely used as a food preservative for its antioxidizing property. This small, hydrophobic molecule has been found to be a potent inactivator of lipid-containing mammalian and bacterial viruses.


Electron spin resonance for detecting polyadenylate tracts in RNA's.

Electron spin resonance is used to detect RNA's that contain polyadenylate tracts. The method depends on the ability of RNA's that contain polyadenylate sequences to associate with poly(2'-deoxy-2'-fluoro)uridylic acid, which has been spin-labeled with 4-(2-iodoacetamido)-2,2,6,6-tetramethylpiperidinooxyl. The formation of the hybridization product can be detected by monitoring the decrease in mobility of the spin probe.


Formation of the enzymatic apparatus of respiration in growing cells. Communication II. Reorganization of the respiratory cycle of mitochondria in the corn root tip.

The content of cytochromes a,b and c, the activity of marker enzymes of the matrix and inner membrane of the mitochondria: glutamate dehydrogenase and cytochrome oxidase, as well as the rate of absorption of O2 by root segments in the presence of respiratory substrates, oxygen, inhibitors of respiration, and dinitrophenol, were determined. The intensification of cell respiration in the phase of elongation is determined not so much by new formation of cytochrome components of the respiratory cycle (during this period there is an accumulation only of cytochrome c) as by reorganization of the respiratory cycle (primarily its portion NADH - cytochrome b) and synthesis of enzymes of the matrix.


Investigation of oogenesis in hydra. Communication I. Ultrastructure of interstitial cells at early stages of their transformation into oocytes.

We studied ultrastructure of the interstitial cells (i-cells) at successive stages of their transformation into oocytes. The i-cells that form the epidermal thickening in the genital zone of the animal start to proliferate in hydras approaching sexual reproduction. Undifferentiated i-cells are characterized by a high density of diffusely disposed ribosomes and almost total absence of membranous structures. Femal sex cells starting to undergo differentiation are characterized by the appearance of aggregations of finely filamentous material in the cytoplasm. This material is of nuclear origin and is often surrounded by mitochondria. Dimensions of the i-cells increase rapidly, and single elongated cisterns of the granular endoplasmic reticulum appear in them. These cisterns run parallel to the cell surface and give rise to minute smooth-surfaced vesicles, whose membranes fuse wtih the cytoplasmic membrane in such a way that their contents are emptied into the intercellular space. Different sectors of the cell are marked by the appearance of grouped cisterns of the granular endoplasmic reticulum. Such cisterns give rise to smooth-surfaced vesicles, which form numerous Golgi complexes. The number of mitochondria increases simultaneously; aggregations of lipid drops with glycogen granules among them start to appear; and escape of nuclear material into the cytplasm intensifies. Such cells at the stage of cytoplasmic growth and accumulation of organelles and yolk inclusions. In connection with this, it is suggested that the term "oogonium" (which is used to designate such cells in the literature) be retained only for proliferating i-cells containing finely filamentous nuclear material in the cytoplasm in the genital zone of the hydra.


Mesothelial reaction of asbestos and other irritants after intraperitoneal injection.

Ten groups of rats were injected intraperitoneally with one of the following suspensions; (i) standard reference crocidolite; (ii) acid-treated crocidolite (iii) crocidolite plus iron oxide; (iv) crocidolite plus silica; (v) iron oxide; (vi) silica; (vii) long fibre crocidolite; (viii) short fibre crocidolite; (ix) long fibre glass and (x) short fibre glass. Two rats from each group were killed at 45, 90, 150, 240 and 330 days respectively, and the pathology induced by the different suspensions was studied histologically at each time interval. No evidence in support of the chemical induction theory or mechanical irritation theory in the pathogenesis of peritoneal mesotheliomas could be found, although all the suspensions except iron oxide caused a reactive mesothelium.


Technique and results of endoscopic retrograde pancreaticocholangiography. A preliminary report on 140 patients.

Endoscopic retrograde pancreaticocholangiography (ERPC) has been performed in 140 patients, mainly Blacks and Indians. The first 100 patients have been analysed. The greatest diagnostic yield in this series is in (suspected) obstructive jaundice, where 26 diagnoses were made in 35 patients. In 40 patients with pancreatitis, the widest ducts were seen in 12 patients with calcific pancreatitis, but the procedure was of less help than expected. This was because no patients with continual pain after cessation of alcohol intake were found with operable strictures of the main pancreatic duct. The pancreatic function test with secretin and cholecystokinin-pancreozymin correctly diagnosed 4 patients with non-calcific pancreatitis in whom the ERPC was normal. There was a useful diagnostic yield in patients with unexplained upper gastrointestinal symptoms (15 diagnoses were made in 23 patients).


The inhibition of c-AMP-phosphodiesterase by phenobarbitone.

The early effects of phenobarbitone, theophylline, thyroxine and of combinations of these drugs, on rat liver microsomal aniline hydroxylase activity, were studied, and the results were compared with the effect of phenobarbitone on purified c-AMP-phosphodiesterase in vitro. The stimulatory effect of phenobarbitone on hepatic microsomal aniline hydroxylase activity was found to be simulated by theophylline, and also by thyroxine. When phenobarbitone and thyroxine were used, the effect was approximately equal to the sum of the individual effects, but no summation was seen when phenobarbitone and theophylline were used. Phenobarbitone caused an inhibition of c-AMP-phosphodiesterase activity in vitro. The magnitude of this inhibitory effect was found to be dependent on the dose of phenobarbitone. The significance of c-AMP-phosphodiesterase inhibition by phenobarbitone is discussed.


Ultrasound in diagnosis of congenital hydronephrosis due to obstruction of pelviureteric junction.

The use of ultrasonography in the diagnosis of upper abdominal masses with nonfunctioning kidneys is described. Two cases of congential hydronephrosis due to obstruction of the pelviuretic junction are presented, both of which were diagnosed by B-scan ultrasound examination. Diagnostic ultrasound is a simple, noninvasive and reliable method of differentiating cystic from solid lesions and of assessing whether or not a mass is renal or extrarenal. It is recommended that all patients seen with an upper abdominal mass and/or nonfunctioning kidney be examined by ultrasound.


Feline leukaemia virus and its clinical effects in cats.

Feline leukemia virus (FeLV) infection is common among cats where contact is high. The virus can be transmitted readily between cats. It causes a variety of haemopoietic and lymphoid neoplasms; the most common types are alimentary, multicentric and thymic lymphosarcoma and lymphatic leukaemia. The virus is involved in the aetiology of certain other diseases including anaemia, glomerulonephritis and an immunosuppressive syndrome which predisposes cats to intercurrent infections. Many infected cats mount an immune response and do not suffer from any of these. The immune status is shown by serum antibody levels to feline leukaemia virus associated cell membrane antigens. Cats with a titre of 32 or more are most unlikely to suffer any ill effects and may eliminate the virus infection. The outcome of infection in an individual cat depends on the immunological competence of the cat, the dose of virus received and its ability to induce immunosuppression. FeLV infection can be detected by examination of tissues by electron microscopy, and by culture of virus from plasma and other tissues. In the United States, a method is now in use for the detection of leukaemia virus antigen in peripheral blood leukocytes; this is carried out on ordinary blood films. Successful prototype vaccines have been developed against FeLV. This paper describes the natural history of the virus, the diseases in which it is implicated and discusses recently developed diagnostic methods.


