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Variations of ornithine decarboxylase activity and S-adenosyl-L-methionine and 5'-methylthioadenosine contents during the development of diethylnitrosamine-induced liver hyperplastic nodules and hepatocellular carcinoma.

Liver ornithine decarboxylase (ODC) activity and content of S-adenosyl-L-methionine (SAM) and its catabolite 5'-methylthioadenosine (5'-MTA) were determined in the late stages of hepatocarcinogenesis. Wistar rats received one diethylnitrosamine dose, followed by a partial hepatectomy at the midpoint of a 15-day treatment with 2-acetylaminofluorene (2-AAF), and then by an 18-week phenobarbital (PB) treatment. Thirty-eight per cent of liver was gamma-glutamyltranspeptidase (GGT)-positive and no visible nodules and hepatocellular carcinomas developed 16 weeks after starting 2-AAF feeding. Hyperplastic nodules and hepatocellular carcinomas were found on weeks 24 and 56 respectively. On weeks 24 and 56 only approximately 10% of liver was occupied by GGT-positive foci. At all times studied the foci exhibited a low labeling index (LI), and liver ODC activity was near control values. By contrast, a high ODC activity and LI and a low SAM and 5'-MTA levels were found in hyperplastic nodules and neoplasia. These tissues exhibited a high 5'-MTA phosphorylase activity. SAM administration during PB treatment, caused a 25-36% fall of GGT-positive liver and prevented the development of hyperplastic nodules and hepatocellular carcinomas. This was coupled to a sharp increase of SAM and 5'-MTA liver contents. SAM and 5'-MTA inhibited hepatocyte DNA synthesis in vitro. The addition of 5'-MTA to the reaction mixture for the ODC assay strongly inhibited ODC activity. However, the preincubation of SAM with liver homogenates or hepatocytes, used to prepare crude ODC, was necessary to inhibit ODC activity by SAM. Adenine, an inhibitor of 5'-MTA-phosphorylase, enhanced inhibition of DNA synthesis and ODC activity by SAM and 5'-MTA. Thus, during a prolonged promoting treatment a selected population of GGT-positive foci appears to acquire a stable phenotype characterized by a high DNA and polyamine synthesis. The development of nodules and carcinomas is associated with low SAM and 5'-MTA contents and high ODC activity and LI. 5'-MTA accumulation, during SAM administration, is probably responsible for the inhibition of promotion by SAM.

2-Acetylaminofluorene↗

Massive exophytic abscesses and fibrotic masses of the chin: a variant of the follicular occlusion triad.

We present a patient with an extensive cluster of exophytic nodules that developed on his chin. These nodules consisted of abscesses and fibrotic areas. Lesion morphology, histology, and microbiology support a follicular occlusion triad entity. However, the distribution is striking and does not fit the entities described in the triad. We present the case to show that follicular occlusion was the inciting factor in our patient's eruption and to broaden our concept of clinical manifestations that can arise from this pathologic process.

Abscess↗

Persistent subcutaneous nodules in patients hyposensitized with aluminum-containing allergen extracts.

BACKGROUND: The development of persistent nodules that cause pain and itching at a vaccination or hyposensitization injection site is a rare event. These lesions have been mainly attributed to a hypersensitivity reaction to aluminum hydroxide, which is used as an absorbing agent in many vaccines and hyposensitization preparations. Patch tests with standard antigens and aluminum compounds and histopathologic and ultrastructural studies were performed on 10 patients with persistent subcutaneous nodules on the upper part of their arms after injection of aluminum-adsorbed dust and/or pollen extracts. OBSERVATIONS: The nodules appeared 1 month to 6.5 years after injections. The results of patch tests with 2% aluminum chloride were positive in five patients. Histopathologic examination revealed two different patterns: some biopsy specimens (from lesions of less than 9 months' duration) showed a pure foreign body histiocytic reaction characterized by extracellular amorphous dermal basophilic deposits with a histiocytic-macrophagic reaction; others showed a delayed hypersensitivity granulomatous reaction in association with an histiocytic foreign body response. The lesions were characterized by a unifocal or multifocal unencapsulated granulomatous reaction in the deep dermis and/or subcutaneous tissue. Eosinophilic necrotic areas surrounded by dense fibrous bands and a massive inflammatory infiltrate (lymphoid follicles, large histiocytic cells, abundant eosinophils, and some plasma cells) were observed. A granular basophilic material in extracellular spaces and within the cytoplasm of some histiocytes was also noted. Electron microscopic studies revealed intracytoplasmic and extracellular deposits of a fibrillar electron-dense material. CONCLUSIONS: Persistent subcutaneous nodules that develop after the administration of aluminum-containing preparations may show two characteristic histopathologic patterns. A pure histiocytic foreign body reaction was observed in early lesions, and a delayed hypersensitivity granulomatous reaction was seen in older lesions. No relationship between histopathologic pattern and patch test results was observed. Aluminum-free preparations should be used in patients in whom these nodules develop.

