Evidence for the early reduction of the 24,25 double bond in the conversion of lanosterol to cholesterol in cerebrotendinous xanthomatosis

The metabolism of lanosterol and 24,25-dihydrolanosterol (DL) was examined in a patient with cerebrotendinous xanthomatosis after intravenous pulse labeling with a mixture of DL-2-¹⁴C and 3S,4S,3R, 4R-(4-³H)mevalonate. Sterols were isolated from the feces and purified by silver nitrate thin-layer chromatography, and their identities were confirmed by gasliquid chromatography and mass spectrometry. Their specific activities were then determined and plotted as a function of time. These isotope ratio measurements and specific activity decay curves were consistent with 24,25-dihydrolanosterol and Δ⁷-cholestenol being intermediates in the synthesis of cholesterol from mevalonate and lanosterol, and they suggested that reduction of the lanosterol side chain may occur as an early step in the synthesis of cholesterol. These results are in contrast to the results reported after the administration of triparanol, a Δ²⁴-reductase inhibitor.     

Precordial voltage variation in the normal electrocardiagram

Intra-individual precordial voltage variation was examined in serial 12 lead electrocardiograms (ECGs) performed at 10 minute and 24 hour intervals in sixteen young, healthy males forming two age matched groups. Significant variation was found in repeat ECGs at both periods. When precordial electrodes remained in situ between serial 10 minute recordings variation was reduced by approximately 60%We conclude that significant precordial voltage variation is present in serial electrocardiography, even when performed over the short term. Alteration in precordial electrode placement accounts for the major proportion of variation and this may be sufficiently large to interfere with the accurate interpretation of serial precordial voltage changes in an individual subject.     

Evaluation of the hypothalamic-pituitary-gonadal function in the Bardet-Biedl syndrome

The hypothalamic-pituitary-gonadal system was evaluated in three siblings with the Bardet-Biedl syndrome. All patients had mental retardation, pigmentary retinopathy, obesity, polydactyly, and hypogonadism. Serum levels of luteinizing hormone (LH) were above the upper limit of normality in the elder brothers (101.6 and 62.6 ng/ml, respectively) but were within normal limits in the younger patient. Serum follicle-stimulating hormone (FSH) was within the normal range for all three patients. After 100 μg of intravenous gonadotropin-releasing hormone (LH-RH), the LH and FSH serum levels showed a response that correlated well with the respective pubertal stages of the patients. Chronic stimulation with synthetic LH-RH (500 μg for 3 days) was also followed by a marked rise in both LH and FSH. Clomiphene administration induced a marked rise in serum LH, while FSH values did not show a clear elevation. Although plasma testosterone was found to be normal for each individual patient, repeated stimulation with human chorionic gonadotrophin failed to further increase plasma testosterone in the two elder brothers. Basal levels of serum prolactin and growth hormone were within the normal range and stimulatory and supressive tests for these pituitary hormones were also normal in these patients. An oral glucose tolerance test revealed high basal levels and an exaggerated rise in plasma insulin values. Testicular biopsy performed in the three patients showed a nonuniform degenerative lesion of the seminiferous tubules with marked reduction of spermatogenic activity. Only scant groups of Leydig cells were seen in the interstitium with a clear decrease of the total number of these cells. These findings indicated a trend to an evolutive gonadal disorder possibly beginning near the onset of puberty and progressing throughout the adult life.     

A developmental study of progesterone, corticosterone, cortisol, and cortisone in the adrenal glands of the embryonic chick.

Pairs of adrenal glands were removed from embryonic chicks at 2-day intervals between 9 and 21 days of incubation. Four corticosteroids (progesterone, corticosterone, cortisol, and cortisone) were separated by column chromatography and their concentrations were determined using the competitive protein-binding assay of Murphy [(1967) J. Clin. Endocrinol. Metab.27, 973–990]. Further identification of cortisol in embryonic chicks was carried out using thin layer and paper chromatography followed by the double isotope assay. Total corticosteroid/pair adrenal glands rose from 9 ng at 9 days to a peak of 38 ng at 15 days. The concentration declined to 21 ng at 19 days and then rose again at hatching.Over the 12-day period studied corticosterone accounted for one third of the total adrenal corticosteroids measured. At hatching corticosterone and its precursor, progesterone accounted for 71% of the total, indicating establishment of the adult pattern of predominance of corticosterone.This report, along with our previous paper [(1974) Gen. Comp. Endocrinol.24, 364–372], provides base line normal gland and circulating steroid levels. It emphasizes that several corticosteroids are being synthesized and secreted during embryonic development.     