Equine infectious respiratory disease.

During the past 20 years the equine population of Great Britain and Ireland has increased with the result that the practising veterinary surgeon is more frequently called upon to advise on equine problems. A significant portion of this advice is concerned with the examination of horses showing signs of this advice is concerned with the examination of horses showing signs of respiratory disease. Numerous pathogens, which include viruses, bacteria, parasites and moulds invade the respiratory tract causing similar signs of illness. It is therefore difficult to provide an aetiological diagnosis based on a clinical examination. Field studies supported by laboratory investigations have established that influenza and herpes viruses are frequently responsible for outbreaks of disease. Epidemiological studies suggest that other factors including the immune state of the equine population influence the distribution and severity of respiratory disease. The aetiology, diagnosis, treatment and control of equine infectious respiratory disease are discussed below.


Viral enteritis of calves.

Calf diarrhoea is an important cause of economic loss.  The aetiology of the disease is considered with particular reference to the role of viruses.  Although many microbial organisms have been associated with the disease, there is doubt concerning their true role as causative agents.  Two viruses, neonatal calf diarrhoea reovirus-life agent and calf coronavirus, have been discovered recently which appear to play an important role in many cases of diarrhoea and the evidence for considering them to be primary causes of the disease is discussed.


Bedding materials for cubicles.

With the shortage of straw, its increasing cost, its handling and storage, farmers are seeking suitable alternative bedding materials for cubicles.


Mixed Müllerian tumors of the uterus. Ultrastructural studies on the differentiation of rhabdomyoblasts.

In the present study the differentiation of rhabdomyoblasts of two carcinosarcomas of the uterus is analysed electronmicroscopically. During the development of rhabdomyoblasts three cell types can be distinguished: 1. the undifferentiated mesenchymal cell with abundant ribosomes but few other cell organelles. Usually these cells are already associated to each other in strands of 2-4 cells. Occasionally cytoplasmic areas with numerous nonspecific filaments can be observed. 2. the light rhabdomyoblast which is characterized by its conspicuous nonspecific cytoplasmic filaments and its reduction in ribosomes. Specific myofilaments can be visualized only occasionally in this cell type. 3. more differentiated rhabdomyoblasts. These cells can be identified clearly by the presence of large numbers of myofibrils and myofibrillar fragments. Higly organized myofibrils as seen in skeletal muscle are seldom found. Transitional forms between these cell types are also observed. The functions of Z-bodies and of the sarcotubular system in the process of myofibrillar differentiation are discussed.


The development of the primitive epithelium and true tegument in the cercaria of Schistosoma mansoni.

The formation of the final cercarial tegument of Schistosoma mansoni is preceded by that of a so-called primitive epithelium. The primitive epithelium is derived from the tegument of the daughter sporocyst. The final cercarial tegument is formed from peripherally located somatic cells of the cercarial embryo, which expand and coalesce beneath the primitive epithelium. The primitive epithelium degenerates and disappears. The ultrastructure of both epithelia in the course of the development of the cercaria is described in detail. Possible functions are discussed.


Serum growth hormone and gonadotrophins and urinary steroids in adolescent girls.

In a series of 146 school girls and nurses in the serum levels of growth hormone (GH), follicle stimulating hormone (FSH), and luteinizing hormone (LH) were determined in the afternoon after 4-5 hours' fast. Blood specimens of the menstruating girls were taken on the 7th to 10th day from the beginning of the preceding menstrual bleeding. From the 24-hour urines collected on the previous day the excretion of total oestrogens, 17-ketosteroids and 17-hydrocorticosteroids was determined. The series was grouped according to skeletal age which varied from 8.0 years to the adult stage. In the girls aged 11-13 years the GH curve showed a significant rise parallel with the mean height curve. The FSH values at the early age of 8-9 years corresponded to the follicular phase of adult women. The LH level increased syteeply up to the 15th year of bone age and mean values of adults were found to be about three times those of childhood. The excretion of total oestrogens and 17-ketosteroids increased steadily up to the full maturity of skeletal age. In the oldest group of girls the excretion was about four times that of the group aged 8-9 years. The hormonal maturation seems to continue until late puberty. The 17-OHCS, on the other hand, reached the adult level in the group with a bone age of 13 years. The excretion of 17-OHCS shows a steep rise from the age of 11 to 12 years and this acceleration of excretion perhaps exceeds the increase in surface area.


Studies on isolated rat adrenal cells. I. Continuous flow and batch incubation.

A procedure for the continuous flow incubation of isolated adrenal cells is described. In this way the advantages of continuous flow incubations of adrenal tissue are combined with those of isolated adrenal cells. Suspensions of isolated adrenal cells were prepared by a modification of the collagenase method. A sigmoid dose-response curve was obtained when these cells were incubated with ACTH in batch incubations. Under these conditions (in the presence of 1 mU ACTH/ml) the corticosterone production rate remained constant during at least 240 min. This production rate was linearly related to the number of cells. Pre-incubation of the cells during 3 h resulted in an increased response to ACTH. In continuous flow incubations without ACTH the corticosterone production was negligible. With 100 mu U ACTH/ml corticosterone production increased sharply after a short lag period. A maximum was reached after 60-75 min followed by a slow decrease. Cells pre-incubated in the continuous flow apparatus had a slightly diminished ACTH response without loss of affinity to ACTH. The continuous flow incubation of isolated adrenal cells offers new possibilities for the dynamic study of steroid biosynthesis in vitro. The method may also be valuable to study processes in a wide variety of other tissues.


Affinity and specificity of antisera against human FSH and TSH obtained by immunizing rabbits with highly purified hormone preparations.

Two groups of 4 rabbits were immunized according to the method described by Vaitukaitis et al. (1971). One group was given 55 mu g (900 IU) FSH/animal and the other 100 mu g (o.5 IU) TSH/animal. Two highly specific antisera against FSH and one specific antiserum against TSH were obtained. The FSH antisera showed affinities towards LH and TSH of 0.13 and 0.25% respectively as compared to that of FSH. The TSH antisera showed affinities towards LH and FSH of 2.2 and 1.7% respectively as compared to that of TSH. The specific antisera showed no or minor affinities towards the LH-alpha subunit and they were sufficient specific to be used in the radioimmunoassay of serum from pregnant women without pre-absorption with HCG. Scatchard plots showed the association constants of the FSH antisera to be 1.3 times 10-11 and 1.2 times 10-11 1/mol respectively, and the association constant of the TSH antiserum to be 6 times 10-10 1/mol. All 3 antisera showed high titers.


The cytopathology of metastatic breast cancer.

