Comparison of the prognosis of hypertension associated with chronic glomerulonephritis with that of essential hypertension.

The difference of the prognosis between essential and renal hypertension (chronic glomerulonephritis) was examined by compairing the survival rate of the patients, and the effect of lability of blood pressure and the effect of the response to hypotensive drugs on the prognosis of the two types of hypertension was observed. The prognosis of renal hypertensives was remarkedly worse when it was compaired with the prognosis of essential hypertensives. More then 80% of the latter was still alive after ten years, while the mortality rate of the former after 5 years was only 20%. Each factor of severity (diastolic pressure, optic fundi, cardiac, cerebrovascular and renal complication) in non severe patients (group O-II) did not differently affect the survival rate of both hypertensives. Diverse prognosis was observed in severe patients (group III-IV), depending on each factor of severity. In renal hypertension the survival rate was extremely low when the patients had high diastolic pressure, severe cardiac and cerebrovascular complication. It was not so low in the patients with severe ophthalmoscopic change. The prognosis of essential hypertension was poor in the order of severe cerebrovascular complication, renal complication and cardiac complication. The survival rate of the patients with high diastolic pressure or severe ophthalmoscopic change was considerably high. The patients with both renal and essential hypertension showed greater survival rate when the blood pressure was much more reduced by bed rest or antihypertensive drugs during the first hospitalization.


Prognosis of chronic glomerulonephritis with special reference to hypertension and renal function.

Incidence of hypertension in chronic glomerulonephritis and its influence on the clinical course of the disease were studied using statistic technique, especially that of Markovian process. 1. Incidence of hypertension in a total of 283 cases was 15.2%, while in the patients of which renal function reduced to approximately one half of the normal was about 50%. 2. The average of blood pressure in this disease tends to elevate with the decrease in 15 minute value of PSP excretion test and with the increasing serum creatinine level, although the variations are large. 3. After a fall of renal function to approximately one-third of the normal, the rate of clinical course is markedly rapid. 4. The prognosis of the progressive type of chronic glomerulonephritis is obviously affected to be shorten by the presence of hypertension. 5. According to the results obtained by the Markovian approach, survival years of the patients with wide range of renal function can be predicted with relative accuracy.


Diagnostic value of plasma renin activity and plasma angiotensin II in renovascular hypertension.

The plasma renin activity in both peripheral venous blood and the renal vein of the involved kidney showed high values. Angiotensin infusion elevated the urine volume and angiotensin excretion on the intact side, and the difference in urine volume and angiotensin excretion between the two sides was accentuated after angiotensin infusion. These findings are useful for the diagnosis of the stenotic side in renovascular hypertension. No difference in the prognosis of extirpation of the involved kidney and of vascular reconstruction of the stenotic artery was found for the treatment of renovascular hypertension. However, autotransplantation of the involved kidney was found to be more useful, since it allowed improvement of renal circulation, suppression of thrombosis formation, and the maintenance of kidney tissue.


Comparison of absorption and excretion of cefazolin with cephalothin and cephapirin.

Since the discovery of cephalothin in 1962, many semi-synthetic cephalosporins have appeared. To choose the most suitable drug for the clinical treatment of infections, the characteristics of these antibiotics must be sufficiently understood. When cephalosporins which are or will be commercially available are divided into two categories, one consists of cephaloridine, cefazolin and cephalexin which are comparatively stable in the living body; and the other cephalothin, cephaloglycin, cephapirin and cephacetrile which are metabolized into desacetyl compounds with low antibacterial activity. In this study, the author compared the absorption, excretion and some other properties of cefazolin and cephalothin, (widely used clinically), and cephapirin (still under study in Japan).


[Absorption, distribution and excretion of 14C-josamycin and 14C-josamycin propionate in rats (author's transl)].

Abosrption, distribution and excretion of 14C-josamycin (JM) and 14C-josamycin propionate (JM-P) were studied in rats by measuring both antibacterial activity and radioactivity. 1. In antibacterial activity, plasma and tissue concentrations of JM-P showed a similar tendency to those of JM. Those concentrations of JM reached a peak at 1 hour after administration with a subsequent rapid decrease, while the peak level of JM-P appeared 2 approximately 4 hours after administration and then fell down very slowly. 2. In radioactivity, oral administration of JM-P rapidly produced a very high plasma and tissue concentrations which were in lung, liver, kidney and spleen more than twice those of JM. These results showed that when given orally, JM-P is well absorbed with distributions at high concentrations especially in lung, liver, and kidney and spleen. 3. The ratios of bioactivity/radioactivity in JM administration were the highest in lung and the lowest in liver at 1 hour after. But those of JM-P were generally much lower than those of JM because of higher distribution of JM-P radioactivity into tissues. 4. Four days after oral administration of JM and JM-P, 23.1% and 21.8% of the given radioactivity were recovered respectively from urine. However, the antibacterial activities recovered were 0.40% for JM and 0.65% for JM-P. 5. Biliary recoveries of JM and JM-P were 17.2% and 12.1% of administered radioactivity 2 days after oral administration. On the other hand, 0.47% of JM and 0.17% of JM-P were excreted into bile as antibacterial activity. These results showed that JM and JM-P were excreted into rat urine and bile as some metabolites with less biological activity. 6. The amounts of JM and JM-P recovered from feces were 75.7% and 60.2%, respectively, of the orally given radioactivity. The amount of radioactivity recovered from expiration air was about 1% of either orally given JM or JM-P.


Serum levels and urinary excretion of parent antibiotics and desacetyl forms after parenteral administration of cephalothin and cephapirin.

When the antibacterial substances of cephalothin and cephapirin in the serum and urine after intramuscular injection were separated and assayed, desacetyl metabolities of both drugs were detected. These tendencies were especially apparent in the tissue concentrations. When both the drugs were given intravenously to healthy volunteers, the amounts of their desacetyl metabolites were not greater in man than in rats.


Left ventricular asynergy in mitral valve diseases. A cineangiographic study.

Mode of left ventricular contraction was studied by cine left ventriculography in 22 cases with mitral valve diseases and 7 control cases. In rheumatic mitral valve diseases, local hypokinesis of the left ventricular wall and poor contraction of the mitral annulus were observed frequently, at various location and to various extent. Transient asynergic motion of local wall was also seen either during systole or during diastole. Local hypokinesis was seen even in normal-sized left ventricles, and was associated with decreased cardiac pump performance, when its localization was extensive. Severe mitral regurgitation of rheumatic nature was always associated with poor contraction of the mitral annulus, although the reverse was not true.


Clinical manifestations of papillary muscle dysfunction in Ehlers Danlos Syndrome.

A total of 14 cases of papillary muscle dysfunction have been observed in Ehlers Danlos syndrome. Five patients had clinically identifiable syndrome of prolapsing mitral leaflets. This form of rare interesting cardiovascular abnormality in Ehlers Danlos syndrome is discussed. The relevant literature is reviewed.


A nonlinear regression model as applied to the comparison of axis-angles of electrocardiographic systems.

The systematic nonlinearity exhibited in a comparison of 2 commonly used electrocardiographic lead-systems, when the net QRS axis-angle from one system is plotted against the other, is quantitatively analyzed. A family of nonlinear correlation curves is implemented using the ratio of 2 correction factors, fc/fo, as a parameter. Such curves, replacing linear regression lines, provide a more realistic representation of the actual problem of this type. Between the Frank and the 12-lead systems, the value of fc/fo is found to be 0.53 for the frontal plane from a sample of 1,000 subjects. The combination of correction factors, fc=1.155 and fo=2.18, is a possibility among countless others to make up the same fc/fo of 0.53. Appreciable improvement in axis correlation is demonstrated after the data are corrected by such factors.


Effect of increasing age on hemodynamics of spontaneously hypertensive rats.

Arterial pressure, cardiac output, and total peripheral resistance were compared between spontaneously hypertensive rats (SHR) and normotensive control rats (NCR) at 4, 7, and 12 months of age. The rats were anesthetized with pentobarbital sodium, thoracotomized and kept under positive pressure respiration. Cardiac output was measured with an electromagnetic flowmeter probe placed at the ascending aorta. On all the age groups, arterial pressure and total peripheral resistance were significantly higher in SHR than in NCR, while cardiac output per body weight was not different. However, the significant differences in pressure and resistance at each age disappeared after ganglion blockade with hexamethonium bromide. Total peripheral resistance was not higher in SHR than in NCR even after cardiac output, which had once been diminished by blockade, was restored to the pre-blockade level by dextran infusion. Phenoxybenzamine, an alpha adrenergic receptor blocker, also equalized arterial pressure and total peripheral resistance between SHR and NCR, both aged about 10 months, without decrease in cardiac output. It is concluded that, in both young and old SHR's, the hypertensive state is maintained by an increase in total peripheral resistance ascribable to sympathetic activity.


Sustained decreased in coronary blood flow and excitation of cardiac sensory fibers following sympathetic stimulation.

The effect of electrical stimulation of the efferent cardiac sympathetic nerves on activity of afferent cardiac fibers in the sympathetic nerves and coronary hemodynamics of anesthetized dogs has been examined. During partial constriction of the coronary artery, a brief stimulation of the efferent cardiac sympathetic nerves resulted in sustained excitation of the afferent fibers and a sustained decrease in blood flow of the constricted artery which were associated with systolic bulge of the left ventricle and elevation of the ST segment of electrocardiogram. These changes were not produced without constriction. Pretreatment with phentolamine suppressed excitation of the afferent fibers, development of systolic bulge and elevation of the ST segment. Also, the decrease in coronary blood flow induced by stimulation was replaced by an increase after the administration of the agent. Propranolol suppressed excitation of the fibers, systolic bulge and elevation of the ST segment, but could not eliminate the decrease in blood flow. The results indicate that sympathetic stimulation caused a decrease in coronary blood flow through excitation of the alpha-adrenergic receptors while increasing cardiac work load and energy requirements through excitation of the beta-adrenergic receptors, leading to more severe myocardial ischemia and excitation of the afferent fibers.


Cardiovascular effects of dopamine after experimental coronary occlusion in the dog.

