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In the nitrogenase system of Klebsiella pneumoniae, nifT is located between nifDK, the structural genes for dinitrogenase, and nifY, whose product is involved in nitrogenase maturation. It is, therefore, a reasonable hypothesis that the NifT protein might also have a role in the maturation of nitrogenase. However, the phenotypic characterization of nifT and nifT-overexpressing strains for effects on the regulation, maturation, and activity of nitrogenase identified no properties that were distinct from those of the wild type. We conclude that the K. pneumoniae NifT protein is not essential for nitrogen fixation under the conditions examined.

Dinitrogenase, the enzyme capable of catalyzing the reduction of N2, is a heterotetramer (alpha 2 beta 2) and contains the iron-molybdenum cofactor (FeMo-co) at the active site of the enzyme. Mutant strains unable to synthesize FeMo-co accumulate an apo form of dinitrogenase, which is enzymatically inactive but can be activated in vitro by the addition of purified FeMo-co. Apodinitrogenase from certain mutant strains of Azotobacter vinelandii has a subunit composition of alpha 2 beta 2 gamma 2. The gamma subunit has been implicated as necessary for the efficient activation of apodinitrogenase in vitro. Characterization of gamma protein in crude extracts and partially pure fractions has suggested that it is a chaperone-insertase required by apodinitrogenase for the insertion of FeMo-co. These are three major forms of gamma protein detectable by Western analysis of native gels. An apodinitrogenase-associated form is found in extracts of nifB or nifNE strains and dissociates from the apocomplex upon addition of purified FeMo-co. A second form of gamma protein is unassociated with other proteins and exists as a homodimer. Both of these forms of gamma protein can be converted to a third form by the addition of purified FeMo-co. This conversion requires the addition of active FeMo-co and correlates with the incorporation of iron into gamma protein. Crude extracts that contain this form of gamma protein are capable of donating FeMo-co to apodinitrogenase, thereby activating the apodinitrogenase. These data support a model in which gamma protein is able to interact with both FeMo-co and apodinitrogenase, facilitate FeMo-co insertion into apodinitrogenase, and then dissociate from the activated dinitrogenase complex.

Background: In changing our technique to performing needle localization breast biopsies (NLBB) using local anesthesia in an outpatient setting, we investigated whether or not our complication rates with local anesthesia were acceptable when compared with complications from a cohort of biopsies of the breast performed for palpable masses. We were also interested in determining whether or not our rate of missed biopsies was within acceptable ranges., Study Design: Complications occurring in 283 patients who underwent 301 NLBB using local anesthesia between 1983 and 1991 were compared with complications occurring after excision of 249 palpable masses of the breast excised using local anesthesia during this period., Results: Complications associated with NLBB were missed lesions, six (1.99 percent) of 301; hematoma, 12 (3.99 percent) of 301; abscess, three (0.99 percent) of 301; seroma, one (0.33 percent) of 301, and wound separation, two (0.66 percent) of 301, for a total of 24 complications (7.96 percent). These rates were not statistically different from the rates of complication after biopsies of palpable lesions using local anesthesia (p < 0.49). The 301 NLBB revealed 87 carcinomas (28.9 percent); 50 invasive and 37 in situ. Of the nonpalpable carcinomas, 43 percent were in situ. Only 11 percent carcinomas, 43 percent were in situ. Only 11 percent of the palpable lesions were in situ (p < 0.001). Forty-four patients with nonpalpable invasive carcinoma had a 25 percent rate of positive axillary lymph nodes., Conclusions: Needle localization breast biopsies can be performed using local anesthesia exclusively with less than a 2 percent chance of missed lesions and complication rates similar to those associated with biopsies of palpable lesions. The biology of these lesions varies. Although there is a high rate of in situ carcinoma, there is a significant rate of node positivity in the patients with nonpalpable invasive carcinoma.

Calcifications located in the dermis of the breast may appear indistinguishable from intramammary calcifications. The authors present a sign, called the tattoo sign, that can help radiologists identify dermal calcifications. When mammograms are compared, calcifications that maintain a fixed relationship to each other suggest a dermal location. This can be verified with standard techniques. Understanding the tattoo sign may help prevent unnecessary needle localization and biopsy procedures.