A comparison was made between the histopathologic and cytopathologic appearances of 45 cases of metastatic breast cancer and the histopathologic appearance of their primary neoplasms. Metastatic infiltrating duct carcinoma in body cavity fluids presented with an admixture of single cells and tissue fragments in a ratio of 0.86 to 1. The most commonly occurring tissue fragments were well circumscribed round to oval masses of cells, true acini and cells in tandem arrangement. The cells of metastatic infiltrating duct carcinoma were very pleomorphic ranging from 11.5 to 22 micrometers in diameter. Metastatic infiltrating lobular carcinoma in body cavity fluids presented as a population of primarily single cells with a ratio of 13 single cells to each tissue fragment. The rare tissue fragment encountered was a group loosely cohesive cells without nuclear molding by the cytoplasm of adjacent cells. The individual cells had extremely high nuclear/cellular ratios and were uniform in size ranging in diameter from 10.5 to 14 micrometers. The presentation of metastatic infiltrating lobular carcinoma was very similar to that of lymphomas in body cavity fluids and cerebrospinal fluids and may pose a problem in differential diagnosis.


Accumulation of cyclic AMP in hypothyroidism. Decreased sensitivity to norepinephrine in rat adipocytes.

The effect of hypothyroidism on the noradrenaline-induced accumulation of 3H-cyclic-AMP was measured in rat epididymal adipose tissue. Adipocytes from hypothyroid animals showed a decreased response to noradrenaline 0.02-0.2 times 10-5 m, while higher concentrations of the catecholamine seemed to elicit the same response in cells obtained from euthyroid or hypothyroid animals. The diminished sensitivity to noradrenaline was unaltered after the addition of phentolamine. It is suggested that thyroid hormones modulate the catecholamine-induced lipolytic response at least partly through the adenyl cyclase cyclic-AMP system.


Seasonal patterns of sleep stages and secretion of cortisol and growth hormone during 24 hour periods in northern Norway.

A group of 7 healthy male subjects was studied in regard to sleep stages and 24 h plasma cortisol and growth hormone patterns during the 4 seasons of the year in an Arctic environment (Tromsø, Norway). No difference in total sleep or sleep stage per cents was found for any of the yearly seasons. A small but statistical significant increase in mean plasma cortisol concentration and amount secreted for 24 h was found for the autumn-winter seasons, as compared with the spring and summer. However, no difference in the circadian curve of cortisol hormonal pattern was found. All subjects secreted growth hormone shortly after sleep onset at night and no difference was found as a function of season of the year.


Virilizing adrenocortical adenoma responsive to gonadotrophin.

A virilizing adrenocortical adenoma was demonstrated in a yound female. Urinary 17-ketosteroid excretion and subfractions, plasma testosterone level and urinary 17-ketogenic steroid excretion were markedly increased. Dehydroepiandrosterone was the main constituent of the androgen excess. Otherwise the adrenocortical function was found to be normal as evaluated from measurements of cortisol, corticosterone and their metabolites under basal conditions and during dynamic tests. The androgen excess showed an unexpected response to trophic hormones. Human chorionic gonadotrophin stimulation resulted in a pronounced increase in androgen production, whereas no gonadotrophin-dependency could be demonstrated by means of the oestrogen suppression test. Similarly, no corticotrophin-dependency could be demonstrated by corticotrophin stimulation and suppression tests. Removal of the tumour resulted in normalization of the androgen production and no abnormal response upon human chorionic gonadotrophin administration could now be found. The inappropriate response of tumours to trophic hormones is discussed. It is concluded that the reliability of stimulation and suppression tests in determining the site of excessive androgen production should be accepted with reservation.


Dissociation of in vivo and in vitro "autonomy" in human adrenocortical tumour.

The diagnosis of Cushing's syndrome due to "autonomous adrenocortical tumour" has been established in a patient by appropriate examinations (especially dexamethasone suppression test, ACTH stimulation test, ACTH measurement by radioimmunoassay). Isolated cells have been prepared from a piece of the tumour by a trypsin technique so that the action of ACTH on steriodogenesis in these cells could be studied in vitro. Basal production of corticosteroids by the isolated tumour cells was low (0.3 mu plus or minus 0.04/2 h/10-5 cells). Addition of ACTH induced a dose-dependent stimulation of corticosteroid production. The tumour cells appeared to be unable to produce corticosteroids in the absence of ACTH; maximal production was rather low (1.38 mu plus or minus 0.07/2 h/10-5 cells). A possible explanation for the discrepancies between endocrine function tests and the results of the in vitro studies is given.


Oestradiol-17 beta uptake in vitro into the nuclei of endometrium from different regions of the human uterus.

Specimens of endometrium from the vault, body and lower body regions of the same human uteri were incubated separately for 30 min in vitro in the presence of 1-6 times 10-9 M 3H-oestradiol. Uptake into the nuclei was variable but in general the vault region endometrium was least active in nuclear accumulation of the hormone, especially in secretory phase endometrium. This suggests that intra-uterine variations found in oestradiol uptake in vivo are due to regional differences in the state of the tissue itself.


The sick-sinus syndrome in Africans.

Fifteen cases of the sick-sinus syndrome in young Negroes are presented. The etiology was unknown in all cases; organic heart disease was absent. The very high default rate suggests that the prognosis may be grave. This disorder is by no means uncommon in young persons in tropical countries and the dangers of a mistaken diagnosis of epilepsy or a psychiatric illness have been emphasized. In the absence of an artificial pacemaker, it is suggested that sympathomimetic drugs, while not affecting the heart rate, may be useful in reducing the frequency of syncopal attacks.


Bronchiolo-alveolar carcinoma-cell of origin.

Bronchiolo-alveolar carcinoma is the least common of the primary pulmonary carcinomas, and there is controversy as to its cell of origin. In this light- and electron microscopic study of five bronchiolo-alveolar carcinomas, at least two cell types were found, both of bronchiolar origin. One cell type is a metaplastic bronchiolar mucous cell and the other a bronchiolar stem cell that has ultrastructural features of both the respiratory ciliated and the respiratory nonciliated ("Clara") cell. It would not be unusual if tumors of the bronchiolo-alveolar region differentiate into cells of either the bronchiole or the alveolus, for embryologically they have a common origin. However, as information about the ultrastructure of these tumors accumulates, it is becoming apparent that an alveolar-cell carcinoma must be a rare occurrence. Hyperplastic Type II aleveolar epithelial cells may be found about the margins of these tumors and can be mistaken for the neoplastic cells.


Pyrophosphate arthropathy.

A scanning electron microscopic study of six cases of pyrophosphate arthropathy has been conducted. In the majority of cases the crystals were rectangular. In some cases giant crystals were present. In one case, the crystals were pyramidal. It is concluded that many geometrically different forms of calcium pyrophosphate crystal exist and that the scanning electron microscope is a useful tool in the differentiation of pyrophosphate arthropathy from other forms of crystal synovitis.


An outbreak of severe pneumonia due to respiratory syncytial virus in isolated Arctic populations.

