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Biomedical subjects

J H Harrison

Publications and source records attributed to J H Harrison.

At least 91 records · Page 5Linked to original sources

Frog lysozyme. V. Isolation and some physical and immunochemical properties of lysozyme isozymes of the leopard frog, Rana pipiens.

Frog Lysozyme has been purified by sequential application of acid extraction, salt fractionation, CM-cellulose chromatography, heat treatment, and gel filtration. Eight isozymes of purified lysozyme were found to be stable during prolonged storage. Isozymes were separated by preparative polyacrylamide gel electrophoresis, Ninety percent of the lytic activity of frog ovarian egg was represented by forms 7 and 8, the most highly charged isozymes. Seventy-eight percent of frog liver lysozyme activity was that of form 4. Forms 7 and 8 differed from form 4 by being larger (apparent molecular weight of 18,000 vs. 16,000), by remaining active in more acidic environment, and by exhibiting a dependency upon NaCl for activity. Antiserum prepared against frog form 4 did not react with frog forms 7 and 8 and antiserum to chicken egg-white lysozyme did not react with any frog lysozymes. All frog lysozymes showed identical reversible binding to deaminated chitin. Apparent size differences and lack of immunological cross-reactivity suggest that at least some of the isozymes are non-allelic.

Animals↗

Functioning and nonfunctioning cysts of the adrenal cortex and medulla.

Adrenal cysts are rare clinical and pathologic entities. The vast majority are minute in size, unilateral, and found in females at autopsy. They come to the physician's attention when they produce symptoms or are identified on x-ray studies. When symptomatic, they generally produce lumbar discomfort and gastrointestinal symptoms, and occasionally are palpable by abdominal examination. There is no significant agreement as to cause and pathogenesis of the disease. The most common histologic types are lymphangiomatous endothelial cysts, secondary to lymphangiectasis, and the fibrous wall or hemorrhagic pseudocysts. In many patients preoperative diagnosis is now possible with high quality nephrotomography, ultrasonography, and adrenal arteriography. The presence of a suprarenal mass with peripheral or laminar calcification strongly suggests the presence of an adrenal pseudocyst. Selective biochemical studies are mandatory to rule out the presence of an occult cystic pheochromocytoma, and adrenal cortical tumor. Adrenal cysts must be differentiated from all space-occupying lesions of the upper abdomen. Surgical exploration is recommended in almost all patients for accurate diagnosis and to rule out malignant disease or occult pheochromocytoma. The choice of the surgical approach should be planned to provide for safe and adequate exposure, depending on the size and location of the lesion. Careful dissection with preservation of the adjacent kidney, liver, and pancreas should be performed.

Adrenal Cortex↗

The familial liver donor in renal transplantation.

A survey is made of the 20-year experience with more than 300 living donors in renal transplantation at the Peter Bent Brigham Hospital. Details are given pertaining to the first transplantation of the kidney from one living person to another in December 1954. The surgical technique, the complications and the results of renal transplantation from a living donor are summarized. The philosophic and psychologic problems encountered are described. A comparison of results summarized by Murray of living, related donor transplants to cadaveric donor transplants is included. This paper constitutes a salute to the familial living donor.

Adult↗

Malignant pheochromocytoma: clinical course and treatment.

We describe 7 patients with 16 malignant pheochromocytomas, with followup for 7 to 21 years. Five patients are free of disease at a mean of 13.5 years and 2 patients died of malignancy at 10 and 13 years. The 3 criteria believed important for a maximum tumor-free interval are: 1) adjunctive lymphadenectomy at the initial operation when 1 or more lymph nodes contain tumor, 2) close followup of all patients with pheochromocytoma by diagnostic biochemical assay for 15 years and 3) an aggressive excision of all single or multiple recurrent pheochromocytomas as soon as a biochemical diagnosis is established.

Adolescent↗

Inactivation of porcine heart cytoplasmic malate dehydrogenase by pyridoxal 5'-phosphate.