Adsorption↗

[Development and/or increase of rheumatoid nodules in RA patients following leflunomide therapy].

This is the first description of the development of rheumatoid nodules in 3 rheumatoid arthritis patients following leflunomide therapy. The nodules were localized at typical sites with preference of the extensor side of hands and elbow. One nodule examined histologically revealed the typical architecture of RA nodules. In all 3 patients the time of onset of nodulosis was about 6 months after initiating the leflunomide therapy. In all 3 patients leflunomide was clinically efficacious concerning RA: remission or near remission was achieved. Due to the extent of nodulosis, the leflunomide therapy had to be stopped in 2 patients. Progression and acceleration of nodulosis is well known following MTX therapy in RA patients. It is caused by adenosine A1 receptor promotion of multinucleated giant cell formation by human monocytes. Leflunomide has no known influence on adenosine metabolism, so different pathogenetic mechanisms must be assumed for the induction of nodulosis by leflunomide.

Adult↗

Dose-response relationships for radiation-induced thyroid cancer and thyroid nodules: evidence for the prolonged effects of radiation on the thyroid.

The risk of developing thyroid cancer and other thyroid neoplasms after radiation exposure is well known, but specific modifiers of the dose-response relationship are not. We have identified 4296 subjects who received treatment before their sixteenth birthday with orthovoltage radiation for benign conditions in the head and neck area. Individual thyroid dose estimates were calculated for 3843 subjects. Of the 2634 subjects who have been found, 1043 have developed thyroid nodules of all types, and 309 have developed thyroid cancer. The radiation dose-response relationship was consistent with a linear excess relative risk model for thyroid cancer and thyroid nodules within the range of observed doses. Women developed thyroid cancer and thyroid nodules at a higher rate, but the slopes of the dose-response curves were the same for men and women. Age at radiation exposure was a significant factor of the risk, with a lower age at exposure associated with a higher risk. To determine the effect of the wide publicity and our screening program, which began in 1974, we compared the dose-response relationship for cases diagnosed before and after 1974. The overall rates increased dramatically after 1974, but the estimates of the slopes of the dose-response curves were not statistically different. The slope of the dose-response curve for thyroid neoplasms appears to have reached a maximum 25-29 yr after radiation exposure, but the dose response continued to be elevated at the end of follow-up. These data are consistent with the tumorigenic effects of radiation lasting at least 40 yr.

Adult↗

[Computed tomography for evaluation of hepatocellular carcinoma after treatment with transarterial chemoembolization].

Totally 135 series of computed tomography (CT) and angiographic examination were performed in 53 patients with proved hepatoma treated by TAE. CT examination was performed four to six weeks after TAE, and a comparative angiographic examination was performed within three weeks after CT examination. The pictures of CT scanning were read to determine 1). the grading of lipiodol retention inside the tumor, 2). the presence/absence of filling defect in the tumor margins coated by lipiodol, 3). the presence/absence of residual tumor tissue within or surrounding the main tumor, and 4). the presence/absence of developed satellite nodules. In comparison with angiographic findings, CT demonstrated 96.3% specificity and 58.2% sensitivity in the grading of lipiodol filling, and 96.3% specificity and 65.7% sensitivity in the tumor margins of lipiodol coating. However, it was difficult for CT to detect small nodules, especially those less than 1 cm in diameter. We find no statistically significant association between newly developed satellite nodules and grading of lipiodol retention inside the tumor or tumor margins of lipiodol coating. Therefore, when CT pictures reveal filling defect over the margins of the tumor coated by lipiodol or less-than-50% lipiodol filling inside the tumor, repeated angiography and further treatment with TAE are suggested.

