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Effects of hydrogen peroxide on cardiac function and post-ischaemic functional recovery in the isolated 'working' rat heart.

The effects of hydrogen peroxide on the normal and ischaemic myocardium were investigated using the isolated 'working' rat heart preparation. In the range 0-3 microM no changes in heart rate, aortic flow, coronary flow, or aortic pressure were observed. Between 3 and 30 microM, however, there was a dose-dependent fall in aortic flow and an accompanying increase in coronary flow, the total cardiac output remaining unchanged. At concentrations about 30 microM functional failure occurred. Following a 24-min ischaemic period during which time 6 microM hydrogen peroxide was infused via the aorta at a constant rate to remove any vasodilatory effect, all hearts failed to recover. In contrast, 50% of control hearts recovered pump function. In conclusion, therefore, hydrogen peroxide can reduce function in the aerobic working rat heart and may exert a vasodilatory effect. When this effect is eliminated hydrogen peroxide affords no protection during ischaemia and appears to exacerbate tissue injury.

Animals

Survival and functional results after valve replacement for aortic regurgitation from 1976 to 1983: impact of preoperative left ventricular function.

Recent studies suggest that preoperative left ventricular function may no longer be an important determinant of survival or functional results after operation for aortic regurgitation because of improved operative techniques. To assess the effect of left ventricular function on prognosis in the current surgical era, we performed echocardiographic and radionuclide angiographic studies in 80 consecutive patients undergoing valve replacement from 1976 to 1983. No patient had associated coronary artery disease. For all patients, 5 year survival was 83 +/- 5%, significantly better than the 62 +/- 9% 5 year survival in our patients operated on from 1972 to 1976. Preoperative resting left ventricular ejection fraction (p less than .001), fractional shortening (p less than .001), and end-systolic dimension (p less than .01) were the most significant predictors of survival (univariate life-table analysis). Five year survival was 63 +/- 12% in patients with subnormal ejection fraction (n = 50) compared with 96 +/- 3% in those with normal ejection fraction (n = 30). Patients with subnormal left ventricular ejection fraction and poor exercise tolerance or prolonged duration of left ventricular dysfunction (greater than 18 months) comprised the high-risk subgroup (5 year survival 52 +/- 11%). Patients in this subgroup also had persistent left ventricular dysfunction after operation, with greater left ventricular end-diastolic dimensions and reduced ejection fraction (both p less than .001) compared with patients with normal preoperative left ventricular ejection fraction or a brief duration of left ventricular dysfunction (less than 14 months). Cold hyperkalemic cardioplegia was used for myocardial preservation in 46 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis

Topographical distribution of barrier function in cervico-cephalic arteries of dog. Major cerebral arteries possess definite barrier function?

Topographic distribution of barrier function in normal canine cervico-cephalic arteries was studied using horseradish peroxidase (HRP) and Evans blue as tracers. The carotid sinus of the internal carotid artery (ICA) was conspicuously permeable to HRP when compared to other areas of major cervical arteries. The cavernous portion of the ICA also showed prominent permeation of HRP, especially through the outer surface, which is covered with venous endothelial cells. On the luminal side of the cavernous portion of the ICA, barrier deficiency was noted at angulated segments such as the carotid siphon. Intracranial segments of both ICA and vertebral arteries demonstrated incomplete barrier function of the first 1 to 4 mm from the origin of the intradural segments. These areas were considered to be transitional sites in barrier function between extra- and intracranial arteries. Focal, but definite, barrier disruption was also noted at the distal ends of the ICA and other arterial branching sites of major intracranial arteries. While opening of the interendothelial junctions was considered to be one of the mechanisms causing increased permeability in the cavernous ICA, the mechanisms for the permeation of HRP into the major cerebral arteries could not be confirmed ultrastructurally.

Animals

Longitudinal study of pulmonary function development in childhood, adolescence, and early adulthood. Development of pulmonary function.

