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Biomedical subjects

R Holland

Publications and source records attributed to R Holland.

At least 199 records · Page 11Linked to original sources

Reduction of breast cancer mortality through mass screening with modern mammography. First results of the Nijmegen project, 1975-1981.

Since 1975 four rounds of screening with modern mammography for breast cancer have been carried out among 30 000 Nijmegen women born before 1940. The results up to the end of 1981 shows that the odds ratio of screened vs unscreened subjects among women who died from breast cancer compared with women who did not, was 0.48 (95% confidence interval 0.23-1.00) in all age groups.

Adult↗

Mammary carcinoma with osteoclast-like giant cells. Additional observations on six cases.

Six cases of mammary carcinoma with osteoclast-like giant cells are reported. In addition to the multinucleated giant cells and the prominent stromal angiogenesis reported in earlier reports, other characteristic features of the tumors were observed: (1) the gross appearance, characterized by a well-outlined, lump-shaped, dark brown tumor mass; (2) the round tumor shadow on the mammograms, originally interpreted as a cyst, a fibroadenoma, or a medullary carcinoma; and (3) the "adenocystic" pattern of the invasive tumor growth. The light and electron microscopic observations point to the intimate relationship between the tumor cell clusters and the giant cells and provide further support to the theory that these giant cells develop from mononuclear histiocytes in response to the production of some sort of extracellular material by the tumor cells. All of the 26 positive axillary nodes of three patients, and many intramammary lymphatics with tumor thrombi of two patients contained giant cells. These observations indicate that the benign giant cells comprise an integral part of the invasive tumor growth. The six cases were recognized in a series of 527 consecutive breast cancers, during a period of 4 years, in a population of about 75,000 adult women. These data question the reported rarity of this distinctive variant of mammary carcinoma.

Adenocarcinoma↗

Glucagon inhibits fatty acid synthesis in isolated hepatocytes via phosphorylation of acetyl-CoA carboxylase by cyclic-AMP-dependent protein kinase.

If isolated rat hepatocytes are preincubated for 90 min before addition of hormone, glucagon causes a significant (50%) decrease in fatty acid synthesis without concomitant large decreases in the cellular content of the allosteric activator, citrate. We present evidence that this inhibition can be entirely accounted for by the phosphorylation of the rate-limiting enzyme, acetyl-CoA carboxylase, by cyclic-AMP-dependent protein kinase. In particular: (1) the effect is associated with a 50% decrease in acetyl-CoA carboxylase activity (measured at physiological citrate concentration) which survives purification of the enzyme; (2) the effect is associated with a selective increase in the phosphorylation of a chymotryptic peptide (peptide 1) which is identical to the peptide containing the major site phosphorylated on purified acetyl-CoA carboxylase by cyclic-AMP-dependent protein kinase; (3) the effects of glucagon on the kinetic parameters of the enzyme are very similar to the effect of phosphorylation of the purified enzyme, i.e. a decrease in V and an increase in Ka for citrate; and (4) all of these effects occur at physiological concentrations of glucagon identical to those producing inhibition of fatty acid synthesis.

Acetyl-CoA Carboxylase↗

In vivo fixative effect of formocresol on pulpotomized deciduous teeth of dogs.

Formocresol was checked with respect to its in vivo fixative effect after pulpotomy, through observation of tissue resistance to necrosis. The root pulps were freed from their hard-tissue wrapping and processed for 48 hours, followed or not by capping (15 days) with zinc oxide-eugenol or with zinc oxide-eugenol-formocresol. The effect of only capping with zinc oxide-eugenol, with or without formocresol, was also recorded.

Animals↗

Mammographically occult breast cancer. A pathologic and radiologic study.

Fifteen mammographically occult breast cancers, 3 of which were preinvasive and 12 invasive, and 52 breast cancers, which presented only microcalcifications mammographically without an associated tumor shadow (33 preinvasive and 19 invasive), were reviewed pathologically and radiologically. This study suggests that most of the preinvasive cancers, without mammographically significant calcifications, are, and some of the invasive cancers situated in dense breasts may be, mammographically occult. The mean diameter of the five mammographically occult invasive ductal carcinomas and the five invasive lobular carcinomas was 20 mm and 50 mm, respectively. Histologic characteristics, which may explain why invasive lobular carcinomas could be occult mammographically, even in an advanced stage, include a diffuse invasive pattern and, frequently, a poor desmoplastic reaction in contrast to the invasive ductal carcinomas. The implications of mammographically occult cancers on management of symptomatic and asymptomatic patients are discussed.

Breast Neoplasms↗

Malignant histiocytosis. Clinical and cytogenetic studies in a newborn and a child.