Adult↗

Natural history of thyroid nodules in survivors of pediatric Hodgkin lymphoma.

BACKGROUND: Survivors of Hodgkin lymphoma and other patients who receive neck irradiation are at increased risk of thyroid cancer. Ultrasonography provides an inexpensive and non-invasive method of thyroid screening, but the clinical significance of thyroid nodules detected by ultrasound screening is uncertain. PROCEDURE: We reviewed the demographics, clinical characteristics, method of detection, and outcome of patients who developed thyroid nodules after treatment for pediatric Hodgkin lymphoma at our institution. One radiologist reviewed all imaging studies. RESULTS: Sixty-seven children treated for Hodgkin lymphoma from 1962 to 2001 developed thyroid nodules. The study group represented 9,024 person-years of follow-up after the diagnosis of Hodgkin lymphoma and 581 person-years after diagnosis of a thyroid nodule. A median of 10.5 years (range, 0.2-24.8 years) elapsed between the diagnoses of Hodgkin lymphoma and thyroid nodule(s). All but one patient had received neck irradiation for Hodgkin lymphoma, with a median thyroid radiation dose of 35 Gy (range, 12-45 Gy). Thyroid nodules were found to be malignant in seven patients (10%), at a median of 16.2 years (range, 8.4-23.7 years) after diagnosis of Hodgkin lymphoma. Only one malignancy was found through screening ultrasonography. All patients with thyroid cancer remained disease-free at 0.4-16.2 years of follow-up. CONCLUSIONS: Thyroid nodules are common in Hodgkin lymphoma survivors treated with neck irradiation, but the majority of these lesions have an indolent clinical course and do not undergo malignant transformation. Only patients with a palpable mass or clinical symptoms need more extensive evaluation, including Doppler-flow ultrasonography and fine-needle aspiration.

Disease-Free Survival↗

Bleomycin toxicity simulating metastatic nodules to the lungs.

Pulmonary nodules may develop following bleomycin therapy, a previously undescribed entity that may simulate metastatic disease. Two asymptomatic patients are reported with nodules that developed following low dose bleomycin treatment for testicular tumors. One patient had previously documented pulmonary metastases that had resolved after chemotherapy. The other patient had nodular-appearing densities on routine chest examination without a history of previous metastatic lung involvement.

Adult↗

Fine needle aspiration of tophi for crystal identification in problematic cases of gout. A report of two cases.

BACKGROUND: The definitive diagnosis of gout is best established by demonstration of monosodium urate (MSU) crystals in the synovial fluid or biopsy. Fine needle aspiration cytology (FNAC) of tophi can play a crucial role in diagnosis. CASES: A 36-year-old chronic alcoholic male developed subcutaneous nodules on both malleoli without a history of arthropathy and with normal serum uric acid levels. FNAC of the nodules demonstrated stacks and sheaves of needle-shaped crystals of MSU. A 50-year-old diabetic male developed multiple nodules on the feet. He gave a past history of painful athropathy. A roentgenogram of the feet was suspicious for gout; however, joint aspiration failed, and the serum uric acid levels were normal. At this juncture FNAC of the feet tophi clinched the diagnosis of gout. In both cases, polarization of needle washings (wet mount) and the fixed, Papanicolaoustained smears showed negatively birefringent, needle-shaped crystals of MSU, thus confirming the diagnosis of gout. CONCLUSION: FNAC of gouty tophi is an easy alternative to synovial biopsy and joint fluid analysis. It is simpler, easier and less painful. As crystals are preserved in stained smears, they can be employed for polarization and confirmation of gout.

Adult↗

Cutaneous metastasis of osteosarcoma.

Cutaneous metastases of solid tumors have been reported with a frequency that ranges from 0.7% to 4.4% with recent studies reporting 9% and 10%. Osteosarcomas seldom metastasize to the skin. The most frequent metastatic sites are to the lungs, bones, and kidneys. We report 2 cases of osteosarcoma that metastasized to the skin. A 75-year-old patient with known osteosarcoma of the tibia developed cutaneous nodules overlying the site of the primary tumor. A 46-year-old woman with a history of osteosarcoma of the knee developed a nodule on her scalp. Histologic examination of both lesions revealed metastatic osteosarcoma. This is a rare event that, to our knowledge, has previously only been reported 6 times.