Hemodynamic effects of dopamine were studied on 30 open-chest dogs with experimental myocardial infarction. These dogs were divided into 3 groups. Three different doses of intravenous dopamine, 5, 10, and 20 mug/Kg/min, were administered for 30 min. Heart rate and myocardial contractility were increased dose-dependently. Total peripheral vascular resistance was reduced with 5 or 10 mug/Kg/min of dopamine. With 20 mug/Kg/min of dopamine, it became the lowest 5 min after the initiation of infusion but increased above the control value 20 min after the start of administration. Renal vascular resistance was decreased with 5 mug/Kg/min of dopamine but increased with 20 mug/Kg/min. These results suggested that this drug would be useful for treatment of shock state.


Case report. Two cases of pulmonary hypertension with Raynaud's phenomenon. Primary pulmonary hypertension and systemic lupus erythematosus.

Two cases of hypertensive pulmonary vascular disease with Raynaud's phenomenon are reported. One is a 32-year-old housewife of primary pulmonary hypertension with some immunological disorders and the other is a 28-year-old female of systemic lupus erythematosus. It may be considered that some immunological process could play a role in the etiology of some cases of primary pulmonary hypertension and the relationship of pathogenesis between these 2 cases was discussed.


Changes of cardiac performance in renal failure.

Clinical and experimental studies were carried out in order to evaluate the role of myocardial dysfunction in the genesis of circulatory congestion associated with renal failure. Among the patients with chronic renal failure, those with circulatory congestion had greater blood volume and higher venous pressure while lower cardiac index and stroke work index than those without circulatory congestion. After peritoneal dialysis, although blood volume and venous pressure decreased in both groups, cardiac index increased in the former while it decreased in the latter group. In 15 dogs, acute renal failure was produced by ligating both ureters. As uremia developed, blood volume and left ventricular end-diastolic pressure increased with or without an increase in cardiac index. The depression of ventricular function curve was evident in all the dogs. The peritoneal dialysis performed at this stage resulted in a prompt recovery of left ventricular end-diastolic pressure with minimum change in cardiac index. The measurement of dp/dt/IIT also indicated a depression of myocardial contractility at uremic stage and its recovery after dialysis. We conclude that impairment of myocardial function is implicated in the development of circulatory congestion in renal failure.


Excitation of afferent cardiac sympathetic nerve fibers induced by vagal stimulation.

The effect of vagal stimulation on activity of afferent sympathetic nerve fibers from the dog's left ventricle has been examined. During partial constriction of the coronary artery, a brief electrical stimulation of the cervical vagus nerves resulted in a decrease in blood flow of the constricted artery, systolic bulge of the left ventricle, elevation of the ST segment of electrocardiogram and excitation of the afferent nerve fibers, which continued for up to 15 min. These changes were not produced without coronary artery constriction. Intravenous injection of phentolamine eliminated the decrease in blood flow, and suppressed systolic bulge, elevation of the ST segment and excitation of afferent fibers. Propranolol could not eliminate the decrease in blood flow while suppressed the other changes. Atropine eliminated all of these changes. The results indicate participation of adrenergic alpha-receptors in sustained decrease of coronary blood flow and excitation of afferent cardiac sympathetic nerve fibers which can be produced by a brief vagal excitation.


Experimental evaluation of some controversial points regarding the A-V conduction disturbances in the clinical His bundle electrogram.

Although the recordings of the His potential have been shown to be very useful in the study of cardiac conduction and rhythm disturbances, there remain some problems regarding the clinical His bundle electrogram. Some of the studies were performed to solve in the perfused dog hearts and in situ dog hearts, and consequently the following results were obtained. In some experiments, recording of the His potential could not be achieved even in the perfused hearts in spite of the preserved A-V conduction, suggesting that, as experienced sometimes in the clinical cases, inability to record the His potential might not be due to the technical failure or the anatomical abnormalities of the His bundle. On the other hand, real "splitting of H" occurred in association with the increase in the duration and decrease in the amplitude of the His potential after the ligation of the anterior septal artery. In addition, the true Mobitz II type A-H block, and Wenckebach type intra-Hisian and H-V block could be produced experimentally.


Slowered turnover of norepinephrine in the brain associated with an acute elevation in blood pressure of rats.

Acute responses of blood pressure and turnover of norepinephrine in the brain to intracisternally injected guanethidine were studied in rats. Systolic blood pressure in guanethidine-treated rats showed a dose-relating rise for over 9 hrs, while norepinephrine contents in cortex-cerebellum, brain stem and heart were not affected. The endogenous norepinephrine in brain samples, however, did not decrease against alpha-methyl-p-tyrosine to result in regression coefficients significantly different from those in the saline-treated group whereas norepinephrine in heart was reduced similarly in the 2 groups, indicating a slowered turnover of norepinephrine selectively in the brain. The results may indicate that the retarded norepinephrine turnover in the brain is causatively related with an acute elevation in blood pressure.


Maximal rate of the left ventricular pressure fall (peak negative dP/dt) in early stage of myocardial ischemia following experimental coronary occlusion.

Short-term, repeated myocardial ischemia was produced in 20 opened-chest anesthetized dogs by left anterior descending (LAD) branch occlusion. Left ventricular pressure (LVP) and its dP/dt were recorded by Satham SF-1 transducer, and isometric local force (F) was measured by a Walton-Brodie strain gauge arch sewn onto LV free wall. In all experiments, within a few beats after LAD occlusion, peak negative dP/dt started to diminish its amplitude, reaching a nadir after 20-30 sec (63 +/- 5% of control, 9 dogs). It recovered to 83 +/- 3% of control level in 45 sec and remained essentially unchanged thereafter. This change preceded those of LVP and max dP/dt, which showed only minor falls. In 6 dogs, changes by occluding root of LAD were compared with those by its branch occlusion. The greater the extent of ischemia, the more marked and prolonged were the changes. While F in the ischemic center (Fc) rapidly lost its contractile activity following LAD occlusion, F in marginal zone between infarcted and non-infarcted region (Fm) showed variable extent and different time-course of its diminution. Thus, it was concluded that the change in peak negative dP/dt following LAD occlusion was one of the sensitive signs of early ischemic changes, and was attributed at least in part to characteristic changes in contractile activity of myocardium surrounding the ischemic injury.


Calcified left ventricular aneurysm and non-atherosclerotic myocardial infarction in a child.

A 14-year-old boy, admitted with intractable chest pain, was found to have an enlarged heart and calcification in the apical region, with electrocardiographic features of massive inferolateral myocardial infarction. Left ventricular angiography revealed a large left ventricular aneurysm. He died following resection of the aneurysm and post mortem examination showed changes of a non-specific chronic myocarditis. A vasculitis involving small coronary arterioles was also found in the vicinity of the aneurysm, and the possibility of a rheumatic vasculitis was suggested by a transient episode of an erythema marginatum-like eruption. It is concluded that the association of infarction pattern on the electrocardiogram together with calcification of the heart in children is highly suggestive of a ventricular aneurysm secondary to a myocarditis or a vasculitis involving small, intramyocardial branches of the coronary arteries.


QT prolongation and syncopal attacks. A case of the Romano-Ward syndrome.

The Romano-Ward syndrome is very rare as hereditary disease. Only 5 families have been reported in Japan before the present report. The patient, a 15-year-old female, had been treated for epilepsy due to syncopal attacks. Electrocardiography revealed occurrence of an augmented and labile U wave and prolongation of the Q-T interval, with recordings of frequent multifocal extrasystoles and transient ventricular fibrillation. Also noticed was sinus bradycardia. Clinical examinations presented no results coinciding with those specific ECG findings. It was inferred through surveys of her family tree that the present case had an autosomal dominant trait, heterozygously affected through the male line. Severe arrhythmias detected on her ECGs were suppressed by oral administration of 30 mg/day propranolol. Judging from the fact, propranolol may be the first to be administered among a variety of anti-arrhythmic agents in the Romano-Ward syndrome.


Wenckebach periods associated with high grade second degree (2 : 1 and 3 : 1) A-V block.

An electrocardiogram (ECG) of bilateral bundle branch block (BBBB) which may be attributable to a mixture of 2 : 1 and 3 : 1 atrioventricular (A-V) block is described. The irregularity of QRS complexes with left bundle branch block (LBBB) pattern during 2 : 1 A-V block may be ascribable to "Wenckebach periods", which might be due either to A-V nodal or His bundle or bundle branch delay. However, it was impossible to distinguish between them precisely because appropriate His bundle studies were not performed during the active arrhythmic phase. Although the exact mechanism involved were not established with certainty, different rates of recovery in conduction in the bundle branches in association with a marked prolongation of the refractoriness would seem to be the unique feature of this complex arrhythmia. An ECG tracing of BBBB indicating high grade second degree (2 : 1 and 3 : 1) A-V block, in which "spontaneous" occurrence of "Wenckebach periods" with 2 consecutive blocked P waves can be observed during 2 : 1 A-V block, has never been reported previously as far as can be ascertained from published records.


Studies on the potency test of antiserum for Weils disease by the intracutaneous method.

A method for estimating the leptospiricidal activity of therapeutic antiserum for Weil's disease was improved by using the intracutaneous method in guinea pigs. The neutralization curves between the leptospiral suspensions for challenge and the antisera were shown to be linear over a wide range of the dosis of the pathogen. Although the reproducibility of the neutralization experiments was high, a significant divergence was observed among the slopes in various test samples. However, the trouble due to such a discrepancy in the slope may practically be reduced if such an antiserum preparation that has a regression coefficient close to the mean of those of various neutralization lines constructed by many different products is adopted as the reference. A practical method for the potency test was suggested.


Toxicities of influenza vaccine: peripheral leukocytic response to live and inactivated influenza viruses in mice.

Intraperitoneal or intravenous inoculation of live or inactivated influenza virus induced two characteristic responses of the peripheral leukocytes in mice, an early appearing leukopenic response and late appearing  lymphopenia. The former response usually developed and subsided within several hours, though the change in leukocyte population was fairly complicated depending upon the activity of the inoculated material, while the latter began several hours after inoculation and reached its minimum level in 10 to 20 hr. The agent responsible for the former may be virus pyrogen, while the latter seems to be caused by some substance(s) other than that. The early appearing leukopenic response was similar to that due to bacterial endotoxin in respect to the characteristic pattern of the change in peripheral leukocyte population, though it was relatively easy to distinguish one from the other by the length of the latent period and by the heat stability of the causative agent. Live or inactivated influenza virus causing the early appearing leukopenic response was found also to have the mouse body weight-decreasing toxicity. The significance of these findings in the laboratory control test of influenza vaccine for untoward reactions often observed in human inoculated with some inactivated influenza vaccines was discussed. The possible roles of the two agents, virus pyrogen and endotoxin, in the febrile response were mentioned.