Pressure-flow studies in man: the nature of the aortic flow pattern in both valvular mitral insufficiency and the prolapsing mitral valve syndrome

In five normal patients and in six patients with various forms of mitral insufficiency, ascending aortic pressure-flow relationships were studied using the pressure gradient technique. Stroke volume, peak flow, mean aortic pressure, and the per cent of aortic flow during the first half of ejection were calculated in the control state, following amyl nitrite inhalation, and following the intravenous injection of 0.4 mg. of phenylephrine. In normal patients, an average of 52 per cent of flow occurred in the first half of ejection both during control and following phenylephrine, and increased to 60 per cent after amyl nitrite. A patient with the prolapsing mitral valve syndrome but without mitral insufficiency had flow curves similar to the normal. Two patients with moderate and severe mitral insufficiency, respectively, and a prolapsing mitral valve had a marked increase in flow during the first half of ejection (68 and 66 per cent) during control; the per cent of flow decreased with amyl nitrite and phenylephrine administration. Patients with mitral insufficiency secondary to either rheumatic heart disease or papillary muscle dysfunction had 58 to 64 per cent of flow during the first half of ejection during control; this pattern did not change significantly with amyl nitrite or phenylephrine.     

Elasticity of the smallest noncapillary pulmonary blood vessels in the cat

We have previously described the compliance behavior of the pulmonary interalveolar capillary blood vessels in the cat and now characterize the compliance coefficient of the pulmonary arterioles and venules less than 50 μm in diameter in that species. These observations are unclassified with respect to arterioles and venules. Our method of silicone rubber microvascular casting under 0 to 23.75 cm H₂O pressures was used and diameter measurements were made from histological slides. Since the exact position of the vessels in branching hierarchy was not known, we called these vessels juxta-alveolar. The diameters of the smallest noncapillary blood vessels were measured and were analyzed by extreme-value statistics. We obtain a compliance coefficient, α, of 0.274 μm/cm H₂O over the pressure range measured, and a mean diameter of 14.5 μm for the smallest noncapillary blood vessels, 0Δp. These vessels are compliant.     

The effect of hormones on the haemodynamics in animals of different age groups

The investigation was undertaken to study to effect of varying doses of epinephrine, vasopressin, insulin, thyroxin, estradiol-dipropionate on the haemodynamics and contractility of the myocardium of rats in different age groups, as well as the effect of epinephrine and vasopressin on coronary blood circulation in dogs of various age groups. The age group peculiarities of reactions to the hormones were compared with changes in their content in the blood of animals of different age groups.Upon administering small concentrations of the hormones in this study, more pronounced changes in haemodynamics and contractility of the myocardium were observed in senile animals. The administration of larger doses led to more pronounced changes in mature animals. During the process of aging, there is a decrease in the range of the reactions of the cardiovascular system to the action of hormones.In case of long term (14 days) administration of thyroxin, it was found that in senile animals the contractility of the heart was lower than that in short term (4 days) administration. In long term administration of thyroxin, it was found that in mature animals the index for the myocardium's contracting ability was more pronounced than in short term administration.Irregular changes in the concentrations of different hormones in the blood, changes in sensitivity and ability of the myocardium to respond to their action lead to changes in the hormonal regulation of the heart, and to the development of aging metabolic and functional changes.     

Changing views on the mechanism of the first and second heart sounds

The mechanism of production of the first and second heart sounds is re-examined on the basis of known physical laws and physiologic experiments of the last decade.A general theory is propounded, which agrees with the observed facts and is in line with previous conclusions of both early and present physiologists.Three power sources are identified in the cardiovascular system; valve closures occur before each sound while value tensions play only a secondary role.The accelerations and decelerations of the cardiovascular structures and of the blood they contain is the cause of all cardiac vibrations, both inaudible and audible.This theory agrees with the conclusions of Luciani and of Wiggers, and confirms the concept propounded by Rushmer.     