Aged↗

Development of a digital image database for chest radiographs with and without a lung nodule: receiver operating characteristic analysis of radiologists' detection of pulmonary nodules.

OBJECTIVE: We developed a digital image database (www.macnet.or.jp/jsrt2/cdrom_nodules.html ) of 247 chest radiographs with and without a lung nodule. The aim of this study was to investigate the characteristics of image databases for potential use in various digital image research projects. Radiologists' detection of solitary pulmonary nodules included in the database was evaluated using a receiver operating characteristic (ROC) analysis. MATERIALS AND METHODS: One hundred and fifty-four conventional chest radiographs with a lung nodule and 93 radiographs without a nodule were selected from 14 medical centers and were digitized by a laser digitizer with a 2048 x 2048 matrix size (0.175-mm pixels) and a 12-bit gray scale. Lung nodule images were classified into five groups according to the degrees of subtlety shown. The observations of 20 participating radiologists were subjected to ROC analysis for detecting solitary pulmonary nodules. Experimental results (areas under the curve, Az) obtained from observer studies were used for characterization of five groups of lung nodules with different degrees of subtlety. RESULTS: ROC analysis showed that the database included a wide range of various nodules yielding Az values from 0.574 to 0.991 for the five categories of cases for different degrees of subtlety. CONCLUSION: This database can be useful for many purposes, including research, education, quality assurance, and other demonstrations.

Adult↗

Infection of soybean and pea nodules by Rhizobium spp. purine auxotrophs in the presence of 5-aminoimidazole-4-carboxamide riboside.

Purine auxotrophs of various Rhizobium species are symbiotically defective, usually unable to initiate or complete the infection process. Earlier studies demonstrated that, in the Rhizobium etli-bean symbiosis, infection by purine auxotrophs is partially restored by supplementation of the plant medium with 5-amino-imidazole-4-carboxamide (AICA) riboside, the unphosphorylated form of the purine biosynthetic intermediate AICAR. The addition of purine to the root environment does not have this effect. In this study, purine auxotrophs of Rhizobium fredii HH303 and Rhizobium leguminosarum 128C56 (bv. viciae) were examined. Nutritional and genetic characterization indicated that each mutant was blocked in purine biosynthesis prior to the production of AICAR. R. fredii HH303 and R. leguminosarum 128C56 appeared to be deficient in AICA riboside transport and/or conversion into AICAR, and the auxotrophs derived from them grew very poorly with AICA riboside as a purine source. All of the auxotrophs elicited poorly developed, uninfected nodules on their appropriate hosts. On peas, addition of AICA riboside or purine to the root environment led to enhanced nodulation; however, infection threads were observed only in the presence of AICA riboside. On soybeans, only AICA riboside was effective in enhancing nodulation and promoting infection. Although AICA riboside supplementation of the auxotrophs led to infection thread development on both hosts, the numbers of bacteria recovered from the nodules were still 2 or more orders of magnitude lower than in fully developed nodules populated by wild-type bacteria. The ability to AICA riboside to promote infection by purine auxotrophs, despite serving as a very poor purine source for these strains, supports the hypothesis that AICAR plays a role in infection other than merely promoting bacterial growth.

Aminoimidazole Carboxamide↗

A Rhizobium leguminosarum AcpXL mutant produces lipopolysaccharide lacking 27-hydroxyoctacosanoic acid.

The structure of the lipid A from Rhizobium etli and Rhizobium leguminosarum lipopolysaccharides (LPSs) lacks phosphate and contains a galacturonosyl residue at its 4' position, an acylated 2-aminogluconate in place of the proximal glucosamine, and a very long chain omega-1 hydroxy fatty acid, 27-hydroxyoctacosanoic acid (27OHC28:0). The 27OHC28:0 moiety is common in lipid A's among members of the Rhizobiaceae and also among a number of the facultative intracellular pathogens that form chronic infections, e.g., Brucella abortus, Bartonella henselae, and Legionella pneumophila. In this paper, a mutant of R. leguminosarum was created by placing a kanamycin resistance cassette within acpXL, the gene which encodes the acyl carrier protein for 27OHC28:0. The result was an LPS containing a tetraacylated lipid A lacking 27OHC28:0. A small amount of the mutant lipid A may contain an added palmitic acid residue. The mutant is sensitive to changes in osmolarity and an increase in acidity, growth conditions that likely occur in the nodule microenvironment. In spite of the probably hostile microenvironment of the nodule, the acpXL mutant is still able to form nitrogen-fixing root nodules even though the appearance and development of nodules are delayed. Therefore, it is possible that the acpXL mutant has a host-inducible mechanism which enables it to adapt to these physiological changes.

