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Biomedical subjects

M A Block

Publications and source records attributed to M A Block.

At least 19 recordsLinked to original sources
PubMed1992

Feedback inhibition of phosphatidate phosphatase from spinach chloroplast envelope membranes by diacylglycerol.

Because the envelope phosphatidate phosphatase plays a pivotal role in chloroplast glycerolipid metabolism, we have analyzed whether diacylglycerol could be a regulatory factor of the enzyme. Using isolated envelope membranes in which the level of diacylglycerol was modified by thermolysin treatment of intact chloroplasts to destroy the galactolipid:galactolipid galactosyltransferase, we have demonstrated that phosphatidate phosphatase activity was reduced when the membrane was enriched in diacylglycerol. All 1,2-diacylglycerol molecular species assayed were demonstrated to inhibit the enzyme to about the same extent. Kinetic studies with envelope from thermolysin-treated chloroplasts were performed in the absence and presence of diacylglycerol, and diacylglycerol was shown to be a powerful competitive inhibitor of the reaction. Finally, using isolated intact spinach chloroplasts, we have demonstrated that in situ phosphatidate phosphatase activity can be modulated by the level of diacylglycerol present in the membrane. The relevance of phosphatidate phosphatase inhibition by diacylglycerol in the regulation of chloroplast glycerolipid biosynthesis is discussed.

Cell Fractionation↗
PubMed1992

Localization within chloroplasts of protoporphyrinogen oxidase, the target enzyme for diphenylether-like herbicides.

Plant protoporphyrinogen oxidase is of particular interest since it is the last enzyme of the common branch for chlorophyll and heme biosynthetic pathways. In addition, it is the target enzyme for diphenyl ether-type herbicides, such as acifluorfen. Two distinct methods were used to investigate the localization of this enzyme within Percoll-purified spinach chloroplasts. We first assayed the enzymatic activity by spectrofluorimetry and we analyzed the specific binding of the herbicide acifluorfen, using highly purified chloroplast fractions. The results obtained give clear evidence that chloroplast protoporphyrinogen oxidase activity is membrane-bound and is associated with both chloroplast membranes, i.e. envelope and thylakoids. Protoporphyrinogen oxidase specific activity was 7-8 times higher in envelope membranes than in thylakoids, in good agreement with the number of [3H]acifluorfen binding sites in each membrane system: 21 and 3 pmol/mg protein, respectively, in envelope membranes and thylakoids. On a total activity basis, 25% of protoporphyrinogen oxidase activity were associated with envelope membranes. The presence of protoporphyrinogen oxidase in chloroplast envelope membranes provides further evidence for a role of this membrane system in chlorophyll biosynthesis. In contrast, the physiological significance of the enzyme associated with thylakoids is still unknown, but it is possible that thylakoid protoporphyrinogen oxidase could be involved in heme biosynthesis.

Chloroplasts↗
PubMed1991

Purification and characterization of E37, a major chloroplast envelope protein.

We have purified to homogeneity E37, the second major polypeptide of the inner membrane of the chloroplast envelope. The protein was retained on a Mono S column at pH 7, indicating it is a basic protein. After cyanogen cleavage, the protein was partially sequenced at 2 different sites. The sequence is compared with the deduced amino acid sequence of a cDNA coding for a 37 kDa envelope polypeptide recently published by Dreses-Werringloer et al. (Eur. J. Biochem. (1991) 195, 361-368.)

Amino Acid Sequence↗
PubMed1991

Avoiding reoperation for indeterminate thyroid nodules identified as malignant after surgery.

Thyroid nodules that are indeterminate as carcinoma by needle biopsy before surgery and by study of frozen sections at the time of surgery are occasionally identified to be malignant in later studies. If only a lobectomy has been performed, the advisability of reoperation to remove the remaining thyroid tissue to facilitate radioactive iodine therapy may cause concern. To obviate this difficulty as well as to reduce the occurrence of nodules later in a preserved contralateral thyroid lobe and to provide additional thyroid tissue for study, contralateral subtotal or near total lobectomy has been performed for indeterminate thyroid nodules. The small remnant of remaining thyroid tissue can later be ablated by radioactive iodine if desired. Of 37 patients with indeterminate thyroid nodules, none required reoperation, although the diagnosis of carcinoma was established after surgery for eight patients, three of whom were treated with radioactive iodine.