A rapidly developing outbreak of pneumonia in young infants was documented in two isolated Artic populations in May 1972. These were studied virologically, serologically and clinically. In addition to the two stricken communities, one apparently unaffected with serious clinical illness and a fourth, in which are located the major hospital and airport in the eastern Arctic, were also studied. One hundred and twenty-four patients were studied serologically and 81 respiratory and other specimens were obtained for virus isolation from 40 of these patients. Clinical records were kept of the outbreak in each area and a detailed questionnaire was filled out for 140 children and their families. Respiratory syncytial  irus (RSV) was cultured from eight ill children. Electron microscopy provided the first evidence of RSV infection. A seroconversion rate of approximately 50% was seen in both affected communities as well as in the clinically unaffected one. The epidemic in the first two communities was characterized by severe pneumonia and frequent hospitalization but no cases of bronchiolitis were seen. No evidence for other causes of this outbreak could be obtained by testing for antibodies to influenza A and B, parainfluenza 1, 2 and 3, adenovirus and herpes simplex viruses. Unusual features of this epidemic of RSV infection include the high attack rate, severe morbidity, illness manifest almost exclusively as pneumonia rather than bronchiolitis and the difference between the expression of disease in different communities. Historical data and clinical observations were inadequate to explain these unusual features.


Immunologic significance of the mumps virus skin test in infants, children and adults.

The biologic validity of cell-mediated immunity to mumps virus was evaluated in 395 children, adolescents and adults. The study protocol included the determination of cutaneous delayed hypersensitivity to viral and avian control antigens and in 79% of the subjects an essential double bleeding was performed before and after mumps virus skin test for assay of neutralizing antibody. Seven per cent of subjects expressed sufficient delayed hypersentitivity to the control antigen to erase an apparently positive mumps virus skin test. Anamnestic conversions from seronegativity to seropositivity, elicited by the mumps virus skin test, increased from 4% in children to 25% in adults, which suggests waning B-cell recognition of prior mumps virus infection in adults. Although pregnancy diminished the difference (p smaller than .001), adults showed greater cutaneous delayed hypersensitivity to mumps virus antigen than did children (p smaller than .001), suggesting that mumps virus reinfection or persistence induced the escalation of more sensitive T-cell recognition with increasing age. Humoral immunity, assessed by the double bleeding technique in the vast majority of individuals, rose form 16% (1-4 years), 45% (5-9 years) and 80% (10-14 years) to 94% in adolescents and adults. Ordinarily 75-95% in other age groups, the decline of correlation between mumps virus cellular and humoral immunity to 60% in school children may result from prior parainfluenza virus infection, inconsistent potency of the skin test antigen, concurrent immunosuppressive infection, and lagging induction of mumps virus cellular immunity in recently infected individuals. Immunologic study of a large colony of subhuman primates failed to establish an hierarchial antigenic interrelationship among mumps virus and two additional paramyxoviruses.


The role of renal adenosine 3',5'-monophosphate in the control of erythropoietin production.

A regulatory role for adenosine 3',5'-monophosphate (cyclic AMP) in the production of the renal hormone rythropoietin following erythropoietic stimulation with cobaltous chloride hexahydrate is proposed. Studies in rates reveal a temporal relationship between renal cyclic AMP levels and plasma titers of erythropoietin. In addition, cobalt increases the activity of an erythropoietin-generating enzyme (renal erythropoietic factor) with maximal enzyme activity occurring after the rise in cyclic AMP levels but before the increase in erythropoietin titers. This increase in renal cyclic AMP is localized to the renal cortex. Cobalt stimulates renal cortical adenylate cyclase but has no effect on renal cyclic nucleotide phosphodiesterase. The addition of cyclic AMP (3 time 10-6 M) and a partially purified cyclic AMP-dependent protein kinase from rat kidney to an inactive preparation of renal erythropoietic factor increases the ability of renal erythropoietic factor to generate erythropoietin. Data from the polycythemic mouse assay, a bioassay used to quantitate erythropoietic activity of test substances, indicate that dibutyryl cyclic AMP is erythropoietically active with respect to its ability to increase radioactive-labelled iron (59Fe) incorporation into heme of newly formed red blood cells. Theophylline, which by itself is erythropoietically inactive, potentiated the erythropoietic effect of cobalt in polycythemic mice. These results suggest that cyclic AMP plays a significant role in the renal production of erythropoietin following cobalt administration. It is postulated that cobalt stimulates renal cortical adenyoate cyclase, thus increasing renal cyclic AMP levels. Cyclic AMP then activates a protein kinase which subsequently stimulates renal erythropoietic factor to generate erythropoietin. A similar cyclic AMP mechanism may be operative after erythropoietic stimulation by exposure to hypoxia or prostaglandin treatment.


The kidney as an endocrine organ involved in the function of vitamin D.

Vitamin D3 must be metabilically altered first in the liver to 25-hydroxyvitamin D3 (25 OH-D3) and subsequently in the kidney to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) before it can function. Because 1,25-(OH)2D3 is formed in the kidney and acts in intestine and bone to elevate serum calcium and phosphate concentrations, it can be considered a hormone. The production of 1,25-(OH)2D3 is feedback regulated either directly or indirectly by serum calcium and serum phosphate concentrations. The hypocalcemic regulation is mediated by the parathyroid glands. The hypophosphatemic stimulus, however, does not involve either the parathyroid or thyroid glands. Under conditions whereby the synthesis of 1,25-(OH)2D3 is repressed, 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3 is formed. This metabolite can be converted further to 1,24,25-trihydroxyvitamin D3 (1,24,25-(OH)3D3), which stimulate intestinal calcium transport but not bone calcium mobilization or phosphate transport reactions. A number of vitamin D-resistant bone diseases may be related to defective vitamin D metabolism. For example, bone disease related to choric renal failure likely results from defective formation of 1,25-(OH)2D3 in the kidney. Treatment of this disease with intravenously administered 1,25-(OH)2D3 is effective in correcting the bone lesions. 1Alpha-hydroxyvitamin D3 (1alpha-OH-D3), a new synthetic analog of 1,25-(OH)2D3 which is less expensive to produce than 1,25-(OH)2D3, is effective in anephric animals and may have several advantages over 1,25-(OH)2D3 in treating bone diseases.


The protean manifestations of Mycoplasma pneumoniae infection in adults.

Mycoplasma pneumoniae is a well recognized respiratory pathogen in children and young adults. In addition, M. pneumoniae infections may also involve other organ systems. Reviewed here are the various clinical syndromes in adults caused by this infectious agent, with emphasis on those which have recently been seen at The New York Hospital. Two previously unreported manifestations of M. pneumoniae infection, cranial nerve mononeuropathy and hepatitis, are described, and the laboratory methods for diagnosis are discussed.


American Burkitt's lymphoma: a clinicopathologic study of 30 cases. II. Pathologic correlations.

Thirty cases of malignant lymphoma, undifferentiated, Burkitt's type are reviewed. An older median age and a predominance of presentation in abdominal and pelvic sites rather than in the jaw distinguishes this series of American patients from those reported from endemic regions in Africa. Bone marrow involvement invariably consisted of massive infiltration recognizable in smear, clot and biopsy preparations. Involvement of the central nervous system or bone marrow was always associated with short survival. In all eight long-term survivors lymphoma was apparently confined to a single site at presentation. At autopsy, the most consistent finding was widespread multiorgan involvement without predilection for lymphoreticular structures. The histologic appearance of the tumor changed after chemotherapy, varying from diffuse necrosis within 48 hours of initial therapy to extreme pleomorphism of tumor cells after 9 months of therapy. In one patient, there was almost complete absence of lymphoma at autopsy in an organ site shown clinically to have been extensively involved by tumor prior to treatment. The diagnostic and therapeutic implications of these findings are discussed.