Objective: The purpose of this study was to determine if the presence or absence of tumor at the surgical margin in cases of impalpable breast carcinoma could be predicted accurately with specimen radiography., Materials and Methods: We obtained single-view radiographs of 119 consecutive surgical biopsy specimens of impalpable invasive or in situ ductal carcinoma. Radiographic lesions were classified as a mass with moderately well defined margins, a mass with poorly defined margins, or microcalcifications without an associated mass. The radiographic appearance of the impalpable cancer, the margin as judged from the specimen radiograph, the tumor's histologic appearance, and the histologic appearance of the tumor margin were then correlated., Results: Specimen radiographs showed tumor at the surgical margin in 63 cases; 62 of these were confirmed histologically (positive predictive value, 98%). Specimen radiographs showed tumor-free surgical margins in 56 cases; 18 of these were confirmed histologically (negative predictive value, 32%). These results were independent of the radiographic appearance of the lesion or the tumor's histologic appearance., Conclusion: Decisions based on findings on specimen radiographs were valid only if the radiographs showed tumor at the margin of the specimen.

The requirements for iron-molybdenum cofactor (FeMo-co) activation of apodinitrogenase from Azotobacter vinelandii strain UW97, which lacks dinitrogenase reductase activity as assayed by substrate reduction, have been examined. Activation of apodinitrogenase from strain UW97 by FeMo-co requires the addition of both dinitrogenase reductase and MgATP. When the same apodinitrogenase is pretreated with dinitrogenase reductase and MgATP and then partially purified, however, it does not require these components for activation by FeMo-co. This suggests that dinitrogenase reductase and MgATP are involved in processing apodinitrogenase to a FeMo-co activatable form. This processing step coincides with a change in the subunit composition of apodinitrogenase from alpha 2 beta 2 to a form with an additional subunit (gamma) attached. The apodinitrogenase with the associated gamma subunit is apparently the form of the protein that is competent for activation by FeMo-co.

Purpose: Between 1982 and 1988 233 American Joint Committee on Cancer Stage I and II invasive breast carcinomas were prospectively treated in 225 women with conservative tumor excision, careful assessment of histopathological margins, and dose-adjusted irradiation to maximum doses of 70 Gy to the tumor bearing quadrant of the breast., Methods and Materials: The pathological stages at presentation were T1N0 and T1N1 in 57% and 13% and T2N0 and T2N1 in 19% and 10% of the patients, respectively. All patients were irradiated according to a policy that, beyond the 50 Gy to the whole breast and draining lymphatics, the tumor-bearing quadrant was boosted in adjustment to the histopathological margin. Normal tissue margins of < 2 mm were considered positive, margins 2-5 mm close, and margins > 5 mm negative and were boosted with 20, 15, and 10 Gy, respectively. Patients in whom the margin could not be assessed were re-excised or boosted to 20 Gy. Re-excisions with no residual carcinoma were not boosted. Most patients boosted to 20 Gy to the tumor-bearing quadrant received interstitial 192-Ir implantations., Results: The actuarial local control rates in the treated breast were 97.5% at 10 years with three recurrences having occurred at a median of 4.5 years after completion of radiotherapy. An additional two patients failed regionally outside the irradiation portals. The overall and disease-free survival of the whole group is 87.5% and 77%, respectively., Conclusion: The approach to breast conservation therapy followed in this study has resulted in outstanding local control rates and suggests that there may be a subset of patients that could be irradiated to the tumor bearing quadrant only.

Apodinitrogenase, which lacks the iron-molybdenum cofactor at its active site, is an oligomer that contains an additional protein not found in the active dinitrogenase tetramer. This associated protein in Klebsiella pneumoniae is shown to be the product of the nifY gene. When apodinitrogenase is activated by the addition of the iron-molybdenum cofactor, NifY dissociates from the apodinitrogenase complex. The conditions for this dissociation are described. Finally, there are aspects of the dissociation and insertion process in K. pneumoniae that are different from that in Azotobacter vinelandii.

In a series of 500 consecutive needle localizations, there were 165 biopsies for benign microcalcifications without a mass. An incisional biopsy was performed in 49 of these cases (30%). Follow-up mammograms were available for review in 39 of the cases. The average length of follow-up was 32 months. In no case did malignancy develop at the biopsy site. When an incisional biopsy is performed, careful follow-up mammography is an alternative to a repeated needle localization and biopsy in selected cases.

The use of mammography to screen patients for the presence of early breast cancer results in the detection of nonpalpable lesions. As screening becomes more widespread, the number of needle localizations performed will continue to increase. This procedure requires involvement of the radiologist, surgeon, and pathologist. Close cooperation between these disciplines will ensure optimal patient care.

A series of 100 consecutive occult mammographic abnormalities were localized with a curved-end retractable wire system. A true-positive rate of 24% and a failure rate of 4% for initial excision were found. The pitfalls and advantages of this new needle-wire breast localizer are presented.