The growth of pulmonary function between 5.5 and 25 yr of age was determined using 1,511 observations over time on 353 subjects from a representative population sample of white non-Mexican-Americans in Tucson. There was an average of 8.8 yr of follow-up, with a maximum of 12. The method used was shown to be robust for span of follow-up from 3 to 12 yr (3 to 7 observations), and the results were verified by standard statistical methods. The standard error of the estimate decreased linearly with follow-up, indicating the need for longitudinal evaluation. Respiratory symptoms and diagnoses had the biggest negative impact on growth of lung function, using FVC, FEV1, Vmax50, and size-compensated flows (Vmax50/FVC). Smoking had the next biggest negative impact. Smoking cessation was shown to have a positive impact on growth of pulmonary function. Using a second linear model to adjust for individual variability and the random variability over surveys, individual growth showed similar trends. Further negative impacts were due to parental smoking, especially as it interacts with active smoking and respiratory disease. Flows at end of follow-up (Vmax50, Vmax50/FVC) were more sensitive than FEV1 to the effects of concurrent disease and smoking, and more persistent effects of these factors in early adulthood.

Adolescent

Functional and morphologic maturation of the superficial nephrons. Relationship to total kidney function.

The functional and morphologic pattern of superficial nephron development was studied in guinea pigs ranging in age between 2 h and 38 days. Concomitent measurements of total kidney function and glomerular counts were also performed. Superficial nephron glomerular filtration rate was found to increase from 0.92 to 19.32 nl/min. The filtration rate of the entire kidney rose from 0.19 to 1.31 ml/min. During the first 15 days of life the average rate of increase in glomerular filtration rate per nephron (0.48 nl/min.day), obtained by dividing the increase in total kidney glomerular filtration rate by glomerular number, was more than twice the observed rate of increase in the superficial nephrons (0.21 nl/min.day). During the remainder of the first month, the increase in superficial nephron glomerular filtration rate (0.97 nl/min.day) was greater than the average increase for all nephrons (0.71 nl/min.day). Thus, the initial increase in total kidney glomerular filtration rate was primarily a consequence of the activity of the deep nephrons, whereas during the ensuing period the superficial nephrons appeared to be the sole contributors to the change in total kidney glomerular filtration rate.The increase in superficial nephron glomerular filtration rate was found to correlate closely with the increase in proximal tubular length. Functional glomerulotubular balance was maintained throughout the entire period of renal maturation.

Aging

Assessment of testicular function after acute and chronic irradiation: further evidence for an influence of late spermatids on Sertoli cell function in the adult rat.

To study cell to cell communications within the testis of adult Sprague-Dawley rats, we used acute whole body neutron plus gamma-irradiation (0.99 Gray of neutron and 0.24 Gray of gamma-rays, 3 min; Exp A) over 7-121 days postirradiation and chronic whole body gamma-irradiation (7 cGy/day 60Co gamma-rays; Exp B) over 14-84 days of irradiation and 7-86 days postirradiation. Neither irradiation protocol had an effect on the body weight of the animals. Neutron plus gamma-rays induced dramatic damages to spermatogonia, preleptotene spermatocytes, spermatozoa, and, to a lesser extent, pachytene spermatocytes. In contrast, gamma-rays induced a selective destruction of spermatogonia. Subsequently, in both experiments a maturation-depletion process led to a marked decrease in all germ cell types. A complete or near complete recovery of the different germ cell types and spermatozoa took place during the two postirradiation periods. Under both irradiation protocols Sertoli cells number was unchanged. Androgen-binding protein and FSH levels were normal in spite of the disappearance of most germ cells from spermatogonia to early spermatids. However, the decline of androgen-binding protein as well as the rise of FSH and their subsequent recovery were highly correlated to the number of late spermatids and spermatozoa. Moreover, it appeared that spermatocytes may also interfere with the production of inhibin (Exp B). With neither irradiation was Leydig cell function altered, except in Exp B in which elevated LH levels were temporarily observed. Correlation analysis suggested a relationship between preleptotene spermatocytes and Leydig cell function. In conclusion, this study establishes that chronic gamma-irradiation is particularly useful in the study of intratesticular paracrine regulation in vivo and provides further support to the concept that late spermatids play a major role in controlling some aspects of Sertoli cell function in the adult rat.