Clinical evaluation of patients with infectious mononucleosis and development of antibodies to the R component of the Epstein-Barr virus-induced early antigen complex.

Previous reports have emphasized that the transitory antibody responses to Epstein-Barr virus (EBV)-induced early antigens (EA) in the course of infectious mononucleosis are usually directed against the D (diffuse) component of the EA complex. In this report clinical and serologic data have been presented on 14 patients with infectious mononucleosis who responded either solely with antibodies to the R (restricted) component of the EA complex or revealed anti-R after the initial anti-D responses had subsided weeks or months after onset of the disease. Anti-R persisted usually for many months , as many as 39, but in some patients it was no longer detectable in late follow-up serum spectimens. Although many patients had an unremarkable course of illness, others, mostly those with late anti-R responses, showed unusual or protracted clinical manifestations and several complained over periods of 4 to 28 months of recurrent symptoms resembling those experienced during the acute stage of disease. The presence of anti-R and the relatively high continuous titers of antibodies to EB viral capsid antigens (VCA) may reflect a more than usual, persistent EBV activity which, in turn, may account for the recurrent symptoms.


Fanconi syndrome in adults. A manifestation of a latent form of myeloma.

From a review of 17 cases of Fanconi syndrome with Bence Jones proteinuria and myeloma or amyloidosis, including three new cases reported here in detail, there emerges a well defined set of characteristics. In most cases, the diagnosis of Fanconi syndrome preceded the development of myeloma or amyloidosis. Myeloma preceding the development of Fanconi syndrome has not been reported. All the patients had Bence Jones proteinuria, but in some it could be detected only by electrophoresis or immunoelectrophoresis, In the seven cases in which the Bence Jones protein was typed, it was of kappa type. There were no serum protein monoclonal abnormalities. In the bone marrow and renal samples of half of the patients, crystalline cytoplasmic inclusion bodies were present in lymphoplasmacytic elements and renal tubular cells. It is proposed that patients with Fanconi syndrome and Bence Jones proteinuria have a distinct type of plasma cell disorder or variant of the monoclonal gammopathies, characterized by a slow progression of the tumor and by an early phase dominated by the metabolic complications of the renal proximal tubular dysfunction. Adult patients with Fanconi syndrome should be carefully investigated for the presence of Bence Jones protein and a plasmacytic dyscrasia should be excluded.


Aberrant hormone activity by tumors of gynecologic importance.

Increasing numbers of endocrine active tumors are being reported. The production of hormonal substances not generally associated with the tissues involved may directly or indirectly concern the gynecologist. Identification of these occurrences may be important in the diagnosis of occult neoplasms or obscure tumor effects. In addition, observation of the level of aberrant hormone secretion may be important therapeutic and prognostic measure. Detection may result from the investigation of apparent inappropriate and endocrine syndromes or routine screening in cases of known tumors. Proof of the actual production of hormone by the tumors and complete identification of the material in question generally requires extensive biologic, chemical, physical, and immunologic investigation. The most likely mechanisms for aberrant hormone production by tumors are derepression of the genome or the occurrence of chance biosynthetic anomalies coincident with neoplastic nuclear alterations. Endocrine active substances of interest to the gynecologist produced under these circumstances include gonadotropin, lactogens, thyrotropins, and adrenocortico-tropin, as well as calcium-mobilizing and erythropoietic substances.


Carcinoembryonic antigen in patients with gynecologic malignancies.

The determination of carcinoembryonic antigen (CEA) in plasma has been of much interest currently concomitant with the search for an immunologic diagnosis test. Recent reports have shed some doubt on the specificity of carcinoembryonic antigens for gastrointestinal tract malignancies. This report details the plasma CEA values in 341 patients with varying gynecologic malignancies. These studies have demonstrated that plasma CEA is elevated in close to 50 per cent of patients with invasive gynecologic cancer. The incidence of positive values is appreciably higher in the advanced stages of disease. Of particular interest was that 84 per cent (21 of 25) of the patients with recurrent squamous-cell carcinoma of the cervix had a positive CEA value. Similar results were found in patients with cancer of the vulva, ovary, and endometrium.


Effect of progesterone on estrogen receptors in the rabbit uterus.

The macromolecular binding of estradiol was investigated in the rabbit uterus under various hormonal states in a search for evidence of progesterone antagonism of the estrogen-receptor complex interaction. Progesterone did not alter the sucrose gradient sedimentation characteristics of the estrogen-receptor complex in estrus or castrate animals. Progesterone treatment of castrated animals did not alter the absolute number of EBS (estrogen-binding sites) per cell, but did result in decreased relative concentration of EBS by increasing the soluble protein content of the cells over that seen in untreated castrates. Castration did not alter the absolute number of EBS per cell but did increase the relative concentration of estrogen binding in the cytosol.


Hormones in human pregnancy. IV. Plasma progesterone.

The plasma concentration of progesterone (P) has been measured by radioimmunoassay in maternal peripheral vein (M.P.V.) at early pregnancy and in M.P.V. umbilical artery (U.A.) and umbilical vein (U.V.) at term pregnancy. In early preganacy marked hour-to-hour fluctuation of plasma progesterone was noted. At term pregnancy plasma P levels of U.V. were higher than those of U.A. and the umbilical venous arterial differences of plasma P did not differ between male and femal fetuses. Administration of hydrocortisone and ACTH to patients scheduled to undergo cesarean section had no effect on M.P.V., U.A., and U.V. plasma P concentration. On the basis of the differences between U.V. and U.A. plasma P concentrations and reported umbilical flow it was estimated that the secretion rate of P into the fetal circulation is approximately 23 mg. per 24 hr. and would amount to approximately 10 per cent of the reported total daily production rate of P at term pregnancy. The fraction of P which is unbound to the plasma proteins was estimeated by equilibrium dialysis at 37 degrees C. The per cent unbound P in M.P.V. plasma of pregnant patients at term was not different from that of nonpregnant patients but was 40 per cent lower than that in umbilical cord plasma (P LESS THAN 0.01), and the ratio between the concentrations of unbound P and estradiol in M.P.V. increased as pregnancy progressed. Plasma P in re-eclamptic patients who subsequently sustained intrauterine fetal death had no value in assessing placental function.


On the regulation of fetal and maternal 16 alpha- hydroxydehydroepiandrosterone and its sulfate by cortisol and ACTH in human pregnancy at term.