Biopsy, Needle↗
PubMed1991

Isolation, transcription, and inactivation of the gene for an atypical alkaline phosphatase of Synechococcus sp. strain PCC 7942.

The alkaline phosphatase of Synechococcus sp. strain PCC 7942 is 145 kDa, which is larger than any alkaline phosphatase previously characterized and approximately three times the size of the analogous enzyme in Escherichia coli. The gene for the alkaline phosphatase, phoA, was cloned and sequenced, and the protein that it encodes was found to have little similarity to other phosphatases. Some sequence similarities were observed between the Synechococcus sp. strain PCC 7942 alkaline phosphatase, the alpha subunit of the ATPase from bacteria and chloroplasts, and the UshA sugar hydrolase of E. coli. Also, limited sequence similarity was observed between a region of the phosphatase and a motif implicated in nucleotide binding. Interestingly, although the alkaline phosphatase is transported across the inner cytoplasmic membrane and into the periplasmic space, it does not appear to have a cleavable signal sequence at its amino terminus. The half-life of the mRNA encoding the alkaline phosphatase, measured after inhibition of RNA synthesis, is approximately 5 min. Similar kinetics for the loss of alkaline phosphatase mRNA occur upon the addition of phosphate to phosphate-depleted cultures, suggesting that high levels of this nutrient inhibit transcription from phoA almost immediately. The phoA gene also appears to be the first gene of an operon; the largest detectable transcript that hybridizes to a phoA gene-specific probe is 11 kb, over twice the size needed to encode the mature protein. Other phosphate-regulated mRNAs are also transcribed upstream of the phoA gene. Insertional inactivation of phoA results in the loss of extracellular, phosphate-regulated phosphatase activity but does not alter the capacity of the cell for phosphate uptake.

Alkaline Phosphatase↗
PubMed1990

Surgical treatment of medullary carcinoma of the thyroid.

Medullary thyroid carcinoma, comprising approximately 7% of thyroid carcinoma, produces calcitonin, which can be monitored by immunoassay for diagnosis, at preclinical stages, and for persistent disease and its extent. It presents as sporadic and hereditary forms. The latter consists of the multiple endocrine neoplasia (MEN)-2A syndrome, which includes pheochromocytomas and hyperparathyroidism in some families, and the MEN-2B syndrome, which consistently includes mucosal neuromas and somatic features. The carcinoma, especially the MEN-2B variety, is more aggressive than well-differentiated thyroid carcinoma. After the presence and management of a possible pheochromocytoma is resolved, treatment is by total thyroidectomy, the MEN-2 syndromes always indicating bilateral involvement. Gross evidence of medullary thyroid carcinoma is associated with metastases to regional lymph nodes, justifying removal of lymph nodes in the central neck, anterior superior mediastinum, and lateral neck. At operation, attention is given to preservation of parathyroid glands but also to removal of hyperplastic parathyroid glands; subtotal parathyroidectomy usually is needed if clinical hyperparathyroidism is evident. Diagnosis at the preclinical stage, C-cell hyperplasia, permits total thyroidectomy. Lateral cervical lymph node dissection is determined by biopsy of midjugular lymph nodes. In this situation, serum calcitonin levels are usually normal after operation, indicating cure. However, for palpable medullary thyroid carcinoma, serum calcitonin levels are often elevated after appropriate neck surgery. In this event, scanning techniques are used to monitor patients, and reoperation is performed if localization of medullary thyroid carcinoma is achieved. The mediastinum is particularly observed for recurrence. Reoperation is justified for recurrence in the neck and mediastinum. Early diagnosis and monitoring permits long-term survival. In the future it is anticipated that diagnostic genetic techniques will provide definitive and early diagnosis in the hereditary form, permitting earlier treatment with assurance of cure.

Adrenal Gland Neoplasms↗
PubMed1979

The two-mutational-event theory in medullary thyroid cancer.