Virucidal effect of sodium p-chloromercuribenzoate on influenza viruses attributable to inhibition of virus particle-associated RNA-dependent RNA polymerase.

Sodium p-chloromercuribenzoate (PCMB) caused a noticeable reduction of infectivity of prototype strains of type A and Lee strain of type B influenza viruses at concentrations of 100 and 200 mug/ml, respectively, after an incubation at 37 C for 60 min. The virucidal effect on A/AA/2/60 (H2N2) strain was dependent on the concentration of the drug and temperature as well as on the time of incubation. The reagent exerted this effect at a concentration which induced little change in the hemagglutinating and neuraminidase activities of the virus. PCMB inhibited by 50% the virus particle-associated RNA polymerase activity of all prototype strains of type A influenza virus at about 2 mug/ml and that of Lee strain of type B influenza virus at 8.5 mug/ml. Other sulfhydryl reagent such as phenylmercuric nitrate also exhibited virucidal effect on A/AA/2/60 virus which paralleled their inhibition of the virus particle-associated RNA polymerase activity. From these results it was considered likely that the virucidal action of PCMB on influenza viruses was attributable to inhibition of the virus particle-associated RNA polymerase activity.


An electron microscopic study of antagonism between cephalexin and erythromycin in Staphylococcus aureus.

This study concerns investigations at the cellular level of antagonism between cephalexin (CEX) and erythromycin (EM) with the aid of electron microscopes and a liquid scintillation counter. Exposure of Staphylococcus aureus 209-P to CEX and EM in combination was found to result in a marked antagonism between the two antibiotics in their effects on the growth of the organism. Observations under a scanning electron microscope revealed lysed cells in the presence of CEX alone but almost no lysis in the presence of a combination of CEX and EM. Observations under a transmission electron microscope, on the other hand, disclosed that nearly all of the cells exposed to 20 mug/ml of CEX were transformed into protoplasts with their morphological changes being most marked after 4 hr of exposure. When 1 mug/ml of EM was allowed to act alone, this exposure resulted in thickening of the cell walls. The combined use of CEX and EM, however, resulted in neither thickening of the cell walls as in the presence of EM alone nor in the formation of protoplasts as in the presence of CEX alone but merely produced the swelling of separating walls. Cellular uptake of 14C-L-lysine and N-acetylglucosamine-1-14C into the cell wall fraction and the protein fraction was affected by CEX and EM, respectively, when used alone or in combination.


Effects of chemotherapeutics on bacterial ecology in the water of ponds and the intestinal tracts of cultured fish, ayu (Plecoglossus altivelis).

Drug-resistant gram-negative bacilli conferred with R factors were isolated with high frequencies from the intestinal tracts of ayu (Plecoglossus altivelis) cultured in ponds, in which chemotherapeutics had often been used, and with relatively low frequencies from ayu which received no administration of chemotherapeutics. Drug-resistant bacteria were also isolated at low frequencies from the intestinal tracts of wild ayu in rivers, as well as from the water of ayu-culturing ponds and some of them carried R factors. The drug-resistant bacteria carrying R factors were Aeromonas liquefaciens, Citrobacter, Enterobacter cloacae, Escherichia coli, Hafnia and unidentified strains. All the R factors were classified as the Fi-(F) type, except the two R factors detected in an E. coli strain and in an unidentified strain.


Oral cholecystography: osmotic activity of iopanoic glucuronide in bile.

The cholecystographic agent iopanoic acid (Telepaque) is excreted in high concentrations in the bile as the glucuronide, but produces little or no choleresis. In order to determine the osmotic characteristics of the excretory product, bile was collected from treated and untreated anesthetized dogs and the major solute concentrations and biliary osmolality were determined. After iopanoic acid, there was no change in biliary osmolality or in chloride or bicarbonate concentration. However, the calculated osmolality exceeded the measured osmolality to a significant degree. The data suggest that iopanoic glucuronide, like bile salts, is osmotically inactive because of micelle formation. From physiological considerations, low osmotic activity of the excreted contrast agent might enhance radiographic quality.


Uses of the electrical skin resistance method in the study of patients with neck and upper extremity pain.

Use of the electrical skin resistance method for the study of neck and upper extremity pain is reported. Skin resistance was mapped for 20 patients who had neck or upper extremity pain without clinical or radiographic evidence of spinal cord or nerve root irritation, but who did present evidence of an abnormality within a cervical intervertebral disc or involving a facet joint of the cervical spine. In general, areas of low skin resistance (sympathetic hyperactivity) corresponded well to areas of subjective pain. The skin resistance pattern has not led to localization of the level of abnormality within the cervical spine, but has been of value in confirming the clinical impression that a pain-producing mechanical or degenerative lesion is present. The test thus adds objective evidence in an area often fraught with subjectivity.


A 62-year-old black female with Kaposi's sarcoma associated with multiple myeloma is reported. The co-existence of the two entities in the same patient appears more than coincidental. The case is the first woman and only the fifth described with Kaposi's sarcoma associated with multiple myeloma.


Influence of glomerular filtration rate on the rate of para-aminohippurate secretion by the rat kidney: micropuncture and clearance studies.

Net secretion rate of para-aminohippurate (PAH) in the proximal convolution of the rat kidney changes concomitantly with single nephron glomerular filtration rate (GFR) and intratubular flow rate.  Reabsorption of PAH in the proximal convolution is negligible.  The PAH concentration profile along the length of the proximal convolution does not change markedly with variations in GFR.  Net PAH secretion by single nephrons, measured at the end of proximal convolutions, is about one-half that measured at the beginning of distal convolutions and in final urine.  As in the entire kidney, at constant renal plasma flow and concentration of PAH, renal secretion rate of PAH also changes concomitantly with GFR.  It is concluded that PAH secretion along the loop of Henle (i.e., probably along the pars recta) is also related to single nephron GFR, as is PAH secretion in the proximal convolution.


Effect of sodium intake on single nephron glomerular filtration rate and sodium reabsorption in experimental uremia.

Sodium balance, clearance and micropuncture studies were performed on three groups of uremic rats in which renal mass was reduced experimentally by approximately 85%. All animals received a sodium-free synthetic diet to which a measured amount of NaCl was added. Sodium intake was 3 mEq/day in one group, 1 mEq/day in a second group and 0.13 mEq/day in the third. In the latter, the Na intake was reduced (from an initial level of 1 mEq/day) as renal mass was reduced in proportion to the estimated reduction in renal mass in an effort to obviate the requirement for an increased natriuresis/nephron. Clearance and micropuncture studies also were performed in a group of normal rats maintained on 1 mEq/day of Na. All three groups of uremic rats on the standard diet maintained external Na balance. Single nephron glomerular filtration rate (SNGFR) in superficial nephrons was increased in all three groups of uremic rats and seemed to be independent of the Na intake; fractional fluid reabsorption was decreased in the proximal tubules in all three groups of uremic rats. Furthermore, absolute proximal Na reabsorption was markedly increased; and calculated values for distal reabsorption were markedly increased in all groups of uremic rats. The data suggest that the increase in SNGFR and the decrease in tubular fluid to plasma (TF/P) inulin ratios in superficial proximal tubules correlate poorly with the dictates for an increase in sodium excretion rate per residual nephron. These data also have implications regarding the operation of the control system in the regulation of external Na balance in uremia.


Age-dependent characteristics of compensatory renal growth.

The age-dependent characteristics of compensatory renal growth were studied in neonatal, weanling and young adult rats. Compensatory growth was demonstrated to be greater in young, sexually immature animals than in adults following unilateral nephrectomy. In the four-week interval following surgery in 21-day-old weanling rats, renal mass increased 240% in control animals (group A) and 407% after unilateral nephrectomy (group B). In similarly prepared adult animals, renal weight increased 31 and 81% in the same groups, respectively. The remarkable response in compensatory growth achieved by the young animal was further demonstrated by a greater absolute increase in renal mass in the experimental kidney of young rats compared to adults. Further studies were performed to determine whether the mechanism of compensatory growth in young rats involved formation of new nephrons. The total glomerular count in the remaining kidney of rats after removal of one kidney at 5 (neonatal) and 21 (weanling) days of life did not differ from the value obtained in control neonatal, weanling or adult kidneys. These data indicate that compensatory renal hypertrophy is age-dependent and is greater in young animals. The mechanism for enhanced compensatory renal growth in young animals does not involve glomerular neogenesis since there was no evidence for formation of additional nephrons following nephrectomy either in weanling or neonatal animals.


Pathophysiology of a nephrotoxic model of acute renal failure.

Studies were performed in the dog to determine the mechanism of the renal functional impairment which follows the administration of the nephrotoxic agent, uranyl nitrate. In the first series of 28 experiments, total renal blood flow was determined with the radioactive microsphere method before and after uranyl nitrate administration, 10 mg/kg. Total blood flow fell from 199 to 121 ml/min 6 hr after administration of uranyl nitrate (P less than 0.001) but was unchanged 48 hr after administration of the drug. Yet the blood urea nitrogen concentration had increased from a control value of 13 to 120 mg/100 ml at 48 hr (P less than 0.001). Since renal blood flow was normal at 48 hr, micropuncture studies were performed to further evaluate the mechanism of the renal impairment. In the first group of nine studies using a 10 mg/kg dose of uranyl nitrate, nephron glomerular filtration rate (GFR) was reduced 37% while total kidney GFR averaged less than 1% of normal. A similar disparity between superficial and total GFR was noted after a 5 mg/kg dose even though urine flow was comparable to values found in normal hydropenic dogs. Proximal tubular transit time and intratubular pressure were normal. The recovery of 3H-inulin injected into the proximal tubule was 97% in normal dogs and 14% in uranyl nitrate dogs (P less than 0.001). Since there was no difference between early and late proximal tubular nephron GFR, it was suggested that the pars recta, the segment most severely involved histologically, was the main site of inulin leak. Scanning electron microscopy revealed an alteration in epithelial architecture which may have accounted, at least in part, for the diminution in nephron GFR. These studies are interpreted to indicate that the impairment in renal function in this model is due to both leakage of filtrate across damaged tubular epithelium and a modest decrease in nephron GFR.


Altered blood volume regulation in sustained essential hypertension: a hemodynamic study.