In studying the mechanisms which govern estriol production in human pregnancy at term, 16 alpha OH-DHEA, 16alpha-OH-DHEA sulfate, and unbound unconjugated cortisol were measured in peripheral venous plasma of 28 healthy women and in cord venous and arterial plasms of their newborn infants at the time of elective cesarean section prior to the onset of labor. In eight cases treated with 150 mg. of cortisol, maternal and cord plasma 16alpha-OH-DHEA and its sulfate were considerably lower than in 10 control cases. Approximately 4 to 8 1/2 hours after injection of 40 I.U. of Depot-ACTH, both of these estriol precursors were also significantly decreased. It is concluded from these experiments that cortisol causes a decrease of estriol mainly by suppressing fetal 16alpha-OH-DS.


Human atherosclerotic plaque cells and leiomyoma cells. Comparison of in vitro growth characteristics.

Cells derived from human atherosclerotic plaques and from arterial media were compared with cells obtained from human leiomyomata and myometrium with respect to growth behavior in long-term cell culture. None of numerous variations in culture media, including alterations of serum concentration and source, improved the rate of cell multiplication or in vitro longevity. Both uterine cell types, but neither arterial cell type, multiplied after tissue dissociation with enzymes (elastase, collagenase, hyaluronidase). The replicative life-span of each of eight samples of arterial plaque cells was equal to or less than that of the corresponding medial cells. A similar relationship was observed for eight paired sets of leiomyoma and myometrial cells. The results indicate that, under the conditions of culture in vitro, cells of a bona fide smooth muscle tumor have a finite replicative life-span and smooth muscle cells of atherosclerotic plaques behave in a similar manner.


Immunohistochemical demonstration of serine dehydratase in rat liver.

Serine dehydratase (L-serine hydro-lyase, EC 4.2.1.13) WAS DEMONSTRATED IN LIVER TISSUE OF RATS BY AN INdirect immunofluorescent method. In the adult rat liver, serine dehydratase was localized to periportal hepatocytes, diffusely in their cytoplasm. The enzyme-specific fluorescence was absent or extremely low in the centrolobular hepatocytes. It was not demonstrated in nonparenchymal cells. Feeding a 90% protein diet for 5 days caused marked induction of this enzyme in the periportal and midzonal hepatocytes but no induction in the centrolobular hepatocytes. In the newborn rat liver, there was no apparent intralobular heterogeneity seen in the distribution of serine dehydratase, either before or after dietary induction. After 1 week of age, there was a gradual development of the intralobular hetero-geneity of the enzyme, which was emphasized by dietary stimulation. A comparative study of the induction pattern between the livers of intact and adrenalectomized rats suggested that there is no heterogeneity among serine-dehydratase-positive cells with respect to hormonal regulation of this enzyme by either glucagon or cortisone.


Nuclear bodies produced in astrocytes by tilorone.

Large, eosinophilic, nonglycogenic nuclear inclusions were produced in the central nervous system by the drug tilorone. At the light microscope level, the inclusions occurred predominantly in astrocytes. Ultrastructurally, they were identical to the nuclear bodies described in many cell types under many conditions. The bodies were produced by tilorone in small numbers in the median eminence, a part of the hypothalamus that lacks a blood-brain barrier. They were produced in only 2 or 3 days in large numbers adjacent to zones of thermal or traumatic necrosis or in areas of inflammation. These facts, and the distribution of affected astrocytes, indicated that permeability factors and cerebrospinal fluid flow were involved in the development of the nuclear bodies. The large size and large number of nuclear bodies produced by tilorone should facilitate studies of this poorly understood nuclear organelle.


Effect of inhibition of peptidase activity on distribution of intrarenal blood flow.

Experiments were performed in dogs to determine the effects of the intravenous administration of the dipeptide hydrolase inhibitor SQ 20,881 on renal hemodynamics, intrarenal blood flow distribution, and renal function. Dipeptide hydrolase converts angiotensin I to angiotensin II and inactivates bradykinin. SQ 20,881 causes an inhibition of the vasoconstrictor response after angiotensin I and potentiation of the vasodilatory activity of bradykinin. Total renal blood flow, cortical distribution of blood flow, and glomerular filtration rate were determined. In seven animals administration of SQ 20,881 (1 mg/kg) resulted in a decrease in mean systemic blood pressure of 11 mmHg, an increase in total renal blood flow of 0.71 ml/min per g, and a significant fall in glomerular filtration rate. Fractional blood flow to the superficial cortex decreased and to the juxtamedullary cortex increased. Absolute flow was unchanged in the superficial cortex and increased significantly in the deep cortex. The findings are compatible with reported effects of bradykinin on intrarenal blood flow distribution, although the experiments do not distinguish between potentiation of bradykinin or inhibition of angiotensin I conversion.


Release of cyclic AMP by toad urinary bladder.

Cyclic AMP accumulates in the Ringer solution bathing the toad urinary bladder in vitro. At least 4 times more cyclic AMP is released into the solution bathing the serosal surface than into the solution bathing the mucosal surface. Most of the cyclic AMP originates in the epithelial cells rather than the stroma. Vasopressin increased the content of cyclic AMP in the epithelial cells and increases the amount of cyclic AMP in the Ringer solution. Since there is not an increase in medium cyclic AMP when cell cyclic AMP levels are increased by theophylline, it is suggested that theophylline may reduce the permeability of the cell membrane to cyclic AMP. Finally, it is demonstrated that 10 mM NaF increase the amount of cyclic AMP in the epithelial cells and in the solution bathing the bladder, but block the effect of vasopressin on water permeability, presumably at a step subsequent to the formation of cyclic AMP.


Roentgen problems in evaluating the atrophic stomach of the elderly.

Gastric atrophy in the elderly may cause problems in the interpretation of gastrointestinal studies.  Seventeen such cases are reported: 8 patients showed limited distensibility and irregularity of the distal stomach simulating scirrhous carcinoma; 6 patients showed gastric retention of food; and 2 patients showed gastric retention of oral cholecystographic medium.  Awareness of these phenomena may prevent serious errors in roentgen diagnosis.


Porcine malignant hyperthermia: effects of halothane on mitochondrial respiration and calcium accumulation.

Vastus lateralis muscle was excised from normal pigs and from pigs susceptible to malignant hyperthermia. Anesthesia consisted of diazepam, N2O:O2, and a lidocaine field block. In the susceptible (MHS) pigs, respiratory control in mitochondria of excised muscle was normal, while electron transport was accelerated. Glutamate log Q3's and log Q4's were in inverse linear relationship to porcine weights. In the presence of glutamate, state 3 respiration was 3.5 times, and state 4 respiration 3.2 times, higher in MHS than in normal mitochondria (independent of weight or halothane dose). Thus, the MHS mitochondria were able to produce ATP more efficiently than normal mitochondria. In vitro, halothane inhibited glutamate Q3's and R.C.I.'s, slightly increased succinate Q3's and R.C.I.'s, had no significant effect on glutamate or succinate Q4's, and, moderately lowered glutamate and succinate P/O ratios. These changes were similar to those observed in normal pigs. Calcium uptake into MHS mitochondria was markedly less than normal but was not significantly altered by in-vitro halothane. These results suggest a mitochondrial membrane component for the defect of procine malignant hyperthermia since calcium is normally associated with the formation of the phospholipid lattice of this membrane. (Key words: Hyperthermia, malignant; Metabolism, mitochondrial; Muscle, skeletal, mitochondria; Anesthetics, volatile, halotbane; Ions, calcium.)