Malignant histiocytosis (MH) was diagnosed on the cytologic and cytochemical features of the malignant cells present in bone marrow smears from an infant and a child. The diagnosis of MH was confirmed by light and electron microscopic studies on bone marrow and skin biopsy specimens, and bone marrow and liver biopsy specimens, respectively. Both patients showed a deterioration while receiving prednisone monotherapy, but they responded well to a combination of vincristine and cyclophosphamide. The infant has remained disease-free for 52+ months now, but the child died of a relapse 11 months after diagnosis. Cytogenetic studies of blood and/or bone marrow cells were performed before treatment. In the infant, a pathologic cell line with a translocation t(8;16)(p11;p13) was found; this abnormality was no longer present after remission was obtained. In the second patient, a hyperdiploid cell line with major karyotypic anomalies was found. When studied in relapse and shortly before death, additional chromosomal abnormalities were seen. The data from this study show that prednisone should be used with caution in MH, and that it should be omitted from combination chemotherapy when adverse effects are noted during short-term monotherapy. Also, cytogenetic studies should be performed more often in MH to determine the significance and possible nonrandomness of chromosomal abnormalities in this disease.

Antineoplastic Agents↗

Evidence that amiloride antagonises insulin-stimulated protein phosphorylation by inhibiting protein kinase activity.

The diuretic drug amiloride antagonises the insulin-dependent increase in phosphorylation of ATP-citrate lyase in hepatocytes isolated from rats that had been starved and refed a fat-free diet. Studies with a range of protein kinases and protein phosphatases that have been shown to phosphorylate or dephosphorylate purified ATP-citrate lyase in vitro revealed that amiloride was a non-specific inhibitor of all protein kinases tested, but did not significantly affect any of the protein phosphatases. These results cast doubt on previous claims that growth factors stimulate phosphorylation of ribosomal protein S6 by activating an amiloride-sensitive Na+/H+ exchange system, and that insulin inhibits a protein phosphatase that is activated by amiloride.

ATP Citrate (pro-S)-Lyase↗

Influence of bony resorption on endodontic treatment.

A review of prognosis studies has examined success rates between samples of teeth, both with and without radiolucent lesions, treated conventionally. The presence of a lesion predisposes the endodontic case to a lower success rate. On the basis of experimental data on the use of calcium hydroxide, investigation of increasing success with placement of calcium hydroxide in the canals of teeth with periapical lesions for 3 to 10 months prior to conventional filling is proposed.

Alveolar Process↗

The effect of the filling material in the tissue reactions following apical plugging of the root canal with dentin chips. A histologic study in monkeys' teeth.

The object of the present work was to observe whether the root canal filling material has some influence in the periapical healing process after apical plugging with dentin chips. Monkeys' teeth were filled with nine different filling materials in use today. Ninety days after the treatment, the histologic data showed no differences in the results with the nine materials studied. This fact suggests that the filling material does not influence the healing process when the plug is present.

Animals↗

[Simultaneous bilateral Wilms' tumors].

Wilms' tumors occur in 4-14% bilaterally, partially simultaneously, partially metachronously. Therefore in every case with Wilms' tumor the contralateral kidney has to be examined thoroughly too. 5 children of a series of 52 patients with Wilms' tumor showed simultaneous bilateral occurrence (9,6%). The radiological procedures and their importance in diagnosis of bilateral Wilms' tumor are discussed. The prognosis of simultaneous bilateral Wilms' tumors is much better than that of metachronous ones and almost the same as that of unilateral ones.

Child, Preschool↗

Differential phosphorylation of ribosomal protein S6 in isolated rat hepatocytes after incubation with insulin and glucagon.

Glucagon and insulin both stimulated the 32P-labelling of ribosomal protein S6 in rat hepatocytes that had been incubated with 32Pi. Glucagon selectively enhanced the labelling of the tryptic peptide phosphorylated by cyclic AMP-dependent protein kinase, demonstrating that 6 S is a physiological substrate for this enzyme. Insulin stimulated the phosphorylation of distinct tryptic peptides, at least one of which appears to be very close in the primary structure to the sites phosphorylated by cyclic AMP-dependent protein kinase.

Animals↗

So-called interval cancers of the breast. Pathologic and radiologic analysis of sixty-four cases.

Within a population-based breast cancer screening programs, 209 cancers were detected by regular mammographic screening. Additionally, 66 cancers were discovered between two consecutive screenings after one, two, or three negative screening examinations (interval cancers). The study group consisted of 25,920 women who have been participating since 1975 in a breast cancer screening program in Nijmegen, the Netherlands. In this program, single view mammography (lateromedial projection) was administered as the sole screening examination every two years. Physical examination was not part of the screening program. All previous histologic and radiologic material from 64 of those "interval" patients was available and was reviewed. In 19 of the 64 patients, direct or indirect signs of tumor were seen on the previous screening mammogram on review (observers error). In four cases the site of the tumor lay outside the imaging field (technical error). In 41 cases, no signs of tumor could be seen on the mammograms even on review. By calculated tumor doubling times, 20 of these 41 cases were probably too small to be detected at the last screening ("real" interval cancers). However, 21 cases were probably large enough but were somehow masked from radiologic detection. The mean reasons for this "masking" proved to be: 1) dense breast, 2) poorly outlined tumor mass of diffuse infiltrative type, mainly invasive lobular carcinomas, and 3) intraductal localization. The authors suggest that women with dense breasts be screened more frequently, using more views and modalities and with broader criteria for advising surgical biopsy. They also note that in general the two-year interval between screenings is probably longer than the optimal interval.

Aged↗