Acyl Carrier Protein↗

Effects on bone mineral density by treatment of benign nodular goiter with mildly suppressive doses of L-thyroxine in a cohort women study.

OBJECTIVES: Thyroid diseases and their treatment may influence the osseous system. The influence that prolonged suppressive L-thyroxine (LT4) therapy may have on inducing subclinical hyperthyroidism on bone metabolism is still a matter of debate. The aim of the present study was to assess the effects of chronic LT4 treatment at mildly inhibiting serum thyroid-stimulating hormone (TSH) doses on bone mineral density (BMD) and biochemical bone remodeling markers in a cohort of women with benign nodular goiter, and to verify the efficacy of the treatment on nodule size. SUBJECTS AND STUDY DESIGN: A total of 200 euthyroid Caucasian women with nodular goiter (age 52.1 +/- 9; 80 pre- and 120 postmenopausal) were enrolled: 96 had been treated with LT4 for at least 3 years and a matched group of 104 had untreated goiter. LT4 therapy was given at a dose sufficient to reduce TSH under the lower limit of the normal range (0.27-4.20 microIU/ml) without suppressing it below the limit of assay sensitivity (0.005 microIU/ml) and maintaining normal serum values of free triiodothyronine (FT3) and free thyroxine (FT4). The adequacy of the dose was evaluated on the basis of serum TSH levels. The osteopenic effect of LT4 treatment was evaluated directly by total body and lumbar spine dual-energy X-ray absorptiometry (DEXA) and indirectly by biochemical parameters (alkaline phosphatase, osteocalcin, calcium, parathyroid hormone) at the baseline and throughout the follow-up. The efficacy of LT4 schedule on thyroid nodule size was assessed on the basis of the ultrasonographic evaluation. RESULTS: Mineralometric data showed no significant difference between BMD values for treated and untreated patients in both pre- and postmenopausal status. In all patients, serum markers of bone turnover were in the normal range, with no differences in the treated and control groups. The TSH concentrations were significantly lower in treated than in untreated patients (p < 0.0001); FT3 and FT4 were in the normal range for all patients. Evaluation of nodule size during follow-up showed a reduction of > or = 30% in 32 of 96 treated patients (33.3%) versus none in those untreated, whilst nodule size remained unmodified in 60 treated patients (62.5%) versus 35 (33.6%) in those untreated, and an increase in nodule size and/or development of new nodules was found in 4 treated patients (4.2%) versus 69 of the 104 untreated patients (66.3%). CONCLUSIONS: This study suggests that at slightly suppressing TSH doses, LT4 therapy has no adverse effects on BMD in both pre- and postmenopausal women, while having an efficacy on nodule size comparable with that reported using an LT4 schedule able to maintain TSH near or below the assay sensitivity limit.

Absorptiometry, Photon↗

[Embryonal development of grouped lymphoid nodules (Peyer's patches) in the human ileum].

Embryogenesis of Payer's patches (PP) of the ileum, has been studied in 183 human fetuses 8-40-week-old. Their anlages appear on the 8th-9th week as an accumulation of atypical villi. At first the PP are localized in the cranial part of the ileum, and then spread caudally. Their most active increase in amount takes place from the 15th up to 17th weeks of development. From the 8th up to the 40th weeks the PP amount increase from 10 up to 37. During the same time their length develops from 0.7 up to 8.3 mm, their width--from 0.3 up to 2.2. The first lymphoid nodules++ in the PP are detected on the 14th week, then their number rises from 200 up to 3,500. The superficial area of all the PP, turning into the lumen of the ileum widens from 1.4 up to 620 mm2. Their predominate form is ellipsoid. During the whole prenatal period in the lymphoid nodules++ no germinative centers are revealed. Lymphocytes in the PP are identified in 8-9-week-old fetuses. By the 29th week the whole amount of lymphocytes in them increase up to 9.6 x 10(6) cells. Lymphocytic suspension of the PP of 8-9-week-old fetuses contains 1.7% of T-lymphocytes (E = POK) and 0.1% of B-lymphocytes (EAC = POK). By the 29th week their amount increases up to 9% and 7%, respectively, but by birth it does not reach their amount in the PP of mature organisms.