Patients treated for early breast cancer have an excellent prognosis. The 20-year survival rate of patients with minimal breast cancer exceeds 90 percent. While both physical examination and mammography should be used in diagnosing breast cancer, mammography is superior in detecting smaller lesions. Most minimal breast cancers are nonpalpable. Preoperative percutaneous localization techniques facilitate excision of nonpalpable lesions. Close monitoring with specimen radiography is often required for positive identification.

We reviewed 101 consecutive biopsy specimens of nonpalpable breast lesions obtained by needle localization. Forty-six biopsies were done on outpatients under local anesthesia and 16 more on inpatients under local anesthesia. The remaining 39 biopsies were performed on inpatients under general anesthesia. The complications and accuracy of the outpatient procedure were acceptable and comparable to those of the inpatient procedure. In our institution, there is almost a fivefold cost increase for the performance of this procedure under general anesthesia as an inpatient. We recommend that surgeons and radiologists work together to perfect preoperative localization techniques, and we strongly support the concept that this procedure should be performed on outpatients under local anesthesia for the majority of patients with nonpalpable mammographic abnormalities.

The records of 21 consecutive patients referred for breast-conservation treatment of early-stage mammary carcinoma contained insufficient histopathologic documentation of adequate resection margins after tumor excision at other hospitals. All patients underwent postbiopsy mammography before reexcision of the tumor bed. In 12 of the 21 cases, there was pathologic evidence of macroscopic or microscopic residual tumor. In seven of the 12 cases, there was no clinical or mammographic evidence to suggest residual carcinoma. The findings indicate that mammography is insufficient to evaluate the completeness of tumor excision in the absence of histopathologic documentation.

A national survey was undertaken to ascertain whether a consensus exists regarding follow-up of patients who have nonpalpable mammographic abnormalities that are not biopsied. The three abnormalities evaluated were: an uncalcified breast mass, an area of asymmetric breast density, and a cluster of microcalcification. Irrespective of the type of lesion, the schedule of follow-up was identical. More than 90% of all the participants recommended repeat initial examination within 3-6 months. More than 50% follow suspected abnormalities for at least 2 years.

Early detection of breast cancer by mammography depends on the production of excellent images and competent interpretation. Some of the more important pitfalls encountered with and controversies about mammography are presented in this article. In many cases, the radiologist is unable to declare whether the mammogram is unequivocally normal or abnormal and instead should aid the clinician in formulating rational management options for the woman. Practical options for some of these very complicated problems are proposed.

Mammography plays an important role in the examination of the patient with palpable breast mass. The benefits as well as the limitations of mammography in this clinical setting are examined, and the implications of a normal mammogram report are emphasized. Physicians must be aware that the decision of whether to biopsy a palpable breast mass should not be determined solely by the mammographic findings. It is recommended that patients undergo a mammographic examination before having a breast biopsy.

Seven cases of acute diverticulitis in patients 35 years of age or younger are presented. This disease is not rare in young adults. There seems to be a higher incidence in males and an increased need for surgical intervention when younger individuals are affected. The barium enema is useful in confirming the diagnosis.

While only a few benign lesions in the breast have a characteristic appearance, many others have a high probability of being benign. In those situations, follow up by palpation and mammography is a reasonable alternative to excisional biopsy. The appearance of characteristically benign lesions of the breast and an approach to the management of probably benign lesions is presented.

A new needle-wire system has been developed for localization of nonpalpable breast lesions. The curved-end wire, which is made of a tough pseudoelastic alloy, eliminates many of the pitfalls of this procedure for both the radiologist and the surgeon. Advantages of this new system include the ability to anchor the needle during filming, the ability to easily reposition the needle if necessary, the option of injecting dye, the inability to transect the wire during surgery, and the option of leaving both the needle and wire in place in the subject to allow easier dissection during biopsy.

The use of a post-localization needle which can be palpated during percutaneous localization of nonpalpable breast lesions is described. No difficulties or complications resulted when utilizing the needle in five patients.

Two patients with Gaucher's disease and radiographic findings in the spine similar to sickle cell hemoglobinopathy are reported, making a total of four known patients with Gaucher's disease who have these steplike vertebral endplate deformities. Serial films of a patient having Gaucher's disease compared with patients having sickle cell hemoglobinopathy suggest that different events lead to formation of the vertebral deformities. In Gaucher's disease, there is an initial collapse of the entire vertebral body with subsequent growth recovery peripherally. In sickle cell hemoglobinopathy, the endplate deformity is nontraumatic and is caused by an underlying growth arrest.