Infectious bovine rhinotracheitis-infectious pustular vulvovaginitis viral isolates from cattle with epididymitis and vaginitis.

Infectious bovine rhinotracheitis-infectious pustular vulvovaginitis (IBR-IPV) viral isolates were obtained from cattle affected with epididymitis-vaginitis. Isolation of virus from the diseased animals indicated that the genital form of IBR-IPV virus infection exists in Kenya and that epididymitis-vaginitis may be associated with IBR-IPV virus. Serums prepared from cattle having the genital form of the disease did not always have detectable antibody titers.


Porcine parvovirus: frequency of naturally occurring transplacental infection and viral contamination of fetal porcine kidney cell cultures.

The frequency of naturally occurring transplacental infection of swine with porcine parvovirus (PPV) and one of the possible consequences of such infection--the presence of PPV in cell cultures prepared from fetal tissues--were investigated. Transplacental infection was indicated by the presence of high titers of hemagglutination inhibiting (HI) antibody for PPV in serums of 0-day-old, hysterectomy-derived, colostrum-deprived pigs of 3 of 82 litters. All letters were farm-raised dams. Moreover, cell cultures prepared from 3 of 49 lots of fetal porcine kidneys (FPK) collected from an abattoir during an interval of 14 months were found contaminated with PPV. Because each lot was usually comprised of kidneys from 2 litters, the latter finding suggests that 3 of approximately 98 litters were infected. Prior infection of FPK cell cultures with PPV resulted in only slight interference of replication of other selected viruses; i.e., porcine enterovirus (PEV), pseudorabies virus (PRV), vesicular stomatitis virus (VSV), and hemagglutinating encephalomyelitis virus (HEV). Moreover, PPV and HEV were propagated in the same cell cultures during 5 serial passages of the viruses. In contrast, when copropagation of PPV and VSV was attempted, PPV was not detected after the 2nd serial passage.


Immunogenic and protective effects of the F-2 strain of feline viral rhinotracheitis virus.

The F-2 strain of feline viral rhinotracheitis (FVE) virus was administered by intramuscular (IM) injection to susceptible cats. The cats developed serum-neutralizing antibodies and were protected to a significant degree when given, by intranasal (IN) instillation challenge inoculum of a virulent strain of FVR virus.


Broad-beta disease (type III hyperlipoproteinemia) in a large kindred. Evidence for a monogenic mechanism.

The inheritance of broad-beta disease (as specified by a type III lipoprotein pattern) has remained an enigma. Previous reports have variously implicated a single gene (autosomal dominant mode), a double dose of a single gene (autosomal recessive), two separate genes (mixed heterozygosity), or multiple genes (polygenic inheritance). The present study of a single, large kindred of 108 members spanning 4 generations provides evidence for an autosomal dominant mode, since at least 1 member of the first generation pair was normal, at least 5 of their 9 children had type III patterns, and at least 2 of these (whose spouses were normal) transmitted this pattern to their offspring. The findings also suggest that in this kindred the common occurrence of hypertriglyceridemia (in a type IV pattern) may represent either a variable phenotypic expression of the gene for broad-beta disease or the coexistence of a second, independent genetic lipid disorder.


Type III hyperlipoproteinemia: an analysis of two contemporary definitions.

Two current definitions of type III hyperlipoproteinemia, "floating beta" lipoproteins and an estimate of the relative content of cholesterol and triglyceride in lipoproteins of density less than 1,006 (very low-density [VLD] lipoproteins), have been compared. Over 3100 complete lipoprotein analyses of 182 adults with primary familial hyperglyceridemia, covering a wide range of plasma lipid concentrations, formed the data base for this retrospective analysis: The ratio of VLD lipoprotein cholesterol to the plasma triglyceride concentration (VLDL/TG=r) proved capable of segregating an apparently unique subpopulation with persistently abnormal very low-density lipoprotein composition. Although floating beta lipoproteins were present in nearly all patients with a high r value, they also appeared inconsistently in many other patients. It is concluded that the chemical index to VLD lipoprotein composition is the better, albeit, temporary definition for this disorder. When the plasma triglyceride concentration is between 150 and 1000 mg/100 ml, an r not less than 0.25 should be considered as suggestive and a value not less than 0.30 as diagnosttc of type III hyperlipoproteinemia.


The biochemical, clinical, and genetic features of type III hyperlipoproteinemia.

The clinical and biochemical features of type III hyperlipoproteinemia are described in 49 patients from 23 to 70 years of age. An increase in very low-density lipoproteins (VLDL) of abnormal chemical composition was the basis for diagnosis. The untreated patients all had hypercholesterolemia and hyperglyceridemia, and, on the average, decreased concentrations of both low- and high-density lipoproteins. Seventy-four percent had xanthomas, and classic "xanthoma striata palmaris" was found in more than half. Twenty-seven percent had ischemic heart disease, detected earlier in men than in women. Twenty-seven percent had peripheral vascular disease (compared to 4% of subjects with type II hyperlipoproteinemia). Twenty-five of 35 subjects achieved normal lipid levels with dietary therapy alone. Analysis of 29 kindred showed hyperlipidemia in half of adult blood relatives; half of these had type III, the remainder usually had sample endogenous hyperglyceridemia (type IV). Only 2 of 55 children less than 20 years of age were affected, both with type IV.


The lipid storage diseases: new concepts and control.

The nature of the enzymatic defect is now well established in ten inherited disorders of lipid metabolism. This information has provided for the development of facile, sensitive tests using readily available materials such as washed leukocytes or cultured skin fibroblasts for the diagnosis of these disorders; the detection of heterozygous carriers of these traits; and the monitoring of pregnancies at risk for any of these conditions. Recent investigations of enzyme replacement therapy have shown great promise for the treatment of patients with Fabry's disease and those with the adult form of Gaucher's disease. Additional procedures must be developed for successful enzyme replacement in patients where the central nervous system is damaged by the accumulation of lipids.


Insulinoma with low circulating insulin levels: the diagnostic value of proinsulin measurements.

Hypoglycemia coexisting with very low plasma immunoreactive insulin concentrations was found in a 78-year-old woman with an insulinoma. However, the absolute proinsulin levels during hypoglycemia were elevated (0.9 to 1.4 ng/ml), accounting for 66.5% of the total circulating immunoreactive insulinlike material. The raised serum proinsulin concentrations together with an abnormal proinsulin:insulin ratio proved to be of critical importance in establishing the diagnosis of an islet-cell tumor in this patient.


Collagenolytic activity of some marine bacteria.