Cardiac and renal hemodynamics and total blood volume were determined in 28 normal subjects and 60 patients with untreated essential well-established hypertension. Endogenous creatinine clearance was within normal ranges and sodium intake was 110 mEq/day. A significant negative volume-resistance relationship was observed both in normal subjects (P less than 0.005) and hypertensive patients (P less than 0.001). In comparison with the normal curve, the hypertensive curve has two characteristics: 1) the curve was reset on the right-hand side and, 2) the slope was significantly shallower, indicating a reduced ability to decrease the volume per unit rise in resistance. By using the normal curve as a reference system, a quantitative evaluation of the blood volume disturbance was proposed. In hypertensives, the value of the total peripheral resistance could correspond to two different values of the total blood volume: the real value and the theoretical value extrapolated from the normal curve. The difference between the two values was called "relative variation in blood volume" and was used as a mathematical model. In hypertensives, the real blood volume was significantly reduced (P less than 0.001) while a significant "relative increase" in total blood volume was observed (P less than 0.001). This "relative increase" was directly correlated with the diastolic arterial pressure (r=0.064; P less than 0.00001) and was inversely related to the renal blood flow (r=-0.54; P less than 0.0001) and the creatinine clearance. Such correlations were not observed with the real blood volume. In agreement with Guyton's theory, this study highly suggests that sustained hypertension is related to an increase in blood volume relative to the capacity of the circulatory system and that a renal defect is necessary for the blood pressure elevation mechanism.


Effects of extracellular fluid volume contraction and expansion on the bicarbonaturia of parathyroid hormone.

To evaluate the effect of extracellular fluid volume alterations on the bicarbonaturia of parathyroid hormone, thyroparathyroidectomized dogs were made alkalotic and volume-contracted or expanded through hemodialysis. Clearance studies were performed before and after infusion of purified bovine parathyroid extract (PTE). Glomerular filtration rate and blood bicarbonate concentrations were kept constant throughout the experiments. A significant increase in fractional bicarbonate excretion was observed following PTE infusion in both the volume-contracted (8.67 +/- 3.25 to 14.70 +/- 3.63%, P less than 0.010) and the volume-expanded state (22.80 +/- 3.04 to 37.26 +/- 3.38%, P less than 0.050). It is concluded that PTE decreases reabsorption of bicarbonate independent of the volume state of the animal.


Calcium-binding protein in the duodenal mucosa of uremic patients and normal subjects.

In the present study we measured the content and determined the localization of a calcium-binding protein (CaBP) in the intestinal biopsy specimen of ten patients with severe renal insufficiency and in eight healthy individuals. In each patient a biopsy specimen of the iliac crest was obtained for evaluation of the degree of osteodystrophy. The CaBP was isolated from human kidneys. Its identity with human intestinal CaBP was suggested by acrylamid gel electrophoresis. Specific antibodies against it were developed in rabbits. The content of CaBP in duodenal mucosa biopsy material was measured by quantitative radial immunodiffusion. Its mean value in the duodenum of patients with renal insufficiency was 3.65 +/- 1.14 mug; in that of normal persons, 10.80 +/- 3.20 mug/mg of protein in the supernatant. There was neither a correlation between the type and duration of renal insufficiency and the CaBP content of the specimens nor between the degree of renal osteodystrophy and CaBP content. In normal persons the specific immunohistological activity indicating the presence of CaBP was found uniformly along the brush border and basement membrane of duodenal epithelial and the goblet cells. In uremic patients the fluorescence was markedly reduced in the typical locations, especially in the brush border area.


Heparin therapy in anti-basement membrane nephritis.

The effect of heparin on the development and progression of a form of antiglomerular basement membrane nephritis was examined in the rat. Animals which received heparin before and throughout the period of immunological insult developed lesions which were as severe, and perhaps more severe, than rats which did not receive heparin. Inulin clearances were lower in heparin-treated animals than in untreated rats. Animals in both groups exhibited renal fibrin-fibrinogen deposition and had increased rates of urinary fibrin-fibrinogen related antigen excretion. These results indicate that heparin per se has no beneficial effect on the development of this form of glomerulonephritis in this species.


Effect of angiotensin on the filtration of protein in the rat kidney: a micropuncture study.

We have analyzed the protein content of proximal tubular fluid (PTF) by ultramicro disc electrophoresis and measured total protein excretion rates both in control conditions and during angiotensin infusion to the rat. Under control conditions PTF albumin concentration was 1.49 +/- 1.12 (SD) mg/100 ml and did not increase with distance from the glomerulus. Immediate postcapsular samples (Munich-Wistar strain) yielded nearly identical values so that both probably represent filtered albumin concentration. During infusion of angiotensin (0.15 mug/mix x 100 g of body wt), PTF albumin concentration increased on the average 26-fold in re-collections from control tubules. Total protein excretion increased from a control of 7.91 to 24.37 mg/24 hr x 100 g of body wt. Glomerular filtration rate (FGR), single nephron GFR (SNGFR), proximal transit time and tubular fluid to plasma (tf/p) inulin values did not change significantly. Net afferent filtration pressure decreased from 24.7 to 15.6 mm Hg and renal plasma flow fell from 2.16 to 1.31 mo/min x g of kidney wt. Data describe a protein reabsorptive system normally operating near capacity. Angiotensin-induced proteinuria derives from an increase in filtered protein (mostly albumin) resulting from permeability changes in the glomerular membrane.


A survey of naturally occurring diseases of the Syrian hamster.

Questionnaires on research activities, mortality rates observed in various age groups, extent of examination of dead hamsters, and natural disease conditions and their relative importance were returned by 24 of 43 organisations surveyed in the United States. The average preweaning mortality rate due to all causes was 11-9%. Comparative data from 6 organisations that raised 87 880 hamsters in the calendar year 1971 indicated that 97-5% of total preweaning mortality was due to cannibalism. 13-7% of all animals died before use for experiments. "Wet tail" was the most frequently recognized disease (71%), and it was also listed as the most important. Pneumonia was recognized by 43% of the respondents and was most commonly listed as second in importance. A selective review of the literature is presented on those diseases recognized by more than one survey respondent.


The response of growing rats to a diet supplemented with the antibiotic ampicillin.

Ampicillin was included (25 mg/litre) in the drinking water supplied to growing rats over periods of 2,3,4,5,6,7 or 8 weeks. 32 rats were used in each experimental period, half being given the antibiotic and half being left as controls. The antibiotic increased the liveweight gain in each period, the results being significant after the 2- and 4-week feeding periods. Significant decreases were observed in the average percentage weights of the spleens of the rats given the antibiotic at the end of all the feeding periods except one. The few other significant changes in the percentage weights of other organs were, with one exception, noted at or before the end of the 4th week.


An epizootic outbreak of ringworm in a guinea-pig colony caused by Trichophyton mentagrophytes.

The disease was characterized by loss of hair, initially occurring at the tip of the nose and spreading throughout the body. Lesions appeared as circular, scaley alopecia with occasional scarring. Although spread of the infection in the colony was random, the most severe infection occurred in an inbred line with light coat colour. The unusually high temperature and humidity, and the open type of outdoor management, appear to have contributed to the high incidence and severity of infection. Electron microscopic observation indicated that the organism multiplied in the keratin layer of the skin. The hyphae as well as chlamydospores were readily demonstrable by electron microscopy.


Subacute sclerosing panencephalitis in the hamster. Ultrastructure of the acute disease in newborns and weanlings.

Acute subacute sclerosing panencephalitis has been investigated in both newborn and weanling hamsters intracerebrally inoculated with a human subacute sclerosing panencephalitis isolate (HBS) adapted to grow in hamster central nervous system (CNS) tissue. Newborn animals developed a disease which was fatal in approximately 1 week whereas most weanlings showed signs of an acute disease after day 8, from which a significant number recovered. Ultrastructurally, the human subacute sclerosing panencephalitis isolate (HBS) replicated rapidly in the CNS of newborn hamsters in the absence of an immune response. Giant cells developed from neurons and some demyelination was evident, most probably due to oligodendrocytic damage. Virus replication involved the proliferation of both typical measles virions and morphologically defective particles. Intracytoplasmic viral nucleocapsids were seen, but none were found within nuclei during the acute disease in newborns. Weanling hamsters developed a demonstrable immune response approximately 6 days after inoculation. Virions were seen and the majority appeared morphologically defective, lacking the associated nucleocapsids beneath the viral envelope. Abundant intranuclear, as well as intracytoplasmic, viral inclusions were seen. The results are of significance in the examination of myxoviruses (a group frequently linked to a number of chronic diseases of the CNS), in terms of viral replication in the CNS, in the response of different CNS cell types to infection, and in the influence of age and immune status upon the course of CNS disease.


The effect of high and low doses of cycloheximide on nucleolar ribonucleic acid synthesis.

In resting rat liver a dose of cycloheximide (1 mg. per kg.) inhibits leucine incorporation by 80 per cent whereas doses above 15 mg. per kg. inhibit it more than 90 per cent, when tested at 90 minutes following intraperitoneal injection. Initial stimulation of incorporation of orotate into total cellular, nuclear, and nucleolar fractions was seen at all doses tested. After 3 hours, however, marked suppression of incorporation particularly into nucleolar RNA was seen at 5 mg. per kg. and above while 1 mg. per kg. continued to stimulate. At 5 hours there was continued marked inhibition of RNA synthesis by 30 mg. per kg. and slight depression of RNA synthesis even by 1 mg. per kg. Preliminary ultrastructural studies failed to show objective nucleolar alterations even after 5 hours of cycloheximide treatment at a dose of 30 mg. per kg. No direct effect of several concentrations of cycloheximide on RNA synthesis was seen in an in vitro nucleolar system.


Skeletal muscle function and structure after depletion of creatine.