Pyridoxal 5'-phosphate (pyridoxal-5'-P) has been found to act as a bifunctional reagent during the inactivation of porcine heart cytoplasmic malate dehydrogenase (L-malate: NAD+ oxidoreductase, EC 1.1.1.37). The biphasic kinetics and X-azolidine-like structure formed were similar to those observed for mitochondrial malate dehydrogenase (Wimmer, M.J., Mo, T., Sawyers, D.L., and Harrison, J.H. (1975) J. Biol. Chem. 250, 710-715). In the cytoplasmic enzyme, however, irreversible inactivation representing X-azolidine formation was found to be the dominant characteristic of the interaction with pyridoxal-5'-P. Spectral evidence indicated that at total inactivation 2 mol of pyridoxal-5'-P were incorporated per mol of enzyme or one pyridoxal-5'-P per enzymatic active site. The presence of NADH protected the enzyme from inactivation suggesting interaction of pyridoxal-5'-P at or near the enzymatic active centers of this enzyme. Fluorometric titrations indicated that pyridoxal-5'-P-inactivated enzyme failed to bind NADH or at least failed to bind NADH in the same fashion as native enzyme.

Cytoplasm↗

Venacavography, corticosteroids and surgery in the management of idiopathic retroperitoneal fibrosis.

Four patients with idiopathic retroperitoneal fibrosis were found to have characteristic obstruction and anterior displacement of the lumbar vena cava. Varying degrees of venous collateral circulation were present, depending on the degree of vena caval compression. All 4 patients underwent ureterolysis to relieve the hydronephrosis and to confirm diagnosis by biopsy. Two patients were treated with corticosteroids postoperatively. Followup venacavography demonstrated improved filling and decrease in the collateral circulation in these 2 patients. Of the remaining 2 untreated patients 1 was lost to followup and the other revealed no change. Diagnosis of idiopathic retroperitoneal fibrosis can be made if characteristic changes are present on inferior venacavography and may provide an objective measure for following the basic disease process during medical treatment.

Adult↗

Identification of an essential lysine in porcine heart mitochondrial malate dehydrogenase.

The reversible inactivation of porcine heart mitochondrial malate dehydrogenase by pyridoxal 5'-phosphate yields an irreversible modification upon sodium borohydride reduction. A 200-fold molar excess of pyridoxal-5'-P over enzyme results in inactivation to the extent of 54%, and incorporation of 5.7 mol of inactivator per mol of enzyme. The same inactivation carried out in the presence of 80 mM coenzyme, NADH, produces malate dehydrogenase which is approximately 94% active and contains 4.6 mol of pyridoxal-5'-P per mol of enzyme. The incorporation difference between inactivated and protected samples suggests, for total inactivation, the modification of 2 residues per mol of enzyme (i.e. 1 residue per subunit, or 1 per enzymatic active site). This specificity was confirmed by the isolation of a single pyridoxyl-5'-P-labeled "difference peptide" obtained by comparison of the Dowex 1-X2 elution profiles of tryptic digests of protected and inactivated samples, respectively. Amino acid analysis of the peptide demonstrated the presence of N6-pyridoxyl-L-lysine (Lys(Pyx)), establishing the existence of an essential lysing residue in the active center of malate dehydrogenase. The amino acid sequence of the active center hexapeptide has been determined to be: H2NLys(Pyx)Pro-Gly-Met-Thr-Arg-COOH.

Amino Acid Sequence↗

Identification of essential arginyl residues in cytoplasmic malate dehydrogenase with butanedione.

The inactivation of cytoplasmic malate dehydrogenase (L-malate: NAD+ oxidoreductase, EC 1.1.1.37) from porcine heart and the specific modification of arginyl residues have been found to occur when the enzyme is inhibited with the reagent butanedione in sodium borate buffer. The inactivation of the enzyme was found to follow pseudo-first order kinetics. This loss of enzymatic activity was concomitant with the modification of 4 arginyl residues per molecule of enzyme. All 4 residues could be made inaccessible to modification when a malate dehydrogenase-NADH-hydroxymalonate ternary complex was formed. Only 2 of the residues were protected by NADH alone and appear to be essential. Studies of the butanedione inactivation in sodium phosphate buffer and of reactivation of enzymatic activity, upon the removal of excess butanedione and borate, support the role of borate ion stabilization in the inactivation mechanism previously reported by Riordan (Riordan, J.F. (1970) Fed. Proc. 29, Abstr. 462; Riordan, J.F. (1973) Biochemistry 12, 3915-3923). Protection from inactivation was also provided by the competitive inhibitor AMP, while nicotinamide exhibited no effect. Such results suggest that the AMP moiety of the NADH molecule is of major importance in the ability of NADH to protect the enzyme. When fluorescence titrations were used to monitor the ability of cytoplasmic malate dehydrogenase to form a binary complex with NADH and to form a ternary complex with NADH and hydroxymalonate, only the formation of ternary complex seemed to be effected by arginine modification.