Whether existing equipment is modified for use in mammography or a dedicated system is purchased, the services of a qualified medical physicist are necessary. Factors to consider in modifying existing equipment and in purchasing new equipment are detailed, as well as features concerning patient safety. Guidelines for quality assurance tests and their respective time intervals are given.

One hundred forty-six breast biopsies in 143 patients were done on outpatient basis, without general anesthesia, on a gynecologic service between 1975 and 1980. This procedure has advantages over in-hospital biopsy in terms of cost, time, reduced immediate risk, and patient acceptance. Greater long-term risk, if carcinoma is found, has not been substantiated. Gynecologists need this procedure as an adjunct to the management of benign breast conditions and should be trained to do it.

Mammography, whether film or xerography, is a complementary examination to breast palpation in the detection of breast cancer. According to the guidelines of the American Cancer Society, mammography should be performed on every asymptomatic woman, at least once, over the age of 35. Annual mammography after 50 is also advised. The radiation dose to the breast from current equipment is so low as to not be considered a factor in denying a woman this screening examination. Mammography has a role in evaluating the woman with solitary and multiple breast masses. It is the only proved reliable modality able to detect nonpalpable breast cancers and small tumors less than 2 cm in size. All nonpalpable lesions should be excised by directed biopsy, using a preoperative localization technique.

Percutaneous needle localization should be performed before biopsy of a nonpalpable breast lesion, thereby eliminating the need for blind biopsy. With small cancers, transoperative localization is just as important to confirm excision of the lesion and ensure that representative sections are obtained from the area in question for histologic study.

During a period of two years, nine patients were found who had a solitary geographic cluster of microcalcifications which appeared to be intramammary on two standard mammographic views. In two instances, the women underwent unsuccessful excisional biopsies. In the other seven patients, the true location of the microcalcifications was recognized and proved preoperatively so biopsy was avoided. When intradermal microcalcifications are fortuitously imaged in tangent or when they assume characteristic polygonal shapes with lucent centers, their intradermal location should be suspected. However, if the form is not typical of intradermal calcifications and when the location appears to be intramammary on the routine mammographic views, an excisional biopsy will usually be recommended. If skin is not included in the excised tissue, then the biopsy will be unsuccessful. A simple technique using a metallic marker can confirm the true intradermal location of calcifications.

This investigation establishes the usefulness of the hilar height ratio concept and reviews those disease processes that may become manifest by an abnormal left hilar height ratio. In the absence of lower lobe volume loss and extrapulmonary disease, an abnormal left hilar height ratio may reflect upper lobe emphysema.

The true-positive biopsy rate for nonpalpable breast abnormalities demonstrated by mammography is in the range of 20 to 30%. This is comparable to the true-positive biopsy rate for palpable breast lesions. Both radiologists and surgeons must be familiar with the limitations of mammography, since unrealistic expectations of this examination can lead to its underutilization.

A national survey evaluated the different methods used to teach mammography. Many programs do not allow residents sufficient responsibility in supervising this examination, while 13% of the programs do not have any required training in mammography. Residents must be directly involved in monitoring and interpreting this examination in order to achieve minimal competency.

In this final part of a two-part article, fundamental imaging principles are related to the design features of mammography equipment, to give readers information helpful in making equipment decisions and selections.

Two cases are described in which a palpable mass and a nonpalpable mass disappeared during the performance of mammography. The disappearance is presumed to be caused by cyst rupture, resulting from the firm compression used to perform the examination. This occurrence can create confusing clinical and radiographic situations, and radiologists should be aware that occasional cyst rupture may occur.

The advantages of a wire localization guide for nonpalpable breast lesions have been demonstrated in 16 patients. The hooked end will not move after placement when the external end is anchored by a strong clamp. The malleable wire permits post-insertion compression mammograms to be performed. With the wire left in situ, orientation of the biopsy specimen with post-localization mammograms can guide the surgeon if further resection is necessary.

Forty consecutive cases of nonpalpable breast carcinoma presenting on the mammogram as microcalcifications without an associated mass were reviewed. The precise relationship between the mammographic microcalcification and the histologic carcinoma was determined in each case. In 25 cases (63%), the mammographic calcium was confined to the tumor, and in 13 cases (33%), the calcification was present both within the tumor and contiguous to the tumor margin. In two cases (5%), the calcium was not contained within the tumor but was located next to it. In one of these cases, the calcium was within 4 mm of the malignant neoplasm and in the other it was within 13 mm. No difference was seen between the appearance of the calcifications located within the tumor and the appearance of calcification next to the tumor. Precise histologic analysis revealed that microcalcifications that had prompted biopsy were confined to the tumor in 63%, within and contiguous to the tumor in 32%, and within 13 mm of the tumor in 5%.