Experiments were conducted to determine if normal skeletal muscle function and structure are dependent upon their ability to store large quantities of metabolic energy in the form of N-phosphorylcreatine. Muscle levels of creatine and N-phosphorylcreatine were reduced by feeding young male rats diets containing 1 per cent beta-guanidinopropionic acid (beta-GPA). Muscle function was evaluated by monitoring performance during a 4-week, short duration, high intensity exercise program in a control running wheel. Structural effects were determined by histochemistry, morphometric analysis, and routine histologic procedures using light microscopy. Evidence of abnormal creatine metabolism of rats fed beta-GPA included: excessive creatinuria, reduction in urine creatinine, reduced levels of muscle and brain creatine, and a reduced activity of muscle creatine kinase. In separate experiments, beta-GPA inhibited the reaction of creatine with creatine kinase in vitro. When muscle function was evaluated by running, the percentage of expected revolutions for the group of rats fed beta-GPA was below the expected normal values. The white (type II) fibers from the gastrocnemius of exercised rats fed beta-GPA were smaller than fibers from the same muscle areas of rats fed normal diets. The histochemical characteristics of red (type I) and white fibers of all rats tested were within normal limits. It is concluded that feeding beta-GPA will result in structural and functional changes in skeletal muscles of exercised young male rats. These changes are believed to result from the ability of beta-GPA to block creatine entry into muscle and thereby prevent muscle from accumulating and maintaining its normal complement of creatine and N-phosphorylcreatine.


An improved system for hemoglobin-free perfusion of isolated rat livers.

Fine structure and several parameters of hepatic function were evaluated in isolated rat livers perfused with a hemoglobin-free medium in a newly designed organ perfusion system. The preservation of hepatic fine structure and the maintenance of certain functional criteria, including oxygen consumption, bile secretion rate, and the retention of intracellular potassium ions, demonstrated that these livers had been successfully perfused for up to 5 hours. The medium contained neither red blood cells nor other oxygen carriers, such as fluorocarbon emulsions. The use of hyperbaric oxygenation eliminates the requirement for hemoglobin in the perfusion medium. In addition, the extensive endothelial cell injury associated with the use of hemoglobin-free media is avoided since this system permits perfusion at near physiologic hepatic portal vein flow rates. The quality of isolated livers perfused without albumin in medium suggests that an oncotic agent is not required for rat liver perfusion.


Intercellular junctions in podocytes of the nephrotic glomerulus as seen with freeze-fracture.

The glomeruli of rats rendered nephrotic by administration of aminonucleoside of puromycin were studied with the freeze-fracture technique. The alterations of the podocytes consisted of a progressive blunting of the foot processes and of the disappearance of the extracellular space normally present between the foot processes at the level of the slit pore. In parallel with the closure of the extracellular space, fracture faces of the plasma membrane of the latered podocytes revealed the presence of peculiar membrane differentiations represented mainly by irregular chains of membrane-associated particles in the fracture face A and by variegated grooves in the fracture face B. The presence of grooves in fracture face B indicates that the chains of particles in fracture face A are likely to be tight junctions rather than linear gap junctions. However, since the presence of continuous ridges is exceptional, it is suggested that the tight junctions are the "leaky" -type and that the podocytes many have only limited capacities for assembling junctions of the "tight" -type.


Pathologic analysis of chemical nephritis in rats induced by N-(3,5-dichlorophenyl)succinimide.

The effects of N-(3,5-dichlorophenyl)succinimide (NDPS) administration to rats were studied by blood chemical, histopathologic, histochemical, and ultrastructural examinations. Administration of 5000 p.p.m. of NDPS induced severe damage of the kidneys, but did not affect other organs. Administration of 2500 p.p.m. of NDPS had little effect, even on the kidneys. Chemical analysis of the blood showed that the urea nitrogen level increased with the increase in the period of NDPS administration. Histopathologic examination showed intensive cell infiltration, mainly of lymphocytes, into the renal interstitium after NDPS administration for only 4 weeks. After NDPS administration for 12 weeks or more, typical interstitial nephritis was observed. Histochemical analysis showed that after only 1 week various enzymatic activities in the proximal convoluted tubules were markedly decreased whereas their activities in the distal convoluted tubules were relatively well preserved for at least 4 weeks. These results indicate that NDPS predominantly attacked the proximal convoluted tubules. After 4 weeks, the most prominent ultrastructural changes were seen in the proximal convoluted tubules where the epithelial cells lost their polarity and had a very abnormal arrangement. These cells showed well developed, edematous microvilli, poorly developed basal infoldings, swollen mitochondria of various sizes, aggregated beta-type glycogen granules, and debris of erythrocytes. Development of the endoplasmic reticulum, Golgi complex, ribosomes, and lysosomes was poor in the cytoplasm. These investigations indicate that NDPS affects the function of the proximal convoluted tubules. NDPS is a selective nephrotoxic substance. That is, it initially damages the proximal convoluted tubules, and subsequently causes interstitial nephritis. It is suggested that nephritis induced by NDPS is useful as a model of interstitial nephritis in man.


Use of thermolysin for the dissociation of lung tissue into cellular components.

A method is described for the dissociation of rat lungs into individual viable cells. Thermolysin was perfused through the vasculature and trachea. The lung was then minced and further dissociated by washing with sequential additions of thermolysin. The results indicate this procedure to be an effective means of dispersing lung tissue into its cellular components. Standard trypsinizing procedures generally yield approximately 5 per cent of the total available lung cells whereas the thermolysin treatment increases cell yield 10-fold without significantly affecting cell viability.


Lysosomal degradation of cell organelles. I. Ultrastructural analysis of uptake and digestion of intravenously injected mitochondria by Kupffer cells.

An experimental model comparable to autophagocytosis is presented to evaluate lysosomal degradation of biologic membranes in vivo. This design takes advantage of the efficient phagocytic capacity of Kupffer cells. For this purpose, mitochondria were isolated from one rat liver (inbred strain) and subsequently injected intravenously into a series of rats, which were sacrificed at various time points. The uptake and intralysosomal digestion were examined by electron microscopy. Mitochondria were seen in the sinusoids and attached to the surface of Kupffer cells 1 to 3 minutes after injection. One or two mitochondrial profiles were trapped in cavelike structures often embraced by long hyaloplasmic pseudopods. By 5 and 10 minutes, the mitochondria were in single membrane-bound phagosomes within the Kupffer cells and early signs of mitochondrial alterations were present, e.g., loss of cristae and condensation. At 30 minutes and 1 hour the mitochondria were seen in large vacuoles which contained up to 20 profiles in a single section. The mitochondria showed evident signs of digestion such as membrane fragmentation and flocculent densities. By 4 hours and especially by 8 hours, most digestive vacuoles were laden with flocculent membrane debris. By 24 hours, the Kupffer cells showed multiple lysosomal structures which were irregular in shape and small. These often contained a number of lipid-like droplets of various electron densities and pentalaminar structures. By 2 and 5 days, the Kupffer cells had returned to their normal appearance although the lysosomal apparatus was still prominent. No uptake of mitochondria was seen in endothelial cells, fat-storing cells, or hepatocytes. It is concluded that lysosomes have an efficient capacity to digest mitochondria. Some lipid remnants are not completely or slowly degraded by Kupffer cell lysosomes but remain in "residual bodies" for up to 1 or 2 days.


Lysosomal degradation of cell organelles. II. Ultrastructural analysis of uptake and digestion of intravenously injected microsomes and ribosomes by Kupffer cells.

Rough and smooth microsomes, "mixed" or total microsomes, and ribosomes were isolated from one single rat liver and subsequently injected intravenously into a series of inbred rats. The uptake and the degradation of the injected organelles by Kupffer cells were followed by means of electron microscopic analysis. By 1 minute after injection, microsomes were seen attached to the surface of Kupffer cells separated by a gap of 200 to 300 A. No attachment to hepatocytes, fat-storing cells, or endothelial cells was seen. By 5 and 10 minutes, most microsomes were phagocytosed and sequestered in large numbers within single membrane-enclosed vacuoles or phagosomes. The engulfment proceeded by two mechanisms: (1) most frequently, flaplike processes of cytoplasm embraced aggregates of microsomes,  concomitant with the formation of indention of the cytoplasm; (2) occasionally, single microsomal profiles were taken up by bristle-coated endocytic vacuoles. Ribosomes were also seen penetrating into the wormlike structures (micropinocytosis vermiformis) at the cell surface. At 30 minutes after injection, clear signs of alteration were noted starting with vesicle aggregation, clumping, and elongation of the microsomal profiles. The ribosomes were quickly stripped from their microsomal membranes and marginated to the inside of the vacuoles but separated from the limiting membrane by a distance of 200 to 300 A. By 1 and 2 hours, disruption of the vesicles into membrane fragments and formation of dense material in and between the profiles occurred. By 8 hours it was difficult to recognize the degradation products as membrane derivatives. The digestive vacuoles retained their size at this time interval. Typical pentalaminar structures were observed. By 14 to 24 hours the digestive vacuoles became electron lucent and appeared to shrink, and in addition to containing various types of granular material, many were laden with lipid-like droplets presumed to be conglomerates of phospholipid remnants. Rough microsomes, when compared to smooth microsomes, gave rise to more granular material within the digestive vacuoles. Ribosomes were still identifiable 24 hours after injection, indicative of a somewhat slower rate of degradation. Accumulation of various types of lipid-like droplets in the "residual bodies" was typical after microsomal injections. It is concluded that although microsomes appear to be phagocytosed at a quicker rate than mitochondria, they are digested within the lysosomal apparatus of  the Kupffer cells at a somewhat slower rate. This especially seems to be the case for ribosomes. Heterophagy of microsomes is one source of residual bodies.


Lysosomal degradation of cell organelles. III. Uptake and disappearance in Kupffer cells of intravenously injected isotope-labeled mitochondria and microsomes in vivo and in vitro.

14C-leucine and 3H-glycerol-labeled microsomes and mitochondria were intravenously injected into a series of highly inbred rats. The uptake and disappearance of the organelles were followed in a crude liver lysosomal fraction and in serum. Approximately half of the injected dose was recovered in the liver, and only smaller amounts were found in lungs, kidneys, spleen, and heart. The clearance in serum was more rapid for microsomes (t1/2, 5 to 15 minutes) than for mitochondria (t1/2 30 to 60 minutes). Both organelles showed a biphasic type of disappearance curve consistent with the two-phase theory of phagocytosis: attachment and engulfment. The estimated half-life for mitochondria of the liver was in the range of 3 to 4 hours, whereas that of the microsomes was considerably longer, or 8 hours. There was an increase of trichloroacetic acid-soluble material in the crude lysosomal fraction up to 2 hours after injection of glycerol-labeled microsomes, whereas the peak was reached at 60 minutes after 14C-leucine labeling. In vitro hydrolysis rate of hydrolysis. Experiments with Kupffer cells previously labeled with Thorotrast and biochemical assay of hydrolysis indicated that there was a lag phase of approximately 10 to 20 minutes before the phagosomes gained acid hydrolases, presumably by fusion with lysosomes. It is concluded at somewhat different rates. The remnants from lipid degradation, in comparison with protein degradation, seem to remain for a longer period within the lysosomal apparatus. These results are compatible with the concept that lysosomes represent an important, and at the present the only well defined locus for organelle turnover.