Comparisons are presented of the ages of onset of 20 cases of hereditary medullary carcinoma of the thyroid (MCT) and of 22 sporadic cases of this same type of cancer. These data are compatible with what might be expected by the two-mutational-event theory of the initiation of cancer postulated by Knudson. It had been previously postulated that C-cell hyperplasia of the thyroid was a premalignant change resulting from the first or genetic mutational event in the initiation of this type of cancer. The finding of C-cell hyperplasia in thyroid glands of each of the 10 patients with the hereditary condition and in none of the 10 sporadic patients is compatible with this theory. The C-cell hyperplasia is believed to be the expression of the genetic mutation, which requires a subsequent somatic mutation to transform the initially mutated cell into a cancer cell.

Adolescent↗
PubMed1978

Management of occult medullary thyroid carcinoma: evidenced only by serum calcitonin level elevations after apparently adequate neck operations.

Following operation for medullary thyroid carcinoma, elevated serum calcitonin levels were present in 18 patients who had no clinically evident residual tumor. In eight of these patients, additional operations have been performed to achieve an appropriate thyroidectomy and cervical lymph node dissection. In six of these eight, elevated serum calcitonin concentrations persist. Extensive clinical examinations failed to identify a metastatic focus of carcinoma. Serum calcitonin concentrations have remained relatively stable for up to six years (average, 3.9 years) of observations in 12 patients after initial or only operations performed from one to 13 years (average 7.3 years) previously. This suggests that microscopic metastases of this carcinoma can remain relatively dormant for years. The management of medullary thyroid carcinoma requires initially adequate cervical operations, periodic serum calcitonin measurements postoperatively, reoperation if adequate neck surgery has not been performed and if serum calcitonin levels remain elevated and only periodic reevaluation for other asymptomatic patients with persistently elevated concentrations of serum calcitonin.

Calcitonin↗
PubMed1977

Multicellular origin of parathyroid "adenomas".

Most cases of primary hyperparathyroidism are associated with enlargement of a single gland (i.e., an "adenoma") or with chief-cell hyperplasia, but there is controversy about the relative frequency of each of these entities. It has even been postulated that adenomas do not arise spontaneously, bu- result from prolonged hyperplasia in response to unknown stimuli. We studied four parathyroid adenomas from three women with heterozygosity (GdB/GdA) for the X-chromosome-linked enzyme, glucose-6-phosphate dehydrogenase, to determine the number of cells from which the growths arise. Unicellular origin would be compatible with a rare oncogenic event, whereas multicellular origin might be seen with hyperplasia. Both B and A isoenzymes were found in each "adenoma" in proportions similar to those observed in normal tissues, indicating that the lesions have multicellular origin. Thus, parathyroid hyperplasia and adenomas, which at best are difficult to distinguish from one another pathologically, may also be similar biologically.

Adenoma↗
PubMed1977

Primary hyperparathyroidism. A cause of hypercalciuria and renal stones in patients with medullary sponge kidney.

Three patients with nephrolithiasis were found to have both medullary sponge kidney (MSK) and primary hyperparathyroidism. In all cases, urine calcium excretion returned to normal after parathyroidectomy. The passage of stones was abolished for more than 20 years in one case and for more than 12 years in another. The available data suggest that many patients with MSK are asymptomatic and that the risk of stone formation is increased by an associated metabolic abnormality such as hypercalciuria or hyperparathyroidism.

Adult↗
PubMed1977

Absence of pancreatic duct dilation in chronic pancreatitis: surgical significance.

Of 22 patients treated surgically for intractable pain from chronic alcoholic pancreatitis, eight did not show notable dilation of the main pancreatic duct by endoscopic retrograde cholangiopancreatography (ERCP), operative pancreatography, and/or operative and microscopical studies of the pancreas after subtotal pancreatectomy. In all patients, far advanced parenchymal pancreatitis was evident at operation and by microscopical study of the removed portion of the pancreas. These findings indicate that the basic problem in a considerable number of patients with symptomatic alcoholic chronic pancreatitis is not related primarily to obstruction with dilation of the major pancreatic duct, but to intrinsic changes in the parenchymal pancreas. The preoperative use of ERCP and individualization of operative procedures with a preference for subtotal or partial pancreatectomy for symptomatic chronic alcoholic pancreatitis are supported.

Adult↗