Transvenous endomyocardial biopsy using the gastrointestinal biopsy (Olympus GFB) catheter

The use of a GFB biopsy catheter (Olympus) for endomyocardial biopsy in 23 patients is described. The catheter may be introduced alone or through a Cournand catheter. This technique is simple and safe and has a success rate of 100 per cent. There is little problem with cleaning out the blood. The technique of introducing the biopsy catheter through an already positioned Cournand catheter avoids any damage to the veins or perforation through the vein or right atrium; even in patients with large right atria, the procedure of first manipulating a soft rather than a stiff catheter into the right ventricle, and then introducing the biopsy through the Cournand catheter, becomes technically easy. The biopsy specimens measure 2 by 2.5 mm., which are adequate for microscopic examination and bacterial or viral culture studies. There have been no immediate or late complications.     

Renal studies in the hypothyroid rat

Whole kidney clearance studies were performed on 27 hypothyroid rats (H) and 25 euthyroid littermate rats (C). Absolute glomerular filtration rate (GFR) was less in hypothyroid rats (1.02 versus 1.39 ml/min), but when factored by body surface area (BSA) the two groups were comparable ($\text{GFR}\text{BSA}\text{= 2.26 versus 2.24 μl}\text{/min/sq/cm}$). Absolute and fractional (per GFR) sodium clearance was greater in the hypothyroid animals ($\text{C}{}_{\mathrm{Na}}\text{GFR:H}\text{= 0.36, C = 0.11, p < 0.001}$), but total electrolyte (Na⁺ + K⁺) excretion and clearance were comparable. End proximal tubular fluid (TF) micropuncture collections in 20 animals revealed no change in fractional reabsorption ($\text{TF}\text{P}$ inulin) in hypothyroid rats ($\text{TF}\text{P}$ insulin, 2.5 versus 2.7), but showed a decrease in single nephron GFR (Vo, 17 versus 36 nl/min) and absolute reabsorption (11 versus 20 nl/min). Hypothyroidism is associated with a decrease of sodium reabsorption at nephron sites distal to the convoluted proximal tubule. With ad libitum electrolyte and water intake most rats can maintain themselves in volume-sodium balance, but an occasional animal may display this distal leak syndrome in the extreme. One such rat had a urinary sodium concentration U_Na of 147 mEq/liter and a urinary flow rate of 56.0 μl/min (H = 3.33, C = 1.39). In addition, its hydropenic normal end proximal $\text{TF}\text{P}$ inulin mean of 2.7 confirmed the inability of the proximal nephron to compensate for this late leak. This rat's plasma sodium was 128 mEq/liter (H = 147, C = 148), dilutional hyponatremia. These renal problems are similar to those reported in man and suggest that the rat is an appropriate model for the study of human hypothyroidism.     

Chromatin condensation in the aging housefly

Computer analysis of digitized images of Feulgen-stained optic lobe and Malpighian tubule nuclei from the adult male housefly has shown significant age-related changes in several image features. These features relate to the amount and spatial distribution of a high and medium density chromatin component (HDC, MDC). Total DNA content in both the brain and tubule nuclei did not change with age.The amount of HDC nearly doubles by day 3 (post-eclosion) in the brain, while the amount in the tubules increases nearly four-fold by day 8. This condensation event is accompanied by a seven-to-eight-fold increase in the symmetry of the HDC distribution pattern. The number of MDC clusters in the tubule shows a five-fold decrease, while the number of MDC clusters in the brain remains unchanged.The condensation pattern in the brain nuclei changed more rapidly than it did in the tubule nuclei. The changes in the brain nuclei were found to occur between day 1 and day 4, while the tubule nuclei showed significant changes between day 1 and day 8. The significance of this difference is discussed with respect to Hypothalamic theories on the aging process in animals.     

Percutaneous myocardial and pericardial biopsy with the Menghini needle

A simple, safe method of obtaining myocardial or pericardial tissue for analysis by light or electron microscopy or for culture has obvious application. The Menghini needle has been demonstrated to be a safe and effective instrument for the aspiration biopsy of liver and kidney. Therefore, application of aspiration biopsy with a 17 gauge Menghini needle to the heart by means of the left ventricular apical percutaneous approach has been evaluated in humans in 27 myocardial and 8 pericardial biopsies. Adequate tissue was obtained in all except one pericardial and two myocardial biopsy attempts. Of the eight pericardial biopsies, the diagnosis of tuberculous pericarditis was made in two cases and carcinomatous invasion of the pericardium was made in another two cases. Three cases showed nonspecific pericarditis. Of the 27 myocardial biopsies, 6 were examined by light microscopy and 21 were examined by electron microscopy. Light microscopy revealed no specific findings. However, electron microscopy showed moderate to severe intracellular abnormalities, the significance of which remains to be determined. Biopsy procedure takes 5 minutes or less under local anesthesia following mild premedication. Pneumothorax occurred in two patients and transient mild pleuritic chest pain occurred in four patients. Both complications were well tolerated. The technique seems effective and safe. Its utility and application remain to be determined.     