Chronic experimental hyperuricemic nephropathy.

Sustained, moderately severe hyperuricemia and severe uricosuria were produced in male Wistar rats by feeding dietary supplements of oxonic acid (0.4 gm. per day) and uric acid (0.6 gm per day). After 1 month, the kidneys showed the previously described histologic features of urate-blockade nephropathy characterized by intratubular deposits, tubular injury, and an exudative response consisting of neutrophilic granulocytes with early tophus formation. After 36 and 52 weeks of hyperuricemia, and with no gross evidence of renal failure, the kidneys showed a predominantly interstitial mononuclear cell infiltrate around regenerated tubules, an increase in interstitial fibrous tissue, infrequent renal tophi, and renal stones. The glomeruli and blood vessels appeared completely normal. There was no evidence of arthritis and no other target organ damage was detected. The chronic renal changes present in this animal model of induced hyperuricemia resemble those seen in human gouty nephropathy. The evolution of the experimental urate nephropathy observed during 1 year suggests that a primary acute inflammatory tubular injury is followed by a diffuse chronic interstitial nephritis and that the glomeruli and blood vessels are not primarily involved in the renal disease. This animal model may provide the opportunity to study factors influencing the renal sequelae of sustained hyperuricemia.


Insulin and hydrocortisone effects on viability and glycogen stores of postnatal rat liver organ culture.

Organ cultures prepared from 3- to 6-day-old newborn rat liver were maintained for as long as 6 days in medium CMRL-1066 supplemented with horse serum, glucose, and L-glutamine; the atmosphere for culture was 95 per cent O2 and 5 per cent CO2. Medium alone was used for control cultures, whereas insulin, hydrocortisone, or insulin plus hydrocortisone were used in experimental groups. Explant glycogen stores and viability were better preserved in cultures grown in hormone-supplemented media than in control cultures. Insulin caused glycogen storage of explant glycogen. Results of light and electron microscopic abservations are confirmed by isotope studies. The effect of hydrocortisone on glycogen synthesis is apparently dependent on the presence of insulin, and insulin appears to be required for glycogen storage in vitro in these cultures of postnatal rat liver.


Effects of prolonged administration of triton WR-1339 to the rat on morphology and phospholipids of liver.

Rats received 10 injections of Triton WR-1339 over a 4-week period. Light and electron microscopy and analysis of lipids and acid phosphatase were performed on livers of untreated controls, of animals taken during the period of treatment, and of animals allowed 2 weeks to recover. The only morphologic change resulting from the treatment was the appearance in both hepatocytes and Kupffer cells of after cessation of treatment, the change in hepatocytes had almost disappeared whereas it had become accentuated in the Kupffer cells. The treatments resulted in a 75 per cent increase in the concentration of lipids which includes Triton taken into the liver, a 17 per cent decrease in concentration of total phospholipid and a 26 per cent increase in acid phosphatase. Among phospholipid classes, there were small decreases in phosphatidylethanolamine, phosphatidylcholine, and diphosphatidylglycerol, a small increase in sphingomyelin and a striking increase of bis(monscylglyceryl)phosphate from 2.5 to 55 mug. of P per gm. of fresh weight. Cerebrosides were also increased. In rats allowed  2 weeks to recover, values for those classes which had been decreased by the treatment showed a trend of return toward controls. These observations suggest that lysosomal material is transferred from hepatocytes to Kupffer cells.


Scanning electron microscopy of proliferating bile ductules.

Rats were subjected to ligation of the common bile duct to provoke bile ductular proliferation and  were studied at intervals from 1 day to 6 weeks. After perfusion fixation with glutaraldehyde, and ethanol dehydration, blocks of liver were frozen in liquid nitrogen, fractured, and returned to ethanol prior to critical point drying. Examination with the scanning electron microscope showed a remarkable proliferation of bile ductules and preductules in addition to canalicular dilation. The ductules were surrounded by a longitudinal array of collagen fibers. The luminal surfaces contained many microvilli and cable-like structures, some identifiable as cilia by transmission electron microscopy. The present techniques offer the possibility for a reevaluation of obstructive jaundice and cholestasis.


Myocardial cell damage during experimental infective endocarditis.

Infective endocarditis was induced in 15 catheterized rabbits by a single intravenous injection of Streptococcus viridans and the papillary muscles from the left ventricle were examined for histologic and ultrastructural changes at 3 and 6 days of infection. Papillary muscles from 10 normal and 12 catheterized uninfected animals were used for comparison. Catheterized animals, infected and uninfected, had cardiac hypertrophy and papillary muscles which showed an increase in myofiber size and some interstitial edema. The muscle from infected hearts had areas of focal necrosis, diffuse monocytic infiltration, and loss of normal myocardial architecture. The papillary muscles from catheterized uninfected animals showed some degree of mitochondrial and sarcotubular swelling as  well as contracture of myofibrils; the infected myocardium exhibited dramatic changes in ultrastructure such as mitochondrial swelling and destruction, sarcotubular swelling, separation of the intercalated disc, and myofibrillar contracture and disruption. These histopathologic and ultrastructural changes in papillary muscles from rabbits with bacterial endocarditis are indicative of the presence of myocardial cell damage.


Myocardium of hypothermic rats with and without administration of dextran. Electrocardiographic and electron microscopic studies.

Electrocardiographic and electron microscopic alterations in the myocardium were investigated in rats subjected to hypothermia with and without injection of dextran. Twenty-two animals were divided into four groups and studied. The first group of five rats served as the control group. The second group of six rats, which were subjected to total body hypothermia developed arrhythmia (from first degree atrioventricular block to complete heart block) at a mean rectal temperature of 18 degrees C., with prolongation of P,P-R, and QRS duration, as well as a marked separation of intercalated discs, articularly at the level of the fascia adherens. The third group of six rats was subjected to hypothermia and to an injection of dextran. The resulting threshold temperature tthe temperature at which the arrhythmia appeared) was lower (16 degrees C.) than in the preceding group (p less than 0.005), but neither advanced atrioventricular block nor remarkable subcellular structural changes developed. The fourth group of five rats was sacrificed 18 to 24 hours following recovery from hypothermia and, at that time, showed no significant electrocardiographic or electron microscopic alterations.


Pulmonary deposits of titanium dioxide in cytologic and lung biopsy specimens. Light and electron microscopic x-ray analysis.

Although titanium dioxide (TiO2) is widely used in industry, its biologic effects have not been determined. In the present investigation, open lung biopsy samples and sputum specimens from three former TiO2 factory workers and bronchial aspirations from seven TiO2 factory workers were analyzed by conventional and x-ray microanalytic light and electron microscopic methods. These studies showed that in the alveolar macrophages, lysosomes contained a significant amount of titanium as well as smaller amounts of silicon, aluminum, iron, and potassium. It appeared that titanium dioxide was situated in round or oval-shaped particles whereas silica or silicon compounds were localized in  separate, more rectangular structures. There fore, the adverse effects may be induced by such quartz or silicon compounds. The latter are utilized as covering substances in the manufacture of TiO2 pigment.


Bile constituents in blood and lymph during biliary obstruction. I. The dynamics of absorption and transport of ions and colloid molecules.

Na125I and 131I-labeled albumin was infused in dogs into the common bile duct at pressures of 20 to 25 and 40 mmHg. At 40 mmHg, the amounts of the iodide ion and labeled albumin in circulating plasma were, after correction for the secondary loss from the circulation, nearly identical. At 20-25 mmHg more iodid than labeled albumin was found in the circulation. In thoracic duct lymph the same fraction of the infused amount of albumin was recovered at both pressures. Lymphatic concentrations of albumin were in both types of experiments substantially higher than plasma concentrations. It is concluded, that at increased pressure fluid leaks first from the small biliary ducts into the Mall's spaces. In consequence of water absorption and the diffusion of ions and small molecules into the blood capillaries the concentrations of protein or protein bound molecules in this part of the hepatic interstitial fluid increases. This is reflected in their high concentration in the lymph. If bile pressure rises further, fluid leaks also into the Disse's spaces. This leads to a bulk flow of solvent and solutes into the sinusoids and to the near disappearance of the differences in the venous transport of ions and colloids.


Bile constituents in blood and lymph during biliary obstruction. II. The absorption and transport of bile acids and bilirubin.

The lymphatic and venous transport of bilirubin and total bile acid was examined in dogs after the occlusion of the common bile duct. Lymphatic concentrations of both substances attained maximum levels between the 4 th and 6 th hours, but remained during the entire time of observation (24 hours) above plasma concentrations. The concentrations in blood plasma rose more slowly, but continuously. The amounts of both substances transported by the lymphatics rose steadly for 6 or 8 hours respectively and exceeded after 2 hours of occlusion the amounts transported by the veins. The results are explained by the changes in bilirubin and bile acid formation and secretion during biliary obstruction and on the basis of observations made in experiments with electrolyte and colloid infusions into the biliary passages.


Concentrating ability of lymphatic vessels.

The fluid from implanted capsules was analyzed for plasma proteins and compared with fluid sampled from small lymphatics which drained the region of the implanted capsules. The plasma protein concentration of capsular and lymphatic fluids were not found to be statistically different, for capsules implanted for greater than one month. Capsules implanted for less than one month demonstrate a much higher total protein than lymphatic fluid. This difference is thought to be due to several factors: (1) length of time that capsule has been implanted, (2) inflammation surrounding capsule, (3) time lag between sampling of lymphatic and tissue fluids. If capsules were used that had been implanted for greater than 1-1/2 months, then capsular and lymphatic fluids are not statistically different. A model is presented which predicts that the small initial lymphatics could or could not concentrate plasma proteins depending on the fate of the leaked fluid. The concentrating ability of the initial lymphatics will depend on whether or not the fluid leaked from the initial lymphatic is large relative to the surrounding volume, the time course of protein diffusion to the vicinity of the lymphatic and the rate of fluid removal from the space immediately surrounding the lymphatic. While there is a distinct possibility, since the forces exist, for a concentrating mechanism in larger lymphatic vessels, the data from implanted capsules indicate that we can assume that lymphatic vessels, especially in the subcutaneous region, contain plasma protein concentrations that are fairly representative of the tissue fluids of that region.