Animals

Clinical application of the functional matrix: mandibular reconstruction and monobloc functional therapy.

A 13-year-old black girl with an extensive ameloblastoma of the mandible required subtotal mandibular resection and immediate reconstruction with use of an autogenous, ipsilateral, corticocancellous graft from the iliac crest and monobic functional therapy. Twenty-seven months later, clinical evaluation showed normal mandibular function and no facial asymmetry. Bony architectural changes after 27 months included reformation of the coronoid process, angular process, and external oblique ridge; preservation of mandibular length and thickness; and maintenance of the alveolar ridge height. The reformation of the coronoid process suggests the importance of the functional matrix (temporalis muscle) in skeletal tissue growth. The monobloc appliance in conjunction with bone grafting is an effective means for transmission of biophysical stimuli and for maintenance of appropriate stress for remodeling of bone in the mandible.

Activator Appliances

Deterioration of renal function during angiotensin converting enzyme inhibition in hypertensive patients with a poorly functioning solitary kidney.

During treatment with the angiotensin converting enzyme inhibitor, Captopril, glomerular filtration rate (GFR) decreased in three unilaterally nephrectomized hypertensive patients with a poorly functioning remaining kidney. The fall in GFR was not related to changes in the blood pressure, and was reversed when Captopril was stopped. In a fourth nephrectomized patient the initially normal GFR was not affected by captopril. These observations point to a functional reduction in GFR due to a withdrawal of an intrarenal action of angiotensin II. Maintenance of GFR may become critically dependent on a functioning renin-angiotensin system when renal perfusion pressure is reduced to a certain degree. Inhibition of angiotensin II formation may lead to a decrease in GFR in patients with renal hypertension and pre-existing renal insufficiency.

Aged

Renal pelvic function following total alloplastic replacement of ureter in pigs. Electrophysiology, renal function and morphology.

Total replacement of one ureter was under-taken in pigs. After an observation period of 2-3 months further studies were made. Pelvic peristaltic activity as reflected by pelvic pressure waves and electrical activity was indistinguishable from that in normal pigs. In particular, retrograde activity was not observed. It appears that ureteric peristalsis is not a prerequisite of normal pelvic function. Providing only that the calibre is sufficient, function of a ureteric prosthesis is satisfactory, and no changes in kidney or pelvis function and morphology are apparent.

Action Potentials

Long-term functional results of surgery for coronary artery disease in patients with poor ventricular function.

Thirty-two patients with coronary artery disease and an ejection fraction (EF) below 0.40 had coronary bypass and/or left ventricular aneurysm (LVA) resection. Twenty-four patients had a previous infarction, 12 had congestive heart failure (CHF), and left ventricular end-diastolic pressure averaged 15 mm. Hg. Nineteen patients had three-vessel involvement and there was an average of 2.4 vessels involved per patient. Bypass was accomplished on 87 per cent of vessels; 11 patients had resection of LVA; 11 had coronary endarterectomy. There were no hospital deaths, 63 per cent of the patients were improved, and 56 per cent were able to return to work or full activity. There were five late deaths (16 per cent). There was good functional improvement in 83 per cent of the survivors, followed 1 to 4 years. We believe that patients with poor ventricular function due to severe coronary artery disease should not categorically be denied surgery, and that operation can be done with a low hospital mortality rate and good functional results.

Adult

[Breath rate as a function of parameters of pulmonary function in body plethysmography (author's transl)].

Parameters of pulmonary function were measured at resting breathing rates (mean 15-17/min) and at breathing rates of 20-40/min in 238 subjects (79 normals, 44 patients with normal pulmonary function in spite of lung disease, and 115 patients, most of whom had obstructive-emphysematous lesions) in a constantvolume body plethysmograph with a respiratory bag. In the subjects with normal pulmonary function the resistance increased significantly by 25 and 45 percent, resp., with more rapid respiration (p smaller than 0,01). Nevertheless it is assumed that this rarely accounts for false interpretations in everyday routine practice. No relationship of breathing rate to respiratory passage resistance was observed in patients with increased total resistance. By way of contrast, ventilation work of breathing (pV diagram) and the index of ventilation work of breathing (defined Vp ratio) showed a close correlation to breathing rate in all 3 groups. This leads us to conclude that these parameters provide more exact information on the breathing mechanism than does total resistance. Studies on ventilation work of breathing must be conducted under clearly defined breathing rates and consideration of the respiratory volume. intrathoracic gas volume was not correlated to the breath rate.