Adenosine Monophosphate↗

Biphasic inactivation of procine heart mitochondrial malate dehydrogenase by pyridoxal 5'-phosphate.

Temperature studies have indicated that from 0 to 37 degrees, the time-dependent inactivation of mitochondrial malate dehydrogenase from porcine heart by pyridoxal 5-phosphate (pyridoxal-5-P) is biphasic. The initial phase of the inactivation is reversible but can be made irreversible by reduction with sodium borohydride. The reduced pryidoxal-5-P-enzyme adduct exhibits a new absorbance maximum at 325 nm and a fluorescence emission at 392 nm when excited at 325. The irreversible second phase of the inactivation is accompanied by the appearance of a new 325-nm absorbance maximum, in the absence of reduction, and a fluorescence emission centered about 390 to 400 nm when excited at 325. The evidence presented suggests the formation of a Schiff base between pyridoxal-5-P and a nucleophilic residue, most likely lysine, of malate dehydrogenase during the first phase of inactivation. An X-azolidine-like structure, a further derivative of the Schiff base, possessing spectral properties consistent with the reported data, may be formed during the second phase; this presumably involves a second nucleophilic residue of the enzyme, implicating the action of pyridoxal-5-P as a bifunctional reagent in this instance. The presence of the coenzyme, NADH, protects the enzyme from inactivation, suggesting that pyridoxal-5-P interacts at or near the malate dehydrogenase active center. Simultaneous binding studies using pyridoxal-5-P with known malate dehydrogenase competitive inhibitors AMP, ADP, and nicotinamide indicate that the pyridoxal-5-P modification occurs in the general area of the ADP portion of the coenzyme binging site. Furthermore, the presence of nicotinamide enhances pyridoxal-5-P binding to and inactivation of malate dehydrogenase.

Animals↗

Bilateral anorchism.

A case of surgically proved bilateral anorchism is reported. Emphasis is placed on the importance of early diagnosis and treatment in the proper management of this rare entity.

Adult↗

Post-diversion pre-cystectomy irradiation for carcinoma of the bladder.

In 47 patients treated sequentially with urinary diversion and laparotomy staging, irradiation therapy and total cystectomy for invasive carcinoma of the bladder, the mortality rate was 2 per cent and the complication rate was 20 per cent. The survival rate was most favorable in patients in whom the pathologic specimen revealed no tumor after irradiation. The lower mortality and morbidity rates are attributed to staging of surgical procedures and the challenge remains to increase the number of patients in whom carcinoma of the bladder is converted by irradiation therapy to a lower stage or no tumor.

Carcinoma↗

Renal cell carcinoma: natural history and chemotherapeutic experience.

Eght-four patients with renal cell carcinoma were analyzed retrospectively in order to 1) determine the effectiveness of systemic chemotherapy-hormonal and non-hormmonal, 2) identify the clinical features of renal cell carcinoma that may be important in prognosis and 3) characterize the paraneoplastic features of renal cell carcinoma. Metastatic disease was present at diagnosis in 57 per cent of the cases and developed within 1 year in an additional 19 per cent of the cases were paradoxically associated with a longer survival (20 months median) compared to single-organ metastasis (5 to 11 months median). Paraneoplastic syndromes occurred in up to 40 per cent of patients with variable survival. Metastatic disease was unresponsive objectively to either primary nephrectomy or to a variety of chemotherapy trials.

Adenocarcinoma↗