Functional anatomy of the lymphatic fluids and pathways.

The present sets of studies indicate that the fibrous capsule which encloses each tissue module divides the interstitial fluids into an intracapsular pool, and an extracapsular pool. Fluid that filters out of the capsules into the extracapsular clefts is the source of the lymph. Because of the limited permeability of the capsular barrier the composition of lymph differs from that of the capillary ultrafiltrate. Lymphatic vessels are means for the drainage of the extracapsular fluids and other materials. This appraoch differentiates two entirely separate types of edema: an intracapsular dependent pitting edema and an extracapsular generalized non-pitting edema. Three sets of experiments that support the foregoing hypothesis are briefly presented.


Polycystic kidney disease: recognition of the "adult form" (autosomal dominant) in infancy.

This case report and reports from the literature emphasize that the so-called adult form of polycystic renal disease can be diagnosed in infancy. The tern "adult form of polycystic disease" probably should be abandoned and the disease considered the autosomal dominant form of polycystic kidney disease.


An undergraduate program in family medicine in a setting that lacked a clinical base in that discipline.

When a medical school rises anew, lacking encrusted traditions, many difficult situations lend themselves to naive-but n not therefore necessarily trivial-solutions. When Mayo Medical School began, the moral and pragmatic pressures to provide instruction in family medicine came together. To many observers, the whole concept had connotations of incredibility. How could a subspecialty medical institution like Mayo undertake to offer such instruction? Yet now, as we approach the enrollment of our fourth class, a Department of Family Medicine exists in Mayo Medical School. Every student in his or her sophomore year has 4 weeks of instruction in family medicine-2 weeks of relatively didactic introduction and 2 weeks of preceptorship. In addition, the junior and senior classes must elect a "track," and one of the seven available tracks is in family medicine. For the class of 1976, 12 of the 39 students are in the family medicine track and for the class of 1977, 15 of 39.


5,7-Dihydroxytryptamine induced changes in the postnatal development of central 5-hydroxytryptamine neurons.

Systemic administration of the neurotoxic compound 5,7-dihydroxytryptamine (5,7-HT) to newborn rats led acutely (within 1--2 h) to a marked reduction of the in vitro uptake of [3H]5-hydroxytryptamine (5-HT) in homogenates from the cerebral cortex (75% decrease) and the pons-medulla (60% decrease). When 5,7-HT was administered postnatally we found that between days 5 an7 resistance developed in the cerebral cortex towards the 5,7-HT induced reduction in 3H-5-HT uptake. This was most likely the result of the postnatal development of the blood-brain barrier. These results show that 5,7-HT can pass the blood-brain barrier in the neonate stage and enter the brain to exert its well-known neurotoxic action on 5-HT neurons. The [3H]5-HT uptake in the cerebral cortex was reduced quantitatively to the same extent up to the 28th postnatal day, after which time a moderate recovery took place. Endogenous 5-HT was reduced by 40% in the cerebral cortex when measured in adult animals. In the pons-medulla there was a rapid recovery of the [3H]5-HT uptake during the first week after the 5,7-HT treatment and on the 14th postnatal day the increase was as much as 75% compared with the control. Endogenous 5-HT and [3H]5-HT uptake was increased by 40--50% when the analysis was performed 2 months after the 5,7-HT treatment. Studies of [3H]noradrenaline (NA) uptake after 5,7-HT administration at birth showed that this treatment similarly affected the NA neurons, though to a lesser extent. The effects on the NA neurons could be abolished by pretreatment with the "membrane pump" blocker desipramine, leaving the action of 5,7-HT on 5-HT neurons almost unaffected. Analysis of the [3H]5-HT uptake kinetics in the pons-medulla showed that the 5,7-HT treatment did not affect the Km while the Vmax was increased. It is concluded that neonatal 5,7-HT treatment produces a marked 5-HT denervation of the cerebral cortex, while there is a stimulated postnatal outgrowth of 5-HT nerve terminals in the pons-medulla, after an initial partial damage of the neurons.


5-Hydroxytryptamine and learning: long-term effects of P-chloroamphetamine on acquisition.

The effect of p-chloroamphetamine (PCA) on the acquisition of a conditioned avoidance response in the rat was examined. Eleven rats were injected with saline or 2 X 10 mg/kg of PCA i.p. on two consecutive days and the learning procedure was started eight days later and lasted for six days. The acquisition of the conditioned avoidance response was strongly impaired by PCA compared with the control group. It is suggested that the impaired learning is due to a long-term effect of PCA on a 5-hydroxytryptamine system directly or indirectly linked to learning.


Nicotine induced tremor and antidiuresis and brain nicotine levels in the rat.

Injection of rats with 14C-labelled nicotine (3 mg/kg sc) resulted in tremor measured by an electronic device during the first minutes after the injection. The animals were decapitated immediately afterwards and tissue was removed for the measurement of nicotine and cotinine. In another set of experiments nicotine (2 mg/kg sc) was injected into alcohol anaesthetized rats, their urinary excretion was measured up to 40 min, and they were decapitated as above. Pretreatment with mecamylamine prevented nicotine-induced tremor and antidiuresis. It also lowered the brain and blood nicotine levels in tremor experiments but not in antidiuresis experiments. Restoration of tremor by arecoline did not modify the mecamylamine effects on the nicotine levels. The 2 mg/kg sc nicotine dose did not produce tremor although the brain nicotine levels at 10 min exceeded those measured at 2 min after 3 mg/kg of nicotine. It is concluded that the rate of receptor occupation is important in the nicotine tremor. Both tremor and antidiuresis correlate fairly well with brain nicotine levels whereas mecamylamine-nicotine antagonism is less clearly reflected in brain nicotine levels.


Evidence for an inhibitory gabergic control of the meso-limbic dopamine neurons: possibility of improving treatment of schizophrenia by combined treatment with neuroleptics and gabergic drugs.

Changes in dopamine (DA) turnover have been studied in rats after treatment with pimozide and/or gabergic drugs such as beta-(p-chlorophenyl)-GABA and aminooxyacetic acid using the tyrosine-hydroxylase inhibitor alpha-methyltyrosine and methylester (H44/68). The changes in DA levels were determined by quantitative microfluorimetrical analysis of the fluorescence in various DA terminal systems. Beta-(p-chlorophenyl)-GABA (5--20 mg/kg) and aminooxyacetic acid (25 mg/kg) counteracted the pimozide (1 mg/kg) induced increase in DA turnover in subcortical and cortical limbic regions but not in the caput of the caudatus. These findings indicate the existence of a strong and preferential inhibitory gabergic control of the mesolimbic DA neurons and offer the possibility of improving the treatment of schizophrenia provided that limbic DA receptors are involved in this disease. If so, lesions of gabergic pathways may exist in the schizophrenic brain.


Alcoholism in cancer of the head and neck.

One hundred patients with a diagnosis of head and neck cancer were investigated carefully for a history of alcoholism. A majority of cases had a severe drinking problem; in fact, alcoholism was twice as common as initially anticipated. Patients were frequently able to hide the problem from their physician. Often the true diagnosis was obtained only by closely questioning relatives and friends. Most patients with cancer of the tongue, tonsil and oro-pharynx were alcoholic. About one-half of the patients with supraglottic carcinoma were alcoholic. In the nasopharnx and true vocal cords, there was no association with heavy drinking. The study is of epidemiological interest but also has implications in the management of the malignancy, depending upon the anatomic site involved.


Laser excision of carcinoma of the larynx.

The CO2 surgical laser and microscope assembly have been used to excise carefully selected T1 carcinomas of the membranous portions of the cord. Healing has been prompt and return of function satisfactory. General anesthesia and suspension laryngoscopy have provided excellent definitions of the lesions; the laser has provided a precise method of dissection. Initial results have been excellent and long term results will depend on the accuracy with which the margins of the tumor are defined and the presence or absence of the tendency of the larynx to produce multicentric disease.


Laryngofissure and cordectomy.

Laryngofissure and cordectomy is one of the first of the successful surgical procedures for the cure of cancer limited to the vocal cord. When the lesion is confined to the membranous cord and the motion of the cord is not impaired, cure rates ranging from 85 to 98 percent have been reported. Decline in the use of the procedure is due to the success of radiation therapy in achieving comparable cure rates while preserving normal voice quality. Hemilaryngectomy procedures are now done where laryngofissure and cordectomy had previously been indicated. The more extensive procedure gives greater security due to wider margins of resection and increase applicability, particularly when the lesion involves the anterior commissure. Although the indications for laryngofissure have diminished, the surgeon may use it when a simple, less extensive procedure is called for.


Supraglottic cancer.

Supraglottic cancer, because of the embryological development of the larynx, and of the arrangement of its lymphatic network, tends to remain limited within the vestibule of the larynx and the pre-epiglottic space also in its advanced stages of evolution. The cancer spread may superiorly involve the epilarynx, the vallecula, the base of the tongue, and the pyriform fossa; however, inferiorly, the invasion of the glottis is quite exceptional (1 percent of cases); therefore, supraglottic laryngectomy is the operation of choice. The lower the location of cancer in the vestibule, the safer the indication. The higher location generally requires an extension of surgical excision toward the tongue, arytenoids and hypopharnx. In view of the high percentage of lymph node metastases, supraglottic laryngectomy should be associated with neck dissection, mainly bilateral, also in cases with no evidence of enlarged lymph nodes. Supraglottic laryngectomy has been performed in 240 cases in the course of the last 14 years and the five-year cure rate has been 79 percent. Five postoperative deaths have been recorded. Rehabilitation time for the breathing and swallowing function has been three weeks as an average. Complications, such as fistula or infection have been exceedingly rare: uneventful recovery followed in all cases.


Radical neck dissection.