Adult

[Search for functional domain boundaries and localization of functional sites based on oligopeptide vocabularies].

A new method based on the analysis of oligopeptide composition of the amino acid sequences from different protein families is presented. We assume, that any protein family can be characterized by the set of oligopeptides (oligopeptides vocabulary). We demonstrate, that oligopeptides vocabulary comparison can distinguish different families from each other and from random sequences. It should be noted, that this comparison can be successfully performed on the set of only 25 dipeptides and without preliminary alignment. We demonstrate, that characteristic peptides are localized in the regions of functional significance, as shown on the example of GTP-binding domain of translation elongation factors. We suggest how to use this method to localize the boundaries of functional domains in amino sequences. On the example of few functional domains we demonstrate, that the average error of prediction does not exceed 3-4 amino acid residue.

Amino Acid Sequence

A site-directed approach for constructing temperature-sensitive ubiquitin-conjugating enzymes reveals a cell cycle function and growth function for RAD6.

We have determined the gene sequence of a temperature-sensitive allele of the cell cycle-related ubiquitin-conjugating enzyme CDC34 (UBC 3) from Saccharomyces cerevisiae. The basis of temperature sensitivity is a missense mutation resulting in a proline to serine substitution at a residue that is conserved in all ubiquitin-conjugating enzymes identified thus far. This observation raised the possibility that other temperature-sensitive ubiquitin-conjugating enzymes could be generated in the same way. We therefore created the corresponding substitution in the DNA repair-related ubiquitin-conjugating enzyme, RAD6 (UBC2), and examined the effect of temperature on the cell proliferation and DNA repair-related functions of this altered polypeptide. Yeast strains carrying this mutation proved to be temperature-sensitive with respect to cell proliferation but not with respect to the DNA damage-processing phenotypes exhibited by other rad6 mutants. Upon further investigation of the proliferation defect exhibited by this mutant, we discovered that other rad6 gene mutants deleted for the gene undergo cell cycle arrest at the nonpermissive temperature, whereas the engineered temperature-sensitive allele showed no evidence of a cell cycle defect. From these findings, we conclude that the proliferation function of RAD6 can be subdivided into a growth component and a cell division cycle component and that the growth component is unrelated to the DNA repair functions of RAD6. A reasonable interpretation of these results is that different proteins are targeted for ubiquitination in each case. The conserved proline residue of RAD6 and CDC34 is part of a turn motif common to all ubiquitin-conjugating enzymes. It is therefore likely that site-directed substitution of prolines located in turns can be generally applied for the creation of other temperature-sensitive ubiquitin-conjugating enzymes and possibly other proteins as well.

Alleles

Evaluation of CSF shunt function: value of functional examination with contrast material.

Functional positive-contrast shuntography includes a patency check of both limbs of the shunt and the shunt valve by fluoroscopy following the injection of an iodinated contrast agent (anatomic shuntogram) and an assessment of the adequacy of ventricular fluid drainage under physiologic conditions by using serial CT scans to assess the rate of iodine dissipation from the ventricular system (physiologic shuntogram). To demonstrate its efficacy and utility, 82 functional shuntograms were obtained in 55 patients. Fifty-one of the 82 studies were abnormal. Of these, 22 demonstrated patency of both the proximal and distal limbs with an accompanying slow dissipation of contrast material after injection (21 of 22 patients were adults). Eighteen of these 22 patients improved following the reduction of shunt drainage pressure. In the case of frank shunt obstruction, the site of obstruction was delineated clearly in all 29 cases. Correlation of clinical outcome with test results confirmed the utility of this technique, especially when applied to the shunted adult hydrocephalic patient whose response to the shunt had been inadequate. The technique described here allows the clinician to differentiate between physiologic and anatomic shunt failure and between shunt failure and normal shunt function. It also allows for precise localization of the shunt obstruction in anatomic shunt failure and for demonstration of physiologic shunt failure when shunt patency is demonstrated in the presence of the slow dissipation of intraventricular contrast medium.