Embryonic and Fetal Development↗

Newly featured infection events in a supernodulating soybean mutant SS2-2 by Bradyrhizobium japonicum.

Supernodulating soybean (Glycine max L. Merr.) mutant SS2-2 and its wild-type counterpart, Sinpaldalkong 2, were examined for the microstructural events associated with nodule formation and development. SS2-2 produced a substantially higher percentage of curled root hairs than the wild type, especially at 14 days after inoculation with Bradyrhizobium japonicum. In addition, there was new evidence that in SS2-2, B. japonicum also entered through fissures created by the emerging adventitious root primordia. Early steps of nodule ontogeny were faster in SS2-2, and continued development of initiated nodules was more frequent and occurred at a higher frequency than in the wild type. These data suggest that the early expression of autoregulation is facilitated by decreasing the speed of cortical cell development, leading to the subsequent termination of less-developed nodules. The nodules of SS2-2 developed into spherical nodules like those formed on the wild type. In both the wild type and supernodulating mutant, vascular bundles bifurcate from root stele and branch off in the nodule cortex to surround the central infected zone. These findings indicate that SS2-2 has complete endosymbiosis and forms completely developed nodule vascular bundles like the wild type, but that the speed of nodule ontogeny differs between the wild type and SS2-2. Thus, SS2-2 has a novel symbiotic phenotype with regard to nodule organogenesis.

Bradyrhizobium↗

Mammary nodules in beagle dogs administered investigational oral contraceptive steroids.

Of 172 beagle dogs administered oral contraceptive steroids for 5-7 years, 114 developed 1,156 nodules in the mammary gland region. Most of these nodules arose 2.5-3.5 years after initiation of treatment. Approximately 16% of the nodules were transient and disappeared spontaneously from the mammary gland during the study. A total of 925 nodules were present in 99 dogs at the time of death or necropsy. These nodules were classified as benign mammary dysplasias (7.0%), lobular or intraductal hyperplasias (31.4%), simple adenomas (20.8%), complex adenomas (25.4%), benign mixed tumors (5.3%), malignant tumors (3.6%), or nonmammary lesions (6.5%). Histologically, the mammary nodules were representative primarily of the hyperplasias and tumors that occur spontaneously in the mammary glands of the dog. The only major exception was the presence of 82 simple adenomas that had basaloid features. Most of the contraceptive-related mammary nodules developed in dogs receiving the combination of progestion and mestranol at 10 or 25 times the proposed human dosage. Control dogs and dogs receiving mestrenol alone had few mammary nodules. Combinations of anagestone acetate and mestranol and chloroethynyl norgestrel (WY-4355) and mestranol produced large numbers of nodules at 10 and 25 times the proposed human dosage, whereas ethynerone plus mestranol produced large numbers of nodules only at 25 times the proposed human dosage. Ethynerone, when given alone at 25 times the proposed human dosage, was associated with fewer mammary nodules. Malignant neoplasms were seen in dogs given 10 and 25 times the proposed human dosage of anagestone acetate plus mestranol and 25 times the proposed human dosage of WY-4355 plus mestranol and ethynerone plus mestranol. This study strongly associates certain combinations of progestin and mestranol with mammary neoplasia in dogs.

Adenoma↗

Development and structure of bacterial leaf nodules in Psychotria bacteriophila Val. (Rubiaceae).

The development and mature structure of bacterial leaf nodules in Psychotria bacteriophila were studied by using light and electron microscopy. Bacteria in mucilage surrounding the shoot apex pass through certain stomates in leaf primordia into the substomatal chamber. These chambers enlarge and become nodules as the yound leaves grow out of the apical region. Surrounding mesophyll cells grow into each nodule and form a cellular reticulum whose interstices are occupied by bacteria. Each intrusive mesophyll cell wall is unusually thick and continually supplemented by vesicles originating from dictyosomes. The gram-negative bacteria are often surrounded by capsules. Nodule bacteria contain several crystal-like dense bodies. A population of normal, dividing, and degenerating bacteria is found in each nodule. Extensive membranes occur between the bacteria. A hypothesis is proposed to explain certain aspects of this obligate symbiotic relationship.

Bacteria↗