Radical neck dissection has evolved into a standard surgical technique over the past century. It has been the most effective method of attempting to control suspected or gross metastasis to the cervical region. The technique embraces the en masse removal of all tissue elements in the space between the subdermis and the fascia colli. The perimeters of the dissection extend from the midline anteriorly to the anterior border of the trapezius muscle posteriorly, and from the clavicle to the mandible. The essential portion of this large mass of tissue is the cervical lymph system with its lymph nodes and afferent and efferent connecting vessels. Controllability of the cancer process is in direct proportion to the number of nodes involved, their size and their position in the neck. Complications in the routine radical neck dissection are minimal. Cure rates are influenced by the type, size and site of the primary cancer, the possibilities for the adjunctive treatment such as radiotherapy and chemotherapy, and the, as yet, little understood immunological factors. The radical neck dissection has proven itself to be an essential tool in the management of cancer in the head and neck.


Anastomosis between the two facial nerves.

A case of traumatic facial palsy incurred during the removal of an acoustic neuroma via a sub-occipital craniectomy is presented. The palsy was rehabilitated to a satisfactory degree by anastomosing the normal to the paralyzed facial nerve using an autoplastic peripheral nerve graft of suitable length to join the two.


Effects of noise bands on contralateral pure tone adaptation.

The purpose of this study was to investigate the changes in threshold tone decay which result from contralaterally presented stimuli at an intensity less than interaural crossover. Five tone decay tests were administered at both 1,000 Hz and 2,000 Hz to 25 normal hearing adults. At each test frequency five contralateral conditions (no competing noise, white noise, narrow band noise centered at the test frequency, narrow band noise centered below the test frequency, and narrow band noise centered above the test frequency), were presented at 40 db above detection threshold to the nontest ear. Results showed a significant shift in tone decay scores when the conditions of white noise and narrow band noise centered around the test frequency were compared to the condition of no competing noise. A shift was seen at both frequencies but that occuring at 2,000 Hz was significantly greater than the shift at 1,000 Hz. No significant increase in tone decay was found for contralateral noise bands above or below the test frequencies.


Blue light endoscopy.

The introduction of high intensity proximal light sources has greatly improved the already high standard in technique of endoscopy. The enable us to illuminate the periphery of the bronchi. The advantage of better illumination must, nevertheless, be paid for with a levelling of contrast, as the bright light outshines the fine differences (e.g., tubercles in yhr mucous membrane). In order to heighten the contrast, first theoretical, then practical tests were carried out with different colored lights. Filters (red, green, yellow and light blue) were placed in front of the light source and the subjective perceptible changes in contrast examined. These tests showed that the light blue filter gave a heightened contrast between light and dark red as well as between yellow and red. Intra- and submucosal nodules, scars, metaplasias, hyper- and parakeratoses as well as precancerous conditions are more clearly visible in the mucous membrane. Circumscribed lesions are better seen and specimens for histological vertification are more accurately located for biopsy. Foreign bodies are more easily grasped. The remaining filters heighten the contrast in special cases (such as mycosis and colored foreign bodies). Individual filters or multifilter disc placed between the light source and the glass fiber light carrier are easy to manipulate, so that colored light can be employed in routine bronchoscopy in order to improve diagnosis.


Delayed C.N.S. complications.

Patients with esophageal stricture being treated with dilatation, who developed esophageal perforation or local peritonitis and subsequent central nervous system infection, are reviewed. It is suggested that the vertebral  venous system may be the route by which the metastatic infection is carried. Physicians caring for patients with esophageal stricture, who are receiving dilatation, should be aware of the possible intracranial complications and should be alert to the first sign of central nervous system abnormality.


Vestibular involvement in Bell's palsy.

Vestibular involvement in the acute phase of idiopathic facial paralysis (Bell's palsy) was observed in 22 percent and 14 patients. These patients were evaluated by history, physical examination and caloric tests with electronystagmography (ENG) employing the Cawthorne-Hallpike technique. Bell's palsy has been considered a mononeuropathy limited to the facial nerve. Evidence of occasional involvement of other cranial nerves (Vth and/or VIIIth) suggests a polyneuropathy. Several theories have been advanced to explain the involvement of the vestibular nerve.


Fractionation and analysis of fluorescent products of lipid peroxidation.

The fluorescence excitation spectrum of model conjugated Schiff base compounds that arise from the reaction of malonaldehyde with amino acids was shown to contain a maximum at 260-280 nm in addition to the previously observed maximum at 350-390 nm. Excitation at either maximum results in emission at a single maximum at 440-480 nm. The excitation and emission maxima of the model fluorescent compounds, together with the characteristic reductions in fluorescence intensity caused by alkaline pH or heavy metal coordination provide criteria with which to examine lipid peroxidation products for the presence of the conjugated Schiff base fluorophore. Silicic acid column chromatography and silica gel thin layer chromatography were employed to fractionate the fluorescent products of model lipid peroxidation systems and of rat testicular lipid soluble extracts. These products contained large families of compounds whose fluorescence characteristics were the same as those of the Schiff base fluorophores. The fractionation methods used enabled more thorough fluorescence characterization of many of the products of lipid peroxication, but the fluorescence criteria available do not provide definitive proof of structure.


Substitution reactions of linoleic acid hydroperoxide isomerase.

Linoleic acid hydroperoxide isomerase was extracted from corn germ and partially purified by differential centrifugation. This enzyme catalyzed the isomerization of linoleic acid hydroperoxide.(see article) Isomerase also catalyzed the substitution of various reagents at the carbon bearing the hydroperoxide group. These fatty acid products had the following functional groupings: (see article) where X is either oleoyloxy, ethylthio, or methoxy resulting from the presence of oleic acid, ethanethiol, or methanol, respectively. A crude wheat germ extract containing both lipoxygenase and isomerase enzymes reacted with linoleic acid to yield alpha-ketols, gamma-ketols, and a substitution product, the linoleoyloxy ester of alpha-ketol. Characterization of these products from wheat germ enzymes showed that the substitution reaction was not unique to corn germ. Because anions of the reagents tested are typical nucleophiles, the substitution reactions may proceed by a nucleophilic mechanism as mediated by the isomerase enzyme.


24-Methylenelanost-9(11)-en-3beta-ol, new triterpene alcohol from shea butter.

A new triterpene alcohol was isolated fron shea butter and its structure was shown to be 24-methylenelanost-9(11)-en-3beta-ol. Gas chromatographic correlations between this triterpene alcohol and other related compounds are discussed.


Dietary fats and properties of endoplasmic reticulum: I. Dietary lipid induced changes in composition of microsomal membranes in liver and gastroduodenal mucosa of rat.

Rats were fed for four weeks with different lipid diets to determine the effects on the endoplasmic reticulum membranes of the liver and on the postmitochondrial supernatant fraction of the gastroduodenal mucosa. The diets contained cholesterol, cacao butter, olive oil, and these in combination. The results showed that dietary lipids were able to modify the composition of the hepatic endoplasmic reticulum and, to a lesser extent, that of postmitochondrial fraction of gastroduodenal mucosa. Cacao butter in the diet decreased the relative proportion of protein in hepatic microsomes. Cholesterol and olive oil were able to increase the cholesterol content of microsomes. The trypsin digestion of membranes revealed that cholesterol increased the solubility of microsomal protein and decreased the trypsin sensitive protein-lipid binding. The neutral fat diets increased the binding of proteins to the membrane, and cholesterol had no effect when it was given in combination. The low power photomicrographs revealed vacuolization of the cytoplasm of the hepatocytes when rats were fed on lipid rich diets. Also fatty degeneration was present. Cholesterol in combination with olive oil, however, did normalize the structure of the hepatocytes to a marked extent.


Effect of glucose administration on cholesterol and bile acid metabolism in rats.

Glucose administered to fasted rats caused a marked stimulation in hepatic cholesterogenesis and cholesterol 7 alpha-hydroxylation, and an increase in biliary excretion of cholesterol and total bile acids. The excretion of cholic acid was not incluenced during the first few hr after glucose administration, but was significantly increased after 5 hr. Chenodeoxycholic acid showed a similar change, but the increase was only ca. one tenth of that of cholic acid. The excretion of deoxycholic acid was markedly increased by 1 hr, but gradually decreased thereafter. Pretreatment with neomycin abolished the increase in deoxycholic acid by fasting and glucose administration. Other bile acid components showed no significant change. It thus was presumed that cholesterol endogenously synthesized in the liver was metabolized mainly to cholic acid. In contrast, exogenous cholesterol was metabolized mainly to chenodeoxycholic acid. During the period of the acute enhancement of cholic acid formation from the endogenous cholesterol, biliary excretion of deoxycholic acid was increased. This probably occurred through the depression of 7 alpha-rehydroxylation of deoxycholic acid, or through the enhancement of microbial formation of deoxycholic acid in the lumen, and through the increase of intestinal absorption.


Occurrence of 7-methyl-7-hexadecenoic acid, the corresponding alcohol, 7-methyl-6-hexadecenoic acid, and 5-methyl-4hexadecenoic acid in sperm whale oils.

Two sperm whale oils from the northern hemisphere and two from the southern hemisphere were fractionated. Triglyceride and wax esters were examined for fatty acids and alcohols with monoethylenic unsaturation bearing a methyl branch on an ethylenic carbon. The 7-methyl-7-hexadecenoic acid (0.37-1.37%) was accompanied by the corresponding alcohol (0.28-0.72%), but these materials were not accompanied by shorter chain homologues. The 7-methyl-6-hexadecenoic acid was relatively less important (0.23-0.68%), but was accompanied by 5-methyl-4-hexadecenoic acid (0.10-0.39%), and a partially identified C13 compound. Chromatographic properties on silver nitrate impregnated silicic acid TLC and on three GLC liquid phases are reported.


Response of lipogenesis and fatty acid synthetase to physical training and exhaustive exercise in rats.

The effect of physical training and exhaustive exercise on fatty acid synthesis in rat liver and adipose tissue has been investigated. Exercise training (treadmill running) significantly (p less than 0.05) decreased body wt, eipdidymal fat pad wt, adipocyte size, and hepatic fatty acid synthetase activity. Training did not significantly affect adipose tissue cell number, lipogenesis from glucose-U-14C, or fatty acid synthetase. Exercise to exhaustion immediately prior to sacrifice significantly (p less than 0.05) decreased lipogenesis from glucose-U-14C and fatty acid synthetase in adipose tissue from trained but not untrained rats. Liver fatty acid synthetase was not significantly influenced by exhaustive exercise. The results of this study indicate that rats may adapt to physical training by decreasing adipose tissue lipogenesis during exhaustive exercise. This adaptation in energy metabolism may facilitate physically trained animals in conserving blood glucose during exhaustive exercise, thereby prolonging endurance.