Adult

[Improvement of hearing function through ear reoperation. The role of tympanic revision for functional indications].

Recurrent middle ear disease may carry a high probability of complications, and there is no doubt of the necessity of revision surgery for either cholesteatoma or tumor. However, failures in function should be individually analyzed before a second procedure is decided upon. A pre-requisite for surgical improvement of hearing is adequate tubal and inner ear function. Chronic suppurative otitis media has a higher tendency for reperforation than cholesteatoma. Adhesive otitis indicates poor tubal function. Tympanosclerosis may cause refixation requiring stapedectomy at a second stage. Middle ear fibrosis recurs in about 50% of cases. Post-operative failures such as extrusion of ossicles, lateralization of the tympanic membrane, and blunting of the anterior tympanomeatal angle as well as failures after stapes surgery are discussed.

Aged

[Development of functional jaw orthopedics and function regulator].

Functional jaw orthopedics is an orthodontic treatment which uses muscle stimuli developed from the functions and tonus changes of masticatory, tongue, lip and cheek muscles. The functional regulator which is one of the appliances used in this treatment, takes support not from the teeth, but directly from the soft tissues in order to make changes in alveolar bone and teeth.

Activator Appliances

Structure-function analysis of the human interferon gamma. The COOH terminus is not essential for functional activity.

The structure-function relationships for the human interferon gamma (HuIFN-gamma) were studied using recombinant variants that had various deletions at the carboxyl terminus. Four COOH-terminal deletion variants were constructed that contained the amino-terminal 122, 117, 111, and 106 amino acid residues. These variants were constructed by specific DNA modifications and were expressed in Escherichia coli. The deletion of 21 amino acid residues resulted in only 2- and 3-fold reduction in the antiviral and antiproliferative specific activities, respectively. Thus, the carboxyl-terminal 21 residues are not directly involved in the function of the HuIFN-gamma. The level of intracellular accumulation was also decreased by 3-5-fold. Further deletions of 26, 32, and 37 residues from the COOH terminus resulted in the lack of detectable activity as well as in 50-100-fold reduction in the level of accumulation in the bacterial cell. However, each of the modified plasmids was found to have comparable efficiency in directing the production of the respective variant molecules relative to the full-length HuIFN-gamma molecule in an in vitro transcription-translation assay. Thus, the failure of some of the deletion variant molecules to accumulate in the E. coli cell is likely due to their instability in vitro. The loss of the COOH-terminal 21 amino acid residues of HuIFN-gamma also resulted in a substantial reduction in the ability of the molecule to be renatured in vitro from the treatment with chaotrophic agents, a method frequently used to extract and purify recombinant polypeptides from E. coli host. The latter result may account for some earlier reports which inferred the involvement of the COOH terminus in the functions of the HuIFN-gamma molecule due to their failure to detect activity upon deletions of only 11-18 residues.

Amino Acid Sequence

[Study of the somatotropic function of the pituitary gland and the glucocorticoid function of the adrenal glands in rats with alloxan diabetes].

The somatotropichormone (STH) content was studied in the hypophysis and the peripheral blood of rats with alloxan diabetes; the corticosterone content was determined in their peripheral blood. The STH content in the peripheral blood and the hypophysis of these rats failed to differ from that in the control group, but the blood STH content rose considerably in the sick animals. Exclusion of the insular apparatus function was accompanied by the adrenal gland hypertrophy, which correlated with the rise of the blood corticosterone level. The data obtained indicated that the insular apparatus insufficiency induced by alloxan was accompanied by changes in the somatotropic function of the hypophysis and of glucocorticoid function of the adrenal glands.

Adrenal Cortex