Reconstituted, acid-extracted collagen was used to prepare a medium to screen proteolytic marine bacteria for their ability to elaborate collagenolytic enzymes.  The medium was resistant to solubilization by trypsin, hyaluronidase, chondroitinase ABC, and various marine proteinases, but was readily hydrolyzed by commercial Clostridium collagenases.  Eighty-seven marine isolates collected in the vicinity of Bermuda, Oahu (Hawaii), and Stone Harbor and Cape May, N. J., were screened.  Approximately 44 per cent of the isolates were capable of elaborating enzymes that hydrolyzed reconstituted collagen gels.  Several cultures produced collagenolytic enzymes only when grown in the presence of collagen or degradation products of collagen, and with very few exceptions the presence of collagen in the medium greatly enhanced collagenolytic enzyme production.  The enzymes from a collagenolytic Bermuda marine isolate were studied in more detail to illustrate that the enzymes capable of hydrolyzing reconstituted collagen were separable from nonspecific proteinases by zone electrophoresis and that these enzymes were true collagenases by virtue of their ability to hydrolyze native bovine Achilles'tendon obtained from three different sources.


Uptake and elimination of poliovirus by West Coast oysters.

Accumulation of poliovirus Lsc-2ab by West Coast oysters was determined by using a stationary seawater system, and depuration was determined by using both stationary and free-flow systems. Results indicate that these shellfish have the same pattern of accumulation and localization of viruses as do East Coast species. However, uptake appeared to occur more rapidly than described for East Coast shellfish. There appeared to be a gradual diffusion of virus from the digestive area into the body. Depuration was found to occur more rapidly and completely under free-flow conditions than in a stationary system.


Inactivation of viruses and bacteria by ozone, with and without sonication.

Selected organisms with public health significance were placed in a reaction chamber for treatment by ozonation, by ozonation and sonication, by sonication, or by sonication during oxygenation. Vesicular stomatitis virus, encephalomyocarditis virus, GDVII virus, Staphylococcus aureus, Pseudomonas fluorescens, Salmonella typhimurium, enteropathogenic Escherichia coli, Vibrio cholerae, and Shigella flexneri were inactivated by treatment with ozone. When microorganisms were suspended in phosphate-buffered saline, they were inactivated rapidly by treatment with ozone. However, microorganisms suspended in secondary effluent from a wastewater treatment plant required longer contact times with ozone for complete inactivation. Simultaneous treatments by ozonation and sonication reduced the contact time for complete inactivation of microorganisms in secondary effluent. Treatment by sonication alone or sonication and oxygenation did not inactivate microorganisms. Therefore, the simultaneous treatment of microorganisms in secondary effluent with ozone and sonication resulted in a synergistic effect.


Influence of carbohydrates on growth and sporulation of Clostridium perfringens type A.

Growth and sporulation of Clostridium perfringens type A in Duncan and Strong (DS) sporulation medium was investigated. A biphasic growth response was found to be dependent on starch concentration. Maximal levels of heat-resistant spores were formed at a starch concentration of 0.40%. Addition of glucose, maltose, or maltotriose to a sporulating culture resulted in an immediate turbidity increase, indicating that biphasic growth in DS medium may be due to such starch degradation products. Amylose and, to a lesser extent, amylopectin resulted in biphasic growth when each replaced starch in the sporulation medium. A levels of heat-resistant spores approximately equal to the control was produced with amylopectin but not amylose as the added carbohydrate. Addition of glucose or maltose to a DS medium without starch at stage II or III of sporulation did not alter the level of heat-resistant spores as compared with the level obtained in DS medium with starch. Omission of starch or glucose or maltose resulted in an approximately 100-fold decrease in the number of heat-resistant spores, although the percentage of sporulation (90%) was unaffected. The role of starch and amylopectin in the formation of heat-resistant spores probably involves the amyloytic production of utilizable short-chain glucose polymers that provide an energy source for the completion of sporulation.


Bacterial metabolism of arylsulfonates: role of meta cleavage in benzene sulfonate oxidation by Pseudomonas testosteroni.

Pseudomonas testosteroni H-8 oxidizes certain lower alkylbenzene sulfonates at rates inversely related to the length of the alkyl group. Appreciable Q(O)2 values were observed for benzene sulfonate (BS), toluene sulfonate (TS), and ethylbenzene sulfonate (EBS), but not for propylbenzene sulfonate (PS) and higher homologues. Catechol oxidation was catalyzed by a constitutive catechol-2,3-oxygenase (EC 1.99.2.a). Yellow meta cleavage products accumulated when BS-grown cells were exposed to catechol, 4-methylcatechol, 3-methylcatechol, EBS and PS, but not BS or TS. Traces of a yellow metabolite (probably 2-hydroxymuconic semialdehyde) were detectable during growth on BS. PS completely inhibited growth on BS, but not on L-leucine or nutrient broth. Also, PS antagonized respiration on BS and catechol, but not glutamate, the extent of inhibition being directly related to PS concentration. Formation of a meta cleavage product from PS, and inhibition of catechol oxidation by PS, suggested that the actual inhibitor may not be PS itself, but a metabolite.


Mummified cutaneous mixed tumor.

A 34-year-old man had an unusual mummified cutaneous mixed tumor that developed shortly after trauma. The apocrine type of tumor cells and pilar differentiation could explain the presence of mummification.


Intracavitary cardiac extension of hepatoma.

Acute right atrial obstruction in a 62-year-old man was demonstrated angiographically to be due to a tumor, which was later proved to be metastatic hepatoma. Resection of the tumor resulted in total symptomatic relief.


Effects of diazepam on photosynthesis, respiration, rubidium uptake, and finestructure of Scenedesmus obliquus in synchronous cultures.

Effects of diazepam (Valium) on photosynthesis, chlorophyll/photosynthesis ratios, respiration, uptake of rubidium ions, and ultrastructure of Scenedesmus obliquus synchronized by a light-dark regimen of 14:10 hrs were determined. 80 and 160 muM diazepam, added to the nutrient medium at the start of the light-dark change (i.e., start of the cell cycle) gradually reduced rates of photosynthesis, below the initial rates from the beginning of the experiment. Contents of chlorophyll, however, remained nearly unaffected. Consequently, the diazepam-treated cells had a higher chlorophyll/photosynthesis ratio--also with regard to respiration in order to calculate the gross photosynthesis. The occurrence of photorespiration cannot be assumed. The net influx of rubidium was slightly reduced by 100 muM diazepam 0.5 and 2.0 hrs after the start of the cell cycle and was strongly inhibited after 5 to 14 hrs. 80 and 160 muM diazepam caused separation of thylakoids, formation of giant mitochondria and enlargement of vacuoles.


Ultrastructural changes occurring during germination and outgrowth of spores of the thermophile Bacillus acidocaldarius.

Spores of the thermophilic, acidophilic, Bacillus acidocaldarius were covered by a thick outer coat and a laminated inner coat (5.5 nm periodicity). Small membranous vesicles were present in the spore core and they disappeared as germination proceeded. After depolymerization of the cortex, and a 30% increase in spore diameter a localized gap appeared in the laminated inner coat only. This inner coat gap was narrow and could be the whole length of the spore. The germ cell appeared to grow, or to be pushed towards the inner coat gap, at which stage the outer coat disappeared in the same localized area. As the vegetative cell grew out the spore coat fell away, with loose cortical material still attached to it. The young germ cell developed a large spherical electron dense inclusion body in the cytoplasm, at the same time as the ribosomal and nuclear areas became distinct.