Circadian variations in the monoamine levels and monoamine oxidase activity in different regions of the rat brain as a function of age

Time-related changes in the levels of norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT) and monoamine oxidase (EC 1.4.3.4, MAO) activity have been studied in the cerebral cortex, cerebellum, medulla oblongata, hypothalamus, striatum and midbrain of 21 day, 3, 6, 12 and 24 month old rats maintained at 12 hours of light and 12 hours of dark condition. Maximum NE level was seen during the dark phase in all the regions of 3, 6, 12 and 24 month old rats, whereas in 21 day old, the maximum NE level occurred during the light phase. In the cerebral cortex and in the cerebellum of 21 day old rat DA was absent at all times. In all the other age groups, the maximum DA level was seen during the dark phase, while for 5-HT higher level was during the light phase in all the age groups. MAO activity of 3, 6, 12 and 24 month old rats showed the peak activity at the beginning of the light phase (06:00 hours), whereas cerebral cortex, cerebellum and medulla oblongata of 21 day old rat had its peak MAO activity at 14:00 hours and at 22:00 hours in other regions.     

Intravenous leiomyomatosis of the uterus with extension into the heart

A 42 year old woman presented with impaired filling of the right atrium and right ventricle two years after removal of uterine leiomyomas. At the time of hysterectomy, intravenous leiomyomatosis was noted, with extension of the tumor into the inferior vena cava. The tumor subsequently extended into the right atrium and coronary sinus, and protruded through the tricuspid orifice. It was successfully removed from the heart, and proved to be histologically benign.     

Myocardial infarction and rupture of the heart: a macroscopic pathologic study

From an anatomical point of view, the various elements which seem to individualize myocardial infarctions complicated by rupture are: a limited increase in the volume of the heart; a propensity for the rupture to follow the first infarction of a previously healthy cardiac muscle; a myocardial necrosis of sometimes small extension with clear limits and a destruction of the muscle so severe as to amount in two thirds of the cases to a variable parietal dissection; a lesser extension and diffusion of coronary stenosis; an ever-present and totally occlusive coronary thrombosis; an insignificant or absent substitutive circulation. Those strictly anatomical facts can be reason to extend the indications of a very early direct myocardial revascularization (almost a third of all cardiac ruptures occur within 24 hours) or to contemplate an infarctectomy after the eighth hour (the necroses are usually of a moderate size and well deliminated) if it appears possible to draw the "clinical profile" of those patients prone to cardiac rupture or to read the signs that may announce the likelihood of this dreadful complication.     

Congenital atresia of the left coronary ostium and hypoplasia of the left main coronary artery

The clinical and pathological findings are described in a six-month-old female with an unusual congenital malformation, atresia of the orifice and hypoplasia of the left main coronary artery. The literature is reviewed and the clinical findings are discussed. A comparison has been made with the anatomic findings in true single coronary artery and with the angiographic findings in anomalous origin of the left coronary artery from the main pulmonary artery.     

In vivo DNA synthesis in the dietary restricted long-lived rat

Male CFY Sprague-Dawley rats maintained at 50% growth rate of ad libitum fed, age-matched control animals showed a 42% extension in maximum lifespan and an increase in the overall doubling time of the rate of mortality from 102 days to 203 days. The slower growth rate of animals on the restricted diet was reflected in lower DNA, RNA, and protein content of liver, kidney and heart with age. DNA synthesis in vivo measured by the incorporation of 3H-thymidine was severely inhibited in liver, kidney, heart, and abdominal skin, particularly during the first six months of life. The developmental peak in DNA synthesis observed in liver and kidney of ad libitum fed animals before 100 days of age was completely inhibited. No effect of restricted feeding on DNA synthesis in the small intestine was observed; however, DNA synthesis was higher in thymic tissue from the experimental animals. A decrease in RNA content of liver, kidney, and heart preceded any change in protein or DNA in animals subjected to restricted feeding. The capacity for protein synthesis (RNA/DNA ratio) was decreased by restricted feeding and was associated with a reduced protein/DNA ratio indicative of reduced cell size during the first six months of life. The translational activity per ribosome (protein/RNA ratio) was not disturbed by undernutrition in any of the tissues studied.